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Stroke

Stroke is the clinical designation for a rapidly developing loss of brain function due to an interruption in the blood supply to all or part of the brain. This phenomenon can be caused by thrombosis, embolism, or hemorrhage.

Stroke is a medical emergency and can cause permanent neurologic damage or even death if not promptly diagnosed and treated. It is the third leading cause of death and the leading cause of adult disability in the United States and industrialized European nations. On average, a stroke occurs every 45 seconds and someone dies from a stroke every 3 minutes.

The symptoms of stroke can be quite heterogeneous, and patients with the same cause of stroke can have widely differing handicaps. Conversely, patients with the same clinical handicap can in fact have different underlying causes.

The cause of stroke is an interruption in the blood supply, with a resulting depletion of oxygen and glucose in the affected area. This immediately reduces or abolishes neuronal function, and also initiates an ischemic cascade which causes neurons to die or be seriously damaged, further impairing brain function.

Risk factors for stroke include advanced age,hypertension (high blood pressure), diabetes mellitus, high cholesterol, cigarette smoking, atrial fibrillation, migraine with aura, and thrombophilia. Cigarette smoking is the most important modifiable risk factor of stroke.

In recognition of improved methods for the treatment of stroke, the term “brain attack” is being promoted in the United States as a substitute for stroke. The new term makes an analogy with “heart attack” (myocardial infarction), because in both conditions, an interruption of blood supply causes death of tissue which is life-threatening. Many hospitals have “brain attack” teams within their neurology departments specifically for swift treatment of stroke.

  • Types of stroke

Strokes can be classified into two major categories: ischemic and hemorrhagic. Ischemia can be due to thrombosis, embolism, or systemic hypoperfusion. Hemorrhage can be due to intracerebral hemorrhage, subarachnoid hemorrhage subdural hemorrhageand epidural hemorrhage. ~80% of strokes are due to ischemia.

Ischemic stroke

In an ischemic stroke, which is the cause of approximately 80% of strokes, a blood vessel becomes occluded and the blood supply to part of the brain is totally or partially blocked. Ischemic stroke is commonly divided into thrombotic stroke, embolic stroke, systemic hypoperfusion (Watershed or Border Zone stroke), or venous thrombosis. Cocaine abuse doubles the risk of ischemic strokes.

Thrombotic stroke

In thrombotic stroke, a thrombus-forming process develops in the affected artery. The thrombus – a built up clot – gradually narrows the lumen of the artery and impedes blood flow to distal tissue. These clots usually form around atherosclerotic plaques. Since blockage of the artery is gradual, onset of symptomatic thrombotic strokes is slower. A thrombus itself (even if non-occluding) can lead to an embolic stroke (see below) if the thrombus breaks off-at which point it is then called an “embolus.” Thrombotic stroke can be divided into two types depending on the type of vessel the thrombus is formed on: Large vessel disease involves the common and internal carotids, vertebral, and the Circle of Willis. Diseases that may form thrombi in the large vessels include (in descending incidence):

  • Atherosclerosis
  • Vasoconstriction
  • Dissection
  • Takayasu arteritis
  • Giant cell arteritis
  • Arteritis/vasculitis
  • Noninflammatory vasculopathy
  • Moyamoya syndrome
  • Fibromuscular dysplasia

Small vessel disease involves the intracerebral arteries, branches of the Circle of Willis, middle cerebral artery, stem, and arteries arising from the distal vertebral and basilar artery. Diseases that may form thrombi in the small vessels include (in descending incidence): Lipohyalinosis (lipid hyaline build-up secondary to hypertension and aging) and fibrinoid degeneration (stroke involving these vessels are known as lacunar infarcts) Microatheromas from larger arteries that extend into the smaller arteries (atheromatous branch disease)

Embolic stroke

Embolic stroke refers to the blockage of arterial access to a part of the brain by an embolus-a traveling particle or debris in the arterial bloodstream originating from elsewhere. An embolus is most frequently a blood clot, but it can also be a plaque broken off from an atherosclerotic blood vessel or a number of other substances including fat (e.g., from bone marrow in a broken bone), air, and even cancerous cells. Another cause is bacterial emboli released in infectious endocarditis.
Because an embolus arises from elsewhere, local therapy only solves the problem temporarily. Thus, the source of the embolus must be identified. Because the embolic blockage is sudden in onset, symptoms usually are maximal at start. Also, symptoms may be transient as the embolus lyses and moves to a different location or dissipates altogether. Embolic stroke can be divided into four categories:

  1. those with known cardiac source
  2. those with potential cardiac or aortic source (from transthoracic or
    transesophageal echocardiogram)
  3. those with an arterial source
  4. those with unknown source

High risk cardiac causes include:

  • Atrial fibrillation and paroxysmal atrial fibrillation
  • Rheumatic mitral or aortic valve disease
  • Bioprosthetic and mechanical heart valves
  • Atrial or ventricular thrombus
  • Sick sinus syndrome
  • Sustained atrial flutter
  • Recent myocardial infarction (within one month)
  • Chronic myocardial infarction together with ejection fraction
  • Symptomatic congestive heart failure with ejection fraction
  • Dilated cardiomyopathy
  • Libman-Sacks endocarditis
  • Antiphospholipid syndrome
  • Marantic endocarditis from cancer
  • Infective endocarditis
  • Papillary fibroelastoma
  • Left atrial myxoma
  • Coronary artery bypass graft (CABG) surgery

Potential cardiac causes include:[3]

  • Mitral annular calcification
  • Patent foramen ovale
  • Atrial septal aneurysm
  • Atrial septal aneurysm with patent foramen ovale
  • Left ventricular aneurysm without thrombus
  • Isolated left atrial smoke on echocardiography (no mitral stenosis or atrial fibrillation)
  • Complex atheroma in the ascending aorta or proximal arch

Systemic hypoperfusion is the reduction of blood flow to all parts of the body. It is most commonly due to cardiac pump failure from cardiac arrest or arrhythmias, or from reduced cardiac output as a result of myocardial infarction, pulmonary embolism, pericardial effusion, or bleeding. Hypoxemia (low blood oxygen content) may precipitate the hypoperfusion. Because the reduction in blood flow is global, all parts of the brain may be affected, especially “watershed” areas — border zone regions supplied by the major cerebral arteries. Blood flow to these areas does not necessarily stop, but instead it may lessen to the point where brain damage can occur.

Hemorrhagic stroke

A hemorrhagic stroke, or cerebral hemorrhage, is a form of stroke that occurs when a blood vessel in the brain ruptures or bleeds. Like ischemic strokes, hemorrhagic strokes interrupt the brain’s blood supply because the bleeding vessel can no longer carry the blood to its target tissue. In addition, blood irritates brain tissue, disrupting the delicate chemical balance, and, if the bleeding continues, it can cause increased intracranial pressure which physically impinges on brain tissue and restricts blood flow into the brain. In this respect, hemorrhagic strokes are more dangerous than their more common counterpart, ischemic strokes. There are two types of hemorrhagic stroke: intracerebral hemorrhage, and subarachnoid hemorrhage. Amphetamine abuse quintuples, and cocaine abuse doubles, the risk of hemorrhagic strokes.

Subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is bleeding into the cerebrospinal fluid (CSF) of the subarachnoid space surrounding the brain. The two most common causes of SAH are rupture of aneurysms from the base of the brain and bleeding from vascular malformations near the pial surface. Bleeding into the CSF from a ruptured aneurysm occurs very quickly, causing rapidly increased intracranial pressure. The bleeding usually only lasts a few seconds but rebleeding is common. Death or deep coma ensues if the bleeding continues. Hemorrhage from other sources is less abrupt and may continue for a longer period of time. SAH has a 40% mortality over 30 day period.

Signs and symptoms

The symptoms of stroke depend on the type of stroke and the area of the brain affected. Ischemic strokes usually only affect regional areas of the brain perfused by the blocked artery. Hemorrhagic strokes can affect local areas, but often can also cause more global symptoms due to bleeding and increased intracranial pressure.
If the area of the brain affected contains one of the three prominent Central nervous system pathways-the spinothalamic tract, corticospinal tract, and dorsal column (medial lemniscus), symptoms may include:

  • muscle weakness (hemiplegia)
  • numbness
  • reduction in sensory or vibratory sensation

In most cases, the symptoms affect only one side of the body. The defect in the brain is usually on the opposite side of the body (depending on which part of the brain is affected). However, the presence of any one of these symptoms does not necessarily suggest a stroke, since these pathways also travel in the spinal cord and any lesion there can also produce these symptoms.
In addition to the above CNS pathways, the brainstem also consists of the 12 cranial nerves. A stroke affecting the brainstem therefore can produce symptoms relating to deficits in these cranial nerves:

  • altered smell, taste, hearing, or vision (total or partial)
  • drooping of eyelid (ptosis) and weakness of ocular muscles
  • decreased reflexes: gag, swallow, pupil reactivity to light
  • decreased sensation and muscle weakness of the face
  • balance problems and nystagmus
  • altered breathing and heart rate
  • weakness in tongue (inability to protrude and/or move from side to side)
  • weakness in sternocleidomastoid muscle (SCM) with inability to turn head to one side

If the cerebral cortex is involved, the CNS pathways can again be affected, but also can produce the following symptoms:

  • aphasia (inability to speak or understand language from involvement of Broca’s or Wernicke’s area)
  • apraxia (altered voluntary movements)
  • visual field defect
  • memory deficits (involvement of temporal lobe)
  • hemineglect (involvement of parietal lobe)
  • disorganized thinking, confusion, hypersexual gestures (with involvement of frontal lobe)

If the cerebellum is involved, the patient may have the following:

  • altered movement coordination
  • trouble walking
  • vertigo and or disequilibrium

Loss of consciousness, headache, and vomiting usually occurs more often in hemorrhagic stroke than in thrombosis because of the increased intracranial pressure from the leaking blood compressing on the brain. If symptoms are maximal at onset, the cause is more likely to be a subarachnoid hemorrhage or an embolic stroke.

Subarachnoid hemorrhage

The symptoms of SAH occur abruptly due to the sudden onset of increased intracranial pressure. Often, patients complain of a sudden, extremely severe and widespread headache. The pain may or may not radiate down into neck and legs. Vomiting may occur soon after the onset of headache. Usually the neurologic exam is nonfocal-meaning no deficits can be identified that attributes to certain areas of the brain-unless the bleeding also occurs into the brain. The combination of headache and vomiting is uncommon in ischemic stroke.

Transient ischemic attack (TIA)
If the symptoms resolve within an hour, or maximum 24 hours, the diagnosis is transient ischemic attack (TIA), which is in essence a mini or brief stroke. This syndrome may be a warning sign, and a large proportion of patients develop strokes in the future. Recent data indicate that there is about a ten to fifteen percent chance of suffering a stroke in the year following a TIA, with half of that risk manifest in the first month, and, further, with much of that risk manifest in the first 48 hours. The chances of suffering an ischemic stroke can be reduced by using aspirin or related compounds such as clopidogrel, which inhibit platelets from aggregating and forming obstructive clots; but, for the same reason, such treatments (slightly) increase the likelihood and effects of hemorrhagic stroke since they impair clotting.

Diagnosis
Stroke is diagnosed through several techniques: a neurological examination, blood tests, CT scans (without contrast enhancements) or MRI scans, Doppler ultrasound, and arteriography.

Physical examination
A systematic review by the Rational Clinical Examination found that acute facial paresis, arm drift, or abnormal speech, are the best findings.

Imaging
For diagnosing ischemic stroke in the emergency setting:
CT scans (without contrast enhancements)
sensitivity= 16%
specificity = 96%
MRI scan
sensitivity = 83%
specificity = 98%
For diagnosing hemorrhagic stroke in the emergency setting:
CT scans (without contrast enhancements)
sensitivity= 89%
specificity = 100%
MRI scan
sensitivity = 81%
specificity = 100%
For detecting hemorrhages, MRI scan is better
Investigation of underlying etiology
If a stroke is confirmed on imaging, various other studies may be performed to determine whether there is a peripheral source of emboli:
an ultrasound/doppler study of the carotid arteries (to detect carotid stenosis)
an electrocardiogram (ECG) and echocardiogram (to identify arrhythmias and resultant clots in the heart which may spread to the brain vessels through the bloodstream)
a Holter monitor study to identify intermittent arrhythmias
an angiogram of the cerebral vasculature (if a bleed is thought to have originated from an aneurysm or arteriovenous malformation)

Treatment

Early assessment
It is important to identify a stroke as early as possible because patients who are treated earlier are more likely to survive and have better recoveries. As many doctors note, “Time lost is brain lost.” If you feel you or someone you know has had a stroke, call the ambulance, even if the symptoms have dissipated or apparently resolved – speed of reaction time is critical, receiving hospital treatment within three hours of the attack to have a hope of avoiding irreversible brain damage.
Some suggest that a simple set of tasks may help those without medical training help to identify someone who is having a stroke, but remember that, while many individuals with stroke may find the following tasks difficult, not all stroke symptoms can be encompassed in the following tasks:
Ask the individual to smile.
Ask the individual to raise both arms and keep them raised.
Ask the individual to speak a simple sentence (coherently). For example, “It is sunny out today.”

In addition, there are cases of individuals who exhibit none of the above, but suddenly experience imbalance while walking or veering to one side which also may be symptomatic of having a stroke.
Stroke can also manifest itself in a myriad of ways, including the transient loss of vision in one or both eyes.
While the ideal hospital for stroke treatment would be a hospital with a dedicated stroke unit, any ER is better than no ER or a distant ER. The faster stroke therapies aspirin) are started for hemorrhagic and ischemic stroke, the greater the chances for recovery from the stroke.
Only detailed physical examination and medical imaging provide information on the presence, type, and extent of stroke.
Studies show that patients treated in hospitals with a dedicated Stroke Team or Stroke Unit and a specialized care program for stroke patients have improved odds of recovery. Again, however, the patient has to get to the ER promptly to get the immediate and appropriate care they need.

Ischemic stroke

As ischemic stroke is due to a thrombus (blood clot) occluding a cerebral artery, a patient is given antiplatelet medication (aspirin, clopidogrel, dipyridamole), or anticoagulant medication (warfarin), dependent on the cause, when this type of stroke has been found. Hemorrhagic stroke must be ruled out with medical imaging, since this therapy would be harmful to patients with that type of stroke.

Whether thrombolysis is performed or not, the following investigations are required:
Stroke symptoms are documented, often using scoring systems such as the National Institutes of Health Stroke Scale, the Cincinnati Stroke Scale, and the Los Angeles Prehospital Stroke Screen. The latter is used by emergency medical technicians (EMTs) to determine whether a patient needs transport to a stroke center.
A CT scan is performed to rule out hemorrhagic stroke
Blood tests, such as a full blood count, coagulation studies (PT/INR and APTT), and tests of electrolytes, renal function, liver function tests and glucose levels are carried out.

Other immediate strategies to protect the brain during stroke include ensuring that blood sugar is as normal as possible (such as commencement of an insulin sliding scale in known diabetics), and that the stroke patient is receiving adequate oxygen and intravenous fluids. The patient may be positioned so that his or her head is flat on the stretcher, rather than sitting up, since studies have shown that this increases blood flow to the brain. Additional therapies for ischemic stroke include aspirin (50 to 325 mg daily), clopidogrel (75 mg daily), and combined aspirin and dipyridamole extended release (25/200 mg twice daily).

It is common for the blood pressure to be elevated immediately following a stroke. Studies indicated that while high blood pressure causes stroke, it is actually beneficial in the emergency period to allow better blood flow to the brain.
If studies show carotid stenosis, and the patient has residual function in the affected side, carotid endarterectomy (surgical removal of the stenosis) may decrease the risk of recurrence. If the stroke has been the result of cardiac arrhythmia (such as atrial fibrillation) with cardiogenic emboli, treatment of the arrhythmia and anticoagulation with warfarin or high-dose aspirin may decrease the risk of recurrence.

Thrombolysis
In increasing numbers of primary stroke centers, pharmacologic thrombolysis (“clot busting”) with the drug Tissue plasminogen activator, tPA, is used to dissolve the clot and unblock the artery. However, the use of tPA in acute stroke is controversial. On one hand, it is endorsed by the American Heart Association and the American Academy of Neurology as the recommended treatment for acute stroke within three hours of onset of symptoms as long as there are not other contraindications (eg, abnormal lab values, high blood pressure, recent surgery…). This position for tPA is based upon the findings of one study (NINDS; N Engl J Med 1995;333:1581-1587.) which showed that tPA improves the chances for a good neurological outcome. When administered within the first 3 hours, 39% of all patients who were treated with tPA had a good outcome at three months, only 26% of placebo controlled patients had a good functional outcome. However, 55% of patients with large strokes developed substantial brain hemorrhage as a complication from being given tPA. tPA is often misconstrued as a “magic bullet” and it is important for patients to be aware that despite the study that supports its use, some of the data were flawed and the safety and efficacy of tPA is controversial. A recent study found the mortality to be higher among patients receiving tPA versus those who did not. Additionally, it is the position of the American Academy of Emergency Medicine that objective evidence regarding the efficacy, safety, and applicability of tPA for acute ischemic stroke is insufficient to warrant its classification as standard of care. (http://www.aaem.org/positionstatements/thrombolytictherapy.shtml)
Until additional evidence clarifies such controversies, physicians are advised to use their discretion when considering its use. Given the cited absence of definitive evidence, AAEM believes it is inappropriate to claim that either use or non-use of intravenous thrombolytic therapy constitutes a standard of care issue in the treatment of stroke.

Mechanical Thrombectomy
Another intervention for acute ischemic stroke is removal of the offending thrombus directly. This is accomplished by inserting a catheter into the femoral artery, directing it up into the cerebral circulation, and deploying a corkscrew-like device to ensnare the clot, which is then withdrawn from the body. In August 2004, based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial, the FDA cleared one such device, called the Merci Retriever.[8][9] Already newer generation devices are being tested in the Multi MERCI trial. Both the MERCI and Multi MERCI trials evaluated the use of mechanical thrombectomy up to 8 hours after onset of symptoms.

Hemorrhagic stroke
Patients with bleeding into (intracerebral hemorrhage) or around the brain (subarachnoid hemorrhage), require neurosurgical evaluation to detect and treat the cause of the bleeding. Anticoagulants and antithrombotics, key in treating ischemic stroke, can make bleeding worse and cannot be used in intracerebral hemorrhage. Patients are monitored and their blood pressure, blood sugar, and oxygenation are kept at optimum levels.

Care and rehabilitation
Stroke rehabilitation is the process by which patients with disabling strokes undergo treatment to help them return to normal life as much as possible by regaining and relearning the skills of everyday living. It also aims to help the survivor understand and adapt to difficulties, prevent secondary complications and educate family members to play a supporting role.
A rehabilitation team is usually multidisciplinary as it involves staff with different skills working together to help the patient. These include nursing staff, physiotherapy, occupational therapy, speech and language therapy, and usually a physician trained in rehabilitation medicine. Some teams may also include psychologists, social workers, and pharmacists since at least one third of the patients manifest post stroke depression.
Good nursing care is fundamental in maintaining skin care, feeding, hydration, positioning, and monitoring vital signs such as temperature, pulse, and blood pressure. Stroke rehabilitation begins almost immediately.
For most stroke patients, physical therapy (PT) and occupational therapy (OT) are the cornerstones of the rehabilitation process. Repetitive active practice and biofeedback are very useful to improve motor learning and recovery. Often, assistive technology such as a wheelchair, walkers, canes, and orthesis may be beneficial. PT and OT have overlapping areas of working but their main attention fields are; PT involves re-learning functions as transferring, walking and other gross motor functions. OT focusses on exercises and training to help relearn everyday activities known as the Activities of daily living (ADLs) such as eating, drinking, dressing, bathing, cooking, reading and writing, and toileting. Speech and language therapy is appropriate for patients with problems understanding speech or written words, problems forming speech and problems with eating (swallowing).
Patients may have particular problems, such as complete or partial inability to swallow, which can cause swallowed material to pass into the lungs and cause aspiration pneumonia. The condition may improve with time, but in the interim, a nasogastric tube may be inserted, enabling liquid food to be given directly into the stomach. If swallowing is still unsafe after a week, then a percutaneous endoscopic gastrostomy (PEG) tube is passed and this can remain indefinitely.
Stroke rehabilitation should be started as immediately as possible and can last anywhere from a few days to several months. Most return of function is seen in the first few days and weeks, and then improvement falls off with the “window” considered officially by U.S. state rehabilitation units and others to be closed after six months, with little chance of further improvement. However, patients have been known to continue to improve for years, regaining and strengthening abilities like writing, walking, running, and talking. Daily rehabilitation exercises should continue to be part of the stroke patient´s routine. Complete recovery is unusual but not impossible and most patients will improve to some extent : a correct diet and exercise are known to help the brain to self-recover. Stem-cell research in the coming years may provide new concepts as to how the “plasticity” of the brain may help it to repair itself.

Prognosis

Disability affects 75% of stroke survivors enough to decrease their employability. Stroke can affect patients physically, mentally, emotionally, or a combination of the three. The results of stroke vary widely depending on size and location of the lesion. Dysfunctions correspond to areas in the brain that have been damaged.
Some of the physical disabilities that can result from stroke include paralysis, numbness, pressure sores, pneumonia, incontinence, apraxia (inability to perform learned movements), difficulties carrying out daily activities, appetite loss, vision loss, and pain. If the stroke is severe enough, coma or death can result.
Emotional problems resulting from stroke can result from direct damage to emotional centers in the brain or from frustration and difficulty adapting to new limitations. Post-stroke emotional difficulties include anxiety, panic attacks, flat affect (failure to express emotions), mania, apathy, and psychosis.
30 to 50% of stroke survivors suffer post stroke depression (Post stroke depression), which is characterized by lethargy, irritability, sleep disturbances, lowered self esteem, and withdrawal. Depression can reduce motivation and worsen outcome, but can be treated with antidepressants.
Emotional lability, another consequence of stroke, causes the patient to switch quickly between emotional highs and lows and to express emotions inappropriately, for instance with an excess of laughing or crying with little or no provocation. While these expressions of emotion usually correspond to the patient’s actual emotions, a more severe form of emotional lability causes patients to laugh and cry pathologically, without regard to context or emotion. Some patients show the opposite of what they feel, for example crying when they are happy. Emotional lability occurs in about 20% of stroke patients.
Cognitive deficits resulting from stroke include perceptual disorders, speech problems, dementia, and problems with attention and memory. A stroke sufferer may be unaware of his or her own disabilities, a condition called anosognosia. In a condition called hemispatial neglect, a patient is unable to attend to anything on the side of space opposite to the damaged hemisphere. Up to 10% of all stroke patients develop seizures, most commonly in the week subsequent to the event; the severity of the stroke increases the likelihood of a seizure.

Risk factors and prevention

Prevention of stroke can work at various levels including:
primary prevention – the reduction of risk factors across the board, by public health measures such as reducing smoking and the other behaviours that increase risk; secondary prevention – actions taken to reduce the risk in those who already have disease or risk factors that may have been identified through screening; and tertiary prevention – actions taken to reduce the risk of complications (including further strokes) in people who have already had a stroke. The most important modifiable risk factors for stroke are hypertension, heart disease, diabetes, and cigarette smoking. Other risks include heavy alcohol consumption (see Alcohol consumption and health), high blood cholesterol levels, illicit drug use, and genetic or congenital conditions. Family members may have a genetic tendency for stroke or share a lifestyle that contributes to stroke. Higher levels of Von Willebrand factor are more common amongst people who have had ischemic stroke for the first time. The results of this study found that the only significant genetic factor was the person’s blood type. Having had a stroke in the past greatly increases one’s risk of future strokes. One of the most significant stroke risk factors is advanced age. 95% of strokes occur in people age 45 and older, and two-thirds of strokes occur in those over the age of 65. A person’s risk of dying if he or she does have a stroke also increases with age. However, stroke can occur at any age, including in fetuses.
Sickle cell anemia, which can cause blood cells to clump up and block blood vessels, also increases stroke risk. Stroke is the second leading killer of people under 20 who suffer from sickle-cell anemia.
Men are 1.25 times more likely to suffer CVAs than women, yet 60% of deaths from stroke occur in women. Since women live longer, they are older on average when they have their strokes and thus more often killed (NIMH 2002).[19] Some risk factors for stroke apply only to women. Primary among these are pregnancy, childbirth, menopause and the treatment thereof (HRT). Stroke seems to run in some families.
Prevention is an important public health concern. Identification of patients with treatable risk factors for stroke is paramount. Treatment of risk factors in patients who have already had strokes (secondary prevention) is also very important as they are at high risk of subsequent events compared with those who have never had a stroke. Medication or drug therapy is the most common method of stroke prevention. Aspirin (usually at a low dose of 75 mg) is recommended for the primary and secondary prevention of stroke. Treating hypertension, diabetes mellitus, smoking cessation, control of hypercholesterolemia, physical exercise, and avoidance of illicit drugs and excessive alcohol consumption are all recommended ways of reducing the risk of stroke.
In patients who have strokes due to abnormalities of the heart, such as atrial fibrillation, anticoagulation with medications such as warfarin is often necessary for stroke prevention. Procedures such as carotid endarterectomy or carotid angioplasty can be used to remove significant atherosclerotic narrowing (stenosis) of the carotid artery, which supplies blood to the brain. These procedures have been shown to prevent stroke in certain patients, especially where carotid stenosis leads to ischemic events such as transient ischemic attack. (The value and role of carotid artery ultrasound scanning in screening has yet to be established.)

Pathophysiology

Ischemic stroke occurs due to a loss of blood supply to part of the brain, initiating the Ischemic cascade. Brain tissue ceases to function if deprived of oxygen for more than 60 to 90 seconds and after a few hours will suffer irreversible injury possibly leading to death of the tissue, i.e., infarction. Atherosclerosis may disrupt the blood supply by narrowing the lumen of blood vessels leading to a reduction of blood flow, by causing the formation of blood clots within the vessel, or by releasing showers of small emboli through the disintegration of atherosclerotic plaques. Embolic infarction occurs when emboli formed elsewhere in the circulatory system, typically in the heart as a consequence of atria fibriliation, or in the carotid arteries. These break off, enter the cerebral circulation, then lodge in and occlude brain blood vessels.

Due to collateral circulation, within the region of brain tissue affected by ischemia there is a spectrum of severity. Thus, part of the tissue may immediately die while other parts may only be injured and could potentially recover. The ischemia area where tissue might recover is referred to as the ischemic penumbra.
As oxygen or glucose becomes depleted in ischemic brain tissue, the production of high energy phosphate compounds such as adenine triphosphate (ATP) fails leading to failure of energy dependent processes necessary for tissue cell survival. This sets off a series of interrelated events that result in cellular injury and death. These include the failure of mitochondria, which can lead further toward energy depletion and may trigger cell death due to apoptosis. Other processes include the loss of membrane ion pump function leading to electrolyte imbalances in brain cells. There is also the release of excitatory neurotransmitters, which have toxic effects in excessive concentrations.
Ischaemia also induces production of oxygen free radicals and other reactive oxygen species. These react with and damage a number of cellular and extracellular elements. Damage to the blood vessel lining or endothelium is particularly important. In fact, many antioxidant neuroprotectants such as uric acid and NXY-059 work at the level of the endothelium and not in the brain per se. Free radicals also directly initiate elements of the apoptosis cascade by means of redox signaling . These processes are the same for any type of ischemic tissue and are referred to collectively as the ischemic cascade. However, brain tissue is especially vulnerable to ischemia since it has little respiratory reserve and is completely dependent on aerobic metabolism, unlike most other organs. Brain tissue survival can be improved to some extent if one or more of these processes is inhibited. Drugs that scavenge Reactive oxygen species, inhibit apoptosis, or inhibit excitotoxic neurotransmitters, for example, have been shown experimentally to reduce tissue injury due to ischemia. Agents that work in this way are referred to as being neuroprotective. Until recently, human clinical trials with neuroprotective agents have failed, with the probable exception of deep barbiturate coma. However, more recently NXY-059, the disulfonyl derivative of the radical-scavenging spintrap phenylbutylnitrone, is reported be neuroprotective in stroke. This agent appears to work at the level of the blood vessel lining or endothelium. Unfortunately, after producing favorable results in one large-scale clinical trial, a second trial failed to show favorable results.
In addition to injurious effects on brain cells, ischemia and infarction can result in loss of structural integrity of brain tissue and blood vessels, partly through the release of matrix metalloproteases, which are zinc- and calcium-dependent enzymes that break down collagen, hyaluronic acid, and other elements of connective tissue. Other proteases also contribute to this process. The loss of vascular structural integrity results in a breakdown of the protective blood brain barrier that contributes to cerebral edema, which can cause secondary progression of the brain injury.
As is the case with any type of brain injury, the immune system is activated by cerebral infarction and may under some circumstances exacerbate the injury caused by the infarction. Inhibition of the inflammatory response has been shown experimentally to reduce tissue injury due to cerebral infarction, but this has not proved out in clinical studies.
Hemorrhagic strokes result in tissue injury by causing compression of tissue from an expanding hematoma or hematomas. This can distort and injure tissue. In addition, the pressure may lead to a loss of blood supply to affected tissue with resulting infarction, and the blood released by brain hemorrhage appears to have direct toxic effects on brain tissue and vasculature.

Epidemiology

Stroke will soon be the most common cause of death worldwide. Stroke is the third leading cause of death in the Western world, after heart disease and cancer[22], and causes 10% of world-wide deaths. The incidence of stroke increases exponentially from 30 years of age, and etiology varies by age.

History

Hippocrates (460 to 370 BC) was first to describe the phenomenon of sudden paralysis. Apoplexy, from the Greek word meaning “struck down with violence,” first appeared in Hippocratic writings to describe this phenomenon.
In 1658, in his Apoplexia, Johann Jacob Wepfer (1620-1695) identified the cause of hemorrhagic stroke when he suggested that people who had died of apoplexy had bleeding in their brains. Wepfer also identified the main arteries supplying the brain, the vertebral and carotid arteries, and identified the cause of ischemic stroke when he suggested that apoplexy might be caused by a blockage to those vessels.
The word stroke was used as a synonym for apoplectic seizure as early as 1599, and is a fairly literal translation of the Greek term.

Hand Anatomy

drawing of Hand Anatomy

Introduction

Few structures of the human anatomy are as unique as the hand. The hand needs to be mobile in order to position the fingers and thumb. Adequate strength forms the basis for normal hand function. The hand also must be coordinated to perform fine motor tasks with precision. The structures that form and move the hand require proper alignment and control in order for normal hand function to occur.

This guide will help you understand

  • what parts make up the hand
  • how those parts work together

Important Structures

The important structures of the hand can be divided into several
categories. These include

  • bones and joints
  • ligaments and tendons
  • muscles
  • nerves
  • blood vessels

The front, or palm-side, of the hand is referred to as the palmar side. The back of the hand is called the dorsal side.

Bones and Joints

There are 27 bones within the wrist and hand. The wrist itself contains eight small bones, called carpals. The carpals join with the two forearm bones, the radius and ulna, forming the wrist joint. Further into the palm, the carpals connect to the metacarpals. There are five metacarpals forming the palm of the hand. One metacarpal connects to each finger and thumb. Small bone shafts called phalanges line up to form each finger and thumb.

The main knuckle joints are formed by the connections of the phalanges to the metacarpals. These joints are called the metacarpophalangeal joints (MCP joints). The MCP joints work like a hinge when you bend and straighten your fingers and thumb.

Distal and Proximal Joints

The three phalanges in each finger are separated by two joints, called interphalangeal joints (IP joints). The one closest to the MCP joint (knuckle) is called the proximal IP joint (PIP joint). The joint near the end of the finger is called the distal IP joint (DIP joint). The thumb only has one IP joint between the two thumb phalanges. The IP joints of the digits also work like hinges when you bend and straighten your fingers and thumb.

The joints of the hand, fingers, and thumb are covered on the ends with articular cartilage. This white, shiny material has a rubbery consistency. The function of articular cartilage is to absorb shock and provide an extremely smooth surface to facilitate motion. There is articular cartilage essentially everywhere that two bony surfaces move against one another, or articulate.

Ligaments and Tendons

Ligaments are tough bands of tissue that connect bones together. Two important structures, called collateral ligaments, are found on either side of each finger and thumb joint. The function of the collateral ligaments is to prevent abnormal sideways bending of each joint.

In the PIP joint (the middle joint between the main knuckle and the DIP joint), the strongest ligament is the volar plate. This ligament connects the proximal phalanx to the middle phalanx on the palm side of the joint. The ligament tightens as the joint is straightened and keeps the PIP joint from bending back too far (hyperextending). Finger deformities can occur when the volar plate loosens from disease or injury.

The tendons that allow each finger joint to straighten are called the extensor tendons. The extensor tendons of the fingers begin as muscles that arise from the backside of the forearm bones. These muscles travel towards the hand, where they eventually connect to the extensor tendons before crossing over the back of the wrist joint. As they travel into the fingers, the extensor tendons become the extensor hood. The extensor hood flattens out to cover the top of the finger and sends out branches on each side that connect to the bones in the middle and end of the finger.

The place where the extensor tendon attaches to the middle phalanx is called the central slip. When the extensor muscles contract, they tug on the extensor tendon and straighten the finger. Problems occur when the central slip is damaged, as can happen with a tear.

Muscles

Many of the muscles that control the hand start at the elbow or forearm. They run down the forearm and cross the wrist and hand. Some control only the bending or straightening of the wrist. Others influence motion of the fingers or thumb. Many of these muscles help position and hold the wrist and hand while the thumb and fingers grip or perform fine motor actions.

Most of the small muscles that work the thumb and pinky finger start on the carpal bones. These muscles connect in ways that allow the hand to grip and hold. Two muscles allow the thumb to move across the palm of the hand, an important function called thumb opposition.

The smallest muscles that originate in the wrist and hand are called the intrinsic muscles. The intrinsic muscles guide the fine motions of the fingers by getting the fingers positioned and holding them steady during hand activities.

Nerves

All of the nerves that travel to the hand and fingers begin together at the shoulder: the radial nerve, the median nerve, and the ulnar nerve. These nerves carry signals from the brain to the muscles that move the arm, hand, fingers, and thumb. The nerves also carry signals back to the brain about sensations such as touch, pain, and temperature.

Median, Ulnar and Radial nerves

The radial nerve runs along the thumb-side edge of the forearm. It wraps around the end of the radius bone toward the back of the hand. It gives sensation to the back of the hand from the thumb to the third finger. It also supplies the back of the thumb and just beyond the main knuckle of the back surface of the ring and middle fingers.

The median nerve travels through a tunnel within the wrist called the carpal tunnel. This nerve gives sensation to the thumb, index finger, long finger, and half of the ring finger. It also sends a nerve branch to control the thenar muscles of the thumb. The thenar muscles help move the thumb and let you touch the pad of the thumb to the tips each of each finger on the same hand, a motion called opposition.

The ulnar nerve travels through a separate tunnel, called Guyon’s canal. This tunnel is formed by two carpal bones, the pisiform and hamate, and the ligament that connects them. After passing through the canal, the ulnar nerve branches out to supply feeling to the little finger and half the ring finger. Branches of this nerve also supply the small muscles in the palm and the muscle that pulls the thumb toward the palm.

The nerves that travel to the hand are subject to problems. Constant bending and straightening of the wrist and fingers can lead to irritation or pressure on the nerves within their tunnels and cause problems such as pain, numbness, and weakness in the hand, fingers, and thumb.

Blood Vessels

Traveling along with the nerves are the large vessels that supply the hand with blood. The largest artery is the radial artery that travels across the front of the wrist, closest to the thumb. The radial artery is where the pulse is taken in the wrist. The ulnar artery runs next to the ulnar nerve through Guyon’s canal (mentioned earlier). The ulnar and radial arteries arch together within the palm of the hand, supplying the front of the hand, fingers, and thumb. Other arteries travel across the back of the wrist to supply the back of the hand, fingers, and thumb.

Summary

The hand is formed of numerous structures that have an important role in normal hand function. Conditions that change the way these structures work can greatly impact whether the hand functions normally. When our hands are free of problems, it’s easy to take the complex anatomy of the hand for granted.

Motor Skill

A motor skill is a skill that requires an organism to utilize their skeletal muscles effectively. Motor skills and motor control depend upon the proper functioning of the brain, skeleton, joints, and nervous system. Most motor skills are learned in early childhood, although disabilities can affect motor skills development. Motor development is the development of action and coordination of one’s limbs, as well as the development of strength, posture control, balance, and perceptual skills.
Motor skills are divided into two parts:

  • Gross motor skills include lifting one’s head, rolling over, sitting up, balancing, crawling, and walking. Gross motor development usually follows a pattern. Generally large muscles develop before smaller ones. Thus, gross motor development is the foundation for developing skills in other areas (such as fine motor skills). Development also generally moves from top to bottom. The first thing a baby usually learns is to control its head.
  • Fine motor skills include the ability to manipulate small objects, transfer objects from hand to hand, and various hand-eye coordination tasks. Fine motor skills may involve the use of very precise motor movement in order to achieve an especially delicate task. Some examples of fine motor skills are using the pincer grasp (thumb and forefinger) to pick up small objects, cutting, coloring and writing, and threading beads. Fine motor development refers to the development of skills involving the smaller muscle groups.

Fine Motor Skills

Fine motor skills can be defined as coordination of small muscle movements which occur e.g., in the fingers, usually in coordination with the eyes. In application to motor skills of hands (and fingers) the term dexterity is commonly used.

The abilities which involve the use of hands, develop over time, starting with primitive gestures such as grabbing at objects to more precise activities that involve precise hand-eye coordination. Fine motor skills are skills that involve a refined use of the small muscles controlling the hand, fingers, and thumb. The development of these skills allows one to be able to complete tasks such as writing, drawing, and buttoning.

During the infant and toddler years, children develop basic grasping and manipulation skills, which are refined during the preschool years. The preschooler becomes quite adept in self-help, construction, holding grips, and bimanual control tasks requiring the use of both hands.

Motor Learning

Motor learning is the process of improving the motor skills, the smoothness and accuracy of movements. It is obviously necessary for complicated movements such as speaking, playing the piano and climbing trees, but it is also important for calibrating simple movements like reflexes, as parameters of the body and environment change over time. The cerebellum and basal ganglia are critical for motor learning.

As a result of the universal need for properly calibrated movement, it is not surprising that the cerebellum and basal ganglia are widely conserved across vertebrates from fish to humans.

Although motor learning is capable of achieving very skilled behavior, much has been learned from studies of simple behaviors. These behaviors include eyeblink conditioning, motor learning in the vestibulo-ocular reflex, and birdsong. Research on Aplysia californica, the sea slug, has yielded detailed knowledge of the cellular mechanisms of a simple form of learning.

An interesting type of motor learning occurs during operation of a brain- computer interface. For example, Mikhail Lebedev, Miguel Nicolelis and their colleagues recently demonstrated cortical plasticity that resulted in incorporation of an external actuator controlled through a brain-machine interface into the subject’s neural representation.

Parkinson’s disease

Parkinson’s disease (also known as Parkinson disease or PD) is a degenerative disorder of the central nervous system that often impairs the sufferer’s motor skills and speech.

Parkinson’s disease belongs to a group of conditions called movement disorders. It is characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia) and, in extreme cases, a loss of physical movement (akinesia). The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. Secondary symptoms may include high level cognitive dysfunction and subtle language problems. PD is both chronic and progressive.

PD is the most common cause of Parkinsonism, a group of similar symptoms. PD is also called “primary parkinsonism” or “idiopathic PD” (“idiopathic” meaning of no known cause). While most forms of parkinsonism are idiopathic, there are some cases where the symptoms may result from toxicity, drugs, genetic mutation, head trauma, or other medical disorders.

History

Symptoms of Parkinson’s disease have been known and treated since ancient times. However, it was not formally recognized and its symptoms were not documented until 1817 in An Essay on the Shaking Palsy by the British physician James Parkinson. Parkinson’s disease was then known as paralysis agitans, the term “Parkinson’s disease” being coined later by Jean-Martin Charcot. The underlying biochemical changes in the brain were identified in the 1950s due largely to the work of Swedish scientist Arvid Carlsson, who later went on to win a Nobel Prize. L-dopa entered clinical practice in 1967, and the first study reporting improvements in patients with Parkinson’s disease resulting from treatment with L-dopa was published in 1968.

Symptoms

Parkinson disease affects movement (motor symptoms). Typical other symptoms include disorders of mood, behavior, thinking, and sensation (non-motor symptoms). Individual patients’ symptoms may be quite dissimilar and progression of the disease is also distinctly individual.

Motor symptoms

The cardinal symptoms are:
  • tremor: normally 4-7Hz tremor, maximal when the limb is at rest, and decreased with voluntary movement. It is typically unilateral at onset. This is the most apparent and well-known symptom, though an estimated 30% of patients have little perceptible tremor; these are classified as akinetic-rigid.
  • rigidity: stiffness; increased muscle tone. In combination with a resting tremor, this produces a ratchety, “cogwheel” rigidity when the limb is passively moved.
  • bradykinesia/akinesia: respectively, slowness or absence of movement. Rapid, repetitive movements produce a dysrhythmic and decremental loss of amplitude. Also “dysdiadokinesia”, which is the loss of ability to perform rapid alternating movements
  • postural instability: failure of postural reflexes, which leads to impaired balance and falls.

Other motor symptoms include:

  • Gait and posture disturbances:
  • Shuffling: gait is characterized by short steps, with feet barely leaving the ground, producing an audible shuffling noise. Small obstacles tend to trip the patient
  • Decreased arm swing: a form of bradykinesia
  • Turning “en bloc”: rather than the usual twisting of the neck and trunk and pivoting on the toes, PD patients keep their neck and trunk rigid, requiring multiple small steps to accomplish a turn.
  • Stooped, forward-flexed posture. In severe forms, the head and upper shoulders may be bent at a right angle relative to the trunk (camptocormia).
  • Festination: a combination of stooped posture, imbalance, and short steps. It leads to a gait that gets progressively faster and faster, often ending in a fall.
  • Gait freezing: “freezing” is another word for akinesia, the inability to move. Gait freezing is characterized by inability to move the feet, especially in tight, cluttered spaces or when initiating gait.
  • Dystonia (in about 20% of cases): abnormal, sustained, painful twisting muscle contractions, usually affecting the foot and ankle, characterized by toe flexion and foot inversion, interfering with gait. However, dystonia can be quite generalized, involving a majority of skeletal muscles; such episodes are acutely painful and completely disabling.
  • Speech and swallowing disturbances
  • Hypophonia: soft speech. Speech quality tends to be soft, hoarse, and monotonous. Some people with Parkinson’s disease claim that their tongue is “heavy”.
  • Festinating speech: excessively rapid, soft, poorly-intelligible speech.
  • Drooling: most likely caused by a weak, infrequent swallow and stooped posture.
  • Non-motor causes of speech/language disturbance in both expressive and receptive language: these include decreased verbal fluency and cognitive disturbance especially related to comprehension of emotional content of speech and of facial expression.
  • Dysphagia: impaired ability to swallow. Can lead to aspiration, pneumonia.

Other motor symptoms:

  • fatigue (up to 50% of cases);
  • masked faces (a mask-like face also known as hypomimia), with infrequent blinking;
  • difficulty rolling in bed or rising from a seated position;
  • micrographia (small, cramped handwriting);
  • impaired fine motor dexterity and motor coordination;
  • impaired gross motor coordination;
  • Poverty of movement: overall loss of accessory movements, such as decreased arm swing when walking, as well as spontaneous movement.

Non-motor symptoms:

Mood disturbances

  • Estimated prevalence rates of depression vary widely according to the population sampled and methodology used. Reviews of depression estimate its occurrence in anywhere from 20-80% of cases. Estimates from community samples tend to find lower rates than from specialist centres. Most studies use self-report questionnaires such as the Beck Depression Inventory, which may overinflate scores due to physical symptoms. Studies using diagnostic interviews by trained psychiatrists also report lower rates of depression.
  • More generally, there is an increased risk for any individual with depression to go on to develop Parkinson’s disease at a later date.
  • 70% of individuals with Parkinson’s disease diagnosed with pre-existing depression go on to develop anxiety. 90% of Parkinson’s disease patients with pre-existing anxiety subsequently develop depression; apathy or abulia.

Cognitive disturbances

  • Slowed reaction time; both voluntary and involuntary motor responses are significantly slowed.
  • Executive dysfunction, characterized by difficulties in: differential allocation of attention, impulse control, set shifting, prioritizing, evaluating the salience of ambient data, interpreting social cues, and subjective time awareness. This complex is present to some degree in most Parkinson’s patients; it may progress to:
  • Dementia: a later development in approximately 20-40% of all patients, typically starting with slowing of thought and progressing to difficulties with abstract thought, memory, and behavioral regulation. Hallucinations, delusions and paranoia may develop.
  • Short term memory loss; procedural memory is more impaired than declarative memory. Prompting elicits improved recall.
  • medication effects: some of the above cognitive disturbances are improved by dopaminergic medications, while others are actually worsened.

Sleep disturbances

  • Excessive daytime somnolence
  • Initial, intermediate, and terminal insomnia
  • Disturbances in REM sleep: disturbingly vivid dreams, and REM Sleep Disorder, characterized by acting out of dream content – can occur years prior to diagnosis .

Sensation disturbances

  • impaired visual contrast sensitivity, spatial reasoning, colour discrimination, convergence insufficiency (characterized by double vision) and oculomotor control
  • dizziness and fainting; usually attributable orthostatic hypotension, a failure of the autonomous nervous system to adjust blood pressure in response to changes in body position
  • impaired proprioception (the awareness of bodily position in three-dimensional space)
  • reduction or loss of sense of smell (microsmia or anosmia) – can occur years prior to diagnosis,
  • pain: neuropathic, muscle, joints, and tendons, attributable to tension, dystonia, rigidity, joint stiffness, and injuries associated with attempts at accommodation

Autonomic disturbances

  • oily skin and seborrheic dermatitis.
  • urinary incontinence, typically in later disease progression
  • nocturia (getting up in the night to pass urine) – up to 60% of cases
  • constipation and gastric dysmotility that is severe enough to endanger comfort and even health
  • altered sexual function: characterized by profound impairment of sexual arousal, behavior, orgasm, and drive is found in mid and late Parkinson disease. Current data addresses male sexual function almost exclusively
  • weight loss, which is significant over a period of ten years – 8% of body weight lost compared with 1% in a control group.

Diagnosis

 

MRI brain scans

 

18F PET scan shows decreased dopamine activity in the basal ganglia, a pattern which aids in diagnosing Parkinson’s disease. There are currently no blood or laboratory tests that have been proven to help in diagnosing PD. Therefore the diagnosis is based on medical history and a neurological examination. The disease can be difficult to diagnose accurately. The Unified Parkinson’s Disease Rating Scale is the primary clinical tool used to assist in diagnosis and determine severity of PD. Indeed, only 75% of clinical diagnoses of PD are confirmed at autopsy.[12] Early signs and symptoms of PD may sometimes be dismissed as the effects of normal aging. The physician may need to observe the person for some time until it is apparent that the symptoms are consistently present. Usually doctors look for shuffling of feet and lack of swing in the arms. Doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases. However, CT and MRI brain scans of people with PD usually appear normal.

Descriptive epidemiology

Parkinson’s disease is widespread, with a prevalence estimated between 100 and 250 cases per 100,000 in North America; and was 1.7 per hundred (95% CI 1.5-1.9) in China (for those aged > or =65 years) . Because prevalence rates can be affected by socio-ecomically driven differences in survival as well as biased by survey technique problems , incidence is a more sensitive indicator : rates to a high of 20.5 per 100,000 in the U.S.A. . A study carried out in northern California observed an age and sex corrected incidence.

Cases of PD are reported at all ages, though it is uncommon in people younger than 40. The average age at which symptoms begin in the U.S.A. is 58-60; it is principally a disease of the elderly. It occurs in all parts of the world, but appears to be more common in people of European ancestry than in those of African ancestry. Those of East Asian ancestry have an intermediate risk. It is more common in rural than urban areas and men are affected more often than women in most countries.

Related diseases

There are other disorders that are called Parkinson-plus diseases. These include:

  • Multiple system atrophy (MSA)
  • Progressive supranuclear palsy (PSP)
  • Corticobasal degeneration (CBD)

Some people include dementia with Lewy bodies (DLB) as one of the ‘Parkinson-plus’ syndromes. Although idiopathic Parkinson’s disease patients also have Lewy bodies in their brain tissue, the distribution is denser and more widespread in DLB. Even so, the relationship between Parkinson disease, Parkinson disease with dementia (PDD) and dementia with Lewy bodies (DLB) might be most accurately conceptualized as a spectrum, with a discrete area of overlap between each of the three disorders. The natural history and role of Lewy bodies is very little understood.

Patients often begin with typical Parkinson’s disease symptoms which persist for some years; these Parkinson-plus diseases can only be diagnosed when other symptoms become apparent with the passage of time. These Parkinson-plus diseases usually progress more quickly than typical ideopathic Parkinson disease. The usual anti-Parkinson’s medications are typically either less effective or not effective at all in controlling symptoms; patients may be exquisitely sensitive to neuroleptic medications like haloperidol. Additionally, the cholinesterase inhibiting medications have shown preliminary efficacy in treating the cognitive, psychiatric, and behavioral aspects of the disease, so correct differential diagnosis is important.

Wilson’s disease (hereditary copper accumulation) may present with parkinsonistic features; young patients presenting with parkinsonism may be screened for this rare condition. Essential tremor is often mistaken for Parkinson’s disease but usually lacks all features besides tremor. Torsion dystonia is another disease related to Parkinson’s disease.

Pathology

 

Pathology

 

Dopaminergic pathways of the human brain in normal condition (left) and Parkinson’s disease (right). Red Arrows indicate suppression of the target, blue arrows indicate stimulation of target structure.

The symptoms of Parkinson’s disease result from the loss of pigmented dopamine-secreting (dopaminergic) cells, secreted by the same cells, in the pars compacta region of the substantia nigra (literally “black substance”). These neurons project to the striatum and their loss leads to alterations in the activity of the neural circuits within the basal ganglia that regulate movement, in essence an inhibition of the direct pathway and excitation of the indirect pathway.

The direct pathway facilitates movement and the indirect pathway inhibits movement, thus the loss of these cells leads to a hypokinetic movement disorder. The lack of dopamine results in increased inhibition of the ventral lateral nucleus of the thalamus, which sends excitatory projections to the motor cortex, thus leading to hypokinesia.

There are four major dopamine pathways in the brain; the nigrostriatal pathway, referred to above, mediates movement and is the most conspicuously affected in early Parkinson’s disease. The other pathways are the mesocortical, the mesolimbic, and the tuberoinfundibular. These pathways are associated with, respectively: volition and emotional responsiveness; desire, initiative, and reward; and sensory processes and maternal behavior. Disruption of dopamine along the non-striatal pathways likely explains much of the neuropsychiatric pathology associated with Parkinson’s disease.

The mechanism by which the brain cells in Parkinson’s are lost may consist of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. The alpha-synuclein-ubiquitin complex cannot be directed to the proteosome. This protein accumulation forms proteinaceous cytoplasmic inclusions called Lewy bodies. Latest research on pathogenesis of disease has shown that the death of dopaminergic neurons by alpha-synuclein is due to a defect in the machinery that transports proteins between two major cellular organelles – the endoplasmic reticulum (ER) and the Golgi apparatus. Certain proteins like Rab1 may reverse this defect caused by alpha-synuclein in animal models.

Excessive accumulations of iron, which are toxic to nerve cells, are also typically observed in conjunction with the protein inclusions. Iron and other transition metals such as copper bind to neuromelanin in the affected neurons of the substantia nigra. So, neuromelanin may be acting as a protective agent. Alternately, neuromelanin (an electronically active semiconductive polymer) may play some other role in neurons.[18] That is, coincidental excessive accumulation of transition metals, etc. on neuromelanin may figure in the differential dropout of pigmented neurons in Parkinsonism. The most likely mechanism is generation of reactive oxygen species.

Iron induces aggregation of synuclein by oxidative mechanisms. Similarly, dopamine and the byproducts of dopamine production enhance alpha-synuclein aggregation. The precise mechanism whereby such aggregates of alpha-synuclein damage the cells is not known. The aggregates may be merely a normal reaction by the cells as part of their effort to correct a different, as-yet unknown, insult. Based on this mechanistic hypothesis, a transgenic mouse model of Parkinson’s has been generated by introduction of human wild-type alpha-synuclein into the mouse genome under control of the platelet-derived-growth factor-beta promoter.

Causes of Parkinson’s disease

Most people with Parkinson’s disease are described as having idiopathic Parkinson’s disease (having no specific cause). There are far less common causes of Parkinson’s disease including genetic, toxins, head trauma, and drug-induced Parkinson’s disease.

Genetic

In recent years, a number of specific genetic mutations causing Parkinson’s disease have been discovered, including in certain populations (Contursi, Italy). These account for a small minority of cases of Parkinson’s disease. Somebody who has Parkinson’s disease is more likely to have relatives that also have Parkinson’s disease. However, this does not mean that the disorder has been passed on genetically.
Genetic forms that have been identified include:

  • external links in this section are to OMIM
  • PARK1 (OMIM #168601), caused by mutations in the SNCA gene, which codes for the protein alpha-synuclein. PARK1 causes autosomal dominant Parkinson disease. So-called PARK4 (OMIM #605543) is probably caused by triplication of SNCA.[22]
  • PARK2 (OMIM *602544), caused by mutations in protein parkin. Parkin mutations may be one of the most common known genetic causes of early-onset Parkinson disease. In one study, of patients with onset of Parkinson disease prior to age 40 (10% of all PD patients), 18% had parkin mutations, with 5% homozygous mutations.[23] Patients with an autosomal recessive family history of parkinsonism are much more likely to carry parkin mutations if age at onset is less than 20 (80% vs. 28% with onset over age 40).[24]Patients with parkin mutations (PARK2) do not have Lewy bodies. Such patients develop a syndrome that closely resembles the sporadic form of PD; however, they tend to develop symptoms at a much younger age.
  • PARK3 (OMIM %602404), mapped to 2p, autosomal dominant, only described in a few kindreds.
  • PARK5, caused by mutations in the UCHL1 gene (OMIM +191342) which codes for the protein ubiquitin carboxy-terminal hydrolase L1
  • PARK6 (OMIM #605909), caused by mutations in PINK1 (OMIM *608309) which codes for the protein PTEN-induced putative kinase 1.
  • PARK7 (OMIM #606324), caused by mutations in DJ-1 (OMIM 602533)
  • PARK8 (OMIM #607060), caused by mutations in LRRK2 which codes for the protein dardarin. In vitro, mutant LRRK2 causes protein aggregation and cell death, possibly through an interaction with parkin.[25] LRRK2 mutations, of which the most common is G2019S, cause autosomal dominant Parkinson disease, with a penetrance of nearly 100% by age 80.[26] G2019S is the most common known genetic cause of Parkinson disease, found in 1-6% of U.S. and European PD patients.[27] It is especially common in Ashkenazi Jewish patients, with a prevalence of 29.7% in familial cases and 13.3% in sporadic.[28]
  • PARK9 (OMIM #606693), gene locus 1p36. Caused by mutations in the ATP13A2 gene, and also known as Kufor-Rakeb Syndrome. PARK9 may be allelic to PARK6.
  • PARK10 (OMIM %606852), gene map locus 1p.
  • PARK11 (OMIM %607688), gene map locus 2q36-37. However, this gene locus has conflicting data, and may not have significance.
  • PARK12 (OMIM %300557), maps to the X chromosome.
  • PARK13 (OMIM #610297), gene map locus 2p12.

Toxins

One theory holds that the disease may result in many or even most cases from the combination of a genetically determined vulnerability to environmental toxins along with exposure to those toxins. This hypothesis is consistent with the fact that Parkinson’s disease is not distributed homogeneously throughout the population: rather, its incidence varies geographically. It would appear that incidence varies by time as well, for although the later stages of untreated PD are distinct and readily recognizable, the disease was not remarked upon until the beginnings of the Industrial Revolution, and not long thereafter become a common observation in clinical practice. The toxins most strongly suspected at present are certain pesticides and transition-series metals such as manganese or iron, especially those that generate reactive oxygen species, and or bind to neuromelanin, as originally suggested by G.C. Cotzias. In the Cancer Prevention Study II Nutrition Cohort, a longitudinal investigation, individuals who were exposed to pesticides had a 70% higher incidence of PD than individuals who were not exposed.

MPTP is used as a model for Parkinson’s as it can rapidly induce parkinsonian symptoms in human beings and other animals, of any age. MPTP was notorious for a string of Parkinson’s disease cases in California in 1982 when it contaminated the illicit production of the synthetic opiate MPPP. Its toxicity likely comes from generation of reactive oxygen species through tyrosine hydroxylation.

Other toxin-based models employ PCBs, paraquat (a herbicide) in combination with maneb (a fungicide) rotenone (an insecticide), and specific organochlorine pesticides including dieldrin and lindane. Numerous studies have found an increase in Parkinson disease in persons who consume rural well water; researchers theorize that water consumption is a proxy measure of pesticide exposure. In agreement with this hypothesis are studies which have found a dose-dependent an increase in PD in persons exposed to agricultural chemicals.

Head trauma

Past episodes of head trauma are reported more frequently by sufferers than by others in the population.[41][42][43] A methodologically strong recent study[41] found that those who have experienced a head injury are four times more likely to develop Parkinson’s disease than those who have never suffered a head injury. The risk of developing Parkinson’s increases eightfold for patients who have had head trauma requiring hospitalization, and it increases 11-fold for patients who have experienced severe head injury. The authors comment that since head trauma is a rare event, the contribution to PD incidence is slight. They express further concern that their results may be biased by recall, i.e., the PD patients because they reflect upon the causes of their illness, may remember head trauma better than the non-ill control subjects. These limitations were overcome recently by Tanner and colleagues,[44] who found a similar risk of 3.8, with increasing risk associated with more severe injury and hospitalization.

Drug-induced

Antipsychotics, which are used to treat schizophrenia and psychosis, can induce the symptoms of Parkinson’s disease (or parkinsonism) by lowering dopaminergic activity. Due to feedback inhibition, L-dopa can also eventually cause the symptoms of Parkinson’s disease that it initially relieves. Dopamine agonists can also eventually contribute to Parkinson’s disease symptoms by decreasing the sensitivity of dopamine receptors.

Treatment

Parkinson’s disease is a chronic disorder that requires broad-based management including patient and family education, support group services, general wellness maintenance, exercise, and nutrition. At present, there is no cure for PD, but medications or surgery can provide relief from the symptoms. Recently, Botox injections are being investigated as a non-FDA approved possible experimental treatment.

Levodopa

 

Stalevo for treatment of Parkinson's disease

 

The most widely used form of treatment is L-dopa in various forms. L-dopa is transformed into dopamine in the dopaminergic neurons by L-aromatic amino acid decarboxylase (often known by its former name dopa-decarboxylase). However, only 1-5% of L-DOPA enters the dopaminergic neurons. The remaining L-DOPA is often metabolised to dopamine elsewhere, causing a wide variety of side effects. Due to feedback inhibition, L-dopa results in a reduction in the endogenous formation of L-dopa, and so eventually becomes counterproductive. Carbidopa and benserazide are dopa decarboxylase inhibitors. They help to prevent the metabolism of L-dopa before it reaches the dopaminergic neurons and are generally given as combination preparations of carbidopa/levodopa (co-careldopa) (e.g. Sinemet, Parcopa) and benserazide/levodopa (co-beneldopa) (e.g. Madopar). There are also controlled release versions of Sinemet and Madopar that spread out the effect of the L-dopa. Duodopa is a combination of levodopa and carbidopa, dispersed as a viscous gel. Using a patient-operated portable pump, the drug is continuously delivered via a tube directly into the upper small intestine, where it is rapidly absorbed.

Tolcapone inhibits the COMT enzyme, thereby prolonging the effects of L-dopa, and so has been used to complement L-dopa. However, due to its possible side effects such as liver failure, it’s limited in its availability.

A similar drug, entacapone, has similar efficacy and has not been shown to cause significant alterations of liver function. A recent follow-up study by Cilia and colleagues[45] looked at the clinical effects of long-term administration of entacapone, on motor performance and pharmacological compensation, in advanced PD patients with motor fluctuations: 47 patients with advanced PD and motor fluctuations were followed for six years from the first prescription of entacapone and showed a stabilization of motor conditions, reflecting entacapone can maintain adequate inhibition of COMT over time.[45] Mucuna pruriens, is a natural source of therapeutic quantities of L-dopa.

Dopamine agonists

The dopamine-agonists bromocriptine, pergolide, pramipexole, ropinirole , cabergoline, apomorphine, and lisuride, are moderately effective. These have their own side effects including those listed above in addition to somnolence, hallucinations and /or insomnia. Several forms of dopamine agonism have been linked with a markedly increased risk of problem gambling. Dopamine agonists initially act by stimulating some of the dopamine receptors. However, they cause the dopamine receptors to become progressively less sensitive, thereby eventually increasing the symptoms.

Dopamine agonists can be useful for patients experiencing on-off fluctuations and dyskinesias as a result of high doses of L-dopa. Apomorphine can be administered via subcutaneous injection using a small pump which is carried by the patient. A low dose is automatically administered throughout the day, reducing the fluctuations of motor symptoms by providing a steady dose of dopaminergic stimulation. After an initial “apomorphine challenge” in hospital to test its effectiveness and brief patient and caregiver, the primary caregiver (often a spouse or partner) takes over maintenance of the pump. The injection site must be changed daily and rotated around the body to avoid the formation of nodules. Apomorphine is also available in a more acute dose as an autoinjector pen for emergency doses such as after a fall or first thing in the morning.

MAO-B inhibitors

Selegiline and rasagiline reduce the symptoms by inhibiting monoamine oxidase-B (MAO-B), which inhibits the breakdown of dopamine secreted by the dopaminergic neurons. Metabolites of selegiline include L-amphetamine and L-methamphetamine (not to be confused with the more notorious and potent dextrorotary isomers). This might result in side effects such as insomnia. Use of L-dopa in conjunction with selegiline has increased mortality rates that have not been effectively explained. Another side effect of the combination can be stomatitis. One report raised concern about increased mortality when MAO-B inhibitors were combined with L-dopa; however subsequent studies have not confirmed this finding. Unlike other non selective monoamine oxidase inhibitors, tyramine-containing foods do not cause a hypertensive crisis.

Surgical interventions

Surgical interventions
Illustration showing an electrode placed deep seated in the brain

Treating Parkinson’s disease with surgery was once a common practice. But after the discovery of levodopa, surgery was restricted to only a few cases. Studies in the past few decades have led to great improvements in surgical techniques, and surgery is again being used in people with advanced PD for whom drug therapy is no longer sufficient. Deep brain stimulation is presently the most used surgical means of treatment, but other surgical therapies that have shown promise include surgical lesion of the subthalamic nucleus[48] and of the internal segment of the globus pallidus, a procedure known as pallidotomy.

Speech therapies

The most widely practiced treatment for the speech disorders associated with Parkinson’s disease is Lee Silverman Voice Treatment (LSVT). LSVT focuses on increasing vocal loudness. A study found that an electronic device providing frequency-shifted auditory feedback (FAF) improved the clarity of Parkinson’s patients’ speech.

Physical exercise

Regular physical exercise and/or therapy, including in forms such as yoga, tai chi, and dance can be beneficial to the patient for maintaining and improving mobility, flexibility, balance and a range of motion. Physicians and physical therapists often recommend repetitive active exercises ,biofeedback and basic exercises, such as bringing the toes up with every step, carrying a bag with weight to decrease the bend having on one side, and practicing chewing hard and move the food around the mouth.

Methods undergoing evaluation

Gene therapy

Currently under investigation is gene therapy. This involves using a harmless virus to shuttle a gene into a part of the brain called the subthalamic nucleus (STN). The gene used leads to the production of an enzyme called glutamic acid decarboxylase (GAD), which catalyses the production of a neurotransmitter called GABA. GABA acts as a direct inhibitor on the overactive cells in the STN.
GDNF infusion involves the infusion of GDNF (glial-derived neurotrophic factor) into the basal ganglia using surgically implanted catheters. Via a series of biochemical reactions, GDNF stimulates the formation of L-dopa. GDNF therapy is still in development.
Implantation of stem cells genetically engineered to produce dopamine or stem cells that transform into dopamine-producing cells has already started being used. These could not constitute cures because they do not address the considerable loss of activity of the dopaminergic neurons. Initial results have been unsatifactory, with patients still retaining their drugs and symptoms.

Neuroprotective treatments

Neuroprotective treatments are at the forefront of PD research, but are still under clinical scrutiny. These agents could protect neurons from cell death induced by disease presence resulting in a slower pregression of disease. Agents currently under investigation as neuroprotective agents include apoptotic drugs (CEP 1347 and CTCT346), lazaroids, bioenergetics, antiglutamatergic agents and dopamine receptors[54]. Clinically evaluated neuroprotective agents are the monoamine oxidase inhibitors selegiline and rasagiline, dopamine agonists, and the complex I mitochondrial fortifier coenzyme Q10.

Neural transplantation

The first prospective randomised double-blind sham-placebo controlled trial of dopaminergic transplants failed to show an improvement in quality of life although some significant clinical improvements were seen in patients below the age of 60

Nutrients

Nutrients have been used in clinical studies and are widely used by people with Parkinson’s disease in order to partially treat Parkinson’s disease or slow down its deterioration. The L-dopa precursor L-tyrosine was shown to relieve an average of 70% of symptoms.[57] Ferrous iron, the essential cofactor for L-dopa biosynthesis was shown to relieve between 10% and 60% of symptoms in 110 out of 110 patients.[58] [59] More limited efficacy has been obtained with the use of THFA, NADH, and pyridoxine-coenzymes and coenzyme precursors involved in dopamine biosynthesis. Vitamin C and vitamin E in large doses are commonly used by patients in order to theoretically lessen the cell damage that occurs in Parkinson’s disease. This is because the enzymes superoxide dismutase and catalase require these vitamins in order to nullify the superoxide anion, a toxin commonly produced in damaged cells. However, in the randomized controlled trial, DATATOP of patients with early PD, no beneficial effect for vitamin E compared to placebo was seen.

Coenzyme Q10 has more recently been used for similar reasons. MitoQ is a newly developed synthetic substance that is similar in structure and function to coenzyme Q10. However, proof of benefit has not been demonstrated yet.

Qigong
There have been two studies looking at qigong in Parkinson’s disease. In a trial in Bonn, an open-label randomised pilot study in 56 patients found an improvement in motor and non-motor symptoms amongst patients who had undergone one hour of structured Qigong exercise per week in two 8-week blocks. The authors speculate that visualizing the flow of “energy” might act as an internal cue and so help improve movement.

The second study, however, found Qigong to be ineffective in treating Parkinson’s disease. In that study, researchers used a randomized cross-over trial to compare aerobic training with Qigong in advanced Parkinson’s disease. Two groups of PD patients were assessed, had 20 sessions of either aerobic exercise or qigong, were assessed again, then after a 2 month gap were switched over for another 20 sessions, and finally assessed again. The authors found an improvement in motor ability and cardiorespiratory function following aerobic exercise, but found no benefit following Qigong. The authors also point out that aerobic exercise had no benefit for patients’ quality of life.

Prognosis
PD is not considered to be a fatal disease by itself, but it progresses with time. The average life expectancy of a PD patient is generally lower than for people who do not have the disease. In the late stages of the disease, PD may cause complications such as choking, pneumonia, and falls that can lead to death.
The progression of symptoms in PD may take 20 years or more. In some people, however, the disease progresses more quickly. There is no way to predict what course the disease will take for an individual person. With appropriate treatment, most people with PD can live productive lives for many years after diagnosis.
In at least some studies, it has been observed that mortality was significantly increased, and longevity decreased among nursing home patients as compared to community dwelling patients.
One commonly used system for describing how the symptoms of PD progress is called the Hoehn and Yahr scale. Another commonly used scale is the Unified Parkinson’s Disease Rating Scale (UPDRS). This much more complicated scale has multiple ratings that measure motor function, and also mental functioning, behavior, mood, and activities of daily living; and motor function. Both the Hoehn and Yahr scale and the UPDRS are used to measure how individuals are faring and how much treatments are helping them. It should be noted that neither scale is specific to Parkinson’s disease; that patients with other illnesses can score in the Parkinson’s range.

Notable Parkinson’s sufferers

Further information: People with Parkinson’s disease
One famous sufferer of young-onset Parkinson’s is Michael J. Fox, whose book, Lucky Man (2000), focused on his experiences with the disease and his career and family travails in the midst of it. Fox established The Michael J. Fox Foundation for Parkinson’s Research to develop a cure for Parkinson’s disease within this decade.

Other famous sufferers include Pope John Paul II, playwright Eugene O’Neill, artist Salvador Dal?, evangelist Billy Graham, former US Attorney General Janet Reno, and boxer Muhammad Ali. Political figures suffering from it have included Adolf Hitler, Francisco Franco, Deng Xiaoping and Mao Zedong, and former Prime Minister of Canada Pierre Trudeau. Numerous actors have also been afflicted with Parkinson’s such as: Terry-Thomas, Deborah Kerr, Kenneth More, Vincent Price, Jim Backus and Michael Redgrave. Helen Beardsley (of Yours, Mine and Ours fame) also suffered from this disease toward the end of her life. Director George Roy Hill (The Sting, Butch Cassidy and the Sundance Kid) also suffered from Parkinson’s disease.

The film Awakenings (starring Robin Williams and Robert De Niro and based on genuine cases reported by Oliver Sacks) deals sensitively and largely accurately with a similar disease, postencephalitic parkinsonism.

References

  • This article contains text released into the public domain from:
  • National Institute of Neurological Disorders and Stroke (January 2006). Parkinson’s Disease: Hope Through Research. National Institutes of Health.
  • Manyam; Sanchez-Ramos JR (1999). Traditional and complementary therapies in Parkinson’s disease. PubMed.gov. Retrieved on 2006-10-29.
  • Parkinson, J. (2002). “An essay on the shaking palsy. 1817.” (Reproduced\). J Neuropsychiatry Clin Neurosci 14 (2): 223-36; discussion 222. PMID 11983801.
  • O., Hornykiewicz. L-DOPA: from a biologically inactive amino acid to a successful therapeutic agent. Institute for Brain Research, University of Vienna. Retrieved on 2006-10-29.
  • Cotzias, G. (1968). “L-Dopa for Parkinsonism.”. N Engl J Med 278 (11): 630. PMID 5637779.
  • Lepoutre A, Devos D, Blanchard-Dauphin A, Pardessus V, Maurage C, Ferriby D, Hurtevent J, Cotten A, Dest?e A, Defebvre L (2006). “A specific clinical pattern of camptocormia in Parkinson’s disease”. J. Neurol. Neurosurg. Psychiatr. 77 (11): 1229-34. PMID 16735399.
  • Pell M (1996). “On the receptive prosodic loss in Parkinson’s disease.”. Cortex 32 (4): 693-704. PMID 8954247.
  • Gunther Deuschl, Christof Goddemeier (1998). “Spontaneous and reflex activity of facial muscles in dystonia, Parkinson’s disease, and in normal subjects”. Journal of neurology, neurosurgery, and psychiatry 64 (March): 320-324.
  • Lieberman A (2006). “Depression in Parkinson’s disease — a review.”. Acta Neurol Scand 113 (1): 1-8. PMID 16367891.
  • Ishihara L, Brayne C (2006). “A systematic review of depression and mental illness preceding Parkinson’s disease.”. Acta Neurol Scand 113 (4): 211-20. PMID 16542159.
  • Michael J Frank (2005). “Dynamic Dopamine Modulation in the Basal Ganglia: A Neurocomputational Account of Cognitive Deficits in Medicated and Non-mediacated Parkinsonism”. Journal of Cognitive Neuroscience 17: 51-73.
  • Gupta A, Bluhm R (2004). “Seborrheic dermatitis”. Journal of the European Academy of Dermatology and Venereology : JEADV 18 (1): 13-26; quiz 19-20. PMID 14678527.
  • Gelb D, Oliver E, Gilman S (1999). “Diagnostic criteria for Parkinson disease.”. Arch Neurol 56 (1): 33-9. PMID 9923759.
  • Zhang Z., Roman G., Hong Z., Wu C., Qu Q., Huang J., Zhou B., Geng Z., Wu J., Wen H., Zhao H., Zahner G.. “Parkinson’s disease in China: prevalence in Beijing, Xian, and Shanghai.”. Lancet 365 (9459): 595-7. PMID 15708103.
  • Bermejo F. et al (2001). “Problems and issues with door-to-door, two-phase surveys: An illustration from central Spain.”. Neuroepidemiology 20: 225.
  • Rajput (1984). “Epidemiology of Parkinson’s disease”. Can J Neurol Sci. 11 (1): 156-159. PMID 6713314.
  • Van Den Eeden S, Tanner C, Bernstein A, Fross R, Leimpeter A, Bloch D, Nelson L (2003). “Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity.”. Am J Epidemiol 157 (11): 1015-22. PMID 12777365.
  • “Parkinson’s Disease Mechanism Discovered,” HHMI Research News June 22, 2006.
  • McGinness J., Corry P., Proctor P. (1974). “Amorphous semiconductor switching in melanins.” (Reprint). Science 183 (127): 853-5. PMID 4359339.
  • a b Jenner P (1998). “Oxidative mechanisms in nigral cell death in Parkinson’s disease.”. Mov Disord 13 Suppl 1: 24-34. PMID 9613715.
  • Kaur D, Andersen J (2002). “Ironing out Parkinson’s disease: is therapeutic treatment with iron chelators a real possibility?” (PDF). Aging Cell 1 (1): 17-21. PMID 12882349.
  • Eliezer Masliah, Edward Rockenstein, Isaac Veinbergs, Margaret Mallory, Makoto Hashimoto, Ayako Takeda, Yutaka Sagara, Abbyann Sisk, Lennart Mucke (2000). “Dopaminergic Loss and Inclusion Body Formation in alpha-Synuclein Mice: Implications for Neurodegenerative Disorders”. Science 287 (5456): 1265-1269. PMID 10678833.
  • Singleton A, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson M, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K (2003). “alpha-Synuclein locus triplication causes Parkinson’s disease.”. Science 302 (5646): 841. PMID 14593171.
  • P Poorkaj et al. (2004). “parkin mutation analysis in clinic patients with early-onset Parkinson’s disease”. American Journal of Medical Genetics Part A 129A (1): 44-50.
  • Ebba Lohmann et al. (2003). “How much phenotypic variation can be attributed to parkin genotype?”. Annals of Neurology 54 (2): 176-185.
  • Wanli W. Smith et al. (2005). “Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration”. Proceedings of the National Academy of Sciences of the United States of America 102 (51): 18676-18681.
  • Kachergus J, Mata I, Hulihan M, Taylor J, Lincoln S, Aasly J, Gibson J, Ross O, Lynch T, Wiley J, Payami H, Nutt J, Maraganore D, Czyzewski K, Styczynska M, Wszolek Z, Farrer M, Toft M (2005). “Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations.”. Am J Hum Genet 76 (4): 672-80. PMID 15726496.
  • A Brice (2005). “Genetics of Parkinson’s disease: LRRK2 on the rise (Scientific Commentary)”. Brain 128 (12): 2760-2762.
  • Ozelius L, Senthil G, Saunders-Pullman R, Ohmann E, Deligtisch A, Tagliati M, Hunt A, Klein C, Henick B, Hailpern S, Lipton R, Soto-Valencia J, Risch N, Bressman S (2006). “LRRK2 G2019S as a cause of Parkinson’s disease in Ashkenazi Jews.”. N Engl J Med 354 (4): 424-5. PMID 16436782.
  • DA Di Monte, M Lavasani, AB Manning-Bog (2002). “Environmental factors in Parkinson’s disease”. Neurotoxicology 23 (4-5): 487-502.
  • Chiueh C, Andoh T, Lai A, Lai E, Krishna G (2000). “Neuroprotective strategies in Parkinson’s disease: protection against progressive nigral damage induced by free radicals.”. Neurotox Res 2 (2-3): 293-310. PMID 16787846.
  • Cotzias G (1966). “Manganese, melanins and the extrapyramidal system.”. J Neurosurg 24 (1): Suppl:170-80. PMID 4955707.
  • Barbeau A (1984). “Manganese and extrapyramidal disorders (a critical review and tribute to Dr. George C. Cotzias).”. Neurotoxicology 5 (1): 13-35. PMID 6538948.
  • Ascherio A, Chen H, Weisskopf M, O’Reilly E, McCullough M, Calle E, Schwarzschild M, Thun M (2006). “Pesticide exposure and risk for Parkinson’s disease.”. Ann Neurol 60 (2): 197-203. PMID 16802290.
  • Chiueh C, Wu R, Mohanakumar K, Sternberger L, Krishna G, Obata T, Murphy D (Nov 17 1994). “In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia.”. Ann N Y Acad Sci 738: 25-36. PMID 7832434.
  • Orr, Leslie. “PCBs, fungicide open brain cells to Parkinson’s assault”, Medical News Today, February 10, 2005.
  • Amy B. Manning-Bog et al. (2002). “The Herbicide Paraquat Causes Up-regulation and Aggregation of ?-Synuclein in Mice”. Journal of Biological Chemistry 277 (3): 1641-1644.
  • Mona Thiruchelvam et al. (2000). “The Nigrostriatal Dopaminergic System as a Preferential Target of Repeated Exposures to Combined Paraquat and Maneb: Implications for Parkinson’s Disease”. Journal of Neuroscience 20 (24): 9207-9214.
  • Ranjita Betarbet et al. (2000). “Chronic systemic pesticide exposure reproduces features of Parkinson’s disease”. Nature Neuroscience 3: 1301-1306.
  • Masashi Kitazawaa, Vellareddy Anantharama and Anumantha G. Kanthasamy (2001). “Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells”. Free Radical Biology and Medicine 31 (11): 1473-1485.
  • F.M. Corrigan, C.L. Wienburg, R.F. Shore, S.E. Daniel, D. Mann (2000). “Organochlorine Insecticides in Substandia Nigra in Parkinson’s Disease”. Journal of Toxicology and Environmental Health Part A 59 (4): 229-234.
  • a b J. H. Bower et al. (2003). “Head trauma preceding PD”. Neurology 60: 1610-1615.
  • M. Stern et al. (1991). “The epidemiology of Parkinson’s disease”. Archives of Neurology 48 (9): 903-907.
  • Uryu K, Giasson B, Longhi L, Martinez D, Murray I, Conte V, Nakamura M, Saatman K, Talbot K, Horiguchi T, McIntosh T, Lee V, Trojanowski J (2003). “Age-dependent synuclein pathology following traumatic brain injury in mice.”. Exp Neurol 184 (1): 214-24. PMID 14637093.
  • Goldman SM, Tanner CM, Oakes D, Bhudhikanok GS, Gupta A, Langston JW (2006). “Head injury and Parkinson’s disease risk in twins.”. Ann Neurol 60 (1): 65 -72. PMID 16718702.
  • a b R. Cilia et al. (2006). [http://www.touchneurology.com/articles.cfm?article_id=5728&level=2 Long-term Efficacy of Entacapone in Patients with Parkinson’s Disease and Motor Fluctuations – A Six-Year Clinical Follow-Up Study].
  • Thorogood M, Armstrong B, Nichols T, Hollowell J (1998). “Mortality in people taking selegiline: observational study.”. BMJ 317 (7153): 252-4. PMID 9677215.
  • Marras C, McDermott M, Rochon P, Tanner C, Naglie G, Rudolph A, Lang A (2005). “Survival in Parkinson disease: thirteen-year follow-up of the DATATOP cohort.”. Neurology 64 (1): 87-93. PMID 15642909.
  • J. Guridi, J.A. Obeso (2001). “The subthalamic nucleus, hemiballismus and Parkinson’s disease: reappraisal of a neurosurgical dogma.”. Brain 124 (1): 5-19.
  • M.K. York, H.S. Levin, R.J. Grossman, W.J. Hamilton (1999). “Neuropsychological outcome following unilateral pallidotomy.”. Brain 122 (12): 2209-2220.
  • “What is LSVT?” http://www.lsvt.org/main_site.htm
  • Lowit, A., Brendel, B. “The response of patients with Parkinson’s Disease to DAF and FSF,” Stammering Research April 2004.
  • Garg, R and Lakhan, S. Parkinson’s Disease – Pharmaceutical and Physical Therapies. GNIF Brain Blogger. August, 2006.
  • Bonuccelli U, Del Dotto P (2006). “New pharmacologic horizons in the treatment of Parkinson disease”. Neurology 67 (2): 30-38.
  • R. Djaldetti & E. Melamed (2002). “New drugs in the future treatment of Parkinson’s disease”. J Neurol 249 (“:II): 30-35.
  • (1993) “Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. The Parkinson Study Group.”. NEJM 328 (“:3): 176-83.
  • C. R. Freed et al. (2001). “Transplantation of embryonic dopamine neurons for severe Parkinson’s disease”. N Engl J Med 8 (344(10)): 710-719. PMID: 11236774.
  • Lemoine P, Robelin N, Sebert P, Mouret J (1986). “La L-tyrosine : traitement au long cours de la maladie de Parkinson [L-tyrosine : A long term treatment of Parkinson’s Disease]”. Comptes rendus academie des sciences 309: 43-47.
  • W. Birkmayer and J. G. D. Birkmayer (1986). “Iron, a new aid in the treatment of Parkinson patients”. Journal of Neural Transmission 67 (3-4): 287-292.
  • (March 1989) in Editors Przuntek H , Riederer P: Early diagnosis and preventive therapy in Parkinson’s disease. Springer, p323. ISBN 0-387-82080-9.
  • Dopamine biosynthesis (Word doc). University of Chicago Personal Web Pages. Retrieved on 2006-11-04.
  • (1993) “Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. The Parkinson Study Group.”. N Engl J Med 328 (3): 176-83. PMID 8417384.
  • Schmitz-Hubsch T (2006). “Qigong exercise for the symptoms of Parkinson’s disease: a randomized, controlled pilot study.”. Mov Disord 21 (4): 543-548. PMID 16229022.
  • Burini D (2006). “A randomised controlled cross-over trial of aerobic training versus Qigong in advanced Parkinson’s disease.”. Eura Medicophys Epub ahead of print. PMID 16971865.
  • Parkinson’s Disease. Mayo Clinic: College of Medicine. Retrieved on 2006-11-04.

Cerebral Palsy

CP is an umbrella term encompassing a group of non-progressive, non- contagious neurological disorders that cause physical disability in human development, specifically the human movement and posture.
The incidence in developed countries is approximately 2-2.5 per 1000 live births. Incidence has not declined over the last 60 years despite medical advances (such as electro-fetal monitoring) because these advances allow extremely low birth weight and premature babies to survive. Cerebral refers to the brain and palsy refers to disorder of movement. CP is caused by damage to the motor control centers of the young developing brain and can occur during pregnancy (about 75 percent), during childbirth (about 5 percent) or after birth (about 15 percent) up to about age three. Eighty percent of causes are unknown; for the small number where cause is known this can include infection, malnutrition, and/or head trauma in very early childhood. It is a non- progressive disorder; meaning the brain damage does not worsen, but secondary orthopedic deformities are common. There is no known cure for CP. Medical intervention is limited to the treatment and prevention of complications possible from CP’s consequences. Overall, CP ranks among the most costly congenital conditions in the world to manage effectively.

CP is divided into four major classifications to describe the different movement impairments. These classifications reflect the area of brain damaged. The four major classifications are:

  • Spastic
  • Athetoid/Dyskinetic
  • Ataxic
  • Mixed

In 30 percent of all cases of CP, the spastic form is found along with one of the other types. There are a number of other minor types of CP, but these are the most common. Onset of arthritis and osteoporosis can occur much sooner in adults with CP. Further research is needed on adults with CP, as the current literature body is highly focused on the pediatric patient. CP’s resultant motor disorder(s) are sometimes, though not always, accompanied by “disturbances of sensation, cognition, communication, perception, and/or behavior, and/or by a seizure disorder” (Rosenbaum et al, 2005).

General classificatio

  • Spastic (ICD-10 G80.0-G80.1) is by far the most common type of CP, occurring in 70% to 80% of all cases. People with this type are hypertonic and have an essentially neuromuscular condition stemming from damage to the corticospinal tract, motor cortex, or pyramidal tract that affects the nervous system’s ability to receive gamma amino butyric acid in the area(s) affected by the spasticity. Spastic CP is further classified by topography dependent on the region of the body affected; these include:
    • Spastic hemiplegia (One side being affected). Generally, injury to the left side of the brain will cause a right hemiplegia and injury to the right side a left hemiplegia. Childhood hemiplegia is a relatively common condition, affecting up to one child in 1,000.
    • Spastic diplegia (Whole body affected, but the lower extremities affected more than the upper extremities). Most people with spastic diplegia do eventually walk. The gait of a person with spastic diplegia is typically characterized by a crouched gait. Toe walking and flexed knees are common. Hip problems, dislocations, and side effects like strabismus are common. Strabismus is the turning in or out of one eye, commonly called cross – lazy eye, affects three quarters of people with spastic diplegia. This is due to weakness of the muscles that control eye movement. In addition, these individuals are often nearsighted. In many cases the IQ of a person with spastic diplegia is normal.
    • Spastic quadriplegia (Whole body affected; all four limbs affected equally). Some children with quadriplegia also suffer from hemiparetic tremors; an uncontrollable shaking that affects the limbs on one side of the body and impairs normal movement. A common problem with children suffering from quadriplegia is fluid buildup. Diuretics and steroids are medications administered to decrease any buildup of fluid in the spine that is caused by leakage from dead cells. Hardened feces in a quadriplegia patient are important to monitor because it can cause high blood pressure. Autonomic dysreflexia can be caused by hardened feces, urinary infections, and other problems, resulting in the overreaction of the nervous system and can result in high blood pressure, heart attacks, and strokes. Blockage of tubes inserted into the body to drain or enter fluids also needs to be monitored to prevent autonomic dysreflexia in quadriplegia. The proper functioning of the digestive system needs to be monitored as well.
  • Ataxia (ICD-10 G80.4) is damage to the cerebellum which results in problems with balance, especially while walking. It is the most rare type, occurring in at most 10% of all cases. Some of these individuals have hypotonia and tremors. Motor skills like writing, typing, or using scissors might be difficult and it is common for these individuals to have difficulty with visual or auditory processing of objects and instability in balance and relation to gravity.
  • Athetoid or dyskinetic (ICD-10 G80.3) is mixed muscle tone – sometimes hypertonia and sometimes hypotonia. Children with athetoid CP have trouble holding themselves in an upright, steady position for sitting or walking, and often show involuntary motions.
    For some children with athetoid CP, it takes a lot of work and concentration to get their hand to a certain spot (like to scratch their nose or reach for a cup). Because of their mixed tone and trouble keeping a position, they may not be able to hold onto things (like a toothbrush or fork or pencil). About one-fourth of all people with CP have athetoid CP. The damage occurs to the extrapyramidal motor system and/or pyramidal tract and to the basal ganglia. It occurs in ~20% of all cases.

Incidence and prevalence

Prevalence is best calculated around the school entry age of about six years. In the industrialized world, the incidence is about 2 per 1000 live births. In the United States, the rate is thought to vary from between 1.5 to 4 per 1000 live births. This amounts to approximately 5,000-10,000 babies born with CP each year in the United States.
Each year, around 1,500 preschoolers are diagnosed with the disorder in the USA. There is mental retardation in 60% of the cases, due to brain damage outside the parietal, occipital, temporal or Basal Ganglia. The rate is most likely much lower then 60%, because the physical and communicational limitations of people with CP lowers their IQ scores if not given a correctly modified test. Mental retardation can occur if the child is not given the opportunities to learn; it does not solely occur from brain damage, but from an individual(s)’s ability to 1) communicate with the child and 2) be able to have the child effectively communicate through speech or other means. For example, a child that had CP who suffers from blindness/deafness due to damage that occurred in the occipital and temporal lobes during birth could use tactile sign-language or tulonoma to communicate. Tulonoma is a type of technique where the user puts his/her hands on the speakers mouth and is able to interpret what they say solely based on the lip movement patterns associated with particular word(s). Other disorders paired with CP include disorders of hearing, eyesight, epilepsy, perception of obstacles (such as judging how far away things are when driving a car), speech difficulties, and eating and drinking difficulties. These estimates include individuals who did not have access to an equal opportunity education prior to the Americans with Disabilities Act of 1990.
Overall, advances in care of pregnant mothers and their babies has not resulted in a noticeable decrease in CP. Only the introduction of quality medical care to locations with less than adequate medical care has shown any decreases. The incidence increases with premature or very low-weight babies regardless of the quality of care.
Most recently, Apgar scores have been indicated to not be a reliable method of determining whether or not an individual has CP; it really depends on how quickly oxygen reaches the brain and the body’s vital organs that matter, instead.
Despite medical advances, the incidence and severity of CP has actually increased over time. This may be attributed to medical advances in areas related to premature babies (which results in a greater survival rate).

Signs and Symptoms:

All types of CP are characterized by abnormal muscle tone, posture (i.e. slouched over while sitting), reflexes, or motor development and coordination. There are joint and bone deformities and contractures (permanently fixed, tight muscles and joints). The classical symptoms are spasticity, unsteady gait, problems with balance, and soft tissue findings consist largely of decreased muscle mass. Scissor walking (where the knees cross and come in) and toe walking is common among people who are able to walk, but taken on the whole, CP symptomatology is very diverse. This is an extremely heterogeneous group of individuals. Each has their own unique abilities and needs.
Babies born with severe CP often have an irregular posture; their bodies may be either very floppy or very stiff. Birth defects, such as spinal curvatures , small jawbone, or small head, sometimes occur along with CP. Symptoms may appear, change, or become more severe as a child gets older. This is why some babies born with CP do not show obvious signs right away.
Secondary conditions can include seizures, spasms, and other involuntary movements (i.e. facial gestures) ,epilepsy, speech or communication disorders, eating problems, sensory impairments: hearing or vision impairments, mental retardation, learning disabilities, and/or behavioral disorders.

History

CP, then known as “Cerebral Paralysis”, was first identified by English surgeon William Little in 1860. Little raised the possibility of asphyxia during birth as a chief cause of the disorder. It was not until 1897 that Sigmund Freud, then a neurologist, suggested that a difficult birth was not the cause but rather only a symptom of other effects on fetal development. Research conducted during the 1980s by the National Institute of Neurological Disorders and Stroke (NINDS) suggested that only a small number of cases of CP are caused by lack of oxygen during birth.
Motor difficulties are common in individuals with CP. This can vary from paralysis of movement to minor levels of clumsiness. The brain’s plasticity at a young age is probably one of the main reasons for the steep differences between individuals with CP.

Causes

Doctors aren’t sure what causes CP. This matter has been debated over the years with no obvious answers or conclusions. Since CP refers to a group of disorders, there is no known precise cause. Some major causes are asphyxia, hypoxia of the brain, birth trauma or premature birth. The three most common causes of asphyxia in the young child are: choking on foreign objects such as toys and pieces of food; poisoning; and near drowning. Between 40% and 50% of all children who develop cerebral palsy are born prematurely. In addition, the risk of a baby having CP increases as the birth weight decreases. A baby who is born prematurely usually has a low birth weight, less than 5.5 lb, but full-term babies can also have low birth weights. Multiple-birth babies are more likely than single-birth babies to be born early or with a low birth weight. Certain infections in the mother during and before birth such as strep infections, central nervous system infections, trauma, consecutive hematomas, and placenta abruptio. After birth, the condition may be caused by toxins, severe jaundice, lead poisoning, physical brain injury, shaken baby syndrome, incidents involving hypoxia to the brain (such as near drowning), and encephalitis or meningitis. However the cause of most individual cases of CP is unknown.
Recent research has demonstrated that intrapartum asphyxia is not the most important cause, probably accounting for no more than 10 percent of all cases; rather, infections in the mother, even infections that are not easily detected, may triple the risk of the child developing the disorder, mainly as the result of the toxicity to the fetal brain of cytokines that are produced as part of the inflammatory response.
Premature babies have a higher risk because their organs are not yet fully developed. This increases the risk of asphyxia and other injury to the brain, which in turn increases the incidence of CP. Periventricular leukomalacia is an important cause of CP.
Also, some structural brain anomalies such as lissencephaly cause symptoms of CP, although whether that could be considered CP is a matter of opinion (some people say CP must be due to brain damage, whereas these people never had a normal brain). Often this goes along with rare chromosome disorders and CP is not genetic of hereditary.

Diagnosis

The diagnosis of CP requires several things:
The presence of symptoms indicating brain damage or dysfunction
The presence of motor dysfunction
The absence of change in symptoms – CP is by definition a static pathology, which is almost always reflected by static symptomatology Because of the final requirement, CP may take some time to diagnose; Sometimes it is unclear whether a child’s condition is worsening or not.
However, most children with CP are diagnosed by about 18 months of age. If a child is born with a severe form of CP, a health professional may be able to diagnose the condition within the first few weeks of life. However, parents and caregivers usually are the first to notice that a baby has developmental delays that may be early signs of CP.
Usually a health professional diagnoses CP based on a baby’s medical history (including parents’ observations of developmental delays), physical examination, and results of screening tests. Additional tests, such as developmental questionnaires, computed tomography (CT) scan or magnetic resonance image (MRI) of the head, or an ultrasound of the brain may be done.

Bones
In order for bones to attain their normal shape and size, they require the stresses from normal musculature. Osseous findings will therefore mirror the specific muscular deficits in a given person with CP. The shafts of the bones are often thin (gracile). When compared to these thin shafts (diaphyses) the metaphyses often appear quite enlarged (ballooning). With lack of use, articular cartilage may atrophy, leading to narrowed joint spaces. Depending on the degree of spasticity, a person with CP may exhibit a variety of angular joint deformities. Because vertebral bodies need vertical gravitational loading forces to develop properly, spasticity and an abnormal gait can hinder proper and/or full bone and skeletal development. People with CP tend to be shorter in height than the average person because their bones are not allowed to grow to their full potential. Sometimes bones grow at different lengths, so the person may have one leg longer than the other.

Prognosis

CP is not a progressive disorder meaning the actual brain damage does not worsen, but the symptoms can become worse over time due to ‘wear and tear’. A person with the disorder may improve somewhat during childhood if he or she receives extensive care from specialists, but once bones and musculature become more established, orthopedic surgery may be required for fundamental improvement. People who suffer from CP tend to develop arthritis at a younger age than normal because of the pressure placed on joints by excessively toned and stiff muscles.
The first questions usually asked by parents after they are told their child has CP are “What will my child be like?” and “Will she/he walk?” Predicting what a young child with CP will be like or what he will or will not do is very difficult. It is generally assumed that if a child is not sitting up by himself by age four or walking by age eight, then he will never be an independent walker. However this is a generalisation, and there are many cases where a person who has CP has become an independant walker at a later age.
It is even more difficult to make early predictions of speaking ability or mental ability than it is to predict motor function. Predictions can start being made after the age of two, though the child’s full intellectual potential won’t really be known until the child starts school. People with CP are more likely to have some type of learning disability, but having a learning disability has nothing to do with a person’s intellect and IQ level.
Intellectual level varies widely from genius to mentally retarded, as it can for any person, with or without CP. The important thing is to not under estimate the child’s capabilities and to give them every opportunity to learn.
The ability to live independently with CP also varies widely depending on severity of the disability. Some individuals with CP will require personal assistant services for all activities of daily living. Others can live semi-independently in the community with support for certain activities. Still others can live with complete independence. The need for personal assistance often changes with increasing age and the associated functional decline. However, in most cases, persons with CP can expect to have a normal life expectancy; survival has been shown to be associated with the ability to ambulate, roll and self-feed. As the condition does not directly affect reproductive function, some persons with CP have children and parent successfully. There is no increased chance of a person with CP having a child with CP.

Hypotonia

Hypotonia is a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength. Recognizing hypotonia, even in early infancy, is usually relatively straightforward, but diagnosing the underlying cause can be difficult and often unsuccessful. The long-term effects of hypotonia on a child’s development and later life depend primarily on the severity of the muscle weakness and the nature of the cause. Some disorders have a specific treatment but the principal treatment for most hypotonia of idiopathic or neurologic cause is physical therapy to help the person compensate for the neuromuscular disability.

Hand surgery

The field of hand surgery deals with both surgical and non-surgical treatment of conditions and problems that may take place in the hand or upper extremity (commonly from the tip of the hand to the shoulder). Hand surgery may be practiced by graduates of general surgery, orthopaedic surgery and plastic surgery. Plastic surgeons and orthopaedic surgeons receive significant training in hand surgery during their residency training, with some graduates continuing on to do an additional one year hand fellowship.

These fellowships are sometimes also pursued by general surgeons. Plastic surgeons are particularly well suited to handle traumatic hand and digit amputations that require a “replant” operation. Plastic surgeons are trained to reconstruct all aspects to salvage the appendage: blood vessels, nerves, tendons, muscle, bone. Orthopaedic surgeons are particularly well suited to handle complex fractures of the hand and injuries to the carpal bones that alter the mechanics of the wrist. Hand surgeons perform a wide variety of operations such as fracture repairs, nerve decompressions, releases, transfeer and repairs of tendons and reconstruction of injuries, rheumatoid deformities and congenital defects.

The central nervous system

The central nervous system (CNS) represents the largest part of the nervous system, including the brain and the spinal cord. Together with the peripheral nervous system, it has a fundamental role in the control of behavior. The CNS is contained within the dorsal cavity, with the brain within the cranial subcavity, and the spinal cord in the spinal cavity.

Since the strong theoretical influence of cybernetics in the fifties, the CNS is conceived as a system devoted to information processing, where an appropriate motor output is computed as a response to a sensory input. Yet, many threads of research suggest that motor activity exists well before the maturation of the sensory systems and then, that the senses only influence behavior without dictating it. This has brought the conception of the CNS as an autonomous system.

In the developing fetus, the CNS originates from the neural plate, a specialised region of the ectoderm, the most external of the three embryonic layers. During embryonic development, the neural plate folds and forms the neural tube. The internal cavity of the neural tube will give rise to the ventricular system. The regions of the neural tube will differentiate progressively into transversal systems. First, the whole neural tube will differentiate into its two major subdivisions: spinal cord (caudal) and brain (rostral/cephalic). Consecutively, the brain will differentiate into brainstem and prosencephalon. Later, the brainstem will subdivide into rhombencephalon and mesencephalon, and the prosencephalon into diencephalon and telencephalon.

the CNS is covered by the meninges, the brain is protected by the skull and the spinal cord by the vertebrae. The rhombencephalon gives rise to the pons, the cerebellum and the medulla oblongata, its cavity becomes the fourth ventricle. The mesencephalon gives rise to the tectum, pretectum, cerebral peduncle and its cavity develops into the mesencephalic duct or cerebral aqueduct. The diencephalon give rise to the subthalamus, hypothalamus, thalamus and epithalamus, its cavity to the third ventricle. Finally, the telencephalon gives rise to the striatum (caudate nucleus and putamen), the hippocampus and the neocortex, its cavity becomes the lateral (first and second) ventricles.

The basic pattern of the CNS is highly conserved throughout the different species of vertebrates and during evolution. The major trend that can be observed is towards a progressive telencephalisation: while in the reptilian brain that region is only an appendix to the large olfactory bulb, it represent most of the volume of the mammalian CNS. In the human brain, the telencephalon covers most of the diencephalon and the mesencephalon. Indeed, the allometric study of brain size among different species shows a striking continuity from rats to whales, and allows us to complete the knowledge about the evolution of the CNS obtained through cranial endocasts.

The Peripheral Nervous System

The peripheral nervous system, or PNS, is part of the nervous system, and consists of the nerves and neurons that reside or extend outside the central nervous system (the brain and spinal cord) to serve the limbs and organs, for example. Unlike the central nervous system, however, the PNS is not protected by bone or the blood-brain barrier, leaving it exposed to toxins and mechanical injuries. The peripheral nervous system is divided into the somatic nervous system and the autonomic nervous system.

Naming of specific nerves

The 10 out of the 12 cranial nerves originate from the brainstem, and mainly control the functions of the anatomic structures of the head with some exceptions. CN X (10) receives visceral sensory information from the thorax and abdomen, and CN XI (11) is responsible for innervating the sternocleidomastoid and trapezius muscles, neither of which is exclusively in the head. Spinal nerves take their origins from the spinal cord. They control the functions of the rest of the body. In humans, there are 31 pairs of spinal nerves: 8 cervical, 12 thoracic, 5 lumber, 5 sacral and 1 coccygeal. The naming convention for spinal nerves is to name it after the vertebra immediately above it. Thus the fourth thoracic nerve originates just below the fourth thoracic vertebra. This convention breaks down in the cervical spine. The first spinal nerve originates above the first cervical vertebra and is called C1. This continues down to the last cervical spinal nerve, C8. There are only 7 cervical vertebrae and 8 cervical spinal nerves.

Cervical spinal nerves (C1-C4)

The first 4 cervical spinal nerves, C1 through C4, split and recombine to produce a variety of nerves that subserve the neck and back of head. Spinal nerve C1 is called the suboccipital nerve which provides motor innervation to muscles at the base of the skull. C2 and C3 form many of the nerves of the the weirdly shaped heck neck, providing both sensory and motor control. These include the greater occipital nerve which provides sensation to the back of the head, the lesser occipital nerve which provides sensation to the area behind the ears, the greater auricular nerve and the lesser auricular nerve. See occipital neuralgia. The phrenic nerve arises from nerve roots C3, C4 and C5. It innervates the diaphragm, enabling breathing. If the spinal cord is transected above C3, then spontaneous breathing is not possible.

Brachial plexus (C5-T1)

The last 4 cervical spinal nerves, C5 through C8, and the first thoracic spinal nerve, T1,combine to form the brachial plexus, or plexus brachialis, a tangled array of nerves, splitting, combining and recombining, to form the nerves that subserve the arm and upper back. Although the brachial plexus may appear tangled, it is highly organized and predictable, with little variation between people.

Before forming three cords

The first nerve off the brachial plexus, or plexus brachialis, is the dorsal scapular nerve, arising from C5 nerve root, and innervating the rhomboids and the levator scapulae muscles. The long thoracic nerve arises from C5, C6 and C7 to innervate the serratus anterior. The brachial plexus first forms three trunks, the superior trunk, composed of the C5 and C6 nerve roots, the middle trunk, made of the C7 nerve root, and the inferior trunk, made of the C8 and T1 nerve roots. The suprascapular nerve is an early branch of the superior trunk. It innervates the suprascapular and infrascapular muscles, part of the rotator cuff. The trunks reshuffle as they traverse towards the arm into cords. There are three of them. The lateral cord is made up of fibers from the superior and middle trunk. The posterior cord is made up of fibers from all three trunks. The medial cord is composed of fibers solely from the medial trunk.

Lateral cord

The lateral cord gives rise to the following nerves:

  • The lateral pectoral nerve, C5, C6 and C7 to the pectoralis major muscle, or musculus pectoralis major.
  • The musculocutaneous nerve which innervates the biceps muscle
  • The median nerve, partly. The other part comes from the medial cord. See below for details.

Posterior cord

The posterior cord gives rise to the following nerves:

  • The upper subscapular nerve, C7 and C8, to the subscapularis muscle, or musculus supca of the rotator cuff.
  • The lower subscapular nerve, C5 and C6, to the teres major muscle, or the musculus teres major.
  • The thoracodorsal nerve, C6, C7 and C8, to the latissimus dorsi muscle, or musculus latissimus dorsi.
  • The axillary nerve, which supplies sensation to the shoulder and motor to the deltoid muscle or musculus deltoideus, and the teres minor muscle, or musculus teres minor, also of the rotator cuff.
  • The radial nerve, or nervus radialis, which innervates the triceps brachii muscle, the brachioradialis muscle, or musculus brachioradialis,, the extensor muscles of the fingers and wrist (extensor carpi radialis muscle), and the extensor and abductor muscles of the thumb. See radial nerve injuries.

Medial cord

The medial cord gives rise to the following nerves:

  • The median pectoral nerve, C8 and T1, to the pectoralis muscle
  • The medial brachial cutaneous nerve, T1
  • The medial antebrachial cutaneous nerve, C8 and T1
  • The median nerve, partly. The other part comes from the lateral cord. C7, C8 and T1 nerve roots. The first branch of the median nerve is to the pronator teres muscle, then the flexor carpi radialis, the palmaris longus and the flexor digitorum superficialis. The median nerve provides sensation to the anterior palm, the anterior thumb, index finger and middle finger. It is the nerve compressed in carpal tunnel syndrome.
  • The ulnar nerve originates in nerve roots C7, C8 and T1. It provides sensation to the ring and pinky fingers. It innervates the flexor carpi ulnaris muscle, the flexor digitorum profundus muscle to the ring and pinky fingers, and the intrinsic muscles of the hand (the interosseous muscle, the lumbrical muscles and the flexor pollicus brevis muscle). This nerve traverses a groove on the elbow called the cubital tunnel, also known as the funny bone. Striking the nerve at this point produces an unpleasant sensation in the ring and little fingers.

Dysphasia / Dyspraxia

Dysphasia is the partial loss of the ability to coordinate and perform certain purposeful movements and gestures in the absence of motor or sensory impairments. Dyspraxia may be acquired (e.g. as a result of brain damage suffered from a stroke or other trauma), or associated with failure / delay of normal neurological development – i.e. developmental dyspraxia.

The term apraxia is more often used to describe this symptom in clinical practice, although strictly apraxia denotes a complete (as opposed to partial) loss of the relevant function. In the UK and elsewhere the term dyspraxia is now more often used as shorthand for ‘developmental dyspraxia’ in referring to one or all of a heterogeneous range of disorders affecting the initiation, organization and performance of action.

Developmental dyspraxia

Developmental dyspraxia (referred to as developmental coordination disorder (DCD) in the US) is a life-long condition that is more common in males than in females, and has been believed to affect 8% to 10% of all children (Dyspraxia Trust, 1991). Ripley, Daines, and Barrett state that ‘Developmental dyspraxia is difficulty getting our bodies to do what we want when we want them to do it’, and that this difficulty can be considered significant when it interferes with the normal range of activities expected for a child of their age. Madeline Portwood makes the distinction that dyspraxia is not due to a general medical condition, but that it may be due to immature neuron development. The word “dyspraxia” comes from the Greek words “dys” meaning bad and “praxis”, meaning action or deed.

Part of a continuum of related disorders, dyspraxia is also known as developmental coordination disorder, and may also be present in people with autism spectrum disorder, dyslexia and dyscalculia, among others. Dyspraxia is described as having two main elements:

  1. Ideational dyspraxia
    Difficulty with planning a sequence of coordinated movements.
  2. Ideo-Motor dyspraxia
    Difficulty with executing a plan, even though it is know.

Assessment and diagnosis

Assessments for dyspraxia typically require a developmental history, detailing ages at which significant developmental milestones, such as crawling and walking, occurred. Motor skills screening includes activities designed to indicate dyspraxia, including balancing, physical sequencing, touch sensitivity, and variations on walking activities. A baseline motor assessment establishes the starting point for developmental intervention programs. Comparing children to normal rates of development may help to establish areas of significant difficulty.

Developmental profiles

There are six main areas of difficulty which can be profiled within dyspraxia; the four main areas are listed below:

Speech and language

Developmental verbal dyspraxia is a type of ideational dyspraxia, causing linguistic or phonological impairment. Key problems include:

  • Difficulties controlling the speech organs
  • Difficulties making speech sounds
  • Difficulty sequencing sounds
  • Difficulty controlling breathing and phonation
  • Slow language development
  • Difficulty with feeding

Fine motor control

Difficulties with fine motor co-ordination lead to problems with handwriting, which may be due to either ideational or ideo-motor difficulties. Problems associated with this area may include:

  • Learning basic movement patterns.
  • Developing a desired writing speed.
  • The acquisition of graphemes – e.g. the letters of the Latin alphabet, as well as numbers.
  • Establishing the correct pencil grip.
  • Hand aching while writing.

Whole body movement, coordination, and body image

Issues with gross motor coordination mean that major developmental targets include walking, running, climbing and jumping are affected. One area of difficulty involves associative movement, where a passive part of the body moves or twitches in response to a movement in an active part. For example, the support arm and hand twitching as the dominant arm and hand move, or hands turning inwards or outwards to correspond with movements of the feet. Problems associated with this area may include:

  • Poor timing
  • Poor balanc
  • Difficulty combining movements into a controlled sequence.
  • Difficulty remembering the next movement in a sequence.

Physical play

Difficulties in areas relating to physical play may lead to dyspraxic children standing out from their peers. Major developmental targets include ball skills, use of wheeled toys and manipulative skills, including pouring, threading and using scissors.

  • Problems with spatial awareness, or proprioception.
  • Mis-timing when catching.
  • Complex combination of skills involved in using scissors.

The other two developmental profiles concern dressing and feeding.

General Difficulties

Due to poor muscle control, many people with dyspraxia have trouble picking up and holding onto simple objects — quite often, objects literally slip through a dyspraxic’s fingers. This disorder causes an individual to be clumsy to the point of knocking things over and bumping into people accidentally. Tripping over one’s own feet is also not uncommon, as is a poor sense of balance in general. Dyspraxics often have difficulty in determining left from right, and this may cause problems that persist through life. Cross-laterality, ambidexterity, and a shift in the preferred hand are also common in people with dyspraxia.

Some people with this condition have poor spatial awareness in that it may be difficult to determine the speed and position of a particular object, such as potentially a baseball. Dyspraxics may also have trouble determining the distance between them and other objects.

Dyspraxic people may have Sensory Integration Dysfunction, a condition that creates abnormal oversensitivity or undersensitivity to physical stimuli, such as touch, light, and sound. This may manifest itself as an inability to tolerate certain textures such as sandpaper or certain fabrics, or even being touched by another individual (in the case of touch oversensitivity) or may require the consistent use of sunglasses outdoors since sunlight may be intense enough to cause discomfort to a dyspraxic (in the case of light oversensitivity). An aversion to loud music and naturally loud environments (such as clubs and bars) is typical behavior of a dyspraxic individual who suffers from auditory oversensitivity, while only being comfortable in unusually warm or cold environments is typical of a dyspraxic with temperature oversensitivity. This typically occurs if the dyspraxia is comorbid to an autistic spectrum disorder (PDD) such as autistic disorder or Asperger syndrome.

Dyspraxic people sometimes have difficulty moderating the amount of sensory information that their body is constantly sending them, so as a result these people are prone to panic attacks. Having other autistic traits (which is common with dyspraxia and related conditions) may also contribute to sensory-induced panic attacks.

Dyspraxics (along with people who have similar conditions) may have difficulty sleeping since there is an inability to force the brain to stop thinking and “shut down”. A dyspraxic is nearly always thinking about several unrelated things at once, (the inverse is also possible, with only one dominant thought occupying the dyspraxic’s entire attention span at any given time) so this may cause easy distractibility and daydreaming. It is quite easy for someone with dyspraxia to concentrate entirely on a particular thought instead of on the situation at hand. For this reason, dyspraxia may be misdiagnosed as ADHD since on the surface both conditions have similar symptoms in some areas. Many people with dyspraxia have short-term memory issues and may forget instructions they received only seconds before, tend to forget important deadlines, and are constantly misplacing items.

Moderate to extreme difficulty doing physical tasks is experienced by dyspraxics, and fatigue is common because so much extra energy is expended while trying to execute physical movements correctly [4]. Some (but not all) dyspraxics suffer from hypotonia, which in this case is chronically low muscle tone caused by dyspraxia. People with this condition have very low muscle strength and endurance (even in comparison with other dyspraxics) and even the simplest physical activities may quickly cause soreness and fatigue, depending on the severity of the hypotonia. Hypotonia may worsen a dyspraxic’s already poor balance to the point where it is necessary to constantly lean on sturdy objects for support.

Positive Aspects

Despite having considerable difficulty in the areas described above, dyspraxia like other neurodiverse disorders carries some potential benefit. A large amount of dyspraxics tend to be highly articulate and are known to be having extremely high verbal IQs. A number of famous authors are thought to have shown symptoms of dyspraxia including Ernest Hemingway, The Bronte sisters and Jack Kerouac.

Overlap with other conditions

Dyspraxics may have other difficulties that are not due to dyspraxia itself but often co-exist with it. They may have characteristics of dyslexia (difficulty with reading and spelling), dyscalculia (difficulty with mathematics) ADHD (poor attention span), or Aspergers Syndrome (poor social cognition, and a literal understanding of language, making it hard to understand idioms or sarcasm). However, they are unlikely to have problems in all of these areas. The pattern of difficulty varies widely from person to person, and it is important to understand that a major weakness for one dyspraxic can be a strength or gift for another. For example, while some dyspraxics have difficulty with reading and spelling due to an overlap with dyslexia, or numeracy due to an overlap with dyscalculia, others may have brilliant reading and spelling or mathematical abilities. Similarly, some have autistic traits such as lacking an appreciation of irony or social cues, while others thrive on an ironic sense of humour as a bonding tool and a means of coping.

Frustration and low self-esteem are common to many dyspraxics, whatever their profile of difficulties.

Other names

Collier first described dyspraxia as ‘congenital maladroitness’. A. Jean Ayers referred to it as a disorder of sensory integration in 1972 while in 1975 Dr Sasson Gubbay called it the ‘clumsy child syndrome’. It has also been called minimal brain dysfunction although the two latter names are no longer in use. Other names include:

  • Developmental Co-ordination Disorder
  • Sensorimotor dysfunction
  • Perceptuo-motor dysfunction
  • Motor Learning Difficulties

Spinal Cord Injury

Spinal cord injury, or myelopathy, is a disturbance of the spinal cord that results in loss of sensation and/or mobility. The two common types of spinal cord injury are:

  • Trauma: automobile accidents, falls, gunshots, diving accidents, war injuries, etc.
  • Disease: polio, spina bifida, tumors, Friedreich’s ataxia, etc.

It is important to note that the spinal cord does not have to be completely severed for there to be a loss of function. In fact, the spinal cord remains intact in most cases of spinal cord injury.
Spinal cord injuries are not the same as back injuries such as ruptured disks, spinal stenosis or pinched nerves. It is possible to “break one’s neck or back” and not sustain a spinal cord injury if only the vertebrae are damaged and the spinal cord remains intact.
About 450,000 people in the United States live with spinal cord injury, and there are about 11,000 new spinal cord injuries every year. The majority of them (78%) involve males between the ages of 16-30 and result from motor vehicle accidents (42%), violence (24%), or falls (22%).

The Effects of Spinal Cord Injury The exact effects of a spinal cord injury vary according to the type and level injury, and can be organized into two types:

  • In a complete injury, there is no function below the level of the injury. Voluntary movement is impossible and physical sensation is impossible. Complete injuries are always bilateral, that is, both sides of the body are affected equally.
  • A person with an incomplete injury retains some sensation below the level of the injury. Incomplete injuries are variable, and a person with such an injury may be able to move one limb more than another, may be able to feel parts of the body that cannot be moved, or may have more functioning on one side of the body than the other.

In addition to a loss of sensation and motor function below the point of injury, individuals with spinal cord injuries will often experience other changes.
Bowel and bladder function is associated with the sacral region of the spine, so it is very common to experience dysfunction of the bowel and bladder. Sexual function is also associated with the sacral region, and is often affected. Injuries very high on the spinal cord (C-1, C-2) will often result in a loss of many involuntary functions, such as breathing, necessitating mechanical ventilators or phrenic nerve pacing. Other effects of spinal cord injury can include an inability to regulate heart rate (and therefore blood pressure), reduced control of body temperature, inability to sweat below the level of injury, and chronic pain and also incontinence. Physical therapy and orthopedic instruments (e.g., wheelchairs, standing frames) are often necessary, depending on the location of the injury.

The Location of the Injury

Knowing the exact level of the injury on the spinal cord is important when predicting what parts of the body might be affected by paralysis and loss of function.
Below is a list of typical effects of spinal cord injury by location (refer to the spinal cord map to the right). Please keep in mind that the prognosis of complete injuries are predictable, incomplete injuries are very variable and may differ form the descriptions below.

Cervical injuries

Cervical (neck) injuries usually result in full or partial tetraplegia. Depending on the exact location of the injury, one with a spinal cord injury at the cervical may retain some amount of function as detailed below, but are otherwise completely paralyzed.

  • C3 vertebrae and above: Typically lose diaphragm function and require a ventilator to breathe.
  • C4: May have some use of biceps and shoulders, but weaker.
  • C5: May retain the use of shoulders and biceps, but not of the wrists or hands.
  • C6: Generally retain some wrist control, but no hand function.
  • C7 and T1: Can usually straighten their arms but still may have dexterity problems with the hand and fingers. C7 is the level for functional independence.

Thoracic injuries

Injuries at the thoracic level and below result in paraplegia. The hands, arms, head, and breathing are usually not affected.

  • T1 to T8 : Most often have control of the hands, but lack control of the abdominal muscles so control of the trunk is difficult or impossible. Effects are less severe the lower the injury.
  • T9 to T12 : Allows good trunk and abdominal muscle control, and sitting balance is very good.

Lumbar and Sacral injuries

The effect of injuries to the lumbar or sacral region of the spinal canal is decreased control of the legs and hips, and anus.

Central Cord and Other Syndromes

Central cord syndrome

Central cord syndrome (picture 1) is a form of incomplete spinal cord injury characterized by impairment in the arms and hands and, to a lesser extent, in the legs. This is also referred to as inverse paraplegia, because the hands and arms are paralyzed while the legs and lower extremities work correctly.

Most often the damage is to the cervical or upper thoracic regions of the spinal cord, and characterized by weakness in the arms with relative sparing of the legs with variable sensory loss.

This condition is associated with ischemia, hemorrhage, or necrosis involving the central portions of the spinal cord (the large nerve fibers that carry information directly from the cerebral cortex). Corticospinal fibers destined for the legs are spared due to their more external location in the spinal cord.

This clinical pattern may emerge during recovery from spinal shock due to prolonged swelling around or near the vertebrae, causing pressures on the cord. The symptoms may be transient or permanent.

Anterior Cord Syndrome (picture 2) is also an incomplete spinal cord injury. Below the injury, motor function, pain sensation, and temperature sensation is lost; touch, propioception (sense of position in space), and vibration sense remain intact. Posterior Cord Syndrome (not pictured) can also occur, but is very rare.

Brown-Sequard Syndrome (picture 3) usually occurs when the spinal cord is hemisectioned or injured on the lateral side. On the ipsilateral side of the injury (same side), there is a loss of motor function, propioception, vibration, and deep touch. Contralaterally (opposite side of injury), there is a loss of pain, temperature, and light touch sensations.

Treatment

Treatment for acute traumatic spinal cord injuries has consisted of giving high dose methylprednisolone if the injury occurred within 8 hours. The recommendation is primarily based on the National Acute Spinal Cord Injury Studies (NASCIS) II and III. Some of the claims of the studies have been challenged as being from faulty intrepretation of the data.

Head Injury

Head injury is a trauma to the head that may or may not include injury to the brain.
The incidence (number of new cases) of head injury is 300 per 100,000 per year (0.3% of the population), with a mortality of 25 per 100,000 in North America and 9 per 100,000 in Britain. Head trauma is a common cause of childhood hospitalization.

Causes

Common causes of head injury are traffic accidents, home and occupational accidents, falls, and assaults. Bicycle accidents are also a common cause of head injury-related death and disability, especially among children.

Types of head injury

Head injuries include both injuries to the brain and those to other parts of the head, such as the scalp and skull. Head injuries may be closed or open. A closed (non-missile) head injury is one in which the skull is not broken. A penetrating head injury occurs when an object pierces the skull and breaches the dura mater. Brain injuries may be diffuse, occurring over a wide area, or focal, located in a small, specific area.
A head injury may cause a skull fracture, which may or may not be associated with injury to the brain. Some patients may have linear or depressed skull fractures.
If intracranial hemorrhage, or bleeding within the brain occurs, a hematoma within the skull can put pressure on the brain. Types of intracranial hematoma include subdural, subarachnoid, extradural, and intraparenchymal hematoma. Craniotomy surgeries are used in these cases to lessen the pressure by draining off blood.
Brain injury can be at the site of impact, but can also be at the opposite side of the skull due to a contrecoup effect (the impact to the head can cause the brain to move within the skull, causing the brain to impact the interior of the skull opposite the head-impact). If the impact causes the head to move, the injury may be worsened, because the brain may ricochet inside the skull (causing additional impacts), or the brain may stay relatively still (due to inertia) but be hit by the moving skull.
Specific problems after head injury can include:

  • Lacerations
  • Skull fracture to the scalp and resulting hemorrhage of the skin
  • Traumatic subdural hematoma, a bleeding below the dura mater which may develop slowly
  • Traumatic extradural, or epidural hematoma, bleeding between the dura mater and the skull
  • Traumatic subarachnoid hemorrhage
  • Cerebral contusion, a bruise of the brain
  • Concussion, a temporary loss of function due to trauma
  • Dementia pugilistica, or “punch-drunk syndrome”, caused by repetitive head injuries, for example in boxing or other contact sports
  • A severe injury may lead to a coma or death

Concussion

Mild concussions are not associated with any sequelae. However, a slightly greater injury can be associated with both anterograde and retrograde amnesia (inability to remember events before or after the injury). The amount of time that the amnesia is present correlates with the severity of the injury. In some cases the patients may develop postconcussion syndrome, which can include memory problems, dizziness, and depression. Cerebral concussion is the most common head injury seen in children.

Epidural hematoma

Epidural hematoma (EDH) is a rapidly accumulating hematoma between the dura mater and the cranium. These patients have a history of head trauma with loss of consciousness, then a lucid period, followed by loss of consciousness. Clinical onset occurs over minutes to hours. Many of these injuries are associated with lacerations of the middle meningeal artery. A “lenticular”, or convex, lens-shaped extracerebral hemorrhage will likely be visible on a CT scan of the head. Although death is a potential complication, the prognosis is good when this injury is recognized and treated.

Subdural hematoma

Subdural hematoma occurs when there is tearing of the bridging vein between the cerebral cortex and a draining venous sinus. At times they may be caused by arterial lacerations on the brain surface. Patients may have a history of loss of consciousness but they recover and do not relapse. Clinical onset occurs over hours. A crescent shaped hemorrhage compressing the brain will be noted on CT of the head. Surgical evacuation is the treatment. Complications include uncal herniation, focal neurologic deficits, and death. The prognosis is guarded.

Cerebral contusion

Cerebral contusion is bruising of the brain tissue. The majority of contusions occur in the frontal and temporal lobes. Complications may include cerebral edema and transtentorial herniation. The goal of treatment should be to treat the increased intracranial pressure. The prognosis is guarded.

Diffuse axonal injury

Diffuse axonal injury, or DAI, usually occurs as the result of an acceleration or deceleration motion, not necessarily an impact. Axons are stretched and damaged when parts of the brain of differing density slide over one another. Prognoses vary widely depending on the extent of damage.

Symptoms

Presentation varies according to the injury. Some patients with head trauma stabilize and other patients deteriorate. A patient may present with or without neurologic deficit.
Patients with concussion may have a history of seconds to minutes unconsciousness, then normal arousal. Disturbance of vision and equilibrium may also occur.
Common symptoms of head injury include those indicative of traumatic brain injury:

  • loss of consciousness
  • confusion
  • drowsiness
  • personality change
  • seizures
  • nausea and vomiting
  • headache
  • a lucid interval, during which a patient appears conscious only to deteriorate later

Symptoms of skull fracture can include:

  • Leaking cerebrospinal fluid (a clear fluid drainage from nose, mouth or ear) may be and is strongly indicative of basilar skull fracture and the tearing of sheaths surrounding the brain, which can lead to secondary brain infection.
  • Visible deformity or depression in the head or face; for example a sunken eye can indicate a maxillar fracture
  • An eye that cannot move or is deviated to one side can indicate that a broken facial bone is pinching a nerve that innervates eye muscles
  • Wounds or bruises on the scalp or face.

Because brain injuries can be life threatening, even people with apparently slight injuries, with no noticeable signs or complaints, require close observation. The caretakers of those patients with mild trauma who are released from the hospital are frequently advised to rouse the patient several times during the next 12 to 24 hours to assess for worsening symptoms.
The Glasgow Coma Scale is a tool for measuring degree of unconsciousness and is thus a useful tool for determining severity of injury. The Pediatric Glasgow Coma Scale is used in young children.

Diagnosis and prognosis

Head injury may be associated with a neck injury. Bruises on the back or neck, back pain, pain radiating to the arms is a sign of cervical spine injury meriting spinal immobilization and application of a cervical collar. It is common for head trauma patients to have drowsiness but to be easily aroused, headaches, and vomiting after injury. If exam and consciousness are preserved, this is of no concern. But if these symptoms persist > 1 or 2 days, a CT of the head is needed. In some cases transient neurologic disturbance may occur, lasting minutes to hours and causing occipital blindness and a state of confusion. Malignant post traumatic cerebral swelling can develop unexpectedly in stable patients after an injury, as can post traumatic seizures. Recovery in children with neurologic deficits will vary. Children with neurologic deficits who improve daily are more likely to recover. Children who are vegetative for months are less likely to improve. Most patients without deficits have full recovery. However, persons who sustain head trauma resulting in unconsciousness for an hour or more have twice the risk of developing Alzheimer’s disease later in life.

Management

Unfortunately, once the brain has been damaged by trauma, there is no quick fix. However, there are some steps that can be taken to prevent secondary damage. If left untreated many patients with head injury will rapidly develop complications which may lead to death or permanent disability. Prompt medical treatment may prevent the worsening of symptoms and lead to a better outcome. Medical treatment should begin at the scene of the trauma. Paramedics will generally immobilize the patient to insure no further damage to the spine or nervous system, insert an airway to insure uninterrupted breathing, and perform endotracheal intubation if indicated. One or more IVs will be inserted to maintain perfusion status. In some cases medications may be administered to sedate or paralyze the patient to prevent additional movement which may worsen the brain injury. The patient should be delivered promptly to a hospital with neurosurgical capabilities. The management of brain injury requires the involvement of subspecialists who are generally available only at larger hospitals.

References

  • National Safe Kids Campaign (NSKC) (2004). Bicycle injury fact sheet. NSKC. Retrieved on 2006-12-19.
  • Small, Gary W (2002-06-22). “What we need to know about age related memory loss”.
    British Medical Journal: 1502-1507. Retrieved on 2006-11-05.

Complex Regional Pain Syndrome

Complex Regional Pain Syndrome (CRPS) is a chronic condition characterized by severe pain following injury to bone and soft tissue. The International Association for the Study of Pain has divided CRPS into two types based on the presence of nerve lesion following the injury. Type I, also known as Reflex sympathetic dystrophy (RSD), Sudeck’s atrophy, Reflex neurovascular dystrophy (RND) or algoneurodystrophy, does not have demonstrable nerve lesions, while type II, also known as causalgia, has evidence of obvious nerve lesions. The cause of these syndromes is currently unknown. Precipitating factors include illness, injury.

History and nomenclature

The condition currently known as CRPS was originally described by Silas Weir Mitchell during the American Civil War, who named the condition causalgia. In the 1940s, the term reflex sympathetic dystrophy came into use to describe this condition, based on the theory that sympathetic hyperactivity was involved in the pathophysiology (Evans, 1946). Misuse of the terms, as well as doubts about the underlying pathophysiology, led to calls for better nomenclature. In 1993, a special consensus workshop held in Orlando, Florida, provided the umbrella term, complex regional pain syndrome, with causalgia and RSD as its subtypes (see Stanton-Hicks et al, 1995).

pathophysiology

The pathophysiology of CRPS remains unclear.

Susceptibility

CRPS can strike at any age, but is more common between the ages of 40 and 60. It affects both men and women, but is more frequently seen in women. The number of reported CRPS cases among adolescents and young adults is increasing.
Investigators estimate that two to five percent of those with peripheral nerve injury and 12 to 21 percent of those with hemiplegia (paralysis of one side of the body) will suffer from CRPS.

Symptoms

The symptoms of CRPS usually occurs near the site of an injury, either major or minor, and usually spreads beyond the original area. It may spread to involve the entire limb and, rarely, the opposite limb. The most common symptom is burning pain. The patient may also experience muscle spasms, local swelling, increased sweating, softening of bones, joint tenderness or stiffness, restricted or painful movement, and changes in the nails and skin.
The pain of CRPS is continuous and may be heightened by emotional stress. Moving or touching the limb is often intolerable. Eventually the joints become stiff from disuse, and the skin, muscles, and bone atrophy. The symptoms of CRPS vary in severity and duration. There are three variants of CRPS, previously thought of as stages. It is now believed that patients with CRPS do not progress through these stages sequentially and/or that these stages are not time limited. Instead, patients are likely to have one of the three following types of disease progression:

  1. Type one is characterized by severe, burning pain at the site of the injury. Muscle spasm, joint stiffness, restricted mobility, rapid hair and nail growth, and vasospasm (a constriction of the blood vessels) that affects color and temperature of the skin can also occur.
  2. Type two is characterized by more intense pain. Swelling spreads, hair growth diminishes, nails become cracked, brittle, grooved, and spotty, osteoporosis becomes severe and diffuse, joints thicken, and muscles atrophy.
  3. Type three is characterized by irreversible changes in the skin and bones, while the pain becomes unyielding and may involve the entire limb. There is marked muscle atrophy, severely limited mobility of the affected area, and flexor tendon contractions (contractions of the muscles and tendons that flex the joints). Occasionally the limb is displaced from its normal position, and marked bone softening is more dispersed.

Diagnosis

CRPS types I and II share the common diagnostic criteria shown below.
Spontaneous pain or allodynia/hyperalgesia is not limited to the territory of a single peripheral nerve, and is disproportionate to the inciting event. There is a history of edema, skin blood flow abnormality, or abnormal sweating in the region of the pain since the inciting event.
No other conditions can account for the degree of pain and dysfunction.
The two types differ only in the nature of the inciting event. Type I CRPS develops following an initiating noxious event that may or may not have been traumatic, while type II CRPS develops after a nerve injury.
No specific test is available for CRPS, which is diagnosed primarily through observation of the symptoms. However, thermography, sweat testing, x-rays, electrodiagnostics, and sympathetic blocks can be used to build up a picture of the disorder. Diagnosis is complicated by the fact that some patients improve without treatment. A delay in diagnosis and/or treatment for this syndrome can result in severe physical and psychological problems. Early recognition and prompt treatment provide the greatest opportunity for recovery.

Thermography

Thermography is a diagnostic technique for measuring blood flow by determining the variations in heat emitted from the body. A color-coded “thermogram” of a person in pain often shows an altered blood supply to the painful area, appearing as a different shade (abnormally pale or violet) than the surrounding areas of the corresponding part on the other side of the body. A difference of 1.0°C between two symmetrical body parts is considered significant, especially if a large number of asymmetrical skin temperature sites are present. He affected limb may be warmer or cooler than the unaffected limb.

Sweat testing

Abnormal sweating can be detected by several tests. A powder that changes color when exposed to sweat can be applied to the limbs; however, this method does not allow for quantification of sweating. Two quantitative tests that may be used are the resting sweat output test and the quantitative sudomotor axon reflex test. These quantitative sweat tests have been shown to correlate with clinical signs of CRPS (Sandroni, 1998).

Radiography

Patchy osteoporosis, which may be due to disuse of the affected extremity, can be detected on X-ray as early as 2 weeks after the onset of CRPS. Bone scan of the affected limb may detect these changes even sooner. Bone densitometry can also be used to detect changes in bone mineral density. It can also be used to monitor the results of treatment, as bone densitometry paramters improve with treatment.

Electrodiagnostic testing

The nerve injury that characterizes type II CRPS can be detected by electromyography. In contrast to peripheral mononeuropathy, the symptoms of type 2 CRPS extend beyond the distribution of the affected peripheral nerve.

Treatment

Physicians use a variety of drugs to treat CRPS, including antidepressants, anti-inflammatories such as corticosteroids and COX-inhibitors such as piroxicam, vasodilators, GABA analogs such gabapentin and pregabalin, and alpha- or beta-adrenergic-blocking compounds. Elevation of the extremity and physical therapy are also used to treat CRPS.
Injection of a local anesthetic, such as lidocaine, is often the first step in treatment. Injections are repeated as needed. However, early intervention with non-invasive management may be preferred to repeated nerve blockade. The use of topical lidocaine patches has been shown to be of use in the treatment of CRPS-1 and -2 . TENS (transcutaneous electrical nerve stimulation), a procedure in which brief pulses of electricity are applied to nerve endings under the skin, has helped some patients in relieving chronic pain.
Neurostimulation (spinal cord stimulators) may also be surgically implanted to reduce the pain by directly stimulating the spinal cord. These devices place electrodes either in the epidural space (space above the spinal cord) or directly over nerves located outside the central nervous system. Implantable drug pumps may also be used to deliver pain medication directly to the cerebrospinal fluid which allows powerful opioids to be used in a much smaller dose than when taken orally. Prednisolone (a corticosteroid) has been shown to be superior to piroxicam in the treatment of reflex sympathetic dystrophy.
Surgical, chemical, or radiofrequency sympathectomy – interruption of the affected portion of the sympathetic nervous system – can be used as a last resort in patients with impending tissue loss, edema, recurrent infection, or ischemic necrosis (Stanton-Hicks et al, 1998). However, there is little evidence that these permanent interventions alter the pain symptoms of these devastated patients.
Physical therapy is the most important part of treatment, though it should be noted that many patients are incapable of participating in physical therapy due to muscular and bone problems. People struggling with CRPS often develop guarding behaviors where they avoid using or touching the affected limb. Unfortunately, inactivity can exacerbate the disease and perpetuate the pain cycle. Physical therapy works best for most patients, especially goal-directed therapy, where the patient begins from an initial point, regardless of how minimal, and then endeavors to increase activity each week. Therapy should be directed at facilitating the patient to engage in physical therapy, movement and stimulation of the affected areas.
Some treating physicians have even initiated physical therapy under light general anesthesia, in an attempt to remobilize the extremity. While the unpredictability of this illness often causes a frustrating pattern of progress and regress, it is essential to continue to try to increase and normalize physicial activity.
Biofeedback, and Feldenkrais can also be important modalities of treatment.

Ketamine Therapy

Ketamine, a potent anesthetic, is being used as an experimental and controversial treatment for Complex Regional Pain Syndrome. The theory of ketamine use in CRPS/RPS is primarily advanced by neurologist Dr Robert J. Schwartzman of Drexel University College of Medicine in Philadelphia, and researchers at the University of T?bingen in Germany. The hypothesis is that ketamine manipulates NMDA receptors which might reboot aberrant brain activity.
There are two treatment modalities, the first consist of a low dose ketamine infusion of between 25-90 mg per day, over five days either in hospital or as an outpatient. This is called the awake technique. Open label, prospective, pain journal evaluation of a 10-day infusion of intravenous ketamine (awake technique) in the CRPS patient concluded that “A four-hour ketamine infusion escalated from 40-80 mg over a 10-day period can result in a significant reduction of pain with increased mobility and a tendency to decreased autonomic dysregulation”.
The second treatment modality consists of putting the patient into a medically-induced coma and given an extremely high dosage of ketamine; typically between 600-900 mg.[5] This version, currently not allowed in the United States, is most commonly done in Germany but some treatments are now also taking place in Monterrey, Mexico.
According to Dr Schwartzman, 14 cases out of 41 patients in the coma induced ketamine experiments were completely cured. “We haven’t cured the original injury,” he says, “but we have cured the RSD or kept it in remission. The RSD pain is gone.”
“No one ever cured it before,” he adds. “In 40 years, I have never seen anything like it. These are people who were disabled and in horrible pain. Most were completely incapacitated. They go back to work, back to school, and are doing everything they used to do. Most are on no medications at all. I have taken morphine pumps out of people. You turn off the pain and reset the whole system.”
No trials have been done for the coma induced method to date.

Prognosis

Good progress can be made in treating CRPS if treatment is begun early, ideally within 3 months of the first symptoms. Early treatment often results in remission. If treatment is delayed, however, the disorder can quickly spread to the entire limb and changes in bone and muscle may become irreversible. In 50 percent of CRPS cases, pain persists longer than 6 months and sometimes for years. In teens and younger patients with CRPS, the prognosis is excellent. Even without invasive therapy, upwards of 75% of children have full recovery with virtually 100% of the patients have marked improvement.

Similar disorders

CRPS has characteristics similar to those of other disorders, such as shoulder-hand syndrome, which sometimes occurs after a heart attack and is marked by pain and stiffness in the arm and shoulder; Sudeck syndrome, which is prevalent in older people and women and is characterized by bone changes and muscular atrophy, but is not always associated with trauma; and Steinbrocker syndrome, which includes symptoms such as gradual stiffness, discomfort, and weakness in the shoulder and hand. Erythromelalgia also shares many components of CRPS (burning pain, redness, tempurature hypersensative, autonomic dysfunction, vasospasm)they both involve small fiber sensory neurosympathetic components. Interestingly Erythromelalgia involves a lack of sweating, whereas CRPS often involves increased sweating. Subvariations of both exist.

Current research

The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health (NIH), supports and conducts research on the brain and central nervous system, including research relevant to RSDS, through grants to major medical institutions across the country. NINDS-supported scientists are working to develop effective treatments for neurological conditions and, ultimately, to find ways of preventing them.Investigators are studying new approaches to treat RSDS and intervene more aggressively after traumatic injury to lower the patient’s chances of developing the disorder. In addition, NINDS-supported scientists are studying how signals of the sympathetic nervous system cause pain in RSDS patients. Using a technique called microneurography, these investigators are able to record and measure neural activity in single nerve fibers of affected patients. By testing various hypotheses, these researchers hope to discover the unique mechanism that causes the spontaneous pain of RSDS and that discovery may lead to new ways of blocking pain.Other studies to overcome chronic pain syndromes are discussed in the pamphlet “Chronic Pain: Hope Through Research,” published by the NINDS.
Research into treating the condition with Mirror Visual Feedback is being undertaken at the Royal National Hospital for Rheumatic Disease in Bath. Patients are taught how to desensitize in the most affective way then progress on to using mirrors to rewrite the faulty signals in the brain that appear responsible for this condition. It is important to note that around 50% of patients recover from this condition.

CRPS in animals

CRPS has also been described in non-human animals (Bergadano et al, 2006).

References

1. sDevers A, Galer BS. (2000). “Topical Lidocaine Patch Relieves a Variety of Neuropathic Pain Conditions: An Open-Label Study.”. Clinical Journal of Pain 16: 205-208.
2. Frost, SG. (2003). “Treatment of Complex Regional Pain Syndrome Type 1 in a Pediatric Patient Using the Lidocaine Patch 5%: A Case Report.”. Current Therapeutic Research 64 (8): 626-629.
3. Kalita J, Vajpayee A, Misra UK. (2006). “Comparison of prednisolone with piroxicam in complex regional pain syndrome following stroke: a randomized controlled trial.”. QJM 99 (2): 89-95.
4. Goldberg ME, Domsky R, Scaringe D, Hirsh R, Dotson J, Sharaf I, Torjman MC, Schwartzman RJ. “Multi-day low dose ketamine infusion for the treatment of complex regional pain syndrome”.Pain Physician. 2005 Apr;8(2):175-9.
5. CNN report on Ketamine therapy for CRPS/RSD September 1, 2006 Szalavitz, Maia. “Tackling depression with ketamine”, New Scientist, January 20, 2007.
6. Sandroni P, Low PA, Ferrer T, Opfer-Gehrking TL, Willner CL, Wilson PR (1998). “Complex regional pain syndrome I (CRPS I): prospective study and laboratory evaluation”. Clin J Pain 14 (4): 282-9.
7. Stanton-Hicks M, Janig W, Hassenbusch S, Haddox JD, Boas R, Wilson P (1995). “Reflex sympathetic dystrophy: changing concepts and taxonomy”. Pain 63 (1): 127-33.
8. Stanton-Hicks M, Baron R, Boas R, Gordh T, Harden N, Hendler N, Koltzenburg M, Raj P, Wilder R (1998). “Complex Regional Pain Syndromes: guidelines for therapy”. Clin J Pain 14 (2): 155-66.
9. Wilder, R.T. et al. (1992). “Reflex sympathetic dystrophy in children. Clinical characteristics and follow-up of seventy patients”. Journal of Bone & Joint Surgery – American volume 74 (6): 910-19.

Brachial Plexus

The brachial plexus is an arrangement of nerve fibres (a plexus) running from the spine (vertebrae C5-T1), through the neck, the axilla (armpit region), and into the arm.
The brachial plexus is responsible for cutaneous and muscular innervation of the entire upper limb, with two exceptions: the trapezius muscle innervated by the spinal accessory nerve and an area of skin near the axilla innervated by the intercostobrachialis nerve. Therefore, lesions of the plexus can lead to severe functional impairment.

Anatomy

One can remember the order of brachial plexus elements by way of the mnemonic, – Roots, Trunks, Divisions, Cords, Branches or – Roots, Trunks, Divisions, Cords, Collateral/Pre-terminal Branches, and (Terminal) Branches.

  • The five roots are the five anterior rami of the spinal nerves, after they have given off their segmental supply to the muscles of the neck.
  • These roots merge to form three trunks:
    • “superior” or “upper” (C5-C6)
    • “middle” (C7)
    • “inferior” or “lower” (C8-T1)
  • Each trunk then splits in two, to form six divisions:
    • anterior division of the superior, middle, and inferior trunks
    • posterior division of the superior, middle, and inferior trunks
  • These six divisions will regroup to become the three cords. The cords are named by their position in respect to the axillary artery.
  • The posterior cord is formed from the three posterior divisions of the trunks (C5-T1)
  • The lateral cord is the anterior divisions from the upper and middle trunks (C5-C7)
  • The medial cord is simply a continuation of the lower trunk (C8-T1)
  • The branches are listed below. Most branch off of the cords, but a few branch (indicated in italics) directly off of earlier structures. The five in bold are considered “terminal branches”.

Specific branches

From Nerve Roots Muscles Cutaneous
roots dorsal scapular nerve C5 rhomboid muscles and levator scapulae
roots long thoracic nerve C5, C6, C7 serratus anterior
superior trunk nerve to the subclavius C5, C6 subclavius muscle
superior trunk suprascapular nerve C5, C6 supraspinatus and infraspinatus
lateral cord lateral pectoral nerve C5, C6, C7 pectoralis major and pectoralis minor (by communicating with the medial pectoral nerve)
lateral cord musculocutaneous nerve C5, C6, C7 coracobrachialis, brachialis and biceps brachii becomes the lateral cutaneous nerve of the forearm
lateral cord lateral root of the median nerve C5, C6, C7 fibres to the median nerve
posterior cord upper subscapular nerve C5, C6 subscapularis (upper part)
posterior cord thoracodorsal nerve C6, C7, C8 latissimus dorsi
posterior cord lower subscapular nerve C5, C6 lower part of subscapularis and teres major
posterior cord axillary nerve C5, C6 anterior branch: deltoid and a small area of overlying skin
posterior branch: teres minor and deltoid muscles
posterior branch becomes upper lateral cutaneous nerve of the arm
posterior cord radial nerve C5, C6, C7, C8, T1 triceps brachii, anconeus, the extensor muscles of the forearm, and brachioradialis skin of the posterior arm as the posterior cutaneous nerve of the arm
medial cord medial pectoral nerve C8, T1 pectoralis major and pectoralis minor
medial cord medial root of the median nerve C8, T1 fibres to the median nerve portions of hand not served by ulnar or radial
medial cord medial cutaneous nerve of the arm C8, T1 front and medial skin of the arm
medial cord medial cutaneous nerve of the forearm C8, T1 medial skin of the forearm
medial cord ulnar nerve C8, T1 flexor carpi ulnaris, the medial 2 bellies of flexor digitorum profundus, most of the small muscles of the hand the skin of the medial side of the hand and medial one and a half fingers on the palmar side and medial two and a half fingers on the dorsal side

Diagram

Injuries

Brachial plexus lesions are classified as traumautic or obstetric. These typically result from excessive stretching and avulsion injury. Traumatic injuries are often caused by high-velocity motor vehicle accidents, especially in motorcyclists. Injury from a direct blow to the lateral side of the scapula is also possible.

Most commonly, forceps delivery or falling on the neck at an angle causes upper plexus lesions (Erb’s Palsy). This type of injury produces a very characteristic sign called Waiter’s tip deformity due to loss of the lateral rotators of the shoulder, arm flexors, and hand extensor muscles.

Much less frequently, sudden upward pulling on an abducted arm (as when someone breaks a fall by grasping a tree branch) produces a lower plexus injury. This results in the sign known as clawed hand due to loss of function of the ulnar nerve and the intrinsic muscles of the hand it supplies.
The cardinal signs of brachial plexus avulsion are:

  • a weakness in the arm
  • diminished reflexes
  • corresponding sensory deficits

In most cases the nerve roots are stretched or torn from their origin, since the meningeal coverings of the nerve roots are thinner than the sheaths enclosing the peripheral nerves. The epineurium of the peripheral nerve is contiguous with the dural mater, providing extra support to the peripheral nerves. In cases where the nerve roots have been torn, recovery is unlikely without invasive experimental surgical techniques.
The diagnosis may be confirmed by an EMG examination in 5-7 days. The evidence of denervation will be evident. If there is no nerve conduction 72 hours after the injury, then avulsion is most likely.

Traumatic Brain Injury

Traumatic brain injury (TBI), traumatic injuries to the brain, also called intracranial injury, or simply head injury, occurs when a sudden trauma causes brain damage. TBI can result from a closed head injury or a penetrating head injury and is one of two subsets of acquired brain injury (ABI). The other subset is non-traumatic brain injury (i.e. stroke, meningitis, anoxia). Parts of the brain that can be damaged include the cerebral hemispheres, cerebellum, and brain stem (see brain damage). Symptoms of a TBI can be mild, moderate, or severe, depending on the extent of the damage to the brain. Outcome can be anything from complete recovery to permanent disability or death. A coma can also affect a child’s brain.

Epidemiology

TBI is a major public health problem, especially among males ages 15 to 24, and among elderly people of both sexes 75 years and older. Children aged 5 and younger are also at high risk for TBI.[1] Males account for two thirds of childhood and adolescent head trauma patients. Each year in the United States:

  • approximately 1 million head-injured people are treated in hospital emergency rooms
  • approximately 270,000 people experience a moderate or severe TBI
  • approximately 60,000 new cases of epilepsy occur as a result of head trauma
  • approximately 50,000 people die from head injury
  • approximately 230,000 people are hospitalized for TBI and survive
  • approximately 80,000 of these survivors live with significant disabilities as a result of the injury

Signs and symptoms

Some symptoms are evident immediately, while others do not surface until several days or weeks after the injury.
With mild TBI, the patient may remain conscious or may lose consciousness for a few seconds or minutes. The person may also feel dazed or not like him- or herself for several days or weeks after the initial injury. Other symptoms include:

  • Headache
  • Mental confusion
  • Lightheadedness
  • Dizziness
  • Double vision, blurred vision, or tired eyes
  • Ringing in the ears
  • Bad taste in the mouth
  • Fatigue or lethargy
  • A change in sleep patterns
  • Behavioral or mood changes
  • Trouble with memory, concentration, or calculation
  • Symptoms may remain the same or get better; worsening symptoms indicate a more severe injury

With moderate or severe TBI, the patient may show these same symptoms, but may also have:

  • Loss of consciousness
  • Personality change
  • A severe, persistent, or worsening headache
  • Repeated vomiting or nausea
  • Seizures
  • Inability to awaken
  • Dilation (widening) of one or both pupils
  • Slurred speech
  • Weakness or numbness in the extremities
  • Loss of coordination
  • Increased confusion, restlessness, or agitation
  • Vomiting and neurological deficit (e.g. weakness in a limb) together are important indicators of prognosis and their presence may warrant early CT scanning and neurosurgical intervention.

Small children with moderate to severe TBI may show some of these signs as well as signs specific to young children, including:

  • Persistent crying
  • Inability to be consoled
  • Refusal to nurse or eat

Anyone with signs of moderate or severe TBI should receive immediate emergency medical attention.

Causes of and risk factors

Half of all TBIs are due to transportation accidents involving automobiles, motorcycles, bicycles, and pedestrians. These accidents are the major cause of TBI in people under age 75.
For those 75 and older, falls cause the majority of TBIs.
Approximately 20% of TBIs are due to violence, such as firearm assaults and child abuse, and about 3% are due to sports injuries. Fully half of TBI incidents involve alcohol use.
Traumatic brain injury is a frequent cause of major long-term disability in individuals surviving head injuries sustained in war zones. This is becoming an issue of growing concern in modern warfare in which rapid deployment of acute interventions are effective in saving the lives of combatants with significant head injuries.

Types

The damage from TBI can be focal, confined to one area of the brain, or diffuse, involving more than one area of the brain. Diffuse trauma to the brain is frequently associated with concussion (a shaking of the brain in response to sudden motion of the head), diffuse axonal injury, or coma. Localized injuries may be associated with neurobehavioral manifestations, hemiparesis or other focal neurologic deficits.

Types of focal brain injury include bruising of brain tissue called a contusion and intracranial hemorrhage or hematoma, heavy bleeding in the skull. Hemorrhage, due to rupture of a blood vessel in the head, can be extra-axial, meaning it occurs within the skull but outside of the brain, or intra-axial, occurring within the brain. Extra-axial hemorrhages can be further divided into subdural hematoma, epidural hematoma, and subarachnoid hemorrhage. An epidural hematoma involves bleeding into the area between the skull and the dura. With a subdural hematoma, bleeding is confined to the area between the dura and the arachnoid membrane. A subarachnoid hemorrhage involves bleeding into the space between the surface of the brain and the arachnoid membrane that lies just above the surface of the brain, usually resulting from a tear in a blood vessel on the surface of the brain. Bleeding within the brain itself is called an intracerebral hematoma. Intra-axial bleeds are further divided into intraparenchymal hemorrhage which occurs within the brain tissue itself and intraventricular hemorrhage which occurs into the ventricular system.

TBI can result from a closed head injury or a penetrating head injury. A closed injury occurs when the head suddenly and violently hits an object but the object does not break through the skull. A penetrating injury occurs when an object pierces the skull and enters brain tissue. As the first line of defense, the skull is particularly vulnerable to injury. Skull fractures occur when a bone in the skull cracks or breaks. A depressed skull fracture occurs when pieces of the broken skull press into the tissue of the brain. A penetrating skull fracture occurs when something pierces the skull, such as a bullet, leaving a distinct and localized traumatic injury to brain tissue. Skull fractures can cause cerebral contusion.

Another insult to the brain that can cause injury is anoxia. Anoxia is a condition in which there is an absence of oxygen supply to an organ’s tissues, even if there is adequate blood flow to the tissue. Hypoxia refers to a decrease in oxygen supply rather than a complete absence of oxygen, and ischemia is inadequate blood supply, as is seen in cases in which the brain swells. In any of these cases, without adequate oxygen, a biochemical cascade called the ischemic cascade is unleashed, and the cells of the brain can die within several minutes. This type of injury is often seen in near-drowning victims, in heart attack patients (particularly those who have suffered a cardiac arrest, or in people who suffer significant blood loss from other injuries that then causes a decrease in blood flow to the brain due to circulatory (hypovolemic) shock.

Effects on consciousness

Generally, there are six abnormal states of consciousness that can result from a TBI: stupor, coma, persistent vegetative state, minimally conscious state, locked-in syndrome, and brain death.
Stupor is a state in which the patient is unresponsive but can be aroused briefly by a strong stimulus, such as sharp pain. Coma is a state in which the patient is totally unconscious, unresponsive, unaware, and unarousable.
Patients in a persistent vegetative state are unconscious and unaware of their surroundings, but they continue to have a sleep-wake cycle and can have periods of alertness. A vegetative state can result from diffuse injury to the cerebral hemispheres of the brain without damage to the lower brain and brainstem. Anoxia, or lack of oxygen to the brain, which is a common complication of cardiac arrest, can also bring about a vegetative state.

Patients in a minimally conscious state have a reduced level of arousal and may appear, on the surface, to be in a persistent vegetative state but are capable of demonstrating the ability to actively process information. In the minimally conscious state a patient exhibits deliberate, or cognitively mediated, behavior often enough, or consistently enough, for clinicians to be able to distinguish it from the entirely unconscious, reflexive responses that are seen in the persistent vegetative state. Differentiating a patient in a persistent vegetative state from one in a minimally conscious state can be challenging but remains a critically important clinical task.
Locked-in syndrome is a condition in which a patient is aware and awake, but cannot move or communicate due to complete paralysis of the body.

Brain death is the lack of measurable brain function due to diffuse damage to the cerebral hemispheres and the brainstem, with loss of any integrated activity among distinct areas of the brain. Brain death is irreversible. Removal of assistive devices will result in immediate cardiac arrest and cessation of breathing.

Recent studies have brought into question the nature of coma and consciousness in TBI. For example, a 23 year old woman in a vegetative state after a severe brain injury due to a car accident was able to communicate with a team of British researchers at Cambridge University in England via functional magnetic resonance imaging.[3] While cautious about accepting the study’s results, Nicholas Schiff, a neurologist at the Weill Cornell Medical College in New York, agrees that the research was groundbreaking. “It’s the first time we’ve ever seen something like this. It really is kind of shocking,” he said.

Complications

Sometimes, health complications occur in the period immediately following a TBI. These complications are not types of TBI, but are distinct medical problems that arise as a result of the injury. Although complications are rare, the risk increases with the severity of the trauma.
Complications of TBI include immediate seizures, hydrocephalus or post-traumatic ventricular enlargement, cerebrospinal fluid leaks, infections, vascular injuries, cranial nerve injuries, pain, bed sores, multiple organ system failure in unconscious patients, and polytrauma (trauma to other parts of the body in addition to the brain).

About 25% of patients with brain contusions or hematomas and about 50% of patients with penetrating head injuries will develop immediate seizures, seizures that occur within the first 24 hours of the injury. These immediate seizures increase the risk of early seizures – defined as seizures occurring within 1 week after injury – but do not seem to be linked to the development of post-traumatic epilepsy (recurrent seizures occurring more than 1 week after the initial trauma). Generally, medical professionals use anticonvulsant medications to treat seizures in TBI patients only if the seizures persist.

Hydrocephalus or post-traumatic ventricular enlargement occurs when cerebrospinal fluid (CSF) accumulates in the brain resulting in dilation of the cerebral ventricles (cavities in the brain filled with CSF) and an increase in ICP. This condition can develop during the acute stage of TBI or may not appear until later. Generally it occurs within the first year of the injury and is characterized by worsening neurological outcome, impaired consciousness, behavioral changes, ataxia (lack of coordination or balance), incontinence, or signs of elevated ICP. The condition may develop as a result of meningitis, subarachnoid hemorrhage, intracranial hematoma, or other injuries. Treatment includes shunting and draining of CSF as well as any other appropriate treatment for the root cause of the condition.

Skull fractures can tear the membranes that cover the brain, leading to CSF leaks. A tear between the dura and the arachnoid membranes, called a CSF fistula, can cause CSF to leak out of the subarachnoid space into the subdural space; this is called a subdural hygroma. CSF can also leak from the nose and the ear. These tears that let CSF out of the brain cavity can also allow air and bacteria into the cavity, possibly causing infections such as meningitis. Pneumocephalus occurs when air enters the intracranial cavity and becomes trapped in the subarachnoid space.

Infections within the intracranial cavity are a dangerous complication of TBI. They may occur outside of the dura mater, below the dura, below the arachnoid (meningitis), or within the brain itself (abscess). Most of these injuries develop within a few weeks of the initial trauma and result from skull fractures or penetrating injuries. Standard treatment involves antibiotics and sometimes surgery to remove the infected tissue. Meningitis may be especially dangerous, with the potential to spread to the rest of the brain and nervous system.
Any damage to the head or brain usually results in some damage to the vascular system, which provides blood to the cells of the brain. The body’s immune system can repair damage to small blood vessels, but damage to larger vessels can result in serious complications. Damage to one of the major arteries leading to the brain can cause a stroke, either through bleeding from the artery (hemorrhagic stroke) or through the formation of a clot at the site of injury, called a thrombus or thrombosis, blocking blood flow to the brain (ischemic stroke). Blood clots also can develop in other parts of the head. Symptoms such as headache, vomiting, seizures, paralysis on one side of the body, and semiconsciousness developing within several days of a head injury may be caused by a blood clot that forms in the tissue of one of the sinuses, or cavities, adjacent to the brain. Thrombotic-ischemic strokes are treated with anticoagulants, while surgery is the preferred treatment for hemorrhagic stroke. Other types of vascular injuries include vasospasm and the formation of aneurysms.

Skull fractures, especially at the base of the skull, can cause cranial nerve injuries that result in compressive cranial neuropathies. All but three of the 12 cranial nerves project out from the brainstem to the head and face. The seventh cranial nerve, called the facial nerve, is the most commonly injured cranial nerve in TBI and damage to it can result in paralysis of facial muscles.

Pain, especially headache, is commonly a significant complication for conscious patients in the period immediately following a TBI. Serious complications for patients who are unconscious, in a coma, or in a vegetative state include bed or pressure sores of the skin, recurrent bladder infections, pneumonia or other life-threatening infections, and progressive multiple organ failure.

General trauma

Other medical complications that may accompany a TBI include pulmonary (lung) dysfunction; cardiovascular (heart) dysfunction from blunt chest trauma; gastrointestinal dysfunction; fluid and hormonal imbalances; and other isolated complications, such as fractures, nerve injuries, deep vein thrombosis, excessive blood clotting, and infections.

As with all conditions that can produce immobility and a decrease in active movement in the legs, the problem of venous thrombosis in the deep veins of the legs (ie. deep vein thrombosis) and the associated life-threatening problem of pulmonary embolism can develop in individuals with TBI. The risk of developing deep vein thrombosis is particularly high if there has been significant trauma to the legs in addition to the TBI. Several other factors are known to raise the risk for deep vein thrombosis. This is a critically important issue because death due to pulmonary embolism is potentially preventable if venous thrombosis in the legs is detected and treated before leading to a pulmonary embolism.

Trauma victims often develop hypermetabolism or an increased metabolic rate, which leads to an increase in the amount of heat the body produces. The body redirects into heat the energy needed to keep organ systems functioning, causing muscle wasting and the starvation of other tissues. The nutritional management of patients with TBI, including the provision of adequate calories and protein through an available route of administration to balance consumption, is thus critically important in order to avoid complications related to hypermetabolism and resulting malnutrition. Provision of food through a feeding tube may be temporarily necessary to meet the nutritional needs of the patient with a severe TBI, until they are awake and able to eat and swallow safely without risking pulmonary aspiration and the development of aspiration pneumonia. Sometimes the use of parenteral feeding is necessary if the patient has associated injuries or complications that prevent direct access to the digestive system. Complications related to pulmonary dysfunction can include neurogenic pulmonary edema (excess fluid in lung tissue), aspiration pneumonia (pneumonia caused by foreign matter in the lungs), and fat and blood clots in the blood vessels of the lungs.
Fluid and hormonal imbalances can complicate the treatment of hypermetabolism and high intracranial pressure (ICP). Hormonal problems can result from dysfunction of the pituitary, the thyroid, and other glands throughout the body. Two common hormonal complications of TBI are syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and hypothyroidism.

Disabilities resulting from TBI

Disabilities resulting from a TBI depend upon the severity of the injury, the location of the injury, and the age and general health of the patient. Some common disabilities include problems with cognition (attention, calculation, memory, judgment, insight, and reasoning), sensory processing (sight, hearing, touch, taste, and smell), communication (language expression and understanding), social function (empathy, capacity for compassion, interpersonal social awareness and facility) and mental health (depression, anxiety, personality changes, aggression, acting out, and social inappropriateness).

Within days to weeks of the head injury approximately 40% of TBI patients develop a host of troubling symptoms collectively called postconcussion syndrome (PCS). A patient need not have suffered a concussion or loss of consciousness to develop the syndrome and many patients with mild TBI suffer from PCS.[1] Symptoms include headache, dizziness, memory problems, trouble concentrating, sleeping problems, restlessness, irritability, apathy, depression, and anxiety. These symptoms may last for a few weeks after the head injury. The syndrome is more prevalent in patients who had psychiatric symptoms, such as depression or anxiety, before the injury. Treatment for PCS may include medicines for pain and psychiatric conditions, and psychotherapy and occupational therapy.

Most patients with severe TBI, if they recover consciousness, suffer from cognitive disabilities, including the loss of many higher level mental skills. The most common cognitive impairment among severely head-injured patients is memory loss, characterized by some loss of specific memories and the partial inability to form or store new ones. Some of these patients may experience post-traumatic amnesia (PTA), either anterograde or retrograde. Anterograde PTA is impaired memory of events that happened after the TBI, while retrograde PTA is impaired memory of events that happened before the TBI.

Many patients with mild to moderate head injuries who experience cognitive deficits become easily confused or distracted and have problems with concentration and attention. They also have problems with higher level, so-called executive functions, such as planning, organizing, abstract reasoning, problem solving, and making judgments, which may make it difficult to resume pre-injury work-related activities. Recovery from cognitive deficits is greatest within the first 6 months after the injury and more gradual after that.

Patients with moderate to severe TBI have more problems with cognitive deficits than patients with mild TBI, but a history of several mild TBIs may have an additive effect, causing cognitive deficits equal to a moderate or severe injury.
Many TBI patients have sensory problems, especially problems with vision. Patients may not be able to register what they are seeing or may be slow to recognize objects. Also, TBI patients often have difficulty with hand-eye coordination. Because of this, TBI patients may seem clumsy or unsteady. Other sensory deficits may include problems with hearing, smell, taste, or touch. Some TBI patients develop tinnitus, a ringing or roaring in the ears. A person with damage to the part of the brain that processes taste or smell may develop a persistent bitter taste in the mouth or perceive a persistent noxious smell. Damage to the part of the brain that controls the sense of touch may cause a TBI patient to develop persistent skin tingling, itching, or pain. These conditions are rare and hard to treat.

Language and communication problems are common disabilities in TBI patients. Some may experience aphasia, defined as difficulty with understanding and producing spoken and written language; others may have difficulty with the more subtle aspects of communication, such as body language and emotional, non-verbal signals.

In non-fluent aphasia, also called Broca’s aphasia or motor aphasia, TBI patients often have trouble recalling words and speaking in complete sentences. They may speak in broken phrases and pause frequently. Most patients are aware of these deficits and may become extremely frustrated.

Patients with fluent aphasia, also called Wernicke’s aphasia or sensory aphasia, display little meaning in their speech, even though they speak in complete sentences and use correct grammar. Instead, they speak in flowing gibberish, drawing out their sentences with non-essential and invented words. Many patients with fluent aphasia are unaware that they make little sense and become angry with others for not understanding them. Patients with global aphasia have extensive damage to the portions of the brain responsible for language and often suffer severe communication disabilities.

TBI patients may have problems with spoken language if the part of the brain that controls speech muscles is damaged. In this disorder, called dysarthria, the patient can think of the appropriate language, but cannot easily speak the words because they are unable to use the muscles needed to form the words and produce the sounds. Speech is often slow, slurred, and garbled. Some may have problems with intonation or inflection, called prosodic dysfunction.

TBI patients have been described as the “walking wounded” owing to psychological problems. Most TBI patients have emotional or behavioral problems that fit under the broad category of psychiatric health. Family members of TBI patients often find that personality changes and behavioral problems are the most difficult disabilities to handle. Psychiatric problems that may surface include depression, apathy, anxiety, irritability, anger, paranoia, confusion, frustration, agitation, insomnia or other sleep problems, and mood swings.
Problem behaviors may include aggression and violence, impulsivity, disinhibition, acting out, noncompliance, social inappropriateness, emotional outbursts, childish behavior, impaired self-control, impaired self-awareness, inability to take responsibility or accept criticism, egocentrism, inappropriate sexual activity, and alcohol or drug abuse or addiction. Some patients’ personality problems may be so severe that they are diagnosed with organic personality disorder, a psychiatric condition characterized by many of the problems mentioned above. Sometimes TBI patients suffer from developmental stagnation, meaning that they fail to mature emotionally, socially, or psychologically after the trauma. This is a serious problem for children and young adults who suffer from a TBI.
Attitudes and behaviors that are appropriate for a child or teenager become inappropriate in adulthood. Many TBI patients who show psychiatric or behavioral problems can be helped with medication and psychotherapy, although the effectiveness of psychotherapy may be limited by the residual neurocognitive impairment. Technological improvements and excellent emergency care have diminished the incidence of devastating TBI while increasing the numbers of patients with mild or moderate TBI. Such patients are more adversely affected by their emotional problems than by their residual physical disabilities.

Other associated long-term problems

Other long-term problems that can develop after a TBI include Parkinson’s disease and other motor problems, Alzheimer’s disease, dementia pugilistica, and post-traumatic dementia.
Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by dementia, memory loss, and deteriorating cognitive abilities. Research suggests an association between head injury in early adulthood and the development of AD later in life; the more severe the head injury, the greater the risk of developing AD. Some evidence indicates that a head injury may interact with other factors to trigger the disease and may hasten the onset of the disease in individuals already at risk. For example, people who have a particular form of the protein apolipoprotein E (apoE4) and suffer a head injury fall into this increased risk category. (ApoE4 is a naturally occurring protein that helps transport cholesterol through the bloodstream.)

Parkinson’s disease and other motor problems as a result of TBI are rare but can occur. Parkinson’s disease may develop years after TBI as a result of damage to the basal ganglia. Symptoms of Parkinson’s disease include tremor or trembling, rigidity or stiffness, slow movement (bradykinesia), inability to move (akinesia), shuffling walk, and stooped posture. Despite many scientific advances in recent years, Parkinson’s disease remains a chronic and progressive disorder, meaning that it is incurable and will progress in severity until the end of life. Other movement disorders that may develop after TBI include tremor, ataxia (uncoordinated muscle movements), and myoclonus (shock-like contractions of muscles).

Dementia pugilistica’, also called chronic traumatic encephalopathy, primarily affects career boxers. The most common symptoms of the condition are dementia and parkinsonism caused by repetitive blows to the head over a long period of time. Symptoms begin anywhere between 6 and 40 years after the start of a boxing career, with an average onset of about 16 years.

Post-traumatic dementia is another potential long-term effect of TBI. The symptoms of post-traumatic dementia are very similar to those of dementia pugilistica, except that post-traumatic dementia is also characterized by long-term memory problems and is caused by a single, severe TBI that results in a coma.

Treatment

Medical care usually begins when paramedics or emergency medical technicians arrive on the scene of an accident or when a TBI patient arrives at the emergency department of a hospital. Because little can be done to reverse the initial brain damage caused by trauma, medical personnel try to stabilize the patient and focus on preventing further injury. Primary concerns include insuring proper oxygen supply, maintaining adequate blood flow, and controlling blood pressure. Since many head-injured patients may also have spinal cord injuries, the patient is placed on a back-board and in a neck restraint to prevent further injury to the head and spinal cord.

Medical personnel assess the patient’s condition by measuring vital signs and reflexes and by performing a neurological examination. They check the patient’s temperature, blood pressure, pulse, breathing rate, and pupil size and response to light. They assess the patient’s level of consciousness and neurological functioning using the Glasgow Coma Scale.

Imaging tests help in determining the diagnosis and prognosis of a TBI patient. Patients with mild to moderate injuries may receive skull and neck X-rays to check for bone fractures. For moderate to severe cases, the gold standard imaging test is a computed tomography (CT) scan, which creates a series of cross-sectional X-ray images of the head and brain and can show bone fractures as well as the presence of hemorrhage, hematomas, contusions, brain tissue swelling, and tumors. Magnetic resonance imaging (MRI) may be used after the initial assessment and treatment of the TBI patient. MRI uses magnetic fields to detect subtle changes in brain tissue content and can show more detail than X-rays or CT. The use of CT and MRI is standard in TBI treatment, but other imaging and diagnostic techniques that may be used to confirm a particular diagnosis include cerebral angiography, electroencephalography (EEG), transcranial Doppler ultrasound, and single photon emission computed tomography (SPECT).

Approximately half of severely head-injured patients will need surgery to remove or repair hematomas or contusions. Patients may also need surgery to treat injuries in other parts of the body. These patients usually go to the intensive care unit after surgery.
Sometimes when the brain is injured swelling occurs and fluids accumulate within the brain space. It is normal for bodily injuries to cause swelling and disruptions in fluid balance. But when an injury occurs inside the skull-encased brain, there is no place for swollen tissues to expand and no adjoining tissues to absorb excess fluid. This leads to increased pressure is called intracranial pressure (ICP). High ICP can cause delicate brain tissue to be crushed, or parts of the brain to herniate across structures within the skull, causing severe damage.

Medical personnel measure a patient’s ICP using a probe or catheter. The instrument is inserted through the skull to the subarachnoid level and is connected to a monitor that registers the patient’s ICP. If a patient has high ICP, he or she may undergo a ventriculostomy, a procedure that drains cerebrospinal fluid (CSF) from the ventricles to bring the pressure down by way of an external ventricular drain (EVD). Barbiturates can be used to decrease ICP; mannitol was thought to be useful, but it appears likely that the studies suggesting it was of use may have been falsified. Decompressive craniectomy is a last-resort surgical procedure in which part of the skull is removed in an attempt to reduce severely high ICP.

Rehabilitation

Rehabilitation is an important and critical part of the recovery process for a TBI patient. During the acute stage, moderately to severely injured patients may receive treatment and care in an intensive care unit of a hospital followed by movement to a step-down unit or to a neurosurgical ward. Once medically stable, the patient may be transferred to a subacute unit of the medical center, to a long-term acute care (LTAC) facility, to a rehabilitation inpatient treatment unit contained within the acute trauma center, or to an independent off-site or ‘free-standing’ rehabilitation hospital. Patients are best managed on an inpatient treatment unit that has a specialty focus in Brain Injury Rehabilitation. Rehabilitation programs may be reviewed and accredited for this type of specialty care by the Commission on Accreditation of Rehabilitation Facilities.

Decisions regarding when and where an individual should be treated at a particular point during the recovery process are complex and depend on many different factors including the level to which the person can be engaged actively and can participate to some degree in the rehabilitation process. Moderately to severely injured patients may receive specialized rehabilitation treatment that draws on the skills and knowledge of many specialists, involving treatment programs in the areas of physical therapy, occupational therapy, speech/language therapy, physiatry (medical specialist in physical medicine and rehabilitation), psychology, psychiatry, and social work, among others.
The services and efforts of this team of healthcare professionals are generally applied to the practical concerns of and the pragmatic problems encountered by the brain injury survivor in their daily life. This treatment program is generally provided through a coordinated and self-organized process in the context of a transdisciplinary model of team healthcare delivery. This model keeps the primary focus on the overarching goal of optimizing patient function and independence through the coordinated application of discipline-specific expertise brought to bear on this issue by individual experts from various specific disciplinary backgrounds.

The overall goal of rehabilitation after a TBI is to improve the patient’s ability to function at home and in society in the face of the residual effects of the injury, which may be complex and multifaceted (see Disabilities Resulting from TBI section above). Therapists help the patient adapt to disabilities or change the patient’s living space and conditions to make everyday activities easier and to accommodate residual impairments. Education and training for identified caregivers who will be involved in assisting the patient after discharge are also critically important components of the rehabilitation program.

Once the patient has been discharged from the inpatient rehabilitation treatment unit, the outpatient phase of care begins and goals often will shift from assisting the person to achieve independence in basic routines of daily living to assessing and treating broader psychosocial issues associated with long-term adjustment and community re-integration. Patients/clients will often have problems in the areas of general cognition, social cognition/awareness, behavior and emotional regulation that present significant challenges, in terms of being able to resume expected social roles. Often these problems are complicated by adjustment issues that emerge as the person becomes more aware of their residual deficits and faces the challenges of coming to terms with the long-term effects of the injury. Other concerns such as posttraumatic stress disorder associated with preserved remembrance of emotionally provocative circumstances of injury, may emerge and complicate the recovery process.

An additional goal of the rehabilitation program is to prevent, wherever possible, but otherwise to diagnose and treat in an efficient and effective manner, any complications (e.g. posttraumatic hydrocephalus, neuro-endocrine deficiencies, adjustment reactions, deep venous thromboembolism, etc.) that may cause additional morbidity and mortality.
Some patients may need medication for psychiatric and physical problems resulting from the TBI, and various medications are available that may lessen or moderate the problematic manifestations of the injury without directly altering the underlying pathology. Great care must be taken in prescribing medications because TBI patients are more susceptible to side effects and may react adversely to some pharmacological agents or may be inordinately sensitive to them, for example, due to a more permeable blood-brain barrier due to injury effects.

It is important for the family caregivers to provide assistance and encouragement for the patient by being involved in the rehabilitation program. Family members may also benefit from psychotherapy and social support services. Support for caregivers becomes particularly important during the outpatient phase of care when behavioral and cognitive problems may complicate and impair the relationships that patients have with those around them. Major challenges occur in sustaining these relationships, particularly in the context of marriage, when the impact of the injury significantly alters the relationship in such a way that the resumption of an adult-level interactive relationship may be deeply undermined. It should be noted that similar principles of rehabilitation for diffuse brain injury can be applied to individuals with brain injury of both traumatic and nontraumatic etiologies. Acquired Brain Injury (ABI) is an all-encompassing term that can be applied to the various etiologies producing global encephalopathies with diffuse and/or multi-focal brain dysfunction that is precipitated during life in a previously fully functional individual. The etiologic processes associated with ABI can be subdivided into those related to trauma and those not directly related to trauma. TBI can therefore be viewed as a particular instance of ABI caused by trauma, and the principles of rehabilitation referred to here for TBI can be readily adapted and applied to individuals with all forms of ABI, independent of specific etiology.

Caretakers of traumatically brain injured patients can often feel a great deal of emotional stress, which can reduce the quality of care. Respite care such as supported living and residential holidays, supported days out doing activities like walking, cycling, kayaking and climbing offers relief for them and a new area of brain stimulation for the patient. When dealing with caretakers, providers of respite care need to be sensitive and reassuring, and should be aware that some caretakers may have feelings of guilt or inadequacy.

Prevention

Unlike most neurological disorders, head injuries can be prevented. The Centers for Disease Control and Prevention (CDC) have suggested taking the following safety precautions for reducing the risk of suffering a TBI.

  • Wearing a seatbelt when driving or riding in a car.
  • Buckling children into a child safety seat, booster seat, or seatbelt (depending on the child’s age) every time the child rides in a car.
  • Wearing a helmet and making sure children wear helmets when riding a bike or motorcycle;
  • playing a contact sport such as football or ice hockey;
  • using in-line skates or riding a skateboard;
  • batting and running bases in baseball or softball;
  • riding a horse;
  • rock climbing;
  • sledding;
  • Skiing or snowboarding.
  • Keeping firearms and bullets stored in a locked cabinet when not in use.
  • Avoiding falls by using a step-stool with a grab bar to reach objects on high shelves;
  • installing handrails on stairways;
  • installing window guards to keep young children from falling out of open windows;
  • Using safety gates at the top and bottom of stairs when young children are around.
  • Using only playgrounds with surfaces made of shock-absorbing material (e.g., hardwood mulch, sand).

Famous persons with TBI

  • Mohammed Ali
  • James Brady
  • Phineas Gage
  • Chris Irwin
  • Ahad Israfil
  • Eric Lindros
  • Bob Woodruff

Multiple Sclerosis

Multiple Sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is a chronic, inflammatory, demyelinating disease that affects the central nervous system (CNS). MS can cause a variety of symptoms, including changes in sensation, visual problems, muscle weakness, depression, difficulties with coordination and speech, severe fatigue, cognitive impairment, problems with balance, overheating, and pain. MS will cause impaired mobility and disability in more severe cases.

Multiple sclerosis affects neurons, the cells of the brain and spinal cord that carry information, create thought and perception, and allow the brain to control the body. Surrounding and protecting some of these neurons is a fatty layer known as the myelin sheath, which helps neurons carry electrical signals. MS causes gradual destruction of myelin (demyelination) and transection of neuron axons in patches throughout the brain and spinal cord. The name multiple sclerosis refers to the multiple scars (or scleroses) on the myelin sheaths. This scarring causes symptoms which vary widely depending upon which signals are interrupted.

The predominant theory today is that MS results from attacks by an individual’s immune system on the nervous system and it is therefore usually categorized as an autoimmune disease. There is a minority view that MS is not an autoimmune disease, but rather a metabolically dependent neurodegenerative disease. Although much is known about how MS causes damage, its exact cause remains unknown.

Multiple sclerosis may take several different forms, with new symptoms occurring either in discrete attacks or slowly accruing over time. Between attacks, symptoms may resolve completely, but permanent neurologic problems often persist, especially as the disease advances. MS currently does not have a cure, though several treatments are available that may slow the appearance of new symptoms.

MS primarily affects adults, with an age of onset typically between 20 and 40 years, and is more common in women than in men.

Signs and symptoms

MS can cause a variety of symptoms, including changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty to move; difficulties with coordination and balance (ataxia); problems in speech (Dysarthria) or swallowing (Dysphagia), visual problems (Nystagmus, optic neuritis, or diplopia), fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology (mainly depression).

The initial attacks are often transient, mild (or asymptomatic), and self-limited. They often do not prompt a health care visit and sometimes are only identified in retrospect once the diagnosis has been made based on further attacks. The most common initial symptoms reported are: changes in sensation in the arms, legs or face (33%), complete or partial vision loss (optic neuritis) (16%), weakness (13%), double vision (7%), unsteadiness when walking (5%), and balance problems (3%); but many rare initial symptoms have been reported such as aphasia or psychosis. Fifteen percent of individuals have multiple symptoms when they first seek medical attention. For some people the initial MS attack is preceded by infection, trauma, or strenuous physical effort.

Cognitive and emotional

Cognitive impairments are common (40 to 60 percent of patients) and are already present in the beginnings of the disease. Some of the most common declines are in recent memory, attention, processing speed, visual-spatial abilities and executive functions. Other cognitive-related symptoms are emotional instability, and fatigue, including purely neurological fatigue. The cognitive impairments in MS are usually mild; and only in 5% of patients can we speak of dementia. Nevertheless they are related with unemployment and reduced social interactions.

Emotional symptoms are also common and are thought to be both the normal response to having a debilitating disease and the result of damage to specific areas of the central nervous system that generate and control emotions. Clinical depression is the most common neuropsychiatric condition: lifetime depression prevalence rates of 40-50% and 12 month prevalence rates around 20% have been typically reported; being these figures considerably higher than those reported for sane people or with other chronic illnesses. Other feelings such as anger, anxiety, frustration, and hopelessness also appear frequently, and suicide is a very real threat since 15% of deaths in MS sufferers are due to this cause.

Diagnosis

Monthly multiple sclerosis MRI

T1-weighted MRI scans (post-contrast) of same brain slice at monthly intervals. Bright spots indicate active lesions.

Multiple sclerosis is difficult to diagnose in its early stages. In fact, definite diagnosis of MS cannot be made until there is evidence of at least two anatomically separate demyelinating events occurring at least thirty days apart.

Historically different criteria were used. The Schumacher criteria and Poser criteria were both popular. Currently, McDonald criteria represents international efforts to standardize the diagnosis of MS using clinical data, laboratory data, and radiologic data.

  • Clinical data alone may be sufficient for a diagnosis of MS. If an individual has suffered two separate episodes of neurologic symptoms characteristic of MS, and the individual also has consistent abnormalities on physical examination, a diagnosis of MS can be made with no further testing. Since some people with MS seek medical attention after only one attack, other testing may hasten the diagnosis and allow earlier initiation of therapy.
  • Magnetic resonance imaging (MRI) of the brain and spine is often used to evaluate individuals with suspected MS. MRI shows areas of demyelination as bright lesions on T2-weighted images or FLAIR (fluid attenuated inversion recovery) sequences. Gadolinium contrast is used to demonstrate active plaques on T1-weighted images. Because MRI can reveal lesions which occurred previously but produced no clinical symptoms, it can provide the evidence of chronicity needed for a definite diagnosis of MS.
  • Testing of cerebrospinal fluid (CSF) can provide evidence of chronic inflammation of the central nervous system. The CSF is tested for oligoclonal bands, which are immunoglobulins found in 85% to 95% of people with definite MS (but also found in people with other diseases). Combined with MRI and clinical data, the presence of oligoclonal bands can help make a definite diagnosis of MS. Lumbar puncture is the procedure used to collect a sample of CSF.
  • The brain of a person with MS often responds less actively to stimulation of the optic nerve and sensory nerves. These brain responses can be examined using visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs). Decreased activity on either test can reveal demyelination which may be otherwise asymptomatic. Along with other data, these exams can help find the widespread nerve involvement required for a definite diagnosis of MS.

Another test which may become important in the future is measurement of antibodies against myelin proteins such as myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). As of 2007, however, there is no established role for these tests in diagnosing MS.

The signs and symptoms of MS can be similar to other medical problems, such as neuromyelitis optica, stroke, brain inflammation, infections such as Lyme disease (which can produce identical MRI lesions and CSF abnormalities), tumors, and other autoimmune problems, such as lupus. Additional testing may be needed to help distinguish MS from these other problems.

Disease course and clinical subtypes

Graph representing the different types of multiple sclerosis
Graph representing the different types of multiple sclerosis

The course of MS is difficult to predict, and the disease may at times either lie dormant or progress steadily. Several subtypes, or patterns of progression, have been described. Subtypes use the past course of the disease in an attempt to predict the future course. Subtypes are important not only for prognosis but also for therapeutic decisions. In 1996 the United States National Multiple Sclerosis Society standardized the following four subtype definitions:

Relapsing-remitting
Relapsing-remitting describes the initial course of 85% to 90% of individuals with MS. This subtype is characterized by unpredictable attacks (relapses) followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits suffered during the attacks may either resolve or may be permanent. When deficits always resolve between attacks, this is referred to as “benign” MS.

Secondary progressive
Secondary progressive describes around 80% of those with initial relapsing-remitting MS, who then begin to have neurologic decline between their acute attacks without any definite periods of remission. This decline may include new neurologic symptoms, worsening cognitive function, or other deficits. Secondary progressive is the most common type of MS and causes the greatest amount of disability.

Primary progressive
Primary progressive describes the approximately 10% of individuals who never have remission after their initial MS symptoms. Decline occurs continuously without clear attacks. The primary progressive subtype tends to affect people who are older at disease onset.

Progressive relapsing
Progressive relapsing describes those individuals who, from the onset of their MS, have a steady neurologic decline but also suffer superimposed attacks; and is the least common of all subtypes.

Special cases of the disease with non-standard behavior have also been described although many researchers believe they are different diseases. These cases are: Neuromyelitis optica (NMO), Balo concentric sclerosis, Schilder disease, Marburg multiple sclerosis, acute disseminated encephalomyelitis (ADEM) and autoimmune variants of peripheral neuropathies.

Factors triggering a relapse

Multiple sclerosis relapses are often unpredictable and can occur without warning and with no obvious inciting factors. Some attacks, however, are preceded by common triggers. In general, relapses occur more frequently during spring and summer than during autumn and winter.

Infections, such as the common cold, influenza, and gastroenteritis, increase the risk for a relapse. Emotional and physical stress may also trigger an attack, as can severe illness of any kind. Statistically, there is no good evidence that either trauma or surgery trigger relapses. People with MS can participate in sports, but they should probably avoid extremely strenuous exertion, such as marathon running. Heat can transiently increase symptoms, which is known as Uhthoff’s phenomenon. This is why some people with MS avoid saunas or even hot showers. However, heat is not an established trigger of relapses.

Pregnancy can directly affect the susceptibility for relapse. The last three months of pregnancy offer a natural protection against relapses. However, during the first few months after delivery, the risk for a relapse is increased 20%-40%. Pregnancy does not seem to influence long-term disability. Children born to mothers with MS are not at increased risk for birth defects or other problems.

Many potential triggers have been examined and found not to influence relapse rates in MS. Influenza vaccination is safe, does not trigger relapses, and can therefore be recommended for people with MS. There is also no evidence that hepatitis B, varicella, tetanus, or Bacille Calmette-Guerin (BCG – immunization for tuberculosis) increases the risk for relapse.

Pathophysiology

Although much is known about how multiple sclerosis causes damage, the reasons why multiple sclerosis occurs are not known.

How multiple sclerosis causes damage

Multiple sclerosis is a disease in which the myelin (a fatty substance which covers the axons of nerve cells, important for proper nerve conduction) degenerates. This includes not only the usually known white matter demyelination, but also demyelination in the cortex and deep gray matter (GM) nuclei, as well as diffuse injury of the normal-appearing white matter. GM atrophy is independent of the MS lesions and is associated with physical disability, fatigue, and cognitive impairment in MS.

According to the view of most researchers, a special subset of lymphocytes, called T cells, plays a key role in the development of MS. Under normal circumstances, these lymphocytes can distinguish between self and non-self. However, in a person with MS, these cells recognize healthy parts of the central nervous system as foreign and attack them as if they were an invading virus, triggering inflammatory processes and stimulating other immune cells and soluble factors like cytokines and antibodies.

Normally, there is a tight barrier between the blood and brain, called the blood-brain barrier, built up of endothelial cells lining the blood vessel walls. It should prevent the passage of antibodies through it, but in MS patients it does not work. A deficiency of uric acid has been implicated in this process. Uric acid added in physiological concentrations (i.e. achieving normal concentrations) is therapeutic in MS by preventing the breakdown of the blood brain barrier though inactivation of peroxynitrite. The low level of uric acid found in MS victims is manifestedly causative rather than a consequence of tissue damage in the white matter lesions, but not in the grey matter lesions. Nevertheless, whether BBB dysfunction is the cause or the consequence of MS is still disputed.

According to a strictly immunological explanation of MS, the inflammatory processes triggered by the T cells create leaks in the blood-brain barrier. These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins such as matrix metalloproteinases. The final result is destruction of myelin, called demyelination. Repair processes, called remyelination, also play an important role in MS. Remyelination is one of the reasons why, especially in early phases of the disease, symptoms tend to decrease or disappear temporarily. Nevertheless, nerve damage and irreversible loss of neurons occur early in MS. Proton magnetic resonance spectroscopy has shown that there is widespread neuronal loss even at the onset of MS, largely unrelated to inflammation. Often, the brain is able to compensate for some of this damage, due to an ability called neuroplasticity. MS symptoms develop as the cumulative result of multiple lesions in the brain and spinal cord. This is why symptoms can vary greatly between different individuals, depending on where their lesions occur.

The oligodendrocytes that originally formed a myelin sheath cannot completely rebuild a destroyed myelin sheath. However, the brain can recruit stem cells, which migrate from other unknown regions of the brain, differentiate into mature oligodendrocytes, and rebuild the myelin sheath. These new myelin sheaths are often not as effective as the original ones. Repeated attacks lead to successively fewer effective remyelinations, until a scar-like plaque is built up around the damaged axons. Under laboratory conditions, stem cells are quite capable of differentiating and remyelinating axons; it is therefore suspected that inflammatory conditions or axonal damage somehow inhibit stem cell differentiation in the body.

Pathophysiology research

Until recently, most of the data available came from post-mortem brain samples and animal models of the disease, such as the experimental autoimmune encephalomyelitis (EAE), an autoimmune disease that can be induced in rodents, and which is considered a possible animal model for multiple sclerosis.; but since 1998 brain biopsies apart from the post-mortem samples have been used to identify four different damage patterns in the scars of the brain. The four patterns that were identified are T-Cell and macrophages mediated demyelination, complement mediated demyelination, distal oligodendrogliopathy and primary oligodendrocyte degeneration.

Causes

Although many risk factors for multiple sclerosis have been identified, no definitive cause has been found. MS likely occurs as a result of some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations. Although most accept an autoimmune explanation, several theories suggest that MS is an appropriate immune response to an underlying condition. In support of alternative theories is the fact that present therapies have not been as successful as was expected based on the autoimmune theory.

Environmental

The most popular hypothesis is that a viral infection or retroviral reactivation primes a susceptible immune system for an abnormal reaction later in life. On a molecular level, this might occur if there is a structural similarity between the infectious virus and some component of the central nervous system, leading to eventual confusion in the immune system.

Since MS seems to be more common in people who live farther from the equator, another theory proposes that decreased sunlight exposure and possibly decreased vitamin D production may help cause MS. This theory is bolstered by recent research into the biochemistry of vitamin D, which has shown that it is an important immune system regulator. A large, 2006 study by the Harvard School of Public Health, reported evidence of a link between Vitamin D deficiency and the onset of multiple sclerosis.

Other theories, noting that MS is less common in children with siblings, suggest that less exposure to illness in childhood leads to an immune system which is not primed to fight infection and is thus more likely to attack the body. One explanation for this would be an imbalance between the Th1 type of helper T-cells, which fight infection, and the Th2 type, which are more active in allergy and more likely to attack the body. Other theories describe MS as an immune response to a chronic infection. The association of MS with the Epstein-Barr virus suggests a potential viral contribution in at least some individuals. Still others believe that MS may sometimes result from a chronic infection with spirochetal bacteria, a hypothesis supported by research in which cystic forms were isolated from the cerebrospinal fluid of all MS patients in a small study. When the cysts were cultured, propagating spirochetes emerged. Another bacterium that has been implicated in MS is Chlamydophila pneumoniae; it or its DNA has been found in the cerebrospinal fluid of MS patients by several research laboratories, with one study finding that the oligoclonal bands of 14 of the 17 MS patients studied consisted largely of antibodies to Chlamydophila antigens. Severe stress may also be a factor – a large study in Denmark found that parents who had lost a child unexpectedly were 50% more likely to develop MS than parents who had not. Smoking has also been shown to be an independent risk factor for developing MS.

Genetic

MS is not considered a hereditary disease. However, increasing scientific evidence suggests that genetics may play a role in determining a person’s susceptibility to MS:
Some populations, such as the Roma, Inuit, and Bantus, rarely if ever get MS. The indigenous peoples of the Americas and Asians have very low incidence rates.

In the population at large, the chance of developing MS is less than a tenth of one percent. However, if one person in a family has MS, that person’s first-degree relatives-parents, children, and siblings-have a one to three percent chance of getting the disease. For identical twins, the likelihood that the second twin may develop MS if the first twin does is about 30%; for fraternal twins (who do not inherit identical gene pools), the likelihood is closer to that for non-twin siblings, or about 4%. The fact that the rate for identical twins both developing MS is significantly less than 100% suggests that the disease is not entirely genetically controlled. Some (but definitely not all) of this effect may be due to shared exposure to something in the environment, or to the fact that some people with MS lesions remain essentially asymptomatic throughout their lives.

Further indications that more than one gene is involved in MS susceptibility comes from studies of families in which more than one member has MS. Several research teams found that people with MS inherit certain regions on individual genes more frequently than people without MS. Of particular interest is the human leukocyte antigen (HLA) or major histocompatibility complex region on chromosome 6. HLAs are genetically determined proteins that influence the immune system. However, there are other genes in this region which are not related to the immune system.

The HLA patterns of MS patients tend to be different from those of people without the disease. Investigations in northern Europe and America have detected three HLAs that are more prevalent in people with MS than in the general population. Studies of American MS patients have shown that people with MS also tend to exhibit these HLAs in combination-that is, they have more than one of the three HLAs-more frequently than the rest of the population. Furthermore, there is evidence that different combinations of the HLAs may correspond to variations in disease severity and progression.

Studies of families with multiple cases of MS and research comparing proteins expressed in humans with MS to those of mice with EAE suggest that another area related to MS susceptibility may be located on chromosome 5. Other regions on chromosomes 2, 3, 7, 11, 17, 19, and X have also been identified as possibly containing genes involved in the development of MS.

These studies strengthen the theory that MS is the result of a number of factors rather than a single gene or other agent. Development of MS is likely to be influenced by the interactions of a number of genes, each of which (individually) has only a modest effect. Additional studies are needed to specifically pinpoint which genes are involved, determine their function, and learn how each gene’s interactions with other genes and with the environment make an individual susceptible to MS.

Treatment

There is no known definitive cure for multiple sclerosis. However, several types of therapy have proven to be helpful. Different therapies are used for patients experiencing acute attacks, for patients who have the relapsing-remitting subtype, for patients who have the progressive subtypes, for patients without a diagnosis of MS who have a demyelinating event, and for managing the various consequences of MS attacks. Treatment is aimed at returning function after an attack, preventing new attacks, and preventing disability.

Various disease-modifying treatments have been approved by the USA’s Food and Drug Administration (FDA); as well as in other countries; for multiple sclerosis.

  • INTERFERONs:
    These are medications derived from human cytokines which help regulate the immune system. Betaseron has been approved by the FDA for relapsing forms of secondary progressive MS.
  • Interferon beta-1a: (trade names Avonex , Rebif and CinnoVex [Biogereric/biosimolar form of Avonex])
  • Beta-1b: (trade name Betaseron [in Europe and Japan Betaferon]).
  • GLATIRAMER ACETATE: (trade name Copaxone)
    A synthetic medication made of four amino acids that are found in myelin. This drug stimulates T cells in the body’s immune system to change from harmful, pro-inflammatory agents to beneficial, anti-inflammatory agents that work to reduce inflammation at lesion sites.
  • MITOXANTRONE: (trade name Novantrone)
    This medication is effective, but is limited by cardiac toxicity. Novantrone has been approved by the USA’s FDA for secondary progressive, progressive-relapsing, and worsening relapsing-remitting MS.
  • NATALIZUMAB: (trade name Tysabri).
    This medication is effective and safe alone but in combination with other immunotherapies can lead to PML.

Relapsing-remitting symptomatic attacks can be treated. Patients are typically given high doses of intravenous corticosteroids, such as methylprednisolone, to end the attack sooner and leave fewer lasting deficits. Patients’ self-reporting indicates that many find benefit from a number of other medicines.

Currently there are no approved treatments for primary progressive multiple sclerosis, though several medications are being studied. Pain relief medications and treatments for symptoms are described at Therapies for multiple sclerosis.

Prognosis

The prognosis (expected future course of the disease) for a person with multiple sclerosis depends on the subtype of the disease; the individual’s sex, race, age, and initial symptoms; and the degree of disability the person experiences. The life expectancy of people with MS is now nearly the same as that of unaffected people. This is due mainly to improved methods of limiting disability, such as physical therapy and speech therapy, and more successful treatment of common complications of disability, such as pneumonia and urinary tract infections. Nevertheless half of the deaths in people with MS are directly related to the consequences of the disease, while 15% more are due to suicide.

  • Individuals with progressive subtypes of MS, particularly the primary progressive subtype, have a more rapid decline in function. In the primary progressive subtype, supportive equipment (such as a wheelchair or standing frame) is often needed after six to seven years. However, when the initial disease course is the relapsing-remitting subtype, the average time until such equipment is needed is twenty years. This means that many individuals with MS will never need a wheelchair. There is also more cognitive impairment in the progressive forms than in the relapsing-remitting course.
  • The earlier in life MS occurs, the slower disability progresses. Individuals who are older than fifty when diagnosed are more likely to experience a chronic progressive course, with more rapid progression of disability. Those diagnosed before age 35 have the best prognosis. Females generally have a better prognosis than males. Although black individuals tend to develop MS less frequently, they are often older at the time of onset and may have a worse prognosis.
  • Initial MS symptoms of visual loss or sensory problems, such as numbness or tingling, are markers for a relatively good prognosis, whereas difficulty walking and weakness are markers for a relatively poor prognosis. Better outcomes are also associated with the presence of only a single symptom at onset, the rapid development of initial symptoms, and the rapid regression of initial symptoms.
  • The degree of disability varies among individuals with MS. In general, one of three individuals will still be able to work after 15-20 years. Fifteen percent of people diagnosed with MS never have a second relapse, and these people have minimal or no disability after ten years. The degree of disability after five years correlates well with the degree of disability after fifteen years. This means that two-thirds of people with MS with low disability after five years will not get much worse during the next ten years. It should be noted that most of these outcomes were observed before the use of medications such as interferon, which can delay disease progression for several years.

Currently there are no clinically established laboratory investigations available that can predict prognosis or response to treatment. However, several promising approaches have been proposed. These include measurement of the two antibodies anti-myelin oligodendrocyte glycoprotein and anti-myelin basic protein, and measurement of TRAIL (TNF-related apoptosis-inducing ligand).

Epidemiology

global prevalence of multiple sclerosis
World map showing that risk for MS increases with greater distance from the equator

In northern Europe, continental North America, and Australasia, about one of every 1000 citizens suffers from multiple sclerosis, whereas in the Arabian peninsula, Asia, and continental South America, the frequency is much lower. In sub-Saharan Africa, MS is extremely rare. With important exceptions, there is a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere, with MS being much less common in people living near the equator. Climate, diet, geomagnetism, toxins, sunlight exposure, genetic factors, and infectious diseases have all been discussed as possible reasons for these regional differences. Environmental factors during childhood may play an important role in the development of MS later in life. This idea is based on several studies of migrants showing that if migration occurs before the age of fifteen, the migrant acquires the new region’s susceptibility to MS. If migration takes place after age fifteen, the migrant keeps the susceptibility of his home country.

MS occurs mainly in Caucasians. It is twentyfold lower in the Inuit people of Canada than in other Canadians living in the same region. It is also rare in the Native American tribes of North America, Australian Aborigines and the M?ori of New Zealand. These few examples point out that genetic background plays an important role in the development of MS.

As observed in many autoimmune disorders, MS is more common in females than males; the mean sex ratio is about two females for every male. In children (who rarely develop MS) the sex ratio may reach three females for each male. In people over age fifty, MS affects males and females equally. Onset of symptoms usually occurs between twenty to forty years of age, rarely before age fifteen or after age sixty. As previously discussed, there is a genetic component to MS. On average one of every 25 siblings of individuals with MS will also develop MS. Almost half of the identical twins of MS-affected individuals will develop MS, but only one of twenty fraternal twins. If one parent is affected by MS, each child has a risk of only about one in forty of developing MS later in life.

Finally, it is important to remark that advances in the study of related diseases have shown that some cases formerly considered MS are not MS at all. In fact, all the studies before 2004 can be affected by the impossibility to distinguish MS and NMO reliably before this date. The error can be important in some areas, and is considered to be 30% in Japan.

History

The French neurologist Jean-Martin Charcot (1825-93) was the first person to recognize multiple sclerosis as a distinct, separate disease in 1868. Summarizing previous reports and adding his own important clinical and pathological observations, Charcot called the disease sclerose en plaques. The three signs of MS now known as Charcot’s triad are dysarthria (problems with speech), ataxia (problems with coordination), and tremor. Charcot also observed cognition changes in MS since he described his patients as having a “marked enfeeblement of the memory” and “with conceptions that formed slowly”.

Prior to Charcot, Robert Hooper (1773-1835), a British pathologist and practicing physician, Robert Carswell (1793-1857), a British professor of pathology, and Jean Cruveilhier (1791-1873), a French professor of pathologic anatomy, had described and illustrated many of the disease’s clinical details.

After this, several people, such as Eug?ne Devic (1858-1930), Jozsef Balo (1895-1979), Paul Ferdinand Schilder (1886-1940), and Otto Marburg (1874-1948) found special cases of the disease that some authors consider different diseases and now are called the borderline forms of multiple sclerosis.

There are several historical accounts of people who probably had MS. Saint Lidwina of Schiedam (1380-1433), a Dutch nun, may be one of the first identifiable MS patients. From the age of sixteen until her death at age 53, she suffered intermittent pain, weakness of the legs, and vision loss-symptoms typical of MS. Almost a hundred years before there is a story from Iceland of a young woman called Halla. This girl suddenly lost her vision and capacity to talk; but after praying to the saints recovered them seven days after. Augustus Frederick d’Este (1794-1848), an illegitimate grandson of King George III of Great Britain, almost certainly suffered from MS. D’Este left a detailed diary describing his 22 years living with the disease. His symptoms began at age 28 with a sudden transient visual loss after the funeral of a friend. During the course of his disease he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbances, and erectile dysfunction. In 1844, he began to use a wheelchair. Despite his illness, he kept an optimistic view of life. Another early account of MS was kept by the British diarist W. N. P. Barbellion, who maintained a detailed log of his diagnosis and struggle with MS. His diary was published in 1919 as The Journal of a Disappointed Man.

Cultural references

The German propaganda film Ich klage an (1941) by Wolfgang Liebeneiner had the main character suffering from MS and wishing herself to be killed because she had become unable to do so by herself. In “Duet for One,” Julie Andrews plays a concert violinist who must sacrifice her career when she is diagnosed with MS. In the American television series The West Wing, the fictional United States President, Josiah “Jed” Bartlet, has the relapsing-remitting subtype of MS. The storylines have educated many viewers about the nature of MS and have helped to dispel some of the misconceptions about the disease. Another American TV series, Extreme Makeover: Home Edition, aired a two-part episode on February 12, 2006 that featured a new home for Carol Crawford-Smith of Blacksburg, Virginia, a former principal dancer with the Dance Theatre of Harlem who was diagnosed with MS in 2000. Ty Pennington and his team not only built her a new home, but also renovated her Blacksburg dance studio, “The Center of Dance.”

British cellist Jacqueline du Pr? died with MS in 1987 when she was 42. After a long struggle with the disease, she was robbed of her capacity to perform as she progressively lost sensitivity in her fingers, hearing, and muscle coordination. This decline was portrayed in the 1998 film, Hilary and Jackie. The above-mentioned play “Duet for One” was inspired by du Pre’s life.

Actor Vidya Balan played an MS patient in a real-life-based Bollywood movie Guru (2007 film). The character suffers with impaired legs and extreme weakness. The film portrays the problems that people having MS face in their daily life.