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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.

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.

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)


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.

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.


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.)


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.


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.


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


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.


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.


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.


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.


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.


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.



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.





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.


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.


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.


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.


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.



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 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.

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.

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.


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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.


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.


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.


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.

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.


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 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 plexu