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Parkinson's disease - Wikipedia, the free encyclopedia http://en.wikipedia.


Parkinson's disease
From Wikipedia, the free encyclopedia

Parkinson's disease (also known as Parkinson disease or Parkinson's disease

PD) is a degenerative disease of the brain (central nervous Classification and external resources
system) that often impairs motor skills, speech, and other

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
Illustration of the Parkinson disease by Sir William Richard
may include high level cognitive dysfunction and subtle Gowers from A Manual of Diseases of the ervous System
language problems. PD is both chronic and progressive. in 1886
ICD-10 G20. (
PD is the most common cause of chronic progressive /classifications/apps/icd
Parkinsonism, a term which refers to the syndrome of /icd10online/?gg20.htm+g20) ,
tremor, rigidity, bradykinesia and postural instability. PD F02.3 (
is also called "primary parkinsonism" or "idiopathic PD"
(classically meaning having no known cause although
ICD-9 332 (
many genetic mutations associated with PD have since
been discovered). While many forms of parkinsonism are
DiseasesDB 9651
"idiopathic", "secondary" cases may result from toxicity
most notably of drugs, head trauma, or other medical /ddb9651.htm)
disorders. The disease is named after English physician
MedlinePlus 000755 (
James Parkinson, who made a detailed description of the /medlineplus/ency/article
disease in his essay: "An Essay on the Shaking Palsy" /000755.htm)
(1817). eMedicine neuro/304
/topic304.htm) neuro/635
Contents /topic635.htm#) in young
1 Classification (
2 Signs and symptoms /pmr/topic99.htm#) rehab
2.1 Motor symptoms
2.2 Neuropsychiatric
2.3 Sleep
2.4 Perception
2.5 Autonomic
3 Causes
3.1 Genetic
3.2 Toxins
3.3 Head trauma
4 Pathophysiology

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5 Diagnosis
6 Treatment
6.1 Levodopa
6.2 COMT inhibitors
6.3 Dopamine agonists
6.4 MAO-B inhibitors
6.5 Surgery and deep brain stimulation
6.6 Neurorehabilitation
7 Prognosis
8 Epidemiology
9 History
10 Research directions
10.1 Gene therapy
10.2 Neuroprotective agents
10.3 Neural transplantation
10.4 Complementary therapies
11 Famous sufferers
12 See also
13 References
14 External links

"Parkinson's disease" is the synonym of "primary parkinsonism", i.e. isolated parkinsonism due to a
neurodegenerative process without any secondary systemic cause. In some cases, it would be inaccurate to
say that the cause is "unknown", because a small proportion is caused by genetic mutations. It is possible for
a patient to be initially diagnosed with Parkinson's disease but then to develop additional features, requiring
revision of the diagnosis.[2]

There are other disorders that are called Parkinson-plus diseases. These include: multiple system atrophy
(MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Some include dementia
with Lewy bodies (DLB)—while 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 little understood.

These Parkinson-plus diseases may progress more quickly than typical idiopathic Parkinson disease. If
cognitive dysfunction occurs before or very early in the course of the movement disorder then DLBD may
be suspected. Early postural instability with minimal tremor especially in the context of ophthalmoparesis
should suggest PSP. Early autonomic dysfunction including erectile dysfunction and syncope may suggest
MSA. The presence of extreme asymmetry with patchy cortical cognitive defects such as dysphasia and
apraxias especially with "alien limb" phenomena should suggest CBD.

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.

Essential tremor may be mistaken for Parkinson's disease but lacks all other features besides tremor, and has
particular characteristics distinguishing it from Parkinson's, such as improvement with beta blockers and

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alcoholic beverages.[1]

Wilson's disease (hereditary copper accumulation) may present with parkinsonian features; young patients
presenting with parkinsonism or any other movement disorder are frequently screened for this rare
condition, because it may respond to medical treatment. Typical tests are liver function, slit lamp
examination for Kayser-Fleischer rings, and serum ceruloplasmin levels.

Signs and symptoms

Parkinson disease affects movement (motor symptoms). Other typical symptoms include disorders of mood,
behavior, thinking, and sensation (non-motor symptoms). Patients' individual symptoms may be quite
dissimilar and progression of the disease is also distinctly individual.

Motor symptoms

The cardinal symptoms are (mnemonic "TRAP"):[1]

Tremor: normally 4–6 Hz 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-
Rigidity: stiffness; increased muscle tone. In combination with a resting tremor, this produces a
ratchety, "cogwheel" rigidity when the limb is passively moved.
Akinesia/bradykinesia: absence of movement and slowness, respectively. Rapid, repetitive
movements produce a dysrhythmic and decremental loss of amplitude.
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 cause the patient to trip.
Decreased arm-swing.
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). [3]
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 a manifestation of akinesia (an inability to move). Gait freezing is
characterized by an inability to move the feet which may worsen in tight, cluttered spaces or
when attempting to initiate gait.
Dystonia (in about 20% of cases): abnormal, sustained, painful twisting muscle contractions,
often affecting the foot and ankle (mainly toe flexion and foot inversion) which often interferes
with gait.
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" or have cluttered speech.[4]
Monotonic speech.
Festinating speech: excessively rapid, soft, poorly-intelligible speech.
Drooling: most likely caused by a weak, infrequent swallow and stooped posture.
Dysphagia: impaired ability to swallow. Can lead to aspiration pneumonia.
Other motor symptoms:

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Fatigue (up to 50% of cases);

Masked faces (a mask-like face also known as hypomimia), with infrequent blinking;[5]
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;
Akathisia, the inability to sit still.


PD causes cognitive and mood disturbances, being in many cases related.

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.[6] 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.[7] Seventy percent of individuals with Parkinson's disease diagnosed with pre-existing
depression go on to develop anxiety. Ninety percent of Parkinson's disease patients with pre-existing anxiety
subsequently develop depression; apathy or abulia.

Cognitive disturbances include:

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.
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.[8]
Medication effects: some of the above cognitive disturbances are improved by dopaminergic
medications, while others are actually worsened.[9]


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


Impaired visual contrast sensitivity, spatial reasoning, color discrimination, convergence insufficiency
(characterized by double vision) and oculomotor control
Dizziness and fainting; usually attributable orthostatic hypotension, a failure of the autonomic nervous
system to adjust blood pressure in response to changes in body position

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Impaired proprioception (the awareness of bodily position in three-dimensional space)

Reduction or loss of sense of smell (hyposmia 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


Oily skin and seborrheic dermatitis[10]

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.

Most people with Parkinson's disease are described as having idiopathic Parkinson's disease (having no
specific known cause). There are far less common causes of Parkinson's disease including genetic, toxins,
head trauma, cerebral anoxia, 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. Someone 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.


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.[11] This
hypothesis is consistent with the fact that Parkinson's disease is not distributed homogeneously throughout
the population; its incidence varies geographically. However, the fact that the first appearance of the
syndrome predates the first synthesis of the compounds often attributed to causing Parkinson's disease
indicates that these recently synthesized compounds cannot be the sole cause of Parkinsonism. 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,[12][13] and/or bind to neuromelanin, as
originally suggested by G.C. Cotzias.[14][15] 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.[16]

The tragedy of a group of drug addicts in California in the early 1980s who consumed a contaminated and
illicitly produced batch of the synthetic opiate MPPP brought to light MPTP (pro-toxin N-methyl-4-phenyl-
1,2,3,6-tetrahydropyidine) as a specific cause of Parkinson symptoms. This made it possible to develop the
first animal model for Parkinson's. MPTP's toxicity likely comes from the generation of reactive oxygen
species through tyrosine hydroxylation.[17] The Case of the Frozen Addicts by J. William Langston (Vintage,
New York, June 25, 1996) documents this tragedy and describes the first attempts at fetal brain tissue
transplants to treat PD.

Other toxin-based models employ PCBs,[18] paraquat[19] (a herbicide) in combination with maneb (a

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fungicide),[20] rotenone[21] (an insecticide), and specific organochlorine pesticides including dieldrin[22] and
lindane.[23] Rotenone is an inhibitor of complex 1 of the electron transport chain. It easily crosses
membranes due to its extremely hydrophobic properties. Rotenone, therefore, does not rely on the dopamine
transporter to enter into the cytoplasm. Numerous studies have found an increase in PD 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 increase in PD
in persons exposed to agricultural chemicals.

Head trauma

Past episodes of head trauma are reported more frequently by individuals with Parkinson's disease than by
others in the population.[24][25][26] A recent methodologically strong retrospective study[24] 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 had
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,[27] who found a similar risk of 3.8, with increasing risk associated with more severe injury and
hospitalization. However, whether the head trauma actually contributed to Parkinson's disease development
or the early symptoms of clumsiness associated with Parkinson's causes individuals to have more head
trauma is still unknown.

The symptoms of Parkinson's disease result from the loss of
pigmented dopamine-secreting (dopaminergic) 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

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 Dopaminergic pathways of the human brain
increased inhibition of the ventral anterior nucleus of the in normal condition (left) and Parkinson's
thalamus, which sends excitatory projections to the motor disease (right). Red Arrows indicate
cortex, thus leading to hypokinesia. suppression of the target, blue arrows
indicate stimulation of target structure.
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.
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. The latest research on pathogenesis of disease has shown that the death of dopaminergic

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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.[28]

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. Neuromelanin may be acting as a protective agent. The most likely
mechanism is generation of reactive oxygen species.[12] Iron also induces aggregation of synuclein by
oxidative mechanisms.[29] 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-β promoter.[30]

Typically, the diagnosis is based on medical history and neurological
examination conducted by interviewing and observing the patient in
person using the Unified Parkinson's Disease Rating Scale. A radiotracer
for SPECT scanning machines called DaTSCAN and made by General
Electric is specialized for diagnosing Parkinson's Disease, but it is only
marketed in Europe. Due to this, the disease can be difficult to diagnose
accurately, especially in its early stages. Due to symptom overlap with
other diseases, only 75% of clinical diagnoses of PD are confirmed to be
idiopathic PD at autopsy.[31] 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 18F PET scan shows decreased
the symptoms are consistently present. Usually doctors look for shuffling dopamine activity in the basal
of feet and lack of swing in the arms. Doctors may sometimes request ganglia, a pattern which aids in
brain scans or laboratory tests in order to rule out other diseases. diagnosing Parkinson's disease.
However, CT and MRI brain scans of people with PD usually appear

Clinical practice guidelines introduced in the UK in 2006 state that the diagnosis and follow-up of
Parkinson's disease should be done by a specialist in the disease, usually a neurologist or geriatrician with an
interest in movement disorders.[2]

Parkinson's disease is a chronic disorder that requires broad-based management including patient and family
education, support group services, general wellness maintenance, physiotherapy, exercise, and nutrition.[2]
At present, there is no cure for PD, but medications or surgery can provide relief from the symptoms.


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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.

Stalevo for treatment of Parkinson's disease
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. There is also Stalevo (Carbidopa,
Levodopa and Entacapone).

COMT inhibitors

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 is limited in its
availability. A similar drug, entacapone has not been shown to cause significant alterations of liver function
and maintains adequate inhibition of COMT over time.[32]

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 primary caregiver (often a
spouse or partner), the latter of whom 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. Nausea and vomiting are common, and may require domperidone (an antiemetic).

MAO-B inhibitors

Selegiline and rasagiline reduce the symptoms by inhibiting monoamine oxidase-B (MAO-B), thereby
inhibiting the breakdown of dopamine secreted by the dopaminergic neurons. Metabolites of selegiline
include levoamphetamine and levomethamphetamine. This might result in side effects such as insomnia. A
side effect of selegiline in conjunction with L-dopa can be stomatitis. One report raised concern about
increased mortality when MAO-B inhibitors were combined with L-dopa;[33] however subsequent studies

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have not confirmed this finding.[34] In contrast to non-selective monoamine oxidase inhibitors, tyramine-
containing foods do not cause a hypertensive crisis.

Surgery and deep brain stimulation

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[35] and of the internal
segment of the globus pallidus, a procedure known as pallidotomy.[36]


There is partial evidence that speech or mobility problems can improve

with rehabilitation although studies are still scarce and of low quality.
Regular physical exercise and/or therapy can be
beneficial to the patient for maintaining and improving mobility, Photograph showing an electrode
[39] being inserted during deep brain
flexibility, strength, gait speed, and quality of life; and speech stimulation
therapy may improve voice and speech function.[40] One of the most
widely practiced treatment for the speech disorders associated with
Parkinson's disease is the Lee Silverman Voice Treatment (LSVT). LSVT focuses on increasing vocal

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.[42] 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 to be fatal. 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 with community dwelling patients.[43]

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. 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


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According to some sources, Parkinsons disease is slightly less prevalent in the African-American community.
The average crude prevalence is estimated at being from 120-180 out of 100,000 among the Caucasian
(white) community.[44] The Parsi community in Mumbai, India suffers from particularly high rates of
Parkinson's disease.[45][44]

Symptoms of Parkinson's disease have been known and treated since medieval times, most notably by
Averroes.[46] However, it was not formally recognized and its symptoms were not documented until 1817 in
An Essay on the Shaking Palsy[47] 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,[48] and the first large study reporting improvements in patients with Parkinson's disease resulting from
treatment with L-dopa was published in 1968.[49]

Research directions
Gene therapy

Currently under investigation is gene therapy. This involves using a non-infectious 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.[50] 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
unsatisfactory, with patients still retaining their drugs and symptoms.

europrotective agents

Neuroprotective treatments are at the forefront of PD research, but are still under clinical scrutiny.[51] These
agents could protect neurons from cell death induced by disease presence resulting in a slower progression of
disease. Agents currently under investigation as neuroprotective agents include anti-apoptotic drugs (CEP
1347 and CTCT346), lazaroids, bioenergetics, antiglutamatergic agents and dopamine receptors.[52]
Clinically evaluated neuroprotective agents are the monoamine oxidase B inhibitors selegiline[53] and
rasagiline, dopamine agonists, and the complex I mitochondrial fortifier coenzyme Q10. Alpha6beta2
nAChR may represent a relevant target for PD therapeutics.[54]

eural transplantation

The first prospective randomised double-blind sham-placebo controlled trial of dopamine-producing cell
transplants failed to show an improvement in quality of life although some significant clinical improvements
were seen in patients below the age of 60.[55] A significant problem was the excess release of dopamine by
the transplanted tissue, leading to dystonias.[56] Research in African green monkeys suggests that the use of

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stem cells might in future provide a similar benefit without inducing dystonias.[57]

Complementary therapies

Nutrients have been used in clinical studies and are used by people with PD in order to partially treat PD or
slow down its deterioration. The L-dopa precursor L-tyrosine was shown to relieve an average of 70% of
symptoms.[58] 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.[59] [60] More limited efficacy has been obtained with
the use of THFA, NADH, and pyridoxine—coenzymes and coenzyme precursors involved in dopamine
biosynthesis.[61] Vitamin C and vitamin E in large doses are commonly used by patients in order to
theoretically lessen the cell damage that occurs in PD. 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.[53] 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.

Mucuna pruriens is plant of the legume family that has been used by Ayurvedic practitioners to treat
Parkinson's for more than 4,500 years; Western medicine is now accepting mucuna as an alternative
treatment to, or complementary therapy with, L-dopa, as study after study is proving its effectiveness.
Research cited by the National Parkinson Foundation found that "dose for dose, mucuna was two to three
times more effective than equivalent amounts of synthetic L-dopa [and] [t]he side effects were minimal....
Further, the cost of the drug was much cheaper compared to the synthetic drugs." [62][63]

Studies looking at qigong in PD have not reached consensus on its efficacy.[64][65]

Famous 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

Another foundation that supports Parkinson's research was established by Davis Phinney, a notable figure in
the cycling world. Phinney has competed in the Olympics, Pan-Am Games and has competed as a
pro-cyclist for nearly twenty years. The Davis Phinney Foundation strives to improve the lives of those
living with Parkinson's disease.

Other famous sufferers include Pope John Paul II, playwright Eugene O'Neill, artist Salvador Dalí, evangelist
Billy Graham, boxer Muhammad Ali, electric guitar pioneer Leo Fender, and former US Attorney General
Janet Reno. Political figures suffering from it have included Francisco Franco, Booth Gardner, 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.

11 of 15 27/03/2009 6:20 PM
Parkinson's disease - Wikipedia, the free encyclopedia

Michael Gibson, host of MTV Select, was diagnosed with Parkinson's at the age of 18. Gibson lived in denial
about his condition for six years. He then pitched a documentary proposal to Channel 4 who commissioned
him to make a documentary following Gibson's journey with Parkinson's. All shook up: Parkinson's at 25
( aired on
Channel 4 in 2006.

In addition, former Arsenal and Liverpool FC footballer Ray Kennedy, who won every domestic English
honour as well as the European Cup and UEFA Cup, is a sufferer of the disease, having been diagnosed at

See also
Dopamine dysregulation syndrome

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External links
European Parkinson's Disease Association (
Parkinson's Disease (
/Parkinson's_Disease//) at the Open Directory Project
Parkinson's Disease: Hope Through Research (National Institute of Neurological Disorders and
Stroke) (
World Parkinson Disease Association (

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