Park in Sons Diseas e

8/14/2019 Park in Sons Diseas e

1/24

Wikipedia is sustained by people like you. Please donate today.

Parkinson's disease

From Wikipedia, the free encyclopediaJump to:navigation, search

Parkinson's diseaseClassification and external

resources

Illustration of the Parkinson disease by Sir William Richard Gowersfrom A Manual of Diseases of the

Nervous System in 1886

ICD -10 G20. , F02.3

ICD -9 332

DiseasesDB 9651

MedlinePlus 000755

eMedicine neuro/304 neuro/635inyoung pmr/99rehab
http://wikimediafoundation.org/wiki/Fundraising?source=enwiki_02http://en.wikipedia.org/wiki/Parkinson's_disease#column-one%23column-onehttp://en.wikipedia.org/wiki/Parkinson's_disease#column-one%23column-onehttp://en.wikipedia.org/wiki/Parkinson's_disease#searchInput%23searchInputhttp://en.wikipedia.org/wiki/ICDhttp://en.wikipedia.org/wiki/List_of_ICD-10_codeshttp://en.wikipedia.org/wiki/ICD-10_Chapter_Ghttp://www.who.int/classifications/apps/icd/icd10online/?gg20.htm+g20http://www.who.int/classifications/apps/icd/icd10online/?gg20.htm+g20http://en.wikipedia.org/wiki/ICD-10_Chapter_Fhttp://www.who.int/classifications/apps/icd/icd10online/?gf00.htm+f023http://en.wikipedia.org/wiki/ICDhttp://en.wikipedia.org/wiki/List_of_ICD-9_codeshttp://www.icd9data.com/getICD9Code.ashx?icd9=332http://en.wikipedia.org/wiki/Diseases_Databasehttp://www.diseasesdatabase.com/ddb9651.htmhttp://en.wikipedia.org/wiki/MedlinePlushttp://www.nlm.nih.gov/medlineplus/ency/article/000755.htmhttp://en.wikipedia.org/wiki/EMedicinehttp://www.emedicine.com/neuro/topic304.htmhttp://www.emedicine.com/neuro/topic635.htmhttp://www.emedicine.com/pmr/topic99.htmhttp://en.wikipedia.org/wiki/Image:Sir_William_Richard_Gowers_Parkinson_Disease_sketch_1886.jpghttp://wikimediafoundation.org/wiki/Fundraising?source=enwiki_02http://en.wikipedia.org/wiki/Parkinson's_disease#column-one%23column-onehttp://en.wikipedia.org/wiki/Parkinson's_disease#searchInput%23searchInputhttp://en.wikipedia.org/wiki/ICDhttp://en.wikipedia.org/wiki/List_of_ICD-10_codeshttp://en.wikipedia.org/wiki/ICD-10_Chapter_Ghttp://www.who.int/classifications/apps/icd/icd10online/?gg20.htm+g20http://en.wikipedia.org/wiki/ICD-10_Chapter_Fhttp://www.who.int/classifications/apps/icd/icd10online/?gf00.htm+f023http://en.wikipedia.org/wiki/ICDhttp://en.wikipedia.org/wiki/List_of_ICD-9_codeshttp://www.icd9data.com/getICD9Code.ashx?icd9=332http://en.wikipedia.org/wiki/Diseases_Databasehttp://www.diseasesdatabase.com/ddb9651.htmhttp://en.wikipedia.org/wiki/MedlinePlushttp://www.nlm.nih.gov/medlineplus/ency/article/000755.htmhttp://en.wikipedia.org/wiki/EMedicinehttp://www.emedicine.com/neuro/topic304.htmhttp://www.emedicine.com/neuro/topic635.htmhttp://www.emedicine.com/pmr/topic99.htm


2/24

Parkinson's disease (also known asParkinson disease or PD ) is a degenerative disorder of thecentral nervous systemthat often impairs the sufferer'smotor skills, speech, andother functions.[1]

Parkinson's disease belongs to a group of conditions calledmovement 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 arethe results of decreased stimulation of themotor cortexby the basal ganglia, normallycaused by the insufficient formation and action of dopamine, which is produced in thedopaminergic neuronsof the brain. Secondary symptoms may include high levelcognitive dysfunction and subtle language problems. PD is bothchronicand progressive.

PD is the most common cause of chronic progressive parkinsonism, a term which refersto the syndrome of tremor, rigidity, bradykinesia and postural instability. PD is alsocalled "primary parkinsonism" or "idiopathicPD" (classically meaning having no knowncause although this term is not strictly true in light of the plethora of newly discovered

genetic mutations). While many forms of parkinsonism are "idiopathic", "secondary"cases may result from toxicity most notably of drugs, head trauma, or other medicaldisorders. The disease is named after English physicianJames Parkinson, who made adetailed description of the disease in his essay: "An Essay on the Shaking Palsy" (1817).

Contents

[hide]

1 Classification 2 Signs and symptoms

o 2.1 Motor symptomso 2.2 Neuropsychiatrico 2.3 Sleepo 2.4 Perceptiono 2.5 Autonomic

3 Causeso 3.1 Genetico 3.2 Toxinso 3.3 Head trauma

4 Pathophysiology 5 Diagnosis 6 Treatment

o 6.1 Levodopao 6.2 COMT Inhibitorso 6.3 Dopamine agonistso 6.4 MAO-B inhibitorso 6.5 Surgery and deep brain stimulationo 6.6 Neurorehabilitation
http://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Motor_skillhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jankovic2008-0%23cite_note-Jankovic2008-0http://en.wikipedia.org/wiki/Movement_disorderhttp://en.wikipedia.org/wiki/Bradykinesiahttp://en.wikipedia.org/wiki/Akinesiahttp://en.wikipedia.org/wiki/Motor_cortexhttp://en.wikipedia.org/wiki/Basal_gangliahttp://en.wikipedia.org/wiki/Basal_gangliahttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Dopaminergic_neuronhttp://en.wikipedia.org/wiki/Chronic_(medicine)http://en.wikipedia.org/wiki/Parkinsonismhttp://en.wikipedia.org/wiki/Idiopathichttp://en.wikipedia.org/wiki/James_Parkinsonhttp://en.wikipedia.org/wiki/James_Parkinsonhttp://toggletoc%28%29/http://en.wikipedia.org/wiki/Parkinson's_disease#Classification%23Classificationhttp://en.wikipedia.org/wiki/Parkinson's_disease#Signs_and_symptoms%23Signs_and_symptomshttp://en.wikipedia.org/wiki/Parkinson's_disease#Motor_symptoms%23Motor_symptomshttp://en.wikipedia.org/wiki/Parkinson's_disease#Neuropsychiatric%23Neuropsychiatrichttp://en.wikipedia.org/wiki/Parkinson's_disease#Sleep%23Sleephttp://en.wikipedia.org/wiki/Parkinson's_disease#Perception%23Perceptionhttp://en.wikipedia.org/wiki/Parkinson's_disease#Autonomic%23Autonomichttp://en.wikipedia.org/wiki/Parkinson's_disease#Causes%23Causeshttp://en.wikipedia.org/wiki/Parkinson's_disease#Genetic%23Genetichttp://en.wikipedia.org/wiki/Parkinson's_disease#Toxins%23Toxinshttp://en.wikipedia.org/wiki/Parkinson's_disease#Head_trauma%23Head_traumahttp://en.wikipedia.org/wiki/Parkinson's_disease#Pathophysiology%23Pathophysiologyhttp://en.wikipedia.org/wiki/Parkinson's_disease#Diagnosis%23Diagnosishttp://en.wikipedia.org/wiki/Parkinson's_disease#Treatment%23Treatmenthttp://en.wikipedia.org/wiki/Parkinson's_disease#Levodopa%23Levodopahttp://en.wikipedia.org/wiki/Parkinson's_disease#COMT_Inhibitors%23COMT_Inhibitorshttp://en.wikipedia.org/wiki/Parkinson's_disease#Dopamine_agonists%23Dopamine_agonistshttp://en.wikipedia.org/wiki/Parkinson's_disease#MAO-B_inhibitors%23MAO-B_inhibitorshttp://en.wikipedia.org/wiki/Parkinson's_disease#Surgery_and_deep_brain_stimulation%23Surgery_and_deep_brain_stimulationhttp://en.wikipedia.org/wiki/Parkinson's_disease#Neurorehabilitation%23Neurorehabilitationhttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Motor_skillhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jankovic2008-0%23cite_note-Jankovic2008-0http://en.wikipedia.org/wiki/Movement_disorderhttp://en.wikipedia.org/wiki/Bradykinesiahttp://en.wikipedia.org/wiki/Akinesiahttp://en.wikipedia.org/wiki/Motor_cortexhttp://en.wikipedia.org/wiki/Basal_gangliahttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Dopaminergic_neuronhttp://en.wikipedia.org/wiki/Chronic_(medicine)http://en.wikipedia.org/wiki/Parkinsonismhttp://en.wikipedia.org/wiki/Idiopathichttp://en.wikipedia.org/wiki/James_Parkinsonhttp://toggletoc%28%29/http://en.wikipedia.org/wiki/Parkinson's_disease#Classification%23Classificationhttp://en.wikipedia.org/wiki/Parkinson's_disease#Signs_and_symptoms%23Signs_and_symptomshttp://en.wikipedia.org/wiki/Parkinson's_disease#Motor_symptoms%23Motor_symptomshttp://en.wikipedia.org/wiki/Parkinson's_disease#Neuropsychiatric%23Neuropsychiatrichttp://en.wikipedia.org/wiki/Parkinson's_disease#Sleep%23Sleephttp://en.wikipedia.org/wiki/Parkinson's_disease#Perception%23Perceptionhttp://en.wikipedia.org/wiki/Parkinson's_disease#Autonomic%23Autonomichttp://en.wikipedia.org/wiki/Parkinson's_disease#Causes%23Causeshttp://en.wikipedia.org/wiki/Parkinson's_disease#Genetic%23Genetichttp://en.wikipedia.org/wiki/Parkinson's_disease#Toxins%23Toxinshttp://en.wikipedia.org/wiki/Parkinson's_disease#Head_trauma%23Head_traumahttp://en.wikipedia.org/wiki/Parkinson's_disease#Pathophysiology%23Pathophysiologyhttp://en.wikipedia.org/wiki/Parkinson's_disease#Diagnosis%23Diagnosishttp://en.wikipedia.org/wiki/Parkinson's_disease#Treatment%23Treatmenthttp://en.wikipedia.org/wiki/Parkinson's_disease#Levodopa%23Levodopahttp://en.wikipedia.org/wiki/Parkinson's_disease#COMT_Inhibitors%23COMT_Inhibitorshttp://en.wikipedia.org/wiki/Parkinson's_disease#Dopamine_agonists%23Dopamine_agonistshttp://en.wikipedia.org/wiki/Parkinson's_disease#MAO-B_inhibitors%23MAO-B_inhibitorshttp://en.wikipedia.org/wiki/Parkinson's_disease#Surgery_and_deep_brain_stimulation%23Surgery_and_deep_brain_stimulationhttp://en.wikipedia.org/wiki/Parkinson's_disease#Neurorehabilitation%23Neurorehabilitation


3/24

7 Prognosis 8 Epidemiology 9 History 10 Research directions

o 10.1 Gene therapyo 10.2 Neuroprotective treatmentso 10.3 Neural transplantationo 10.4 Alternative Treatments

11 Notable sufferers 12 References

13 External links

[edit ] Classification

"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 initiallydiagnosed with Parkinson's disease but then to develop additional features, requiringrevision of the diagnosis.[2]

There are other disorders that are called Parkinson-plus diseases . These include:multiplesystem atrophy(MSA), progressive supranuclear palsy(PSP) andcorticobasaldegeneration(CBD). Some includedementia with Lewy bodies (DLB) whileidiopathic Parkinson's disease patients also haveLewy bodiesin their brain tissue, thedistribution is denser and more widespread in DLB. Even so, the relationship betweenParkinson disease, Parkinson disease with dementia (PDD), and dementia with Lewy bodies (DLB) might be most accurately conceptualized as a spectrum, with a discretearea 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 idiopathicParkinson disease. If cognitive dysfunction occurs before or very early in the course of the movement disorder then DLBD may be suspected. Early postural instability withminimal tremor especially in the context of ophthalmoparesis should suggest PSP. Earlyautonomic dysfunction including erectile dysfunction and syncope may suggest MSA.The presence of extreme asymmetry with patchy cortical cognitive defects such asdysphasia and apraxias especially with "alien limb" phenomena should suggest CBD.

The usual anti-Parkinson's medications are typically either less effective or not effectiveat all in controlling symptoms; patients may be exquisitely sensitive to neurolepticmedications likehaloperidol. Additionally, thecholinesterase inhibitingmedications haveshown preliminary efficacy in treating the cognitive, psychiatric, and behavioral aspectsof the disease, so correct differential diagnosis is important.
http://en.wikipedia.org/wiki/Parkinson's_disease#Prognosis%23Prognosishttp://en.wikipedia.org/wiki/Parkinson's_disease#Epidemiology%23Epidemiologyhttp://en.wikipedia.org/wiki/Parkinson's_disease#History%23Historyhttp://en.wikipedia.org/wiki/Parkinson's_disease#Research_directions%23Research_directionshttp://en.wikipedia.org/wiki/Parkinson's_disease#Gene_therapy%23Gene_therapyhttp://en.wikipedia.org/wiki/Parkinson's_disease#Neuroprotective_treatments%23Neuroprotective_treatmentshttp://en.wikipedia.org/wiki/Parkinson's_disease#Neural_transplantation%23Neural_transplantationhttp://en.wikipedia.org/wiki/Parkinson's_disease#Alternative_Treatments%23Alternative_Treatmentshttp://en.wikipedia.org/wiki/Parkinson's_disease#Notable_sufferers%23Notable_sufferershttp://en.wikipedia.org/wiki/Parkinson's_disease#References%23Referenceshttp://en.wikipedia.org/wiki/Parkinson's_disease#External_links%23External_linkshttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=1http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-nice35-1%23cite_note-nice35-1http://en.wikipedia.org/wiki/Parkinson_plus_syndromehttp://en.wikipedia.org/wiki/Parkinson_plus_syndromehttp://en.wikipedia.org/wiki/Multiple_system_atrophyhttp://en.wikipedia.org/wiki/Multiple_system_atrophyhttp://en.wikipedia.org/wiki/Progressive_supranuclear_palsyhttp://en.wikipedia.org/wiki/Corticobasal_degenerationhttp://en.wikipedia.org/wiki/Corticobasal_degenerationhttp://en.wikipedia.org/wiki/Dementia_with_Lewy_bodieshttp://en.wikipedia.org/wiki/Dementia_with_Lewy_bodieshttp://en.wikipedia.org/wiki/Lewy_bodyhttp://en.wikipedia.org/wiki/Haloperidolhttp://en.wikipedia.org/wiki/Acetylcholinesterase_inhibitorhttp://en.wikipedia.org/wiki/Parkinson's_disease#Prognosis%23Prognosishttp://en.wikipedia.org/wiki/Parkinson's_disease#Epidemiology%23Epidemiologyhttp://en.wikipedia.org/wiki/Parkinson's_disease#History%23Historyhttp://en.wikipedia.org/wiki/Parkinson's_disease#Research_directions%23Research_directionshttp://en.wikipedia.org/wiki/Parkinson's_disease#Gene_therapy%23Gene_therapyhttp://en.wikipedia.org/wiki/Parkinson's_disease#Neuroprotective_treatments%23Neuroprotective_treatmentshttp://en.wikipedia.org/wiki/Parkinson's_disease#Neural_transplantation%23Neural_transplantationhttp://en.wikipedia.org/wiki/Parkinson's_disease#Alternative_Treatments%23Alternative_Treatmentshttp://en.wikipedia.org/wiki/Parkinson's_disease#Notable_sufferers%23Notable_sufferershttp://en.wikipedia.org/wiki/Parkinson's_disease#References%23Referenceshttp://en.wikipedia.org/wiki/Parkinson's_disease#External_links%23External_linkshttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=1http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-nice35-1%23cite_note-nice35-1http://en.wikipedia.org/wiki/Parkinson_plus_syndromehttp://en.wikipedia.org/wiki/Multiple_system_atrophyhttp://en.wikipedia.org/wiki/Multiple_system_atrophyhttp://en.wikipedia.org/wiki/Progressive_supranuclear_palsyhttp://en.wikipedia.org/wiki/Corticobasal_degenerationhttp://en.wikipedia.org/wiki/Corticobasal_degenerationhttp://en.wikipedia.org/wiki/Dementia_with_Lewy_bodieshttp://en.wikipedia.org/wiki/Lewy_bodyhttp://en.wikipedia.org/wiki/Haloperidolhttp://en.wikipedia.org/wiki/Acetylcholinesterase_inhibitor


4/24

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, suchas improvement with beta blockersandalcoholic 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 medicaltreatment. Typical tests areliver function, slit lamp examination for Kayser-Fleischer rings, and serumceruloplasminlevels.

[edit ] Signs and symptoms

Parkinson disease affects movement (motor symptoms). Other typical symptoms includedisorders of mood, behaviour, thinking, and sensation (non-motor symptoms). Patients'individual symptoms may be quite dissimilar and progression of the disease is alsodistinctly individual.

[edit ] Motor symptoms

Thecardinal symptomsare (mnemonic "TRAP"):[1]

Tremor : normally 4-6Hz tremor, maximal when the limb is at rest, and decreasedwith voluntary movement. It is typically unilateral at onset. This is the mostapparent and well-known symptom, though an estimated 30% of patients havelittle 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 dysrhythmicand decremental loss of amplitude.

Postural instability : failure of posturalreflexes, which leads to impaired balanceand falls.

Other motor symptoms include:

Gaitand posture disturbances:o Shuffling: gait is characterized by short steps, with feet barely leaving the

ground, producing an audible shuffling noise. Small obstacles tend tocause the patient to trip.

o Decreased arm-swing.o 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, requiringmultiple small steps to accomplish a turn.

o 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]
http://en.wikipedia.org/wiki/Essential_tremorhttp://en.wikipedia.org/wiki/Essential_tremorhttp://en.wikipedia.org/wiki/Beta_blockerhttp://en.wikipedia.org/wiki/Alcoholic_beveragehttp://en.wikipedia.org/wiki/Alcoholic_beveragehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jankovic2008-0%23cite_note-Jankovic2008-0http://en.wikipedia.org/wiki/Wilson's_diseasehttp://en.wikipedia.org/wiki/Liver_enzymeshttp://en.wikipedia.org/wiki/Kayser-Fleischer_ringhttp://en.wikipedia.org/wiki/Kayser-Fleischer_ringhttp://en.wikipedia.org/wiki/Ceruloplasminhttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=2http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=3http://en.wikipedia.org/wiki/Cardinal_symptomhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jankovic2008-0%23cite_note-Jankovic2008-0http://en.wikipedia.org/wiki/Tremorhttp://en.wikipedia.org/wiki/Hertzhttp://en.wikipedia.org/wiki/Spasticityhttp://en.wikipedia.org/wiki/Bradykinesiahttp://en.wikipedia.org/wiki/Akinesiahttp://en.wikipedia.org/wiki/Rhythmhttp://en.wikipedia.org/wiki/Rhythmhttp://en.wikipedia.org/wiki/Amplitudehttp://en.wikipedia.org/wiki/Amplitudehttp://en.wikipedia.org/wiki/Postural_instabilityhttp://en.wikipedia.org/wiki/Reflexeshttp://en.wikipedia.org/wiki/Gaithttp://en.wikipedia.org/wiki/Right_anglehttp://en.wikipedia.org/wiki/Right_anglehttp://en.wikipedia.org/wiki/Right_anglehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-2%23cite_note-2http://en.wikipedia.org/wiki/Essential_tremorhttp://en.wikipedia.org/wiki/Beta_blockerhttp://en.wikipedia.org/wiki/Alcoholic_beveragehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jankovic2008-0%23cite_note-Jankovic2008-0http://en.wikipedia.org/wiki/Wilson's_diseasehttp://en.wikipedia.org/wiki/Liver_enzymeshttp://en.wikipedia.org/wiki/Kayser-Fleischer_ringhttp://en.wikipedia.org/wiki/Kayser-Fleischer_ringhttp://en.wikipedia.org/wiki/Ceruloplasminhttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=2http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=3http://en.wikipedia.org/wiki/Cardinal_symptomhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jankovic2008-0%23cite_note-Jankovic2008-0http://en.wikipedia.org/wiki/Tremorhttp://en.wikipedia.org/wiki/Hertzhttp://en.wikipedia.org/wiki/Spasticityhttp://en.wikipedia.org/wiki/Bradykinesiahttp://en.wikipedia.org/wiki/Akinesiahttp://en.wikipedia.org/wiki/Rhythmhttp://en.wikipedia.org/wiki/Amplitudehttp://en.wikipedia.org/wiki/Postural_instabilityhttp://en.wikipedia.org/wiki/Reflexeshttp://en.wikipedia.org/wiki/Gaithttp://en.wikipedia.org/wiki/Right_anglehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-2%23cite_note-2


5/24

o Festination: a combination of stooped posture, imbalance, and short steps.It leads to a gait that gets progressively faster and faster, often ending in afall.

o Gait freezing: "freezing" is a manifestation of akinesia (an inability tomove). Gait freezing is characterized by an inability to move the feet

which may worsen in tight, cluttered spaces or when attempting to initiategait.o Dystonia(in about 20% of cases): abnormal, sustained, painful twisting

muscle contractions, often affecting the foot and ankle (mainly toe flexionand foot inversion) which often interferes with gait.

Speech and swallowing disturbances.o Hypophonia: soft speech. Speech quality tends to be soft, hoarse, and

monotonous. Some people with Parkinson's disease claim that their tongueis "heavy" or havecluttered speech.[4]

o Monotonic speech.o Festinating speech: excessively rapid, soft, poorly-intelligible speech.o Drooling: most likely caused by a weak, infrequent swallow and stooped posture.o Dysphagia: impaired ability to swallow. Can lead toaspiration,

pneumonia. Other motor symptoms:

o Fatigue(up to 50% of cases);o Masked faces (a mask-like face also known ashypomimia), with

infrequent blinking;[5] o Difficulty rolling in bed or rising from a seated position;o Micrographia(small, cramped handwriting);o Impaired fine motor dexterity and motor coordination;o Impaired gross motor coordination;o Akathisia, the inability to sit still.

[edit ] Neuropsychiatric

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

Estimated prevalence rates of depression vary widely according to the populationsampled and methodology used. Reviews of depression estimate its occurrence inanywhere 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 theBeck 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 depressionto go on to develop Parkinson's disease at a later date.[7] Seventy percent of individualswith Parkinson's disease diagnosed with pre-existing depression go on to developanxiety. Ninety percent of Parkinson's disease patients with pre-existing anxietysubsequently develop depression;apathy or abulia.
http://en.wikipedia.org/wiki/Dystoniahttp://en.wikipedia.org/wiki/Cluttered_speechhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-3%23cite_note-3http://en.wikipedia.org/wiki/Droolinghttp://en.wikipedia.org/wiki/Dysphagiahttp://en.wikipedia.org/wiki/Pulmonary_aspirationhttp://en.wikipedia.org/wiki/Pulmonary_aspirationhttp://en.wikipedia.org/wiki/Pneumoniahttp://en.wikipedia.org/wiki/Pneumoniahttp://en.wikipedia.org/wiki/Fatigue_(physical)http://en.wikipedia.org/wiki/Hypomimiahttp://en.wikipedia.org/wiki/Blinkinghttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-4%23cite_note-4http://en.wikipedia.org/wiki/Micrographia_(handwriting)http://en.wikipedia.org/wiki/Motor_coordinationhttp://en.wikipedia.org/wiki/Motor_coordinationhttp://en.wikipedia.org/wiki/Akathisiahttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=4http://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-5%23cite_note-5http://en.wikipedia.org/wiki/Beck_Depression_Inventoryhttp://en.wikipedia.org/wiki/Beck_Depression_Inventoryhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-6%23cite_note-6http://en.wikipedia.org/wiki/Apathyhttp://en.wikipedia.org/wiki/Apathyhttp://en.wikipedia.org/wiki/Abuliahttp://en.wikipedia.org/wiki/Dystoniahttp://en.wikipedia.org/wiki/Cluttered_speechhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-3%23cite_note-3http://en.wikipedia.org/wiki/Droolinghttp://en.wikipedia.org/wiki/Dysphagiahttp://en.wikipedia.org/wiki/Pulmonary_aspirationhttp://en.wikipedia.org/wiki/Pneumoniahttp://en.wikipedia.org/wiki/Fatigue_(physical)http://en.wikipedia.org/wiki/Hypomimiahttp://en.wikipedia.org/wiki/Blinkinghttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-4%23cite_note-4http://en.wikipedia.org/wiki/Micrographia_(handwriting)http://en.wikipedia.org/wiki/Motor_coordinationhttp://en.wikipedia.org/wiki/Akathisiahttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=4http://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-5%23cite_note-5http://en.wikipedia.org/wiki/Beck_Depression_Inventoryhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-6%23cite_note-6http://en.wikipedia.org/wiki/Apathyhttp://en.wikipedia.org/wiki/Abulia


6/24

Cognitive disturbances include:

Slowed reaction time; both voluntary and involuntary motor responses aresignificantly 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. Thiscomplex is present to some degree in most Parkinson's patients; it may progressto:

Dementia: a later development in approximately 20-40% of all patients, typicallystarting with slowing of thought and progressing to difficulties with abstractthought, memory, and behavioral regulation.Hallucinations, delusionsand paranoia may develop.

Short termmemory loss; procedural memory is more impaired thandeclarativememory. Prompting elicits improved recall.

Non-motor causes of speech/language disturbance in both expressive and

receptive language: these include decreased verbal fluency and cognitivedisturbance especially related to comprehension of emotional content of speechand of facial expression.[8]

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

[edit ] Sleep

Excessive daytimesomnolence Initial, intermediate, and terminalinsomnia Disturbances inREMsleep: disturbingly vivid dreams, and REM Sleep Disorder,

characterized by acting out of dream content can occur years prior to diagnosis[edit ] Perception

Impaired visualcontrast sensitivity, spatial reasoning,colour discrimination,convergence insufficiency (characterized bydouble vision) and oculomotor control

Dizzinessand fainting; usually attributableorthostatic hypotension, a failure of theautonomic nervous systemto 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(hyposmiaor 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

[edit ] Autonomic
http://en.wikipedia.org/w/index.php?title=Slowed_reaction_time&action=edit&redlink=1http://en.wikipedia.org/wiki/Executive_dysfunctionhttp://en.wikipedia.org/wiki/Dementiahttp://en.wikipedia.org/wiki/Hallucinationshttp://en.wikipedia.org/wiki/Hallucinationshttp://en.wikipedia.org/wiki/Delusionshttp://en.wikipedia.org/wiki/Paranoiahttp://en.wikipedia.org/wiki/Paranoiahttp://en.wikipedia.org/wiki/Memory_losshttp://en.wikipedia.org/wiki/Procedural_memoryhttp://en.wikipedia.org/wiki/Procedural_memoryhttp://en.wikipedia.org/wiki/Declarative_memoryhttp://en.wikipedia.org/wiki/Declarative_memoryhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-7%23cite_note-7http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-8%23cite_note-8http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-8%23cite_note-8http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=5http://en.wikipedia.org/wiki/Somnolencehttp://en.wikipedia.org/wiki/Insomniahttp://en.wikipedia.org/wiki/Rapid_eye_movement_sleephttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=6http://en.wikipedia.org/wiki/Contrast_sensitivityhttp://en.wikipedia.org/wiki/Contrast_sensitivityhttp://en.wikipedia.org/wiki/Colorhttp://en.wikipedia.org/wiki/Convergence_insufficiencyhttp://en.wikipedia.org/wiki/Convergence_insufficiencyhttp://en.wikipedia.org/wiki/Double_visionhttp://en.wikipedia.org/wiki/Oculomotor_controlhttp://en.wikipedia.org/wiki/Oculomotor_controlhttp://en.wikipedia.org/wiki/Oculomotor_controlhttp://en.wikipedia.org/wiki/Dizzinesshttp://en.wikipedia.org/wiki/Orthostatic_hypotensionhttp://en.wikipedia.org/wiki/Orthostatic_hypotensionhttp://en.wikipedia.org/wiki/Autonomic_nervous_systemhttp://en.wikipedia.org/wiki/Proprioceptionhttp://en.wikipedia.org/wiki/Olfactionhttp://en.wikipedia.org/wiki/Hyposmiahttp://en.wikipedia.org/wiki/Anosmiahttp://en.wikipedia.org/wiki/Anosmiahttp://en.wikipedia.org/wiki/Painhttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=7http://en.wikipedia.org/w/index.php?title=Slowed_reaction_time&action=edit&redlink=1http://en.wikipedia.org/wiki/Executive_dysfunctionhttp://en.wikipedia.org/wiki/Dementiahttp://en.wikipedia.org/wiki/Hallucinationshttp://en.wikipedia.org/wiki/Delusionshttp://en.wikipedia.org/wiki/Paranoiahttp://en.wikipedia.org/wiki/Memory_losshttp://en.wikipedia.org/wiki/Procedural_memoryhttp://en.wikipedia.org/wiki/Declarative_memoryhttp://en.wikipedia.org/wiki/Declarative_memoryhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-7%23cite_note-7http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-8%23cite_note-8http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=5http://en.wikipedia.org/wiki/Somnolencehttp://en.wikipedia.org/wiki/Insomniahttp://en.wikipedia.org/wiki/Rapid_eye_movement_sleephttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=6http://en.wikipedia.org/wiki/Contrast_sensitivityhttp://en.wikipedia.org/wiki/Colorhttp://en.wikipedia.org/wiki/Convergence_insufficiencyhttp://en.wikipedia.org/wiki/Double_visionhttp://en.wikipedia.org/wiki/Oculomotor_controlhttp://en.wikipedia.org/wiki/Oculomotor_controlhttp://en.wikipedia.org/wiki/Dizzinesshttp://en.wikipedia.org/wiki/Orthostatic_hypotensionhttp://en.wikipedia.org/wiki/Autonomic_nervous_systemhttp://en.wikipedia.org/wiki/Proprioceptionhttp://en.wikipedia.org/wiki/Olfactionhttp://en.wikipedia.org/wiki/Hyposmiahttp://en.wikipedia.org/wiki/Anosmiahttp://en.wikipedia.org/wiki/Painhttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=7


7/24

Oily skin andseborrheic dermatitis[10] Urinary incontinence, typically in later disease progression Nocturia (getting up in the night to pass urine) up to 60% of cases Constipationandgastricdysmotility 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. Currentdata addresses male sexual function almost exclusively.

Weight loss, which is significant over a period of ten years.

[edit ] Causes

Most people with Parkinson's disease are described as havingidiopathicParkinson'sdisease (having no specific cause). There are far less common causes of Parkinson'sdisease including genetic, toxins, head trauma, cerebral anoxia, and drug-inducedParkinson's disease.

[edit ] Genetic

In recent years, a number of specific genetic mutations causing Parkinson's disease have been discovered, including in certain populations (Contursi, Italy). These account for asmall minority of cases of Parkinson's disease. Someone who has Parkinson's disease ismore likely to have relatives that also have Parkinson's disease.However, this does notmean that the disorder has been passed on genetically.

[edit ] Toxins

One theory holds that the disease may result in many or even most cases from thecombination of a genetically determined vulnerability to environmentaltoxins along withexposure to those toxins.[11] This hypothesis is consistent with the fact that Parkinson'sdisease is not distributed homogeneously throughout the population; its incidence variesgeographically. However, it is not consistent with the fact that the first appearance of thesyndrome predates the first synthesis of the compounds often attributed to causingParkinson's disease. The toxins most strongly suspected at present are certain pesticides and transition-series metals such as manganese or iron, especially those that generatereactive oxygen species,[12][13] and/or bind to neuromelanin, as originally suggested byG.C. Cotzias.[14][15] In the Cancer Prevention Study II Nutrition Cohort, a longitudinalinvestigation, 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 acontaminated and illicitly produced batch of the synthetic opiate MPPP brought to lightMPTP(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 speciesthrough tyrosine hydroxylation.[17] The Case of the Frozen Addicts byJ. William
http://en.wikipedia.org/wiki/Seborrheic_dermatitishttp://en.wikipedia.org/wiki/Seborrheic_dermatitishttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-9%23cite_note-9http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-9%23cite_note-9http://en.wikipedia.org/wiki/Urinary_incontinencehttp://en.wikipedia.org/wiki/Constipationhttp://en.wikipedia.org/wiki/Gastrichttp://en.wikipedia.org/wiki/Weight_losshttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=8http://en.wikipedia.org/wiki/Idiopathichttp://en.wikipedia.org/wiki/Hypoxia_(medical)http://en.wikipedia.org/wiki/Hypoxia_(medical)http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=9http://en.wikipedia.org/wiki/Contursihttp://en.wikipedia.org/wiki/Contursihttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=10http://en.wikipedia.org/wiki/Toxinhttp://en.wikipedia.org/wiki/Toxinhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-10%23cite_note-10http://en.wikipedia.org/wiki/Pesticidehttp://en.wikipedia.org/wiki/Pesticidehttp://en.wikipedia.org/wiki/Reactive_oxygen_specieshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jenner1998-11%23cite_note-Jenner1998-11http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-12%23cite_note-12http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-12%23cite_note-12http://en.wikipedia.org/wiki/Neuromelaninhttp://en.wikipedia.org/wiki/Neuromelaninhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-13%23cite_note-13http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-14%23cite_note-14http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-15%23cite_note-15http://en.wikipedia.org/wiki/MPPPhttp://en.wikipedia.org/wiki/MPPPhttp://en.wikipedia.org/wiki/MPPPhttp://en.wikipedia.org/wiki/MPTPhttp://en.wikipedia.org/wiki/Reactive_oxygen_specieshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-16%23cite_note-16http://en.wikipedia.org/w/index.php?title=The_Case_of_the_Frozen_Addicts&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=The_Case_of_the_Frozen_Addicts&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=J._William_Langston&action=edit&redlink=1http://en.wikipedia.org/wiki/Seborrheic_dermatitishttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-9%23cite_note-9http://en.wikipedia.org/wiki/Urinary_incontinencehttp://en.wikipedia.org/wiki/Constipationhttp://en.wikipedia.org/wiki/Gastrichttp://en.wikipedia.org/wiki/Weight_losshttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=8http://en.wikipedia.org/wiki/Idiopathichttp://en.wikipedia.org/wiki/Hypoxia_(medical)http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=9http://en.wikipedia.org/wiki/Contursihttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=10http://en.wikipedia.org/wiki/Toxinhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-10%23cite_note-10http://en.wikipedia.org/wiki/Pesticidehttp://en.wikipedia.org/wiki/Reactive_oxygen_specieshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jenner1998-11%23cite_note-Jenner1998-11http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-12%23cite_note-12http://en.wikipedia.org/wiki/Neuromelaninhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-13%23cite_note-13http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-14%23cite_note-14http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-15%23cite_note-15http://en.wikipedia.org/wiki/MPPPhttp://en.wikipedia.org/wiki/MPTPhttp://en.wikipedia.org/wiki/Reactive_oxygen_specieshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-16%23cite_note-16http://en.wikipedia.org/w/index.php?title=The_Case_of_the_Frozen_Addicts&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=J._William_Langston&action=edit&redlink=1


8/24

Langston(Vintage, New York, June 25, 1996) documents this tragedy and describes thefirst attempts at fetal brain tissue transplants to treat PD.

Other toxin-based models employ PCBs,[18] paraquat[19] (a herbicide) in combination withmaneb (a 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 extremelyhydrophobic properties. Rotenone, therefore, does not rely on the dopamine transporter toenter into the cytoplasm. Numerous studies have found an increase in PD in persons whoconsume rural well water; researchers theorize that water consumption is a proxymeasure of pesticide exposure. In agreement with this hypothesis are studies which havefound a dose-dependent increase in PD in persons exposed to agricultural chemicals.

[edit ] 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 methodologicallystrong retrospective study[24] found that those who have experienced a head injury arefour times more likely to develop Parkinsons disease than those who have never suffereda head injury. The risk of developing Parkinsons increases eightfold for patients whohave had head trauma requiring hospitalization, and it increases 11-fold for patients whohad experienced severe head injury. The authors comment that since head trauma is a rareevent, 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 causesof their illness, may remember head trauma better than the non-ill control subjects. Theselimitations 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 diseasedevelopment or the early symptoms of clumsiness associated with Parkinson's causesindividuals to have more head trauma is still unknown.

[edit ] Pathophysiology
http://en.wikipedia.org/w/index.php?title=J._William_Langston&action=edit&redlink=1http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-17%23cite_note-17http://en.wikipedia.org/wiki/Paraquathttp://en.wikipedia.org/wiki/Paraquathttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-18%23cite_note-18http://en.wikipedia.org/wiki/Paraquathttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-19%23cite_note-19http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-19%23cite_note-19http://en.wikipedia.org/wiki/Rotenonehttp://en.wikipedia.org/wiki/Rotenonehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-20%23cite_note-20http://en.wikipedia.org/wiki/Rotenonehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-21%23cite_note-21http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-22%23cite_note-22http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=11http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Bower-23%23cite_note-Bower-23http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-24%23cite_note-24http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Uryu2003-25%23cite_note-Uryu2003-25http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Bower-23%23cite_note-Bower-23http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-26%23cite_note-26http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-26%23cite_note-26http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-26%23cite_note-26http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=12http://en.wikipedia.org/wiki/Image:DA-loops_in_PD.jpghttp://en.wikipedia.org/w/index.php?title=J._William_Langston&action=edit&redlink=1http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-17%23cite_note-17http://en.wikipedia.org/wiki/Paraquathttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-18%23cite_note-18http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-19%23cite_note-19http://en.wikipedia.org/wiki/Rotenonehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-20%23cite_note-20http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-21%23cite_note-21http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-22%23cite_note-22http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=11http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Bower-23%23cite_note-Bower-23http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-24%23cite_note-24http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Uryu2003-25%23cite_note-Uryu2003-25http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Bower-23%23cite_note-Bower-23http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-26%23cite_note-26http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=12


9/24

Dopaminergic pathways of the human brain in normal condition (left) and Parkinson'sdisease (right). Red Arrows indicate suppression of the target, blue arrows indicatestimulation of target structure.

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 thestriatumand their loss leads toalterations in the activity of the neural circuits within the basal ganglia that regulatemovement, in essence an inhibition of thedirect 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 anterior nucleus of the thalamus,which sends excitatory projections to themotor cortex, thus leading to hypokinesia.

There are four major dopamine pathways in the brain; the nigrostriatal pathway, referredto above, mediates movement and is the most conspicuously affected in early Parkinson'sdisease. The other pathways are the mesocortical, the mesolimbic, and thetuberoinfundibular. Disruption of dopamine along the non-striatal pathways likelyexplains 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 anabnormal accumulation of the protein alpha-synucleinbound to ubiquitin in the damagedcells. Thealpha-synuclein-ubiquitin complex cannot be directed to the proteosome. This proteinaccumulation forms proteinaceous cytoplasmic inclusions called Lewy bodies. The 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 Golgiapparatus. Certain proteins like Rab1 may reverse this defect caused by alpha-synucleinin animal models.[28]

Excessive accumulations of iron, which are toxic to nerve cells, are also typicallyobserved in conjunction with the protein inclusions. Iron and other transition metalssuchas copper bind toneuromelanin in the affected neurons of the substantia nigra. Neuromelaninmay be acting as a protective agent. The most likely mechanism isgeneration of reactive oxygen species.[12] Iron also induces aggregation of synuclein byoxidative mechanisms.[29] Similarly, dopamine and the byproducts of dopamine production enhance alpha-synuclein aggregation. The precise mechanism whereby suchaggregates of alpha-synuclein damage the cells is not known. The aggregates may bemerely a normal reaction by the cells as part of their effort to correct a different, as-yetunknown, insult. Based on this mechanistic hypothesis, atransgenic mouse modelof Parkinson's has been generated by introduction of human wild-type alpha-synuclein intothe mouse genome under control of the platelet-derived-growth factor - promoter.[30]

[edit ] Diagnosis
http://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Pars_compactahttp://en.wikipedia.org/wiki/Pars_compactahttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Striatumhttp://en.wikipedia.org/wiki/Direct_pathwayhttp://en.wikipedia.org/wiki/Direct_pathwayhttp://en.wikipedia.org/wiki/Indirect_pathwayhttp://en.wikipedia.org/wiki/Indirect_pathwayhttp://en.wikipedia.org/wiki/Indirect_pathwayhttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Motor_cortexhttp://en.wikipedia.org/wiki/Hypokinesiahttp://en.wikipedia.org/wiki/Hypokinesiahttp://en.wikipedia.org/wiki/Alpha-synucleinhttp://en.wikipedia.org/wiki/Alpha-synucleinhttp://en.wikipedia.org/wiki/Alpha-synucleinhttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Lewy_bodieshttp://en.wikipedia.org/wiki/Lewy_bodieshttp://en.wikipedia.org/wiki/Lewy_bodieshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-27%23cite_note-27http://en.wikipedia.org/wiki/Transition_metalshttp://en.wikipedia.org/wiki/Neuromelaninhttp://en.wikipedia.org/wiki/Neuromelaninhttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Neuromelaninhttp://en.wikipedia.org/wiki/Reactive_oxygen_specieshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jenner1998-11%23cite_note-Jenner1998-11http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jenner1998-11%23cite_note-Jenner1998-11http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jenner1998-11%23cite_note-Jenner1998-11http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-28%23cite_note-28http://en.wikipedia.org/wiki/Genetically_modified_organismhttp://en.wikipedia.org/wiki/Platelet-derived_growth_factorhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-29%23cite_note-29http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=13http://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Pars_compactahttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Striatumhttp://en.wikipedia.org/wiki/Direct_pathwayhttp://en.wikipedia.org/wiki/Indirect_pathwayhttp://en.wikipedia.org/wiki/Indirect_pathwayhttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Motor_cortexhttp://en.wikipedia.org/wiki/Hypokinesiahttp://en.wikipedia.org/wiki/Alpha-synucleinhttp://en.wikipedia.org/wiki/Alpha-synucleinhttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Lewy_bodieshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-27%23cite_note-27http://en.wikipedia.org/wiki/Transition_metalshttp://en.wikipedia.org/wiki/Neuromelaninhttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Neuromelaninhttp://en.wikipedia.org/wiki/Reactive_oxygen_specieshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-Jenner1998-11%23cite_note-Jenner1998-11http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-28%23cite_note-28http://en.wikipedia.org/wiki/Genetically_modified_organismhttp://en.wikipedia.org/wiki/Platelet-derived_growth_factorhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-29%23cite_note-29http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=13


10/24

18F PET scan shows decreased dopamine activity in the basal ganglia, a pattern whichaids in diagnosing Parkinson's disease.

Typically, the diagnosis is based on medical history and neurological examinationconducted by interviewing and observing the patient in person using theUnified

Parkinson's Disease Rating Scale. A radiotracer for SPECTscanning machines calledDaTSCANand made byGeneral Electricis specialized for diagnosing Parkinson'sDisease, but it is only marketed in Europe. Due to this, the disease can be difficult todiagnose 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 atautopsy.[31] Early signs and symptoms of PD may sometimes be dismissed as the effectsof normal aging. The physician may need to observe the person for some time until it isapparent 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.

Clinical practice guidelines introduced in the UK in 2006 state that the diagnosis andfollow-up of Parkinson's disease should be done by a specialist in the disease, usually aneurologistor geriatricianwith an interest in movement disorders.[2]

[edit ] Treatment

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, butmedications or surgery can provide relief from the symptoms.

[edit ] Levodopa
http://en.wikipedia.org/wiki/Basal_gangliahttp://en.wikipedia.org/wiki/Unified_Parkinson's_Disease_Rating_Scalehttp://en.wikipedia.org/wiki/Unified_Parkinson's_Disease_Rating_Scalehttp://en.wikipedia.org/wiki/SPECThttp://en.wikipedia.org/wiki/DaTSCANhttp://en.wikipedia.org/wiki/General_Electrichttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-30%23cite_note-30http://en.wikipedia.org/wiki/Clinical_practice_guidelinehttp://en.wikipedia.org/wiki/Clinical_practice_guidelinehttp://en.wikipedia.org/wiki/United_Kingdomhttp://en.wikipedia.org/wiki/United_Kingdomhttp://en.wikipedia.org/wiki/Neurologyhttp://en.wikipedia.org/wiki/Geriatricianhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-nice35-1%23cite_note-nice35-1http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-nice35-1%23cite_note-nice35-1http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=14http://en.wikipedia.org/wiki/Physiotherapyhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-nice35-1%23cite_note-nice35-1http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=15http://en.wikipedia.org/wiki/Image:PET_scan_Parkinson%27s_Disease.jpghttp://en.wikipedia.org/wiki/Basal_gangliahttp://en.wikipedia.org/wiki/Unified_Parkinson's_Disease_Rating_Scalehttp://en.wikipedia.org/wiki/Unified_Parkinson's_Disease_Rating_Scalehttp://en.wikipedia.org/wiki/SPECThttp://en.wikipedia.org/wiki/DaTSCANhttp://en.wikipedia.org/wiki/General_Electrichttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-30%23cite_note-30http://en.wikipedia.org/wiki/Clinical_practice_guidelinehttp://en.wikipedia.org/wiki/United_Kingdomhttp://en.wikipedia.org/wiki/Neurologyhttp://en.wikipedia.org/wiki/Geriatricianhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-nice35-1%23cite_note-nice35-1http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=14http://en.wikipedia.org/wiki/Physiotherapyhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-nice35-1%23cite_note-nice35-1http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=15


11/24

Stalevo for treatment of Parkinson's disease

The most widely used form of treatment isL-dopain various forms. L-dopa istransformed into dopamine in the dopaminergic neurons by L-aromatic amino aciddecarboxylase (often known by its former name dopa-decarboxylase). However, only 1-

5% of L-DOPA enters the dopaminergic neurons. The remaining L-DOPA is oftenmetabolised to dopamine elsewhere, causing a wide variety of side effects. Due tofeedback inhibition, L-dopa results in a reduction in the endogenous formation of L-dopa,and so eventually becomes counterproductive.

Carbidopaand benserazideare dopa decarboxylase inhibitors. They help to prevent themetabolism of L-dopa before it reaches the dopaminergic neurons and are generally givenas combination preparations of carbidopa/levodopa(co-careldopa) (e.g. Sinemet,Parcopa) and benserazide/levodopa(co-beneldopa) (e.g. Madopar). There are alsocontrolled 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 tubedirectly into the upper small intestine, where it is rapidly absorbed. There is also Stalevo(Carbidopa, Levodopa and Entacapone).

[edit ] COMT Inhibitors

Tolcaponeinhibits theCOMTenzyme, thereby prolonging the effects of L-dopa, and sohas been used to complement L-dopa. However, due to its possible side effects such asliver failure, it's limited in its availability. A similar drug, entacaponehas not been shownto cause significant alterations of liver function and maintains adequate inhibition of COMT over time.[32]

[edit ] Dopamine agonists

The dopamine agonists bromocriptine, pergolide, pramipexole, ropinirole, cabergoline,apomorphine, andlisurideare moderately effective. These have their own side effectsincluding 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
http://en.wikipedia.org/wiki/L-dopahttp://en.wikipedia.org/wiki/Carbidopahttp://en.wikipedia.org/wiki/Benserazidehttp://en.wikipedia.org/wiki/Benserazidehttp://en.wikipedia.org/wiki/Carbidopa/levodopahttp://en.wikipedia.org/wiki/Benserazidehttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=16http://en.wikipedia.org/wiki/Tolcaponehttp://en.wikipedia.org/wiki/COMThttp://en.wikipedia.org/wiki/Entacaponehttp://en.wikipedia.org/wiki/Entacaponehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-TNcilia-31%23cite_note-TNcilia-31http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=17http://en.wikipedia.org/wiki/Bromocriptinehttp://en.wikipedia.org/wiki/Bromocriptinehttp://en.wikipedia.org/wiki/Pergolidehttp://en.wikipedia.org/wiki/Pramipexolehttp://en.wikipedia.org/wiki/Pramipexolehttp://en.wikipedia.org/wiki/Ropinirolehttp://en.wikipedia.org/wiki/Ropinirolehttp://en.wikipedia.org/wiki/Cabergolinehttp://en.wikipedia.org/wiki/Apomorphinehttp://en.wikipedia.org/wiki/Apomorphinehttp://en.wikipedia.org/wiki/Lisuridehttp://en.wikipedia.org/wiki/Image:Stalevo.jpghttp://en.wikipedia.org/wiki/L-dopahttp://en.wikipedia.org/wiki/Carbidopahttp://en.wikipedia.org/wiki/Benserazidehttp://en.wikipedia.org/wiki/Carbidopa/levodopahttp://en.wikipedia.org/wiki/Benserazidehttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=16http://en.wikipedia.org/wiki/Tolcaponehttp://en.wikipedia.org/wiki/COMThttp://en.wikipedia.org/wiki/Entacaponehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-TNcilia-31%23cite_note-TNcilia-31http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=17http://en.wikipedia.org/wiki/Bromocriptinehttp://en.wikipedia.org/wiki/Pergolidehttp://en.wikipedia.org/wiki/Pramipexolehttp://en.wikipedia.org/wiki/Ropinirolehttp://en.wikipedia.org/wiki/Cabergolinehttp://en.wikipedia.org/wiki/Apomorphinehttp://en.wikipedia.org/wiki/Lisuride


12/24

receptors. However, they cause the dopamine receptors to become progressively lesssensitive, thereby eventually increasing the symptoms.

Dopamine agonists can be useful for patients experiencing on-off fluctuations anddyskinesias 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 isautomatically 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 primarycaregiver (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 theformation of nodules. Apomorphine is also available in a more acute dose as anautoinjector 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).

[edit ] MAO-B inhibitors

Selegilineand rasagilinereduce the symptoms by inhibiting monoamine oxidase-B(MAO-B), which inhibits the breakdown of dopamine secreted by the dopaminergicneurons. Metabolites of selegiline include L-amphetamine and L-methamphetamine (notto be confused with the more notorious and potent dextrorotary isomers). This mightresult in side effects such as insomnia. Use of L-dopa in conjunction with selegiline hasincreased mortality rates that have not been effectively explained. Another side effect of the combination can be stomatitis. One report raised concern about increased mortalitywhen MAO-B inhibitors were combined with L-dopa;[33] however subsequent studieshave not confirmed this finding.[34] Unlike other non selectivemonoamine oxidaseinhibitors, tyramine-containing foods do not cause a hypertensive crisis.

[edit ] Surgery and deep brain stimulation
http://en.wikipedia.org/wiki/Primary_caregiverhttp://en.wikipedia.org/wiki/Primary_caregiverhttp://en.wikipedia.org/wiki/Nodule_(medicine)http://en.wikipedia.org/wiki/Autoinjectorhttp://en.wikipedia.org/wiki/Autoinjectorhttp://en.wikipedia.org/wiki/Domperidonehttp://en.wikipedia.org/wiki/Domperidonehttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=18http://en.wikipedia.org/wiki/Selegilinehttp://en.wikipedia.org/wiki/Rasagilinehttp://en.wikipedia.org/wiki/Rasagilinehttp://en.wikipedia.org/wiki/Stomatitishttp://en.wikipedia.org/wiki/Stomatitishttp://en.wikipedia.org/wiki/Stomatitishttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-32%23cite_note-32http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-33%23cite_note-33http://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitorshttp://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitorshttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=19http://en.wikipedia.org/wiki/Image:Parkinson_surgery.jpghttp://en.wikipedia.org/wiki/Primary_caregiverhttp://en.wikipedia.org/wiki/Primary_caregiverhttp://en.wikipedia.org/wiki/Nodule_(medicine)http://en.wikipedia.org/wiki/Autoinjectorhttp://en.wikipedia.org/wiki/Domperidonehttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=18http://en.wikipedia.org/wiki/Selegilinehttp://en.wikipedia.org/wiki/Rasagilinehttp://en.wikipedia.org/wiki/Stomatitishttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-32%23cite_note-32http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-33%23cite_note-33http://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitorshttp://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitorshttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=19


13/24

Illustration showing an electrode placed deep seated in the brain

Treating Parkinson's disease with surgery was once a common practice, but after thediscovery 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 beingused in people with advanced PD for whom drug therapy is no longer sufficient.

Deep brain stimulationis presently the most used surgical means of treatment, but other surgical therapies that have shown promise include surgical lesion of the subthalamicnucleus[35] and of the internal segment of the globus pallidus, a procedure known as pallidotomy.[36]

[edit ] Neurorehabilitation

There is partial evidence that speech or mobility problems can improve with

rehabilitation although studies are still scarce and of low quality.[37][38][39][40]

Regular physical exercise and/or therapy can be beneficial to the patient for maintaining andimproving mobility, flexibility, strength, gait speed, and quality of life;[39] and speechtherapy may improve voice and speech function.[40] One of the most widely practicedtreatment for the speech disorders associated with Parkinson's disease is the LeeSilverman Voice Treatment (LSVT). LSVT focuses on increasing vocal loudness.[41]

[edit ] Prognosis

PD is not considered to be a fatal disease by itself, but it progresses with time. Theaverage life expectancy of a PD patient is generally lower than for people who do nothave the disease.[42] In the late stages of the disease, PD may cause complications such aschoking, 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 thedisease will take for an individual person. With appropriate treatment, most people withPD 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 communitydwelling patients.[43]

One commonly used system for describing how the symptoms of PD progress is calledtheHoehn and Yahr scale. Another commonly used scale is theUnified Parkinson'sDisease Rating Scale (UPDRS). This much more complicated scale has multiple ratingsthat measure motor function, and also mental functioning, behavior, mood, and activitiesof daily living. Both the Hoehn and Yahr scale and the UPDRS are used to measure howindividuals are faring and how much treatments are helping them. It should be noted that
http://en.wikipedia.org/wiki/Deep_brain_stimulationhttp://en.wikipedia.org/wiki/Subthalamic_nucleushttp://en.wikipedia.org/wiki/Subthalamic_nucleushttp://en.wikipedia.org/wiki/Subthalamic_nucleushttp://en.wikipedia.org/wiki/Subthalamic_nucleushttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-34%23cite_note-34http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-34%23cite_note-34http://en.wikipedia.org/wiki/Globus_pallidushttp://en.wikipedia.org/wiki/Globus_pallidushttp://en.wikipedia.org/wiki/Pallidotomyhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-35%23cite_note-35http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=20http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid11687029-36%23cite_note-pmid11687029-36http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid11687029-36%23cite_note-pmid11687029-36http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid11406045-37%23cite_note-pmid11406045-37http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid18181210-38%23cite_note-pmid18181210-38http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid12132992-39%23cite_note-pmid12132992-39http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid18181210-38%23cite_note-pmid18181210-38http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid12132992-39%23cite_note-pmid12132992-39http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid12132992-39%23cite_note-pmid12132992-39http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid12132992-39%23cite_note-pmid12132992-39http://en.wikipedia.org/w/index.php?title=Lee_Silverman_Voice_Treatment&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Lee_Silverman_Voice_Treatment&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Lee_Silverman_Voice_Treatment&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Lee_Silverman_Voice_Treatment&action=edit&redlink=1http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid17117354-40%23cite_note-pmid17117354-40http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid17117354-40%23cite_note-pmid17117354-40http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=21http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-41%23cite_note-41http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-42%23cite_note-42http://en.wikipedia.org/wiki/Hoehn_and_Yahr_scalehttp://en.wikipedia.org/wiki/Unified_Parkinson's_Disease_Rating_Scalehttp://en.wikipedia.org/wiki/Unified_Parkinson's_Disease_Rating_Scalehttp://en.wikipedia.org/wiki/Unified_Parkinson's_Disease_Rating_Scalehttp://en.wikipedia.org/wiki/Deep_brain_stimulationhttp://en.wikipedia.org/wiki/Subthalamic_nucleushttp://en.wikipedia.org/wiki/Subthalamic_nucleushttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-34%23cite_note-34http://en.wikipedia.org/wiki/Globus_pallidushttp://en.wikipedia.org/wiki/Pallidotomyhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-35%23cite_note-35http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=20http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid11687029-36%23cite_note-pmid11687029-36http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid11406045-37%23cite_note-pmid11406045-37http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid18181210-38%23cite_note-pmid18181210-38http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid12132992-39%23cite_note-pmid12132992-39http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid18181210-38%23cite_note-pmid18181210-38http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid12132992-39%23cite_note-pmid12132992-39http://en.wikipedia.org/w/index.php?title=Lee_Silverman_Voice_Treatment&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Lee_Silverman_Voice_Treatment&action=edit&redlink=1http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid17117354-40%23cite_note-pmid17117354-40http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=21http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-41%23cite_note-41http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-42%23cite_note-42http://en.wikipedia.org/wiki/Hoehn_and_Yahr_scalehttp://en.wikipedia.org/wiki/Unified_Parkinson's_Disease_Rating_Scalehttp://en.wikipedia.org/wiki/Unified_Parkinson's_Disease_Rating_Scale


14/24

neither scale is specific to Parkinson's disease; that patients with other illnesses can scorein the Parkinson's range.

[edit ] Epidemiology

According to some sources, Parkinsons disease is slightly less prevalent in theAfrican-American community. The average crude prevalence is estimated at being from 120-180out of 100,000 among thecaucasian (white) community.[44] TheParsicommunity inMumbai, India suffers from particularly high rates of Parkinson's disease.[45][46]

[edit ] History

Symptoms of Parkinson's disease have been known and treated since medieval times,most notably by Averroes.[47] However, it was not formally recognized and its symptomswere not documented until 1817 in An Essay on the Shaking Palsy [48] by the British

physicianJames Parkinson. Parkinson's disease was then known as paralysis agitans , theterm "Parkinson's disease" being coined later byJean-Martin Charcot. The underlying biochemicalchanges in the brainwere identified in the 1950s due largely to the work of Swedish scientistArvid Carlsson, who later went on to win a Nobel Prize. L-dopaenteredclinical practice in 1967,[49] and the first large study reporting improvements in patientswith Parkinson's disease resulting from treatment with L-dopa was published in 1968.[50]

[edit ] Research directions

[edit ] Gene therapy

Currently under investigation is gene therapy. This involves using a non-infectious virusto shuttle a gene into a part of the brain called the subthalamic nucleus (STN). The geneused leads to the production of an enzyme called glutamic acid decarboxylase (GAD),which catalyses the production of a neurotransmitter called GABA.[51] GABA acts as adirect inhibitor on the overactive cells in the STN.

GDNFinfusion involves the infusion of GDNF (glial-derived neurotrophic factor) intothe basal ganglia using surgically implanted catheters. Via a series of biochemicalreactions, GDNF stimulates the formation of L-dopa. GDNF therapy is still indevelopment.

Implantation of stem cells genetically engineered to produce dopamine or stem cells thattransform into dopamine-producing cells has already started being used. These could notconstitute cures because they do not address the considerable loss of activity of thedopaminergic neurons. Initial results have been unsatisfactory, with patients still retainingtheir drugs and symptoms.

[edit ] Neuroprotective treatments
http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=22http://en.wikipedia.org/wiki/African-Americanhttp://en.wikipedia.org/wiki/African-Americanhttp://en.wikipedia.org/wiki/African-Americanhttp://en.wikipedia.org/wiki/Caucasianhttp://en.wikipedia.org/wiki/Caucasianhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-43%23cite_note-43http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-43%23cite_note-43http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-43%23cite_note-43http://en.wikipedia.org/wiki/Parsi_peoplehttp://en.wikipedia.org/wiki/Mumbaihttp://en.wikipedia.org/wiki/Indiahttp://en.wikipedia.org/wiki/Indiahttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-44%23cite_note-44http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-45%23cite_note-45http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=23http://en.wikipedia.org/wiki/Averroeshttp://en.wikipedia.org/wiki/Averroeshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-46%23cite_note-46http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-46%23cite_note-46http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-47%23cite_note-47http://en.wikipedia.org/wiki/James_Parkinsonhttp://en.wikipedia.org/wiki/James_Parkinsonhttp://en.wikipedia.org/wiki/Jean-Martin_Charcothttp://en.wikipedia.org/wiki/Biochemicalhttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Arvid_Carlssonhttp://en.wikipedia.org/wiki/Nobel_Prizehttp://en.wikipedia.org/wiki/L-dopahttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-48%23cite_note-48http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-48%23cite_note-48http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-48%23cite_note-48http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-49%23cite_note-49http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=24http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=25http://en.wikipedia.org/wiki/Glutamate_decarboxylasehttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid17586305-50%23cite_note-pmid17586305-50http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid17586305-50%23cite_note-pmid17586305-50http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid17586305-50%23cite_note-pmid17586305-50http://en.wikipedia.org/wiki/GDNFhttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=26http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=22http://en.wikipedia.org/wiki/African-Americanhttp://en.wikipedia.org/wiki/African-Americanhttp://en.wikipedia.org/wiki/Caucasianhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-43%23cite_note-43http://en.wikipedia.org/wiki/Parsi_peoplehttp://en.wikipedia.org/wiki/Mumbaihttp://en.wikipedia.org/wiki/Indiahttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-44%23cite_note-44http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-45%23cite_note-45http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=23http://en.wikipedia.org/wiki/Averroeshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-46%23cite_note-46http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-47%23cite_note-47http://en.wikipedia.org/wiki/James_Parkinsonhttp://en.wikipedia.org/wiki/Jean-Martin_Charcothttp://en.wikipedia.org/wiki/Biochemicalhttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Arvid_Carlssonhttp://en.wikipedia.org/wiki/Nobel_Prizehttp://en.wikipedia.org/wiki/L-dopahttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-48%23cite_note-48http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-49%23cite_note-49http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=24http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=25http://en.wikipedia.org/wiki/Glutamate_decarboxylasehttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-pmid17586305-50%23cite_note-pmid17586305-50http://en.wikipedia.org/wiki/GDNFhttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=26


15/24

Neuroprotectivetreatments are at the forefront of PD research, but are still under clinicalscrutiny.[52] 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 andCTCT346), lazaroids, bioenergetics, antiglutamatergic agents and dopamine receptors.[53]

Clinically evaluated neuroprotective agents are the monoamine oxidase inhibitorsselegiline[54] and rasagiline, dopamine agonists, and the complex I mitochondrial fortifier coenzyme Q10.

[edit ] Neural transplantation

The first prospective randomised double-blind sham-placebo controlled trial of dopamine-producing cell transplants failed to show an improvement in quality of lifealthough 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 transplantedtissue, leading todystonias.[56] Research in Africangreen monkeyssuggests that the use

of stem cellsmight in future provide a similar benefit without inducing dystonias.[57]

[edit ] Alternative Treatments

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 wasshown 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 110out of 110 patients.[59] [60] More limited efficacy has been obtained with the use of THFA, NADH, and pyridoxinecoenzymes 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 theenzymes superoxide dismutase and catalase require these vitamins in order to nullify thesuperoxide anion, a toxin commonly produced in damaged cells. However, in therandomized controlled trial, DATATOP of patients with early PD, no beneficial effect for vitamin E compared to placebo was seen.[54] Coenzyme Q10 has more recently been usedfor similar reasons. MitoQ is a newly developed synthetic substance that is similar instructure and function to coenzyme Q10.

Studies looking atqigongin PD have not reached consensus on its efficacy.[62][63]

Mucuna pruriens , is a natural source of therapeutic quantities of L-dopa, and has been

under some investigation.[64]

[edit ] Notable sufferers

This article or section is missing citations or needs footnotes .Usinginline citationshelps guard against copyright violations and factual inaccuracies.(August 2008)

Lists of miscellaneous information should be avoided. Pleaserelocateany relevant
http://en.wikipedia.org/wiki/Neuroprotectivehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-51%23cite_note-51http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-51%23cite_note-51http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-52%23cite_note-52http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-PSG_1993-53%23cite_note-PSG_1993-53http://en.wikipedia.org/wiki/Coenzyme_Q10http://en.wikipedia.org/wiki/Coenzyme_Q10http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=27http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-54%23cite_note-54http://en.wikipedia.org/wiki/Dystoniahttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-55%23cite_note-55http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-55%23cite_note-55http://en.wikipedia.org/wiki/Green_monkeyhttp://en.wikipedia.org/wiki/Stem_cellhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-56%23cite_note-56http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=28http://en.wikipedia.org/wiki/L-tyrosinehttp://en.wikipedia.org/wiki/L-tyrosinehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-57%23cite_note-57http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-58%23cite_note-58http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-58%23cite_note-58http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-59%23cite_note-59http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-60%23cite_note-60http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-PSG_1993-53%23cite_note-PSG_1993-53http://en.wikipedia.org/wiki/Qigonghttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-61%23cite_note-61http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-61%23cite_note-61http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-62%23cite_note-62http://en.wikipedia.org/wiki/Mucuna_prurienshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-63%23cite_note-63http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=29http://en.wikipedia.org/wiki/Wikipedia:Citing_sourceshttp://en.wikipedia.org/wiki/Wikipedia:Footnoteshttp://en.wikipedia.org/wiki/Wikipedia:Footnoteshttp://en.wikipedia.org/wiki/Wikipedia:Footnoteshttp://en.wikipedia.org/wiki/Wikipedia:Inline_citationshttp://en.wikipedia.org/wiki/Wikipedia:Trivia_sectionshttp://en.wikipedia.org/wiki/Wikipedia:Trivia_sectionshttp://en.wikipedia.org/wiki/Wikipedia:Handling_trivia#Recommendations_for_handling_triviahttp://en.wikipedia.org/wiki/Neuroprotectivehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-51%23cite_note-51http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-52%23cite_note-52http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-PSG_1993-53%23cite_note-PSG_1993-53http://en.wikipedia.org/wiki/Coenzyme_Q10http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=27http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-54%23cite_note-54http://en.wikipedia.org/wiki/Dystoniahttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-55%23cite_note-55http://en.wikipedia.org/wiki/Green_monkeyhttp://en.wikipedia.org/wiki/Stem_cellhttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-56%23cite_note-56http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=28http://en.wikipedia.org/wiki/L-tyrosinehttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-57%23cite_note-57http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-58%23cite_note-58http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-59%23cite_note-59http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-60%23cite_note-60http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-PSG_1993-53%23cite_note-PSG_1993-53http://en.wikipedia.org/wiki/Qigonghttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-61%23cite_note-61http://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-62%23cite_note-62http://en.wikipedia.org/wiki/Mucuna_prurienshttp://en.wikipedia.org/wiki/Parkinson's_disease#cite_note-63%23cite_note-63http://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=29http://en.wikipedia.org/wiki/Wikipedia:Citing_sourceshttp://en.wikipedia.org/wiki/Wikipedia:Footnoteshttp://en.wikipedia.org/wiki/Wikipedia:Inline_citationshttp://en.wikipedia.org/wiki/Wikipedia:Trivia_sectionshttp://en.wikipedia.org/wiki/Wikipedia:Handling_trivia#Recommendations_for_handling_trivia


16/24

information into appropriate sections or articles.(August 2008) Further information: People with Parkinson's disease

One famous sufferer of young-onset Parkinson's isMichael J. Fox, whose book, LuckyMan (2000), focused on his experiences with the disease and his career and familytravails in the midst of it. Fox establishedThe Michael J. Fox Foundation for Parkinson's

Research to develop a cure for Parkinson's disease within this decade.

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

Other famous sufferers includePope John Paul II, playwrightEugene O'Neill, artistSalvador Dal, boxer Muhammad Ali, evangelist Billy Graham and former US AttorneyGeneralJanet Reno. Political figures suffering from it have included Adolf Hitler ,Francisco Franco, Deng XiaopingandMao Zedong, and former Prime Minister of CanadaPierre Trudeau. Numerous actors have also been afflicted with Parkinson's suchas: Terry-Thomas, Deborah Kerr , Kenneth More, Vincent Price, Jim BackusandMichaelRedgrave. Helen Beardsley(of Yours, Mine and Ours fame) also suffered from thisdisease toward the end of her life. Director George Roy Hill (The Sting, Butch Cassidyand the Sundance Kid) also suffered from Parkinson's disease.

The film Awakenings (starringRobin WilliamsandRobert De Niroand based on genuinecases reported byOliver Sacks) deals sensitively and largely accurately with a similar disease, postencephalitic parkinsonism.

Michael Gibson (TV presenter), host of MTV Select, was diagnosed with Parkinson's atthe age of 18. Michael lived in denial about his condition for six years. He then pitched adocumentary proposal toChannel 4 who commissioned him to make a documentaryfollowing Michael's journey with Parkinson's. All shook up: Parkinson's at 25aired onChannel 4 in 2006.

In addition, former Arsenal andLiverpool FCfootballer Ray Kennedy, who won everydomestic English honour as well as theEuropean Cup andUEFA Cup, is a sufferer of thedisease, having been diagnosed at 35.

[edit ] References

1. ^ a b c Jankovic J (April 2008). "Parkinson's disease: clinical features and diagnosis". J. Neurol. Neurosurg. Psychiatr. 79 (4): 36876.doi:10.1136/jnnp.2007.131045. PMID18344392.

2. ^ a b c National Institute for Health and Clinical Excellence. Clinical guideline 35: Parkinson's disease . London, June 2006.
http://en.wikipedia.org/wiki/Category:People_with_Parkinson's_diseasehttp://en.wikipedia.org/wiki/Michael_J._Foxhttp://en.wikipedia.org/wiki/The_Michael_J._Fox_Foundationhttp://en.wikipedia.org/wiki/The_Michael_J._Fox_Foundationhttp://en.wikipedia.org/wiki/Davis_Phinneyhttp://en.wikipedia.org/wiki/Davis_Phinney_Foundationhttp://en.wikipedia.org/wiki/Davis_Phinney_Foundationhttp://en.wikipedia.org/wiki/Davis_Phinney_Foundationhttp://en.wikipedia.org/wiki/Pope_John_Paul_IIhttp://en.wikipedia.org/wiki/Eugene_O'Neillhttp://en.wikipedia.org/wiki/Salvador_Dal%C3%ADhttp://en.wikipedia.org/wiki/Salvador_Dal%C3%ADhttp://en.wikipedia.org/wiki/Muhammad_Alihttp://en.wikipedia.org/wiki/Billy_Grahamhttp://en.wikipedia.org/wiki/Billy_Grahamhttp://en.wikipedia.org/wiki/Billy_Grahamhttp://en.wikipedia.org/wiki/Janet_Renohttp://en.wikipedia.org/wiki/Adolf_Hitlerhttp://en.wikipedia.org/wiki/Adolf_Hitlerhttp://en.wikipedia.org/wiki/Francisco_Francohttp://en.wikipedia.org/wiki/Deng_Xiaopinghttp://en.wikipedia.org/wiki/Mao_Zedonghttp://en.wikipedia.org/wiki/Pierre_Trudeauhttp://en.wikipedia.org/wiki/Terry-Thomashttp://en.wikipedia.org/wiki/Terry-Thomashttp://en.wikipedia.org/wiki/Deborah_Kerrhttp://en.wikipedia.org/wiki/Kenneth_Morehttp://en.wikipedia.org/wiki/Vincent_Pricehttp://en.wikipedia.org/wiki/Vincent_Pricehttp://en.wikipedia.org/wiki/Vincent_Pricehttp://en.wikipedia.org/wiki/Jim_Backushttp://en.wikipedia.org/wiki/Michael_Redgravehttp://en.wikipedia.org/wiki/Michael_Redgravehttp://en.wikipedia.org/wiki/Helen_Beardsleyhttp://en.wikipedia.org/wiki/Yours,_Mine_and_Ours_(1968_film)http://en.wikipedia.org/wiki/Yours,_Mine_and_Ours_(1968_film)http://en.wikipedia.org/wiki/George_Roy_Hillhttp://en.wikipedia.org/wiki/George_Roy_Hillhttp://en.wikipedia.org/wiki/The_Stinghttp://en.wikipedia.org/wiki/The_Stinghttp://en.wikipedia.org/wiki/Butch_Cassidy_and_the_Sundance_Kidhttp://en.wikipedia.org/wiki/Butch_Cassidy_and_the_Sundance_Kidhttp://en.wikipedia.org/wiki/Awakeningshttp://en.wikipedia.org/wiki/Robin_Williamshttp://en.wikipedia.org/wiki/Robert_De_Nirohttp://en.wikipedia.org/wiki/Oliver_Sackshttp://en.wikipedia.org/wiki/Postencephalitic_parkinsonismhttp://en.wikipedia.org/wiki/Postencephalitic_parkinsonismhttp://en.wikipedia.org/wiki/Michael_Gibson_(TV_presenter)http://en.wikipedia.org/wiki/MTV_Selecthttp://en.wikipedia.org/wiki/Channel_4http://en.wikipedia.org/wiki/Channel_4http://www.channel4.com/health/microsites/0-9/4health/body/ill_parkinsons_shookup.htmlhttp://www.channel4.com/health/microsites/0-9/4health/body/ill_parkinsons_shookup.htmlhttp://en.wikipedia.org/wiki/Liverpool_FChttp://en.wikipedia.org/wiki/Ray_Kennedyhttp://en.wikipedia.org/wiki/European_Cuphttp://en.wikipedia.org/wiki/European_Cuphttp://en.wikipedia.org/wiki/UEFA_Cuphttp://en.wikipedia.org/w/index.php?title=Parkinson%27s_disease&action=edit&section=30http://en.wikipedia.org/wiki/Parkinson's_disease#cite_ref-Jankovic2008_0-0%23cite_ref-Jankovic2008_0-0http://en.wikip

Park in Sons Diseas e

Documents

Transcript of Park in Sons Diseas e