Parkinson Disease

BASICS

Definition: Progressive, adult-onset neurodegenerative disorder due to loss of dopaminergic neurons in the substantia nigra.
Cardinal symptoms: Resting tremor, rigidity, bradykinesia, postural instability
Prevalence: 2nd most common neurodegenerative disease after Alzheimer’s; >1 million in U.S., >6 million worldwide.
Typical onset: Average age ~60 years; slightly more common in men.

Dopamine depletion in substantia nigra and nigrostriatal pathways → classic motor signs.
Lewy bodies (hyaline inclusions) and Lewy neurites present.
Genetic mutations: Some autosomal dominant/recessive forms—consider especially if onset <50y.

Age, family history, pesticide exposure, rural living, well water, repeated head trauma, high iron intake, low vitamin D, osteoporosis (in women).

Caffeine, cigarette smoking, physical activity (e.g., weight training, running, dancing, yoga, martial arts).

History + neurologic exam (bradykinesia PLUS either tremor or rigidity)
Resting tremor: 4–6 Hz, pill-rolling, often asymmetric
Bradykinesia: General slowness, reduced arm swing, difficulty initiating movement
Rigidity: Cogwheel or lead pipe
Postural instability: Unsteady, frequent falls in later disease
Facial masking, soft speech, micrographia
REM sleep behavior disorder may precede motor symptoms.

Essential tremor (symmetric, action-induced)
Dementia with Lewy bodies (hallucinations early, dementia precedes or accompanies parkinsonism)
Multiple system atrophy, progressive supranuclear palsy, secondary (drug-induced) parkinsonism
Alzheimer, Huntington, frontotemporal dementia, spinocerebellar ataxias

Drugs: Neuroleptics (most common), antiemetics, SSRIs, CCBs, amiodarone, lithium, valproic acid
Features: Often bilateral, may resolve weeks–months after stopping culprit.

Carbidopa/levodopa: Most effective, esp. for bradykinesia
Immediate release (Sinemet), ODT (Parcopa)
Side effects: Dyskinesia, motor fluctuations with long-term use
Dopamine agonists (non-ergot: pramipexole, ropinirole, rotigotine patch): For younger patients, mild symptoms
Side effects: Nausea, hypotension, sedation, hallucinations, compulsive behavior
MAO-B inhibitors (selegiline, rasagiline): Mild motor symptoms or as adjuncts
Side effects: Insomnia, jitteriness, hallucinations (mainly selegiline)

COMT inhibitors (entacapone): For end-of-dose wearing off (combine with levodopa)
Amantadine: For dyskinesias, questionable efficacy, livedo reticularis, confusion
Anticholinergics: For tremor in young patients, but increased cognitive risk (trihexyphenidyl, benztropine)
β-blockers: For postural tremor

Psychosis: Pimavanserin (Nuplazid), quetiapine
Insomnia: Rotigotine patch
Orthostatic hypotension: Droxidopa, midodrine, fludrocortisone, increased salt/fluid
Dementia: Rivastigmine
Depression: Pramipexole, nortriptyline, desipramine, venlafaxine, CBT

Deep brain stimulation (DBS): For motor complications refractory to medication, no significant dementia or depression, levodopa responsive.
MRI-guided focused ultrasound: Unilateral pallidotomy for severe, medication-refractory motor symptoms.

Music therapy, yoga, tai chi, dance: May improve motor symptoms and quality of life

Parkinson’s Foundation: https://www.parkinson.org/
Caregiver Resource: https://www.caregiver.org/resource/parkinsons-disease-caregiving/

Chronic, progressive; variable course.
Mortality increased; survival reduced by ~5% per year.
Functional impairment increases over time; quality of life best preserved with early multidisciplinary care.

Classic: Shaky (resting tremor), stiff (rigidity), slow (bradykinesia), stumbling (gait instability)
No cure; aim is symptom control, preserving function
Exercise and movement are essential at every stage
Medication regimens must be individualized and reassessed regularly
Avoid dopamine-blocking agents