Parkinson’s Disease Definitions Disease features Pathology Epidemiology Treatments

(‘lead-pipe’ or ‘cog-wheel’) PARKINSONISM (‘pill-rolling’) (slowed movement) (‘lead-pipe’ or ‘cog-wheel’)

Dx of Parkinson’s Disease

Clinical Features: Secondary motor symptoms Freezing Micrographia Masked faces Unwanted accelerations Rapid stammering speech Festinating gait Stooped posture Dystonia Impaired motor dexterity/coordination Poverty of movement (decreased arm swing) Akathisia Speech problems Hypophonia Slurred aprosody Difficulty swallowing Drooling

Clinical Features: Non-motor symptoms Early Later sleep disturbances incontinence sexual problems excessive saliva weight loss or gain fatigue Cognitive impairment memory difficulties, slowed thinking, confusion, dementia Psychiatric Depression, anxiety loss of sense of smell constipation REM behavior disorder mood disorders orthostatic hypotension

Parkinsonian Syndromes Idiopathic Parkinson’s Disease Symptomatic Infectious Toxic Drug-induced Post-traumatic

NBC Today Show Interview (1991) After Emergence of Post-traumatic Parkinsonism

Basal Ganglia

PD reflects Dopamine Insufficiency

Lewy body Deposition of a-synuclein

EPIDEMIOLOGY Parkinson’s Disease Prevalence ~ 1,000,000 Annual incidence of about 50,000 – 60,000 Net prevalence increase of 15,000 patients annually Average age of onset: 50 – 65 years old 85% of patients over age 65

EPIDEMIOLOGY Parkinson’s Disease Peak age at onset = 60 2% lifetime risk, 4% if affected relative 850K in US M:F = 3:2 Can live 20+ yrs with treatment Incidence by Period Olmstead Co., MN

ENVIRONMENTAL RISK FACTORS Case-control studies show increased risk of PD with exposure to: Herbicides, Pesticides Living in a rural environment Consumption of well water Proximity to industrial plants or quarries Smoking associated with lower risk

PARKINSON’S DISEASE Non-Motor Features Cognitive Dysfunction Depression Hallucinations (late) Autonomic dysfunction Personality change restricted vs. compulsive behavior

PARKINSON’S DISEASE Associated Features Nigro-Striatal Pathway Meso-limbic & Meso-cortical Pathways Hypomimia Shuffling or festinating gait Postural instability Hypophonia Dystonia Dementia Depression Personality Dermatitis Constipation Sensory deficits Extra-CNS Structures

Adjusted for age, gender, education and psychomotor speed Elgh et al., 2009

Symptomatic Treatment for PD Replacement (Levodopa/Carbidopa) – provide exogenous DA most effective in relieving symptoms use is typically delayed may hasten emergence of diurnal fluctuations and dyskinesias typically not prescribed until gait/postural problems arise or job is threatened visual hallucinations, vivid dreams or nightmares occur in 20% of older patients

Motor fluctuations Duration of levodopa benefit for motor symptoms decreases with disease progression OFF “Good” ON without dyskinesia “Bad” ON with dyskinesia Treatment-induced impairment

Treatment goal: Maximize Good ON time OFF “Good” ON without dyskinesia “Bad” ON with dyskinesia

Mid-stage with moderate motor fluctuations Early PD AM midday evening C/L IR 25/100 1 Rasagiline 1mg Mid-stage with moderate motor fluctuations 7AM 10AM 1PM 4PM 7PM bedtime C/L IR 25/100 1.5 1 C/L CR 50/200 Comtan 200mg Pramipexole 0.5mg Advanced with severe motor fluctuations 7AM 9AM 11AM 1PM 3PM 5PM 7PM 9PM 11PM C/L IR 25/100 2 1 1.5 C/L CR 50/200 Comtan 200mg 0.5 Selegiline 5mg Amantadine 100mg Pahwa 2006 Neurology 66:983

∙ changes the brain firing pattern but does not slow the progression of the neurodegeneration ∙ associated with reduction of sxs, so may enable reduction of medication ∙ can lead to a significant improvement in dyskinesias ∙ does not improve cognitive symptoms in PD and indeed may worsen them, so it is not generally used if there are signs of dementia. 

DBS clinical trial endpoint: Patient diaries