Parkinson's Disease for the American Board of Internal Medicine (ABIM) Exam
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Pathophysiology
- Neurodegenerative Disorder: Characterized by the loss of dopaminergic neurons in the substantia nigra.
- Lewy Bodies: Presence of Lewy bodies (intracellular protein aggregates primarily composed of alpha-synuclein) in surviving neurons is a hallmark.
- Dopamine Deficiency: Leads to motor symptoms due to disrupted neurotransmission in the basal ganglia.
Clinical Presentation
- Motor Symptoms:
- Bradykinesia: Slowness of movement and a decrease in spontaneous movement.
- Rigidity: Muscle stiffness affecting both limbs and trunk.
- Resting Tremor: Typically a unilateral, pill-rolling tremor at rest.
- Postural Instability: Impaired balance and coordination, leading to falls.
- Non-Motor Symptoms:
- Cognitive Impairment: Ranges from mild cognitive impairment to Parkinson’s dementia.
- Mood Disorders: Depression and anxiety are common.
- Autonomic Dysfunction: Orthostatic hypotension, constipation, urinary incontinence.
- Sleep Disorders: REM sleep behavior disorder, insomnia.
Diagnostic Approach
- Clinical Diagnosis: Based on history and physical examination, primarily the presence of bradykinesia and at least one other motor symptom (rigidity, tremor, or postural instability).
- Response to Levodopa: A significant and sustained response to levodopa supports the diagnosis.
- Neuroimaging:
- DaTscan (Dopamine Transporter Scan): Can help distinguish PD from other causes of parkinsonism by showing reduced dopamine transporter uptake in the striatum.
Management
- Pharmacological Treatment:
- Levodopa/Carbidopa: Most effective treatment for motor symptoms.
- Dopamine Agonists: Pramipexole, ropinirole used especially in younger patients.
- MAO-B Inhibitors: Selegiline, rasagiline for mild symptoms or as adjunct therapy.
- COMT Inhibitors: Entacapone, tolcapone help prolong the effect of levodopa.
- Non-Pharmacological:
- Physical Therapy: Improves mobility, flexibility, and balance.
- Occupational Therapy: Assists with daily living activities.
- Speech Therapy: For speech and swallowing difficulties.
Complications
- Motor Fluctuations: Variations in the drug’s effects, such as "wearing off" phenomenon or "on-off" fluctuations.
- Dyskinesias: Involuntary movements due to long-term levodopa use.
- Psychiatric: Hallucinations and delusions, particularly in advanced stages or as a side effect of medications.
Differential Diagnosis
- Atypical Parkinsonism:
- Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD): Lack of robust response to levodopa.
- Essential Tremor: Tremor that primarily occurs during action compared to the resting tremor of PD.
- Drug-Induced Parkinsonism: Caused by drugs such as metoclopramide or antipsychotics.
Long-Term Management
- Regular Monitoring: For progression of symptoms and side effects of therapy.
- Adjusting Therapy: Tailoring treatment based on effectiveness and side effects.
- Patient and Caregiver Education: Inform about the nature of the disease, treatment options, and need for adjustments over time.
Prognosis
- Progressive Disease: Gradual progression with variability in the rate of progression among individuals.
- Quality of Life: Significantly impacted; multidisciplinary approach can help manage symptoms and improve quality of life.