Parkinson’s Disease – Advanced Medical Lecture

Overview

Parkinson’s Disease is a chronic, progressive neurodegenerative disorder that primarily affects motor function. It results from the degeneration of dopamine-producing neurons in the substantia nigra of the brain, causing a classic triad of tremor, rigidity, and bradykinesia.

Etiology & Pathophysiology

Loss of dopaminergic neurons in the substantia nigra pars compacta.
Reduced dopamine in the basal ganglia leads to impaired movement regulation.
Lewy bodies (α-synuclein aggregates) are characteristic histological findings.
Potential contributing factors include oxidative stress, genetics (e.g., LRRK2, PARKIN), and environmental toxins (e.g., pesticides).

Clinical Features

Motor Symptoms:

Bradykinesia: Slowness of movement, shuffling gait, facial masking.
Tremor: Resting, "pill-rolling", typically unilateral initially.
Rigidity: Cogwheel stiffness, particularly in limbs.
Postural Instability: Difficulty with balance, falls in late stages.

Non-Motor Symptoms:

Depression, anxiety, sleep disturbances (e.g. REM sleep behavior disorder)
Autonomic dysfunction: constipation, hypotension, urinary urgency
Anosmia (loss of smell), fatigue, pain, and cognitive impairment

Diagnosis

Clinical diagnosis based on presence of bradykinesia + tremor or rigidity.
Excellent response to Levodopa therapy supports the diagnosis.
Rule out atypical parkinsonism (e.g., MSA, PSP).
DaTscan (SPECT imaging) may help in unclear cases.

Management

Medications:

Levodopa/Carbidopa: First-line, effective for most motor symptoms.
Dopamine Agonists: Pramipexole, Ropinirole – used in younger patients or as adjuncts.
MAO-B Inhibitors: Rasagiline, Selegiline – reduce dopamine breakdown.
COMT Inhibitors: Entacapone – used with Levodopa to extend its effect.
Amantadine: Helps reduce dyskinesias.
Anticholinergics: Benztropine – for tremor in younger patients.

Surgical:

Deep Brain Stimulation (DBS) – For patients with medication fluctuations or severe tremor.

Supportive Care:

Physical therapy, gait training, fall prevention
Speech therapy for dysarthria and swallowing
Psychological support and caregiver education

Prognosis

Progressive decline over time. Median survival ~15 years. Motor complications (e.g., dyskinesias), cognitive impairment, and falls can reduce quality of life. Early treatment improves function and symptom control.

Mnemonic: TRAP

T – Tremor (resting)
R – Rigidity
A – Akinesia (bradykinesia)
P – Postural Instability

Recent Clinical Updates

Alpha-synuclein–targeting immunotherapy is under investigation.
Exenatide (GLP-1 receptor agonist) shows neuroprotective promise.
Wearables and digital monitoring are being integrated into treatment monitoring.
Focus on early diagnosis biomarkers (CSF, blood, and imaging).

Clinical Pearls

Tremor improves with voluntary movement (vs. essential tremor).
Early dementia, autonomic dysfunction, or gaze palsy → consider atypical Parkinsonism.
Long-term Levodopa use → watch for wearing-off and dyskinesias.
Early initiation of exercise may delay motor complications.

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Parkinson’s Disease – Advanced Medical Lecture