Parkinson’s Disease 

1. Definition

Parkinson’s disease is a progressive neurodegenerative disorder characterized by:

• Loss of dopaminergic neurons in the substantia nigra pars compacta
• Presence of Lewy bodies (intracytoplasmic α-synuclein aggregates)

➡️ Leads to dopamine deficiency in basal ganglia → motor + non-motor symptoms

2. Pathophysiology 

A. Basal Ganglia Circuitry

• Dopamine acts via:
• D1 receptors → Direct pathway (facilitates movement)
• D2 receptors → Indirect pathway (inhibits movement)

 In PD:

• ↓ Dopamine →
• ↓ Direct pathway activity
• ↑ Indirect pathway activity
  ➡️ Net effect = Hypokinesia (bradykinesia)

B. Pathology

• Substantia nigra depigmentation
• Lewy bodies (α-synuclein + ubiquitin)
• Spread follows Braak staging:
• Early: Olfactory bulb, brainstem
• Late: Cortex → dementia

3. Epidemiology

• Age: >60 years (but early-onset <50 possible)
• M:F = ~1.5:1
• Risk factors:
• Age (strongest)
• Pesticides, rural living
• Protective:
• Smoking, caffeine 

4. Clinical Features

A. Cardinal Motor Features (TRAP mnemonic)

1. Tremor (Resting)
• “Pill-rolling”
• 4–6 Hz
• Improves with movement

2. Rigidity

• Cogwheel (ratchet-like)
• Lead-pipe

3. Akinesia / Bradykinesia (MOST IMPORTANT)

• Slowness of movement
• Reduced arm swing
• Micrographia

4. Postural instability (late feature)

B. Gait & Posture

• Stooped posture
• Festinating gait (accelerating small steps)
• Freezing episodes
• Reduced arm swing

C. Non-Motor Features

Often precede motor symptoms by years

5. Diagnosis 

 No definitive lab test

UK Brain Bank Criteria

Diagnosis requires:

• Bradykinesia + ≥1 of:
• Tremor
• Rigidity
• Postural instability

Plus supportive features:

• Asymmetry
• Good response to levodopa

Red Flags (Suggest Parkinson-plus)

6. Differential Diagnosis 

7. Investigations

• Usually clinical diagnosis
• Supportive:
• MRI brain → rule out secondary causes
• DaTSCAN:
• ↓ Dopamine transporter uptake in PD

8. Management 

A. General Principles

• Symptom control (no cure)
• Individualized therapy (age + severity)

B. Pharmacological Treatment

1. First-Line: Levodopa

Levodopa (+ carbidopa/benserazide)

• Most effective drug
• Converts to dopamine in brain

Adverse effects:

• Dyskinesia
• Motor fluctuations (“on-off”)
• Nausea

2. Dopamine Agonists

• Examples:
• Pramipexole
• Ropinirole

Used in:

• Younger patients
• Delay levodopa use

Side effects:

• Impulse control disorders
• Hallucinations

3. MAO-B Inhibitors

• Selegiline
• Rasagiline

 Reduce dopamine breakdown

4. COMT Inhibitors

• Entacapone

 Used with levodopa to prolong effect

5. Others

• Amantadine → dyskinesia
• Anticholinergics → tremor (young patients only)

C. Advanced Therapy

Deep Brain Stimulation (DBS)

4

• Targets:
• Subthalamic nucleus
• Globus pallidus interna

 Indications:

• Motor fluctuations
• Drug-resistant tremor

9. Complications 

A. Motor Complications

• Wearing-off
• On-off phenomenon
• Dyskinesias

B. Non-Motor

• Dementia
• Psychosis
• Autonomic dysfunction

C. Parkinsonism-Hyperpyrexia Syndrome

• Like NMS
• Trigger: sudden levodopa withdrawal
• Life-threatening

10. Prognosis

• Slowly progressive
• Survival near-normal with treatment
• Major morbidity = falls, dementia

11. Rapid Revision

• Bradykinesia = MUST for diagnosis
• Resting tremor improves with movement
• Asymmetry = classic
• Levodopa response = diagnostic support
• Early autonomic failure → think MSA
• Early falls → PSP
• REM sleep behavior disorder = early PD marker
• DaTSCAN ↓ uptake in PD
• Impulse control disorders → dopamine agonists
• Dyskinesia → long-term levodopa