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Parkinsons disease

By: Isra

Definition

  • Parkinson’s disease is a progressive neurodegenerative disorder due to loss of dopaminergic neurons in the substantia nigra pars compacta, leading to dopamine deficiency in the basal ganglia

Pathophysiology

  • Loss of dopaminergic neurons in substantia nigra pars compacta
  • Lewy bodies (α-synuclein aggregates)
  • Imbalance of dopamine vs acetylcholine → motor symptoms
  • Multifactorial: genetic, oxidative stress, toxins, DM

Clinical Features

Motor Symptoms (TRAP)

  • Tremor (resting, pill-rolling)
  • Rigidity (cogwheel/lead pipe)
  • Akinesia/bradykinesia
  • Postural instability (usually late feature)

Non-Motor Symptoms

  • Depression, anxiety
  • Autonomic: constipation, urinary frequency, orthostatic hypotension
  • Cognitive decline → Parkinson’s dementia
  • Sleep disorders (REM behavior disorder)
  • Hyposmia (early)

Differential Diagnosis of Parkinson’s Disease

1. Other Parkinsonian Syndromes

  • Drug-induced parkinsonism: Caused by antipsychotics (haloperidol, risperidone) or antiemetics (metoclopramide). Features: symmetric, no resting tremor, improves after stopping drug.
  • Vascular parkinsonism: Due to multiple small strokes. Features: gait disturbance > tremor, hyperreflexia and poor levodopa response.
  • Normal Pressure Hydrocephalus (NPH): Triad of gait disturbance, urinary incontinence, and dementia. Imaging shows enlarged ventricles with normal pressure.
  • Essential tremor: Action/postural tremor (not resting), improves with alcohol, no rigidity or bradykinesia.

Differential Diagnosis of Parkinson’s Disease

2. Parkinson-Plus Syndromes (Atypical Parkinsonism)

  • Multiple System Atrophy (MSA): Parkinsonism + autonomic failure + cerebellar signs.
  • Progressive Supranuclear Palsy (PSP): Early falls, vertical gaze palsy, axial rigidity.
  • Corticobasal Degeneration (CBD): Asymmetric rigidity, apraxia, alien limb, cortical sensory loss.
  • Dementia with Lewy Bodies (DLB): Early dementia, visual hallucinations, fluctuating cognition, parkinsonism

Differential Diagnosis of Parkinson’s Disease

3. Other Neurological Disorders

  • Wilson’s disease: Young onset, psychiatric symptoms, liver disease, Kayser–Fleischer rings.
  • Huntington’s disease: Chorea, behavioral changes, family history.
  • Post-encephalitic parkinsonism: Rare, history of encephalitis

Red flags against idiopathic Parkinson’s disease

  • Poor or no response to levodopa
  • Early postural instability or falls
  • Rapid progression
  • Early autonomic failure or dementia
  • Symmetrical onset

Investigations

  • Clinical diagnosis (UK Brain Bank criteria)
  • MRI: usually normal, used to exclude other causes
  • DAT-SPECT: ↓ striatal dopamine uptake

Pharmacological Management

1. Levodopa + Carbidopa

  • Mechanism: Levodopa is a precursor of dopamine, crosses BBB → converted to dopamine. Carbidopa inhibits peripheral DOPA decarboxylase → ↑ central dopamine. Example: Sinemet® Side effects: Nausea, vomiting, orthostatic hypotension, dyskinesias, on-off fluctuations, hallucinations.

2. Dopamine Agonists

  • Mechanism: Direct stimulation of dopamine receptors (D2 > D3). Examples: Pramipexole, Ropinirole. Side effects: Nausea, hypotension, hallucinations, impulse control disorders (gambling, hypersexuality), sleep attacks.

Pharmacological Management

3. MAO-B Inhibitors

  • Mechanism: Inhibit monoamine oxidase-B → ↓ dopamine breakdown in CNS. Examples: Selegiline, Rasagiline Side effects: Insomnia, hypertension (rare), nausea

4. COMT Inhibitors

  • Mechanism: Inhibit COMT → prolong Levodopa half-life. Examples: Entacapone, Tolcapone. Side effects: Diarrhea, orange urine, hepatotoxicity (Tolcapone).

Pharmacological Management

5. Amantadine

  • Mechanism: Enhances dopamine release, inhibits reuptake; NMDA receptor antagonist. Example: Amantadine (Symmetrel®). Side effects: Livedo reticularis, edema, confusion, hallucinations.

6. Anticholinergics

  • Mechanism: Block muscarinic receptors → restore balance between dopamine & acetylcholine. Control tremor more Examples: Trihexyphenidyl, Benztropine. Side effects: Dry mouth, blurred vision, urinary retention, constipation, confusion (avoid in elderly).

Good luck

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