Multiple System Atrophy (MSA)

Related Subjects:Multiple System Atrophy (MSA) |Parkinson Plus syndromes |Parkinsonism |Idiopathic Parkinson disease |Progressive Supranuclear Palsy |Drug Induced Parkinson disease

🧠 Multiple System Atrophy (MSA) is a progressive neurodegenerative disorder with autonomic dysfunction, parkinsonism, and/or cerebellar ataxia. It progresses more rapidly than idiopathic Parkinson’s Disease (IPD), with a median survival of 6–9 years after diagnosis ⏳.

📊 Incidence

• ~6 per 100,000 per year overall.
• ~3 per 100,000 per year in those >50 years.

🔬 Aetiology

• Characterized by alpha-synuclein-positive inclusions in glial cells (a synucleinopathy, like Parkinson’s & Lewy Body Dementia).
• Inclusions contain misfolded, hyperphosphorylated fibrillar alpha-synuclein 🧩.
• Widespread neuronal loss in basal ganglia, cerebellum, pons, inferior olivary nuclei, and spinal cord.
• Autonomic failure + parkinsonism or cerebellar ataxia depending on subtype.

🩺 Clinical Features

• Pyramidal signs ⚡: Hyperreflexia, extensor plantar responses.
• Common symptoms: Dysarthria, frequent falls 🤕, urinary problems 🚻, stridor 😮‍💨, pathological laughter/crying, jerky/myoclonic tremor.
• MSA-C: Olivopontocerebellar atrophy → predominant cerebellar ataxia 🎯.
• MSA-P: Striatonigral degeneration → parkinsonism (rigidity, postural instability, resting tremor, freezing of gait) but poor levodopa response.
• Shy-Drager Syndrome: Severe autonomic dysfunction (orthostatic hypotension, bladder issues, falls).

🧾 Differential Diagnosis

• Idiopathic Parkinson’s Disease (IPD): Slower progression, better levodopa response.
• Vascular Dementia: Stepwise progression & cerebrovascular disease (unlike MSA).

🖥️ Investigations

• MRI: Key supportive findings:
  • MSA-P: Putaminal atrophy (outer margin hyperintensity).
  • MSA-C: Pontine atrophy & the classic “hot cross bun” sign 🥯 in the pons on T2 imaging.
• DWI MRI: Increased diffusivity in the putamen.

💊 Management

• Parkinsonism: Trial of levodopa, but often poor or short-lived response.
• Orthostatic Hypotension 🩸: Salt/fluid loading, compression stockings, midodrine.
• Bladder urgency: Anticholinergics (e.g., oxybutynin).
• Nocturia 🌙: Desmopressin (monitor Na⁺ for hyponatraemia).
• Experimental treatments: Trials ongoing with riluzole, GH, minocycline (evidence inconclusive).

📉 Prognosis

• Median survival 6–9 years from diagnosis.
• More rapid decline than Parkinson’s, but cognitive function relatively preserved 🧩.

📚 References

• The Lancet Neurology, Volume 8, Issue 12, Pages 1172–1178, December 2009.

Cases — Multiple System Atrophy (MSA)

• Case 1 — Parkinsonian Variant (MSA-P) 🤚: A 62-year-old man presents with stiffness, slowness, and a shuffling gait. He has minimal tremor but marked postural instability and poor response to levodopa. Exam: bradykinesia, rigidity, early falls, and autonomic dysfunction (orthostatic hypotension). Diagnosis: MSA-P (parkinsonian subtype). Management: Trial of levodopa (limited benefit), physiotherapy, midodrine/fludrocortisone for hypotension, supportive MDT care.
• Case 2 — Cerebellar Variant (MSA-C) 🎯: A 58-year-old woman develops progressive unsteadiness, slurred speech, and difficulty with fine motor tasks. Exam: truncal and limb ataxia, scanning dysarthria, nystagmus, and autonomic failure (urinary urgency/incontinence). Diagnosis: MSA-C (cerebellar subtype). Management: Supportive — physio, OT, speech therapy, bladder management; BP support for autonomic failure.
• Case 3 — Severe Autonomic Dysfunction 🌡️: A 60-year-old man presents with dizziness on standing, erectile dysfunction, and urinary retention. Exam: orthostatic hypotension, parkinsonism, mild cerebellar signs. Urodynamics: detrusor sphincter dyssynergia. MRI: “hot cross bun” sign in pons. Diagnosis: MSA with predominant autonomic failure. Management: Non-pharmacological BP support (compression stockings, salt/fluid); pharmacological (midodrine, fludrocortisone); catheterisation for bladder; MDT input.

Teaching Commentary 🧠

Multiple System Atrophy is a progressive neurodegenerative α-synucleinopathy with variable combinations of: - Parkinsonism (poor levodopa response, early falls). - Cerebellar ataxia. - Autonomic dysfunction (orthostatic hypotension, urinary/bowel dysfunction, erectile dysfunction). Subtypes: MSA-P (parkinsonian) and MSA-C (cerebellar). Dx: clinical, MRI (“hot cross bun” sign in pons for MSA-C; putaminal changes in MSA-P). Mx: supportive — physio, OT, speech therapy, autonomic management. Prognosis: poor, median survival 6–10 years. MSA should be suspected in “parkinsonism with early autonomic failure and poor levodopa response.”