MSA

Overview

• Rare neurodegen disorder

• Autonomic, Parkinsonian and Cerebellar features

• Alpha-Synuclein aggregation

• Progressive autonomic and motor dysfunction

Names

• Previously known as olivopontocerebellar atrophy (OPCA), striatonigral degeneration, and Shy-Drager syndrome

Onset

• Mean age = 56 years

Epidemiology

• Prevalence = 1 : 50,000

Risk factor

• Age

Pathology

• Neuronal loss and atrophy in basal ganglia, brain-stem nuclei, cerebellum, and corticospinal tracts

• Alpha-synuclein immunostaining is a sensitive markers of inclusion pathology in MSA

Pathogenesis

• Unknown

• Suspect primary glial disorder

Prodrome

• REM sleep behavioural disorder

  • 5 to 10% have MSA

  • 90% have PD / DLB (Parkinson Disease / Dementia with Lewy Body)

• Autonomic Failure

  • LUTS in 18% of MSA occurring 3 years before motor signs

  • Orthostatic hypotension converted to MSA in 25% at median time of 6 years

  • Motor signs especially symmetrically and without tremor

Motor involvement

• MSA with Parkoninsonism (MSA-P)

  • Bradykinesia, Rigidity, Postural Instability, Tremor

• MSA with cerebellar ataxia (MSA-C)

  • Gait ataxia, limb ataxia, dysarthria

Speech

• Dysphagia, Hypophonic monotony, quivering strained voice

Posture

• Camptocormia (anterior flexion of the spine)

• Axial dystonia, myopathy

Dysautonomia

• Urinary Dysfunction

  • Void difficulty (80%), nocturia (74%), urgency (63%), incontinence (63%)

• Erectile dysfn (almost 100% of men)

• Orthostatic hypotension (68%)

• Anhydrosis (80%)

Non-Motor

• Sleep-related breathing (62%)

  • REM Behaviour Disorder RBD (67%)

  • Nocturnal or diurnal laryngeal stridor (40%)

• Cognitive

  • Preserved with MSA relative to PD - estimates 20%

  • Pseudobulbar affect

  • Raynaud’s

  • Olfactory dysfn

Imaging

• MRI shows

  • Atrophy of putamen, pons, middle cerebellar peduncles, cerebellum

  • T2 hypointensity of the posterior putamen

  • Hot cross bun sign in pons

Diagnosis

• Clinical history

• Neuro exam

• Levodopa response = PD, non-response suggests MSA

Criteria

For clinical establish MSA

• Sporadic, progressive, adult-onset disease

• Autonomic dysfunction

  • Unexplained voiding difficulties

  • Unexplained urge incontinence

  • Neurogenic orthostatic hypotension

• At least one of

  • Poor levodopa response

  • CErebella syndrome

• At least two of

  • Rapid progression < 3 years

  • Moderate to severe postural instability

  • Craniocervical dystonia

  • Severe speech impairment

  • Severe dysphagia

  • Babinski

  • Posture deformity

  • STridor

  • Inspiratory sigh

  • Cold hands and feet

  • ED

  • Pathological laughing or crying

• At least one MRI markers

Prognosis

• Disease progression over 1 to 18 years

• Median times from onset to disability milestones

  • Autonomic dysfunction = 2.5 years

  • Need for a walking aid = 3 years

  • Wheelchair = 3.5 years

  • Bedridden = 5 to 8 years

• Median time to death is 6 to 10 years

• Risk factors for shorter survival

  • Incomplete bladder emptying

  • Older age

  • Early or severe autonomic failure

  • Early stridor

  • Female

Management

No effective disease-modifying or neuroprotective treatment

Symptomatic management

• Levodopa and dopaminergic therapy

  • Some patients with probable MSA do better on Levodopa

  • Worth a trial

  • Levodopa-carbidopa

• Ataxia

  • Physical therapy is important

    • Fall prevention

    • Contracture reduction

    • Mobility maintenance

  • Botox for dystonia

• Orthostatic hypotension

  • Avoid large meals

  • Low carb meals

  • Avoid salt restriction

  • Drink water with meals

  • Avoid standing suddenly

  • Walk between meals

  • Medication can help

• Urogenital

  • OAB treatment as per normal

  • Adjunctive include Beta-2 agonists (mirabegron)

• Depression

  • As per normal treatment

• Stridor

  • ENT + Sleep for consideration polysomnography

• Investigational therapies

  • Rapamycin, Lithium, Sirolimus, Nilotinib all found ineffective

Resources

• MSA treatment - Up To Date