Management of Multiple System Atrophy (MSA) and Parkinson's Plus Syndromes
MSA and other Parkinson's plus diseases require aggressive symptomatic management targeting motor symptoms with levodopa trials (despite limited response), autonomic dysfunction with non-pharmacological measures first followed by pharmacological agents, and avoidance of deep brain stimulation which is contraindicated in MSA. 1
Clinical Classification and Diagnosis
MSA presents in three clinical subtypes that guide management priorities 1:
- MSA-P (87% of cases): Predominant parkinsonism with bradykinesia and rigidity, typically with poor levodopa response 1
- MSA-C (64% of cases): Cerebellar ataxia manifesting as postural instability, dysartria, and oculomotor dysfunction 1
- MSA-A: Predominant autonomic failure with urinary dysfunction (83%) and symptomatic orthostatic hypotension (75%) 1
MRI brain imaging is the optimal diagnostic modality, showing characteristic regional atrophy patterns that distinguish MSA from Parkinson's disease 1. Ioflupane SPECT/CT demonstrates abnormal dopaminergic depletion but cannot distinguish MSA from PD, PSP, or CBD 1.
Red Flags for MSA Diagnosis
Early falls are a critical diagnostic feature distinguishing MSA from typical Parkinson's disease 1. Other Parkinson's plus syndromes in the differential include progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and vascular parkinsonism 1, 2.
Motor Symptom Management
Levodopa Therapy
The widely held belief that MSA patients are non-responsive to levodopa is misleading and should be abandoned. 3, 4 Clinical and pathologically proven series document 40-60% levodopa efficacy in MSA patients with predominant parkinsonian features 3, 4, 5.
- All MSA-P patients should receive a levodopa trial despite the reputation for poor response 3, 4
- Initial moderate-to-good dopaminergic response occurs more frequently than previously recognized, though the response is often unsustained with chronic therapy 5
- Dopamine agonists and amantadine may be employed but are not more effective than levodopa 3, 4
A critical pitfall: PD is distinguished by excellent response to dopaminergic medications maintained over many years, in contrast to the limited or unsustained response in MSA and PSP 2. This temporal pattern of response helps confirm the diagnosis retrospectively.
Cerebellar Ataxia
There is no effective drug treatment for cerebellar ataxia in MSA 5. Management focuses on physical therapy and fall prevention strategies.
Deep Brain Stimulation
Deep brain stimulation is contraindicated in MSA and should not be offered, as it is indicated only for PD patients with good levodopa response 1.
Autonomic Dysfunction Management
Orthostatic Hypotension - Non-Pharmacological First
The American Heart Association prioritizes non-pharmacological measures as first-line therapy 1:
- Compression garments (abdominal binders, compression stockings)
- Physical counter-pressure maneuvers (leg crossing, squatting, muscle tensing)
- Acute water ingestion (500 mL rapidly consumed)
- Increased salt intake (6-10 grams daily)
- Avoid aggravating factors: post-prandial hypotension, post-micturition, warm environments, and physiological diurnal changes 3, 4
- Head-of-bed elevation to reduce supine hypertension 1
Orthostatic Hypotension - Pharmacological Options
When non-pharmacological measures are insufficient, the American Heart Association recommends 1:
- Midodrine: Alpha-1 agonist causing peripheral vasoconstriction
- Droxidopa: Synthetic norepinephrine precursor
- Fludrocortisone: Mineralocorticoid for volume expansion
Critical monitoring requirement: All pharmacological agents for orthostatic hypotension carry risk of supine hypertension, requiring careful blood pressure monitoring in both positions 1.
Genitourinary Symptoms
Urinary dysfunction (incontinence, retention) and impotence are present in 83% of MSA patients and significantly impact quality of life 1, 3, 4:
- Urinary retention: Intermittent catheterization or alpha-blockers
- Urinary incontinence: Anticholinergics (with caution for cognitive effects)
- Erectile dysfunction: Phosphodiesterase-5 inhibitors (with careful blood pressure monitoring given autonomic dysfunction)
Treatment of genitourinary symptoms should be prioritized to improve quality of life 3, 4.
Nutritional Considerations
While the available guidelines focus primarily on Parkinson's disease rather than MSA specifically, some principles may apply 6:
- Regular monitoring of body weight and nutritional status is important in neurodegenerative diseases 6
- Medical nutrition therapy should be considered to improve well-being and quality of life 6
Prognosis and Palliative Care
MSA has a mean disease duration of approximately 6 years from diagnosis, with typical onset between ages 55-65 years 1. Because no drug treatment consistently benefits patients with MSA in the long-term, palliative therapies become critically important 5. Management should shift toward comfort measures, fall prevention, aspiration precautions, and end-of-life planning as the disease progresses 5, 7.
Future Directions
The pathological hallmark of MSA is glial cytoplasmic inclusions containing misfolded α-synuclein 1. Experimental evidence confirms the key role of alpha-synuclein aggregation in MSA pathogenesis, and transgenic and toxic animal models are being developed to assess candidate neuroprotective drugs 7. However, no neuroprotective therapies are currently available for clinical use 5, 7.