Orthostatic hypotension (OH): Sustained reduction of SBP ≥20 mmHg or DBP ≥10 mmHg within 3 minutes of standing or head-up tilt
Neurogenic OH: OH caused by failure of autonomic reflexes (as opposed to volume depletion or medication effect)
Supine hypertension: SBP ≥140 mmHg and/or DBP ≥90 mmHg in supine position; common in MSA and complicates OH treatment
DIAGNOSTIC CRITERIA (2022 MDS Criteria for MSA):
Clinically Established MSA:
- Autonomic dysfunction (neurogenic OH with SBP drop ≥20 mmHg or DBP drop ≥10 mmHg within 3 min of standing, OR urinary retention/incontinence with post-void residual ≥100 mL)
- PLUS poorly levodopa-responsive parkinsonism (MSA-P) OR cerebellar syndrome (MSA-C)
- PLUS at least 1 additional feature: RBD, stridor, contractures, postural instability within 3 years, rapid progression, poor levodopa response, dysphagia within 5 years, atrophy on MRI (putaminal, pontine, cerebellar, or MCP)
Clinically Probable MSA:
- Parkinsonism (poorly levodopa-responsive) or cerebellar syndrome
- PLUS at least 1 autonomic feature (OH not meeting criteria, urinary urgency/frequency, erectile dysfunction)
- PLUS at least 1 additional feature from above list
Possible Prodromal MSA (Neuropathologically Established requires autopsy):
- REM sleep behavior disorder with onset after age 40
- PLUS autonomic dysfunction (unexplained OH, urogenital dysfunction, or sudomotor failure)
- No parkinsonism or cerebellar ataxia yet
Red Flags AGAINST MSA:
- Sustained excellent levodopa response (>5 years)
- Visual hallucinations (suggests DLB)
- Dementia within first year (suggests DLB)
- Alien limb phenomenon (suggests CBD)
- Vertical supranuclear gaze palsy (suggests PSP)
- Family history of parkinsonism or ataxia
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
2.5 mg TID; 5 mg TID; 10 mg TID :: PO :: TID :: Start 2.5 mg TID (upon awakening, midday, mid-afternoon); titrate by 2.5 mg q1-2 weeks; max 10 mg TID; last dose no later than 4 PM to avoid supine hypertension
Supine BP (check 30 min post-dose); standing BP; urinary retention symptoms; scalp tingling (expected)
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Fludrocortisone
PO
Neurogenic OH — volume expansion; adjunct to midodrine
0.1 mg daily; 0.2 mg daily :: PO :: daily :: Start 0.1 mg daily; may increase to 0.2 mg daily after 1-2 weeks; max 0.3 mg/day; take with food
Heart failure, severe edema, severe supine hypertension, hypokalemia
Potassium (weekly x4, then monthly), supine BP, weight, edema, BMP
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Droxidopa (Northera)
PO
Neurogenic OH — norepinephrine precursor; FDA-approved for neurogenic OH
100 mg TID; 200 mg TID; 300 mg TID; 600 mg TID :: PO :: TID :: Start 100 mg TID; titrate by 100 mg TID q24-48h; max 600 mg TID; take upon awakening, midday, late afternoon
Supine hypertension (SBP >180 at baseline), closed-angle glaucoma
Supine and standing BP (initial dose and titration); supine hypertension (measure BP supine before bedtime)
30 mg TID; 60 mg TID :: PO :: TID :: Start 30 mg TID; increase to 60 mg TID if tolerated; modest effect on OH; advantage: does NOT worsen supine hypertension
Mechanical GI/GU obstruction, bradycardia
GI symptoms (diarrhea, cramping), heart rate, cholinergic side effects
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Atomoxetine
PO
Neurogenic OH — norepinephrine reuptake inhibitor; may augment other agents
10 mg BID; 18 mg BID :: PO :: BID :: Start 10 mg BID; increase to 18 mg BID after 1 week; off-label use for neurogenic OH
MAOIs, narrow-angle glaucoma, pheochromocytoma, severe cardiac arrhythmia
BP (supine and standing), heart rate, mood changes
2.5 mg BID; 5 mg BID; 5 mg TID :: PO :: BID-TID :: Start 2.5 mg BID; titrate to 5 mg BID-TID; max 20 mg/day; ER formulation preferred (less cognitive impairment)
Uncontrolled narrow-angle glaucoma, urinary retention, GI obstruction, myasthenia gravis
Cognitive function (especially elderly), post-void residual, dry mouth, constipation
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Mirabegron (Myrbetriq)
PO
Neurogenic detrusor overactivity — preferred over antimuscarinics due to less cognitive impairment
25 mg daily; 50 mg daily :: PO :: daily :: Start 25 mg daily; increase to 50 mg after 4-8 weeks if needed; no anticholinergic side effects
Uncontrolled hypertension (may raise BP 1-2 mmHg), severe hepatic impairment
Blood pressure, urinary retention, UTI
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Tamsulosin (Flomax)
PO
Urinary retention with elevated post-void residual — alpha-blocker for bladder outlet relaxation
0.4 mg daily; 0.8 mg daily :: PO :: daily :: 0.4 mg daily 30 min after same meal each day; may increase to 0.8 mg daily after 2-4 weeks; CAUTION: may worsen OH in MSA
Severe orthostatic hypotension (may worsen OH), hypersensitivity
Orthostatic BP (may exacerbate OH — use cautiously in MSA), dizziness, retrograde ejaculation
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Desmopressin (DDAVP)
PO/intranasal
Nocturnal polyuria contributing to morning OH
0.1 mg QHS; 0.2 mg QHS :: PO :: QHS :: 0.1-0.2 mg PO at bedtime; OR 10 mcg intranasal at bedtime; reduces nocturnal urine production
Hyponatremia, heart failure, polydipsia
Serum sodium (check at 1 week, 1 month, then q3 months), weight, fluid balance
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Intermittent self-catheterization
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Urinary retention with PVR >150-200 mL not responsive to medications
- :: - :: 3-4x daily :: Perform clean intermittent catheterization 3-4 times daily or as needed based on symptoms and PVR; clean technique adequate (sterile not required for home use)
Urethral stricture (relative), severe hand dexterity impairment
PVR, UTI surveillance, urethral integrity
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Sildenafil (Viagra)
PO
Erectile dysfunction in MSA — PDE5 inhibitor
25 mg PRN; 50 mg PRN :: PO :: PRN :: Start 25 mg (lower dose due to OH risk); take 30-60 min before activity; max 1 dose/day; CAUTION: may worsen orthostatic hypotension
Nitrate use, severe OH (SBP <90 standing), severe cardiac disease
Blood pressure (standing) after first use; warn about OH risk
Parkinsonism in MSA-P — levodopa trial required for diagnosis (poor response expected in most)
25/100 mg TID; 25/250 mg TID :: PO :: TID :: Start 25/100 mg TID with meals; titrate to 25/250 mg TID over 4-8 weeks; up to 1000-1500 mg levodopa/day to document response; ~30% have partial/transient response
Per muscle group :: IM :: q3 months :: Dystonia: individualized dosing by muscle group (e.g., sternocleidomastoid 25-50 units each side for antecollis); sialorrhea: 30 units per parotid, 20 units per submandibular; repeat q3 months
Myasthenia gravis, Lambert-Eaton, infection at injection site
Dysphagia (especially cervical injections — CRITICAL in MSA), weakness at injection site, bruising
No disease-modifying therapies are currently approved for MSA. All treatment is symptomatic and supportive. Clinical trials for MSA-directed therapies (anti-alpha-synuclein immunotherapy, GLP-1 agonists, neuroprotective agents) are ongoing — refer eligible patients to ClinicalTrials.gov.
25 mcg before meals; 50 mcg before meals :: SC :: TID (before meals) :: Start 25 mcg SC 30 min before meals; increase to 50 mcg if needed; max 50 mcg TID; reduces splanchnic blood pooling
MSA is a progressive neurodegenerative disease; treatments manage symptoms but do not slow progression — early goals of care discussion recommended
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Rise slowly from lying to sitting to standing (staged position changes over 1-2 minutes) to minimize orthostatic hypotension episodes
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Increase dietary salt intake to 6-10 g/day and fluid intake to 2-2.5 L/day unless contraindicated by heart failure or renal disease
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Elevate head of bed 10-15 degrees (4-6 inch blocks) at night to reduce nocturnal supine hypertension and morning orthostatic symptoms
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Avoid large carbohydrate-heavy meals (eat smaller, more frequent meals) to prevent postprandial hypotension
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Do NOT stop orthostatic hypotension medications abruptly; these require gradual tapering under physician guidance
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Report new or worsening stridor (noisy breathing during sleep) immediately — this may indicate vocal cord paralysis requiring urgent evaluation
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Fall prevention measures: remove rugs and tripping hazards, install grab bars in bathroom, use walker or wheelchair as prescribed, avoid standing quickly
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Avoid alcohol as it worsens orthostatic hypotension and cerebellar ataxia
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Avoid medications that worsen OH: diuretics, alpha-blockers, tricyclic antidepressants, sildenafil (use cautiously), nitrates — discuss all new medications with neurologist
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Wear medical alert identification indicating MSA and autonomic dysfunction for emergency situations
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Advance directives and healthcare proxy should be established early while patient can participate fully in decisions
Most MSA patients managed primarily as outpatients; stable autonomic symptoms on current regimen; ambulatory with or without assistive device; adequate home support; able to maintain oral intake
Admit to hospital
Recurrent syncope despite outpatient OH management; severe symptomatic orthostatic hypotension requiring IV fluids and medication titration; new dysphagia with aspiration risk; fall with injury; urinary retention requiring catheterization; need for autonomic function testing not available outpatient
Admit to ICU
Acute stridor with respiratory compromise (vocal cord paralysis); severe autonomic instability (labile BP with end-organ compromise); aspiration pneumonia with respiratory failure; cardiovascular collapse from refractory OH
Discharge from hospital
OH symptoms controlled on oral medications; safe swallowing confirmed; urinary management plan established; falls risk assessed and mitigated; follow-up scheduled within 1-2 weeks
Transfer to higher level of care
Refractory autonomic crises; need for tracheostomy evaluation; respiratory failure; cardiovascular instability not responding to floor-level interventions
Palliative care/hospice referral
Advanced disease with recurrent aspiration, inability to maintain nutrition, respiratory failure, recurrent life-threatening autonomic crises; patient/family goals aligned with comfort-focused care
MSA is a rapidly progressive alpha-synucleinopathy with median survival of 6-10 years from symptom onset
Two main phenotypes: MSA-P (parkinsonian predominant, ~60% in Western populations) and MSA-C (cerebellar predominant, more common in East Asian populations)
Autonomic failure is the hallmark and appears EARLY, distinguishing MSA from Parkinson's disease
Only ~30% of MSA-P patients show a partial and usually transient response to levodopa; response typically wanes within 1-5 years
Supine hypertension is extremely common and complicates OH management; avoid midodrine/droxidopa within 4 hours of bedtime; elevate HOB 10-15 degrees
Stridor from bilateral vocal cord abductor paralysis is a life-threatening complication and cause of sudden death in MSA; urgent laryngoscopy and CPAP/tracheostomy may be needed
REM sleep behavior disorder precedes motor symptoms by years or decades and is one of the strongest prodromal markers
No disease-modifying therapy currently exists; all treatment is symptomatic and supportive
Medications that worsen autonomic dysfunction should be avoided: alpha-blockers, diuretics, vasodilators, tricyclic antidepressants, antipsychotics with alpha-blocking properties
Early palliative care integration is recommended given prognosis and symptom complexity
MIBG cardiac scintigraphy is a useful distinguishing test: PRESERVED uptake in MSA vs REDUCED in PD and DLB