Nervous System & Special Senses

Atypical parkinsonism syndromes: PSP, MSA, CBD

Clinical Overview and When to Suspect Atypical Parkinsonism

— PSP (progressive supranuclear palsy): tauopathy, vertical gaze palsy, early falls

— MSA (multiple system atrophy): α-synucleinopathy with glial cytoplasmic inclusions; autonomic failure + cerebellar (MSA-C) or parkinsonian (MSA-P) features

— CBD (corticobasal degeneration): tauopathy with markedly asymmetric rigidity, apraxia, alien limb

— Symmetric onset of parkinsonism

— Poor or transient response to levodopa

— Early falls (<1 year) → think PSP

— Early autonomic failure (orthostatic hypotension, urinary incontinence, erectile dysfunction) → think MSA

— Early cognitive/behavioral change, apraxia, cortical sensory loss → think CBD

— Rapid progression (wheelchair within 3–5 years)

— Absence of resting tremor; postural instability dominates

Board pearl: The single most useful red flag distinguishing atypical parkinsonism from PD on a Step 3 vignette is early postural instability with falls in the first year combined with suboptimal levodopa response. If the stem describes a 65-year-old with backward falls and trouble looking down at meals or stairs within months of symptom onset → PSP, not PD.

Step 3 management: Suspected atypical parkinsonism warrants neurology referral, MRI brain, and a documented levodopa challenge (escalate to ≥1000 mg/day for 4–8 weeks before declaring nonresponsive) before committing to an atypical diagnosis on chart and disability paperwork.

Atypical parkinsonism (Parkinson-plus syndromes) = neurodegenerative disorders with parkinsonian features plus early additional signs that idiopathic Parkinson disease (PD) lacks

When to suspect atypical rather than PD:

Epidemiology: PSP ~5–7/100,000; MSA ~3–4/100,000; CBD <1/100,000. Onset typically age 50–70, slight male predominance for PSP/MSA

Mean survival ~6–9 years from symptom onset — substantially shorter than PD (~15+ years)

Presentation Patterns and Key History

— Early postural instability with backward falls within first year

— Vertical supranuclear gaze palsy, especially downgaze (trouble with stairs, reading, eating from plate)

— Axial rigidity > limb rigidity; erect "surprised" posture with retrocollis

— Pseudobulbar affect, dysarthria, frontal/executive dysfunction, apathy

— Variants: PSP-Parkinsonism (more levodopa-responsive, slower), PSP-PGF (pure akinesia with gait freezing)

— Symmetric bradykinesia/rigidity, poor levodopa response or levodopa-induced orofacial/cranial dystonia

— Early autonomic failure: orthostatic hypotension (drop ≥30 mmHg systolic/≥15 diastolic within 3 min standing), neurogenic bladder, ED, anhidrosis

— Stridor, nocturnal inspiratory sighs, RBD (REM sleep behavior disorder)

— Gait/limb ataxia, scanning dysarthria, nystagmus + autonomic features

— Strikingly asymmetric akinetic-rigid syndrome

— Limb apraxia, alien limb phenomenon, cortical sensory loss (agraphesthesia, astereognosis)

— Myoclonus, focal limb dystonia (often fixed posturing of one hand)

— Aphasia (nonfluent/agrammatic) or behavioral variant frontal syndrome may dominate

— Driving/reading complaints → downgaze

— Syncope when rising, hot showers → autonomic failure

— Dream enactment behavior (RBD) — common in MSA, PD; rare in PSP/CBD

— Choking, soft/whispery speech, early dysphagia → red flag for atypical

Key distinction: RBD + autonomic failure + parkinsonism = MSA until proven otherwise. RBD is uncommon in PSP (a tauopathy), helping separate synucleinopathies from tauopathies on history alone.

Board pearl: A patient who falls backward in clinic during the pull test within the first year of parkinsonism is virtually diagnostic of PSP for exam purposes.

PSP — Richardson syndrome (classic)

MSA-P (parkinsonian predominant)

MSA-C (cerebellar predominant)

CBD

History pearls to elicit:

Physical Exam Findings and Hemodynamic Assessment

— Vertical supranuclear gaze palsy: voluntary downgaze fails, but oculocephalic (doll's eye) maneuver overcomes it — confirming supranuclear localization

— Slow vertical saccades precede frank palsy (earliest sign)

— Square-wave jerks, eyelid apraxia, blepharospasm

— Axial rigidity > appendicular; positive applause sign (3-clap test → continues clapping; frontal disinhibition)

— Hyperreflexia, frontal release signs

— Orthostatic vitals mandatory: BP/HR supine, then at 1 and 3 min standing

— Neurogenic OH: ≥30/15 mmHg drop without compensatory HR rise (<15 bpm increase)

— Cerebellar signs in MSA-C: dysmetria, intention tremor, gait ataxia, nystagmus

— Pyramidal signs (Babinski, hyperreflexia) common

— Inspiratory stridor on auscultation of neck — high-yield, signals risk of sudden death

— Antecollis (severe neck flexion) — contrast with PSP retrocollis

— Cold, dusky hands ("cold hand sign")

— Asymmetric rigidity, often unilateral fixed dystonic limb

— Ideomotor apraxia: cannot pantomime "brushing teeth" with affected limb despite intact strength

— Alien limb: limb performs purposeful movements involuntarily

— Cortical sensory loss: graphesthesia, stereognosis, two-point discrimination impaired

— Focal/segmental myoclonus, often stimulus-sensitive

CCS pearl: In a suspected MSA stem, order orthostatic vital signs at 1 and 3 minutes and fingerstick glucose; if you skip orthostatics, you'll miss credit for the diagnostic workup. Also document 24-hour BP monitoring showing supine hypertension with orthostatic hypotension, a hallmark MSA pattern.

Board pearl: Doll's eyes that restore vertical gaze = supranuclear (PSP). If vestibulo-ocular reflex doesn't help, suspect a nuclear/infranuclear lesion instead.

PSP exam

MSA exam

CBD exam

Diagnostic Workup — Initial Labs, Imaging, ECG, Biomarkers

— CBC, CMP, TSH, B12, ceruloplasmin (Wilson if <50 years), HIV, RPR

— Heavy metals if exposure history (manganese in welders → parkinsonism)

— Medication review: dopamine blockers (antipsychotics, metoclopramide, prochlorperazine), valproate, lithium

— PSP: midbrain atrophy → "hummingbird" or "penguin" sign (sagittal); "morning glory" sign (axial, concave midbrain tegmentum); reduced midbrain-to-pons ratio

— MSA-P: putaminal atrophy, "putaminal rim sign" (hyperintense lateral putamen on T2), hypointense putamen

— MSA-C: cerebellar/pontine atrophy, "hot cross bun" sign in pons (cruciform T2 hyperintensity); middle cerebellar peduncle atrophy

— CBD: asymmetric frontoparietal cortical atrophy contralateral to clinically affected limb

— α-synuclein RT-QuIC (CSF/skin biopsy): positive in MSA/PD, negative in PSP/CBD (tauopathies)

— Neurofilament light chain (NfL) elevated in atypical > PD

— DaT-SPECT: reduced striatal uptake in both PD and atypical parkinsonism — does not distinguish them; only separates degenerative from essential tremor/drug-induced

Board pearl: "Hummingbird sign" = PSP; "hot cross bun" = MSA-C; "asymmetric parietal atrophy" = CBD. These three MRI signs are nearly guaranteed Step 3 image stems.

Atypical parkinsonism is a clinical diagnosis; workup is to exclude mimics and support the syndrome

Initial labs (rule out reversible/secondary parkinsonism):

MRI brain (3T preferred) — the highest-yield Step 3 imaging study:

Levodopa trial: carbidopa/levodopa titrated to ≥1000 mg/day × 4–8 weeks; sustained, robust improvement argues for PD

Autonomic testing (when MSA suspected): tilt-table, Valsalva, sweat testing, postvoid residual (often >100 mL in MSA)

Polysomnography: RBD documentation supports synucleinopathy

Cognitive screen: MoCA — frontal-executive deficits in PSP/CBD

Emerging biomarkers (board-aware, not yet first-line):

Diagnostic Workup — Advanced or Confirmatory Studies

— Assesses postganglionic cardiac sympathetic innervation

— Reduced uptake in PD (postganglionic denervation)

— Preserved uptake in MSA (preganglionic lesion)

— Helpful when distinguishing MSA from PD with autonomic features; not widely available in US but board-testable

— PSP: midbrain and medial frontal hypometabolism

— MSA-P: putaminal/cerebellar hypometabolism

— MSA-C: cerebellar/brainstem hypometabolism

— CBD: asymmetric frontoparietal + basal ganglia/thalamic hypometabolism contralateral to symptomatic side

— Tilt-table with continuous BP/HR

— Quantitative sudomotor axon reflex test (QSART) — anhidrosis pattern

— Valsalva ratio, deep-breathing HR variability — both reduced

— Plasma norepinephrine: fails to rise on standing in MSA (preganglionic); supine NE often normal — contrast with pure autonomic failure where supine NE is low

Key distinction: Reduced MIBG = PD; preserved MIBG with neurogenic OH = MSA. Plasma NE that fails to rise on standing = preganglionic (MSA); low supine NE = postganglionic (PD, pure autonomic failure).

Step 3 management: When you suspect MSA and document stridor on polysomnography, refer urgently for ENT evaluation and consider CPAP or tracheostomy — stridor predicts sudden nocturnal death.

MIBG cardiac scintigraphy (¹²³I-metaiodobenzylguanidine)

FDG-PET

Tau PET (flortaucipir): research tool; increased binding in PSP/CBD

Skin biopsy for phosphorylated α-synuclein: emerging; positive in MSA/PD, negative in tauopathies

CSF analysis: not routine; rules out NPH, autoimmune, prion disease (14-3-3, RT-QuIC for CJD if rapid progression with myoclonus)

Autonomic battery (MSA workup):

Urodynamics in suspected MSA: detrusor hyperreflexia + sphincter dyssynergia; EMG of external anal sphincter may show denervation (neurogenic)

Sleep study: confirms RBD; identifies nocturnal stridor in MSA (prognostic — sudden death risk)

Risk Stratification and First-Line Management Logic

— Motor disability (rigidity, gait, falls)

— Autonomic/dysautonomic burden (especially MSA)

— Bulbar and respiratory decline (dysphagia, aspiration, stridor)

— PSP: early falls, severe dysphagia, downgaze palsy, frontal dementia

— MSA: stridor, severe OH with syncope, recurrent UTIs, aspiration pneumonia

— CBD: nonambulatory status, severe dysphagia, advanced dementia

— Confirm and document poor levodopa response before labeling atypical (avoids premature closure)

— Stop offending drugs (antipsychotics, antiemetics that block D2)

— Initiate physical, occupational, and speech therapy early — strongest evidence for fall reduction and dysphagia management

— Treat dominant non-motor symptom (OH in MSA, gaze/falls in PSP, dystonia/apraxia in CBD)

— Advance care planning at diagnosis — discuss feeding tube preferences, code status, power of attorney while patient can participate

— Refer to multidisciplinary movement disorders clinic: neurology, PT/OT/SLP, social work, palliative care

— Home safety evaluation (remove rugs, install grab bars, raised toilet seat)

— Front-wheeled walker (PSP patients fall backward with rolling walkers — consider weighted walker)

— Vitamin D, calcium, DEXA, bisphosphonate if osteoporotic

Step 3 management: Early palliative care consultation is appropriate at diagnosis — not end-of-life only. Document advance directives, MOLST/POLST, healthcare proxy before bulbar/cognitive decline limits capacity.

Board pearl: Wheelchair within 3–5 years + poor levodopa response = think atypical, not PD.

Atypical parkinsonism has no disease-modifying therapy — management is symptomatic, multidisciplinary, and anticipatory

Frame care around three trajectories:

Prognostic markers signaling rapid decline / hospice consideration:

Median survival: PSP ~6–8 yr, MSA ~7–9 yr, CBD ~6–8 yr from symptom onset; wheelchair-bound within 3–5 years typical

Tiered first-line management logic:

Falls risk reduction:

Pharmacotherapy — First-Line Drug Regimen

— Carbidopa/levodopa — still first-line trial; titrate to ≥1000 mg/day of levodopa for ≥4–8 weeks before declaring failure

— ~30% of MSA-P patients have modest, often transient response

— PSP-Parkinsonism subtype may respond mildly

— CBD: minimal response, but worth trying

— Amantadine 100 mg BID–TID: best evidence in CBD for rigidity/gait; modest in PSP

— Dopamine agonists generally avoided — limited benefit, worsen OH and cognition

— MAO-B inhibitors (rasagiline, selegiline) — minimal evidence; can worsen OH

— Nonpharm first: liberalize salt (>6–10 g/day) and fluids (2–2.5 L/day), compression stockings (thigh-high) + abdominal binder, head-of-bed elevation 30°, slow positional changes, avoid large carb meals/alcohol

— Midodrine 2.5–10 mg TID (last dose by 6 pm to avoid supine HTN) — α1 agonist

— Droxidopa 100–600 mg TID — norepinephrine prodrug, FDA-approved for neurogenic OH

— Fludrocortisone 0.1–0.2 mg daily — adds volume; watch hypokalemia, edema, supine HTN

— Pyridostigmine 60 mg TID — modest, helpful when supine HTN limits pressors

Board pearl: First step in symptomatic neurogenic OH = nonpharmacologic measures + midodrine. Add fludrocortisone or droxidopa if inadequate. Always check supine BP before each midodrine dose.

Motor symptoms (all three):

Orthostatic hypotension (MSA cornerstone):

Neurogenic bladder (MSA): oxybutynin/mirabegron for urgency; intermittent catheterization if PVR >150 mL

Constipation: polyethylene glycol first-line

Sialorrhea: glycopyrrolate; botulinum toxin to salivary glands (avoid in dysphagia)

Dystonia (CBD): botulinum toxin focal injections — first-line for fixed limb posturing, blepharospasm in PSP

RBD: melatonin 3–12 mg qHS (preferred); clonazepam 0.25–0.5 mg qHS (risk of falls/cognitive side effects)

Pseudobulbar affect (PSP): dextromethorphan/quinidine

Depression: SSRIs (sertraline, escitalopram); avoid TCAs (anticholinergic, orthostatic)

Cognition (PSP/CBD): trial of donepezil/rivastigmine — limited benefit

Procedures and Expanded Pharmacology

— Not indicated in PSP, MSA, or CBD — poor or paradoxical response, can accelerate decline

— A patient labeled "PD" who fails DBS evaluation often turns out to have atypical parkinsonism on re-review

— CCS pearl: If a vignette describes a "PD" patient with early falls, symmetric onset, and poor levodopa response being considered for DBS — recommend deferral and reassessment for atypical parkinsonism before referral

— Blepharospasm and eyelid apraxia (PSP) — orbicularis oculi

— Focal limb dystonia (CBD)

— Cervical dystonia (antecollis in MSA, retrocollis in PSP) — use cautiously; can worsen dysphagia

— Sialorrhea — parotid/submandibular injections

— Indication: recurrent aspiration, weight loss >10%, prolonged mealtimes, NPO during acute aspiration pneumonia

— Discuss before crisis — align with advance directives; PEG does not prolong survival in advanced neurodegenerative disease but may ease caregiving

— Nocturnal CPAP first-line for mild–moderate stridor

— Tracheostomy considered for severe stridor or vocal cord abductor paralysis — reduces sudden death risk but trade-offs significant

— Anti-tau immunotherapies (tilavonemab, gosuranemab) — failed phase 2 in PSP

— α-synuclein–directed therapy in MSA — investigational

— Autologous mesenchymal stem cell trials in MSA — early phase

— Typical and most atypical antipsychotics (worsen parkinsonism); if psychosis necessitates treatment → quetiapine or pimavanserin, low dose

— Metoclopramide, prochlorperazine (D2 blockers)

— Anticholinergics in elderly (delirium, falls, urinary retention)

Step 3 management: Hallucinations in advanced atypical parkinsonism → first reduce dopaminergic burden and rule out infection/metabolic triggers, then add pimavanserin or low-dose quetiapine. Never haloperidol.

Deep brain stimulation (DBS):

Botulinum toxin injections:

Gastrostomy tube (PEG):

Tracheostomy / CPAP for MSA stridor:

Intermittent self-catheterization for high postvoid residual (>150 mL) in MSA neurogenic bladder; prevents recurrent UTIs and upper tract damage

Pacemaker / cardioneuroablation: not standard; consider if symptomatic bradyarrhythmia

Investigational / future-directed (board-awareness):

Avoid:

Special Populations — Elderly and Renal/Hepatic Impairment

— Avoid anticholinergics (oxybutynin → cognitive decline, delirium): prefer mirabegron for overactive bladder

— Avoid benzodiazepines for RBD when possible — use melatonin instead

— Avoid first-generation antipsychotics, metoclopramide, promethazine — all worsen parkinsonism

— Avoid TCAs for depression — substitute SSRIs

— DEXA at diagnosis; vitamin D 800–1000 IU + calcium 1000–1200 mg

— Bisphosphonate if T-score ≤ –2.5 or prior fragility fracture

— Hip protectors in highest-risk patients

— Amantadine — renally cleared; reduce dose when CrCl <60 (50% dose at 30–60; q48h at 15–30; avoid in dialysis-dependent without specialist guidance); accumulation → livedo reticularis, confusion, myoclonus

— Gabapentin/pregabalin (used for myoclonus): renal dose adjust

— Mirabegron: caution if eGFR <30

— Fludrocortisone: monitor potassium and renal function; can worsen CHF

— Carbidopa/levodopa: dose cautiously; levodopa metabolized peripherally and centrally

— Entacapone/tolcapone (COMT inhibitors): avoid tolcapone (hepatotoxic); entacapone safer

— Quetiapine: dose-reduce in hepatic impairment

— Botulinum toxin: no hepatic adjustment

— Capacity assessment for medical decisions; involve healthcare proxy early

— Avoid sedating medications; treat reversible contributors (UTI, dehydration, OH)

— Driving evaluation — report per state law when unsafe; gaze palsy and executive dysfunction are absolute red flags

Board pearl: Amantadine toxicity in elderly with CKD → confusion, hallucinations, livedo reticularis. Hold the drug; symptoms reverse over days to weeks.

Atypical parkinsonism is a disease of the elderly — onset typically 60s–70s — so geriatric principles apply to nearly every patient

Polypharmacy and Beers Criteria:

Falls and fractures:

Renal impairment:

Hepatic impairment:

Cognitive impairment (PSP and CBD particularly):

Supine hypertension with orthostatic hypotension (MSA): elevate HOB rather than adding antihypertensives; if SBP >180 supine, consider short-acting nighttime agent (losartan 50 mg, hydralazine) — never long-acting

Special Populations — Other Demographic Subgroups

— Wilson disease (ceruloplasmin, 24-hr urine copper, slit-lamp for Kayser-Fleischer rings)

— Drug-induced parkinsonism

— Juvenile/young-onset PD (often genetic — PARK2, PARK7, PINK1)

— Dopa-responsive dystonia (Segawa) — diurnal variation, dramatic levodopa response

— Autoimmune/paraneoplastic encephalitis

— Genetic testing: MAPT (FTD-parkinsonism), GRN, C9orf72, LRRK2

— Niemann-Pick type C — vertical supranuclear gaze palsy in adolescents/young adults mimics PSP; check oxysterols, NPC1/NPC2 genes

— Whipple disease — oculomasticatory myorhythmia (pathognomonic), PCR for Tropheryma whipplei

— Anti-IgLON5 disease — sleep disorder, bulbar, parkinsonism, gaze abnormalities; treat with immunotherapy

— Manganese (welders, miners) → parkinsonism with dystonia, "cock-walk" gait

— Carbon monoxide poisoning → delayed parkinsonism with bilateral globus pallidus lesions on MRI

— Repetitive head trauma → chronic traumatic encephalopathy (CTE) with parkinsonism

— Caregiver burden in atypical parkinsonism exceeds PD due to faster decline and cognitive/behavioral features

— Screen primary caregivers for depression at every visit; refer to support groups (CurePSP, MSA Coalition)

— Connect to home health, respite care, and durable medical equipment benefits

— Hospice eligibility: severe dysphagia with aspiration, nonambulatory, weight loss >10%, recurrent infections, FAST stage ≥7

— Most patients die from aspiration pneumonia, pulmonary embolism, or sudden death (MSA stridor)

Key distinction: Vertical supranuclear gaze palsy in a teenager or young adult is Niemann-Pick C, not PSP. Order oxysterols and genetic testing — disease-modifying therapy (miglustat) exists.

Board pearl: Oculomasticatory myorhythmia + parkinsonism + diarrhea/weight loss = Whipple disease — treat with ceftriaxone then long-course TMP-SMX.

Pregnancy: atypical parkinsonism essentially never presents during reproductive years; if a young woman has parkinsonism, exclude:

Young-onset atypical parkinsonism (<45 years) — must reconsider diagnosis:

Veterans / occupational exposures:

Caregiver considerations:

End-of-life / hospice:

Complications and Adverse Outcomes

— Risk factors: dysphagia, weak cough, supine feeding, sedating meds, dementia

— Prevention: speech-language pathology swallow eval, modified diet (thickened liquids, pureed solids), upright positioning ×30 min postprandial, oral hygiene (reduces oropharyngeal bacterial load — strongest evidence for aspiration pneumonia prevention)

— PSP: backward falls without protective response → hip, wrist, head injuries

— Subdural hematoma risk elevated, especially on antiplatelet/anticoagulant

— Falls assessment at every visit (Timed Up and Go, pull test)

— Nocturnal stridor, central sleep apnea, vocal cord abductor paralysis

— Cardiac autonomic dysfunction → arrhythmia

— Levodopa-induced orofacial dystonia in MSA — characteristic; reduce dose

— Midodrine-induced supine hypertension — check supine BP before dosing

— Fludrocortisone → hypokalemia, CHF exacerbation

— Anticholinergic-induced delirium and urinary retention

Step 3 management: A patient with MSA admitted for pneumonia → swallow eval before any PO intake, head of bed elevated, withhold long-acting antihypertensives that worsen OH, treat with antibiotics covering aspiration (ampicillin-sulbactam or ceftriaxone + metronidazole if anaerobic risk; otherwise CAP coverage), and DVT prophylaxis with enoxaparin if not contraindicated.

Board pearl: Best evidence-based intervention to reduce aspiration pneumonia is meticulous oral hygiene — not thickened liquids.

Aspiration pneumonia — leading cause of death across all three syndromes

Falls and fractures

Orthostatic syncope (MSA) → traumatic injury, fractures, intracranial hemorrhage

Sudden death in MSA:

Recurrent UTIs and urosepsis (MSA neurogenic bladder, high PVR)

Pressure ulcers in nonambulatory patients

Venous thromboembolism — immobility risk; consider mechanical/pharmacologic prophylaxis during hospitalizations

Malnutrition and weight loss — dysphagia, depression, dyskinesia (in CBD), prolonged mealtimes

Decubitus complications and contractures in late-stage CBD with fixed dystonia

Iatrogenic complications:

Depression and suicide risk — early to mid-disease, especially with retained insight; screen with PHQ-9 every visit

Caregiver burnout — itself a "complication" of the disease; mental health screening, respite services

When to Escalate Care — ICU, Consult, Inpatient Triage

— Aspiration pneumonia with hypoxia, sepsis, or inability to tolerate POs

— New-onset stridor or worsening dyspnea (MSA)

— Recurrent syncope from refractory OH

— Urosepsis from neurogenic bladder

— Acute mental status change — rule out infection, drug effect, metabolic causes, subdural from falls

— Fall with fracture or head trauma

— Severe dysphagia requiring PEG decision and counseling

— Caregiver crisis / unsafe home environment

— Respiratory failure from aspiration or stridor requiring intubation/NIV

— Septic shock

— Status epilepticus (rare; CBD with cortical involvement)

— Severe autonomic crisis with hemodynamic instability

— Neurology / movement disorders — diagnostic confirmation, medication optimization

— Speech-language pathology — every admission for swallow eval

— Pulmonology + ENT — MSA stridor (laryngoscopy for vocal cord paralysis)

— Urology — neurogenic bladder, ISC training, BPH overlap

— GI / nutrition — PEG decision-making

— Physical medicine & rehab — postacute rehab, equipment

— Palliative care — at diagnosis, not just end-of-life

— Psychiatry — depression, PBA, behavioral disturbance

— Social work — caregiver support, home health, hospice transitions

— Hospital discharge → high readmission risk; medication reconciliation essential (resume levodopa schedule on time; missed doses cause neuroleptic malignant–like syndrome)

— Never abruptly stop levodopa — even when NPO, use NG tube, transdermal rotigotine bridge, or apomorphine SC

— Avoid haloperidol and metoclopramide on order sets — flag in EHR

— Communicate goals of care document to receiving facility

CCS pearl: When admitting a patient with atypical parkinsonism, your first orders should include: continue home levodopa on schedule, NPO until swallow eval, aspiration precautions, fall precautions, DVT prophylaxis, hold dopamine-blocking antiemetics (substitute ondansetron), and palliative care consult.

Board pearl: Abrupt levodopa withdrawal can precipitate parkinsonism-hyperpyrexia syndrome (mimics NMS): fever, rigidity, autonomic instability, elevated CK — treat by restarting dopaminergic therapy and supportive ICU care.

Inpatient admission triggers:

ICU indications:

Consultations:

Transitions of care risk points (Step 3 flavor):

Key Differentials — Same-Category Causes

— Asymmetric onset, resting tremor prominent, robust sustained levodopa response, slow progression, falls late, autonomic features late

— RBD common, anosmia, depression often precede motor symptoms

— Parkinsonism + early dementia + fluctuating cognition + visual hallucinations + RBD + neuroleptic sensitivity

— "1-year rule": dementia within 1 year of parkinsonism → DLB; >1 year → PD dementia

— Lower-body parkinsonism ("lower-half parkinsonism"), wide-based magnetic gait, stepwise progression, vascular risk factors, MRI with extensive white matter disease and lacunes

— Poor levodopa response; treat vascular risk factors aggressively

— D2 blockers: typical and atypical antipsychotics, metoclopramide, prochlorperazine, valproate, lithium, amiodarone

— Symmetric, subacute, may include tremor; reversible over weeks–months after withdrawal

— Step 3 trap: elderly patient on chronic metoclopramide for gastroparesis with new parkinsonism — stop the drug first

— Triad: magnetic gait, urinary incontinence, dementia ("wet, wobbly, wacky")

— MRI: ventriculomegaly out of proportion to atrophy, Evans index >0.3, DESH pattern

— Large-volume LP (tap test) — gait improvement supports VP shunt

Key distinction: Resting tremor + asymmetric onset + dramatic levodopa response = PD. Early falls + downgaze palsy = PSP. Autonomic failure + cerebellar/parkinsonian + stridor = MSA. Asymmetric apraxia + alien limb = CBD.

Board pearl: Lower-half parkinsonism with extensive white matter disease and stepwise progression = vascular parkinsonism — manage with strict BP, statin, antiplatelet, glycemic control.

Idiopathic Parkinson disease (PD) — the most important differential

Dementia with Lewy bodies (DLB)

Vascular parkinsonism

Drug-induced parkinsonism

Normal pressure hydrocephalus (NPH)

PSP-Parkinsonism vs PSP-Richardson — same disease, different phenotypes; PSP-P has better levodopa response and slower course

MSA vs pure autonomic failure (PAF) — PAF lacks motor/cerebellar features; supine NE low (postganglionic); slower course, better prognosis

Frontotemporal dementia (FTD)-parkinsonism — behavioral or language variant FTD with later parkinsonism; MAPT, GRN, C9orf72 mutations

Key Differentials — Other-Category Causes

— Ceruloplasmin <20, 24-hr urinary copper >100 µg, Kayser-Fleischer rings on slit lamp

— Treat with chelation (penicillamine, trientine) + zinc

— Anti-IgLON5 — sleep behavior disorder, gait, bulbar, parkinsonism, gaze abnormalities

— Anti-Ma2 — diencephalic/brainstem, often testicular cancer

— Anti-LGI1 — limbic encephalitis with faciobrachial dystonic seizures

— Treatment: steroids, IVIG, rituximab; screen for occult malignancy

— Manganese, CO poisoning, MPTP, methanol, cyanide

— Hepatic encephalopathy with parkinsonism (cirrhosis)

— Chronic acquired hepatocerebral degeneration — T1 hyperintensity in globus pallidus

Step 3 management: Always screen for reversible parkinsonism mimics (drugs, Wilson if <50, B12, TSH, NPH, structural lesion on MRI) before committing to an irreversible atypical parkinsonism diagnosis. The vignette featuring a "PSP-like" patient on chronic prochlorperazine wants you to stop the drug as the first step.

Board pearl: Rapidly progressive parkinsonism with myoclonus and dementia over weeks → CJD — get DWI MRI and CSF RT-QuIC.

Normal pressure hydrocephalus — already discussed; potentially reversible with shunt

Wilson disease — young patient with parkinsonism, dystonia, dysarthria, hepatic dysfunction, psychiatric symptoms

Huntington disease — choreiform > parkinsonian, but Westphal variant (juvenile-onset) presents with parkinsonism and rigidity; CAG repeat testing

Spinocerebellar ataxias (SCA) — particularly SCA2, SCA3 (Machado-Joseph), SCA17 may mimic MSA-C; family history, genetic testing

Fragile X-associated tremor/ataxia syndrome (FXTAS) — male carriers of FMR1 premutation; intention tremor, ataxia, parkinsonism, cognitive decline; middle cerebellar peduncle T2 hyperintensity ("MCP sign")

Niemann-Pick type C — vertical supranuclear gaze palsy in young patients; oxysterol screen

Whipple disease — oculomasticatory myorhythmia, diarrhea, weight loss; T. whipplei PCR

Autoimmune / paraneoplastic encephalitis

Creutzfeldt-Jakob disease (CJD) — rapidly progressive dementia, myoclonus, ataxia, parkinsonism over weeks–months; MRI DWI cortical ribboning + basal ganglia hyperintensity; CSF 14-3-3, RT-QuIC

Hypothyroidism / B12 deficiency — reversible mimics; check TSH, B12 in every workup

Toxic / metabolic:

Infectious: HIV-associated parkinsonism, neurosyphilis, postencephalitic parkinsonism (historical)

Structural: midbrain stroke, basal ganglia tumor, hydrocephalus

Secondary Prevention, Discharge Medications, Long-Term Plan

— Resume levodopa on home schedule — clock-precise dosing; provide MD-signed order if going to SNF

— Reconcile and remove any inpatient haloperidol, metoclopramide, prochlorperazine, promethazine added during admission

— Restart/titrate midodrine, droxidopa, fludrocortisone after confirming supine BP

— Resume melatonin/clonazepam for RBD

— Bowel regimen: PEG/senna prophylaxis

— DVT prophylaxis if mobility limited

— Vitamin D + calcium; bisphosphonate if indicated

— Aspiration precautions, dysphagia diet per SLP

— Annual influenza

— Pneumococcal (PCV20 or PCV15 + PPSV23) — critical given aspiration risk

— RSV vaccine (age ≥60)

— COVID-19 boosters per current CDC guidance

— Tdap booster q10 years; herpes zoster (Shingrix) at age ≥50

— Statin per ASCVD risk; manage HTN cautiously (avoid worsening OH in MSA)

— Diabetes control

— Advance directive, MOLST/POLST, healthcare proxy

— Discuss PEG, CPR, intubation preferences while patient retains capacity

— Hospice referral when FAST ≥7, recurrent aspiration, profound weight loss

— Driving cessation — formal evaluation when gaze/executive deficits emerge

Step 3 management: Pneumococcal vaccination is among the highest-yield interventions — PCV20 alone OR PCV15 followed by PPSV23 ≥1 year later for adults ≥65 or with chronic disease. Aspiration-prone patients are exactly the target population.

Board pearl: The single most "secondary preventive" item on discharge: medication reconciliation removing D2 blockers — they accelerate decline and can precipitate parkinsonism-hyperpyrexia.

Atypical parkinsonism has no primary prevention; "secondary prevention" = preventing complications, hospitalizations, and accelerated decline

Discharge medication checklist after a hospitalization:

Vaccinations (high-yield Step 3):

Cardiovascular risk management (general geriatric):

Bone health: DEXA q2 years, vitamin D 800–1000 IU, calcium 1000–1200 mg, bisphosphonate or denosumab if osteoporotic

Cancer screening: continue age-appropriate screening as life expectancy allows; deprescribe when life expectancy <10 years (mammography, colonoscopy, PSA discussions)

Long-term care planning:

Equipment: front-wheeled walker, transfer board, hospital bed, raised toilet seat, shower chair, prism glasses (PSP downgaze)

Follow-Up, Monitoring Parameters, Rehab and Counseling

— Motor scales: MDS-UPDRS Part III, Hoehn & Yahr stage; PSP Rating Scale or UMSARS (MSA) in specialty clinic

— Orthostatic vitals (supine, 1 min, 3 min standing)

— Falls in past 3 months (number, mechanism, injuries)

— Swallow status, weight trend

— Cognitive screen (MoCA at baseline and yearly)

— PHQ-9 for depression

— Caregiver assessment (Zarit Burden Interview)

— Medication review and deprescribing opportunities

— BMP q3–6 mo if on fludrocortisone (K+, renal function)

— CBC, LFTs annually

— Vitamin D, B12 yearly

— UA + postvoid residual in MSA every 3–6 months

— Physical therapy — gait, balance, fall prevention, transfer training; LSVT BIG protocol evidence base in PD extrapolated

— Occupational therapy — ADL adaptation, home safety, energy conservation, equipment

— Speech-language pathology — LSVT LOUD for hypophonia; swallow exercises (effortful swallow, Mendelsohn maneuver); communication boards as speech declines

— Pulmonary rehab in MSA with respiratory involvement

— Disease trajectory (median survival, expected milestones)

— Goals-of-care evolution as disease progresses

— Caregiver support: respite, support groups (CurePSP, MSA Coalition, AFTD)

— Financial planning, Social Security Disability, long-term care insurance

— Genetic counseling if young-onset or family history

Board pearl: Aerobic exercise and resistance training have the strongest evidence among all interventions in parkinsonian disorders for slowing functional decline — prescribe 150 min/week moderate-intensity exercise even in atypical parkinsonism.

Step 3 management: Yearly MoCA + PHQ-9 + orthostatic vitals + falls history + medication reconciliation — document each as quality measures during chronic care visits.

Visit cadence: every 3–6 months in stable patients; monthly during medication titration or rapid decline

At every visit, document:

Lab monitoring:

Imaging: repeat MRI not routine; obtain if acute change (suspect stroke, SDH, hydrocephalus)

Rehabilitation:

Counseling content:

Driving evaluation: formal on-road assessment when downgaze palsy, executive dysfunction, or significant motor disability emerges; state reporting per local law

Ethical, Legal, and Patient Safety Considerations

— Complete advance directive, healthcare proxy/durable POA, MOLST/POLST while patient can articulate values

— Discuss feeding tube (PEG), tracheostomy (MSA stridor), CPR, intubation, antibiotics, hospitalization preferences explicitly

— Revisit at each major decline (post-fall, post-hospitalization)

— Capacity is decision-specific and time-specific — a patient may have capacity to refuse PEG but not to manage finances

— Four elements: understand, appreciate, reason, communicate a choice

— When capacity is lost: defer to documented advance directive → healthcare proxy → next-of-kin hierarchy per state law

— PSP downgaze + frontal executive dysfunction = high crash risk

— Several states (e.g., California, Pennsylvania, Oregon, Nevada) mandate physician reporting of cognitive impairment / dementia to DMV

— Even in non-mandatory states, document counseling and recommendation to stop driving; offer formal driving evaluation

— PEG does not prolong survival in advanced neurodegenerative disease — discuss honestly

— Hospice eligibility: align with patient values; symptom-directed care often more beneficial than additional hospitalizations

— Hospital → SNF or home — levodopa schedule must transfer accurately; missed/late doses cause acute deterioration and aspiration risk

— EHR allergy/intolerance flags for haloperidol, metoclopramide, prochlorperazine

— Caregiver education at discharge with teach-back method

Step 3 management: A physician identifying unsafe driving in a PSP patient must, at minimum, counsel the patient and family, document the recommendation, and report to DMV in mandatory-reporting states. Failure to do so can incur liability if a crash occurs.

Board pearl: Restraints, both physical and pharmacologic (especially antipsychotics), are contraindicated for fall prevention in atypical parkinsonism — they worsen parkinsonism and increase falls.

Advance care planning at diagnosis — atypical parkinsonism progresses to loss of decisional capacity faster than PD

Capacity assessments:

Driving safety and mandatory reporting:

Genetic counseling: young-onset or familial cases — discuss implications for relatives, insurance, reproductive decisions

Off-label prescribing: most pharmacotherapy in atypical parkinsonism is off-label — document shared decision-making and limited evidence base

Clinical trials: many patients seek experimental therapy; counsel honestly on early-phase trial limitations and refer to ClinicalTrials.gov

Falls and restraints: physical and chemical restraints increase injury and mortality; use environmental modifications, bed alarms, sitters instead

End-of-life decisions:

Transition-of-care safety (Step 3 flavor):

Elder abuse and neglect screening: high caregiver burden increases risk — mandatory reporting in all states for suspected abuse

High-Yield Associations and Rapid-Fire Clinical Facts

— Tauopathy (4R tau); chromosome 17 MAPT

— Hummingbird/penguin sign (midbrain atrophy on sagittal MRI)

— Vertical supranuclear gaze palsy (downgaze first)

— Early backward falls within 1 year

— Axial rigidity, retrocollis

— Applause sign (frontal disinhibition)

— Levodopa response poor

— Median survival 6–8 years

— α-synucleinopathy with glial cytoplasmic inclusions (Papp-Lantos bodies)

— Subtypes: MSA-P (parkinsonian) and MSA-C (cerebellar)

— Hot cross bun sign in pons (MSA-C); putaminal rim sign (MSA-P)

— Early autonomic failure: OH, neurogenic bladder, ED, anhidrosis

— Inspiratory stridor — sudden death risk

— RBD common; antecollis; cold dusky hands

— Preserved MIBG cardiac uptake; plasma NE fails to rise on standing

— Median survival 7–9 years

— Tauopathy (4R tau)

— Strikingly asymmetric rigidity, apraxia, alien limb, cortical sensory loss

— Asymmetric frontoparietal cortical atrophy on MRI

— Myoclonus, focal limb dystonia

— Can present as corticobasal syndrome clinically with multiple pathologies (CBD, PSP, AD, FTLD-TDP)

— Median survival 6–8 years

— Downgaze palsy + falls + hummingbird sign = PSP

— Orthostasis + RBD + stridor + hot cross bun = MSA

— Asymmetric apraxia + alien limb = CBD

— Lower-half parkinsonism + magnetic gait + WMH = vascular parkinsonism

— Wet/wobbly/wacky + ventriculomegaly = NPH

— Asymmetric tremor + dramatic levodopa response = PD

— Dementia within 1 yr of parkinsonism + visual hallucinations = DLB

— Oculomasticatory myorhythmia = Whipple

— Vertical gaze palsy in young patient = Niemann-Pick C

— Wing-beating tremor + KF rings + young = Wilson

— Manganese exposure + cock-walk gait = manganism

Board pearl: Memorize the three MRI signs — hummingbird (PSP), hot cross bun (MSA-C), asymmetric parietal atrophy (CBD) — they're nearly automatic Step 3 image stems.

Key distinction: Synucleinopathies (PD, DLB, MSA) → RBD common, reduced MIBG (except MSA preserved). Tauopathies (PSP, CBD) → no RBD, preserved MIBG.

PSP

MSA

CBD

Rapid-fire:

Board Question Stem Patterns

Board pearl: When a stem includes the words "early falls," "symmetric onset," or "poor levodopa response" — the answer is almost never PD.

Classic PSP stem: 68-year-old with 9 months of imbalance and recurrent backward falls. Family notes he stares straight ahead and has trouble looking down at his plate; speech slow, axial rigid, levodopa didn't help. MRI shows midbrain atrophy with "hummingbird sign" → answer: PSP. Best management: PT/OT, fall prevention, palliative care; avoid DBS.

Classic MSA stem: 62-year-old with 2 years of parkinsonism, recent syncope on standing, urinary incontinence, ED. Exam: BP 150/90 supine → 100/60 standing with HR change from 78 → 84. Inspiratory stridor at night. MRI shows "hot cross bun" in pons. → MSA. Best next step: head-of-bed elevation, salt/fluid, midodrine; polysomnography for stridor; consider CPAP/tracheostomy.

Classic CBD stem: 64-year-old with 18 months of asymmetric right-arm stiffness and clumsiness; "her arm seems to move on its own"; cannot pantomime brushing teeth on the right; cortical sensory loss; myoclonus. MRI: asymmetric left frontoparietal atrophy. → CBD. Best management: botulinum toxin for focal dystonia, amantadine trial, multidisciplinary rehab.

Drug-induced parkinsonism trap: 75-year-old with new symmetric parkinsonism over months while on chronic metoclopramide for gastroparesis. → Stop metoclopramide; expect resolution over weeks–months.

NPH trap: Elderly patient with magnetic gait, urinary incontinence, mild cognitive decline, ventriculomegaly on MRI → large-volume LP (tap test); if improves, refer for VP shunt.

DLB vs PD dementia: dementia onset within 1 year of parkinsonism + visual hallucinations + fluctuations → DLB. Neuroleptic sensitivity — avoid haloperidol; use pimavanserin or low-dose quetiapine.

Wilson trap: 28-year-old with tremor, dysarthria, hepatic dysfunction, KF rings → ceruloplasmin, 24-hr urinary copper; treat with trientine + zinc (or penicillamine).

Niemann-Pick C trap: Teenager with vertical supranuclear gaze palsy and ataxia → oxysterols, NPC1/NPC2 genes; miglustat available.

DBS trap: "PD" patient with early falls and poor levodopa response being considered for DBS → defer DBS, reassess for atypical parkinsonism.

Inpatient trap: Atypical parkinsonism patient admitted, given haloperidol for agitation → develops fever, rigidity, autonomic instability → parkinsonism-hyperpyrexia / NMS-like → stop haloperidol, resume dopaminergic therapy, supportive care.

One-Line Recap

Atypical parkinsonism (PSP, MSA, CBD) is a group of rapidly progressive, levodopa-resistant neurodegenerative syndromes that you distinguish from idiopathic Parkinson disease by recognizing early-warning red flags — falls and downgaze palsy (PSP), autonomic failure and stridor (MSA), or asymmetric apraxia and alien limb (CBD) — and that you manage symptomatically and longitudinally with multidisciplinary care, anticipatory advance care planning, and meticulous avoidance of dopamine-blocking medications.

Board pearl: When in doubt on a Step 3 vignette, ask three questions — Does levodopa work? Are falls early? Is there autonomic, gaze, or cortical involvement? — and the syndrome usually names itself.

Step 3 management: Build every clinic visit around motor scale, orthostatic vitals, swallow/weight, falls, cognition (MoCA), mood (PHQ-9), caregiver burden, and medication reconciliation — the chronic-care template that wins both the patient's quality of life and the exam item.

Recognition triad: early postural instability + symmetric onset + poor levodopa response → think atypical, not PD; layer on gaze palsy (PSP), dysautonomia/stridor (MSA), or asymmetric apraxia/alien limb (CBD) for syndromic diagnosis

Three MRI signs: hummingbird (PSP midbrain atrophy), hot cross bun (MSA-C pontine), asymmetric frontoparietal atrophy (CBD) — high-yield image stems

Management spine: levodopa trial to ≥1000 mg/day before declaring atypical; PT/OT/SLP early; treat the dominant symptom (OH in MSA → salt/midodrine/droxidopa; dystonia in CBD/PSP → botulinum toxin; RBD → melatonin); avoid haloperidol/metoclopramide; no DBS

Step 3 systems-of-care moves: advance care planning at diagnosis, palliative care from the start, pneumococcal vaccination, fall and aspiration prevention, caregiver support, mandatory DMV reporting where required, hospice when bulbar/respiratory decline dominates