381.4 📋 章末速蚘 Summary

381.4.1 🔑 䞀句話瞜結

Atypical parkinsonism = parkinsonism + additional features that distinguish from idiopathic PD + poor levodopa response often; classification — synucleinopathies (α-synuclein) — PD + DLB + MSA (multiple system atrophy) vs tauopathies (4R tau) — PSP (progressive supranuclear palsy) + CBD (corticobasal degeneration) + FTD-tau; MSA (multiple system atrophy) mean onset 55-65, survival 6-10 years; subtypes MSA-P (parkinsonian) vs MSA-C (cerebellar); severe autonomic failure early (orthostatic hypotension drop ≥ 30/15 within 3 min + urinary incontinence/retention + sexual dysfunction + sweating abnormalities) + inspiratory stridor (laryngeal dystonia — characteristic + can be FATAL — CPAP life-saving) + REM sleep behavior disorder (common) + poor/early-failing levodopa response + pyramidal signs + bulbar dysfunction + cold/discolored hands; MSA pathology α-synuclein in glial cytoplasmic inclusions (GCIs — different from PD/DLB neuronal); MSA imaging — “hot cross bun sign” (pons cruciate hyperintensity on T2 — MSA-C) + putaminal atrophy with hyperintensity rim (MSA-P) + cerebellar atrophy (MSA-C); MIBG cardiac scintigraphy preserved in MSA (decreased in PD/DLB — distinguishing feature); treatment — no disease-modifying + supportive (midodrine/fludrocortisone/droxidopa for OH + catheterization + PEG dysphagia + CPAP for stridor LIFE-SAVING + PT/OT/speech) + levodopa trial may help motor briefly; PSP (progressive supranuclear palsy) mean onset 60-65, survival 5-8 years; hallmark vertical supranuclear gaze palsy (especially DOWNGAZE) + early falls (within 1 year onset — backward falls) + axial rigidity > limb + frontal cognitive impairment (apathy, dysexecutive) + pseudobulbar + dysphagia + dysarthria + apraxia of eyelid opening + square wave jerks + poor levodopa response; variants — Richardson syndrome (classic — gaze palsy + falls + cognitive) + PSP-P (parkinsonism predominant, mimics PD) + PSP-PGF (progressive gait freezing) + PSP-CBS (corticobasal syndrome) + PSP-SL (speech/language); PSP pathology 4R tau deposits + globose tangles + tufted astrocytes; PSP imaging — “hummingbird sign” (midbrain atrophy sagittal) + “Mickey Mouse sign” (midbrain axial) + reduced midbrain : pons area ratio; no disease-modifying (multiple negative trials anti-tau gosuranemab/tilavonemab/BIIB092) + supportive + falls prevention + levodopa trial limited + botulinum for blepharospasm/dystonia + SSRIs pseudobulbar + amantadine sometimes; CBD (corticobasal degeneration) mean onset 60-70, survival 6-8 years; asymmetric parkinsonism + cortical features — alien limb phenomenon (involuntary movements feel “not theirs”, levitation, avoidant, intermanual conflict) + cortical sensory loss (astereognosis, agraphesthesia) + apraxia (ideomotor) + myoclonus + dystonia (often arm) + asymmetric limb rigidity + cognitive impairment + aphasia variants + poor levodopa response; CBS (corticobasal syndrome) clinical vs CBD pathological (CBS can be due to multiple pathologies — CBS-PSP, CBS-AD overlap); CBD pathology 4R tau + astrocytic plaques + ballooned neurons; CBD imaging — asymmetric perirolandic atrophy + DAT-scan reduced; no disease-modifying + supportive; DDx vertical gaze palsy — PSP (most common in elderly) + Whipple disease (oculomasticatory myorhythmia pathognomonic + cognitive + ceftriaxone + TMP-SMX) + Niemann-Pick C (lysosomal storage + miglustat) + Wilson disease + brainstem stroke + dorsal midbrain Parinaud (Sylvian aqueduct compression)。

381.4.2 💊 治療粟芁

  • MSACPAP at night for stridor (LIFE-SAVING — tracheostomy if severe vocal fold paralysis later) + midodrine 5-10 mg TID + fludrocortisone 0.1-0.3 mg/d + droxidopa (Northera) for orthostatic hypotension + intermittent catheterization or alpha blocker for urinary + PEG for dysphagia + levodopa trial (may help briefly motor) + multidisciplinary PT/OT/speech therapy
  • PSPlevodopa trial (limited response) + amantadine sometimes + botulinum toxin for blepharospasm + dystonia + apraxia of eyelid opening + SSRIs + dextromethorphan-quinidine (Nuedexta) for pseudobulbar affect + falls prevention (PT, home modifications, gait aids) + multidisciplinary care
  • CBDlevodopa trial (rarely helps) + botulinum toxin for dystonia + myoclonus (clonazepam, levetiracetam, valproate) + speech therapy for apraxia + multidisciplinary
  • disease-modifying — none for any; multiple anti-tau (PSP) + anti-α-synuclein (MSA) trials disappointing; ongoing research

381.4.3 🎯 盧醫垫的考前提醒

  1. Synucleinopathies vs tauopathies: synucleinopathies (α-synuclein) = PD + DLB + MSA vs tauopathies (4R tau) = PSP + CBD; pathology + clinical features differ
  2. MSA hallmarks: severe autonomic failure early (orthostatic + urinary + sexual) + inspiratory stridor (LIFE-THREATENING — CPAP life-saving!) + REM sleep behavior disorder + poor levodopa response + cerebellar (MSA-C) or parkinsonian (MSA-P) + pyramidal signs + cold hands
  3. MSA imaging: “hot cross bun sign” in pons on T2 (cruciate hyperintensity — MSA-C) + putaminal atrophy with hyperintensity rim (MSA-P) + cerebellar atrophy; MIBG-cardiac scintigraphy PRESERVED in MSA but DECREASED in PD/DLB (key distinguishing feature)
  4. PSP hallmarks: vertical supranuclear gaze palsy (especially DOWNGAZE — “doll’s eye” maneuver overcomes, suggesting supranuclear) + early falls (within 1 year — backward falls!) + axial rigidity > limb + frontal cognitive impairment + Richardson syndrome classic + variants (PSP-P, PSP-PGF, PSP-CBS, PSP-SL)
  5. PSP imaging: “hummingbird sign” on sagittal MRI (midbrain atrophy) + “Mickey Mouse sign” on axial + reduced midbrain : pons area ratio
  6. CBD hallmarks: asymmetric parkinsonism + alien limb phenomenon + cortical sensory loss + apraxia + myoclonus + dystonia + cognitive impairment + aphasia variants; CBS clinical vs CBD pathological (CBS can be PSP/AD/CBD)
  7. PD vs atypical distinguishing: PD has rest tremor + asymmetric + good levodopa response + late falls vs atypical has poor levodopa + early falls + autonomic (MSA) or vertical gaze (PSP) or alien limb/cortical signs (CBD) or symmetric onset
  8. No disease-modifying therapy for any; anti-tau therapies for PSP disappointing (gosuranemab, tilavonemab, BIIB092 — all negative) + supportive management
  9. MSA stridor: CPAP at night LIFE-SAVING + tracheostomy for severe; vocal fold paralysis can develop
  10. DDx vertical gaze palsy: PSP (most common in elderly) + Whipple disease (oculomasticatory myorhythmia PATHOGNOMONIC + GI symptoms + ceftriaxone + TMP-SMX) + Niemann-Pick C (lysosomal storage + miglustat) + Wilson disease + brainstem stroke + dorsal midbrain Parinaud syndrome (Sylvian aqueduct compression — pinealoma, hydrocephalus)