381.3 🏥 內科專科考前版

381.3.1 Mechanistic Deep Dive

381.3.1.1 Synucleinopathy vs Tauopathy

  • Synucleinopathy: α-synuclein in Lewy bodies (PD, DLB) or GCIs (MSA)
  • Tauopathy: hyperphosphorylated tau aggregates
    • 4R: PSP, CBD
    • Mixed 3R/4R: AD
    • 3R: Pick’s

381.3.1.2 Tau Isoforms

  • 3R (3 microtubule-binding repeats): in Pick disease
  • 4R: in PSP, CBD
  • Mixed in AD

381.3.2 Recent Trials & Updates

381.3.2.1 Anti-Tau Therapies for PSP (Disappointing So Far)

  • Gosuranemab (PASSPORT) — negative
  • Tilavonemab (TANGO) — negative
  • BIIB092 — negative
  • Lucanemab (in trials)
  • Approaches: passive immunization, MTBR targeting, anti-sense

381.3.2.2 Anti-α-Synuclein for MSA

  • Lu AF82422 (MERINO)
  • TRADITIONAL approaches

381.3.2.3 α-Synuclein RT-QuIC + Skin Biopsy

  • Distinguishes synucleinopathies
  • Emerging clinical tool

381.3.3 High-Yield Specialist Points

381.3.3.1 MSA Subtype Mixed

  • Many have features of both MSA-P + MSA-C
  • Progression often involves both

381.3.3.2 MSA Stridor Management

  • CPAP at night (life-saving)
  • Tracheostomy for severe
  • Vocal fold paralysis later

381.3.3.3 MSA Cardiac Sympathetic Denervation Pattern

  • MIBG: MSA preserves, PD decreases (differentiation)

381.3.3.4 PSP Gaze Limitations

  • Vertical first (especially downgaze)
  • “Doll’s eye” maneuver overcomes (suggests supranuclear)
  • Later horizontal
  • Square wave jerks
  • Slow saccades

381.3.3.5 PSP Pseudobulbar

  • Pathologic laughing/crying
  • Dextromethorphan-quinidine (Nuedexta)
  • SSRIs

381.3.3.6 PSP “Surprised look”

  • Lid retraction
  • Decreased blinking

381.3.3.7 CBD Alien Limb

  • Levitation (lifting up)
  • Avoidant
  • Intermanual conflict

381.3.3.8 Asymmetric Findings in CBD

  • Cortical: contralateral hemisphere
  • Subcortical: contralateral basal ganglia

381.3.3.9 CBD Aphasia

  • Apraxia of speech
  • Nonfluent variant
  • Logopenic variant rare

381.3.3.10 Apraxia Testing

  • Ideomotor: gestures (use a comb, hammer)
  • Ideational: sequential acts
  • Limb-kinetic

381.3.3.11 MSA-AD Co-Pathology

  • Many “MSA” patients have AD co-pathology at autopsy
  • Cognitive features common in late MSA

381.3.3.12 Genetic Forms

  • Rare familial PSP, CBD, MSA
  • MAPT mutations → FTD-tau (different from PSP)

381.3.3.13 Differential of Vertical Gaze Palsy

  • PSP (most common in elderly)
  • Whipple disease (oculomasticatory myorhythmia + cognitive)
  • Niemann-Pick C
  • Wilson disease
  • Brainstem stroke
  • Dorsal midbrain (Parinaud) — Sylvian aqueduct compression

381.3.3.14 Whipple Disease CNS

  • Tropheryma whipplei
  • Oculomasticatory myorhythmia (pathognomonic)
  • Cognitive
  • GI symptoms (often)
  • Antibiotics (ceftriaxone + TMP-SMX or doxycycline)

381.3.3.15 Niemann-Pick C

  • Lysosomal storage
  • Vertical gaze palsy
  • Ataxia, dementia
  • Miglustat may help

381.3.4 Pearls

  • Synucleinopathy vs tauopathy distinction
  • MSA: autonomic + stridor + RBD + cerebellar/parkinsonian + “hot cross bun”
  • PSP: vertical gaze palsy + early falls + “hummingbird”
  • CBD: asymmetric + alien limb + cortical sensory + apraxia + myoclonus
  • MIBG distinguishes MSA (preserved) from PD/DLB (decreased)
  • CPAP life-saving for MSA stridor
  • No disease-modifying — supportive
  • Anti-tau trials disappointing so far
  • DDx vertical gaze palsy: PSP, Whipple, Niemann-Pick C, Wilson, brainstem