385.3 🏥 內科專科考前版

385.3.1 Mechanistic Deep Dive

385.3.1.1 Prion Protein

  • Normal: PrPC (cellular)
  • Misfolded: PrPSc (scrapie-like)
  • α-helix → β-sheet
  • Self-propagating
  • Resistant to proteases (in part)

385.3.1.2 RT-QuIC Mechanism

  • Real-time quaking-induced conversion
  • Recombinant PrP added to CSF
  • Misfolded PrP seeds aggregation
  • Detected by fluorescence
  • Very sensitive + specific

385.3.1.3 CSF 14-3-3

  • Marker of neuronal damage
  • Less specific than RT-QuIC
  • Can be elevated in other rapidly progressive encephalopathies

385.3.2 Recent Updates

385.3.2.1 sCJD Subtypes

  • MM1, MM2, MV1, MV2, VV1, VV2 based on PRNP codon 129 + PrPSc type
  • Different presentations

385.3.2.2 Anti-Prion Therapies

  • PRN100 (monoclonal antibody) trials
  • BIIB104 (antisense oligonucleotide)
  • Limited efficacy so far

385.3.2.3 Plasma Biomarkers

  • NfL emerging marker
  • Plasma α-syn

385.3.3 High-Yield Specialist Points

385.3.3.1 Heidenhain Variant CJD

  • Visual symptoms predominant initially
  • Occipital lobe involvement
  • Cortical blindness can result

385.3.3.2 Brownell-Oppenheimer Variant

  • Cerebellar predominant
  • Ataxia early

385.3.3.3 Variant CJD Pulvinar Sign

  • Bilateral pulvinar (posterior thalamic) hyperintensity
  • FLAIR/DWI
  • Specific to vCJD

385.3.3.4 Familial Prion Mutations

  • E200K, V210I (CJD)
  • D178N (FFI with codon 129 M; CJD with V)
  • P102L (GSS)

385.3.3.5 Fatal Familial Insomnia (FFI)

  • D178N + 129M
  • Insomnia → autonomic dysfunction → motor → death
  • Thalamus prominent
  • Severe REM disturbance

385.3.3.6 Gerstmann-StrÀussler-Scheinker

  • Cerebellar ataxia primary
  • Late cognitive
  • Longer course
  • P102L common

385.3.3.7 Autoimmune Encephalitis Mimics CJD

  • Rapidly progressive
  • Treatable (immunotherapy)
  • Always rule out before declaring CJD
  • Especially anti-LGI1, anti-NMDA-R, others

385.3.3.8 Limbic Encephalitis

  • Mesial temporal involvement on MRI
  • Seizures, amnesia
  • Autoimmune or paraneoplastic
  • Treatable

385.3.3.10 Sneddon Syndrome

  • Livedo reticularis + recurrent strokes
  • APS often
  • Cognitive decline

385.3.3.11 Anti-IgLON5 Syndrome

  • REM + non-REM sleep disorder
  • Bulbar
  • Movement
  • Chorea, parkinsonism
  • Hyperphosphorylated tau on autopsy
  • Immunotherapy partial response

385.3.3.12 NORSE (New-Onset Refractory Status Epilepticus)

  • Often autoimmune
  • Refractory seizures
  • Immunotherapy
  • See Ch372

385.3.3.13 Hashimoto Encephalopathy

  • SREAT (steroid-responsive encephalopathy associated with autoimmune thyroiditis)
  • Anti-TPO antibodies high
  • Subacute
  • Steroid-responsive
  • Mimics CJD
  • Always check anti-TPO in rapidly progressive

385.3.3.14 Adult-Onset Leukodystrophies

  • Adult metachromatic
  • ALD (X-linked)
  • Vanishing white matter
  • Pelizaeus-Merzbacher-like
  • Genetic testing

385.3.3.15 Cerebrotendinous Xanthomatosis

  • CYP27A1
  • Cataracts + tendon xanthomas + neurological
  • Chenodeoxycholic acid

385.3.4 Pearls

  • Prion (sCJD): rapid + myoclonus + ataxia + visual
  • MRI cortical ribboning, BG hyperintensity
  • RT-QuIC best CSF test
  • vCJD: BSE, younger, psychiatric, pulvinar sign
  • No treatment for prion
  • Hashimoto encephalopathy mimics CJD — steroid-responsive
  • Autoimmune encephalitis treatable
  • VITAMINS mnemonic for rapidly progressive dementia
  • Whipple CNS: oculomasticatory myorhythmia
  • Wilson always consider young
  • Reversible/treatable causes — rule out before declaring degenerative!