254.1 🎓 醫孞生版

254.1.0.1 📌 䞀頁重點

254.1.0.1.1 Prion Concept
  • Proteinaceous infectious particle (PrPSc)
  • Pathologic prion protein (PrPSc) misfolded from normal cellular prion (PrPC)
  • PrPSc converts PrPC to more PrPSc → propagation
  • Resistant to nucleases, heat, formalin, UV
  • Causes transmissible spongiform encephalopathies (TSE)
254.1.0.1.2 Pathology
  • Spongiform vacuolization of gray matter
  • Neuronal loss + astrocytosis
  • PrPSc deposits (amyloid plaques in some forms)
  • No inflammatory response (no fever, no leukocyte infiltration)
254.1.0.1.3 Human Prion Diseases
254.1.0.1.3.1 Creutzfeldt-Jakob Disease (CJD) — Most Common
254.1.0.1.3.2 Sporadic CJD (sCJD)
  • 85% of human prion disease
  • Spontaneous mutation
  • Average age 60 yr
  • Rapid progressive dementia + myoclonus + ataxia + visual disturbances + extrapyramidal signs
  • Median survival 4-6 months from onset
  • 90% die within 1 year
  • Risk: increases with age; ~ 1 case per million/yr
254.1.0.1.3.3 Familial CJD (fCJD)
  • 10-15% of CJD
  • PRNP gene mutations (autosomal dominant)
  • Earlier onset than sporadic
  • Family history clues
254.1.0.1.3.4 Iatrogenic CJD (iCJD)
  • Transmitted via medical procedures:
    • Cadaveric pituitary growth hormone (historic — banned)
    • Dura mater grafts (historic — banned)
    • Corneal transplants (rare)
    • Surgical instruments contaminated (rare)
  • Latent period years-decades
254.1.0.1.3.5 Variant CJD (vCJD)
  • From BSE (Bovine Spongiform Encephalopathy) consumption
  • UK 1996 outbreak + ongoing concern
  • ~ 230 cases reported worldwide (mostly UK)
  • Younger onset (median 28 yr) vs sporadic CJD (60 yr)
  • Psychiatric / sensory + late dementia
  • Median survival 14 months (longer than sporadic)
  • Tonsil + appendix biopsy PrPSc positive (unique to vCJD)
254.1.0.1.3.6 Gerstmann-StrÀussler-Scheinker (GSS)
  • Familial autosomal dominant
  • PRNP mutations
  • Cerebellar ataxia + dementia
  • Slow progression (years)
254.1.0.1.3.7 Fatal Familial Insomnia (FFI)
  • Familial (mostly) — PRNP D178N mutation
  • Progressive untreatable insomnia → dysautonomia + dementia + death
  • Months-years
254.1.0.1.3.8 Kuru
  • Historical (Papua New Guinea Fore tribe)
  • Ritualistic cannibalism transmission
  • Disappeared with cessation of cannibalism
  • Cerebellar ataxia + tremor + dementia
254.1.0.1.4 Animal Prion Diseases
  • Scrapie (sheep, goats) — known centuries
  • BSE (mad cow disease) — UK epidemic 1980s+
  • Chronic Wasting Disease (CWD) — deer + elk in N America (concerning expansion)
  • Feline spongiform encephalopathy (cats from BSE-contaminated food)
  • Transmissible mink encephalopathy
254.1.0.1.5 Risk
  • Sporadic CJD: idiopathic (most common)
  • Familial: genetic
  • Iatrogenic: rare today (banned + improved infection control)
  • vCJD: dietary (BSE-contaminated beef in UK 1990s)
  • Occupational: rare (researchers, abattoir workers — minimal)
254.1.0.1.6 Diagnosis
254.1.0.1.6.1 Clinical
  • Rapidly progressive dementia + myoclonus + ataxia + visual / sensory disturbances + extrapyramidal signs
  • Months-year course (median 4-6 mo sporadic)
254.1.0.1.6.2 EEG
  • Periodic sharp wave complexes (PSWC) — characteristic in sporadic CJD (1-2 Hz biphasic / triphasic)
  • 60-80% sensitivity
254.1.0.1.6.3 MRI Brain
  • DWI / FLAIR hyperintensity:
    • Cortical “ribbon sign” (cortical gyriform)
    • Basal ganglia hyperintensity (caudate, putamen)
    • “Hockey stick sign” (medial thalamus + pulvinar) — characteristic of vCJD
  • Sensitivity > 90% with proper sequences
254.1.0.1.6.4 CSF
  • 14-3-3 protein elevation (sens 90%; nonspecific)
  • Total tau protein elevation
  • RT-QuIC (Real-Time Quaking-Induced Conversion) — most specific and sensitive (95%+) — detects PrPSc seeding activity
  • Standard CSF analysis: usually normal
254.1.0.1.6.5 Tonsil + Appendix Biopsy (vCJD)
  • PrPSc detectable in lymphoid tissue
  • Unique to vCJD (not sporadic CJD)
  • Less invasive than brain biopsy
254.1.0.1.6.6 Brain Biopsy / Autopsy
  • Definitive diagnosis
  • Spongiform vacuolization + neuronal loss + PrPSc deposition (IHC)
  • Genetic testing (PRNP)
  • Strain typing (sporadic vs vCJD vs other)
254.1.0.1.7 Treatment
  • No proven effective treatment
  • Universally fatal
  • Supportive care + symptom management:
    • Anti-myoclonic agents (clonazepam)
    • Antipsychotics for agitation
    • Nutrition + hydration support
    • Hospice + palliative care
  • Research: anti-prion antibodies, PrPC reduction, small molecules — no FDA-approved
  • Doxycycline + pentosan polysulfate had mixed results
254.1.0.1.8 Prevention + Infection Control
  • Surgical instruments: standard sterilization insufficient
    • Special prion decontamination protocols (autoclave 134°C × 18 min + chemical decontamination)
    • Disposable instruments for high-risk procedures (CNS)
  • Blood transfusion: vCJD blood donor screening
    • UK + EU permanent deferral of UK residents 1980-1996 (BSE peak)
    • USA: similar deferrals
  • Medical instruments: special handling for known / suspected
  • No general bioterror concern (low transmissibility)
254.1.0.1.9 BSE Public Health
  • UK BSE outbreak peak 1992 (180K cattle)
  • Cattle feed ban 1989 (preventing recycling animal protein)
  • Ongoing surveillance globally
  • USA + EU surveillance + import restrictions
  • Cattle prion testing
  • BSE rare now but maintained surveillance
254.1.0.1.10 CWD Concern
  • Deer + elk + moose endemic N America (especially CO, WY, WI)
  • Spread to white-tailed deer
  • Captive + wild populations
  • Theoretical human transmission risk (none confirmed but vigilance)
  • Don’t eat deer brain / spinal cord; test high-prevalence areas