STEPTRACKERMICROBIOLOGY + NEUROLOGY + PATHOLOGY | PRIONS & SLOW INFECTIONS | HIGH-YIELD REVIEW

Prions & Slow Infections

Infectious proteins with no nucleic acid, and conventional viruses that smolder in the brain for years — both end in rapidly progressive dementia.

FOCUS ON
Prions: normal α-helical PrPᶜ refolds into β-pleated PrPˢᶜ, which is protease-resistant and converts more PrPᶜ → spongiform encephalopathy (vacuoles, neuronal loss, no inflammation). Resist standard sterilization (formaldehyde, UV, routine autoclaving) — need extended autoclaving plus NaOH/bleach. CJD: sporadic (most), familial (PRNP mutation), iatrogenic (dura grafts, cadaveric growth hormone, corneal transplants, neurosurgical instruments). Rapid dementia + startle myoclonus; periodic sharp-wave EEG; ↑ 14-3-3 protein; RT-QuIC. Variant CJD: beef (BSE), young patients, psychiatric onset. Slow viruses: SSPE (measles), PML (JC).
DISEASE
CAUSE · MECHANISM
CLINICAL PICTURE
DIAGNOSIS · CLUE
Sporadic CJD
Spontaneous PrPᶜ → PrPˢᶜ conversion; most common prion disease
Age ~60: rapidly progressive dementia (months), myoclonus, ataxia, visual symptoms
Periodic sharp-wave complexes · ↑ 14-3-3 · MRI cortical ribboning · RT-QuIC
Familial CJD
Autosomal dominant PRNP mutation
Similar to sporadic, younger
Family history
Iatrogenic CJD
Dura mater grafts, cadaveric pituitary growth hormone, corneal transplants, EEG electrodes, instruments
CJD years after exposure
Single-use or special decontamination
Variant CJD
Bovine spongiform encephalopathy (mad cow) in beef
Young adults: psychiatric symptoms, painful sensory symptoms first, slower course
Pulvinar sign on MRI; florid plaques; prions in tonsil
Kuru
Ritualistic cannibalism (Fore people, Papua New Guinea)
Cerebellar ataxia, tremor, emotional lability ("laughing death")
Historical
Fatal familial insomnia
PRNP mutation; thalamic degeneration
Progressive untreatable insomnia, dysautonomia, dementia
Autosomal dominant
Gerstmann-Sträussler-Scheinker
PRNP mutation; amyloid plaques
Ataxia first, dementia later, slow
—
Prion pathology
Neuronal vacuoles in gray matter, astrogliosis
No inflammation, no immune response
Spongiform change
SSPE
Defective measles virus persists in neurons (M protein mutation); infection before age 2
Years later: behavior change, myoclonus, dementia, death
↑ anti-measles antibody in CSF · periodic EEG complexes
PML
JC virus in oligodendrocytes
Immunosuppressed: progressive focal deficits
See 6.03
Progressive rubella panencephalitis
Persistent rubella after congenital infection
Teen-onset dementia, ataxia
Rare
HTLV-1 myelopathy
Retrovirus (Caribbean, Japan)
Slowly progressive spastic paraparesis; also adult T-cell leukemia
Tropical spastic paraparesis

Mechanism — prion propagation

PrPᶜNormal, α-helix, protease-sensitive
→
Contact with PrPˢᶜTemplated misfolding
→
β-sheet PrPˢᶜ aggregatesProtease-resistant
→
Neuronal death, vacuolesSpongiform brain

Same amino-acid sequence, different shape — no DNA or RNA, so no immune response and no nucleic acid to destroy.

Sporadic vs variant CJD

FEATURE
SPORADIC
VARIANT
Age
~60
~20s
First symptoms
Dementia, myoclonus
Psychiatric, sensory
Course
Months
~1 year or more
EEG
Periodic sharp waves
Usually not
MRI
Cortical, basal ganglia
Pulvinar sign

How it's tested

COMMON CONFUSIONCJD (months, myoclonus, periodic EEG) vs Alzheimer disease (years, no myoclonus early) vs Lewy body dementia (hallucinations, parkinsonism, fluctuation).
THE TRAPRoutine autoclaving and formaldehyde don't inactivate prions — instruments used on suspected CJD need special decontamination or disposal.
YOUR APPROACHDementia over months + myoclonus → prion workup (EEG, 14-3-3, MRI, RT-QuIC) → exposure history (iatrogenic, dietary, familial).

If you see… think…

Rapid dementia over months with startle myoclonus → CJD
Periodic sharp-wave complexes on EEG → CJD
CSF marker of rapid neuronal destruction → 14-3-3 protein
Brain with vacuoles but no inflammation → spongiform encephalopathy
CJD after cadaveric growth hormone or dura graft → iatrogenic CJD
Young adult with psychiatric onset and pulvinar sign → variant CJD
Unrelenting insomnia with thalamic degeneration → fatal familial insomnia
Prion protein shape change → α-helix to β-pleated sheet
Teen with myoclonus and dementia, measles in infancy → SSPE
Slowly progressive spastic legs in a Caribbean immigrant → HTLV-1 myelopathy