Prion Infections

Overview – Prion Infections

Prion infections are rare, universally fatal neurodegenerative conditions caused by abnormally folded host proteins known as prions. Unlike viruses or bacteria, prions contain no DNA or RNA, making them unique and important for exams. These diseases include Creutzfeldt-Jakob Disease (CJD), Gerstmann–Sträussler–Scheinker Syndrome, Fatal Familial Insomnia, and Kuru. They are characterised by rapid neurocognitive decline, spongiform brain degeneration, and profound functional impairment.

Definition

• Prion diseases = infectious, protein-only diseases affecting the CNS.
• Prions = misfolded versions of a host protein (PrP) that accumulate in neural tissue and propagate by inducing misfolding of normal PrP.
• No nucleic acids – no DNA or RNA.

Aetiology

• Spontaneous or inherited genetic mutations in the PrP gene.
• Ingested or iatrogenic transmission of prion-contaminated material (e.g. cannibalism, surgical instruments, human growth hormone).
• Prion types:
  • Normal form = PrPᶜ (α-helix, functional, denaturable)
  • Pathogenic form = PrPˢᶜ (β-sheet, non-functional, indestructible)

Pathophysiology

• PrPˢᶜ accumulates in neurons and propagates by converting PrPᶜ into the abnormal form.
• This leads to:
  • Amyloid plaque formation
  • Neuronal vacuolation
  • Spongiform encephalopathy
  • Neuronal death

Morphology

Macro

• Brain shows empty cystic lesions → spongiform appearance

Micro

• Neuronal vacuolation
• Intracellular amyloid plaques
• No inflammatory response

Clinical Features

• Subacute, rapid progression over weeks to months
• Early:
  • Subtle memory loss
  • Behavioural/personality changes
• Progressive:
  • Rapidly progressive dementia
  • Myoclonus (sudden muscle jerks)
  • Ataxia, dysarthria, dysphagia
  • Visual disturbances, nystagmus

Diagnosis

• Clinical suspicion based on rapid cognitive decline
• MRI: Hyperintensities in basal ganglia, cortex
• EEG: Periodic sharp wave complexes (esp. in sCJD)
• CSF markers: 14-3-3 protein, RT-QuIC assay
• Brain biopsy/autopsy: confirms definitive diagnosis

Management

• Currently no cure or disease-modifying treatment
• Supportive only:
  • Symptom relief (anticonvulsants for myoclonus)
  • Psychological support
  • Palliative care

Prognosis

• All prion diseases are fatal
• Median survival from onset ≈ 7 months
• Death due to progressive neurological failure, aspiration pneumonia or sepsis

Notable Prion Diseases

• Creutzfeldt–Jakob Disease (CJD) – Most common human prion disease
• Gerstmann–Sträussler–Scheinker Syndrome – Autosomal dominant; slower progression
• Fatal Familial Insomnia – Thalamic degeneration; progressive insomnia
• Kuru – Historical; cannibalistic transmission in Papua New Guinea

Summary – Prion Infections

Prion infections are rare, fatal, protein-based neurodegenerative diseases such as Creutzfeldt-Jakob Disease. They cause rapid-onset dementia, myoclonus, and spongiform brain degeneration, with no effective treatment. Early diagnosis is key for supportive management. For a broader context, see our Nervous System Overview.