What are the symptoms of Creutzfeldt-Jakob disease (CJD) and how are they managed?

Symptoms and Management of Creutzfeldt-Jakob Disease (CJD)

Creutzfeldt-Jakob disease (CJD) is characterized by rapidly progressive dementia, followed by myoclonic jerks, ataxia, and movement disorders, ultimately progressing to akinetic mutism and death, with no effective treatment available and management focused on supportive care. 1

Clinical Presentation

Core Symptoms

• Cognitive Symptoms:

  • Rapidly progressive dementia (most common initial presentation)
  • Memory loss
  • Personality changes
  • Behavioral abnormalities
  • Confusion and disorientation

• Neurological Symptoms:

  • Myoclonus (occurs in 90% of cases, often not present initially)
  • Cerebellar ataxia (unsteady gait, poor coordination)
  • Movement disorders (parkinsonism, rigidity)
  • Visual disturbances
  • Speech difficulties (dysarthria, mutism)

• Late-Stage Symptoms:

  • Akinetic mutism
  • Coma
  • Death (typically within 5 months of symptom onset for sporadic CJD) 1

Atypical Presentations

• Psychiatric symptoms (depression, anxiety, psychosis) may be the initial presentation 2, 3
• Stroke-like symptoms with focal neurological deficits 4
• Sensory symptoms (paresthesias)
• Visual hallucinations or cortical blindness (Heidenhain variant)
• Predominant cerebellar ataxia (Brownell-Oppenheimer variant) 1

Diagnostic Approach

Clinical Criteria

The diagnosis of CJD is based on a combination of:

1. Characteristic clinical syndrome (rapidly progressive dementia)
2. Supportive biomarkers
3. Exclusion of other causes

Diagnostic Tests

• Cerebrospinal Fluid (CSF) Analysis:

  • RT-QuIC (Real-time Quaking-Induced Conversion): highest specificity and sensitivity
  • 14-3-3 protein: supportive biomarker but limited specificity
  • Total Tau protein: elevated in CJD
  • Normal or slightly elevated protein concentration
  • Absence of pleocytosis (no inflammatory cells) 1

• Neuroimaging:

  • MRI: Most sensitive imaging modality

    • Diffusion-weighted imaging (DWI) and FLAIR sequences show:
      • Cortical ribboning (hyperintensity in cortical gray matter)
      • Basal ganglia hyperintensity (especially caudate and putamen)
      • Thalamic hyperintensity (pulvinar sign in variant CJD) 1

  • CT: Limited utility, may show atrophy in later stages 1

• Electroencephalography (EEG):

  • Generalized slowing early in disease
  • Periodic sharp wave complexes (PSWCs) in later stages 1

• Genetic Testing:

  • PRNP gene sequencing to rule out genetic forms 1

• Definitive Diagnosis:

  • Brain biopsy or autopsy showing spongiform changes and PrPSc deposition 1

Management

Treatment

• No curative treatment exists for CJD
• No disease-modifying therapies have proven effective

Supportive Care

• Symptom Management:

  • Myoclonus: Clonazepam, valproate, or levetiracetam
  • Psychiatric symptoms: Antipsychotics, anxiolytics (with caution due to potential worsening of cognitive symptoms)
  • Pain management
  • Prevention of complications (aspiration, pressure ulcers)

• End-of-Life Care:

  • Palliative care consultation
  • Hospice referral
  • Anticipatory medications for terminal symptoms
  • Family support and counseling 5

Infection Control

• Standard precautions for patient care
• Special precautions for handling tissue specimens
• No risk of transmission through normal social contact

Prognosis

• Universally fatal disease
• Median survival: 5 months from symptom onset for sporadic CJD
• Most patients die within 1 year of diagnosis 5, 6

Important Clinical Pearls

• Consider CJD in any patient with rapidly progressive dementia, especially when accompanied by myoclonus or ataxia
• Psychiatric symptoms may precede neurological manifestations by weeks to months
• Repeated neurological examinations and serial MRIs may be necessary to establish the diagnosis
• The clinical course is typically much more rapid than other neurodegenerative disorders
• RT-QuIC testing has revolutionized pre-mortem diagnosis and should be performed in all suspected cases 1