Creutzfeldt-Jakob Disease (CJD)

A 67 year old male presents with rapidly progressive memory decline, personality changes, involuntary jerking movements, and progressive gait instability over several weeks. Family members report behavioral changes and worsening confusion. Neurological examination reveals myoclonus, hyperreflexia, and cerebellar ataxia. MRI brain demonstrates characteristic abnormalities involving the basal ganglia and cerebral cortex.

Diagnosis?

Diagnosis is Creutzfeldt-Jakob disease (CJD).

1. Definition

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, fatal neurodegenerative prion disease caused by accumulation of misfolded prion proteins within the central nervous system.

Normal cellular prion protein (PrPᶜ) undergoes conformational conversion into the pathogenic form (PrPˢᶜ), resulting in accumulation of abnormal β-pleated sheet proteins, neuronal injury, and spongiform degeneration.

2. Types

1. Sporadic CJD (most common)
2. Familial CJD
3. Iatrogenic CJD
4. Variant CJD

3. Pathophysiology

1. Normal cellular prion protein (PrPᶜ) has predominantly alpha-helical structure
2. Conversion into abnormal prion protein (PrPˢᶜ) with beta-pleated sheet configuration
3. Abnormal prion proteins induce further misfolding of normal proteins
4. Progressive accumulation causes neuronal dysfunction and degeneration
5. Spongiform degeneration occurs without significant inflammatory response

4. Clinical Features

4.1 Core Features

1. Rapidly progressive dementia
2. Memory impairment
3. Cognitive decline
4. Behavioral and personality changes

4.2 Neurologic Features

1. Myoclonus (classic finding)
2. Hyperreflexia
3. Cerebellar ataxia
4. Visual disturbances
5. Extrapyramidal symptoms
6. Akinetic mutism in advanced disease

4.3 Other Features

1. Sleep disturbances
2. Anxiety
3. Depression
4. Progressive functional decline

5. Diagnosis

Diagnosis is based on:

1. Rapidly progressive dementia
2. Characteristic clinical findings
3. Supportive MRI, CSF, and EEG findings
4. Exclusion of alternative diagnoses

5.1 Electroencephalography (EEG)

1. Periodic sharp wave complexes
2. Typically appear later in disease course
3. Supportive but not required for diagnosis

5.2 Cerebrospinal Fluid (CSF)

1. RT-QuIC assay is highly specific and preferred when available
2. Elevated 14-3-3 protein is supportive but nonspecific
3. Elevated total tau protein may be present

5.3 Neuroimaging

MRI Brain (Most Useful Supportive Test)

1. Diffusion-weighted imaging (DWI) and FLAIR sequences are most sensitive
2. Hyperintensity involving:
• Caudate nucleus
• Putamen
3. Cortical ribboning may be present

T2-weighted imaging alone is less sensitive

5.4 Histopathology (Definitive Diagnosis)

1. Spongiform vacuolar degeneration
2. Neuronal loss
3. Gliosis
4. Prion protein accumulation
5. Minimal or absent inflammation

Brain biopsy is rarely required clinically and is generally reserved when alternative treatable diagnoses remain under consideration

6. Variant CJD

Distinct features:

1. Younger age at presentation
2. Prominent psychiatric symptoms
3. Painful sensory symptoms
4. Longer disease course
5. MRI may demonstrate the pulvinar sign

Associated with exposure to bovine spongiform encephalopathy

7. Differential Diagnosis

1. Autoimmune encephalitis
2. Alzheimer disease
3. Dementia with Lewy bodies
4. Viral encephalitis
5. Frontotemporal dementia
6. Hashimoto encephalopathy

8. Management

Supportive Care

1. Symptom control
2. Nutritional support
3. Physical therapy
4. Family counseling
5. Palliative care

No disease-modifying therapy currently exists

9. Prognosis

1. Progressive and universally fatal disease
2. Rapid neurologic deterioration is typical
3. Most patients with sporadic CJD die within approximately 1 year of symptom onset

10. Key Clinical Insight

Rapidly progressive dementia with myoclonus, ataxia, characteristic MRI abnormalities, and supportive CSF findings strongly suggests Creutzfeldt-Jakob disease

11. Key Exam Points

1. Prion disease caused by PrPᶜ → PrPˢᶜ conversion
2. Sporadic CJD is most common
3. Myoclonus is the classic clinical feature
4. MRI DWI and FLAIR are more sensitive than EEG
5. RT-QuIC is highly specific and preferred CSF testing
6. EEG may show periodic sharp wave complexes
7. Histology shows spongiform degeneration without inflammation
8. Variant CJD may show pulvinar sign
9. No curative treatment exists
10. Supportive and palliative care are the mainstay of management