Creutzfeldt-Jakob Disease (CJD) is a rare and fatal neurodegenerative disorder characterized by rapidly progressive dementia. Accurate and timely diagnosis is crucial for patient management, surveillance, and differentiating CJD from other treatable conditions. Diagnosis relies on a combination of clinical evaluation, neurological testing, and laboratory investigations. The diagnostic criteria for CJD vary based on the certainty of the diagnosis and the type of CJD. This article outlines the established diagnostic criteria for sporadic, iatrogenic, and familial CJD.
Diagnostic Criteria for Sporadic CJD
Sporadic CJD (sCJD) is the most common form, accounting for approximately 85% of cases. Diagnosis is categorized into definite, probable, and possible sCJD based on the strength of evidence.
Definite Sporadic CJD
Definite sCJD requires neuropathological confirmation. This is achieved through:
- Standard Neuropathological Techniques: Examination of brain tissue post-mortem to identify characteristic CJD-related changes.
- Immunocytochemistry: Utilizing antibodies to detect the abnormal prion protein (PrP) associated with CJD in brain tissue.
- Western Blot: Detecting protease-resistant PrP in brain tissue, a hallmark of CJD.
- Scrapie-Associated Fibrils: Identification of these unique fibrils in brain tissue using electron microscopy.
Probable Sporadic CJD
Probable sCJD diagnosis is made based on clinical and laboratory findings in living patients. The criteria include:
Option 1:
- Neuropsychiatric Disorder with a positive Real-Time Quaking-Induced Conversion (RT-QuIC) assay in cerebrospinal fluid (CSF) or other tissues. RT-QuIC is a highly sensitive test that detects misfolded prion protein.
Option 2:
- Rapidly Progressive Dementia
- At least two of the following four clinical features:
- Myoclonus: Sudden, involuntary muscle jerks.
- Visual or Cerebellar Signs: Visual disturbances, incoordination, and balance problems.
- Pyramidal/Extrapyramidal Signs: Muscle weakness, spasticity, rigidity, and movement disorders.
- Akinetic Mutism: Severe reduction in movement and speech.
- Positive Result on at least one of the following laboratory tests:
- Typical Electroencephalogram (EEG): Periodic sharp wave complexes on EEG, although this may not be present in all cases or at all stages.
- Positive 14-3-3 CSF Assay: Detection of the 14-3-3 protein in CSF, indicative of rapid neuronal destruction (especially in disease duration less than 2 years).
- High Signal on Magnetic Resonance Imaging (MRI): Hyperintensity in the caudate nucleus and putamen (basal ganglia) or in at least two cortical regions (temporal, parietal, occipital) on DWI or FLAIR sequences. MRI is a crucial neuroimaging tool in CJD diagnosis.
- Exclusion of Alternative Diagnoses: Routine investigations must not suggest another condition that could explain the clinical presentation.
Possible Sporadic CJD
Possible sCJD is considered when clinical features are suggestive but lack sufficient laboratory confirmation for a “probable” diagnosis. Criteria include:
- Progressive Dementia
- At least two out of the four clinical features (Myoclonus, Visual or Cerebellar signs, Pyramidal/Extrapyramidal signs, Akinetic Mutism) as listed for probable CJD.
- Absence of “Probable” CJD Tests: Not meeting the laboratory criteria for probable CJD (negative or not performed EEG, 14-3-3, MRI, RT-QuIC).
- Disease Duration Less Than Two Years
- Exclusion of Alternative Diagnoses: Routine investigations do not point to an alternative diagnosis.
Diagnostic Criteria for Iatrogenic CJD
Iatrogenic CJD (iCJD) arises from medical procedures involving human-derived materials. It is a rare form, accounting for about 1% of CJD cases.
- Progressive Cerebellar Syndrome in a recipient of human cadaveric-derived pituitary hormone.
- Sporadic CJD criteria met AND documented recognized exposure risk, such as neurosurgery with dura mater implantation, or other procedures involving potential prion-contaminated materials.
Diagnostic Criteria for Familial CJD
Familial CJD (fCJD) is linked to inherited genetic mutations in the prion protein gene (PRNP). It accounts for 5-15% of CJD cases.
- Definite or Probable CJD AND Definite or Probable CJD in a first-degree relative.
- Neuropsychiatric disorder AND disease-specific PRNP gene mutation. Genetic testing is essential for confirming familial CJD.
Accurate application of these diagnostic criteria is essential for the identification and classification of CJD cases, contributing to surveillance efforts and research into this devastating disease. Differential diagnosis is also critical to rule out other conditions that may mimic CJD, ensuring patients receive appropriate management.
