How do I diagnose and manage Creutzfeldt‑Jakob disease in a patient over 50 with rapidly progressive dementia, myoclonus, ataxia, and visual disturbances?

Creutzfeldt-Jakob Disease: Diagnosis and Management

Immediate Diagnostic Approach

In a patient over 50 presenting with rapidly progressive dementia, myoclonus, ataxia, and visual disturbances, order MRI brain with DWI and FLAIR sequences immediately, followed by CSF RT-QuIC testing—these two tests together will establish the diagnosis of probable CJD with near-certainty. 1, 2

Key Clinical Features to Confirm

• Rapidly progressive cognitive decline evolving over weeks to months (not years), with median survival of approximately 5 months from symptom onset 3, 1
• Myoclonus, particularly when startled, often with 1:1 correlation to EEG periodic sharp wave complexes 1, 2
• Movement disorders including ataxia, extrapyramidal signs (rigidity), and cerebellar dysfunction 3, 4
• Visual disturbances (Heidenhain variant when isolated visual symptoms predominate) 4, 5
• Progression to akinetic mutism in later stages 3, 6

Diagnostic Testing Algorithm

First-Line Imaging: MRI Brain

MRI with DWI and FLAIR is the optimal initial imaging modality and should be ordered immediately in any patient with suspected rapidly progressive dementia 3, 2. Standard CT is inadequate and should not be relied upon for diagnosis 3.

Characteristic MRI findings include: 3, 2

• T2 hyperintensity and diffusion restriction in cortical regions (particularly frontal, temporal, and parietal lobes, often asymmetric)
• Involvement of basal ganglia (60% of cases, predominantly caudate and putamen)
• Thalamic involvement (13% of cases): "pulvinar sign" or "hockey stick sign"
• Hallmark feature: prominent gray matter involvement with relative sparing of underlying white matter 3

Gold Standard Biomarker: CSF RT-QuIC

CSF RT-QuIC has emerged as the definitive diagnostic test with sensitivity of 94-96% and specificity of 99-100% 1, 2. This test directly detects misfolded prion proteins through real-time quaking-induced conversion 2.

Critical diagnostic point: RT-QuIC positivity alone is now sufficient for a diagnosis of probable sporadic CJD, even when other classical criteria are not fully met 2. This represents a major advancement over older diagnostic criteria that required multiple supporting features.

Additional Supporting Tests

CSF analysis should also include: 3, 2

• 14-3-3 protein (less specific than RT-QuIC but supportive when elevated) 2, 7
• Total tau protein (typically markedly elevated) 2

EEG findings (not required but supportive): 1, 2

• Periodic sharp wave complexes (PSWCs) with 1:1 relationship to myoclonic jerks
• May be absent in atypical cases, so normal EEG does not exclude diagnosis 1

PRNP gene sequencing should be performed in all suspected cases regardless of apparent family history, as approximately 10-15% of cases are genetic (familial CJD) and phenotypic variability can obscure family history 8, 2

Common Diagnostic Pitfalls

Atypical Presentations That Delay Diagnosis

Be aware that CJD can present with isolated symptoms before classic triad develops: 9, 5

• Isolated visual symptoms (Heidenhain variant) 4, 5
• Isolated language/aphasia symptoms 5
• Non-convulsive status epilepticus 5
• Predominantly dysexecutive syndrome mimicking Alzheimer's disease 9
• Psychiatric symptoms as initial presentation 5

In these atypical cases, FDG-PET may show hypometabolism patterns resembling other dementias (particularly dysexecutive variant Alzheimer's), but MRI diffusion restriction and CSF biomarkers will establish the correct diagnosis 9.

Differential Diagnoses to Exclude

Other causes of rapidly progressive dementia that must be considered: 3, 4

• Autoimmune/inflammatory encephalitis (17% of rapidly progressive dementia cases are potentially treatable, with 50% being autoimmune) 3
• Infectious encephalitis (including HIV) 6, 4
• Paraneoplastic syndromes 4
• Toxic-metabolic causes 3
• Other neurodegenerative diseases: dementia with Lewy bodies, frontotemporal dementia, corticobasal degeneration 4

Use IV contrast with MRI to help identify autoimmune and inflammatory etiologies, even though contrast is not specifically needed for CJD diagnosis itself 3.

Management and Prognosis

There is no effective treatment available for CJD; management is entirely supportive and palliative, focusing on symptom control and end-of-life care. 1, 2, 6 No disease-modifying therapies exist, and all cases are universally fatal regardless of intervention 1, 2.

Immediate Management Steps

Once diagnosis is established: 1, 2, 6

• Initiate palliative care consultation immediately
• Enroll patient in hospice services
• Focus on symptom management (myoclonus control, pain management, comfort measures)
• Provide family counseling regarding prognosis and end-of-life planning
• Median survival is approximately 5 months from symptom onset 3, 1

Critical Management Pitfall

Do not pursue experimental therapies outside formal research protocols—this offers false hope and diverts focus from quality end-of-life care 2. The disease is universally fatal, and early identification allows for appropriate palliative intervention rather than futile aggressive treatment 6.

Infection Control Considerations

For iatrogenic transmission prevention: 8

• Standard sterilization does not reliably eliminate prion infectivity
• Approximately 10 successive decontamination cycles are required to reduce infectivity to negligible levels
• Use disposable instruments when possible for neurosurgical procedures
• Follow institutional protocols for handling tissue from confirmed or suspected CJD patients