What test would most likely be abnormal in a patient with progressive neurological deterioration, including slowing of speech, worsening memory, personality changes, disorientation, confusion, resting tremors, and a coma-like state with myoclonus?

CSF RT-QuIC for Misfolded Prion Proteins Would Most Likely Be Abnormal

This patient's clinical presentation is classic for sporadic Creutzfeldt-Jakob disease (CJD), and CSF RT-QuIC testing to identify misfolded prion proteins would be the most likely abnormal test among the options provided. 1

Clinical Presentation Strongly Suggests CJD

The patient demonstrates the hallmark features of sporadic CJD:

• Rapidly progressive dementia with personality changes and memory impairment evolving over weeks to months 1
• Movement disorders including resting tremors and myoclonus (particularly when startled) 1
• Rapid deterioration to a coma-like state within three months, consistent with the median survival of approximately 5 months for sporadic CJD 1, 2
• Disorientation and confusion progressing to akinetic mutism 1

This constellation of rapidly progressive dementia, myoclonus, and progression to coma is pathognomonic for prion disease, which represents the most common cause of rapidly progressive dementia (62% of cases in specialized centers) 1

Why CSF RT-QuIC Is the Correct Answer

CSF RT-QuIC has emerged as the gold standard biomarker for CJD diagnosis:

• Excellent diagnostic accuracy with sensitivity ranging from 73-97% and specificity of 99-100% across multiple studies 1
• Second-generation RT-QuIC protocols demonstrate sensitivity of 94-96% with maintained 100% specificity 1
• RT-QuIC positivity alone is now sufficient for a diagnosis of probable sCJD according to amended diagnostic criteria, even when other classical criteria are not fully met 1
• The test directly detects misfolded prion proteins (PrPSc) through real-time quaking-induced conversion 1

The Lancet Neurology guidelines explicitly state that "progressive neuropsychiatric syndrome and positive RT-QuIC in CSF or other tissues" establishes a diagnosis of probable CJD 1

Why Other Tests Would Be Normal

Blood cultures for Cryptococcus neoformans would be inappropriate because:

• Cryptococcal meningoencephalitis typically occurs in immunocompromised patients 1
• The presentation would include fever, headache, and CSF pleocytosis 1
• This patient's rapid progression to coma with myoclonus is inconsistent with cryptococcal disease

CSF cultures for Coccidioides immitis would not be positive because:

• Coccidioidomycosis is geographically restricted and requires specific exposure history 1
• The clinical course would be more subacute with fever and meningeal signs 1

PCR for HSV-1 would be negative because:

• HSV encephalitis presents with fever (91% of cases), speech disturbances, and behavioral changes but typically shows temporal lobe involvement on imaging 1
• The progression to coma with prominent myoclonus and the three-month timeline are atypical for HSV encephalitis 1
• HSV encephalitis does not characteristically cause the diffuse cortical and basal ganglia involvement seen in CJD 1

Serology for Taenia solium would be negative because:

• Neurocysticercosis presents with seizures and focal neurological deficits related to cyst location 1
• The rapidly progressive dementia with myoclonus is not characteristic of neurocysticercosis
• Imaging would show characteristic cystic lesions, not the diffusion restriction in gray matter structures typical of CJD 1

Supporting Diagnostic Features

Additional testing that would support the CJD diagnosis includes:

• MRI brain with DWI and FLAIR sequences showing T2 hyperintensity and diffusion restriction in cortical regions, caudate, and putamen (60% involvement of basal ganglia) 1, 2
• EEG potentially showing periodic sharp wave complexes (PSWCs) with 1:1 relationship to myoclonic jerks 1
• CSF 14-3-3 protein elevation (>20,000 AU/mL) and total tau elevation (>1,300 pg/mL), though these are less specific than RT-QuIC 1

Critical Diagnostic Pitfall

The most important pitfall to avoid is dismissing CJD based on atypical features or incomplete classical criteria. The Lancet Neurology emphasizes that RT-QuIC positivity can establish probable CJD even when traditional WHO criteria are not fully met 1. Approximately 17% of rapidly progressive dementia cases have potentially treatable etiologies, making thorough evaluation essential, but this patient's specific presentation of rapid progression with myoclonus and coma makes CJD overwhelmingly likely 1