Case Presentation: A 61-year-old female with a complex psychiatric history presented with gait instability after accidental head trauma, which was initially diagnosed as post-concussive syndrome. Over the next month, the patient began to exhibit progressively erratic behavior with angry outbursts, visual hallucinations, tangential speech, poor sleep, and decreased appetite. Initial serum electrolyte and other blood tests were unremarkable and imaging did not reveal any acute abnormalities. Extensive workups for paraneoplastic, autoimmune, and psychiatric etiologies were unrevealing. Several weeks later, a repeat MRI showed diffuse T2 FLAIR hyperintensities and diffusion restriction throughout the basal ganglia, insular cortices, and frontal cortices. Real-time quaking-induced conversion (RT-QuIC) assay, T-tau protein, and analysis of 14-3-3 in the cerebrospinal fluid returned positive. Given the constellation of clinical, biochemical, and imaging findings, a diagnosis of Creutzfeldt-Jakob disease (CJD) was presumed. The patient was admitted under hospice care and passed away a few weeks later.
Discussion: CJD remains a difficult diagnosis of exclusion antemortem but should be considered in patients with unexplained rapid neurodegeneration and psychiatric symptoms. Diagnosis is challenging due to the condition’s rarity, which is expected to occur in 1-2 cases per million people each year. While the majority of cases are sporadic, reports have been linked to acquired causes and inherited mutations in the prion protein gene, PRNP. Many clinical features are nonspecific and mimic common neurological conditions such as stroke, encephalitis, Alzheimer’s dementia, and other metabolic or toxic encephalopathies. Hallmarks of CJD include myoclonic jerks, rapidly progressive dementia, and cerebellar disturbances. A comprehensive concurrent workup must be completed for other etiologies including hypoglycemia, stroke, tumors, hydrocephalus, B12 deficiency, metabolic encephalopathies, infectious etiologies such as HIV, Syphilis, Lyme, psychiatric etiologies, and neurodegenerative disorders such as Alzheimer’s and Lewy-Body Dementia.Postmortem brain biopsy is the only way to confirm CJD, but diagnostic tools such as the biomarkers 14-3-3 protein, T-tau, and RT-QuIC can aid in diagnosis. 14-3-3 proteins are expressed in the brain and are thought to be involved in neural signaling and cell cycle regulation. Increased concentrations of 14-3-3 in the CSF have a sensitivity of 90% and specificity of 80% for CJD. Newer modalities include RT-QuIC which detects misfolded prion protein (PrP) in the CSF. This is often used in conjunction with 14-3-3 due to its high sensitivity and specificity of 92% and 100% respectively. Despite the high sensitivity and specificity of 14-3-3 and RT-QuIC, they should only be used when clinical suspicion is high and other diagnoses have already been evaluated.
Conclusions: CJD is a rare, untreatable, and rapidly progressive fatal neurodegenerative disease. Although there are findings and tests to suggest CJD, a post-mortem brain biopsy is required for a definitive diagnosis. As a result, CJD often remains a diagnosis of exclusion requiring a degree of suspicion and prompt but thorough evaluation. While workup for common etiologies is being conducted, CJD should continue to be on the differential in patients with unexplained encephalopathy, neurodegeneration, or psychiatric symptoms.