How to Distinguish Creutzfeldt-Jakob Disease from Progressive Multifocal Leukoencephalopathy when the Cerebrospinal Fluid Fails

Abstract

Introduction: Creutzfeldt-Jakob disease is a spontaneous neurodegenerative disease secondary to the accumulation of misfolded prion proteins depositing in neurons. Clinical findings include rapidly progressive dementia, myoclonus, sharp waves on EEG, and an akinetic mutism state. Creutzfeldt-Jakob disease is often mistaken for progressive multifocal leukoencephalopathy as the afflictions share many of the same symptoms; however, given the extremely high mortality rate of Creutzfeldt-Jakob disease, an accurate and early diagnosis is imperative. This is a case report of a patient misdiagnosed with progressive multifocal leukoencephalopathy and later found to have sporadic Creutzfeldt-Jakob disease via diagnosis after MRI. Case Presentation: A 62-year-old male with no significant past medical history presented for evaluation of rapidly progressive dementia and decreased oral intake. Four months prior at baseline, the patient was healthy and athletic but began experiencing dizziness and increasing falls. Imaging done two months prior to admission indicated Creutzfeldt-Jakob disease; however, after multiple examinations, the patient was diagnosed with progressive multifocal leukoencephalopathy via positive Human polyomavirus 2 (JC virus) serum and cerebrospinal fluid PCR tests. During a hospital stay, the progression of the condition led to failure to thrive and urinary and bowel incontinence. Upon resolution of the patient’s acute kidney injury, the patient underwent an MRI of the brain which showed restricted diffusion/cortical ribbon sign in bilateral bifrontal cortical gyri and restricted diffusion in the bilateral basal ganglia and pulvinar. "Hockey-stick sign" with restricted diffusion in the bilateral basal pulvinar and dorsal medial thalamus was also noted. These changes are consistent with the sporadic form of Creutzfeldt-Jakob disease. The patient was discharged home with palliative care. Conclusion: This case underlies the importance of rapid diagnosis and differentiation between progressive multifocal leukoencephalopathy and Creutzfeldt-Jakob disease as either has different morbidity and mortality risks. Studies have shown that stratifying the different types of rapidly progressive neurodegenerative conditions is influenced by hesitance to make a diagnosis with no treatment option versus diagnoses with viable treatment options. Biopsy remains the gold standard of diagnosis for JC virus; however, clinical imaging and cerebrospinal fluid PCR are more commonly used for the diagnosis due to their high specificity. These tests have a lower sensitivity, in which case, patients are often definitively diagnosed with biopsy ante or post-mortem. This case was characterized by clinical suspicion for Creutzfeldt-Jakob disease, but lack of access to medical records delayed repeat MRI and allowed the progression of the disease under the diagnosis of JC virus. Of note, there are no reported cases in the literature of false positive cases of JC virus which is representative of the high specificity of the tests.