Case Presentation: 62-year-old Caucasian female with no significant medical history presented with complaint of worsening generalized weakness, difficulty with word finding, blurred vision, left arm and leg weakness ongoing for 3-4 weeks. 3 weeks ago she was discharged from an outside hospital after evaluation for similar complaints. Since discharge had worsening weakness, and decided to come to our facility due to new onset slurred speech. Neurological exam revealed intact cranial nerves II-XII , normal motor strength and 2/4 deep tendon reflexes in both upper and lower extremities. Sensory exam revealed decreased sensations to light touch, pin prick, and vibration in both feet. Gait was wide based without ataxia. Initial CT angiogram of the brain, neck and cervical spine and MRI with and without contrast of brain was unremarkable. She had continued worsening of symptoms along with low grade fever and dysphagia. She became non-verbal and had myoclonic jerking of upper extremities. Repeat EEG showed lateralized periodic discharges. Due to fever and neurological symptoms CSF studies for herpes family viruses, cryptococcal Ag, Lyme Ab, VDRL and Mayo clinic autoimmune encephalopathy studies were negative. Metabolic encephalopathy work up including TSH, B12, Folate, NH3, Thiamine, Vitamin E and copper were negative. Low grade fever evaluation with extensive imaging were normal. Serum HIV, ANA, Lyme disease, Rickettsia, Rocky Mountain Spotted fever screen were negative. Due to rapidly progressing dementia along with seizure like activity decision was made to test for Prion disease. Repeat CSF studies were positive for 14-3-3 protein, and Real Time-Quaking-Induced Conversion (RT-QuIC) and T-tau protein >20,000pg/ml(range 0-1149pg/ml) showing 98% likelihood of prion disease. Third MRI of brain after repeat CSF studies did reveal faint cortical hyperintensity concerning for Creutzfeldt-Jakob disease. Due to continued clinical deterioration, the patient was transitioned to hospice and passed away before arrival of results of prion disease studies. No autopsy was performed.

Discussion: Creutzfeldt-Jakob disease (CJD) is the most common of human prion diseases (400-500 cases in USA per year). It is caused by a transformation of the normal cellular prion protein into a disease-causing scrapie prion protein (PrPSc). PrPSc then causes abnormality in other native prion proteins, propagating the disease. PrPSc can form spontaneously (sporadic), acquired through direct contact or inherited through a mutation in the prion protein gene. The most common presentation is that of rapidly progressing dementia. Despite CSF study in our case showing 98% likelihood of prion disease initial MRI imaging(>90% sensitivity and specificity for CJD) were normal.

Conclusions: Our report demonstrates that in cases with high clinical suspicion for prion disease and negative brain MRI, CSF studies for prion disease can still be beneficial.

IMAGE 1: National Prion Disease Pathology Surveillance Center Result