A case of Creutzfeldt-Jakob disease: diagnostic dilemmas of a rapidly fatal disease
A 66 yr old male was admitted to the hospital following a fall on 12/29/2011. The fall was under strange circumstances wherein he felt sudden vertigo sensation while shutting his car door. He sustained an intertrochanteric fracture of hip during the fall. His initial evaluation indicated that he had profound dysmmetria in both upper extremities and absent proprioception. Further discussion with patient’s wife, indicated he had problems with balance since 2 months prior to presentation. He saw an otorhinolaryngologist for the same and underwent canolith repositioning procedure with the presumed initial diagnosis of benign positional vertigo. She felt that his balance problems had gotten worse since then.\nDuring post operative course of hip surgery patient spiked temperature and also had mental status changes. A lumbar puncture was done and meningeal infection was rule out. CSF was also sent for 14-3-3 assay along with complete paraneoplastic panel. He was then also noted to have slurred speech. An MRI of the brain was done which showed on FLAIR (fast fluid attenuated inversion recovery) images that there were T2 hyper intense signal changes and restricted diffusion in the bilateral basal ganglia(caudate and putamen nuclei) and right frontal cortex (). Although the official radiology report stated the diagnosis as basal ganglia infarct, teleradiology service hinted at the possibility of CJD along with toxic/metabolic encephalopathy. EEG revealed diffuse slowing but no sharp wave activity. Patients fever subsided but he continued to have severe ataxia.\nBased on the CDC criteria (), since patient had cerebellar problem with myoclonus and also MRI findings a diagnosis of probable CJD was made. Brain biopsy was suggested so that definitive diagnosis of CJD could be made but family refused. Patient was then send to inpatient rehab unit to work on balance and coordination while being closely followed by medicine service.\nIn the Rehab Unit patient had more myoclonus, a kinetic mutism along with worsening cognitive decline. Repeat MRI was obtained which did reveal changes of CJD more clearly. By this time his CSF immunoassay was positive for 14-3-3 protein and a diagnosis of CJD was established. When the diagnosis was told to family they choose palliative care, patient was then discharged to home with hospice. Patient expired 5 days after discharge to home.\nAutopsy an performed at University of Chicago Medical center revealed spongiform changes in basal ganglia, thalamus, substantia nigra and cerebellum with relative cortical sparing (). The spongiform changes in cerebellum were associated with atrophic changes in internal granular layer and Purkinje cell layer (). The morphologic changes fitted into one of the strains associated with relative cortical sparing and more prominent basal ganglia/cerebellar disease. Immunohistochemical exam done at National Prion Disease Pathology Surveillance Center, Cleveland (USA) confirmed sporadic CJD of VV2 type. The VV2 phenotype was based on molecular subtype determined by PRNP genotype and pathologic prion protein according to classification of sporadic CJD proposed by Parchi et al. VV2 is an ataxic variant which has ataxia at onset in 15% and has longer duration of illness. The PrP gene sequencing ruled out the presence of pathogenic mutation in the coding region of PrP gene and further abnormal prion protein type was characterized by Western Blot.