Hyperacusis as the initial presentation of Creutzfeldt-Jakob disease

Case. A 52-year-old man with diabetes presented with 1 month of hyperacusis and trouble discerning noises, including speech and music. He reported that all sounds, both complex and simple, seemed “jarring” and unfamiliar. He denied tinnitus, falls, or imbalance. Over the ensuing 3 months he developed diffuse myalgias and neck pain. Medical and neurologic examination was normal as was audiometry. Laboratory investigations including erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, anti-Ro, anti-La, anti-Jo, creatine kinase, aldolase, and thyroid function testing were normal. An HIV ELISA test was negative. Brain MRI demonstrated abnormal T2 hyperintensity and gyriform restricted diffusion with corresponding signal on apparent diffusion coefficient images in the bilateral parieto-occipital regions (figure, A). CSF analysis demonstrated white blood cell count 0, protein 60 mg/dL, and no oligoclonal bands. CSF was negative for Lyme antibodies and herpes simplex virus PCR. CSF 14-3-3 protein was negative and the total tau level was normal at 631 pg/mL. Ten months after the onset of hyperacusis, he developed hypophonia, dysarthria, and ataxia. Two months later, examination revealed psychomotor slowing and delayed recall, alexia, agraphia, and difficulty with walking. He retained the ability to discuss current events but could no longer work. A brain biopsy 13 months into his course revealed spongiform changes predominantly affecting the gray matter with marked neuronal dropout and associated gliosis (figure, B). There was no evidence of inflammation, demyelination, vasculitis, or amyloid deposition. The patient died 21 months after initial symptom onset. Immunochemistry performed at the National Prion Surveillance Center at Case Western Reserve University confirmed the presence of the abnormal prion protein and the diagnosis of CJD with the MM2 molecular subtype.