Case Presentation: A 57-year-old male patient with a previous history of alcohol use was brought in by his family for progressive myoclonus and confusion. At baseline, this patient performed activities of daily living with ease. He had no history of neurologic disorders, however his mother had been diagnosed with dementia in her 70s. Over the preceding two weeks, the patient developed intermittent clonus and posturing of the right upper extremity, increased muscle tone of the right upper and lower extremities and mild right-sided dysmetria. With an outpatient neurologist, the patient underwent EEG, which revealed evidence of seizure activity at the left temporal area, prompting his visit to the hospital. Based on his EEG findings, the patient was initially started on acyclovir for empiric coverage of herpes simplex encephalitis. A lumbar puncture revealed normal cell counts and negative Gram stain, making CSF infection less likely. CSF found elevated glucose and protein, however was negative for oligoclonal bands. Fosphenytoin, followed by valproate were started to control seizure activity. The patient underwent further extensive vasculitis, paraneoplastic, autoimmune, and heavy metal toxicity evaluation, which returned negative. The patient was started on a 5-day course of IVIg and corticosteroids for empiric treatment of autoimmune encephalitis, without clinical improvement. EEG was then performed which found triphasic waveforms, prominent in the left hemisphere, and moderate asynchronous bihemispheric slowing. FLAIR and DWI MRI imaging found diffuse cortical diffusion restriction involving the left cerebral hemisphere as well as the caudate nuclei, favoring the diagnosis of Creutzfeldt-Jakob Disease (CJD), although his CSF 14-3-3 protein level was negative. The patient continued to decline, with progressive loss of concentration, worsening dyskinesia and mutism, and was ultimately referred to inpatient hospice.
Discussion: CJD can be a diagnostic challenge for hospitalists because the gold standard for diagnosis is brain biopsy, which itself may not be definitive because not all regions of the brain may show histologic evidence of disease. According to the World Health Organization, elevated protein 14-3-3 CSF level, DWI and FLAIR MRI imaging findings of abnormal signal hyperintensity in the caudate nucleus or putamen and EEG findings of periodic sharp wave complexes in the context of myoclonus, cerebellar signs, akinetic mutism or pyramidal signs lend high probability to the diagnosis of CJD. Although elevated protein 14-3-3 CSF levels have been found to have a 92% sensitivity and 80% specificity for CJD, absence of this protein cannot be used to rule out CJD as a diagnosis, thus it is important to examine all diagnostic modalities for patients who have a high pre-test probability of CJD.
Conclusions: Hospitalists who consider CJD in their differential diagnosis for patients presenting with rapidly progressive dementia must complete its diagnostic modalities in their entirety to avoid misdiagnosing this fatal disease.