Case Presentation: A 53-year-old female with no medical history presented with worsening mental status for 3 months. All history was given by family. Three months prior to presentation she began experiencing a generalized, persistent headache. A neurologist prescribed nortriptyline for presumed migraines, with improvement. In the month prior to presentation, the patient had become less talkative, and in the last two weeks her memory, cognition, and oration all drastically declined. Family first brought her to the ED when they found her nortriptyline bottle empty a few days before refill. She was treated for TCA overdose with some improvement, and discharged home. Days later, the patient was brought back after becoming unresponsive. Although the patient was unable to participate or cooperate with exam, she was alert, slowly attentive, oriented to self, and moving all extremities spontaneously. She withdrew to painful stimuli and exhibited myoclonus, but no focal neurologic deficits. Labs were unremarkable, and a nortriptyline level was normal. Initial brain MRI was read as normal. Infectious work up including HIV, VZV, CMV, HSV, Lyme, Cryptococcus and inflammatory markers were all normal. EEG showed non-convulsive status epilepticus (NSCE). Results from initial CSF was unremarkable with a a 14-3-3 protein pending. Repeat MRI showed FLAIR hyperintensities in bilateral basal ganglia suggestive of Creutzfeldt-Jakob Disease (CJD). The 14-3-3 lab returned positive, which was corroborated by the National Prion Disease Center, and a diagnosis of CJD was confirmed.
Discussion: Altered mental status (AMS) is a common problem encountered by the hospitalist. When assessing AMS it is important to distinguish chronicity and cognitive baseline. The three broad categories of AMS are toxic-metabolic, psychiatric, and neurological. Underlying neurocognitive defects, such as dementia, sometimes obscure the true etiology of the presentation. In such cases, it is critical to focus on the most salient features of the case to guide diagnostic evaluation. CJD is a form of prion disease. It is a rare, rapidly degenerative dementia that is caused by the accumulation of misfolded protein. CJD is separated into sporadic (accounting for ~85% of cases), iatrogenic, familial, and variant form. Sporadic CJD is age dependent with the highest rate of mortality in the 60-79 age group and an incidence of one in a million. CJD can presents with a nonspecific prodrome involving headaches in about 10% of cases . Myoclonus is seen in a significant subset of patients. In cases of sporadic CJD seizures occur in 15% of patient but they occur later in the disease process, however only a few cases of NCSE have been described in the literature. Patients tend to live 6-12 months after the initial clinical symptoms appear. The CSF 14-3-3 assays has a sensitivity of 92% and specificity of 80%. While FLAIR hyperintensities in the basal ganglia have a sensitivity of 67% and specificity of 93%. Although the gold standard for diagnosis is a tissue specimen, the nature of the disease and virility of the prions makes this a rare occurrence. In accordance with the CDC, a probable diagnosis is made based on clinical criteria in conjunction with laboratory findings, as in this case.
Conclusions: This case demonstrates classic (rapidly progressive dementia) and atypical (NCSE and headache) features of CJD, an exceedingly rare cause of AMS. Diagnosis requires a high degree of suspicion, with specific features in the history, labs, and imaging that should not be missed.