A 57-year-old man is brought to a neurologist by his wife for abnormal behavior. He was normal until around 3 months ago when he started forgetting important meetings and misplacing items around the house. One month ago, the patient was fired from his job as a software engineer after attempting to grope a coworker. The patient expresses frustration that he is no longer able to concentrate enough to enjoy his hobby of solving puzzles. His medical history is significant for gastroesophageal reflux disease for which he takes omeprazole. He has no family history of neurologic disease. His temperature is 98.6°F (37.0°C), blood pressure is 120/75 mmHg, pulse is 70/min, and respirations are 16/min. During the examination, the patient’s cell phone rings unexpectedly causing the patient to suddenly jerk his arms and legs. Further diagnostic investigation is performed which reveals an elevated 14-3-3 protein on cerebrospinal fluid analysis. Which of the following is the most likely diagnosis?
Alzheimer disease
Creutzfeldt-Jacob disease
Frontotemporal dementia
Subcortical leukoencephalopathy
Creutzfeldt-Jacob disease
This patient with rapidly progressive dementia over 3 months, declining executive function, impaired concentration, decreased memory, startle myoclonus (sudden jerking of extremities in response to unexpected stimulus), and elevated 14-3-3 protein levels on cerebrospinal fluid (CSF) analysis most likely has Creutzfeldt-Jakob disease (CJD).

CJD is a human prion disease in which the normal prion protein (PrPc) converts to a beta-pleated sheet disease-associated form (PrPsc) which is resistant to proteases. CJD is usually spontaneous. Rarely, CJD may be familial or acquired (from iatrogenic transmission or dietary exposure). Aggregates of PrPsc lead to spongiform vacuolation. Clinically, this manifests with rapidly progressive mental deterioration with prominent executive dysfunction (declining concentration, judgment, and memory) and startle myoclonus. Further diagnostic investigation may reveal 14-3-3 protein on CSF analysis and synchronous sharp wave complexes on electroencephalogram (EEG). CJD usually leads to death within 1 year. There is no known effective treatment for this disease.

Uttley et al. review the diagnosis, clinical presentation, and epidemiology of Creutzfeldt-Jakob disease (CJD). They discuss how CJD in a global context is increasing in prevalence and how incubation periods as long as 40 years have been observed for iatrogenic cases. They recommend heightened awareness of this disease in order to mitigate iatrogenic transmission.

Incorrect Answers:
Answer A: Alzheimer disease is characterized by gradual cognitive decline with difficulty completing activities of daily living. Impaired executive function early in the disease course, rapidly progressive disease, elevated 14-3-3 protein on CSF analysis, and startle myoclonus are not found in Alzheimer disease.

Answer C: Lewy body dementia (LBD) presents with alterations in consciousness, disorganized speech, visual hallucinations, extrapyramidal symptoms, and early compromise of executive function. Although this patient’s dementia is characterized by early compromise of executive function, the absence of fluctuating levels of consciousness, absence of extrapyramidal symptoms, and presence of startle myoclonus make CJD more likely than LBD.

Answer D: The behavioral variant of frontotemporal dementia (FTD) is associated with early-onset personality and behavioral changes, and it may be associated with extrapyramidal symptoms. Memory is not usually affected until late in the disease course.

Answer E: Subcortical leukoencephalopathy (Binswanger disease) is a type of small vessel vascular disease that presents with prominent subcortical dementia. This manifests clinically as slowed mental processing, impaired cognition, apathy, and depression. This disease almost always presents in the context of chronic hypertension and is usually seen in older patients.

Bullet Summary:
Creutzfeldt-Jacob disease is a fatal prion disease that presents with sudden-onset and rapidly progressive dementia and startle myoclonus or seizures.