By Ringhauser, Holly DO; Glantz, Sanford MD; Havasy, Stephen P. MD
A 74-year-old woman presented to the emergency department with altered mental status for one week. The patient's husband said the patient had been in her usual state of health until seven days earlier, when she got lost on the way home from a restaurant that she had frequented for several decades. She had become increasingly confused and unable to care for herself, and was now unable to finish a sentence or ambulate without assistance. The patient had been seen by her primary physician and a neurologist. She had blood work, a CT scan, and an MRI performed, but her husband was not yet aware of the results of these tests.
The patient's past medical history was significant for hypertension and hypercholesterolemia, and her medications included enalapril and ezetimibe with no recent changes in dose or frequency. The patient's husband said the patient did not smoke, drink alcohol, or use any illicit drugs, and he denied any recent travel or sick contacts.
The patient's initial vital signs were within normal limits with the exception of mild hypertension (155/59 mm Hg). Her rectal temperature was 99.2°F, and she remained afebrile throughout her workup. She was confused and disoriented. She answered questions inappropriately and nonsensically. She could follow simple commands, such as opening or closing her eyes, but was unable to follow more complicated instructions, such as putting her finger to her nose. She was tremulous throughout the exam. Her gait was not formally tested, but patient's husband described a wide-based, staggering, and uncoordinated gait. The remainder of her exam was normal with the exception of 1+ pitting edema to the mid-calf bilaterally.
The patient's labs revealed the following:
The patient was evaluated in the ED by her neurologist, who recommended performing an LP to send CSF for cell count, gram stain, culture, cryptococcal antigen, AFB, and 14-3-3 protein. The patient was admitted to the hospital, and the EP requested psychiatry and physical therapy consults. The patient had an EEG the following day, which was abnormal with background slowing and periodic to pseudoperiodic sharp-wave discharges, consistent with Creutzfeldt-Jakob disease.
The outpatient MRI was reviewed by neurology, which noted increased cortical ribboning, particularly on FLAIR sequence. The patient developed akinetic mutism and startle myoclonus over the next 72 hours. Her mental status and ability to ambulate continued to deteriorate rapidly during her stay in the hospital, and the patient was ultimately transferred to a skilled nursing facility for hospice care. CSF samples were sent to the National Prion Disease Pathology Surveillance Center in Cleveland, and were found to be positive for 14-3-3 protein and Tau protein, which is consistent with Creutzfeldt-Jakob disease.
Rapidly progressive dementia can be caused by a number of conditions, including human prion diseases. Creutzfeldt-Jakob disease is a neurodegenerative transmissible spongiform encephalopathy caused by a prion, and it is categorized as sporadic or variant. (J Neurol Neurosurg Psychiatry 2001;79:744.) The sporadic form of Creutzfeldt-Jakob disease (sCJD) is the most common prion disorder in humans (Infect Dis Rep 2013;5:e10), and is characterized by rapidly progressive dementia, ataxia, visual disturbances, myoclonus, and extrapyramidal features. (Neurology 2012;79:547.)
sCJD is caused by prion proteins that undergo conformational changes, causing spongiform encephalopathy. (J Neurol Neurosurg Psychiatry 2001;79:744.) The estimated worldwide incidence is 1:1,000,000 (Neurology 2012;79:1499), and human-to-human transmission can occur via direct tissue implantation, use of contaminated medical instruments, administration of contaminated human hormones, and via contaminated blood products. (Infect Dis Rep 2013;5:34.) CJD has no cure, and it is universally fatal.
Histopathologic diagnosis can be performed on brain biopsy samples or at autopsy, but that exposes the pathologist to infectious materials. Several guidelines have been proposed to aid in the diagnosis using less invasive means. The World Health Organization guidelines for diagnosis include progressive dementia with two of the following: myoclonus, pyramidal/extrapyramidal deficits, visual/cerebellar deficits, or akinetic mutism, plus EEG findings of 1-2 Hz periodic pattern or positive 14-3-3 protein and no other explanation for deficits. (Centers for Disease Control and Prevention, 2013; http://www.cdc.gov/ncidod/dvrd/cjd/.)
MRI also plays a significant role in diagnosis because it is reflected in diagnostic guidelines from the University of San Francisco and the European MRI- CJD Consortium. (Neurology 2012;79:1499.) It is important to exclude the numerous alternative diagnoses that may be treatable or curable, such as multiple sclerosis, status epilepticus, Lewy body dementia, Alzheimer's disease, Parkinson disease, sepsis, tuberculosis, lupus, and certain psychiatric disorders, to name a few. (Neurology 2012;79:1499.)
Altered mental status is a common chief complaint in the ED, and the differential diagnosis is broad. Our patient's symptoms of myoclonus, akinetic mutism, ataxia, and tremor are consistent with the WHO criteria for CJD. She was also found to have periodic and pseudoperiodic patterns on EEG, positive CSF biomarkers, and cortical ribboning on FLAIR-MRI. No alternative cause of her symptoms could be found.
It is important to establish this diagnosis because of the potential transmissibility of infectious prions. It is also important to exclude alternative diagnoses that may be treatable or curable.
Dr. Ringhauser is a second-year resident in emergency medicine at Good Samaritan Hospital Medical Center in West Islip, NY. Drs. Glantz and Havasy are emergency physicians at Good Samaritan Hospital Medical Center in West Islip, NY.