COMMENTARY

A Tale of Two Patients: A Prion Disease 30 Years Later

Andrew N. Wilner, MD

Disclosures

September 19, 2017

A Memorable Case

Thirty years ago, I cared for a patient in his early 60s who presented with a rapidly progressive dementia suggestive of Creutzfeldt-Jakob disease (CJD). He had ataxia, akinetic mutism, and a field cut. It was the first time I witnessed "stimulus myoclonus," or myoclonus triggered by an external stimulus.

The patient was all the more memorable because it was my job as a junior resident to perform the lumbar puncture. As cerebrospinal fluid (CSF) can transmit this fatal prion disease, the senior resident advised me to double glove. (It would be 10 years later before Stanley Prusiner would receive the Nobel Prize for his discovery of prions, unique infectious misfolded proteins).

The CSF sample revealed no evidence of encephalitis or meningitis but did contain 14-3-3 protein, a feature of CJD. CT scan was unremarkable, and we didn't yet have MRI. Along with the patient's clinical course and periodic sharp/slow complexes on electroencephalogram (EEG), we made the diagnosis of CJD. The patient died shortly thereafter.

Thirty Years Later

CJD occurs in only 1 in a million people, and it would be 30 years before I saw another case. Last month my neurology team admitted a woman in her 60s who had become confused. Prior to admission, she had lived alone and taken the bus to work every day. According to her sister, her normally tidy house had become a mess, and she was hallucinating, seeing children, deceased relatives, and elephants.

Over the next few days, the patient became fearful, tremulous, and withdrawn. She occasionally uttered a word but did not follow commands. A toxic-metabolic work up for encephalopathy was negative. CSF, this time obtained under fluoroscopy in the radiology department, contained the 14-3-3 protein and no evidence of bacterial or viral infection. EEG demonstrated periodic sharp/slow complexes. MRI diffusion-weighted imaging sequence revealed "cortical ribboning," a characteristic feature of CJD unknown in 1987.

A brand new CSF test, the real-time quaking-induced conversion (RT-QuIC), 100% sensitive and specific, confirmed the diagnosis.[1] The patient continued to deteriorate and died less than a month after admission.

Conclusions

CJD is thankfully rare. Technological advances in MRI over the last few decades have improved diagnostic accuracy. The recent availability of RT-QuIC promises to extinguish any lingering doubt in questionable cases without resorting to biopsy. Since my residency days, much has been learned about the mysterious prion. Unfortunately, patients diagnosed with CJD still face the same dismal prognosis.

As articulated by the Nobel Assembly at the Karolinska Institute in 1997, the discovery of the prion, "establishes a foundation for drug development and new types of medical treatment strategies." However, effective treatments for prion disease still await improved understanding of this unique proteinaceous infectious pathogen.

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