Possible Early Symptom of Creutzfeldt-Jakob Disease Identified

People who died with sporadic Creutzfeldt-Jakob disease were more likely to have been prescribed antidepressants before neurologic symptoms started, a retrospective study in Austria showed.

Compared with controls in the general population, patients with sporadic Creutzfeldt-Jakob disease had higher odds of being prescribed selective serotonin reuptake inhibitors (SSRIs) in the year preceding disease onset (18.6% vs 8.2%, OR 2.86; 95% CI 1.63-4.95, P

The higher prescription rates of SSRIs could be observed as early as 3 years before symptom onset — the difference mediated by sporadic Creutzfeldt-Jakob diagnosis, the researchers said in JAMA Neurology.

“This indicates a higher prevalence of mood disturbances or depressive symptoms, which represent the main indication for SSRIs,” Cetin and co-authors wrote.

“Mood alterations may be a common prodromal feature of sporadic Creutzfeldt-Jakob disease,” they added. “Although sporadic Creutzfeldt-Jakob disease remains an extremely rare cause of mood alterations, increased vigilance for neurodegenerative diseases in this setting could eventually help to extend the diagnostic window.”

Creutzfeldt-Jakob disease is a rare, rapidly worsening brain disorder caused by misfolded prion proteins. It can be diagnosed definitively only at autopsy.

Sporadic disease accounts for about 85% of all Creutzfeldt-Jakob cases. The remaining cases are attributed to either genetic, iatrogenic, or variant disease like bovine spongiform encephalopathy (“mad cow” disease).

The etiology and pathogenesis of sporadic Creutzfeldt-Jakob disease are elusive, the researchers noted.

“The initial presentation typically includes dementia and neurological symptoms such as ataxia, myoclonus, and gait abnormalities as well as behavioral changes,” Cetin and co-authors wrote. Sporadic Creutzfeldt-Jakob disease progresses quickly, and patients have an average survival time of 6 to 8 months from symptom onset.

Despite extensive research, little is known about the disease’s prodromal phase. “A longitudinal study in asymptomatic carriers of a variant causing genetic Creutzfeldt-Jakob disease could not identify characteristic radiological changes until clinically obvious symptoms were present,” Cetin and colleagues observed.

“However, a long preclinical or prodromal phase is common in other neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis,” they pointed out. “Gaining deeper insight into the prodromal phase of sporadic Creutzfeldt-Jakob disease is crucial as it can contribute to earlier diagnosis and improved patient care.”

The case-control study involved 129 patients with autopsy-confirmed sporadic Creutzfeldt-Jakob disease who were matched with 1,350 controls on sex, age at disease onset (index date), and area of residence.

Cases were collected from 2013 through 2020 at the Austrian Reference Center for Human Prion Diseases, which receives all suspected cases in the country. Autopsy is mandatory by law in Austria if sporadic Creutzfeldt-Jakob disease is suspected.

Pharmaceutical records included all drugs prescribed by a physician and dispensed by a pharmacy in the 5 years before the index date. Information about over-the-counter drugs or drugs administered during inpatient stays was not available.

Patients had a median survival time of 3.6 months. Mean age was about 69 years, and 51.9% of the study sample was female.

One limitation of the study was that atypical presentations of sporadic Creutzfeldt-Jakob disease may have been missed, the researchers acknowledged. Additionally, over-the-counter medications were not included, they cautioned, but SSRIs can be obtained only by prescription in Austria.