Characteristics of established and proposed sporadic Creutzfeldt-Jakob disease variants.
BACKGROUND
The classic Creutzfeldt-Jakob disease (CJD), Heidenhain, and Oppenheimer-Brownell variants are sporadic CJD (sCJD) phenotypes frequently described in the literature, but many cases present with neuropsychiatric symptoms, suggesting that there may be additional sCJD phenotypes.


OBJECTIVE
To characterize clinical, diagnostic, and molecular features of 5 sCJD variants.


METHODS
Retrospective analysis.


METHODS
The Johns Hopkins and Veterans Administration health care systems.


METHODS
Eighty-eight patients with definite or probable sCJD.


METHODS
Differences in age at onset, illness progression, diagnostic test results, and molecular subtype.


RESULTS
The age at onset differed among sCJD variants (P = .03); the affective variant had the youngest mean age at onset (59.7 years). Survival time (P < .001) and the time to clinical presentation (P = .003) differed among groups. Patients with the classic CJD phenotype had the shortest median survival time from symptom onset (66 days) and those who met criteria for the affective sCJD variant had the longest (421 days) and presented to clinicians significantly later (median time from onset to presentation, 92 days; P = .004). Cerebrospinal fluid analyses were positive for 14-3-3 protein in all of the affective variants, regardless of illness duration. Periodic sharp-wave complexes were not detected on any of the electroencephalography tracings in the Oppenheimer-Brownell group; basal ganglia hyperintensity was not detected on brain magnetic resonance imaging in this group either. All of the Heidenhain variants were of the methionine/methionine type 1 molecular subtype.


CONCLUSIONS
The classic CJD phenotype and the Heidenhain, Oppenheimer-Brownell, cognitive, and affective sCJD variants differ by age at disease onset, survival time, and diagnostic test results. Characteristics of these 5 phenotypes are provided to facilitate further clinicopathologic investigation that may lead to more reliable and timely diagnoses of sCJD.
Appleby
Brian S
BS
Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. bappleb1@jhmi.edu
Appleby
Kristin K
KK
Crain
Barbara J
BJ
Onyike
Chiadi U
CU
Wallin
Mitchell T
MT
Rabins
Peter V
PV
D048948:14-3-3 Proteins / Q000032:analysis / Q000134:cerebrospinal fluid; D017668:Age of Onset; D000368:Aged; D001479:Basal Ganglia / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification / Q000175:diagnosis* / Q000401:mortality*; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
D048948:14-3-3 Proteins; D015415:Biomarkers