Initial diagnoses of patients ultimately diagnosed with prion disease.

BACKGROUND: Prion diseases are rapidly progressive neurodegenerative diseases that frequently mimic other forms of dementia making them difficult to diagnose. OBJECTIVE: To explore factors associated with the initial diagnoses of cases later determined to be caused by prion disease in an attempt to recognize key clinical variables that impact the timely diagnosis of prion disease. METHODS: A retrospective chart review performed at Johns Hopkins Medicine and the Department of Veterans Affairs Health Care System (1995-2008) was conducted. Ninety-two subjects with definite or probable prion disease were included in the analyses. Demographic, clinical, diagnostic test results, neuropathologic, molecular, and genetic data were collected using a standardized instrument and compared between initial diagnosis groups. RESULTS: Cases were separated into five broad categories pertaining to their initial diagnoses: prion disease, non-prion-related dementia, psychiatric disorder, stroke, and other. The majority of cases did not receive an initial diagnosis of prion disease (n = 76, 83%). The plurality of subjects received an initial diagnosis of a non-prion disease related dementia (n = 33, 36%). Mean survival times varied between initial diagnosis groups (p = 0.042). Times to cerebrospinal fluid 14-3-3 analysis and electroencephalogram also differed between initial diagnosis groups. CONCLUSIONS: Most patients with prion disease are initially diagnosed with a non-prion disease related dementia. Several clinical features were associated with initial diagnoses including survival time, onset of specific symptoms, and times to 14-3-3 analyses and electroencephalogram. Expanding our knowledge of the various clinical presentations of prion disease, especially dementia, may aid in the earlier diagnoses of these rapidly progressive diseases.

Racial and ethnic differences in individuals with sporadic Creutzfeldt-jakob disease in the United States of America.

BACKGROUND: Little is known about racial and ethnic differences in individuals with sporadic Creutzfeldt-Jakob disease (sCJD). The authors sought to examine potential clinical, diagnostic, genetic, and neuropathological differences in sCJD patients of different races/ethnicities. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study of 116 definite and probable sCJD cases from Johns Hopkins and the Department of Veterans Affairs Healthcare Systems was conducted that examined differences in demographic, clinical, diagnostic, genetic, and neuropathological characteristics among racial/ethnic groups. Age at disease onset differed among racial/ethnic groups. Non-Hispanic Whites had a significantly older age at disease onset compared to the other groups (65 vs. 60, p = 0.036). Non-Whites were accurately diagnosed more rapidly than Whites (p = 0.008) and non-Hispanic Whites were more likely to have normal appearing basal ganglia on brain magnetic resonance imaging (MRI) compared to minorities (p = 0.02). Whites were also more likely to undergo post-mortem evaluation compared to non-Whites (p = 0.02). CONCLUSIONS/SIGNIFICANCE: Racial/ethnic groups affected by sCJD demonstrated differences in age at disease onset, time to correct diagnosis, clinical presentation, and diagnostic test results. Whites were more likely to undergo autopsy compared to non-Whites. These results have implications in regards to case ascertainment, diagnosis, and surveillance of sCJD and possibly other human prion diseases.

D178N, 129Val and N171S, 129Val genotype in a family with Creutzfeldt-Jakob disease.

BACKGROUND: Fatal familial insomnia (FFI) and genetic Creutzfeldt-Jakob disease (CJD(D178N,)(129V)) are two phenotypes that share a common point mutation at codon 178 of the prion protein gene (PRNP), but differ in their polymorphism at codon 129 of the mutant allele. A mutation at codon 171 of the PRNP gene has been described in a family with a strong psychiatric history without prion disease. METHODS: Clinical and genetic information of a family with CJD was obtained from medical records and family informants. RESULTS: We identified an African-American family with molecular and genetically confirmed CJD(D178N,)(129V) that also carried the N171S, 129V polymorphism and had a strong psychiatric clinical presentation. CONCLUSION: This is a complex family that carries the D178N, 129V and N171S, 129V genotype. This report is the first description of both genotypes occurring within a family with genetic human prion disease.

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. DESIGN: Retrospective analysis. SETTING: The Johns Hopkins and Veterans Administration health care systems. PARTICIPANTS: Eighty-eight patients with definite or probable sCJD. MAIN OUTCOME MEASURES: 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.

Predictors of depression and anxiety in patients with intracranial neoplasms.

A retrospective review of patients with intracranial neoplasms was performed to identify characteristics of patients with comorbid depression and/or anxiety. This study suggests that depression and anxiety are common comorbidities and that preexisting psychiatric disorders predispose to their occurrence within the neuro-oncology setting.

Does the presentation of Creutzfeldt-Jakob disease vary by age or presumed etiology? A meta-analysis of the past 10 years.

It is not clear whether differences in symptom presentation vary by age or etiological subtype in Creutzfeldt-Jakob disease. A PubMed search was conducted using the keyword "Creutzfeldt-Jakob" and results within the last 10 years were sorted by the English language. We found that certain characteristics, such as affective illness (28.8%), present more commonly in younger patients irrespective of disease type. Young age of onset predicts presenting symptoms of affective illness, sleep disturbance, and poor concentration, as well as certain neurological symptoms, including cerebellar/gait disturbance, visual/oculomotor disturbance, sensory disorder, vertigo/dizziness, and headache.