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

Time to correct diagnosis of sporadic Creutzfeldt-Jakob disease subjects by race/ethnicity.

<p>White race includes non-Hispanic and Hispanic Whites (Mantel-Cox, chi-square  = 7.1, p = 0.008).</p

Neuropathologic and molecular data of study subjects.

<p>PRNP = prion protein gene, M = methionine, V = valine, PSPr = protease sensitive proteinopathy.</p>a<p>It was unknown whether tissue was from an autopsy or biopsy in 3 cases.</p>b<p>Any White race vs. any non-White race (Fisher’s exact test, 2-sided, p = 0.02).</p>c<p>We could not confirm PRNP codon 129 genotype in 2 cases.</p>d<p>Defined as PRNP codon 129 genotype and prion protein type(s).</p

Clinical symptoms of subjects throughout the disease course.

<p><u>Cognitive</u>: cognitive decline, executive dysfunction, amnesia, agnosia, apraxia, alexia, language impairment, disorientation, and/or concentration impairment; <u>Cerebellar</u>: ataxia, nystagmus, and/or vertigo; <u>Movement disorder</u>: tremor, chorea, and/or extrapyramidal symptoms (does not include myoclonus); <u>Visual</u>: diplopia, oculomotor palsy, hemianopia, cortical blindness, visuospatial impairment, and/or visual hallucinations; <u>Mood</u>: depression, anxiety, mania, hypomania, emotional lability, and/or apathy; <u>Psychosis</u>: delusions, hallucinations, and/or psychosis not otherwise specified.</p

Brain magnetic resonance imaging (MRI) characteristics of study subjects.

<p>Brain MRI was not done for 2 subjects and results were unknown in 4 subjects.</p>a<p>imes could not be calculated for 7 subjects.</p>b<p>p<0.05.</p>c<p>13/15 cases also had basal ganglia hyperintensity.</p>d<p>Hyperintensity on DWI/FLAIR in 2 or more cortical areas (temporal, parietal, or occipital lobes) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038884#pone.0038884-Zerr1" target="_blank">[15]</a>.</p>e<p>High signal abnormalities in caudate nucleus and putamen or at least two cortical regions (temporal-parietal-occipital) either in DWI or FLAIR <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038884#pone.0038884-Zerr1" target="_blank">[15]</a>.</p

Diagnostic testing data of study sample.

<p>EEG = electroencephalogram; PSWC  =  periodic sharp wave complexes.</p>a<p>Unknown in 9 cases.</p>b<p>Unknown in 8 cases.</p>c<p>Unknown in 4 cases.</p