Sporadic Jakob-Creutzfeldt Disease Presenting as Primary Progressive Aphasia

Johnson, David Y.; Dunkelberger, Diana L.; Henry, Maya L.; Haman, Aissa; Greicius, Michael D.; Wong, Katherine; DeArmond, Stephen J.; Miller, Bruce L.; Gorno‐Tempini, Maria Luisa; Geschwind, Michael D.

doi:10.1001/jamaneurol.2013.139

Cited by 6 publications

(8 citation statements)

References 8 publications

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“…The previously described cases are younger (mean age = 56.7 ± 12.33, t = 0.002), with a longer disease duration (median duration of 58 weeks) than our cases, although the difference is not statistically significant. Difficulties with individual words were the initial symptom in seven of the previous literature cases , similar to our cases. Word finding difficulty, however, is a non‐specific symptom and can reflect abnormalities in different language‐related domains, as well as other cognitive problems such as agnosia or memory problems .…”

Section: Discussionsupporting

confidence: 90%

Isolated language impairment as the primary presentation of sporadic Creutzfeldt Jakob Disease

et al. 2016

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Section: Discussionsupporting

confidence: 90%

Isolated language impairment as the primary presentation of sporadic Creutzfeldt Jakob Disease

et al. 2016

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“…1 Approximately 85% of human prion disease cases are sporadic CJD (sCJD), 2,3 and therefore, sCJD has been the primary focus of clinical trials thus far. 4 Although the typical duration of sCJD from time of diagnosis to death is 4 to 6 months on average, there is significant interindividual variability, with survival time ranging from weeks to several years, [5][6][7][8] determined in part by prion protein gene (PRNP) codon 129 polymorphism and prion typing. 9,10 Efforts are underway to bring preclinical therapeutics to human patients.…”

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confidence: 99%

Association of Blood and Cerebrospinal Fluid Tau Level and Other Biomarkers With Survival Time in Sporadic Creutzfeldt-Jakob Disease

et al. 2019

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IMPORTANCE Fluid biomarkers that can predict survival time in sporadic Creutzfeldt-Jakob disease (sCJD) will be critical for clinical care and for treatment trials. OBJECTIVE To assess whether plasma and cerebrospinal fluid (CSF) biomarkers are associated with survival time in patients with sCJD. DESIGN, SETTING, AND PARTICIPANTS In this longitudinal cohort study, data from 193 patients with probable or definite sCJD who had codon 129 genotyping referred to a tertiary national referral service in the United States were collected from March 2004 to January 2018. Participants were evaluated until death or censored at the time of statistical analysis (range, 0.03-38.3 months). We fitted Cox proportional hazard models with time to event as the outcome. Fluid biomarkers were log-transformed, and models were run with and without nonfluid biomarkers of survival. Five patients were excluded because life-extending measures were performed. MAIN OUTCOMES AND MEASURES Biomarkers of survival included sex, age, codon 129 genotype, Barthel Index, Medical Research Council Prion Disease Rating Scale, 8 CSF biomarkers (total tau [t-tau] level, phosphorylated tau [p-tau] level, t-tau:p-tau ratio, neurofilament light [NfL] level, β-amyloid 42 level, neuron-specific enolase level, 14-3-3 test result, and real-time quaking-induced conversion test), and 3 plasma biomarkers (t-tau level, NfL level, and glial fibrillary acidic protein level). RESULTS Of the 188 included participants, 103 (54.8%) were male, and the mean (SD) age was 63.8 (9.2) years. Plasma t-tau levels (hazard ratio, 5.8; 95% CI, 2.3-14.8; P < .001) and CSF t-tau levels (hazard ratio, 1.6; 95% CI, 1.2-2.1; P < .001) were significantly associated with survival after controlling for codon 129 genotype and Barthel Index, which are also associated with survival time. Plasma and CSF t-tau levels were correlated (r = 0.74; 95% CI, 0.50-0.90; P < .001). Other fluid biomarkers associated with survival included plasma NfL levels, CSF NfL levels, t-tau:p-tau ratio, 14-3-3 test result, and neuron-specific enolase levels. In a restricted subset of 23 patients with data for all significant biomarkers, the hazard ratio for plasma t-tau level was more than 40% larger than any other biomarkers (hazard ratio, 3.4; 95% CI, 1.8-6.4). CONCLUSIONS AND RELEVANCE Cerebrospinal fluid and plasma tau levels, along with several other fluid biomarkers, were significantly associated with survival time in patients with sCJD. The correlation between CSF and plasma t-tau levels and the association of plasma t-tau level with survival time suggest that plasma t-tau level may be a minimally invasive fluid biomarker in sCJD that could improve clinical trial stratification and guide clinical care.

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“…Survival in Creutzfeldt-Jakob disease is variable: although most patients have a rapid course over a few months, many have a slower course over a year and half up to even a few years. 5,20 Another problem with exclusion of patients on the basis of time from symptom onset is that symptom onset often can be very diffi cult to establish, and the defi nition of the fi rst symptom is not always consistent. 21 In our trial of quinacrine in sporadic Creutzfeldt-Jakob disease, we excluded patients who could not follow simple commands and were unable to swallow.…”

Section: -3mentioning

confidence: 99%

Doxycycline for Creutzfeldt-Jakob disease: a failure, but a step in the right direction

Geschwind

2014

The Lancet Neurology

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Sporadic Jakob-Creutzfeldt Disease Presenting as Primary Progressive Aphasia

Cited by 6 publications

References 8 publications

Isolated language impairment as the primary presentation of sporadic Creutzfeldt Jakob Disease

Isolated language impairment as the primary presentation of sporadic Creutzfeldt Jakob Disease

Association of Blood and Cerebrospinal Fluid Tau Level and Other Biomarkers With Survival Time in Sporadic Creutzfeldt-Jakob Disease

Doxycycline for Creutzfeldt-Jakob disease: a failure, but a step in the right direction

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