Baseline neuropsychological profiles in prion disease predict survival time

Sundaram, Saranya; Staffaroni, Adam M.; Walker, Nicole; Casaletto, Kaitlin B.; Casey, Megan; Golubjatnikov, Aili; Metcalf, Stacy; O'Leary, K. Daniel; Wong, Katherine; Benisano, Kendra; Forner, Sven; Catalan, M. Gonzalez; Allen, Isabel Elaine; Rosen, Howard J.; Kramer, Joel H.; Geschwind, Michael D.

doi:10.1002/acn3.51115

Cited by 4 publications

(3 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Staffaroni et al . 16 identified CSF biomarkers associated with survival and Sundaram et al 17 used a neuropsychological assessment score to predict probability of 3-, 6- and 12-month survival though neither tested combinations of predictors. Llorens et al .…”

Section: Introductionmentioning

confidence: 99%

Development of prognostic models for survival and care status in sporadic Creutzfeldt-Jakob disease

Nihat

Ranson

Harris

et al. 2022

Brain Communications

View full text Add to dashboard Cite

Sporadic Creutzfeldt-Jakob disease, the most common human prion disease, typically presents as a rapidly progressive dementia and has a highly variable prognosis. Despite this heterogeneity, clinicians need to give timely advice on likely prognosis and care needs. No prognostic models have been developed that predict survival or time to increased care status from the point of diagnosis. We aimed to develop clinically useful prognostic models with data from a large prospective observational cohort study. 537 patients were visited by mobile teams of doctors and nurses from the National Health Service National Prion Clinic within 5 days of notification of a suspected diagnosis of sporadic Creutzfeldt-Jakob disease, enrolled to the study between October 2008 and March 2020, and followed up until November 2020. Prediction of survival over 10-, 30- and 100- day periods was the main outcome. Escalation of care status over the same time periods was a secondary outcome for a subsample of 113 patients with low care status at initial assessment. 280 (52.1%) patients were female and the median age was 67.2 (interquartile range 10.5) years. Median survival from initial assessment was 24 days (range 0-1633); 414 patients died within 100 days (77%). Ten variables were included in the final prediction models: sex; days since symptom onset; baseline care status; PRNP codon 129 genotype; Medical Research Council Prion Disease Rating Scale, Motor and Cognitive Examination Scales; count of MRI abnormalities; Mini-Mental State Examination score and categorical disease phenotype. The strongest predictor was PRNP codon 129 genotype (odds ratio 6.65 for MM compared to MV polymorphism; 95% CI 3.02-14.68 for 30-day mortality). Of 113 patients with lower care status at initial assessment, 88 (78%) had escalated care status within 100 days, with a median of 35 days. Area under the curve for models predicting outcomes within 10, 30 and 100 days was 0.94, 0.92 and 0.91 for survival, and 0.87, 0.87 and 0.95 for care status escalation respectively. Models without PRNP codon 129 genotype, which is not immediately available at initial assessment, were also highly accurate. We have developed a model that can accurately predict survival and care status escalation in sporadic Creutzfeldt-Jakob disease patients using clinical, imaging and genetic data routinely available in a specialist national referral service. The utility and generalizability of these models to other settings could be prospectively evaluated when recruiting to clinical trials and providing clinical care.

show abstract

Section: Introductionmentioning

confidence: 99%

Development of prognostic models for survival and care status in sporadic Creutzfeldt-Jakob disease

Nihat

Ranson

Harris

et al. 2022

Brain Communications

View full text Add to dashboard Cite

show abstract

“…Staffaroni et al identified cerebrospinal fluid (CSF) biomarkers associated with survival 16 and Sundaram et al used a neuropsychological assessment score to predict probability of three-, six-and twelve-month survival 17 though neither tested combinations of predictors. Llorens et al developed a prognostic model of 6-month survival from sCJD symptom onset incorporating age, sex, PRNP codon 129 genotype, and CSF tau, which whilst valuable, did not model survival from the point of clinical decision making.…”

Section: Introductionmentioning

confidence: 99%

“…identified cerebrospinal fluid (CSF) biomarkers associated with survival 16 and Sundaram et al . used a neuropsychological assessment score to predict probability of three-, six- and twelve-month survival 17 though neither tested combinations of predictors. Llorens et al .…”

Section: Introductionmentioning

confidence: 99%

Development of Prognostic Models for Survival and Care Status in Sporadic Creutzfeldt-Jakob disease

Nihat

Ranson

Harris

et al. 2022

Preprint

View full text Add to dashboard Cite

Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, typically presents as a rapidly progressive dementia and has a highly variable prognosis. Despite this heterogeneity, clinicians need to give timely advice on likely prognosis and care needs. No prognostic models have been developed that predict survival or time to increased care status from the point of diagnosis. We aimed to develop clinically useful prognostic models with data from a large prospective observational cohort study. 537 patients were visited by mobile teams of doctors and nurses from the NHS National Prion Clinic within 5 days of notification of a suspected diagnosis of sCJD, enrolled to the study between October 2008 and March 2020, and followed up until November 2020. Prediction of survival over 10-, 30- and 100- day periods was the main outcome. Escalation of care status over the same time periods was a secondary outcome for a subsample of 113 patients with low care status at initial assessment. 280 (52.1%) patients were female and the median age was 67.2 (IQR 10.5) years. Median survival from initial assessment was 24 days (range 0-1633); 414 patients died within 100 days (77%). Ten variables were included in the final prediction models: sex; days since symptom onset; baseline care status; PRNP codon 129 genotype; MRC (Medical Research Council) Prion Disease Rating Scale, Motor and Cognitive Examination Scales; count of MRI abnormalities; Mini-Mental State Examination score and categorical sCJD phenotype. The strongest predictor was PRNP codon 129 genotype (odds ratio 6.65 for MM compared to MV polymorphism; 95% CI 3.02-14.68 for 30-day mortality). Of 113 patients with lower care status at initial assessment, 88 (78%) had escalated care status within 100 days, with a median of 35 days. Area under the curve for models predicting outcomes within 10, 30 and 100 days was 0.94, 0.92 and 0.91 for survival, and 0.87, 0.87 and 0.95 for care status escalation respectively. Models without PRNP codon 129 genotype, which is not immediately available at initial assessment, were also highly accurate. We have developed a model that can accurately predict survival and care status escalation in sCJD patients using clinical, imaging and genetic data routinely available in a tertiary national referral service. The utility and generalizability of these models to other settings could be prospectively evaluated when recruiting to clinical trials and providing clinical care.

show abstract

Miscellaneous CNS Viral Infections: Underappreciated Causes of Neurologic Disease

Sami,

Firoze,

Khan

2023

Viral and Fungal Infections of the Central Nervous System: A Microbiological Perspective

View full text Add to dashboard Cite

Baseline neuropsychological profiles in prion disease predict survival time

Cited by 4 publications

References 57 publications

Development of prognostic models for survival and care status in sporadic Creutzfeldt-Jakob disease

Development of prognostic models for survival and care status in sporadic Creutzfeldt-Jakob disease

Development of Prognostic Models for Survival and Care Status in Sporadic Creutzfeldt-Jakob disease

Miscellaneous CNS Viral Infections: Underappreciated Causes of Neurologic Disease

Contact Info

Product

Resources

About