Improving Early Recognition of Treatment‐Responsive Causes of Rapidly Progressive Dementia: The STAM₃P Score

Abstract

ObjectiveTo improve the timely recognition of patients with treatment‐responsive causes of rapidly progressive dementia (RPD).MethodsTwo‐hundred twenty‐six adult patients with suspected RPD were enrolled in a prospective observational study and followed for up to two years. Diseases associated with RPD were characterized as potentially treatment‐responsive or non‐responsive referencing clinical literature. Disease progression was measured using Clinical Dementia Rating® Sum‐of‐Box scores. Clinical and paraclinical features associated with treatment responsiveness were assessed using multivariable logistic regression. Findings informed the development of a clinical criterion optimized to recognize patients with potentially treatment‐responsive causes of RPD early in the diagnostic evaluation.ResultsOne‐hundred fifty‐five patients met defined RPD criteria, of whom 86 patients (55.5%) had potentially treatment‐responsive causes. Median (range) age‐at‐symptom onset in patients with RPD was 68.9 years (22.0‐90.7), with a similar number of males and females. Seizures, tumor (disease‐associated), MRI suggestive of autoimmune encephalitis, mania, movement abnormalities, and pleocytosis (≥10 cells/mm3 in CSF) at presentation were independently associated with treatment‐responsive causes of RPD after controlling for age and sex. Those features at presentation, as well as age‐at‐symptom onset < 50 years (i.e., STAM3P), captured 83/86 (96.4%) cases of treatment‐responsive RPD. The presence of ≥3 STAM3P features had a positive predictive value of 100%.InterpretationSelected features at presentation reliably identified patients with potentially treatment‐responsive causes of RPD. Adaptation of the STAM3P screening score in clinical practice may minimize diagnostic delays and missed opportunities for treatment in patients with suspected RPD.This article is protected by copyright. All rights reserved.

Diagnostic Utility of Cerebrospinal Fluid Biomarkers in Patients with Rapidly Progressive Dementia

“…Diseases associated with RPD were characterized by study authors (N.S., G.S.D.) as potentially responsive or nonresponsive referencing a “treatability index” reflecting observed responsiveness 13 . Treatment‐responsive causes were further stratified by expected responsiveness to high‐dose intravenous steroids (ie, steroid responsive vs nonresponsive).…”

“…as potentially responsive or nonresponsive referencing a "treatability index" reflecting observed responsiveness. 13 Treatment-responsive causes were further stratified by expected responsiveness to high-dose intravenous steroids (ie, steroid responsive vs nonresponsive). Neurodegenerative diseases were considered nonresponsive, with the exception of cerebral amyloid angiopathy with inflammation (CAAri), owing to the potential for response following timely administration of immune-modulating therapies.…”

“…These approaches combine widely available serum and cerebrospinal fluid (CSF) tests with structural neuroimaging to inform the cause(s) and treatment(s) of RPD. 1,6,[11][12][13] However, remarkable overlap in the presenting clinical features and results of investigations continues to confound the etiologic diagnoses of RPD, contributing to diagnostic delays, missed treatment opportunities, and poorer outcomes. 1,7,8,14 These challenges exemplify the need for objective, quantifiable, and accessible measures that define biological signatures associated with specific causes of RPD.…”

“…[15][16][17][18] Similar advances are needed for patients with other causes of RPD. There is a particular need to define objective measures that identify patients with potentially treatment-responsive causes of RPD who comprise an increasing proportion of cases diagnosed in the clinic 2,10,13 and at autopsy. 14,19 CSF biomarkers may be ideally suited for these purposes.…”

“…More recently, the publication of diagnostic criteria 35 and improved access to comprehensive testing for disease‐associated antibodies have improved recognition of patients with autoimmune encephalitis, 9 informed contributions of autoimmune/inflammatory diseases to RPD, 1,2,10 and catalyzed development of diagnostic approaches prioritizing early recognition of patients with potentially treatment‐responsive causes of RPD. These approaches combine widely available serum and cerebrospinal fluid (CSF) tests with structural neuroimaging to inform the cause(s) and treatment(s) of RPD 1,6,11–13 . However, remarkable overlap in the presenting clinical features and results of investigations continues to confound the etiologic diagnoses of RPD, contributing to diagnostic delays, missed treatment opportunities, and poorer outcomes 1,7,8,14 .…”