Publications by authors named "Ralph H Benedict"
Progression independent of relapse activity (PIRA) has been recently proposed in multiple sclerosis (MS) as a model identifying a continuous silent progression of disability without the manifestation of new clinical and magnetic resonance imaging (MRI) events that contribute to MS worsening. Despite evidence suggesting that clinical MS manifestations often affect cognitive functioning and the importance of neuropsychological monitoring over time, attention to silent cognitive progression is lacking, and the PIRA concept does not include a measure of cognitive function. In this personal viewpoint, we highlight the need to include cognition in the PIRA model to have a more comprehensive understanding of clinical progression in patients with MS.
View Article and Find Full Text PDFBackground: Substantial physical-disability worsening in relapsing-remitting multiple sclerosis (RRMS) occurs outside of clinically recorded relapse. This phenomenon, termed progression independent of relapse activity (PIRA), is yet to be established for cognitive decline.
Methods: Retrospective analysis of RRMS patients.
Background: Expanded Disability Status Scale (EDSS) is limited when utilized in highly disabled people with multiple sclerosis (pwMS).
Objetive: To explore the relationship between disability measures and MRI outcomes in severely-affected pwMS.
Methods: PwMS recruited from The Boston Home (TBH), a specialized residential facility for severly-affected pwMS and University at Buffalo (UB) MS Center were assessed using EDSS, MS Severity Scale, age-related MSS, Scripps Neurological Rating Scale (SNRS) and Combinatorial Weight-Adjusted Disability Score (CombiWISE).
Background: A quantitative measurement of serum proteome biomarkers that would associate with disease progression endpoints can provide risk stratification for persons with multiple sclerosis (PwMS) and supplement the clinical decision-making process.
Materials And Methods: In total, 202 PwMS were enrolled in a longitudinal study with measurements at two time points with an average follow-up time of 5.4 years.
Multiple sclerosis remains one of the most common causes of neurological disability in the young adult population (aged 18-40 years). Novel pathophysiological findings underline the importance of the interaction between genetics and environment. Improvements in diagnostic criteria, harmonised guidelines for MRI, and globalised treatment recommendations have led to more accurate diagnosis and an earlier start of effective immunomodulatory treatment than previously.
View Article and Find Full Text PDFBackground: Cognitive phenotyping may be useful for predicting rehabilitation response in multiple sclerosis.
Objective: To evaluate the association between cognitive phenotype(s) and response to restorative cognitive rehabilitation (RRCR).
Methods: In a post hoc retrospective analysis of the RRCR study including 51 multiple sclerosis patients, we evaluated both impairment within specific cognitive domains as well as overall global impairment severity to investigate their relationship to improvement following rehabilitation.
Background: The Symbol Digit Modalities Test (SDMT) is a gold-standard measure of cognitive efficiency and processing speed for people with multiple sclerosis (PwMS) but relies on vision and oculomotor function.
Objectives: To develop and validate a new processing speed test with minimal memory involvement and no eye function requirements.
Methods: We created an Auditory Test of Processing Speed (ATOPS).
Background: Employment deterioration is common in people with multiple sclerosis (PwMS). Clinicians often learn of job loss after its occurrence, leaving no opportunity for preventive measures.
Objectives: Identify which neuropsychological measures discriminate between healthy volunteers (HVs) and employed/disabled PwMS at baseline and predict work deterioration over 2 years.
Background: Paramagnetic rim lesions (PRL) may be linked to relapse risk of people with relapsing-remitting multiple sclerosis (pwRRMS).
Objective: To determine the relationship between presence of PRL lesions and cognitive recovery after relapse.
Methods: PRL load was compared between acutely relapsing pwRRMS and matched stable pwRRMS controls (each group = 21).
Background: The effect of disease modifying therapies (DMTs) on brain atrophy in persons with multiple sclerosis (pwMS) is typically investigated in highly standardized clinical trial settings or single-center academic institutions. We aimed at utilizing artificial intelligence (AI)-based volumetric analysis on routine unstandardized T2-FLAIR scans in determining the effect of DMTs on lateral ventricular volume (LVV) and thalamic volume (TV) changes in pwMS.
Methods: The DeepGRAI (Deep Gray Rating via Artificial Intelligence) registry is a multi-center, longitudinal, observational, real-word study with a convenience sample of 1002 relapsing-remitting (RR) pwMS from 30 United States sites.
Background: The Symbol Digit Modalities Test (SDMT), the most reliable and sensitive measure of cognition in people with multiple sclerosis (PwMS), is increasingly used in clinical trials and care.
Objectives: We aimed to establish how SDMT performance is influenced by repeating forms and frequency of use in PwMS.
Methods: A retrospective analysis was completed on a large database of PwMS (n = 740) with multiple SDMT administrations.
Background And Objective: The COVID-19 pandemic negatively impacted the well-being of persons with neuroinflammatory diseases (pwNID). Identifying factors that influence the response to challenging conditions could guide supportive care.
Methods: 2185 pwNID and 1079 healthy controls (HCs) from five US centers completed an online survey regarding the effects of the COVID-19 pandemic on physical and psychological well-being.
Background: Ocrelizumab is an effective treatment for relapsing and primary-progressive multiple sclerosis (MS). However, the effect of ocrelizumab on leptomeningeal (LM) inflammation is unknown.
Objective: To investigate whether ocrelizumab reduces LM inflammation by reducing the exposure to Epstein-Barr virus (EBV)-infected B cells in relapsing-remitting (RR) MS.
Background: Siponimod significantly reduced the risk of confirmed disability progression (CDP), worsening in cognitive processing speed (CPS), relapses, and magnetic resonance imaging (MRI) measures of brain atrophy and inflammation versus placebo in secondary progressive multiple sclerosis (SPMS) patients in the Phase 3 EXPAND study.
Objective: The aim of this study was to assess long-term efficacy and safety of siponimod 2 mg/day from the EXPAND study including the extension part, up to > 5 years.
Methods: In the open-label extension part, participants receiving placebo during the core part were switched to siponimod (placebo-siponimod group) and those on siponimod continued the same treatment (continuous siponimod group).
Background: Magnetic resonance imaging (MRI) measurements of gray matter (GM) atrophy and magnetization transfer ratio (MTR; correlate of myelination) may provide better insights than conventional MRI regarding brain tissue integrity/myelination in multiple sclerosis (MS).
Objective: To examine the effect of siponimod in the EXPAND trial on whole-brain and GM atrophy, newly formed normalized magnetization transfer ratio (nMTR) lesions, and nMTR-assessed integrity of normal-appearing brain tissue (NABT), cortical GM (cGM), and normal-appearing white matter (NAWM).
Methods: Patients with secondary progressive multiple sclerosis (SPMS) received siponimod (2 mg/day; =1037) or placebo ( = 523).
Background: The Symbol Digit Modalities Test (SDMT) is increasingly utilized in clinical trials. A SDMT score change of 4 points is considered clinically important, based on association with employment anchors. Optimal thresholds for statistically reliable SDMT changes, accounting for test reliability and measurement error, are yet to be applied to individual cases.
View Article and Find Full Text PDFBackground: Previous studies have established benchmarks of clinically meaningful decline on neuropsychological tests. However, little is known about meaningful testing benchmarks based on gains in function.
Objective: Investigate neuropsychological changes in multiple sclerosis (MS) patients with work gains and calculate benchmarks of meaningful improvement on neuropsychological tests.
Background: The sequence in which cognitive domains become impaired in multiple sclerosis (MS) is yet to be formally demonstrated. It is unclear whether processing speed dysfunction temporally precedes other cognitive impairments, such as memory and executive function.
Objective: Determine the order in which different cognitive domains become impaired in MS and validate these findings using clinical and vocational outcomes.
Objectives: To identify Magnetic Resonance Imaging (MRI), clinical and demographic biomarkers predictive of worsening information processing speed (IPS) as measured by Symbol Digit Modalities Test (SDMT).
Methods: Demographic, clinical data and 1.5 T MRI scans were collected in 76 patients at time of inclusion, and after 5 and 10 years.
Background: Cognition is affected by relapses in persons with multiple sclerosis (PwMS), yet the Expanded Disability Status Scale (EDSS) does not readily detect cognitive changes.
Objective: The objective of this study is to improve the detection of cognitive decline during relapses, by incorporating the Symbol Digit Modalities Test (SDMT) into the cerebral Functional System Score (CFSS) of the EDSS.
Methods: This prospective study recruited PwMS from three dedicated MS centers.
Background: Neurofilament light chain level in serum (sNfL) and cerebrospinal fluid (CSF-NfL) is a promising biomarker of disease activity in multiple sclerosis (MS). However, predictive value of neurofilaments for development of cognitive decline over long-term follow-up has not been extensively studied.
Objective: To investigate the relationship between early neurofilament levels and cognitive performance after 9-years.
Background: Physical and cognitive symptoms of multiple sclerosis (MS) correlate with unemployment cross-sectionally. Prospective studies, rarely published, have not accounted for personality traits such as Conscientiousness.
Methods: In a 3-year study of 70 people with MS (PwMS) and 25 healthy controls (HCs), we evaluated employment status using online interviews capturing hours worked, negative work events, employee relations, and accommodations.
Objectives: Determine the validity and reliability of a remote, technician-guided cognitive assessment for multiple sclerosis (MS), incorporating the Symbol Digit Modalities Test (SDMT) and the California Verbal Learning Test, Second Edition (CVLT-II).
Methods: In 100 patients, we compared conventional in-person testing to remote, web-assisted assessments, and in 36 patients, we assessed test-retest reliability using two equivalent, alternative forms.
Results: In-person and remote-administered SDMT ( = 0.
Background: There is evidence of cognitive-motor coupling in multiple sclerosis (MS) such that the slowing of cognitive processing speed correlates with the worsening of walking speed and endurance.
Objective: The current study first established the presence of cognitive-motor coupling and second examined the possibility that volumes of subcortical gray matter (SGM) structures and aerobic capacity might explain the coupling of cognitive and motor functions in persons with MS.
Methods: We included data from 62 persons with clinically definite MS who underwent assessments of cognitive processing speed, walking performance, and aerobic capacity, and completed magnetic resonance imaging (MRI) within 7 days of the aforementioned assessments.