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Multiple Sclerosis and Related Conditions
Published in John W. Scadding, Nicholas A. Losseff, Clinical Neurology, 2011
For example, Kurtzke’s extended disability status scale (EDSS), the most widely accepted measure of impairment, consists of a series of separate rank-order scales requiring non-parametric statistical analysis, has a bimodal distribution in the MS population, is relatively insensitive to change of impairment, and is heavily weighted on ambulation. On the other hand, the EDSS has a reasonable inter- and intra-rater reliability. Efforts continue to identify and to validate other sensitive, reproducible and relevant clinical outcome measures, including scales of quality of life, spasticity, dexterity and cognitive function. The Multiple Sclerosis Functional Composite (MSFC) is a more recent measure which incorporates components measuring walking time, upper limb function and speed of information processing, and efforts continue to improve it by adding measurements of vision using low contrast acuity.
The Role of Fecal Microbiota Transplantation in Neurological Diseases
Published in David Perlmutter, The Microbiome and the Brain, 2019
Thomas Borody, John Bienenstock
Hoban et al. (2016), using a genome-wide transcriptome profiling approach, reported significant upregulation of genes linked to myelination and myelin plasticity in germ-free mice.110 These observed changes in myelin and activity-related gene expression could be reversed by colonization using a conventional microbiota following weaning, leading the authors to identify the microbiota as a potential therapeutic target for psychiatric disorders involving dynamic myelination in the prefrontal cortex. This was further explored by Makkawi et al. (2018),111 who described a 61-year-old female patient with secondary progressive multiple sclerosis (SPMS) treated with FMT. She presented with seven relapses between 1998 and 2001, and her MRI showed numerous periventricular, juxtacortical, brainstem, and corpus callosum lesions confirming relapsing remitting multiple sclerosis. Despite an early positive response to glatiramer acetate treatment, her balance, ambulation, lower limb power, bladder function, and fatigue gradually worsened. Following several episodes of C. difficile enterocolitis in 2005 and 2006, which proved resistant to multiple courses of metronidazole and vancomycin, she received a single FMT from her partner. Following FMT, her Expanded Disability Status Scale immediately stabilized without other treatment or lifestyle changes. Over the next ten years, her Functional System scores minimally improved, as did her Modified Multiple Sclerosis Functional Composite scores, instead of worsening as expected. Taken together, the animal studies and otherwise unexplainable human observations following FMT again suggest that, as with hepatic encephalopathy, the gut microbiome likely plays an unexpected role in de- and re-myelination.
Cognitive measures used in adults with multiple sclerosis: A systematic review
Published in Neuropsychological Rehabilitation, 2022
Hannah Elwick, Gogem Topcu, Christopher Martin Allen, Avril Drummond, Nikos Evangelou, Roshan das Nair
Measures were operationally defined as a named collection of tests if they were a named screening test (e.g., MoCA) or a battery (e.g., BRB-N) that included one or more measure that is considered an individual test. Sixty-one different multi-domain neuropsychological tests or batteries were reported in the included studies, and these were used 913 times in included studies. The most frequently used multi-domain test used was the BRB-N, followed by the Mini-Mental State Examination (MMSE) and the WAIS (See Table 2). The Multiple Sclerosis Functional Composite (MSFC) only includes one neuropsychological measure (the PASAT) and was therefore included as an individual measure rather than a battery. The MoCA was frequently used to screen participants into studies (37%) or to report on cognitive functioning or between group differences (38%). However, 25% of the studies using the MMSE used it as a dependent or independent variable.
Prediction in treatment outcomes in multiple sclerosis: challenges and recent advances
Published in Expert Review of Clinical Immunology, 2021
Deja R. Rose, Moein Amin, Daniel Ontaneda
The Multiple Sclerosis Functional Composite (MSFC) was developed to address the limitations of the EDSS and to be used as its complement in clinical trials. It consists of the Timed 25-Foot Walking Test (T25FWT), which serves as a measure of lower extremity function, the Nine-Hole Peg Test (9HPT), which is a measure of upper extremity function, and originally the Paced Auditory Serial Addition Test (PASAT-3), which assesses cognitive function, though The Symbol Digit Modalities Test (SDMT) is now used in its place. Low-contrast letter acuity test (LCLA) is frequently added to the composite as a measure of visual function. Each measure provides a continuous score that is then converted into a Z score, standardized to a reference population [46]. The MSFC was found to have a better reliability and sensitivity to change compared to EDSS, and in a separate study, correlated with the Short Form-36 Physical Component Summary (SF-36 PCS), a patient-reported outcome (PRO) [47,48].
Visual Pathway Measures are Associated with Neuropsychological Function in Multiple Sclerosis
Published in Current Eye Research, 2018
James Nguyen, Alissa Rothman, Kathryn Fitzgerald, Anna Whetstone, Stephanie Syc-Mazurek, Jannelle Aquino, Laura J. Balcer, Elliot M. Frohman, Teresa C. Frohman, Ciprian Crainiceanu, Meghan Beier, Scott D. Newsome, Peter A. Calabresi, Shiv Saidha
Cognitive impairment is a highly relevant clinical feature of MS evident in 40–70% of patients.5 The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery of neuropsychological testing is established for assessing cognitive function in MS.6 In addition, the Multiple Sclerosis Functional Composite (MSFC) assessment also partially assesses cognition with the Paced Auditory Serial Addition Test (PASAT), as well as dexterity and walking speed. While brain substructure volumes have been shown to correlate with cognitive function in MS, and despite the proposed utility of structural and functional visual pathway (VP) measures (complementary to magnetic resonance imaging (MRI)) in tracking MS patients clinically,7 as well as outcomes in clinical trials, few studies have comprehensively assessed the relationships between VP and neuropsychological measures in MS. Moreover, there have been conflicting results between studies performed. Peripapillary retinal nerve fiber layer (RNFL) thickness has been found to correlate with SDMT scores in some studies,8–10 and low-contrast letter acuity (LA) has been found to be associated with PASAT and SDMT scores.11,12 However, with relatively small sample sizes, limited neuropsychological evaluation, and partial VP assessment (GCIP thickness, e.g., has been shown to be a more superior OCT measure than RNFL thickness as it more greatly reflects global neurodegeneration in MS and is less susceptible to edema1), the relationships between VP measures and neuropsychological function in MS remain unclear.