BackgroundDietary changes impact human physiology and immune function and have potential as therapeutic strategies.ObjectiveAssess the tolerability of a ketogenic diet (KD) in patients with relapsing multiple sclerosis (MS) and define the impact on laboratory and clinical outcome metrics.MethodsSixty-five subjects with relapsing MS enrolled into a 6-month prospective, intention-to-treat KD intervention. Adherence was monitored with daily urine ketone testing. At baseline, fatigue, depression and quality of life (QoL) scores were obtained in addition to fasting adipokines and MS-related clinical outcome metrics. Baseline metrics were repeated at 3 and/or 6 months on-diet.ResultsEighty-three percent of participants adhered to the KD for the study duration. Subjects exhibited significant reductions in fat mass and showed a nearly 50% decline in self-reported fatigue and depression scores. MS QoL physical health (67±16 vs 79±12, p<0.001) and mental health (71±17 vs 82±11, p<0.001) composite scores increased on-diet. Significant improvements were noted in Expanded Disability Status Scale scores (2.3±0.9 vs 1.9±1.1, p<0.001), 6-minute walk (1631±302 vs 1733±330 ft, p<0.001) and Nine-Hole Peg Test (21.5±3.6 vs 20.3±3.7 s, p<0.001). Serum leptin was lower (25.5±15.7 vs 14.0±11.7 ng/mL, p<0.001) and adiponectin was higher (11.4±7.8 vs 13.5±8.4 µg/mL, p=0.002) on the KD.ConclusionKDs are safe and tolerable over a 6-month study period and yield improvements in body composition, fatigue, depression, QoL, neurological disability and adipose-related inflammation in persons living with relapsing MS.Trial registration informationRegistered on ClinicalTrials.gov under registration number NCT03718247, posted on 24 October 2018. First patient enrolment date: 1 November 2018. Link: https://clinicaltrials.gov/ct2/show/NCT03718247?term=NCT03718247&draw=2&rank=1.

Aim To characterize growth trajectories of children who develop multiple sclerosis compared to typically developing, regional peers and Centers for Disease Control (CDC) normative values. Method This case–control study collected weight, height, and body mass index (BMI) in 40 consecutive pediatric patients with multiple sclerosis (28 females, 12 males), in addition to 120 typically developing peers (84 females, 36 males), identified and matched for year of birth, sex, ethnicity, and socio‐economic status. BMI values were converted to z‐scores based on CDC reference values and were compared with respect to age between our two cohorts and by years relative to multiple sclerosis onset for cases. Results Median age for the clinical onset of multiple sclerosis was 15 years. BMI z‐scores are significantly higher for patients with multiple sclerosis compared to typically developing, demographically‐matched peers and CDC standards. These significant differences in BMI are noted from 4 years of age and onward. Height trajectories were similar among case and control individuals and CDC normative values. Interpretation BMI in pediatric multiple sclerosis is markedly higher, beginning in early childhood, years before the clinical‐onset of the disease. What this paper adds Children with multiple sclerosis are significantly more overweight than typically developing peers at the time of diagnosis. Body mass index trajectories are significantly higher years before the clinical manifestation(s) of multiple sclerosis.

Background There is an increasing number of pediatric multiple sclerosis (MS) clinical trials occurring; however, data validating outcome metrics that accurately capture functional disability within pediatric cohorts are limited. Objective The aim of this study was to investigate the ability of the MS Functional Composite (MSFC) and Symbol Digit Modalities Test (SDMT) to distinguish functional disability in pediatric MS patients. Methods A total of 20 pediatric MS patients and 40 age and sex-matched controls completed the SDMT and MSFC components: a timed 25-foot walk (T25FW); 9-hole peg test (9HPT); and paced auditory serial addition test (PASAT). Z scores for MS patients were created for each test based on control means. MS patients underwent Expanded Disability Status Scale (EDSS) examination. Results Pediatric MS patients exhibited low levels of disability on EDSS, median [range]: 1.5 [1.0–3.0]. Compared with controls, MS patients performed significantly lower on SDMT ( p = 0.0002) and all MSFC components: T25FW ( p = 0.001), 9HPT ( p = 0.01), and PASAT ( p = 0.004). SDMT and MSFC performance were not correlated with EDSS. Conclusions Despite low levels of neurologic disability as measured by EDSS, pediatric patients with MS exhibit impaired performance in leg function, upper limb fine motor function, and auditory/visuospatial processing speeds, supporting the value of the MSFC and SDMT in this population. Longitudinal studies are needed to further validate their utility.

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