Serum neurofilament light chain in relapsing multiple sclerosis patients on a ketogenic diet.

BACKGROUND: Ketogenic diets have anti-inflammatory and neuroprotective properties which make these diets an attractive complimentary treatment approach for patients living with multiple sclerosis (MS). The objective of this study was to assess the impact of ketogenic diets on neurofilament light chain (NfL), a biomarker of neuroaxonal injury. METHODS: Thirty-nine subjects with relapsing MS completed a 6-month ketogenic diet intervention. NfL levels were assayed at both baseline (pre-diet) and 6-months on-diet. In addition, ketogenic diet study participants were compared to a cohort (n = 31) of historical, untreated MS controls. RESULTS: Baseline (pre-diet) mean NfL was 5.45 pg/ml (95% CI 4.59 - 6.31). After 6 months on ketogenic diet, mean NfL was not significantly changed (5.49 pg/ml; 95% CI 4.82 - 6.19). Compared to untreated MS controls (mean 15.17 pg/ml), NfL levels for the ketogenic diet cohort were relatively low. MS subjects with higher levels of ketosis (as measured by serum beta-hydroxybutyrate) exhibited greater reductions in NfL between baseline and 6-months on ketogenic diet. CONCLUSIONS: Ketogenic diets do not worsen biomarkers of neurodegeneration in relapsing MS patients, with stable, low levels of NfL observed throughout the diet intervention. Subjects with greater biomarkers of ketosis experienced a higher degree of improvement in serum NfL. CLINICAL TRIAL IDENTIFIER: NCT03718247 - "Utilization of the Ketogenic Diet in Patients with Relapsing-Remitting MS" https://clinicaltrials.gov/ct2/show/NCT03718247.

Six-Minute Walk as a Measure of Walking Capacity and Endurance in Patients With Pediatric-Onset Multiple Sclerosis.

BACKGROUND: Despite low levels of disability, youth with pediatric-onset MS (POMS) engage in less physical activity compared to peers. The contribution of walking capacity, endurance, behavior, and MS co-morbidities remain relatively undefined and may provide valuable insights into the limitations toward physical activity in youth with MS. OBJECTIVE: Investigate differences in walking capacity, endurance and real-world behaviors of daily activity between youth with POMS and controls. DESIGN/METHODS: Youth diagnosed with MS prior to 18 years and aged ≤21 years were recruited in addition to healthy controls. Subjects completed questionnaires to quantify fatigue, depression, and physical activity levels and the timed 2- and 6-minute walk (2MW, 6MW) as an assessment of walk capacity and endurance. Subjects were sent home with a waist-worn accelerometer to assess real-world walking behavior. RESULTS: Forty-five POMS and 85 control subjects were enrolled. The POMS cohort had a mean age of 16.9±2.7 years with a mean disease duration of 2.8±2.6 years. A greater proportion of the POMS cohort was overweight/obese compared to controls (60% versus 33%). Subjects with MS walked a significantly shorter distance in 6 minutes compared to controls (1848 feet vs 2134 feet, p<0.0001) and, unlike controls, were unable to accelerate to their peak speed at the end of the 6MW. BMI category and MS disease significantly impacted 6MW performance. Using continuous accelerometry, subjects with MS spent less time in moderate-to-vigorous physical activity compared to controls (20.4 minutes/day vs 35.4 minutes/day, p=0.0003). The POMS cohort reported significantly higher levels of depression and fatigue, but self-reported similar levels of daily physical activity as controls. CONCLUSIONS: Youth with POMS exhibit slower 6MW performance and less daily engagement in moderate-to-vigorous physical activity, suggesting limitations in functional walking capacity, endurance, and daily activity behavior. Limitations in walking endurance and capacity are most prominent in those youth who are overweight/obese and living with MS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, compared to healthy controls, patients with pediatric-onset MS walk shorter distances on the 6 minute walk test, are less able to accelerate to peak speed at the end of the test, and are less physically active.

Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits.

BACKGROUND: Dietary changes impact human physiology and immune function and have potential as therapeutic strategies. OBJECTIVE: Assess the tolerability of a ketogenic diet (KD) in patients with relapsing multiple sclerosis (MS) and define the impact on laboratory and clinical outcome metrics. METHODS: Sixty-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. RESULTS: Eighty-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. CONCLUSION: KDs 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 INFORMATION: Registered 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.

Body size perceptions & diet modification in youth with multiple sclerosis.

BACKGROUND: Investigate the perceptions of pediatric multiple sclerosis (MS) patients regarding their body size and assess the feasibility of recruitment for a study of diet modification in this unique population. METHODS: This cross-sectional study surveyed a cohort of 43 consecutive youth with MS. The survey queried participant demographics, clinical disease characteristics, body size perception, and opinions of diet modification RESULTS: : While over three quarters of surveyed participants were overweight/obese, 58% of these participants did not self-identify as such. A single participant was attempting a diet at the time of survey, but 88% of participants indicated interest in pursuing diet modification. BMI category did not impact an individual's willingness to pursue diet intervention; however, obese participants were more willing to participate in diet intervention for longer durations. CONCLUSION: A significant proportion of MS youth have an elevated BMI, yet the majority have the self-perception that they are not overweight or obese. Regardless of BMI, most youth with MS have an interest in pursuing diet modification in attempts to benefit their disease course.

The Multiple Sclerosis Functional Composite and Symbol Digit Modalities Test as outcome measures in pediatric 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.

Body mass index trajectories in pediatric multiple sclerosis.

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.

TRAYECTORIAS DEL ÍNDICE DE MASA CORPORAL EN ESCLEROSIS MÚLTIPLE PEDIÁTRICA: OBJETIVO: Caracterizar las trayectorias de crecimiento de los niños que desarrollan esclerosis múltiple en comparación con los valores normativos de desarrollo típico, los pares regionales y los Centros para el Control de Enfermedades (CDC). MÉTODO: Este estudio de casos y controles recopiló el peso, la estatura y el índice de masa corporal (IMC) en 40 pacientes pediátricos consecutivos con esclerosis múltiple (28 mujeres, 12 varones), además de 120 compañeros con desarrollo típico (84 mujeres, 36 varones), identificados y emparejados por año de nacimiento, sexo, etnia y estatus socioeconómico. Los valores de IMC se convirtieron en puntuaciones z basándose en los valores de referencia de los CDC y se compararon con respecto a la edad entre nuestras dos cohortes y por años en relación con el inicio de esclerosis múltiple para los casos. RESULTADOS: La edad media para el inicio clínico de la esclerosis múltiple fue de 15 años. Las puntuaciones z de IMC son significativamente más altas para los pacientes con esclerosis múltiple en comparación con los pares con desarrollo demográfico y estándares CDC. Estas diferencias significativas en el IMC se observan a partir de los 4 años de edad. Las trayectorias de altura fueron similares entre los individuos de casos y controles y los valores normativos de los CDC. INTERPRETACIÓN: El IMC en la esclerosis múltiple pediátrica es notablemente más alto, comenzando en la primera infancia, años antes del inicio clínico de la enfermedad.

TRAJETÓRIAS DO ÍNDICE DE MASSA CORPORAL EM ESCLEROSE MÚLTIPLA PEDIÁTRICA: OBJETIVO: Caracterizar as trajetórias de crescimento de crianças que desenvolvem esclerose múltipla comparadas com pares regionais que se desenvolvem tipicamente e valores normativos do Centro para Controle de Doenças (CDC). MÉTODO: Este estudo de caso-controle coletou peso, altura e índice de massa corporal (IMC) em 40 pacientes pediátricos consecutivos com esclerose múltipla (28 do sexo feminino, 12 do sexo masculino), além de 120 pares com desenvolvimento típico (84 do sexo feminino, 36 do sexo masculino), pareados para ano de nascimento, sexo, etnia, e nível sócio-econômico. Os valores de IMC foram convertidos para escores z com base nos valores de referência do CDC e comparados com relação à idade entre as duas coortes, e por anos com relação ao início da esclerose múltipla para os casos. RESULTADOS: A idade mediana para o início clínico da esclerose múltipla foi 15 anos. Os escores z do IMC foram significativamente mais altos para os pacientes com esclerose múltipla comparados aos pares com desenvolvimento típico e demograficamente pareados, e aos padrões do CDC. Estas diferenças significativas no IMC são notadas a partir dos 4 anos de idade. As trajetórias de altura foram similares entre casos, controles e valores normativos do CDC. INTERPRETAÇÃO: O IMC em esclerose múltipla pediátrica é marcadamente mais alto, iniciando cedo na infância, anos antes do início clínico da doença.