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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.
Assuntos
Dieta Cetogênica , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Dieta Cetogênica/efeitos adversos , Fadiga , Humanos , Esclerose Múltipla Recidivante-Remitente/psicologia , Estudos Prospectivos , Qualidade de VidaRESUMO
BACKGROUND: ADS-5102, a delayed-release, extended-release (DR/ER) amantadine, improved walking speed in MS in a Phase 2 trial. OBJECTIVE: The aim of this study was to present primary results of a Phase 3, double-blind, ADS-5102 trial (INROADS) for walking speed. METHODS: Adult participants with MS and walking impairment, not currently using amantadine or dalfampridine, underwent 4-week placebo run-in before randomization 1:1:1 to placebo, 137 or 274 mg/day ADS-5102 for 12 weeks. Primary outcome was the proportion of responders (20% increase in Timed 25-Foot Walk (T25FW) speed) for 274 mg ADS-5102 versus placebo at end of double-blind (Study Week 16). Additional measures included Timed Up and Go (TUG), 2-Minute Walk Test (2MWT), and 12-item Multiple Sclerosis Walking Scale (MSWS-12). RESULTS: In total, 558 participants were randomized and received double-blind treatment. Significantly more participants responded with 274 mg ADS-5102 (21.1%) versus placebo (11.3%). Mean T25FW speed also significantly improved (0.19 ft/s) versus placebo (0.07 ft/s). Other measures were not significant using prespecified hierarchical testing procedure. Adverse events led to discontinuation for 3.8% (placebo), 6.4% (137 mg ADS-5102), and 20.5% (274 mg ADS-5102). CONCLUSION: INROADS met its primary endpoint, showing a significantly greater proportion of participants with meaningful improvement in walking speed for 274 mg ADS-5102 versus placebo. Numeric dose response was seen for some secondary efficacy outcomes and adverse events.
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Esclerose Múltipla , 4-Aminopiridina/uso terapêutico , Adulto , Amantadina/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Método Duplo-Cego , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Caminhada/fisiologiaRESUMO
BACKGROUND: There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis. METHODS: We enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks. The primary efficacy end point was the rate of brain atrophy, as measured by the brain parenchymal fraction (brain size relative to the volume of the outer surface contour of the brain). Major secondary end points included the change in the pyramidal tracts on diffusion tensor imaging, the magnetization transfer ratio in normal-appearing brain tissue, the thickness of the retinal nerve-fiber layer, and cortical atrophy, all measures of tissue damage in multiple sclerosis. RESULTS: Of 255 patients who underwent randomization, 129 were assigned to ibudilast and 126 to placebo. A total of 53% of the patients in the ibudilast group and 52% of those in the placebo group had primary progressive disease; the others had secondary progressive disease. The rate of change in the brain parenchymal fraction was -0.0010 per year with ibudilast and -0.0019 per year with placebo (difference, 0.0009; 95% confidence interval, 0.00004 to 0.0017; P=0.04), which represents approximately 2.5 ml less brain-tissue loss with ibudilast over a period of 96 weeks. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression. CONCLUSIONS: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. (Funded by the National Institute of Neurological Disorders and Stroke and others; NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942 .).
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Encéfalo/patologia , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Inibidores de Fosfodiesterase/uso terapêutico , Piridinas/uso terapêutico , Adulto , Atrofia/prevenção & controle , Encéfalo/diagnóstico por imagem , Depressão/induzido quimicamente , Imagem de Tensor de Difusão , Progressão da Doença , Método Duplo-Cego , Feminino , Gastroenteropatias/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/patologia , Inibidores de Fosfodiesterase/efeitos adversos , Piridinas/efeitos adversosRESUMO
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.
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Índice de Massa Corporal , Esclerose Múltipla/fisiopatologia , Adolescente , Adulto , Estatura , Peso Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Esclerose Múltipla/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. OBJECTIVES: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. METHODS: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials. CONCLUSION: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS ( http://www.cdisc.org/therapeutic#MS ) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies.
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Bases de Dados Factuais , Avaliação da Deficiência , Esclerose Múltipla , Avaliação de Resultados em Cuidados de Saúde/normas , HumanosRESUMO
BACKGROUND: The 12-item Multiple Sclerosis Walking Scale (12-MSWS) is a validated questionnaire which assessed walking function; it has been widely adopted in multiple sclerosis (MS) clinical research. OBJECTIVE: Identify and validate clinically meaningful 12-MSWS benchmarks in MS. METHODS: Cross-sectional study of 159 MS patients permitted identification of clinically meaningful 12-MSWS benchmarks based on their relationship to real-life anchors. Identified 12-MSWS benchmarks were then validated in a second population of 96 subjects using measures of ambulation, cognition, and patient-reported outcomes. RESULTS: 12-MSWS score of 0-24.99 was associated with working outside the home and assistance-free mobility; 25-49.99 was associated with gait disability and difficulty doing housework; 50-74.99 was associated with unemployment, government healthcare, cane use, and difficulty performing instrumental activities of daily living (IADLs); and 75-100 was associated with change in occupation due to walking, mobility impairment requiring bilateral assistance, and inability to perform IADLs. During the validation step, strong linear associations were identified between 12-MSWS benchmarks and other MS-related disability outcome measures, including ambulatory and non-ambulatory measures. CONCLUSION: We have identified clinically meaningful 12-MSWS benchmarks which define four groups differentiated by increasing levels of mobility impairment and associated loss of functional independence. These data provide insight into how 12-MSWS translate to meaningful functional limitations in MS.
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Benchmarking/métodos , Avaliação da Deficiência , Esclerose Múltipla/complicações , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , CaminhadaRESUMO
BACKGROUND: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. OBJECTIVE: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. METHODS: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm ( n = 215) data, we analyzed disability progression using a novel progression endpoint, "EDSS-Plus," defined as progression on ⩾1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ⩾24 weeks apart and with a ⩾20% minimum threshold change for T25FW and 9HPT. RESULTS: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. CONCLUSION: The 24-week confirmed minimum worsening of ⩾20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.
Assuntos
Esclerose Múltipla Crônica Progressiva/fisiopatologia , Adulto , Avaliação da Deficiência , Pessoas com Deficiência/reabilitação , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/diagnóstico , Índice de Gravidade de Doença , Fatores de Tempo , Extremidade Superior/fisiopatologia , Caminhada/fisiologiaRESUMO
BACKGROUND: Fatigue is a prevalent and functionally disabling symptom for individuals living with multiple sclerosis (MS) which is poorly understood and multifactorial in etiology. Bladder dysfunction is another common MS symptom which limits social engagement and quality of life. To manage bladder issues, individuals with MS tend to limit their fluid intake, which may contribute to a low-hydration (LoH) state and fatigue. OBJECTIVE: To evaluate the relationship between patient-reported MS fatigue, bladder dysfunction, and hydration status. METHODS: We performed a prospective cross-sectional study in 50 women with MS. Participants submitted a random urine sample and completed several fatigue-related surveys. Using a urine specific gravity (USG) threshold of 1.015, we classified MS subjects into two groups: high-hydration (HiH) and LoH states. RESULTS: LoH status was more common in MS subjects with bladder dysfunction. Statistically significant differences in self-reported Fatigue Performance Scale were observed between HiH and LoH subjects (p = 0.022). USG was significantly correlated with fatigue as measured by the MS Fatigue Severity Scale (FSS) score (r = 0.328, p = 0.020). CONCLUSION: Hydration status correlates with self-reported fatigue, with lower fatigue scores found in those with HiH status (USG < 1.015).
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Desidratação/fisiopatologia , Esclerose Múltipla/fisiopatologia , Bexiga Urinaria Neurogênica/fisiopatologia , Equilíbrio Hidroeletrolítico , Adulto , Estudos Transversais , Desidratação/epidemiologia , Comportamento de Ingestão de Líquido , Fadiga , Feminino , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Bexiga Urinaria Neurogênica/epidemiologia , Incontinência Urinária/epidemiologia , Incontinência Urinária/fisiopatologiaRESUMO
BACKGROUND: The Multiple Sclerosis Walking Scale (MSWS-12) is the predominant patient-reported measure of multiple sclerosis (MS) -elated walking ability, yet it had not been analyzed using item response theory (IRT), the emerging standard for patient-reported outcome (PRO) validation. This study aims to reduce MSWS-12 measurement error and facilitate computerized adaptive testing by creating an IRT model of the MSWS-12 and distributing it online. METHODS: MSWS-12 responses from 284 subjects with MS were collected by mail and used to fit and compare several IRT models. Following model selection and assessment, subpopulations based on age and sex were tested for differential item functioning (DIF). RESULTS: Model comparison favored a one-dimensional graded response model (GRM). This model met fit criteria and explained 87 % of response variance. The performance of each MSWS-12 item was characterized using category response curves (CRCs) and item information. IRT-based MSWS-12 scores correlated with traditional MSWS-12 scores (r = 0.99) and timed 25-foot walk (T25FW) speed (r = -0.70). Item 2 showed DIF based on age (χ 2 = 19.02, df = 5, p < 0.01), and Item 11 showed DIF based on sex (χ 2 = 13.76, df = 5, p = 0.02). CONCLUSIONS: MSWS-12 measurement error depends on walking ability, but could be lowered by improving or replacing items with low information or DIF. The e-MSWS-12 includes IRT-based scoring, error checking, and an estimated T25FW derived from MSWS-12 responses. It is available at https://ms-irt.shinyapps.io/e-MSWS-12 .
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Avaliação da Deficiência , Esclerose Múltipla/terapia , Perfil de Impacto da Doença , Caminhada/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We describe the case of a 73-year-old woman presenting with headaches, confusion, and vision disturbances. Brain MRI showed a large T2-hyperintense lesion in the right temporo-occipital region with vasogenic edema and leptomeningeal enhancement. A leptomeningeal biopsy was performed, which led to a definitive diagnosis.
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Confusão , Transtornos da Visão , Idoso , Feminino , Humanos , Edema Encefálico/diagnóstico por imagem , Confusão/etiologia , Imageamento por Ressonância Magnética , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Transtornos da Visão/etiologia , Transtornos da Visão/diagnóstico , Campos Visuais/fisiologia , Substância Branca/patologia , Substância Branca/diagnóstico por imagemRESUMO
Background and Objectives: Multiple sclerosis (MS) commonly affects women in their childbearing years, necessitating discussion between patients and their MS treatment team around the issues of family planning, pregnancy, and postpartum experiences. This study assessed the impact of a diagnosis of MS on women's reproductive decision-making and on their perception of counseling received surrounding pregnancy. It also sought to evaluate trends in pregnancy and postpartum experiences and determine whether experiences differed by race, ethnicity, and zip code. Methods: Women with an MS diagnosis seen at the University of Virginia MS Clinic or at Virginia Commonwealth University (VCU) MS Clinic were invited to participate in a survey study. MS disease and pregnancy history, and, when appropriate, reasons for pregnancy avoidance were collected. Respondents who had >1 pregnancy following MS diagnosis were asked to evaluate the counseling they received from medical professionals and to share their pregnancy experiences including complications during pregnancy, delivery outcomes, and postpartum experience including breastfeeding. Results: Of the 280 respondents, 76.6% were currently receiving MS specialty care. Most of them (79.3%) had not been pregnant following MS diagnosis. Of them, 20.1% indicated that this decision was driven by MS-related concerns: MS worsening with pregnancy (47%); ability to care for child secondary to MS (35%); passing MS onto child (19%); stopping disease-modifying therapies to attempt pregnancy (14%); lack of knowledge about options for pregnancy and MS (9%). Women with a more recent estimated decade of pregnancy were more likely to report neurologist counseling regarding MS and pregnancy (pregnancy before 2000: 40%, 2000-2010: 64.7%, 2010- present: 83.3%; χ2 0.020). Breastfeeding initiation was reported in 71.4% of postdiagnosis pregnancies (median duration 6 months, interquartile range 1.75-11). Discussion: Over the past few decades, women with MS have received a wide range of evolving guidance surrounding family planning, pregnancy, and postpartum care. Survey data suggest improvements in MS/pregnancy counseling and medical management in recent years, which may be driven by an increase in research in the field. There remains an important need and opportunity to improve counseling of women with MS who are considering pregnancy.
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A 42-year-old woman and active cocaine user complained of subacutely worsening blurred vision and imbalance. Examination of the brain MRI showed rapidly expanding white matter lesions. Brain biopsy was consistent with inflammatory demyelination. Given an unusual presentation and a history of cocaine use, a broad differential diagnosis was considered including neurologic toxidromes.
Assuntos
Cocaína , Esclerose Múltipla , Substância Branca , Feminino , Humanos , Adulto , Esclerose Múltipla/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imageamento por Ressonância Magnética , NeuroimagemRESUMO
A 79-year-old woman presented with subacutely worsening headaches and right arm weakness. MRI showed diffuse pachymeningeal enhancement. Serologic workup revealed elevated erythrocyte sedimentation rate and C-reactive protein. CSF demonstrated elevated opening pressure, a lymphocytic pleocytosis, and elevated protein. We discuss our differential diagnosis and distinguish between 2 overlapping clinical entities.
Assuntos
Cefaleia , Humanos , Feminino , Idoso , Cefaleia/etiologia , Diagnóstico Diferencial , Meningite/diagnóstico , Meningite/complicações , Imageamento por Ressonância Magnética , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnósticoRESUMO
BACKGROUND AND OBJECTIVES: To understand the challenges and facilitators of a successful academic neurology research career broadly and to identify gender-based disparities specifically. METHODS: In 2019, participants self-identifying as researchers, preregistered for the American Academy of Neurology (AAN) Annual Meeting, ≥7 years out of residency, and authors of ≥1 AAN meeting abstract submission (2006-2009) were selected to participate in the qualitative study (purposeful sampling strategy). To increase diversity, 15 participants were invited by members involved in the AAN until interviews were complete. The AAN at the time of the study asked gender using sex-based terms. Participants were asked predetermined and open-ended questions. Themes were generated using a flexible coding methodology. RESULTS: Sixty neurologists (31 women, 29 men) participated in the focus groups and individual interviews. Six predetermined domains relevant to a successful neurology research career were explored: success definitions, facilitators, barriers, biases and harassment, mitigation strategies, and participant recommendations. Gender-based differences were noted during discussions focused on barriers and biases and harassment. Lack of women mentors, under-representation of women in senior faculty positions, and competing responsibilities when children are young were identified as barriers to women's success. Participants acknowledged that known gender disparities in compensation, academic promotion, and publications disproportionately affect women. Women shared more experiences of bias and harassment. Some men felt that gender-based biases were minimal to nonexistent. Participants shared their recommendations on ways to mitigate gender disparities and pursue a neurology research career. Leadership involvement locally and nationally in advocating and implementing change outside academic institutions was also mentioned as being valuable. DISCUSSION: Our findings may not be generalizable to academic neurologists outside the United States. Women academic neurology researchers experienced disparities across several domains affecting success: lower compensation, fewer women mentors, bias, and harassment. Women are less likely to be promoted, have less research success, and job satisfaction. Shared experiences of bias and harassment among women neurology researchers indicate continuing opportunity for education among departments and colleagues for preventive measures. These qualitative results indicate gender disparities among US-based neurology researchers and highlight the importance of the continued need to work toward equality and equity in disparate gender-related issues in the careers of neurology researchers.
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Neurologia , Pesquisa Qualitativa , Sexismo , Humanos , Feminino , Masculino , Adulto , Médicas , Mentores , Neurologistas , Pessoa de Meia-Idade , Docentes de MedicinaRESUMO
Background: Multiple Sclerosis (MS) disease progression has notable heterogeneity among patients and over time. There is no available single method to predict the risk of progression, which represents a significant and unmet need in MS. Methods: MS and healthy control (HC) participants were recruited for a 2-year observational study. A latent-variable growth mixture model (GMM) was applied to cluster baseline 6-min walk gait speed trajectories (6MWGST). MS patients within different 6 MWGST clusters were identified and stratified. The group membership of these MS patients was compared against 2-year confirmed-disease progression (CDP). Clinical and patient-reported outcome (PRO) measures were compared between HC and MS subgroups over 2 years. Results: 62 MS and 41 HC participants completed the 2-year study. Within the MS cohort, 90% were relapsing MS. Two distinct patterns of baseline 6 MWGST emerged, with one cluster displaying a faster gait speed and a typical "U" shape, and the other showing a slower gait speed and a "flattened" 6 MWGST curve. We stratified MS participants in each cluster as low- and high-risk progressors (LRP and HRP, respectively). When compared against 2-year CDP, our 6 MWGST approach had 71% accuracy and 60% positive predictive value. Compared to the LRP group, those MS participants stratified as HRP (15 out of 62 MS participants), were on average 3.8 years older, had longer MS disease duration and poorer baseline performance on clinical outcomes and PROs scores. Over the subsequent 2 years, only the HRP subgroup showed a significant worsened performance on 6 MW, clinical measures and PROs from baseline. Conclusion: Baseline 6 MWGST was useful for stratifying MS participants with high or low risks for progression over the subsequent 2 years. Findings represent the first reported single measure to predict MS disease progression with important potential applications in both clinical trials and care in MS.
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BACKGROUND: Ketogenic diets (KDs) are safe and tolerable in people with multiple sclerosis (MS). While many patient-reported and clinical benefits are noted, the sustainability of these diets outside of a clinical trial is unknown. AIMS: Evaluate patient perceptions of the KD following intervention, determine the degree of adherence to KDs post-trial, and examine what factors increase the likelihood of KD continuation following the structured diet intervention trial. METHODS: Sixty-five subjects with relapsing MS previously enrolled into a 6-month prospective, intention-to-treat KD intervention. Following the 6-month trial, subjects were asked to return for a 3-month post-study follow-up, at which time patient reported outcomes, dietary recall, clinical outcome measures, and laboratory values were repeated. In addition, subjects completed a survey to evaluate sustained and attenuated benefits following completion of the intervention phase of the trial. RESULTS: Fifty-two subjects (81%) returned for the 3-month post-KD intervention visit. Twenty-one percent reported continued adherence to a strict KD and an additional 37% reported adhering to a liberalized, less restrictive form of the KD. Those subjects with greater reductions in body mass index (BMI) and fatigue at 6-months on-diet were more likely to continue on KD following trial completion. Using intention-to-treat analysis, patient-reported and clinical outcomes at 3-months post-trial remained significantly improved from baseline (pre-KD), though the degree of improvement was slightly attenuated relative to outcomes at 6-months on KD. Regardless of diet type following the KD intervention, dietary patterns shifted toward greater protein and polyunsaturated fats and less carbohydrate/added sugar consumption. CONCLUSIONS: Following the 6-month KD intervention study, the majority of subjects elected to continue on KD, though many pursued a more liberal limit for carbohydrate restriction. Those who experienced a greater reduction in BMI or fatigue were more likely to continue with strict KD. The 6-month KD intervention induced persistent changes to dietary habits in the months following study completion. TRIAL REGISTRATION INFORMATION: Registered on Clinicaltrials.gov under registration number NCT03718247, posted on Oct 24, 2018. First patient enrollment date: Nov 1, 2018. Link: https://clinicaltrials.gov/ct2/show/NCT03718247?term=NCT03718247&draw=2&rank=1.
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Dieta Cetogênica , Esclerose Múltipla , Humanos , Estudos Prospectivos , Carboidratos , FadigaRESUMO
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.
Assuntos
Dieta Cetogênica , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Filamentos Intermediários , BiomarcadoresRESUMO
BACKGROUND: Researchers have recently advocated for the 2-minute walk (2MW) as an alternative for the 6-minute walk (6MW) to assess long distance ambulation in persons with multiple sclerosis (MS). This recommendation has not been based on physiological considerations such as the rate of oxygen consumption (V·O2) over the 6MW range. OBJECTIVE: This study examined the pattern of change in V·O2 over the range of the 6MW in a large sample of persons with MS who varied as a function of disability status. METHOD: Ninety-five persons with clinically-definite MS underwent a neurological examination for generating an Expanded Disability Status Scale (EDSS) score, and then completion of the 6MW protocol while wearing a portable metabolic unit and an accelerometer. RESULTS: There was a time main effect on V·O2 during the 6MW (p=.0001) such that V·O2 increased significantly every 30 seconds over the first 3 minutes of the 6MW, and then remained stable over the second 3 minutes of the 6MW. This occurred despite no change in cadence across the 6MW (p=.84). CONCLUSIONS: The pattern of change in V·O2 indicates that there are different metabolic systems providing energy for ambulation during the 6MW in MS subjects and steady state aerobic metabolism is reached during the last 3 minutes of the 6MW. By extension, the first 3 minutes would represent a test of mixed aerobic and anaerobic work, whereas the second 3 minutes would represent a test of aerobic work during walking.
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Teste de Esforço , Esclerose Múltipla/diagnóstico , Consumo de Oxigênio/fisiologia , Caminhada , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Fatores de TempoRESUMO
PURPOSE OF REVIEW: This article provides an overview of genetic, environmental, and lifestyle risk factors affecting the disease course of multiple sclerosis (MS) and reviews the pathophysiologic characteristics of both relapsing and progressive MS. RECENT FINDINGS: The prevalence of MS has increased in recent decades, and costs of care for patients with MS have risen dramatically. Black, Asian, and Hispanic individuals may be at risk for more severe MS-related disability. Multiple genetic MS risk factors have been identified. Factors such as low vitamin D levels and a history of Epstein-Barr virus, smoking, and obesity, especially during childhood, also influence MS risk. Traditionally thought to be a T-cell-mediated disease, recent research has highlighted the additional roles of B cells and microglia in both relapsing and progressive MS. SUMMARY: Complex interactions between genetic, environmental, and lifestyle factors affect the risk for MS as well as the disease course. People of color have historically been underrepresented in both MS clinical trials and literature, but current research is attempting to better clarify unique considerations in these groups. MS pathology consists of the focal inflammatory lesions that have been well characterized in relapsing MS, as well as a more widespread neurodegenerative component that is posited to drive progressive disease. Recent advances in characterization of both the inflammatory and neurodegenerative aspects of MS pathophysiology have yielded potential targets for future therapeutic options.
Assuntos
Infecções por Vírus Epstein-Barr , Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Progressão da Doença , Herpesvirus Humano 4 , Humanos , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/genética , Esclerose Múltipla/terapia , Recidiva , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate the relationships among patient-reported balance confidence and social satisfaction and social participation in people with multiple sclerosis (pwMS). METHODS: 75 ambulatory pwMS who had sustained at least two falls or near falls in the prior two months self-reported their balance confidence (Activities-specific Balance Confidence (ABC) questionnaire) and social satisfaction and participation (Patient Reported Outcomes Measurement Information System (PROMIS) measures). Correlations between the ABC and PROMIS measures were examined using Spearman's rank correlation. RESULTS: In a cross-sectional analysis, ABC scores and PROMIS scores for social satisfaction and social participation were statistically significantly correlated (ρ 0.37-0.54, p ≤ 0.001). The correlation between balance confidence and social satisfaction was consistently stronger at each time point than between balance confidence and social participation. CONCLUSION: Self-reported balance confidence is associated with both social satisfaction and social participation in pwMS who fall. The causal direction of this relationship remains uncertain.