Faculty Bibliography
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634
Fatigue in Parkinson's disease: report from a mutidisciplinary symposium
Fatigue is a severe problem for many people living with Parkinson's disease (PD). Best estimates suggest that more than 50% of patients experience this debilitating symptom. Little is known about its etiology or treatment, making the understanding of fatigue a true unmet need. As part of the Parkinson's Disease Foundation Community Choice Research Program, patients, caregivers, and scientists attended a symposium on fatigue on 16 and 17 October 2014. We present a summary of that meeting, reviewing what is known about the diagnosis and treatment of fatigue, its physiology, and what we might learn from multiple sclerosis (MS), depression, and cancer-disorders in which fatigue figures prominently too. We conclude with focused recommendations to enhance our understanding and treatment of this prominent problem in PD.
PMCID:4883681
PMID: 27239558
ISSN: 2373-8057
CID: 2153602
Clinical features of neuromyelitis optica in children: US Network of Pediatric MS Centers report
OBJECTIVE: To compare clinical features of pediatric neuromyelitis optica (NMO) to other pediatric demyelinating diseases. METHODS: Review of a prospective multicenter database on children with demyelinating diseases. Case summaries documenting clinical and laboratory features were reviewed by an adjudication panel. Diagnoses were assigned in the following categories: multiple sclerosis (MS), acute disseminated encephalomyelitis, NMO, and recurrent demyelinating disease not otherwise specified. RESULTS: Thirty-eight cases of NMO were identified by review panel, 97% of which met the revised International Panel on NMO Diagnosis NMO-SD 2014 criteria, but only 49% met 2006 Wingerchuk criteria. Serum or CSF NMO immunoglobulin G (IgG) was positive in 65% of NMO cases that were tested; however, some patients became seropositive more than 3 years after onset despite serial testing. No patient had positive CSF NMO IgG and negative serum NMO IgG in contemporaneous samples. Other than race (p = 0.02) and borderline findings for sex (p = 0.07), NMO IgG seropositive patients did not differ in demographic, clinical, or laboratory features from seronegatives. Visual, motor, and constitutional symptoms (including vomiting, fever, and seizures) were the most common presenting features of NMO. Initiation of disease-modifying treatment was delayed in NMO vs MS. Two years after onset, patients with NMO had higher attack rates, greater disability accrual measured by overall Expanded Disability Status Scale score, and visual scores than did patients with MS. CONCLUSION: The new criteria for NMO spectrum disorders apply well to the pediatric setting, and given significant delay in treatment of NMO compared to pediatric MS and worse short-term outcomes, it is imperative to apply these to improve access to treatment.
PMCID:4733158
PMID: 26683648
ISSN: 1526-632x
CID: 2153522
Subcutaneous interferon beta-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study
BACKGROUND: To further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW). METHODS: Anonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997-2009) of study participants (who received subcutaneous interferon beta-1a before age 18years) from the US and ROW. Samples were stratified by age (preadolescents [<12years] and adolescents [12-17years]). RESULTS: US adolescents had a higher mean body mass index versus ROW adolescents (BMI; 27.2 versus 22.5kg/m(2)), started disease-modifying therapy (DMT) earlier after the first relapse, were more likely to have received a DMT before initiating subcutaneous interferon beta-1a, had a higher relapse rate, and were more likely to switch from subcutaneous interferon beta-1a to another DMT before the end of the observation period. CONCLUSIONS: This retrospective analysis of a multinational sample of pediatric MS patients who received subcutaneous interferon beta-1a found that those from the US had higher BMI, relapsed more frequently, and were managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance.
PMID: 27000217
ISSN: 1878-5883
CID: 2051462
Genetic predictors of relapse rate in pediatric MS
BACKGROUND: Genetic ancestry, sex, and individual alleles have been associated with multiple sclerosis (MS) susceptibility. OBJECTIVE: To determine whether established risk factors for disease onset are associated with relapse rate in pediatric MS. METHODS: Whole-genome genotyping was performed for 181 MS or high-risk clinically isolated syndrome patients from two pediatric MS centers. Relapses and disease-modifying therapies were recorded as part of continued follow-up. Participants were characterized for 25-hydroxyvitamin D serum status. Ancestral estimates (STRUCTURE v2.3.1), human leukocyte antigen (HLA)-DRB1*15 carrier status (direct sequencing), sex, and a genetic risk score (GRS) of 110 non-HLA susceptibility single-nucleotide polymorphisms (SNPs) were evaluated for association with relapse rate with Cox and negative binomial regression models. RESULTS: Over 622 patient-years, 408 relapses were captured. Girls had greater relapse rate than boys (incident rate ratio (IRR) = 1.40, 95% confidence interval (CI) = 1.04-1.87, p = 0.026). Participants were genetically diverse; ~40% (N = 75) had <50% European ancestry. HLA-DRB1*15 status modified the association of vitamin D status (pixn = 0.022) with relapse rate (per 10 ng/mL, in DRB1*15+ hazard ratio (HR) = 0.72, 95% CI = 0.58-0.88, p = 0.002; in DRB1*15- HR = 0.96, 95% CI = 0.83-1.12, p = 0.64). Neither European ancestry nor GRS was associated with relapse rate. CONCLUSION: We demonstrate that HLA-DRB1*15 modifies the association of vitamin D status with relapse rate. Our findings emphasize the need to pursue disease-modifying effects of MS genes in the context of environmental factors.
PMCID:4945462
PMID: 26769066
ISSN: 1477-0970
CID: 2043122
Behavioral Symptoms in Pediatric Multiple Sclerosis: Relation to Fatigue and Cognitive Impairment
The emotional and behavioral problems associated with pediatric multiple sclerosis remain unclear. Participants with pediatric multiple sclerosis or clinically isolated syndrome (n = 140; ages 5-18 years) completed self- and parent ratings using the Behavioral Assessment System for Children, Second Edition, neurologic exam, the Fatigue Severity Scale, and neuropsychological assessment. Mean self- and parent-ratings on the Behavioral Assessment System for Children, Second Edition, were in the typical range across all scales. However, 33.1% indicated a clinically significant problem on a least 1 scale. Although the type of clinical problems varied across participants, attention problems, somatization, and anxiety were found to be most common. Disease features including duration, age of onset, neurologic disability, and fatigue did not distinguish those with and without clinical problems. However, cognitive functioning significantly predicted the presence of a clinical problem (P = .02). Pediatric multiple sclerosis is associated with a range of nonspecific emotional and behavioral clinical problems, occurring more frequently in those patients with cognitive involvement.
PMCID:4925200
PMID: 26961266
ISSN: 1708-8283
CID: 2046722
Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study
OBJECTIVE:To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. METHODS:CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). RESULTS:DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. CONCLUSIONS:The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.
PMCID:4371413
PMID: 25681448
ISSN: 1526-632x
CID: 5348212
[S.l. : American Psychological Society, New York, 2015]
Cognitive impairment and real-world functioning in multiple sclerosis (MS) : test of everyday cognitive ability (TECA)
(Website)CID: 2238962
Fat, fiber and pediatric MS [Meeting Abstract]
ORIGINAL:0011421
ISSN: 1526-632x
CID: 2236642
Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset
BACKGROUND: Growing evidence suggests an association between adolescent obesity and increased risk of multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to investigate whether weight or body mass index (BMI) in adolescence and young adulthood was associated with age at MS symptom onset. METHODS: Our cohort is comprised of a sub-group of 184 women enrolled in the New York State MS Consortium registry. Individuals were asked to recall their weight at the time of first menstruation and at age 25. BMI was calculated accordingly for age 25. Regression analyses were carried out to investigate the association between weight or BMI and age at onset. RESULTS: Weight at menarche was significantly related to younger age at symptom onset (beta = -0.073, p = 0.001). These results were also found at age 25 for weight (beta = -0.080, p < 0.001) and BMI (beta = -0.448, p = 0.001). Significantly earlier disease onset (26.9 years +/-9.9) was observed in individuals who were overweight at 25 compared to those who were not overweight (32.1 years +/-9.2, p = 0.006). CONCLUSIONS: Women who reported higher weight in adolescence and BMI in early adulthood were younger at MS onset. Future research should investigate whether there is a causal link between body weight and MS, as prevention lifestyle and dietary interventions could be implemented.
PMID: 25392327
ISSN: 1477-0970
CID: 2237042
Gut microbiome in early pediatric MS : a case-control study [Meeting Abstract]
ORIGINAL:0011420
ISSN: 1526-632x
CID: 2236632
