Author Of 1 Presentation
PS13.02 - Randomized Trial of Amantadine, Modafinil and, Methylphenidate for Multiple Sclerosis Fatigue
Abstract
Background
Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis (MS); however, the evidence supporting their efficacy is sparse and conflicting.
Objectives
Our goal was to compare the efficacy of these three medications against each other and placebo in patients with MS-related fatigue.
Methods
In this randomized, double-blind, placebo-controlled, four-sequence, four-period crossover trial, patients with MS fatigue received twice-daily oral amantadine, modafinil, methylphenidate, or placebo, each given for up to six weeks. The primary outcome measure was the Modified Fatigue Impact Scale (MFIS) measured while taking the highest tolerated dose. Secondary outcomes included measures of sleepiness, adverse events, and the maximal tolerated dose of each medication.
Results
A total of 141 patients were enrolled and randomly assigned to one of four medication administration sequences. Data from 136 participants were available for the intent-to-treat analysis of the primary outcome. The estimated mean values of MFIS total scores at baseline and the maximal tolerated dose were as follows: 51.3 at baseline, 40.7 with placebo, 41.2 with amantadine, 39.0 with modafinil, and 38.7 with methylphenidate (P=0.20 for the overall medication effect). As compared to placebo (30.6%), higher proportions of participants reported adverse events while taking amantadine (38.6%), modafinil (40.0%), and methylphenidate (39.5%).
Conclusions
Amantadine, modafinil, and methylphenidate were not superior to placebo in improving MS-related fatigue and caused more frequent adverse events. The results of this study do not support an indiscriminate use of amantadine, modafinil, and methylphenidate for the treatment of fatigue in MS. (ClinicalTrials.gov number, NCT03185065.)
Author Of 3 Presentations
P0696 - Characteristics of Myelin Oligodendrocyte Glycoprotein Antibody Positive Children with Demyelinating Disorders (ID 1565)
Abstract
Background
Myelin oligodendrocyte glycoprotein (MOG) antibodies (ab) are detected in approximately 1/3 of children with demyelinating disease at onset; presentations commonly overlap with optic neuritis, neuromyelitis optica spectrum disorder (NMOSD) or acute disseminated encephalomyelitis. Serum MOG-ab titers have unclear relevance to disease course, and optimal treatment strategy is unknown.
Objectives
We aimed to characterize children with CNS demyelinating disorders who tested positive for MOG-ab. We also aimed to evaluate the relevance of serum MOG-ab titers for diagnosis, risk and severity of subsequent demyelinating events. Finally, we aimed to evaluate treatment strategies for MOG-ab positive children.
Methods
This retrospective study evaluated children with demyelinating disorders with onset before 18 years of age seen at the University of California, San Francisco who tested positive for MOG-ab (tested by live cell-based fluorescent activated cell sorting assay at Mayo Clinic) between October 2006-June 2020. Demographic information, clinical presentation at onset, MRI, CSF, brain biopsy, and treatment data were collected by chart review.
Results
Sixty children were included (mean onset age 8.2 years; 53% female; 72% white; 40% Hispanic or Latino). The most common clinical localization at onset included optic nerve (ON) (53%) and/or brainstem/cerebellum (42%). 83% of initial events were severe. Median EDSS assessed within 6 months of onset was 1.5 (range 0-4). 81% of initial brain MRIs had T2 bright lesions and 61% had gadolinium-enhancing lesions; T2 bright lesions were most commonly seen in subcortical areas (50%) and/or brainstem/cerebellum (33%). Oligoclonal bands were positive in 17% of initial CSF. 57% had initial serum MOG-ab titers ≥1:100 (median time from onset to first titer 15.4 months). Titers ≥1:320 were only observed within 2 months of an event (disease onset or relapse). While 38% had no relapses (mean follow-up 1.42 years), those who did had a median of 2 relapses (mean follow-up 3.83 years). The most commonly used treatments were interferon beta (28%) and rituximab (27%). Brain biopsy was performed in 2 patients and showed overt demyelination and prominent infiltration of monocyte lineage and polymorphonuclear cells.
Conclusions
The most common clinical onset localizations in MOG-ab positive children were ON and brainstem/cerebellum. Higher MOG-ab titers were only observed close to a clinical event.
P1117 - Clinical and radiologic disease activity in pregnancy and postpartum in multiple sclerosis (ID 1930)
Abstract
Background
Multiple sclerosis (MS) typically begins between the ages of 20 to 40 years and has a female to male ratio of 3:1. As such, MS is primarily diagnosed in women of reproductive age. Several studies have demonstrated that women experience fewer MS relapses during the immunotolerant state of pregnancy; however, an increase in relapses has been observed postpartum. As clinical inflammatory activity postpartum could be confused with other common neurological conditions, magnetic resonance imaging (MRI) detects new inflammatory lesions objectively. No large case series of MRI-defined postpartum inflammatory activity have been published, to our knowledge.
Objectives
To evaluate clinical and radiological inflammatory activity in women with multiple sclerosis during pregnancy and postpartum.
Methods
We performed a retrospective analysis of prospectively collected clinical and MRI reports for women who became pregnant while followed at the UCSF Multiple Sclerosis Center between 2005 and 2018. Annualized relapse rate (ARR) and proportion of brain MRIs with new T2-hyperintense or gadolinium enhancing (Gd+) lesions were compared before, during and after pregnancy.
Results
We identified 155 pregnancies in 119 women (median EDSS 2.0). For the 146 live birth pregnancies, pre-pregnancy ARR was 0.33; ARR decreased during pregnancy, particularly the third trimester (ARR 0.10, p=0.017) and increased in the three months postpartum (ARR 0.61, p=0.012); 16.5% of women experienced a clinically meaningful increase in EDSS. Among 70 pregnancies with paired brain MRIs available, 52.5% had new T2 and/or Gd+ lesions postpartum compared to 32.2% pre-pregnancy (P=0.023). Postpartum clinical relapses were associated with Gd+ lesions (p<0.0001). However, for patients without postpartum relapses, surveillance brain MRIs revealed new T2 and/or Gd+ lesions in 30.9%. Protective effects of exclusive breastfeeding for ≥3 months (odds ratio (OR)=0.20, 95% CI 0.047-0.82) and early initiation of MS therapy (OR=0.28, 0.080-0.98) were observed for relapses.
Conclusions
We confirm prior reports of decreased relapse rate during pregnancy and increased rate in the three months postpartum. We report a significant association between this clinical activity and inflammation on MRI, as well as postpartum radiologic activity even in the absence of relapses. Both clinical and radiologic reassessment may inform optimal treatment decision-making during the high-risk early postpartum period.
P1135 - Risk factors for peripartum depression in women with multiple sclerosis (ID 1419)
Abstract
Background
Peripartum depression (PPD), i.e. depression in late pregnancy to 1 year postpartum, occurs in 7-19% of women. There are limited data on PPD in multiple sclerosis (MS).
Objectives
To evaluate the prevalence of PPD in women with MS, and to evaluate risk factors for PPD in MS, both factors associated with PPD in the general population, as well as disease-related factors.
Methods
We performed retrospective analysis of prospectively collected clinical data. Women with MS followed at UCSF MS Center who became pregnant from 2015-2018 were identified in the electronic medical record. The primary outcome was PPD determined by clinical record review. Prevalence of PPD was estimated with logistic regression with generalized estimating equations (GEE), accounting for women with multiple pregnancies. Univariable analyses with GEE logistic regression evaluated predictors of PPD (age, marital status, parity, delivery season, prematurity, birth weight, delivery mode, premorbid depression/anxiety, antidepressant discontinuation, sleep disturbance, breastfeeding). Factors significant in univariable analyses were included in multivariable analysis. GEE logistic regression evaluated association between inflammatory disease activity (relapses in pregnancy/postpartum; gadolinium enhancing lesions postpartum), disease severity (Expanded Disability Status Scale, EDSS) and PPD.
Results
We identified 143 pregnancies (age 33.1+/-4.7 years; 93% relapsing remitting MS, 7% clinically isolated syndrome; 45% premorbid depression) in 111 women who had live birth outcomes and known PPD status. PPD was present in 12.6% (95% CI 7.3-17.8) of pregnancies. In univariable analyses, statistically significant factors associated with PPD included older age (OR 1.16, 95% CI 1.03-1.32 for 1-year increase), primiparity (OR 4.02, 95% CI 1.14-14.23), premorbid depression (OR 3.70, 95% CI 1.27-10.01), postpartum sleep disturbance (OR 3.23, 95% CI 1.17-8.91) and breastfeeding difficulty (OR 3.58, 95% CI 1.27-10.08). Maternal age (OR 1.17, 95% CI 1.02-1.34), primiparity (OR 8.10, 95% CI 1.38-47.40) and premorbid depression (OR 3.89, 95% CI 1.04-14.60) remained associated with PPD in multivariable analyses. Relapses, MRI activity and EDSS were not associated with PPD.
Conclusions
PPD in MS was similar to the general population, but was likely underestimated due to lack of standardized screening. PPD could influence maternal self-management of MS. Prospective evaluation with screening for PPD is needed.