Background:
Clinical relapses are the defining feature of relapsing forms of multiple sclerosis (MS), but relatively little is known about the time course of relapse recovery.
Objective:
The aim of ...this study was to investigate the time course of and patient factors associated with the speed and success of relapse recovery in people with relapsing–remitting MS (RRMS).
Methods:
Using data from CombiRx, a large RRMS trial (clinicaltrials.gov identifier NCT00211887), we measured the time to recovery from the first on-trial relapse. We used Kaplan–Meier survival analyses and Cox regression models to investigate the association of patient factors with the time to unconfirmed and confirmed relapse recovery.
Results:
CombiRx included 1008 participants. We investigated 240 relapses. Median time to relapse recovery was 111 days. Most recovery events took place within 1 year of relapse onset: 202 of 240 (84%) individuals recovered during follow-up, 161 of 202 (80%) by 180 days, and 189 of 202 (94%) by 365 days. Relapse severity was the only factor associated with relapse recovery.
Conclusion:
Recovery from relapses takes place up to approximately 1 year after the event. Relapse severity, but no other patient factors, was associated with the speed of relapse recovery. Our findings inform clinical practice and trial design in RRMS.
To evaluate the incidence and prevalence of drug-resistant epilepsy (DRE) as well as its predictors and correlates, we conducted a systematic review and meta-analysis of observational studies.
Our ...protocol was registered with PROSPERO, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology reporting standards were followed. We searched MEDLINE, Embase, and Web of Science. We used a double arcsine transformation and random-effects models to perform our meta-analyses. We performed random-effects meta-regressions using study-level data.
Our search strategy identified 10,794 abstracts. Of these, 103 articles met our eligibility criteria. There was high interstudy heterogeneity and risk of bias. The cumulative incidence of DRE was 25.0% (95% confidence interval CI: 16.8-34.3) in child studies but 14.6% (95% CI: 8.8-21.6) in adult/mixed age studies. The prevalence of DRE was 13.7% (95% CI: 9.2-19.0) in population/community-based populations but 36.3% (95% CI: 30.4-42.4) in clinic-based cohorts. Meta-regression confirmed that the prevalence of DRE was higher in clinic-based populations and in focal epilepsy. Multiple predictors and correlates of DRE were identified. The most reported of these were having a neurologic deficit, an abnormal EEG, and symptomatic epilepsy. The most reported genetic predictors of DRE were polymorphisms of the
gene.
Our observations provide a basis for estimating the incidence and prevalence of DRE, which vary between populations. We identified numerous putative DRE predictors and correlates. These findings are important to plan epilepsy services, including epilepsy surgery, a crucial treatment option for people with disabling seizures and DRE.
Background and purpose
The timed 25‐foot walk (T25FW) and nine‐hole peg test (NHPT) exhibit random variability in the short term. A threshold of ≥20% change from baseline has been used to indicate ...true disability change, but other threshold definitions may be better suited to exclude false and include true change events. The aim of this study was to use patient‐level original trial data to investigate the short‐term variation in T25FW and NHPT, and to compare its extent with disability change at 12‐month follow‐up in people with primary progressive multiple sclerosis (PPMS).
Methods
We used original patient‐level data from PROMISE, a large PPMS trial. In this trial, three separate T25FW and NHPT measurements were performed 1 week apart during screening. We used these repeated measures to describe the extent of short‐term variation. We used binary logistic regression models to investigate the association between screening characteristics and unacceptable short‐term variation.
Results
The traditional 20% threshold excluded a reasonable number of false change events, while also yielding a large number of change events at follow‐up. Increasing index values on the T25FW and NHPT were associated with higher short‐term variation.
Conclusions
The traditional ≥20% change threshold for the T25FW and NHPT represents a reasonable compromise between reducing the number of false change events and achieving the largest number of change events in people with PPMS. Our analyses inform the design of clinical trials in PPMS.
Background
Clinical trials in primary progressive MS (PPMS) generally use the Expanded Disability Status Scale (EDSS) as their primary outcome measure, although different clinical outcomes may be ...more useful. Disability worsening in PPMS trials may be influenced by baseline factors, such as age, sex, and contrast-enhancing lesions.
Methods
We used the dataset of PROMISE, a large randomized controlled trial of glatiramer acetate (GA) versus placebo, to compare the clinical outcomes EDSS, timed 25-foot walk (T25FW), and nine-hole peg test (NHPT). We used Cox regression analyses to investigate the association of the baseline factors age, sex, treatment arm, contrast-enhancing lesions (CELs), and EDSS on the time to 3-month confirmed disability worsening (3MCDW) on the EDSS and the T25FW.
Results
PROMISE included 943 participants. Worsening on the T25FW or EDSS or occurred much more frequently than on the NHPT. Having CELs at baseline was associated with a shorter time to 3MCDW on both the EDSS and T25FW. An additional resampling experiment using the PROMISE dataset showed that increasing representation of participants with CELs at baseline increases the likelihood of having a positive trial result in favor of GA treatment.
Conclusion
Our investigation suggests that the T25FW may be a more useful primary outcome measure than the EDSS in PPMS trials, and that its use may shorten clinical trials. Our findings on the impact of CELs at baseline on disability outcomes inform the critical appraisal of clinical trials in PPMS.
•Redefining the nine hole peg test in progressive MS makes it a more useful outcome.•Non-ambulatory MS patients continue to experience nine hole peg test worsening.•Our findings suggest that ...non-ambulatory people with MS can be included in clinical trials.
The nine-hole peg test (NHPT) is the outcome measure with the least change in secondary and primary progressive MS (SPMS and PPMS) trials. The Standard NHPT is defined as the average of four measurements, two in each hand. Little is known about the performance of alternative NHPT scoring methods as longitudinal outcome measures in progressive MS. Non-ambulatory people with progressive MS are now generally excluded from clinical trials, and there is little information on longitudinal NHPT change in this patient group. In this investigation, we used patient-level data from two large randomized controlled trials in progressive MS to explore alternative NHPT scoring methods and NHPT change in non-ambulatory people with progressive MS.
We used patient-level data from the ASCEND (SPMS, n = 889) and PROMISE (PPMS, n = 943) clinical trials to compare significant change on the Standard NHPT with the alternatives dominant hand (DH), non-dominant hand (NDH), and either hand (EH) NHPT in ambulatory and non-ambulatory trial participants.
The Standard NHPT changed slowly and showed few worsening events, as did the DH and NDH alternatives. Using the EH NHPT resulted in a substantial increase of worsening events. Non-ambulatory trial participants with PPMS experienced more NHPT worsening than ambulatory participants, especially when using the EH NHPT.
Using the EH NHPT yielded substantially more worsening events in people with progressive MS. Clinical trials in non-ambulatory people may be possible with the NHPT as the primary outcome measure. More research into the precision of these measures in this patient group is necessary.
•We present the fourth documented potential case suggestive of “true” neuromyelitis optica spectrum disorder (NMOSD) meeting the current criteria associated with dengue infection.•Most reported cases ...of acute dengue infection presenting with a core clinical phenotype listed in the 2015 NMOSD diagnostic criteria were not tested for AQP4-IgG antibody.•Cases with acute DENV-infection with a neurological manifestation presented with a spinal cord phenotype, the majority with a LETM.•AQP4-IgG status might be helpful in a suggestive neurological presentation associated with dengue infection and subsequent decisions regarding long term immunotherapy.
: Neuromyelitis Optica Spectrum Disorder can be associated with parainfectious and post-infectious triggers. Dengue virus infection is one of the most common arbovirus infections in the world, and may present with neurological manifestations.
: We present a case of DENV-associated with LETM and positive aquaporin-4 IgG, and a systematic review of published cases.
: Medline (Ovid) and PubMed were search through June 2021, for case reports, series and observational studies that described patients with DENV-associated LETM and/or NMOSD.
: An adolescent girl who had recently immigrated from a Dengue-endemic region presented with a LETM with high positive AQP4-IgG titer and seropositive DENV IgM/IgG antibodies. She responded well to steroids and subsequently started maintenance rituximab for her NMOSD diagnosis. Literature review: 22 publications describing 27 patients met inclusion criteria. In addition to this case, three published cases met current criteria for NMOSD with serological evidence of acute DENV infection.
: It is unknown whether there is a pathophysiological association between DENV infection and NMOSD. Regardless, if an immune-mediated event is suspected, particularly NMOSD, appropriate immunotherapy should be considered early. Decision regarding long term immunotherapy may depend on index of suspicion of true NMOSD, and this is where AQP4-IgG status and follow-up is helpful.
