Management of multiple sclerosis in older adults: review of current evidence and future perspectives.

IMPORTANCE: The prevalence of multiple sclerosis (MS) and aging MS patients is increasing worldwide. There is a need to better understand this MS sub-population, which historically is underrepresented in the literature. This narrative review examines the evolving demographics, disease course, and treatments for older adults with MS (OAMS) to address current knowledge gaps and highlight areas critical for future research. OBSERVATIONS: OAMS populations require special consideration by clinicians. Older individuals have different care needs than individuals with adult onset MS who are mid-life or younger. Comorbidities, an aging immune system, increasing neurodegeneration, decreasing neurologic reserve, changing benefit/risk relationship for disease modifying therapies (DMTs), and wellness require special attention to provide holistic comprehensive care. Active areas of research include potential cessation of DMTs and novel disease targets. CONCLUSIONS AND RELEVANCE: This review highlights both the current knowledge and information gaps in the literature that are critical to understanding and properly managing OAMS. The aims are to inform MS clinicians in their current practice, as well as inspire future studies which are critical to providing quality and evidence-based care for OAMS.

Effects of Prenatal Exposure to Second-Generation Antipsychotics on Development and Behavior Among Preschool-Aged Children: Preliminary Results From the National Pregnancy Registry for Psychiatric Medications.

Objective: Data are lacking on the neurodevelopmental outcomes of children prenatally exposed to second-generation antipsychotics (SGAs). The objective of this study is to examine neurodevelopmental outcomes of children exposed in utero to SGAs compared to those unexposed in a cohort of mothers with psychiatric morbidity.Methods: We conducted a cross-sectional assessment of preschool-aged children whose mothers were enrolled in the National Pregnancy Registry for Psychiatric Medications. Two validated, parent-report developmental and behavioral screening assessments, the Ages and Stages Questionnaire, Third Edition (ASQ-3) and the Preschool Child Behavior Checklist for Ages 1½-5 (CBCL/1½-5), respectively, were delivered electronically to eligible participants. Outcomes of children exposed in utero to SGAs were compared to those unexposed to SGAs in a cohort of mothers with a history of psychiatric illness. Exposure to other psychotropic medications during pregnancy was not an exclusion criterion for either group.Results: From January 2, 2018, to February 2, 2021, 520 children were eligible, and 352 responses were collected (67.7%), including 178 children in the SGA-exposed group (mean age = 2.6 years) and 174 children in the unexposed comparison group (mean age = 2.1 years). No significant differences between groups were detected (OR = 1.24, 95% CI, 0.74-2.09) with respect to developmental outcomes assessed by the ASQ-3. Similarly, for behavioral outcomes, adjusted analysis showed no significant differences in odds of an abnormal "clinical" score on the CBCL/1½-5 composite scales.Conclusions: The current study is the first to examine neurobehavioral outcomes of preschool-aged children exposed prenatally to SGAs. No significant differences in overall development or behavior were detected in the exposed versus unexposed group. These preliminary findings are an important step in delineating neurodevelopmental effects of prenatal SGA exposure.

Neuropsychological Testing in Autoimmune Encephalitis: A Scoping Review.

BACKGROUND AND OBJECTIVES: Identifying optimal methods for evaluation and monitoring of cognitive outcomes in AE is important for clinical care and research. This scoping review aimed to evaluate neuropsychological tests (NPT) that are most frequently impaired in AE cohorts to provide recommendations for a standardized NPT battery for AE outcome. METHODS: PubMed search for studies examining NPT in patients with AE was conducted on June 9, 2023. Studies were screened for inclusion/exclusion criteria as follows: at least 1 NPT, individual NPT test scores with comparison with healthy controls or normative data and neural-IgG status, total sample size ≥5, and English manuscript available. RESULTS: The search yielded 5,393 studies, of which 3,359 were screened, 107 were full text reviewed, and 32 met inclusion/exclusion criteria, anti-NMDA-R (k = 18), anti-LGI1 (k = 10), anti-GABAB-R (k = 2), anti-GAD-65 (k = 4), and anti-CASPR2 (k = 3). The cognitive domains most frequently impaired were visual and verbal episodic memory, attention/working memory, processing speed, and aspects of executive functions. DISCUSSION: Given the dearth of literature examining NPT in AE in combination with small sample sizes and methodological differences, more research in this area is needed. However, we provide recommendations for a test battery to be used in future studies, with the aim of standardizing research in this area. Based on the available literature, we recommend the use of comprehensive NPT batteries, spanning all cognitive domains. The highest yield measures may include the tests of (1) visual and verbal learning/memory, (2) basic and sustained attention, (3) processing speed, and (4) executive functions.

Predictors for the development of neurological immune-related adverse events of immune checkpoint inhibitors and impact on mortality.

BACKGROUND AND PURPOSE: Little is known about risk factors for developing neurological immunological adverse events (neuro-irAEs) from immune checkpoint inhibitors (ICIs). We report the incidence, predictors for development, impact on mortality of neuro-irAEs, and impact of ICIs on pre-existing neurological conditions in a large clinical cohort. METHODS: Patients who received ICIs between January 2011 and December 2018 were identified from a tertiary cancer center registry. Descriptive statistics were used to summarize patient, cancer, and treatment data. Odds ratios from univariable and multivariable logistic regression models were calculated to identify potential predictors for developing a neuro-irAE. Impact of neuro-irAEs on overall survival was estimated by Kaplan-Meier and Cox proportional hazard models. RESULTS: Overall frequency of neurological irAEs was 2.3%. Peripheral nervous system complications were most frequent (53.6%). Melanoma, younger age, prior chemotherapy, prior resection, CTLA-4 ICIs exposure, and combination PD-1 and CTLA-4 ICIs exposure had significantly higher odds for developing a neuro-irAE (p < 0.05) in univariate but not multivariate models. Those with a neuro-irAE were less likely to die at 3 years compared to those without a neuro-irAE (69% vs. 55%, p = 0.004) in univariate but not multivariate model. Flare of pre-existing neurological condition after exposure to ICIs was present (15.4%, 2 of 13 patients) but manageable. One patient was rechallenged with ICIs without recurrent flare. CONCLUSIONS: Neuro-irAEs are not associated with increase in overall mortality. Potential predictors for the development of neuro-irAEs are younger age, melanoma, prior chemotherapy and resection, CTLA-4, or combination ICIs exposure.

Clinical and Research Applications of the Electronic Medical Record in Multiple Sclerosis: A Narrative Review of Current Uses and Future Applications.

BACKGROUND: The electronic medical record (EMR) has revolutionized health care workflow and delivery. It has evolved from a clinical adjunct to a multifaceted tool, with uses relevant to patient care and research. METHODS: A MEDLINE literature review was conducted to identify data regarding the use of EMR for multiple sclerosis (MS) clinical care and research. RESULTS: Of 282 relevant articles identified, 29 were included. A variety of EMR integrated platforms with features specific to MS have been designed, with options for documenting disease course, disability status, and treatment. Research efforts have focused on early diagnosis identification, relapse prediction, and surrogates for disability status. CONCLUSIONS: The available platforms and associated research support the utility of harnessing EMR for MS care. The adoption of a core set of discrete EMR elements should be considered to support future research efforts and the ability to harmonize data across institutions.

Cannabis Use and Stroke: Does a Risk Exist?

AIMS: Cannabis use has been reported as a risk factor for stroke. We systematically review the prevalence and outcomes of stroke in people with cannabis use. METHODS: We searched MEDLINE and 6 other databases from inception to January 2020 for studies on the relationship between cannabis use and stroke. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations. Two independent reviewers extracted the data. Study quality was assessed by the Newcastle-Ottawa Scale for cohort and case-control studies. RESULTS: Seventeen studies involving 3,185,560 people with cannabis use were included. Descriptive statistics demonstrated 18,676 (median 1.1%, interquartile range [IQR] 0.3%-1.3%) experienced stroke compared with 0.8% of those without use (Odds Ratio 1.17, 95% CI 1.10-1.25). Among people with cannabis use, median age was 26.2 years (IQR 25.2-34.3 years) and mostly male (median 57.8%). Of stroke subtypes, ischemic stroke was most prevalent (median 1.2%, IQR 0.4%-1.9%), followed by undefined stroke subtype (median 1.2%, IQR 1.1%-1.2%) and hemorrhagic stroke (median 0.3%, IQR 0.1%-0.6%). The majority of people with cannabis use who experienced stroke survived (median: 85.1%, IQR 83%-87.5%) and 64.0% of people experienced a good neurologic outcome, defined as modified Rankin Scale of 0 to 3. Few studies included outcomes of vasospasm or seizure. CONCLUSIONS: In people with cannabis use, the prevalence of ischemic stroke and hemorrhagic stroke was 1.2% and 0.3%, respectively, higher than the prevalence of people without use (0.8% and 0.2%). There is insufficient information on timing, exposure, duration, and dose-responsive relationship.

A Structured Peer Assessment Method with Regular Reinforcement Promotes Longitudinal Self-Perceived Development of Medical Students' Feedback Skills.

BACKGROUND: Given that training is integral to providing constructive peer feedback, we examined the impact of a regularly reinforced, structured peer assessment method on student-reported feedback abilities throughout a two-year preclinical Communication Skills course. METHODS: Three consecutive 32-student medical school classes were introduced to the Observation-Reaction-Feedback method for providing verbal assessment during Year 1 Communication Skills orientation. In biweekly small-group sessions, students received worksheets reiterating the method and practiced giving verbal feedback to peers. Periodic questionnaires evaluated student perceptions of feedback delivery and the Observation-Reaction-Feedback method. RESULTS: Biweekly reinforcement of the Observation-Reaction-Feedback method encouraged its uptake, which correlated with reports of more constructive, specific feedback. Compared to non-users, students who used the method noted greater improvement in comfort with assessing peers in Year 1 and continued growth of feedback abilities in Year 2. Comfort with providing modifying feedback and verbal feedback increased over the two-year course, while comfort with providing reinforcing feedback and written feedback remained similarly high. Concurrently, student preference for feedback anonymity decreased. CONCLUSIONS: Regular reinforcement of a peer assessment framework can increase student usage of the method, which promotes the expansion of self-reported peer feedback skills over time. These findings support investigation of analogous strategies in other medical education settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01242-w.

Adults with autism spectrum disorder: Updated considerations for healthcare providers.

Children with autism spectrum disorder (ASD) eventually grow up and need to make the transition from pediatric services to adult. This is a diverse patient population.

Associations Between Unhealthy Weight-Loss Strategies and Depressive Symptoms.

INTRODUCTION: There appears to be a link between weight loss and improved mental health, but less is known about how using unhealthy weight-loss strategies impacts the odds of reporting depression. METHODS: This study includes respondents from the National Health and Nutrition Examination Survey from 2005 to 2014 who attempted to lose weight over the past year. Analysis occurred in 2017. Multivariable logistic regression was used to describe associations between all weight-loss strategies, including those grouped as unhealthy (smoking, vomiting, laxatives, skipping meals, and using diet pills), and the adjusted odds of depression (Patient Health Questionnaire-9 score ≥10). The model was then stratified by BMI, sex, race, and antidepressant use to compare the effect of using at least one unhealthy weight-loss strategy and depression within certain populations. RESULTS: The sample included 6,765 respondents (weighted n=59.2 million, 95% CI=55.5, 62.9 million). Of these respondents, 18.0% (n=1,270) reported using at least one unhealthy weight-loss strategy. In unadjusted analysis, unhealthy weight-loss strategies were generally associated with higher incidence and odds of reporting depression. In multivariable analysis, using at least one unhealthy weight-loss strategy was significantly associated with odds of reporting depression (AOR=1.47, 95% CI=1.14, 1.91, p<0.01). When the model was stratified, this effect was statistically significant among respondents with class I or II obsesity (AOR=2.20, 95% CI=1.56, 3.10, p<0.01); female respondents (AOR=1.46, 95% CI=1.06, 2.00, p=0.02); and respondents who did not use an antidepressant (AOR=1.57, 95% CI=1.14, 2.15, p=0.01). CONCLUSIONS: Unhealthy weight-loss strategies are associated with increased odds of depression. This may inform screening practices and public health messaging.

Stanniocalcin 2 is a negative modulator of store-operated calcium entry.

The regulation of cellular Ca(2+) homeostasis is essential for innumerable physiological and pathological processes. Stanniocalcin 1, a secreted glycoprotein hormone originally described in fish, is a well-established endocrine regulator of gill Ca(2+) uptake during hypercalcemia. While there are two mammalian Stanniocalcin homologs (STC1 and STC2), their precise molecular functions remain unknown. Notably, STC2 is a prosurvival component of the unfolded protein response. Here, we demonstrate a cell-intrinsic role for STC2 in the regulation of store-operated Ca(2+) entry (SOCE). Fibroblasts cultured from Stc2 knockout mice accumulate higher levels of cytosolic Ca(2+) following endoplasmic reticulum (ER) Ca(2+) store depletion, specifically due to an increase in extracellular Ca(2+) influx through store-operated Ca(2+) channels (SOC). The knockdown of STC2 expression in a hippocampal cell line also potentiates SOCE, and the overexpression of STC2 attenuates SOCE. Moreover, STC2 interacts with the ER Ca(2+) sensor STIM1, which activates SOCs following ER store depletion. These results define a novel molecular function for STC2 as a negative modulator of SOCE and provide the first direct evidence for the regulation of Ca(2+) homeostasis by mammalian STC2. Furthermore, our findings implicate the modulation of SOCE through STC2 expression as one of the prosurvival measures of the unfolded protein response.