•Headache, altered mental status and weakness are the most common reported neurological symptoms in children.•Severe complications such as demyelinating disease, stroke, and encephalopathy have also ...been reported.•Inflammation, direct or indirect, may contribute to the neurological consequence in children.•Further studies are needed to define the short and long-term impact of COVID-19 infection in children.
Coronavirus disease 2019 (COVID-19) usually leads to a mild infectious disease course in children, but serious complications may occur in conjunction with both acute infection and associated phenomena such as the multisystem inflammatory syndrome in children (MIS-C). Neurological symptoms, which have been predominantly reported in adults, range from mild headache to seizure, peripheral neuropathy, stroke, demyelinating disorders, and encephalopathy. Similar to respiratory and cardiac manifestations of COVID-19, neurological complications present differently based on age and underlying comorbidities. This review provides a concise overview of the neurological conditions seen in the context of COVID-19, as well as potential mechanisms and long-term implications of COVID-19 in the pediatric population from literature reviews and primary data collected at NewYork-Presbyterian Morgan Stanley Children's Hospital.
Objective
The radiologically isolated syndrome (RIS) represents the earliest detectable pre‐clinical phase of multiple sclerosis (MS). This study evaluated the impact of therapeutic intervention in ...preventing first symptom manifestation at this stage in the disease spectrum.
Methods
We conducted a multi‐center, randomized, double‐blinded, placebo‐controlled study involving people with RIS. Individuals without clinical symptoms typical of MS but with incidental brain MRI anomalies consistent with central nervous system (CNS) demyelination were included. Within 12 MS centers in the United States, participants were randomly assigned 1:1 to oral dimethyl fumarate (DMF) 240 mg twice daily or placebo. The primary endpoint was the time to onset of clinical symptoms attributable to a CNS demyelinating event within a follow‐up period of 96 weeks. An intention‐to‐treat analysis was applied to all participating individuals in the primary and safety investigations. The study is registered at ClinicalTrials.gov, NCT02739542 (ARISE).
Results
Participants from 12 centers were recruited from March 9, 2016, to October 31, 2019, with 44 people randomized to dimethyl fumarate and 43 to placebo. Following DMF treatment, the risk of a first clinical demyelinating event during the 96‐week study period was highly reduced in the unadjusted Cox proportional‐hazards regression model (hazard ratio HR = 0.18, 95% confidence interval CI = 0.05–0.63, p = 0.007). More moderate adverse reactions were present in the DMF (34 32%) than placebo groups (19 21%) but severe events were similar (DMF, 3 5%; placebo, 4 9%).
Interpretation
This is the first randomized clinical trial demonstrating the benefit of a disease‐modifying therapy in preventing a first acute clinical event in people with RIS. ANN NEUROL 2023;93:604–614
This multi‐center, randomized, double‐blinded trial by Okuda, et al. assessed the impact of dimethyl fumarate (DMF) in the time to onset of first clinical symptoms attributable to a central nervous system (CNS) demyelinating event within a follow‐up period of 96 weeks. Treatment with DMF resulted in over 80% risk reduction relative to placebo in the prevention of a first acute clinical event related to multiple sclerosis. A significant reduction in new and/or newly‐enlarging T2‐weighted hyperintense lesions was also observed.
New-onset psychosis in the pediatric population poses many diagnostic challenges. Given the diversity of underlying causes, which fall under the purview of multiple medical specialties, a timely, ...targeted, yet thorough workup requires a systematic and coordinated approach. A committee of expert pediatric physicians from the divisions of emergency medicine, psychiatry, neurology, hospitalist medicine, and radiology convened to create and implement a novel clinical pathway and approach to the pediatric patient presenting with new-onset psychosis. Here we provide background and review the evidence supporting the investigations recommended in our pathway to screen for a comprehensive range of etiologies of pediatric psychosis.
Neurologic complications are increasingly recognized in the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ...This coronavirus is related to severe acute respiratory syndrome coronavirus (SARS-CoV) and other human coronavirus-related illnesses that are associated with neurologic symptoms. These symptoms raise the question of a neuroinvasive potential of SARS-CoV-2.
Potential neurologic symptoms and syndromes of SARS-CoV-2 include headache, fatigue, dizziness, anosmia, ageusia, anorexia, myalgias, meningoencephalitis, hemorrhage, altered consciousness, Guillain-Barré syndrome, syncope, seizure, and stroke. In addition, we discuss neurologic effects of other coronaviruses, special considerations for management of neurologic patients, and possible long-term neurologic and public health sequelae.
As SARS-CoV-2 is projected to infect a large part of the world's population, understanding the potential neurologic implications of COVID-19 will help neurologists and others recognize and intervene in neurologic morbidity during and after the pandemic of 2020.
To test the association between physical function and the social environment in multiple sclerosis (MS), we quantified personal social networks.
In this cross-sectional study, we analyzed data from 2 ...academic MS centers, with center 1 serving as a discovery group and center 2 as the extension group. We performed a meta-analysis of the centers to extend the analysis. We used responses from a questionnaire to map the structure and health habits of participants' social networks as well as the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) physical function scale (0-100, mean 50 for US general population) as the primary outcome. We applied multivariable models to test the association between network metrics and physical function.
The discovery cohort included 263 patients with MS: 81% were women, 96% non-Hispanic European, 78% had relapsing MS, average age was 50 (12.4) years, and mean disease duration was 17 (12.3) years. The extension group included 163 patients, who were younger, more racially diverse, and less physically disabled, and had shorter disease duration. In the meta-analysis, higher network constraint, a measure of tightly bound networks, was associated with worse physical function (β = -0.163 ± 0.047,
< 0.001), while larger network effective size, a measure of clustered groups in the network, correlated with better physical function (β = 0.134 ± 0.046,
= 0.003).
Our study highlights personal networks as an important environmental factor associated with physical function in MS. Patients with close-knit networks had worse function than those with more open networks. Longitudinal studies are warranted to evaluate a causal relationship between network structure and physical impairment.
Introduction
Dimethyl fumarate (DMF) showed favorable benefit-risk in patients with relapsing-remitting multiple sclerosis (MS) in phase 3 DEFINE and CONFIRM trials and in the ENDORSE extension ...study. Disease activity can differ in younger patients with MS compared with the overall population.
Methods
Randomized patients received DMF 240 mg twice daily or placebo (PBO; years 0–2 DEFINE/CONFIRM), then DMF (years 3–10; continuous DMF/DMF or PBO/DMF; ENDORSE); maximum follow-up (combined studies) was 13 years. This integrated post hoc analysis evaluated safety and efficacy of DMF in a subgroup of young adults aged 18–29 years.
Results
Of 1736 patients enrolled in ENDORSE, 125 were young adults, 86 treated continuously with DMF (DMF/DMF) and 39 received delayed DMF (PBO/DMF) in DEFINE/CONFIRM. Most (
n
= 116 93%) young adults completed DMF treatment in DEFINE/CONFIRM. Median (range) follow-up time in ENDORSE was 6.5 (2.0–10.0) years. Young adults entering ENDORSE who had been treated with DMF in DEFINE/CONFIRM had a model-based Annualized Relapse Rate (ARR; 95% CI) of 0.24 (0.16–0.35) vs. 0.56 (0.35–0.88) in PBO patients. ARR remained low in ENDORSE: 0.07 (0.01–0.47) at years 9–10 (DMF/DMF group). At year 10 of ENDORSE, EDSS scores were low in young adults: DMF/DMF, 1.9 (1.4); PBO/DMF, 2.4 (1.6). At ~ 7 years, the proportion of young adults with no confirmed disability progresion was 81% for DMF/DMF and 72% for PBO/DMF. Patient-reported outcomes (PROs) (SF-36 and EQ-5D) generally remained stable during ENDORSE. The most common adverse events (AEs) in young adults during ENDORSE were MS relapse (
n
= 53 42%). Most AEs were mild (
n
= 20 23.3%,
n
= 7 17.9%) to moderate (
n
= 45 52.3%,
n
= 23 59.0%) in the DMF/DMF and PBO/DMF groups, respectively. The most common serious AE (SAE) was MS relapse (
n
= 19 15%).
Conclusion
The data support a favorable benefit-risk profile of DMF in young adults, as evidenced by well-characterized safety, sustained efficacy, and stable PROs.
Clinical Trial Information
Clinical trials.gov, DEFINE (NCT00420212), CONFIRM (NCT00451451), and ENDORSE (NCT00835770).
Objectives:
To describe the spectrum of pediatric inflammatory neurologic diseases and compare the sensitivity of ancillary testing for these diagnoses.
Methods:
We analyzed clinical features and ...outcomes of 98 children with an immune-mediated central nervous system disorder. We compared sensitivities of each diagnostic modality.
Results:
We identified the following diagnoses: acute cerebellar ataxia (n = 14; 14.3%), acute demyelinating encephalomyelitis (n = 13; 13.3%), multiple sclerosis (MS) (n = 18; 18.4%), anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDAR encephalitis) (n = 15; 15.3%), encephalitis not otherwise specified (n = 12; 12.2%), and “Other” (n = 26; 26.5%). “Other” included acute transverse myelitis, neuromyelitis optica, central nervous system lupus, primary central nervous system vasculitis, Rasmussen encephalitis, opsoclonus myoclonus ataxia syndrome, and clinically isolated syndrome. The mean age of onset of all diagnoses was 7.9 ± 5.5 years. The diagnostic sensitivity of magnetic resonance imaging (MRI) for acute demyelinating encephalomyelitis and multiple sclerosis was 92.3% and 94.4%, respectively. Cerebrospinal fluid was sensitive for multiple sclerosis in 92.3%, where 75% of patients had cerebrospinal fluid oligoclonal bands. Electroencephalogram (EEG) coupled with cerebrospinal fluid studies was highly sensitive for anti-NMDAR encephalitis (100%). EEG was sensitive for acute demyelinating encephalomyelitis and encephalitis not otherwise specified (77.8% and 80%). No diagnostic studies were sensitive for acute cerebellar ataxia. Seventy-three percent of patients with multiple sclerosis had residual deficits. Thirty-six percent of anti-NMDAR encephalitis patients were nonverbal and wheel-chair bound.
Conclusions:
We found that MRI is useful for detecting multiple sclerosis and acute demyelinating encephalomyelitis, cerebrospinal fluid is helpful in diagnosing multiple sclerosis and anti-NMDAR encephalitis, and EEG is often abnormal in suspected anti-NMDAR encephalitis, acute demyelinating encephalomyelitis, and encephalitis not otherwise specified. Neurologic outcome at follow-up was unfavorable in patients with multiple sclerosis and anti-NMDAR encephalitis.
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