Safety and Tolerability of Home Infusions in Down Syndrome Regression Disorder.

Purpose: Down syndrome regression disorder (DSRD) is a rare neuropsychiatric condition affecting otherwise healthy individuals with Down syndrome. Multiple studies on DSRD have revealed that immunotherapy with intravenous immunoglobulin (IVIg) is both safe and effective, although site of infusion has never been studied. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD receiving home-based infusions.

Central nervous system manifestations in acute and chronic graft-versus-host disease.

Despite the growing evidence supporting the existence of CNS involvement in acute and chronic graft-versus-host disease (CNS-GvHD), the characteristics and course of the disease are still largely unknown. In this multicenter retrospective study, we analyzed the clinical, biological, radiological, and histopathological characteristics, as well as the clinical course of 66 patients diagnosed with possible CNS-GvHD (pCNS-GvHD), selected by predetermined diagnostic criteria. Results were then contrasted depending on whether pCNS-GvHD occurred before or after day 100 following allogeneic hematopoietic stem cell transplantation.

Anti-CD20 Therapy in Children With Severe Epstein-Barr Virus-Associated Meningoencephalitis.

Epstein-Barr virus meningoencephalitis is a rare central nervous system infection that lacks standardized treatment. Immunocompetent and immunosuppressed individuals with this condition frequently have poor prognostic outcomes, making the need to identify therapeutic interventions high. Here, we report 2 pediatric cases of severe Epstein-Barr virus meningoencephalitis, both unresponsive to immunoglobulin and corticosteroid therapy, who demonstrated rapid clinical recovery following rituximab administration.

JAK inhibition in Down Syndrome Regression Disorder.

Down Syndrome Regression Disorder (DRSD) is an uncommon but devastating condition affecting primarily adolescents and young adults with Down syndrome (DS). Individuals with DS display a dysregulated immune system associated with hyperactive interferon signaling, which is associated with a high incidence of autoimmune conditions. While the cause of DSRD is unknown, increasing evidence indicates that it may have an immune basis, and some individuals with DSRD have responded to intravenous immunoglobulin therapy.

Isolated Psychiatric Symptoms in Children With Anti-N-Methyl-d Aspartate Receptor Encephalitis.

Background: Isolated psychiatric symptoms can be the initial symptom of pediatric anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis (pNMDARE). Here we report on the prevalence of isolated psychiatric symptoms in pNMDARE. We also assess whether initial neurodiagnostic tests (brain magnetic resonance imaging [MRI], electroencephalography [EEG], and/or cerebrospinal fluid [CSF] white blood cell count) are abnormal in children with isolated psychiatric symptoms and pNMDARE.

The Neurologist's Guide to Drug Pricing in the United States.

As newer, innovative neurology drugs enter the US health care system, neurologists should consider the cost of these treatments in addition to their efficacy, safety, and tolerability. To do so thoughtfully requires an understanding of how prescription drugs are priced in the United States. The process of drug pricing is linked to the distribution supply chain and the many stakeholders involved.

A systematic review of the epidemiology of pediatric autoimmune encephalitis: disease burden and clinical decision-making.

Background: Autoimmune encephalitis (AIE) comprises a group of rare, immune system-mediated conditions. Clinical manifestations among children are not well-characterized, and there are challenges in testing and diagnosis. This can result in treatment delays, which has been found to correlate with poorer long-term outcomes.

Down Syndrome and Autoimmune Disease.

Down syndrome is the most common genetic cause of intellectual disability and has previously been associated with a variety of autoimmune disorders affecting multiple organ systems. The high prevalence of autoimmune disease, in conjunction with other inflammatory and infectious diseases, in this population suggests an intrinsic immune dysregulation associated with triplication of chromosome 21. Emerging data on the role of chromosome 21 in interferon activation, cytokine production, and activation of B-cell mediated autoimmunity are emerging hypotheses that may explain the elevated prevalence of autoimmune thyroid disease, celiac disease, type I diabetes, autoimmune skin disease, and a variety of autoimmune neurologic conditions.

De novo variants in immune regulatory genes in Down syndrome regression disorder.

Background: Down Syndrome Regression Disorder (DSRD) is a rare and poorly understood disorder of the central nervous system, characterized by acute or subacute neuropsychiatric symptoms in previously healthy individuals with Down syndrome (DS). Many patients exhibit immunotherapy-responsiveness, indicative of immune dysregulation as a potential underlying etiology. While hypotheses are emerging regarding the role of interferon signaling in DSRD and other autoimmune conditions associated with DS, it is unclear why a small subset of individuals with DS develop DSRD.

Sexual Health Education and Quality of Counseling in Pediatric-Onset Multiple Sclerosis.

Background: Disease-modifying therapies (DMTs) have revolutionized the management of multiple sclerosis (MS). Many DMTs have a risk of teratogenic outcomes, which is notable as MS disproportionally affects women of reproductive age and the rates of unplanned pregnancies among persons with MS (PwMS) are as high as 34%. Prior research suggests that patients' culture may influence their perspectives surrounding family planning.

Delayed initiation of disease modifying therapy increases relapse frequency and motor disability in pediatric onset multiple sclerosis.

Objective: To evaluate association between time to initiation of disease modifying treatment (DMT) and outcomes in pediatric-onset Multiple Sclerosis (POMS).

Methods: A retrospective analysis of children with POMS from two tertiary referral pediatric Neuroimmunology clinics. Outcome measures comprised annualized relapse rate (ARR), MRI lesion burden (T1, T2-FLAIR, and post-GAD contrast sequences), EDSS, and 25-ft walk duration at the latest follow-up visit.

Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States.

Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States.

The diagnostic workup of children with the radiologically isolated syndrome differs by age and by sex.

Background: Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown.

Objective: To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests.

Neuropathologic Impacts of JAK Inhibitor Treatment in Aicardi-Goutières Syndrome.

Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy characterized by upregulation of type I interferon response. It is associated with increased mortality and severe disabilities. Janus Kinase (JAK) inhibitors have shown effectiveness in treatment of AGS through blocking the downstream effects of interferon activation.

Neuroimaging abnormalities associated with immunotherapy responsiveness in Down syndrome regression disorder.

Objective: To determine the prevalence of neuroimaging abnormalities in individuals with Down syndrome regression disorder (DSRD) and evaluate if neuroimaging abnormalities were predictive of therapeutic responses.

Methods: A multicenter, retrospective, case-control study which reviewed neuroimaging studies of individuals with DSRD and compared them to a control cohort of individuals with Down syndrome (DS) alone was performed. Individuals aged 10-30 years and meeting international consensus criteria for DSRD were included.

Prescription Drug Prices: An AAN Position Statement.

This position statement serves to establish the AAN's stance on the methods to address the cost of prescription drugs being considered by state and federal policymakers so that the AAN can continue to advocate effectively for its members. Neurologists seek to provide high-value care for patients with neurologic diseases at the lowest cost possible. However, many therapies for neurologic diseases are among the most expensive in the United States.

Safety and tolerability of intravenous immunoglobulin infusion in Down syndrome regression disorder.

Three large multi-center studies have identified the clinical utility of intravenous immunoglobulin (IVIg) in the treatment of Down syndrome regression disorder (DSRD). Yet the tolerability of infusions in individuals with DS and the safety of IVIg remains unknown in this population. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD compared to a real-world cohort of individuals with pediatric onset neuroimmunologic disorders.

Impact of endocrine dysregulation on disability and non-motor symptoms in pediatric onset multiple sclerosis.

Background: Pediatric onset multiple sclerosis (POMS) commonly occurs at the time of various endocrine changes. Evaluation of the impact of endocrine status on disease severity in POMS has not been previously explored.

Objective: This study sought to evaluate if sex and stress hormones in children with POMS impact motor and non-motor diseases severity.

Diagnostic Yield of Epilepsy-Genes Sequencing and Chromosomal Microarray in Pediatric Epilepsy.

Background: Around 40% of individuals with epilepsy have an underlying identifiable genetic etiology. Common methods for epilepsy genetic testing are chromosomal microarray (CMA) and epilepsy-genes sequencing (EGS). Historically, CMA was the first-line test for patients with epilepsy, but recent studies have shown that EGS has a superior diagnostic yield.

Hypovitaminosis D in persons with Down syndrome and autism spectrum disorder.

Background: Plasma levels of vitamin D have been reported to be low in persons with Down syndrome (DS) and existing data is limited to small and homogenous cohorts. This is of particular importance in persons with DS given the high rates of autoimmune disease in this population and the known relationship between vitamin D and immune function. This study sought to investigate vitamin D status in a multi-center cohort of individuals with DS and compare them to individuals with autism spectrum disorder (ASD) and neurotypical (NT) controls.

Brain Magnetic Resonance Imaging Abnormalities in Acute Flaccid Myelitis.

Background: Acute flaccid myelitis (AFM) presents with acute onset of flaccid paralysis with involvement of the gray matter on magnetic resonance imaging (MRI) of the spinal cord. Studies have reported brain MRI abnormalities, but the characteristics have not been fully defined. In this multicenter study, we assessed the acute features and evolution of brain MRI abnormalities in AFM.

Ophthalmologic and neuro-ophthalmologic findings in children with Down syndrome.

Down syndrome, also known as Trisomy 21, is a genetic disorder associated with mild-to-moderate intellectual disability, delays in growth, and characteristic facial features. A wide range of ocular complications are seen in children with Down syndrome, including strabismus, nystagmus, refractive errors, congenital cataracts, the presence of keratoconus, and decreased visual acuity. Early ophthalmic examination is needed for early diagnosis and treatment in patients.