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.

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.

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.

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.

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.

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.

Thiamine metabolism dysfunction syndrome 5 (THMD5) mimicking acute disseminated encephalomyelitis.

Thiamine pyrophosphate (TPP), the substrate of Thiamine pyrophosphate kinase (TPK), is an important cofactor in carbohydrate metabolism, specifically as a cofactor of the Pyruvate dehydrogenase complex (PDH) complex. The nervous system is particularly dependent on TPP due to its reliance on glucose metabolism. In this case, a four-year-old girl had a previously unreported pathogenic variant of the gene encoding TPK (TPK1) which presented as Thiamine metabolism dysfunction syndrome 5 (THMD5; OMIM 614458).

Immunotherapy responsiveness and risk of relapse in Down syndrome regression disorder.

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed.

Myelin Oligodendrocyte Glycoprotein (MOG) Associated Diseases: Updates in Pediatric Practice.

Myelin oligodendrocyte glycoprotein (MOG) is a membrane bound protein found on the surface of oligodendrocyte cells and the outermost surface of myelin sheaths. MOG is posited to play a role as a cell surface receptor or cell adhesion molecule, though there is no definitive answer to its exact function at this time. In the last few decades, there has been a recognition of anti-MOG-antibodies (MOG-Abs) in association with a variety of neurologic conditions, though primarily demyelinating and white matter disorders.

The Impact of Neuroimmunologic Disease and Developing Nervous System.

Over the last two decades, neuroimmunologic disorders of childhood have been increasingly described, phenotyped, and treated. These disorders remain rare in the general population and while sharing common therapeutic interventions due to their immune pathophysiology, are heterogeneous with regard to presentation and risk of recurrence. As such, the impact of these disorders on the developing brain has come into the forefront of emerging research in pediatric neuroimmunology.

Adverse childhood experiences and the development of Down syndrome regression disorder.

Down syndrome regression disorder (DSRD) is a clinical symptom cluster of acute or subacute neurocognitive regression in otherwise health persons with Down syndrome. The objective of this study was to evaluate if adverse childhood experiences (ACEs) were more prevalent in children with DSRD than those with DS alone. A survey-based, cohort-based study was performed.

Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder.

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed.

Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus.

Objective: To develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome.

Background: There are no consensus criteria for the evaluation or diagnosis of neurocognitive regression in persons with Down syndrome. As such, previously published data on this condition is relegated to smaller case series with heterogenous data sets.

Child Neurology: Neurodegenerative Encephalomyelopathy Associated With Gain-of-Function Variation Partially Responsive to Immunotherapy.

Acyl-CoA oxidase 1 (ACOX1) is a peroxisomal enzyme involved in beta-oxidation of very-long-chain fatty acids. Although loss of function of had been previously described, gain-of-function variation of gene has been only recently identified, with a paucity of known cases. Gain-of-function variation results in overproduction of reactive oxygen species, resulting in progressive neurodegeneration with discrete relapses.

Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder.

Background: Down syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with Down syndrome regression disorder and determined if abnormalities are indicative of responses to therapeutic intervention.

Methods: A retrospective, multi-center, case-control study was performed.

Inadequate Vaccine Responses in Children With Multiple Sclerosis.

Immunizations against Hepatitis B virus (HBV) and Varicella Zoster virus (VZV), are recommended for patients with pediatric onset multiple sclerosis (POMS) and may be required prior to initiation of some disease modifying therapies. However, the efficacy of routine vaccine administration in POMS has never been studied. We sought to assess the humoral mediated vaccine response to HBV and VZV in children with POMS.

Increased Autoimmunity in Individuals With Down Syndrome and Moyamoya Disease.

To determine if elevated rates of autoimmune disease are present in children with both Down syndrome and moyamoya disease given the high rates of autoimmune disease reported in both conditions and unknown etiology of angiopathy in this population. A multi-center retrospective case-control study of children with Down syndrome and moyamoya syndrome, idiopathic moyamoya disease, and Down syndrome without cerebrovascular disease was performed. Outcome measures included presence of autoimmune disease, presence of autoantibodies and angiopathy severity data.

Post-infectious inflammatory syndrome associated with SARS-CoV-2 in a paediatric patient with Down syndrome.

Neurological complications of SARS-CoV-2 continue to be recognised. In children, neurological phenomenon has been reported generally in the acute infectious period. It is possible that SARS-CoV-2 could trigger an immune-mediated post-infectious phenomenon.

Blood money: Bayer's inventory of HIV-contaminated blood products and third world hemophiliacs.

This article presents an overlooked case of research misconduct and violations of basic principles of medical and business ethics. When Bayer's Cutter Laboratories realized that their blood products, Factor VIII and IX or antihemophiliac factor (AHF), were contaminated with human immunodeficiency virus (HIV), the financial investment in the product was considered too high to destroy the inventory. Cutter misrepresented the results of its own research and sold the contaminated AHF to overseas markets in Asia and Latin America without the precaution of heat treating the product recommended for eliminating the risk.