Diagnostic abnormalities, disease severity and immunotherapy responsiveness in individuals with Down syndrome regression disorder.

Introduction: Down Syndrome Regression Disorder (DSRD) is a neuropsychiatric condition causing insomnia, catatonia, encephalopathy, and obsessive-compulsive behavior in otherwise healthy individuals with Down syndrome (DS). Smaller cohorts have identified heterogenous diagnostic abnormalities which have predicted immunotherapy responsiveness although pattern analysis in a large cohort has never been performed.

Methods: A multi-center, retrospective study of individuals with DSRD was performed.

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.

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.

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.

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.

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.

Association of rare variants in genes of immune regulation with pediatric autoimmune CNS diseases.

Background: There is a gap in the literature regarding genetic underpinnings of pediatric autoimmune CNS diseases. This study explored rare gene variants implicated in immune dysregulation within these disorders.

Methods: This was a single-center observational study of children with inflammatory CNS disorder who had genetic testing through next generation focused exome sequencing targeting 155 genes associated with innate or adaptive immunity.

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.

Autoimmune Encephalitis.

Autoimmune encephalitis is a common and treatable cause of encephalitis in children and adults. Individuals present with a variety of symptoms, including altered mental status, behavioral changes, irritability, insomnia, developmental regression, seizures, dyskinetic movements, and autonomic instability. Evaluation includes electroencephalography, magnetic resonance imaging, and lumbar puncture.

EEG Biomarkers of Repository Corticotropin Injection Treatment.

Purpose: Hypsarrhythmia is one of the major diagnostic and treatment response criteria in infantile spasms (IS). The clinical and electrophysiological effect of repository corticotropin injection treatment on IS was evaluated using electrophysiological biomarkers.

Methods: Consecutive infants (<24 months) treated with repository corticotropin injection for IS were included in this retrospective descriptive study.

Baseline and outcome assessment in pediatric status epilepticus.

Purpose: To summarize different aspects of short and long-term outcomes associated with SE, including mortality, recurrence, subsequent epilepsy, neurocognitive dysfunction, imaging abnormalities, and health-related quality of life.

Methods: We searched MEDLINE for studies that assessed the short-term and long-term outcome of status epilepticus in pediatric population, including mortality, recurrence of seizure and status epilepticus, neurological, cognitive, or behavioral impairment, and health-related quality of life. We excluded studies that exclusively assessed the adult population.

Endoscopic Management of a Fourth Ventricular Cyst.

We report a case of a 12-year-old boy with previously shunted congenital hydrocephalus, presenting with a progressive headache, nausea, vomiting, and lethargy. In the brain magnetic resonance imaging, a large cyst was seen in the superior recess of the fourth ventricle extending through the cerebral aqueduct toward the third ventricle. Endoscopic dual fenestration of the cyst was performed successfully using the posterior suboccipital approach through the foramen of Magendie, which resulted in the relief of symptoms without any complications, and the patient was symptom-free in the subsequent follow-up visits for 4 years.

New-Onset Status Epilepticus in Pediatric Patients: Causes, Characteristics, and Outcomes.

Background: Many pediatric patients presenting with status epilepticus have no history of seizures.

Methods: We retrospectively analyzed the clinical characteristics of patients aged one month to 21 years who presented during six consecutive years with convulsive status epilepticus and without a history of seizures. New-onset refractory status epilepticus was defined as status epilepticus refractory to two lines of treatment, without an identified cause in the first 48 hours.