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Background: Autoimmune encephalitis (AE) and acute disseminated encephalomyelitis (ADEM) are immune-mediated brain conditions that can cause substantial neurological sequalae. Data describing the clinical characteristics, treatments, and neurological outcomes for these conditions are needed., Methods: This is a single-center retrospective review of children diagnosed with AE or ADEM over a nine-year period with discharge outcomes measured by the Modified Rankin Score., Results: Seventy-five patients (23 with ADEM and 52 with AE) were identified. Patients with ADEM had a higher percentage of abnormal magnetic resonance imaging findings (100% vs 60.8%; P < 0.001) and a shorter time from symptom onset to diagnosis (6 vs 14 days; P = 0.024). Oligoclonal bands and serum and cerebrospinal fluid inflammatory indices were higher in patients with AE. Nearly all patients received corticosteroids followed by plasmapheresis or intravenous immunoglobulin, and treatment strategies did not differ significantly between groups. Second-line immune therapies were commonly used in patients with AE. Finally, patients with AE had trends toward longer hospital lengths of stay (21 vs 13 days) and a higher percentage of neurological disability at hospital discharge (59.6% vs 34.8%)., Conclusions: Although patients with ADEM and AE may have similar presenting symptoms, we found significant differences in the frequency of imaging findings, symptom duration, and laboratory and cerebrospinal fluid profiles, which can assist in distinguishing between the diagnoses. Patients in both groups were treated with a combination of immunomodulating therapies, and neurological disability was common at hospital discharge., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy characterized by early onset of severe neurological injury with intracranial calcifications, leukoencephalopathy, and systemic inflammation. Increasingly, a spectrum of neurological dysfunction and presentation beyond the infantile period is being recognized in AGS. The aim of this study was to characterize late-infantile and juvenile-onset AGS., Methods: We conducted a multi-institution review of individuals with AGS who were older than one year at the time of presentation, including medical history, imaging characteristics, and suspected diagnoses at presentation., Results: Thirty-four individuals were identified, all with pathogenic variants in RNASEH2B, SAMHD1, ADAR1, or IFIH1. Most individuals had a history of developmental delay and/or systemic symptoms, such as sterile pyrexias and chilblains, followed by a prodromal period associated with increasing symptoms. This was followed by an abrupt onset of neurological decline (fulminant phase), with a median onset at 1.33 years (range 1.00 to 17.68 years). Most individuals presented with a change in gross motor skills (97.0%), typically with increased tone (78.8%). Leukodystrophy was the most common magnetic resonance imaging finding (40.0%). Calcifications were less common (12.9%)., Conclusions: This is the first study to characterize the presentation of late-infantile and juvenile onset AGS and its phenotypic spectrum. Late-onset AGS can present insidiously and lacks classical clinical and neuroimaging findings. Signs of early systemic dysfunction before fulminant disease onset and loss of motor symptoms were common. We strongly recommend genetic testing when there is concern for sustained inflammation of unknown origins or changes in motor skills in children older than one year., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Aicardi-Goutières syndrome is a rare genetic neurological disorder with variable clinical manifestations. Molecular detection of specific mutations is required to confirm the diagnosis. The aim of this study was to review the clinical and molecular diagnostic findings in 24 individuals with Aicardi-Goutières syndrome who presented during childhood in an Arab population., Materials and Methods: We reviewed the records of 24 patients from six tertiary hospitals in different Arab countries. All included patients had a molecular diagnosis of Aicardi-Goutières syndrome., Results: Six individuals with Aicardi-Goutières syndrome (25%) had a neonatal presentation, whereas the remaining patients presented during the first year of life. Patients presented with developmental delay (24 cases, 100%); spasticity (24 cases, 100%); speech delay (23 cases, 95.8%); profound intellectual disability (21 cases, 87.5%); truncal hypotonia (21 cases, 87.5%); seizures (eighteen cases, 75%); and epileptic encephalopathy (15 cases, 62.5%). Neuroimaging showed white matter abnormalities (22 cases, 91.7%), cerebral atrophy (75%), and small, multifocal calcifications in the lentiform nuclei and deep cerebral white matter (54.2%). Homozygous mutations were identified in RNASEH2B (54.2%), RNASEH2A (20.8%), RNASEH2C (8.3%), SAMHD1 (8.3%), TREX1 (4.2%), and heterozygous mutations in IFIH1 (4.2%), with c.356A>G (p.Asp119Gly) in RNASEH2B being the most frequent mutation. Three novel mutations c.987delT and c.625 + 1G>A in SAMHD1 gene and c.961G>T in the IFIHI1 gene were identified., Conclusions: This is the largest molecularly confirmed Aicardi-Goutières syndrome cohort from Arabia. By presenting these clinical and molecular findings, we hope to raise awareness of Aicardi-Goutières syndrome and to demonstrate the importance of specialist referral and molecular diagnosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The differential diagnosis of encephalitis in childhood is vast, and evaluation for an etiology is often unrevealing. Encephalitis by way of autoimmunity has long been suspected, as in cases of acute disseminated encephalomyelitis; however, researchers have only recently reported evidence of antibody-mediated immune dysregulation resulting in clinical encephalitis., Main Findings: These pathologic autoantibodies, aimed at specific neuronal targets, can result in a broad spectrum of symptoms including psychosis, catatonia, behavioral changes, memory loss, autonomic dysregulation, seizures, and abnormal movements. Autoimmune encephalitis in childhood is often quite different from adult-onset autoimmune encephalitis in clinical presentation, frequency of tumor association, and ultimate prognosis. As many of the autoimmune encephalitides are sensitive to immunotherapy, prompt diagnosis and initiation of appropriate treatment are paramount., Conclusions: Here we review the currently recognized antibody-mediated encephalitides of childhood and will provide a framework for diagnosis and treatment considerations., (Copyright © 2016 Elsevier Inc. All rights reserved.)