Fulminant Anti-Myelin Oligodendrocyte Glycoprotein-Associated Cerebral Cortical Encephalitis: Case Series of a Severe Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Phenotype.

BACKGROUND: We describe a cohort of children with severe myelin oligodendrocyte glycoprotein (MOG)-IgG-associated cerebral cortical encephalitis (CCE), manifesting with bilateral cortical cytotoxic edema and critical neurological illness. METHODS: We retrospectively reviewed our pediatric MOG antibody-associated disease (MOGAD) database and identified patients with specific radiographic pattern of bilateral, multifocal cortical cytotoxic lesions. We collected demographic, clinical, and outcomes data from these patients and compared select variables with radiographically distinct cerebral MOGAD syndromes (case-control analysis). We assessed the correlation of quantitative clinical variables with severity/outcomes measures using simple linear regression. RESULTS: Sixty-five of 88 total MOGAD cases had cerebral disease, and six of 88 met inclusion criteria for fulminant CCE (f-CCE). Age range was 2 to 7 years; five of six were male. Six of six were critically ill with severe encephalopathy and seizures, two of six required barbiturate coma, and two of six required invasive intracranial pressure monitoring. Six of six required treatment escalation beyond steroids. Four of six had favorable outcome; two of six had moderate-severe disability. Compared with other cerebral MOGAD cases (n = 59), children with f-CCE were more likely to have critical illness and poor neurological outcomes scores. Neurofilament light chain and treatment latency positively correlated with intensive care unit length of stay and outcomes scores; cerebrospinal fluid (CSF) white blood cell count and neutrophil-to-lymphocyte ratio did not. CONCLUSIONS: Pediatric CCE with bilateral cytotoxicity is associated with more fulminant disease and worse outcomes than other cerebral MOGAD syndromes.

Coronavirus Infections in the Nervous System of Children: A Scoping Review Making the Case for Long-Term Neurodevelopmental Surveillance.

BACKGROUND: The objective of this study was to describe the case literature of human coronavirus infections in the nervous system of children, including from SARS-CoV-2, and to provide guidance to pediatric providers for managing the potential long-term effects on neurodevelopment of human coronavirus infections in the nervous system. METHODS: Using a structured strategy, the PubMed and Ovid:Embase databases were queried for articles about the clinical presentation and pathophysiology of coronavirus infections in the nervous system of children and young adults, aged 0 to 24 years. RESULTS: Of 2302 articles reviewed, 31 described SARS-CoV-2 infections in the nervous system of children and 21 described other human coronaviruses: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1. Excepting MERS-CoV, we found cases of neurological disease in children from each human coronavirus. Children with non-SARS-CoV-2 infections have suffered acute flaccid paralysis, acute disseminated encephalomyelitis, encephalitis, and seizures. In addition, cases of ischemic, hemorrhagic, and microvascular strokes have occurred in children with SARS-CoV-2. Patients with multisystem inflammatory syndrome in children have suffered encephalitis, stroke, pseudotumor cerebri syndrome, and cytotoxic lesions of deep brain structures. Despite these reports, few articles evaluated the impact of human coronavirus infections on long-term neurodevelopmental domains including cognitive, language, academic, motor, and psychosocial outcomes. CONCLUSIONS: Neurological manifestations of human coronavirus infections can cause severe disease in children. The case literature suggests a critical gap in knowledge of the long-term effects on child neurodevelopment of these infections. As the current SARS-CoV-2 pandemic continues, this gap must be filled to facilitate optimal outcomes in recovering children.

A 14-Year-Old Boy With Fevers, Cytopenias, and Neurocognitive Decline.

A 14-year-old boy presented to our institution with a 1-month history of neurocognitive decline and intermittent fevers. His history was significant for fevers, headaches, and a 10-lb weight loss. Previous examinations by multiple medical providers were significant only for bilateral cervical lymphadenopathy. Previous laboratory workup revealed leukopenia, neutropenia, and elevated inflammatory markers. Despite improvement in his laboratory values after his initial presentation, his fevers persisted, and he developed slowed and "jerky" movements, increased sleep, slurred speech, delusions, visual hallucinations, and deterioration in his school performance. A brain MRI performed at an outside hospital before admission at our institution was concerning for patchy, increased T2 and fluid-attenuated inversion recovery signal intensity in multiple areas, including the basal ganglia. After transfer to our institution and admission to the pediatric hospital medicine team, the patient had an acute decompensation. Our subspecialists will discuss the initial evaluation, workup, differential diagnosis, definitive diagnosis, and subsequent management of this patient.

Preliminary findings of altered functional connectivity of the default mode network linked to functional outcomes one year after pediatric traumatic brain injury.

PURPOSE AND METHOD: This study examined functional connectivity of the default mode network (DMN) and examined brain-behavior relationships in a pilot cohort of children with chronic mild to moderate traumatic brain injury (TBI). RESULTS: Compared to uninjured peers, children with TBI demonstrated less anti-correlated functional connectivity between DMN and right Brodmann Area 40 (BA 40). In children with TBI, more anomalous less anti-correlated) connectivity between DMN and right BA 40 was linked to poorer performance on response inhibition tasks. CONCLUSION: Collectively, these preliminary findings suggest that functional connectivity between DMN and BA 40 may relate to longterm functional outcomes in chronic pediatric TBI.

The Course of Concussion Recovery in Children 6-12 Years of Age: Experience From an Interdisciplinary Rehabilitation Clinic.

BACKGROUND: Current concussion evidence is derived largely from teenagers and adults. Concussion in younger children occurs within the context of neuromaturation, with differing age-based pathophysiological responses to injury. Therefore, our current understanding of concussion in older children and adults is unlikely to directly apply to younger children. OBJECTIVE: To describe patient variables, clinical course, and factors associated with time to discharge from concussion care in children 6-12 years of age with concussion treated in an interdisciplinary rehabilitation-based concussion clinic. DESIGN: Retrospective chart review. SETTING: Interdisciplinary concussion clinic at an academically affiliated rehabilitation center. PATIENTS: Children aged 6-12 years (n = 105; mean 10.8 years of age, 70% male) seen within 60 days of concussive injury. MAIN OUTCOME MEASUREMENTS: Descriptive statistics explored demographic, injury, and clinical features. The primary outcome measure, time to discharge from concussion care, was estimated with survival-analysis methods based on the date of discharge from the clinic. Multivariate models were used to examine factors associated with longer time to discharge. RESULTS: Median time to discharge was 34 days postinjury (range 5-192 days); 75% of children were discharged within 60 days of injury. A minority reported persisting symptoms at discharge. Younger age and increased symptom burden at initial evaluation predicted longer time to discharge. CONCLUSIONS: Although children 6-12 years old treated in a specialty concussion clinic show variability in time to discharge from concussion care, most were discharged within 2 months after injury. Risk factors for prolonged recovery, such as younger age and greater symptom burden at initial visit, can be used when counseling families and planning interventions. There may be varying contributions, including psychosocial stressors, to ongoing symptoms in children who experience persisting symptoms after other concussion-related concerns have resolved. Future work focused on the subset of children who report persisting symptoms will be useful for developing an evidence base related to their care. LEVEL OF EVIDENCE: II.

Functional outcomes in children with abusive head trauma receiving inpatient rehabilitation compared with children with nonabusive head trauma.

OBJECTIVE: To compare clinical features and functional outcomes of age- and sex-matched children with abusive and nonabusive head trauma receiving inpatient rehabilitation. STUDY DESIGN: Children with abusive head trauma (n = 28) and age- and sex-matched children with nonabusive head trauma (n = 20) admitted to an inpatient pediatric rehabilitation unit from 1995-2012 were studied. Acute hospitalization and inpatient rehabilitation records were retrospectively reviewed for pertinent clinical data: initial Glasgow Coma Scale score, signs of increased intracranial pressure, neuroimaging findings, and presence of associated injuries. Functional status at admission to and discharge from inpatient rehabilitation was assessed using the Functional Independence Measure for Children. Outcome at discharge and outpatient follow-up were described based on attainment of independent ambulation and expressive language. RESULTS: Children with abusive and nonabusive head trauma had similar levels of injury severity, although associated injuries were greater in those with abusive head trauma. Functional impairment upon admission to inpatient rehabilitation was comparable, and functional gains during inpatient rehabilitation were similar between groups. More children with nonabusive than with abusive head trauma attained independent ambulation and expressive language after discharge from rehabilitation; the difference was no longer significant when only children aged >12 months at injury were examined. There was variability in delay to obtain these skills and in the quality of gained skills in both groups. CONCLUSIONS: Despite more associated injuries, children with abusive head trauma make significant functional gains during inpatient rehabilitation, comparable with an age- and sex-matched sample with nonabusive head trauma. Key functional skills may be gained by children in both groups following discharge from inpatient rehabilitation.

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus.

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.