Pediatric neuroinflammatory diseases in the intensive care unit.

Inflammatory disorders of the central nervous system (CNS) include a wide spectrum of autoimmune, autoinflammatory, and paraneoplastic diseases. While many affected patients require acute hospital admission, a subset may present with severe neurological symptoms requiring intensive care unit (ICU) escalation due to disordered consciousness, respiratory failure, status epilepticus, intracranial hypertension, and/or severe autonomic dysregulation.

Pediatric Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a demyelinating disease with a high relapse rate and risk of disability accrual. The condition is an astrocytopathy, with antibodies to the aquaporin-4 (AQP4) water channel being detected in AQP4-IgG seropositive disease. Presentation is uncommon in the pediatric age range, accounting for about 3%-5% of cases. NMOSD is more prevalent in populations of Black or East Asian ancestry. Core clinical syndromes include optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, acute diencephalic syndrome, and symptomatic cerebral syndrome. First-line treatment options in pediatrics include rituximab, azathioprine, and mycophenolate mofetil. Over half of children with AQP4-IgG seropositive NMOSD develop permanent disability, particularly in visual and motor domains. Novel therapeutic targets in the adult population have been developed and are changing the treatment landscape for this disorder.

Arterial Spin Labeling Changes Parallel Asymmetric Perisylvian and Perirolandic Symptoms in 3 Pediatric Cases of Anti-NMDAR Encephalitis.

BACKGROUND AND OBJECTIVES: Anti-NMDA receptor autoimmune encephalitis (NMDAR AE) is an autoantibody-mediated disorder characterized by seizures, neuropsychiatric symptoms, movement disorder, and focal neurologic deficits. Conventionally defined broadly as an inflammatory brain disease, the heterotopic localization is rarely discussed in children. Imaging findings are often nonspecific, and there are no early biomarkers of disease other than the presence of anti-NMDAR antibodies. METHODS: We conducted a retrospective analysis of our pediatric NMDAR AE cases (as determined by either positive serum or CSF antibodies or both) at Texas Children's Hospital between 2020-2021 and extracted medical record data of those patients who had arterial spin labeling (ASL) as part of their imaging workup for encephalitis. The ASL findings were described in the context of their symptoms and disease courses. RESULTS: We identified 3 children on our inpatient floor, intensive care unit (ICU), and emergency department (ED) settings who were diagnosed with NMDAR AE and had ASL performed as part of their focal neurologic symptom workup. All 3 patients presented with focal neurologic deficits, expressive aphasia, and focal seizures before the onset of other well-characterized NMDAR AE symptoms. Their initial MRI revealed no diffusion abnormalities but uncovered asymmetric and predominantly unilateral multifocal hyperperfusion of perisylvian/perirolandic regions on ASL that correlated with focal EEG abnormalities and their focal examination findings. All 3 patients were treated with first-line and second-line therapies, and their symptoms improved. DISCUSSION: We found that ASL may be a suitable early imaging biomarker to highlight perfusion changes corresponding to the functional localization of NMDAR AE in pediatric patients. We briefly highlight the neuroanatomic parallels between working models of schizophrenia, chronic NMDAR antagonist administration (ketamine abuse), and NMDAR AE affecting primarily language centers. The regional specificity seen in NMDAR hypofunction may make ASL a reasonable early and specific biomarker of NMDAR AE disease activity. Future studies are necessary to evaluate regional changes in those patients who present with primarily psychiatric phenotypes rather than classical focal neurologic deficits.

Longitudinal neurological analysis of moderate and severe pediatric cerebral visual impairment.

Introduction: Cerebral visual impairment (CVI) results from damage to cerebral visual processing structures. It is the most common cause of pediatric visual impairment in developed countries and rising in prevalence in developing nations. There is currently limited understanding on how neurologic, developmental, and ophthalmic factors predict outcome for pediatric CVI. Method: A retrospective manual chart review of pediatric CVI patients seen at the tertiary pediatric hospital neurology and neuro-ophthalmology service between 2010 and 2019 was conducted. Patients were stratified into severity groups (based on a custom CVI grading score), and followed over time to identify outcome predictors. Collected baseline characteristics included perinatal, genetic, developmental, and neurologic history, along with neuroimaging and fundoscopic findings on examination. Longitudinal data collected included age, seizure control, and type of therapy received. Linear mixed-effect models were used for longitudinal CVI grade outcome analysis. Results: A total of 249 individuals spanning 779 patient visits were identified. Mean age at diagnosis was 18.8 ± 16.8 months (2-108 months). About 64.3% were born at term age. Perinatal history revealed hypoxic ischemic encephalopathy (HIE) in 16.5%, intraventricular hemorrhage (IVH) in 11.6%, and seizures in 21.7%. At presentation, 60.3% had a diagnosis of cerebral palsy and 84.7% had developmental delay. Among all subjects, 78.6% had epilepsy; 33.8% had an epileptic encephalopathy, with spasms/hypsarrhythmia being most common. Abnormal neuroimaging was present in 93.8%. Genetic anomalies were present in 26.9%. Baseline visual examination revealed no blink-to-light (BTL) in 24.5%; only BTL in 34.5%, fixation/tracking in 26.5%, and optokinetic drum follow in 14.4%. Longitudinal data analysis showed that perinatal history of HIE, a positive epilepsy history, using multiple (≥3) epilepsy medications, cerebral palsy, and abnormal fundoscopic findings were all negatively associated with CVI grade change over time. After controlling for significant confounders, receiving any type of therapy [early childhood intervention (ECI), physical and occupational therapy (PT/OT), refractive error correction or glasses] was significantly associated with longitudinal improvement in CVI grade compared to patients who did not receive any therapy, with glasses yielding the largest benefit. Conclusion: This study offers extensive insights into neurologic, developmental and ophthalmologic features in patients with moderate to severe CVI. In concordance with previous findings, aspects of perinatal history and epilepsy/seizure control may help inform severity and prognosis in the general neurology or ophthalmology clinic. Conversely, these aspects, as well as genetic and specific epilepsy traits may alert vision health care providers in the clinic to pursue visual evaluation in at-risk individuals. Longitudinal follow-up of CVI patients showed that interventional therapies demonstrated vision function improvement greater than no therapy and maturational development.

Clinical Profile and Long-Term Outcome in Neonatal Cerebral Sinus Venous Thrombosis.

BACKGROUND: Neonatal cerebral sinus venous thrombosis (CSVT) causes high morbidity and mortality. Factors associated with either favorable or unfavorable long-term outcomes have not been clearly established. This study aimed to determine the factors involved in long-term neurological outcomes in patients with neonatal CSVT. METHODS: This was a retrospective cohort study of patients with neonatal CSVT at a single institution. Clinical factors associated with long-term neurological outcomes were examined. RESULTS: A total of 67 patients met study inclusion criteria for radiologically confirmed neonatal CSVT. The mean patient follow-up duration was four years (range one week to 16 years, median six years). We observed a favorable neurological outcome defined by a pediatric stroke outcome measures (PSOM) score of 0 to 0.5 in 26 (53%) of osurviving patients at follow-up. An unfavorable neurological outcome as defined by PSOM score >0.5 was observed in 23 survivors (47%). Death was reported in 18 (27%) patients, of which 10 patients died due to direct complications of CSVT. Congential heart disease and genetic disease were associated with significantly increased odds for all-cause death. Cardiorespiratory failure and altered mental status during the initial neurological examination were significantly associated with increased odds of death due to CSVT. Among surviving patients, higher PSOM scores were associated with premature birth (i.e., gestational age < 37 weeks), traumatic birth, site of thrombosis in the straight sinus, site of thrombosis in the internal cerebral veins, and hemorrhagic infarct. In contrast, lower PSOM scores were associated with a normal neurological examination at presentation, thrombosis in only superficial sinuses, and hemorrhage without infarct. There was no statistically significant association between the type and duration of CSVT treatment. CONCLUSIONS: The major factors influencing outcome of neonates following CSVT included comorbid medical conditions, abnormal neurological examination at presentation, location of venous thrombosis, and type of cerebral injury. These results can help guide further studies in neonatal CSVT aiming to decrease morbidity and mortality with the goal of improving long-term neurological outcomes.

Pediatric Autoimmune Ocular Myasthenia Gravis: Evaluation of Presentation and Treatment Outcomes in a Large Cohort.

BACKGROUND: In autoimmune myasthenia gravis (MG), autoantibodies target the neuromuscular junction. Ocular myasthenia gravis (OMG) is localized, affecting only extraocular and/or levator palpebrae muscles. OMG presents across all ages, varying in presentation, treatment modalities, and outcomes. Recently, there have been advances in MG/OMG treatment; their utilization and effectiveness are an important part of optimal disease management. METHODS: We completed a retrospective chart review of children aged 18 years or younger with a confirmed diagnosis of OMG presenting from 2002 to 2019. RESULTS: Forty-two patients were included with mean age at presentation of 8.5 years (2 to 18 years). Twenty-one patients (50%) had positive antibodies; 90% had acetylcholine receptor antibodies. Ten patients developed generalized symptoms with mean time to generalization of 13.6 months. Multiple logistic regression showed that older age of onset was a trend predictive factor (P = 0.054; odds ratio 1.17) for generalized disease. All patients were treated with pyridostigmine. Immunomodulating agents included steroids (15), mycophenolate mofetil (four), and intravenous immunoglobulin (one). Three patients underwent thymectomy. Twenty patients reached minimal manifestation status, and 12 achieved remission. Gender, race, and positive antibody status were not statistically significant predictors for advanced immunosuppressive therapy. CONCLUSIONS: We summarize one of the largest cohorts of pediatric patients with OMG who have undergone up-to-date diagnostic and therapeutic regimens. The predictors of outcome and treatment pathway for OMG patients suggested by this report may be further elucidated by future prospective studies.

Current Advances in Pediatric Onset Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune inflammatory disease affecting the central nervous system leading to demyelination. MS in the pediatric population is rare, but has been shown to lead to significant disability over the duration of the disease. As we have learned more about pediatric MS, there has been a development of improved diagnostic criteria leading to earlier diagnosis, earlier initiation of disease-modifying therapies (DMT), and an increasing number of DMT used in the treatment of pediatric MS. Over time, treatment with DMT has trended towards the initiation of higher efficacy treatment at time of diagnosis to help prevent further disease progression and accrual of disability over time, and there is evidence in current literature that supports this change in treatment patterns. In this review, we discuss the current knowledge in diagnosis, treatment, and clinical outcomes in pediatric MS.