Hemorrhagic Transformation Following Childhood Cardioembolic Stroke Is Not Increased in Anticoagulated Patients

Objective: To characterize the risk of hemorrhagic transformation following cardioembolic stroke in childhood, and whether anticoagulation impacts that risk. Methods: Ninety-five children (1 month-18 years) with cardioembolic arterial ischemic stroke between January 1, 2009, and December 31, 2019, at 2 institutions were identified for retrospective chart review. Neuroimaging was reviewed to assess for hemorrhagic transformation. Results: There were 11 cases of hemorrhagic transformation; 8 occurred within 2 days of stroke diagnosis. Risk of hemorrhagic transformation did not differ in patients with and without anticoagulation use (15% vs 9%, estimated risk difference 5%; CI –9%, 19%). Stroke size did not predict hemorrhagic transformation (OR 1.004, 95% CI 0.997, 1.010). Risk of hemorrhagic transformation was higher in strokes that occurred in the inpatient compared with the outpatient setting (16% vs 6%). Conclusion: Hemorrhagic transformation occurred in 11% of pediatric cardioembolic ischemic stroke, usually within 2 days of stroke diagnosis, and was not associated with anticoagulation or stroke size.

Pediatric Autoimmune Encephalitis Following COVID-19 Infection

Similar to the pathogenesis of autoimmune disease, SARS-CoV-2 (COVID-19) infection has been shown to be associated with dysregulated and persistent inflammatory reactions and production of some antibodies. We report 3 pediatric patients found to have serum SARS-CoV-2 antibodies who presented with neurologic findings suggestive of postinfectious autoimmune-mediated encephalitis. All 3 cases showed lymphocytic pleocytosis on cerebrospinal fluid studies and marked improvement in neurologic symptoms after high-dose intravenous corticosteroids. The manifestations of SARS-CoV-2 infection in the pediatric population are still an evolving area of study, and these cases suggest autoimmune-mediated encephalitis as yet another SARS-CoV-2 related complication.

Neurologic Complications in Pediatric Allogeneic Stem Cell Transplantation: Analysis of Risk Factors and Outcome

Neurologic complications following stem cell transplantation are of utmost importance owing to their high morbimortality. Although many studies have been performed in the adult population, reports in children are scarce. Our objective was to determine the most common neurologic complications in a pediatric population and to analyze possible risk factors for their development. We performed an exploratory retrospective study of neurologic complications in pediatric patients who had allogeneic stem cell transplantation over the last 18 years. We identified 66 neurologic complications in 178 allogeneic stem cell transplantations. The most frequent neurologic complications were those involving the peripheral nervous system and those related to drug toxicity. Survival decreased significantly in the presence of neurologic complications. Multivariate logistic regression analysis showed that independent risk factors for developing neurologic complications were development of chronic extensive graft-vs-host disease requiring treatment, cytomegalovirus reactivation, and central nervous system radiation. Prompt diagnosis and preemptive treatment, if possible, are necessary to avoid long-term sequelae or mortality.

PROVE—Phase IV Study of Perampanel in Real-World Clinical Care of Patients with Epilepsy: Interim Analysis in Pediatric Patients

PROVE is a retrospective, phase IV study assessing retention, dosing, efficacy, and safety of perampanel when administered to patients during routine clinical care. We report an interim analysis of preadolescent (1 to <12 years) and adolescent (12 to <18 years) patients. Data were obtained from medical records of patients with epilepsy initiating perampanel after January 1, 2014; cut-off date for this analysis was October 10, 2018. Overall, 151 preadolescent and 183 adolescent patients were included. Retention rates following 24 months on perampanel were 42.5% (preadolescent subgroup; n = 31/73) and 55.7% (adolescent subgroup; n = 54/97). Treatment-emergent adverse events occurred in 53 (35.1%) preadolescent (most common: aggression, irritability, and somnolence) and 78 (42.6%) adolescent patients (most common: somnolence, aggression, and dizziness). These data indicate that daily oral doses of perampanel are generally well tolerated during routine clinical care, with favorable retention rates for ≤2 years, in patients aged 1 to <18 years.

Clinical and molecular spectrum associated with Polymerase-γ related disorders

Background POLG pathogenic variants are the commonest single-gene cause of inherited mitochondrial disease. However, the data on clinicogenetic associations in POLG-related disorders are sparse. This study maps the clinicogenetic spectrum of POLG-related disorders in the pediatric population. Methods Individuals were recruited across 6 centers in India. Children diagnosed between January 2015 and August 2020 with pathogenic or likely pathogenic POLG variants and age of onset <15 years were eligible. Phenotypically, patients were categorized into Alpers-Huttenlocher syndrome; myocerebrohepatopathy syndrome; myoclonic epilepsy, myopathy, and sensory ataxia; ataxia-neuropathy spectrum; Leigh disease; and autosomal dominant / recessive progressive external ophthalmoplegia. Results A total of 3729 genetic reports and 4256 hospital records were screened. Twenty-two patients with pathogenic variants were included. Phenotypically, patients were classifiable into Alpers-Huttenlocher syndrome (8/22; 36.4%), progressive external ophthalmoplegia (8/22; 36.4%), Leigh disease (2/22; 9.1%), ataxia-neuropathy spectrum (2/22; 9.1%), and unclassified (2/22; 9.1%). The prominent clinical manifestations included developmental delay (n = 14; 63.7%), neuroregression (n = 14; 63.7%), encephalopathy (n = 11; 50%), epilepsy (n = 11; 50%), ophthalmoplegia (n = 8; 36.4%), and liver dysfunction (n = 8; 36.4%). Forty-four pathogenic variants were identified at 13 loci, and these were clustered at exonuclease (18/44; 40.9%), linker (13/44; 29.5%), polymerase (10/44; 22.7%), and N-terminal domains (3/44; 6.8%). Genotype-phenotype analysis suggested that serious outcomes including neuroregression (odds ratio [OR] 11, 95% CI 2.5, 41), epilepsy (OR 9, 95% CI 2.4, 39), encephalopathy (OR 5.7, 95% CI 1.4, 19), and hepatic dysfunction (OR 4.6, 95% CI 21.3, 15) were associated with at least 1 variant involving linker or polymerase domain. Conclusions We describe the clinical subgroups and their associations with different POLG domains. These can aid in the development of follow-up and management strategies of presymptomatic individuals.

Masking for School-Age Children With Epilepsy: We Do Have Consensus!

Introduction This study was designed to assess current recommendations from child neurologists and epileptologists on masking for school-age children with epilepsy. Methods A 7-item survey was created and sent out to members of the Child Neurology Society and Pediatric Epilepsy Research Consortium in August of 2021 to assess current practice and provider recommendations on masking. Results One hundred four individuals participated with representation from all regions of the United States. Masking was recommended by 95.1%, with 63.4% (n = 66) noting exception of those with severe intellectual disability, autism, and behavioral problems. Of those who write exemption letters, 54% write these <5% of the time. Only 3% reported potential adverse events associated with masking. Conclusion Nearly all respondents recommended masking for school-age children with epilepsy. Potential risks of masking and adverse events were low. Improved guidance on masking is needed to ensure academic success of our patients with epilepsy.

Experience of Parents of Children with Genetically Determined Leukoencephalopathies Regarding the Adapted Health Care Services During the COVID-19 Pandemic

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. Because of the COVID-19 pandemic, many health care services were suspended, delayed or delivered remotely with telemedicine. We sought to explore the experience of parents of children with genetically determined leukoencephalopathies during the pandemic given the adapted health care services. We conducted semistructured interviews with 13 parents of 13 affected children. Three main themes were identified using thematic analysis: perceived impact of COVID-19 on health care services, benefits and challenges of telemedicine, and expectations of health care after the pandemic. Parents perceived a loss/delay in health care services while having a positive response to telemedicine. Parents wished telemedicine would remain in their care after the pandemic. This is the first study assessing the impact of COVID-19 on health care services in this population. Our results suggest that parents experience a higher level of stress owing to the shortage of services and the children's vulnerability.

Effects of Perinatal Stroke on Executive Functioning and Mathematics Performance in Children

The goal of this study was to examine executive functioning, math performance, and visuospatial processing skills of children with perinatal stroke, which have not been well explored in this population. Participants included 18 children with perinatal stroke (aged 6-16 years old) and their primary caregiver. Each child completed standardized tests of executive function and visuospatial processing skills, Intelligence Quotient (IQ), and math achievement. Performance on executive function, IQ, math, and visuospatial processing tests was significantly lower in children with perinatal stroke when compared to normative means. Poorer inhibitory control was associated with worse math performance. Increased age at testing was associated with better performance on visuospatial ability (using standardized scores), and females performed better than males on a test of inhibitory control. Children with perinatal stroke displayed a range of neuropsychological impairments, and difficulties with executive function (inhibition) may contribute to math difficulties in this population.

Diffusion Tensor Imaging of Auditory Pathway in Patients With Crigler-Najjar Syndrome Type I: Correlation With Auditory Brainstem Response

Aim: To evaluate the role of diffusion tensor imaging of the auditory pathway in patients with Crigler Najjar syndrome type I and its relation to auditory brainstem response. Methods: Prospective study was done including 12 patients with Crigler Najjar syndrome type I and 10 age- and sex-matched controls that underwent diffusion tensor imaging of brain. Mean diffusivity and fractional anisotropy at 4 regions of the brain and brainstem on each side were measured and correlated with the results of auditory brainstem response for patients. Results: There was significantly higher mean diffusivity of cochlear nucleus, superior olivary nucleus, inferior colliculus, and auditory cortex of patients versus controls on both sides for all regions ( P = .001). The fractional anisotropy of cochlear nucleus, superior olivary nucleus, inferior colliculus, and auditory cortex of patients versus controls was significantly lower, with P values of, respectively, .001, .001, .003, and .001 on the right side and .001, .001, .003, and .001 on left side, respectively. Also, a negative correlation was found between the maximum bilirubin level and fractional anisotropy of the left superior olivary nucleus and inferior colliculus of both sides. A positive correlation was found between the mean diffusivity and auditory brainstem response wave latency of the right inferior colliculus and left cochlear nucleus. The fractional anisotropy and auditory brainstem response wave latency of the right superior olivary nucleus, left cochlear nucleus, and inferior colliculus of both sides were negatively correlated. Conclusion: Diffusion tensor imaging can detect microstructural changes in the auditory pathway in Crigler Najjar syndrome type I that can be correlated with auditory brainstem response.