Maryam Nabavi Nouri

Expanding the Neuroimaging Spectrum of 17p13.3 Deletions: Lissencephaly with Cerebellar Hypoplasia as a Novel Phenotype

Objective: Despite advancements in “autoimmune epilepsy,” more accurately referred to herein as seizures or epilepsy of autoimmune etiology, significant variability exists in its recognition, diagnosis, and management internationally. This study assessed clinicians' understanding, access to diagnostic tools, and treatment practices across global regions. Methods: An online survey, “Recognizing Autoimmune Seizures” was disseminated globally through professional networks including the Canadian League Against Epilepsy (CLAE), International League Against Epilepsy (ILAE), Young Epilepsy Section (YES), and American Epilepsy Society (AES). Results: The survey included 157 respondents: adult neurologists (50%), pediatric neurologists (38%), other healthcare professionals (8%), and trainees (6%). Although 69% reported familiarity with updated ILAE definitions for seizures or epilepsy of autoimmune etiology, 43% noted difficulty with clinical identification. Familiarity varied significantly by region ( p = 0.024) and was highest in Europe (76%) and Asia/South/Central America (73%) versus North America (50%). In Asia and South/Central America, 66% of respondents reported difficulty accessing neural antibody testing, compared with 22% in North America and 17% in Europe ( p < 0.001), largely due to financial barriers in resource‐limited regions (87%; p < 0.001). As a result, clinicians in these settings more frequently treated patients empirically with immunotherapy without confirmatory testing (72%; p < 0.001). Further, adult providers more often identified anti‐GAD65 (73% vs. 52%), anti‐LGI1 (83% vs. 36%), and paraneoplastic antibodies (79% vs. 31%), whereas pediatric clinicians more frequently encountered anti‐MOG‐associated seizures (84% vs. 58%; all p ≤ 0.015). Significance: The survey highlights a clear knowledge‐to‐practice gap in the recognition and diagnosis of seizures or epilepsy of autoimmune etiology. While many are familiar with conceptual definitions, a substantial proportion lack confidence in clinical identification. Respondents emphasized that both knowledge gaps and limited access to diagnostic resources contribute to ongoing disparities in care. There is a pressing need for regionally tailored international initiatives to facilitate clinician education and improve equitable access to neural antibody testing. Plain Language Summary: This global survey of 157 clinicians found that while familiarity with conceptual definitions of seizures and epilepsy of autoimmune etiology was high, clinical recognition remained limited, revealing a clear knowledge‐to‐practice gap. Familiarity varied by region, highest in Europe and South/Central America and Asia, and lowest in North America. Access to neural antibody testing was most constrained in Asia and South/Central America, where limited public funding and high out‐of‐pocket costs were major barriers, leading clinicians to rely more often on empirical immunotherapy. These regional differences highlight the need for context‐specific strategies rather than one‐size‐fits‐all solutions to improve equitable care.

Background Accurate localization and lateralization of language areas are essential in the preoperative evaluation of children with drug-resistant epilepsy (DRE) to minimize postoperative neurological deficits. Traditional invasive methods such as the Wada test and electrocortical stimulation remain gold standards but present significant limitations, especially in pediatric populations. Noninvasive techniques leveraging blood oxygen level-dependent (BOLD) signal fluctuations, such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS), offer interesting and convenient alternatives, but clinical evidence is limited. This narrative review aims to synthesize current knowledge on noninvasive BOLD-based imaging techniques, specifically task-based and resting-state fMRI and fNIRS, for language mapping in children with epilepsy. Methods A comprehensive literature search was conducted using PubMed, focusing on studies employing fMRI and fNIRS for language mapping in pediatric epilepsy and cross-referencing. Special consideration was given to higher-impact studies, frequently cited publications, and works by leading experts in the field. Results Task-based fMRI remains the clinical standard for language mapping but is frequently compromised by poor task compliance in children. Resting-state fMRI provides a task-free alternative with high sensitivity but often yields broader, bilateral networks that complicate precise lateralization. fNIRS offers a portable and child-friendly option with excellent tolerability but is limited by its spatial resolution and depth penetration. Further standardization of the various data-processing methods used for these modalities is required. Conclusion BOLD-based noninvasive imaging techniques represent promising advancements in the preoperative evaluation of pediatric epilepsy surgery candidates. Future multicenter studies and the development of pediatric-specific tools are essential to establish standardized clinical use.

Objective: This study was undertaken to understand the circumstances surrounding pediatric sudden unexpected death in epilepsy (SUDEP) and identify clinical factors that may be associated with SUDEP in childhood. Methods: A retrospective case series was conducted. Pediatric SUDEP cases were collected across Canada from the Ontario Forensic Pathology Service, Canadian Pediatric Surveillance Program, and Canadian Pediatric Epilepsy Network. Demographics, epilepsy history, comorbidities, and circumstances surrounding death were analyzed. Results: Forty‐nine children with pediatric SUDEP were analyzed; 25 (51%) were females, and the median age at death was 8 years. Six children (12%) were p < .001); however, epilepsy duration was similar to those without GDD ( p = .170). Similar to adult cohorts, death was often unwitnessed ( n = 41/46, 89%). Information on recent infection before death was known in 37 children. Seventeen children (46%) had a recent infection. Significance: Our study represents the largest pediatric SUDEP case series to date. SUDEP occurred in children of all ages, including infants, with a spectrum of epilepsies with and without neurodevelopmental impairment. The circumstances around death (i.e., timing of death, witnessed/unwitnessed) were similar to previous SUDEP cohorts. A recent infection was often observed, which could decrease seizure threshold and trigger a terminal seizure and may suggest that times of increased seizure risk could warrant heightened surveillance for SUDEP. However, further research is needed to determine the significance of this finding.

Primary small vessel CNS vasculitis (sv-cPACNS) is a challenging inflammatory brain disease in children. Brain biopsy is mandatory to confirm the diagnosis. This study aims to develop and validate a histological scoring tool for diagnosing small vessel CNS vasculitis. A standardized brain biopsy scoring instrument was developed and applied to consecutive full-thickness brain biopsies of pediatric cases and controls at a single center. Stains included immunohistochemistry and Hematoxylin & Eosin. Nine North American neuropathologists, blinded to patients’ presentation, diagnosis, and therapy, scored de-identified biopsies independently. A total of 31 brain biopsy specimens from children with sv-cPACNS, 11 with epilepsy, and 11 with non-vasculitic inflammatory brain disease controls were included. Angiocentric inflammation in the cortex or white matter increases the likelihood of sv-cPACNS, with odds ratios (ORs) of 3.231 (95CI: 0.914–11.420, p = 0.067) and 3.923 (95CI: 1.13–13.6, p = 0.031). Moderate to severe inflammation in these regions is associated with a higher probability of sv-cPACNS, with ORs of 5.56 (95CI: 1.02–29.47, p = 0.046) in the cortex and 6.76 (95CI: 1.26–36.11, p = 0.025) in white matter. CD3, CD4, CD8, and CD20 cells predominated the inflammatory infiltrate. Reactive endothelium was strongly associated with sv-cPACNS, with an OR of 8.93 (p = 0.001). Features reported in adult sv-PACNS, including granulomas, necrosis, or fibrin deposits, were absent in all biopsies. The presence of leptomeningeal inflammation in isolation was non-diagnostic. Distinct histological features were identified in sv-cPACNS biopsies, including moderate to severe angiocentric inflammatory infiltrates in the cortex or white matter, consisting of CD3, CD4, CD8, and CD20 cells, alongside reactive endothelium with specificity of 95%. In the first study of its kind proposing histological criteria for evaluating brain biopsies, we aim to precisely characterize the type and severity of the inflammatory response in patients with sv-cPACNS; this can enable consolidation of this population to assess outcomes and treatment methodologies comprehensively.

Background: Primary small vessel CNS vasculitis (sv-cPACNS) is a challenging inflammatory brain disease in children. Brain biopsy is mandatory to confirm the diagnosis. This study aims to develop and validate a histological scoring tool for diagnosing small vessel CNS vasculitis. Methods: A standardized brain biopsy scoring instrument was developed and applied to consecutive full-thickness brain biopsies of pediatric cases and controls at a single center. Stains included immunohistochemistry and Hematoxylin & Eosin. Nine North American neuropathologists, blinded to patients’ presentation, diagnosis, and therapy, scored de-identified biopsies independently. Results: A total of 31 brain biopsy specimens from children with sv-cPACNS, 11 with epilepsy, and 11 with non-vasculitic inflammatory brain disease controls were included. Angiocentric inflammation in the cortex or white matter increases the likelihood of sv-cPACNS, with odds ratios (ORs) of 3.231 (95CI: 0.914-11.420, p = 0.067) and 3.923 (95CI: 1.13-13.6, p = 0.031). Moderate to severe inflammation in these regions is associated with a higher probability of sv-cPACNS, with ORs of 5.56 (95CI: 1.02-29.47, p = 0.046) in the cortex and 6.76 (95CI: 1.26-36.11, p = 0.025) in white matter. CD3, CD4, CD8, and CD20 cells predominated the inflammatory infiltrate. Reactive endothelium was strongly associated with sv-cPACNS, with an OR of 8.93 (p = 0.001). Features reported in adult sv-PACNS, including granulomas, necrosis, or fibrin deposits, were absent in all biopsies. The presence of leptomeningeal inflammation in isolation was non-diagnostic. Conclusion: Distinct histological features were identified in sv-cPACNS biopsies, including moderate to severe angiocentric inflammatory infiltrates in the cortex or white matter, consisting of CD3, CD4, CD8, and CD20 cells, alongside reactive endothelium with specificity of 95%. In the first study of its kind proposing histological criteria for evaluating brain biopsies, we aim to precisely characterize the type and severity of the inflammatory response in patients with sv-cPACNS; this can enable consolidation of this population to assess outcomes and treatment methodologies comprehensively.