Pediatric Neurology

AIM: To evaluate whether selective motor control quantified from spontaneous infant movement recordings provides diagnostic and prognostic information for cerebral palsy (CP) beyond established movement-based assessments. METHOD: This multicenter diagnostic and prognostic accuracy study included 302 infants (151 with CP) with spontaneous movement recordings obtained between 10 and 20 weeks corrected age from cohorts in Australia and the United States. All eligible infants with CP were included, and a comparison sample without CP was randomly selected. Recordings were scored using the Baby Observational Selective Control Appraisal (BabyOSCAR), Motor Optimality Score Revised (MOS-R), and General Movements Assessment (GMA). Outcomes at 2 years or older included CP diagnosis, Gross Motor Function Classification System (GMFCS) level, and motor distribution. RESULTS: BabyOSCAR discriminated CP diagnosis (area under the curve [AUC] 0.98), including children later classified in GMFCS level I. Among infants with CP, BabyOSCAR discriminated GMFCS levels I - II from III - V (AUC 0.89). BabyOSCAR absolute asymmetry also discriminated unilateral CP from all other infants (AUC 0.90). Diagnostic discrimination was also observed for MOS-R (AUC 0.94) and GMA (AUC 0.86). INTERPRETATION: Quantifying selective motor control from brief infant movement recordings may provide complementary early information about CP diagnosis, functional level, and motor distribution.

Introduction: Functional Neurological Disorder (FND) affects women approximately three times more often than men. This disparity has largely been attributed to higher trauma prevalence and diagnostic bias, while the potential contribution of hormonal influences has received little attention. Methods: An online questionnaire was distributed through FND clinics in thirteen countries, assessing self-reported symptom change across five hormonal events: hormonal contraception, pregnancy, the menstrual cycle, menopause, and gender-affirming hormone therapy. Eligible participants were cisgender women with a diagnosis of FND, or gender minority individuals (transgender or non-binary). Perceived symptom change was rated on a five-point scale ranging from large improvement to large worsening. Results: Among 262 respondents (96% female; mean age 39 years), several hormonal contexts were associated with self-reported symptom changes. Overall, hormonal contraception and pregnancy were frequently associated with worsening of motor and cognitive symptoms, and menopause with worsening across all symptom domains. Menstrual cycle analysis revealed a phase-dependent pattern: worsening was most frequently reported during menstruation and the luteal phase, whereas improvement was most frequent during the follicular phase. Reported changes were not uniform, with a substantial proportion of participants describing no change or improvement. Conclusion: Self-reported FND symptom severity appears to vary with hormonal context, with motor and cognitive symptoms most consistently affected. Given the retrospective, self-report design, these findings are hypothesis-generating and support prospective research into the role of hormonal transitions in FND.

BACKGROUND Children receiving extracorporeal membrane oxygenation (ECMO) are at high risk for focal cerebral injury (FCI). There is emerging evidence that electroencephalography (EEG) may aid FCI detection. The EEG Correlate of Injury to the Nervous System (COIN) index quantifies and displays focal background asymmetries. We evaluated whether COIN is associated with FCI in pediatric ECMO. METHODS Retrospective, cross-sectional study of patients age 28 days to 21 years, on venoarterial ECMO at a tertiary children's hospital, who received EEG monitoring and neuroimaging during ECMO. COIN was calculated from all available EEG data. COIN of 0 implies a symmetric EEG and negative COIN values are observed with FCI. Median COIN values near FCI recognition time were compared to median COIN values from randomly selected control EEG batches using logistic regression. A receiver operator characteristic curve was used to identify multilevel FCI test ranges. Likelihood ratios were calculated to estimate the posttest FCI probability for each COIN range. RESULTS During the 8-year study period (2015-2023), 33 of 142 ECMO runs met study criteria for COIN analysis. Twelve patients (36%) had FCI. The COIN cutoff of -13.3 had 92% sensitivity and 67% specificity for FCI. The COIN cutoff of -27.7 had 67% sensitivity and 90% specificity. Likelihood ratios were 0.13 for COIN (0 to -13.3), 1.1 for COIN (-13.3 to -27.7), and 7.0 for COIN (< -27.7). Posttest probability was 0.02, 0.13, 0.49 in each respective range. CONCLUSION FCI on ECMO is associated with COIN-measured EEG asymmetry. COIN may support FCI risk-stratification during ECMO.

Abstract: Objective: Post-traumatic epilepsy (PTE) is a common sequela of traumatic brain injury (TBI). Research indicates that individuals with PTE tend to experience greater cognitive difficulties compared to those with TBI alone. However, it is plausible that a distinct cognitive profile exists that distinguishes between TBI cases with and without PTE. We aimed to identify longitudinal changes in cognitive measures among TBI patients to better assess the changes associated with developing PTE. Setting: Outpatient. Participants: Prospective subjects who had suffered TBI within 6 months post-injury (TBI-6M, n=32), retrospective subjects with pre-existing PTE diagnoses (PTE, n=20), and healthy control subjects (HC, n=41). Design: We examined cognitive performance for TBI patients within 6 months post-injury, then again within 12 months (TBI-12M, n=26), and within 18-months (TBI-18M, n=25), and compared this with cognitive performance among HC and PTE. Main Measures: Cognitive tests administered yielded 15 test components for analysis. We utilized linear mixed effects modeling to examine cohort-level differences cognitive function. Results: 11/15 tests showed a significant performance deficit in the PTE subjects compared to HC. TBI-6M was not significantly different from the PTE subjects; with time, 9/15 tests showed some degree of recovery in TBI subjects. Tests for information processing speed/working memory and executive function showed strong recovery (TBI-6M vs. TBI-18M, SDMT written: p<0.0001, SDMT oral and COWAT: p<0.001). Tests for visual attention/working memory also showed a smaller but significant recovery (TBI-18M vs. PTE, p<0.05). By contrast, tests for verbal memory [HVLT-R Delayed Recall] showed chronic impairment in TBI (TBI-18M vs HC, p<0.0001). TBI subjects generally trend towards recovery in cognitive performance post-TBI. Conclusions: Information processing speed/working memory are strong indicators for TBI recovery, while auditory learning/memory shows chronic impairment. The stagnation of recovery in cognitive domains typically characterized by robust recovery may correlate with an elevated risk of developing PTE.

Gastrointestinal (GI) conditions are common among children with neurodevelopmental disabilities (NDDs), and are associated with functional impairment, behavioral symptoms, and increased health care utilization. A unique relationship between autism and GI dysfunction has been proposed, leading to a focus on autism in GI research, management guidelines, and clinical tool development. Leveraging >20 years of electronic health record data and a cohort of 42,204 cases with attention-deficit/hyperactivity disorder, autism, cerebral palsy, epilepsy, or intellectual disability and 297,402 controls without NDDs, we quantified associations between NDDs and GI conditions in children. GI conditions were more common in cases than controls across all individual NDDs; intellectual disability and cerebral palsy were most strongly associated with having a GI condition. In this work, clinically recognized GI morbidity was elevated across all NDDs and not unique to autism, suggesting that a broader, transdiagnostic approach to GI dysfunction in children with NDDs is warranted.

Background and Objectives: Deep sequencing of brain tissue in the research setting has established that mosaic variants are a major cause of malformations of cortical development (MCDs) and epilepsy. However, genetic testing in the clinical setting primarily detects germline variants using clinically accessible samples. We aimed to determine the diagnostic yield and clinical utility of deep sequencing in the clinical setting to identify pathogenic mosaic variants for this population. Methods: We performed a retrospective cohort analysis of individuals at Boston Children's Hospital with MCDs with or without epilepsy who received clinical deep sequencing between September 2017 and February 2026. Demographic, clinical, and genetic testing data were abstracted from the medical record. For individuals without systemic features, we classified brain tissue as an affected tissue sample. For individuals with systemic features, we classified brain or relevant non-brain tissue as affected. The primary outcome was the diagnostic yield of clinical deep sequencing performed using affected vs unaffected tissue samples. The secondary outcome was the clinical utility of genetic diagnoses. Results: Our cohort included 37 individuals (19/37 (51%) female, 18/37 (49%) male) with MCDs, of whom 35/37 (95%) had epilepsy (25 with brain tissue samples available from epilepsy surgery) and 8/37 (22%) had systemic features. Most (35/37 (95%)) had dysplasia phenotypes on MRI and 12/27 (44%) with pathology available had Focal Cortical Dysplasia Type I or II. The diagnostic yield was 53% (17/32; 16 mosaic and 1 germline variant) when clinical deep sequencing was performed using an affected tissue sample vs 0% (0/6) using an unaffected tissue sample (p=0.016). Of the diagnosed cases, 13/17 (76%) had testing performed on brain tissue (1 with systemic features) and 4/17 (24%) on non-brain tissue (3 buccal and 1 duodenal tissue, all with systemic features). All but one diagnosis involved the mTOR pathway. All diagnoses had clinical utility. Discussion: Clinical deep sequencing, when performed using an affected tissue sample, has high diagnostic yield and clinical utility for individuals with MCDs, especially dysplasia phenotypes, and epilepsy. Our findings support implementation of clinical deep sequencing for this population, especially as the genetic diagnoses have implications for emerging precision therapies.

Objective: To evaluate long-term neurological, mental, and menstrual health outcomes using a mixed-methods approach among women approximately 2 years after concussion compared with non-head-injured controls. Setting: Participants were recruited from [University X] sites, including the Concussion Clinic, Emergency Departments, Student Health Clinic, and [University X] + Me registry (April 2023 to September 2025). Follow-up occurred October to November 2025. Participants: Eligible participants were assigned female at birth, aged 18 to 45 years, not using hormonal birth control, and, for the concussion group, diagnosed within 7 days of injury. Of 45 concussion patients and 29 controls recruited, 11 concussion patients (mean age 30.4 +/- 8.4 years) and 16 controls (31.3 +/- 7.4 years) completed follow-up. Main Measures: Post-concussion symptoms were assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), depression using the Patient Health Questionnaire-9 (PHQ-9), and anxiety using the Generalized Anxiety Disorder-7 (GAD-7). Menstrual health was assessed using study-specific measures. Qualitative data captured perceived impacts on daily life, with recurring themes summarized using word clouds. Results: At follow-up, concussion patients reported significantly greater symptom burden (RPQ: 31.6 +/- 13.5 vs 9.4 +/- 9.8; p=0.0002; Hedges g=1.90), depression (PHQ-9: 9.5 +/- 6.5 vs 2.3 +/- 2.2; p=0.0005; g=1.60), and anxiety (GAD-7: 9.8 +/- 6.8 vs 2.8 +/- 3.0; p=0.0057; g=1.42). Qualitative findings highlighted persistent headaches, sleep difficulties, reduced interest, and effects on relationships and daily functioning. Conclusions: This study demonstrates significant long-term differences in symptom burden among women with concussions compared to controls. Findings highlight the importance of understanding real-world impacts to improve long-term care.

Background: Altered gamma-aminobutyric acid (GABA) neurotransmission is a proposed mechanism underlying autism spectrum disorder (ASD), prompting evaluation of several GABA-modulating pharmacotherapies. However, it remains unclear whether these interventions improve ASD broadly or preferentially affect specific symptom domains. Methods: We conducted a systematic review and random-effects meta-analysis of randomized controlled trials evaluating GABA-modulating pharmacotherapies in individuals with ASD. PubMed/MEDLINE, Embase, Scopus, and CENTRAL were searched from inception to April 1, 2026. Outcomes were prespecified as global autism severity, social communication, functional communication, restricted and repetitive behaviours (RRBs), adaptive behaviour, and irritability. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using GRADE. Results: Thirteen randomized controlled trials evaluating three GABA-modulating interventions (bumetanide, arbaclofen, and valproate) were included. GABA-modulating therapies were associated with statistically significant improvements in global autism severity (Hedges' g = -0.25, 95% CI -0.46 to -0.03; p = 0.028) and adaptive behaviour (Hedges' g = -0.09, 95% CI -0.15 to -0.02; p = 0.023). No significant pooled effects were observed for social communication (Hedges' g = -0.26, p = 0.077), functional communication (Hedges' g = -0.01, p = 0.869), RRBs (Hedges' g = -0.21, p = 0.126), or irritability (Hedges' g = -0.07, p = 0.543). After Holm-Bonferroni step down procedure, neither global autism severity nor adaptive behaviour remained statistically significant (Holm-adjusted p = .140 and .138, respectively). Adverse events were predominantly gastrointestinal, neurological, metabolic, and appetite-related. Overall risk of bias was variable, and the certainty of evidence ranged from very low to moderate. Conclusions: GABA-modulating pharmacotherapies did not demonstrate a robust, multiplicity-corrected benefit in any of the six prespecified ASD symptom domains. Nominal, unadjusted improvements in global autism severity and adaptive behaviour did not withstand correction for multiple comparisons and should be regarded as hypothesis-generating rather than confirmatory. Larger, adequately powered randomized trials using standardized domain-specific outcome measures are needed to determine whether individual GABA-modulating agents provide clinically meaningful benefit.

Abstract Importance: Socially vulnerable patients have a high burden of obstructive sleep apnea, but the stage of the referral pathway at which access barriers arise is uncertain. Objective: To determine whether area-level social deprivation was associated with appointment scheduling, wait time, cancellations, or no-shows among adults referred for specialist obstructive sleep apnea care. Design: This was a cross-sectional study evaluating patients referred from December 1, 2016 through November 30, 2019. Data were analyzed from January 30, 2026 to May 16, 2026. Setting: Foothills Medical Centre Sleep Centre in Calgary, Canada. Participants: Adults referred to a tertiary academic sleep centre in Calgary, Alberta, Canada. Eligible patients had valid provincial health insurance and either a scheduled clinic appointment or home sleep apnea test data available. Exposures: Quintiles of the four Canadian Index of Multiple Deprivation domains: residential instability, economic dependency, ethnocultural composition, and situational vulnerability. Main Outcomes and Measures: The primary outcome was receipt of a scheduled specialist appointment. Secondary outcomes were time from referral to the first attended appointment and number of appointment cancellations or no-shows. Results: Among 3111 patients (mean [SD] age, 53.7 [14.3] years; 40.7% female), 1766 (56.7%) were scheduled and 1647 (52.9%) attended an appointment. Each quintile increase in situational vulnerability was associated with lower odds of scheduling (adjusted odds ratio [95% confidence interval] 0.86 [0.81-0.92]), whereas each quintile increase in ethnocultural composition was associated with higher odds (adjusted odds ratio [95% confidence interval] 1.32 [1.22-1.43]). Residential instability and economic dependency were not associated with scheduling. No deprivation domain was associated with time to the first attended appointment, cancellations, or no-shows. Conclusions and Relevance: In this cohort, area-level deprivation was associated with whether patients were scheduled for an appointment but not with wait time or missed visits after scheduling. These findings suggest that equity interventions should focus on completion of referral and scheduling processes.

Background: On-call clinicians frequently report the anecdotal impression of 'theme shifts' during which specific acute neurological diagnoses appear to cluster. Whether such clustering reflects a statistically true and reproducible phenomenon has not been systematically investigated; the present paper examines seasonality and temporal clustering within six different acute neurological conditions. Methods: In this retrospective, single-center cohort study, we identified all patients admitted to a tertiary neurological department between July 2016 and June 2026 with acute unilateral vestibulopathy, cerebral artery dissection, generalized epileptic seizures, primary intracerebral hemorrhage, peripheral facial nerve palsy, or transient global amnesia (TGA) (n = 2,140). Monthly and seasonal distributions were assessed using chi-squared goodness-of-fit and cosinor analysis. Short-term temporal clustering was tested by Monte Carlo permutation across time windows from 24 hours to 90 days, and endogenous cluster dynamics were characterized using Hawkes self-exciting point process modeling. Results: Admissions for generalized epileptic seizures showed a statistically significant deviation from a uniform monthly distribution with a winter distribution (p<0.001 and q = 0.002), and a significant temporal clustering across time windows from 72 hours to 90 days (all q < 0.05). Peripheral facial nerve palsy presented significant clustering at the 90-day window (q = 0.029) and TGA at 60-day time window (q = 0.041) without seasonality; the diagnostic groups of acute unilateral vestibulopathy, cerebral artery dissection and primary intracerebral hemorrhage showed neither seasonality nor clustering after correction for multiple comparison. No diagnostic group showed clustering within a 24-hour window, statistically significant self-excitation in Hawkes process modelling, or a significant linear trend in monthly case counts over the study period. Conclusion: The anecdotal impression of diagnostic 'theme shifts' among on-call neurologists appears to have a measurable basis, although clustering is confined to specific conditions and rather on a time scale of weeks to months. Generalized epileptic seizures were the only diagnostic group that uniquely combined seasonality with temporal clustering, suggesting a shared trigger, while facial palsy and TGA showed episodic, yet non-seasonal clustering.

Primary ciliary dyskinesia (PCD) is a rare, genetic, multiorgan disease requiring lifelong management. Although PCD affects everyday life, little is known about how people with PCD experience social functioning (SF). We conducted a study within the international participatory Living with PCD study to comprehensively explore SF. First, we conducted a focus group and two semi-structured interviews with adults and parents of people with PCD. We analysed qualitative data thematically and used the findings to develop a multilingual online questionnaire on SF. The questionnaire was completed by 277 participants: 225 adults and adolescents with PCD (81%) and 52 parents of children with PCD (19%). Participants reported active social lives and strong close relationships. PCD had a positive impact on family relationships for 39% of adult/adolescent participants and 41% of parents reporting for children. Among adult/adolescent participants, 49% reported positive or no impact on romantic/intimate relationships, while 17% had avoided or ended a relationship because of PCD. PCD affected the ability to meet responsibilities for 54% of participants, free time for 58%, and planning effort for 53%. Participants were more comfortable discussing PCD with family, friends, and partners than in work or educational settings, where only 29% reported receiving support. Financial support, flexible work, or educational policies and better-trained healthcare professionals were the most frequently identified unmet needs. This study suggests that maintaining SF with PCD requires substantial individual and relational work. Improving SF for people with PCD requires systemic responses in healthcare, education, and employment, alongside support from close networks.

Background: Neuroimaging studies implicate network alterations in functional motor disorder (FND-motor), yet white matter remains poorly characterized. Objectives: To characterize white matter microstructure in FND-motor relative to healthy (HCs) and psychiatric (PCs) controls and examine symptom associations. Methods: Fifty individuals with FND-motor, 50 age- and sex-matched HCs, and 50 PCs matched on age, sex, depression, anxiety, and post-traumatic stress disorder severity underwent multi-shell diffusion MRI. Voxel-based analyses examined whole-brain white matter using diffusion tensor imaging (fractional anisotropy [FA], mean diffusivity [MD]) and neurite orientation dispersion and density imaging (NODDI) (neurite density index [NDI], orientation dispersion index, and free water fraction [FWF]) metrics. Cross-metric convergence was characterized using atlas-based tract overlap analyses and probabilistic tractography. Associations with FND symptoms and transdiagnostic physical symptoms were also evaluated. Results: Compared with HCs, FND-motor showed higher FA/NDI and lower MD/FWF, predominantly in the middle cerebellar peduncle. Compared with PCs, differences were limited to lower MD/FWF, involving the corpus callosum, middle cerebellar peduncle, and left inferior longitudinal fasciculus. Greater FND symptom severity was associated with a lower FA/NDI and higher MD/FWF in the corpus callosum and right-lateralized association and projection pathways, whereas greater transdiagnostic physical symptom burden across FND-motor and PCs was associated with higher FA and lower MD/FWF in the middle cerebellar peduncle. Conclusions: This study provides a comprehensive multi-metric diffusion-weighted characterization of white matter microstructure in FND-motor relative to both HCs and PCs - highlighting cortico-cerebellar connections via the middle cerebellar peduncle as distinct in FND-motor and associated transdiagnostically with physical symptom burden.

Objective: To describe the self-reported effects of incobotulinumtoxinA treatments on migraine-like headache in participants who experienced traumatic brain injury versus Anomalous Health Incidents. Background: Persistent headache attributed to traumatic injury to the head has been widely recognized as among the most common sequelae of concussion/mild traumatic brain injury. Such persistent headaches often have migraine-like characteristics and are typically treated similarly to idiopathic migraine. Patients who have experienced Anomalous Health Incidents have also commonly reported migraine-like headaches, but to our knowledge, no reports describing treatment for persistent headaches attributed to Anomalous Health Incidents have been published. Methods: We describe the self-reported effects of incobotulinumtoxinA treatments on headache with migraine-like characteristics in 19 participants with traumatic brain injury and 11 who had experienced Anomalous Health Incidents from a single center. Results: Self-reported benefits from incobotulinumtoxinA treatments were generally similar and statistically indistinguishable between groups. The Headache Impact Test-6 score decreased by a mean of 12 points in the traumatic brain injury group and 9.5 points in the Anomalous Health Incidents group from baseline to peak efficacy (p = 0.43), with concomitant reductions in work/school hours lost (62% vs. 50%) and family/leisure hours lost (75% vs. 33%). Furthermore, reductions in headache frequency (67% for the traumatic brain injury group vs. 57% for the Anomalous Health Incidents group), headache severity (36% vs. 23%), headache duration (37% vs. 50%), nausea/vomiting (50% vs. 25%), photophobia (34% vs. 29%), phonophobia (30% vs. 37%), visual aura (50% vs. 29%), vestibular aura (50% vs. 33%), and other aura (21% vs. 25%) from baseline to peak efficacy were similar in both groups. Likewise, time from treatment to response (6.5 vs. 7 days), duration of response (10.2 vs. 9.1 weeks), adverse effects (3/19 for the traumatic brain injury group, 3/11 for the Anomalous Health Incidents group), and improved efficacy of concomitant abortive treatments (30% vs. 50% for pain, 50% vs. 55% for aura) did not differ between groups. Osmophobia and cogniphobia, when present, did not improve on average in either group. Notably, the mean duration of response was less than 12 weeks in both groups, with only 3 participants with traumatic brain injury and 1 participant who had experienced Anomalous Health Incidents reporting benefit beyond the typical 12-week incobotulinumtoxinA treatment interval. Conclusion: Overall, these findings provisionally indicate that at least some patients who have experienced Anomalous Health Incidents may subjectively benefit from incobotulinumtoxinA treatment for persistent migraine-like headaches similarly to patients with traumatic brain injury. Limitations include the open-label, single-center, primarily retrospective design; small sample size; and limited representativeness. Further prospective controlled studies are needed to determine whether these groups truly respond similarly to incobotulinumtoxinA and other standard treatments.

Objective: In KCNQ2-related disorders (KCNQ2-RD), neurodevelopmental outcome remains variable despite established genotype-phenotype correlations. Our aim is to improve counselling, by developing and internally validating models predicting neurodevelopmental outcomes based on early clinical and genetic features, universally available to clinicians. Methods: We conducted a multicentric retrospective cohort study including 277 individuals carrying a (likely) pathogenic variant in the KCNQ2 gene, with a minimum follow-up age of three years. Mosaic variants were excluded. The cohort was randomly split into training (70%) and validation (30%) sets. Ten expert selected parameters with minimal missing data were used to train random forest models to predict (i) dichotomous outcomes and (ii) three-category outcomes for cognition, language, and gross motor milestones. Results: Models incorporated seven clinical (neonatal hypotonia, EEG characteristics, age at seizure onset, seizure type, and seizure frequency at onset, prematurity, and sex) and three genetic variables (de novo status, exon localisation, and position within known KCNQ2-developmental and epileptic encephalopathy (DEE) hotspot regions). Dichotomous models showed the highest predictive performance, with accuracies of 0.83 for normal vs. mild-profound intellectual disability (ID), 0.83 for achievement of first words, and 0.86 for achievement of independent walking. Three category models remained clinically informative: accuracies were 0.79 for normal vs. mild vs. moderate-profound ID, 0.70 for first words [&le;]16 months vs. >16 months vs. never, and 0.71 for independent walking [&le;]18 months vs. >18 months vs. never. The strongest predictors for adverse neurodevelopmental outcomes were presence of hypotonia at birth, seizure onset within the first day of life, multiple seizures per day at onset, tonic seizures at onset, a burst-suppression pattern on EEG at onset, the presence of a de novo variant, and variant location within exons 6-7. Significance: These prediction models demonstrate the feasibility of early prognostication in KCNQ2-RD and support future prospective external validation. They enable more accurate individualised counselling by integrating clinical and genetic information readily available at time of genetic diagnosis and provide an objective foundation for early intervention planning and future precision medicine trial stratification.

Background The global increase in autism spectrum disorder (ASD) diagnoses is expected to substantially increase demand for long-term rehabilitation services. However, little is known about how this increase affects rehabilitation service utilization and capacity in low- and middle-income countries. Methods We conducted a retrospective longitudinal study of children receiving developmental care at a tertiary rehabilitation center in Salvador, Brazil (2017-2026). Patients were classified into Childhood Autism, Other ASD, and non-ASD diagnostic groups according to ICD-10 diagnoses. Temporal trends in admissions and patients under follow-up were analyzed using generalized additive models and segmented Poisson regression. Factors associated with follow-up duration were evaluated using multivariable Cox proportional hazards models. Results Among 2,123 eligible children, 833 (39.2%) had Childhood Autism, 462 (21.8%) had Other ASD, and 828 (39.0%) had non-ASD diagnoses. Compared with children with non-ASD diagnoses, those with Childhood Autism entered care at younger ages, were predominantly male (77.9% vs. 57.2%), attended more visits, and remained under follow-up longer (all P<0.001). Admissions of children with Childhood Autism increased by 30.2% annually before 2023 but declined thereafter (-19.6% annually; P<0.001). Despite this decline, the number of children with Childhood Autism receiving ongoing rehabilitation continued to increase, reflecting prolonged follow-up. In adjusted analyses, Childhood Autism was associated with a substantially lower hazard of reaching the last recorded follow-up visit than non-ASD diagnoses (adjusted hazard ratio, 0.35; 95% CI, 0.30-0.40; P<0.001). Conclusions The rapid increase in ASD admissions fundamentally reshaped rehabilitation service utilization. Because children with ASD remained under follow-up substantially longer than those with other developmental conditions, they accounted for an increasing share of the rehabilitation caseload, even after new admissions began to decline. These findings highlight the importance of planning rehabilitation services according to both new admissions and the cumulative demand generated by long-term follow-up.

Parkinsons disease (PD) arises through disruption of multiple interconnected cellular processes, but the genetic contributions to these processes may differ across ancestries. We investigated functional convergence among genes harboring pathogenic or likely pathogenic (P/LP) variants and variants of uncertain significance (VUS) in a multicenter Indian cohort recruited through the Genetics of Parkinsons Disease in India Young Onset Parkinsons Disease project (GOPI YOPD). The cohort included 668 participants (463 males 69.3%) with a mean age at motor onset of 39.4+/-8.8 years. P/LP variants and VUS identified through previously reported whole-exome or whole genome sequencing were retained as separate evidential categories. The P/LP-associated gene set comprised 11 unique genes and the VUS associated set comprised 40 unique genes. Separate STRING functional-enrichment analyses evaluated Gene Ontology Biological Process, Molecular Function and Cellular Component terms, KEGG pathways, WikiPathways and STRING local network clusters. Terms meeting a Benjamini Hochberg false discovery rate threshold of <0.05 were organized into eight non-mutually-exclusive ontology/pathway categories. Gene to pathway mappings were subsequently projected to individual participants to estimate pathway representation and examine clinical associations. At least one reportable P/LP variant or VUS was identified in 336/668 participants (50.3%): 35 had a P/LP variant alone, 282 had VUS alone and 19 had a P/LP variant together with VUS in one or more additional genes. The most frequently represented categories were mitochondrial organization (247/336, 73.5%), autophagy related processes (228/336, 67.9%) and regulation of synaptic vesicle transport (201/336, 59.8%). PRKN was the most frequent P/LP-associated gene, occurring in 29/54 P/LP carriers, followed by PLA2G6 and PINK1. Lysosomal transport was represented exclusively by VUS-associated genes, particularly GBA1, VPS13C and LRRK2. Among P/LP carriers, additional VUS in distinct genes were not associated with age at onset (P = 0.81) or family history (52.6% versus 31.4%; P = 0.15). No pathway phenotype association remained significant after correction for multiple testing. Genetic findings in this Indian cohort converged across an interconnected mitochondrial autophagic lysosomal vesicular network, with different contributions from P/LP-associated and VUS associated gene sets. This study provides the first pathway resolved South Asian genetic profile and a framework for comparative studies across populations.

Background: Transcranial direct current stimulation (tDCS) is increasingly used as an adjunct to rehabilitation for young people with cerebral palsy (CP), yet considerable variability exists in clinical response. Individualised electric field modelling provides an opportunity to estimate the distribution of electrical fields generated by the stimulation delivered to the brain and explore potential relationships with functional outcomes. Methods: Structural MRI scans from nineteen participants (10-16 years) from a previously published randomised controlled trial (ISRCTN74235136) investigating the effects of tDCS combined with motor training, underwent participant-specific finite element modelling using SimNIBS. Electric field strength was quantified within anatomically defined motor regions of interest, including the primary motor cortex (M1), dorsal premotor cortex (PMd), supplementary motor area (SMA), and a combined motor network. Global grey matter electric field metrics and stimulation focality were also extracted. Results: Estimated electric field strength differed significantly across motor regions (p<0.001), with PMd receiving significantly greater stimulation than both M1 and SMA. Electric field strength within a control region (primary visual cortex) was significantly lower than within M1 (p<0.001). Despite inter-individual variability in regional and global electric field metrics, no significant associations were observed between estimated electric field strength or focality and changes in function following intervention. Conclusion: Individualised electric field modelling demonstrated that an M1-targeted tDCS montage preferentially stimulated PMd rather than M1 in young people with CP. These findings highlight the importance of subject-specific modelling when characterising current distribution and suggest that variability in electric field strength alone does not explain variability in behavioural response.

Background: Infant muscle tone reflects early central nervous system integrity and has been associated with later motor and cognitive development, including autism traits. The cerebellum regulates both motor control and higher-order socio-cognitive functions and has been repeatedly implicated in autism, but its role in linking infant muscle tone to adolescent autistic traits has not previously been studied in a large, prospective population cohort. Methods: We used data from the prospective Generation R Study. Infant muscle tone (hypotonia and hypertonia) was assessed via Prechtl examination, and third-trimester fetal transcerebellar diameter was measured using ultrasound n=6,842). Cerebellar morphology at ages 6, 10, and 14 years (n=4,861) was measured using structural MRI. Linear mixed-effects models tested associations between infant muscle tone and 35 anatomical and 10 functional cerebellar regions. Causal mediation models tested whether cerebellar volume mediated associations between infant muscle tone and adolescent autistic traits at age 14 (Social Responsiveness Scale). Results: Hypotonia predicted larger vermis IX volumes across childhood (beta=0.037, pFDR =0.043). Hypertonia showed an age-dependent association with left lateral lobule IX (beta=-0.0027, pFDR =0.041), with differences diminishing with age. Third-trimester transcerebellar diameter did not predict postnatal muscle tone. Given its significant main effect, vermis IX volume was tested as a mediator, but did not mediate the pathway to adolescent autistic traits. However, infant hypotonia showed a small direct association with elevated autistic traits at age 14, specific to girls (beta=0.0255, p=0.020). Conclusions: Infant muscle tone is associated with localized differences in cerebellar volumes. These associations are specific to vermal and left hemispheric lobule IX, a region commonly implicated in spinocerebellar postural control, axial stability, and higher-order sensorimotor integration. Furthermore, infant muscle tone was not predicted by prenatal cerebellar diameter, and cerebellar volumes did not mediate the association between infant hypotonia and adolescent autistic traits in our study. Future research should further investigate these findings in clinical populations, integrating longitudinal whole-brain, multi-modal imaging to clarify the association between infant muscle tone, the cerebellar functioning, and autistic traits.

Objective To estimate the prevalence of epilepsy-associated malformations of cortical development (MCDs) in Eastern Denmark, and to validate whether epilepsy prevalence in the same population is consistent with national estimates. Methods A retrospective cohort study of people registered with ICD-10 code DG40* and/or DZ033A from 1998 up to 1 July 2023 was conducted. The study population was defined as all living residents in Eastern Denmark with at least one recorded hospital-patient contact within the year preceding 1 July 2023. Magnetic resonance imaging (MRI) availability was required to assess presence of any MCD. MRI radiology reports were manually reviewed or evaluated using a language model to identify MCDs, including encephalocele, focal cortical dysplasia (FCD), hemimegalencephaly, heterotopia, hypothalamic hamartoma, lissencephaly, polymicrogyria and schizencephaly. Prevalence estimates were calculated for each MCD subtype and for epilepsy overall, and compared with the available literature. Results On 1 July 2023, 28,739 people met inclusion criteria, and 14,434 had an available brain MRI, including radiological description of possible MCDs. The prevalence per 100,000 population was 1044.6 (95\% CI 1032.6 to 1056.6) for epilepsy and 32.1 (95\% CI 30.1 to 34.3) for any MCD associated with seizures. Reported MCD prevalence in the literature, when existent, was derived from pediatric age-ranged selected cohorts, except for FCD. No prevalence estimates for hemimegalencephaly and heterotopia were identified. Signifiance We presented the first population-based estimates of seizure-associated MCD prevalence in a large all-age cohort. Direct comparison with prior literature was prevented due to differences in study design and population structure, but epilepsy prevalence was consistent with previously reported national estimates.

Objective: Cognitive impairment is a common comorbidity among people with epilepsy (PWE) and is associated with disability and reduced quality of life. We characterized the burden of cognitive impairment and identified factors associated with cognitive performance in a large, population-based cohort of PWE living in Northern Peru, a region highly endemic for Taenia solium where neurocysticercosis (NCC) is a common cause of acquired epilepsy. Methods: PWE enrolled in a population-based cohort in Northern Peru between 2007 and 2020 completed the Mini-Mental State Examination (MMSE) at enrollment. Cognitive impairment was defined as an MMSE score <24. Demographic and clinical data, including epilepsy characteristics and NCC status, were collected. Negative binomial regression was used to identify factors associated with the number of MMSE errors. Results: Among 764 participants, the mean MMSE score was 26.4 (SD 4.2), and 16.4% met criteria for cognitive impairment. Memory and attention were the most affected domains. In multivariable analysis, older age and lower educational attainment were independently associated with poorer cognitive performance. Conclusion: In this large, community-based cohort from Northern Peru, approximately 1 in 6 PWE had abnormal global cognition on the MMSE, with memory and attention most affected. These findings underscore the importance of incorporating cognitive evaluation and management into comprehensive epilepsy care, particularly in resource-limited settings where cognitive morbidity may be underrecognized. Given the potential for cognitive difficulties to compound disability and adversely affect quality of life, identifying and addressing cognitive morbidity may be especially important in populations already facing substantial barriers to epilepsy care.