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.

Preterm birth is associated with increased risk for communication difficulties, yet early neural markers of later outcomes remain poorly understood. This study examined associations between structural and functional brain connectivity in infancy and communication skills at 24to 30 months in children born very preterm ([≤]32 weeks gestation). Participants (n = 180) MRI at term-equivalent age during natural sleep. Resting-state functional and diffusion data were used to derive structural and functional connectivity across regions implicated in communication. At follow-up, communication outcomes were assessed using Communication and Symbolic Behavior Scales (CSBS), which captures verbal, gestural, social-affective, and symbolic communication skills. We analyzed 22x22 functional and structural connectomes among selected ROIs, using a LASSO regression approach to identify connectivity associated with CSBS scores adjusting for demographic and medical covariates. Significant relationships were observed between both functional and structural connectivity and communication skills, differing by domain. Functional connectivity between left and right temporal regions was positively associated with overall communication scores, whereas several structural connections involving cortical, cerebellar, and subcortical regions showed negative associations. Distinct connectivity patterns were also associated with gestural, verbal, social-affective, and symbolic communication skills. These findings demonstrate that variability in early brain connectivity is associated with later communication outcomes in children born very preterm. We found both significant positive and negative associations after adjusting for relevant covariates; these patterns potentially reflect compensatory or atypical network organization. These results highlight the value of multimodal neuroimaging in identifying early neural correlates of communication in this high-risk population.

Background: The hydrodynamic model of hydrocephalus proposes that ventriculomegaly is driven by exaggerated intraventricular pulsations rather than impaired CSF circulation alone. Under this model, endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) treats hydrocephalus by creating a pulsation absorber and by reducing a primary source of intraventricular pulsation. However, direct intraoperative human evidence supporting this two-step mechanism is lacking. This study aimed to test the hypothesis that ETV followed by CPC would produce measurable, stepwise decreases in mean intraventricular pressure (ICP) and pulsation amplitude in infants with hydrocephalus. Methods: This single-institution proof-of-concept study included infants with symptomatic hydrocephalus undergoing ETV/CPC as the first definitive treatment. A fiber-optic ICP sensor was attached to the operative ventriculoscope and passively recorded mean and pulsatile ICP (pulsation amplitude) throughout the procedure. Longitudinal brain parenchymal volume (BPV) and cerebrospinal fluid volume (CSFV) were obtained through segmentation of clinically acquired T2-weighted MRI and converted to age- and sex-matched z-scores. All patients were followed for a minimum of 6 months postoperatively. Results: Five infants (median corrected age at ETV/CPC 8 months) were included. No surgical complications occurred, and no ETV/CPC failures were observed during follow-up. Overall, mean ICP decreased by 56-97% after the combined procedure in four patients. In three patients (Patients 1, 3, and 5), both mean ICP and pulsation amplitude decreased stepwise following ETV and then CPC, consistent with the hypothesized therapeutic mechanism. Patient 4 demonstrated a large reduction in mean ICP after ETV with minimal additional effect from CPC and no significant change in pulsation amplitude. Patient 2 demonstrated neither a reduction in mean ICP nor a meaningful change in pulsation amplitude after either procedure; this patient also had a delayed and atypical clinical response. Intracranial segmentation demonstrated BPV z-score stabilization within normal range and CSFV plateau in all patients after surgery. Conclusions: This proof-of-concept study provides the first direct intraoperative human evidence supporting the hydrodynamic mechanism of ETV/CPC in a subset of infant with hydrocephalus. Our findings suggest that determination of intraoperative ICP parameters is feasible, safe and might ultimately prove helpful in improving patient selection for ETV/CPC, warranting further investigation in larger cohorts.

Background. Three disease-modifying therapies (DMTs) for spinal muscular atrophy (SMA) have been approved since 2016, yet many adults remain untreated. Identifying them depends on ICD-10 codes that capture SMA but do not reliably distinguish it from other related conditions. We examined, in one U.S. health system, both patients' engagement with therapy and the accuracy of the codes used to find them. Methods. We conducted a retrospective chart review of adults in an academic health system identified by SMA-associated ICD-10 codes, with manual adjudication of diagnosis and DMT status. Confirmed SMA-positive, DMT-naive patients were invited to a structured telephone interview on treatment awareness and barriers. Results. Of 60 charts, 22 (36.7%; 95% CI 25.6-49.3%) were appropriately coded for SMA or a related disorder; only 16 (26.7%) had molecularly confirmed SMA. The other 38 (63.3%) were miscoded, spanning spinal and bulbar muscular atrophy, asymptomatic carriers, prenatal screening, and conditions unrelated to SMA. Ten of the 16 confirmed patients (62.5%) were DMT-naive; one was interviewed, one declined, and eight could not be reached. The non-response is itself a finding: the patients least visible to administrative data are the hardest to reach. Conclusions. ICD-10 ambiguity is a barrier to treatment access in adult SMA, as is loss to follow-up. We make two recommendations: continuous documentation-coding alignment that uses natural language processing to verify the genetic precondition, and type-specific SMA codes (subcodes for Types 0-4) anchored on molecular SMN1 confirmation. Together these would support cohort identification, outreach, and evidence generation without adding to clinician burden.

INTRODUCTION Severe acute brain injury (stroke, traumatic brain injury or hypoxic-ischemic encephalopathy; SABI) is increasingly recognized as a chronic condition with care and communication needs beyond the initial hospitalization. This study aimed to characterize post-acute care patterns among SABI survivors, focusing on healthcare utilization and outpatient communication. METHODS Data were collected from a prospective cohort of hospitalized SABI patients using surveys, chart reviews, and the ED Information Exchange database. Socioeconomic disadvantage was assessed using the Area Deprivation Index (ADI), and qualitative analysis of outpatient notes examined conversations around palliative care needs and goals-of-care. RESULTS Two-thirds of patients (140/222) survived until discharge, primarily to nursing facilities (39%) or inpatient rehabilitation (38%). Among 109 with one-year follow-up, there were 89 hospitalizations, 104 ED visits, and 28 deaths. Patients from the most disadvantaged neighborhoods had significantly higher odds of rehospitalization or ED use within 30 days (OR 3.37, p=0.036). ADI was not linked to one-year utilization. seen outpatient by primary care (40%), neurology/neurosurgery (57%), and palliative care (1%), but conversations rarely revisited prognosis or goals-of-care. CONCLUSIONS Our findings highlight the need for improved long-term care planning and communication, particularly for socioeconomically disadvantaged survivors of SABI.

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.

Acute kidney injury (AKI) is common among neonates in the intensive care unit and has been linked to abnormal neurodevelopment, yet long-term effects on brain structure remain uncharacterized. In this secondary analysis, we compared brain white matter integrity, measured by fractional anisotropy (FA) on 3T MRI, in children ages 5 to 12 years born preterm with (n=5) versus without (n=10) a history of neonatal AKI. Contrary to our hypothesis, children with prior neonatal AKI showed higher FA across seven white matter regions in unadjusted analyses. After adjustment for sex, birth weight, and age at MRI, the AKI group retained significantly greater FA in the corticospinal tract ({beta}=0.7, 95% CI 0.09-1.31) and superior frontooccipital fasciculus ({beta}=0.68, 95% CI 0.02-1.34). Because elevated FA may reflect compensatory glial responses rather than improved neurological function, these findings suggest neonatal AKI may have lasting, complex effects on white matter microstructure. Larger studies pairing neuroimaging with neurocognitive assessment are needed.

Background: Dizziness is a frequent presenting complaint in the emergency department (ED), prompting extensive diagnostic evaluation. Non-contrast brain computed tomography (CT) is often utilized to rule out serious central pathologies, but its diagnostic yield is debated, leading to concerns about overuse. This study aimed to identify clinical predictors associated with abnormal brain CT findings in patients with acute dizziness to help refine imaging selection criteria. Methods: We conducted a retrospective analysis of 291 consecutive adult patients who presented with new-onset dizziness and underwent a non-contrast brain CT scan at Namazi Hospital, a tertiary referral center, between January 2019 and 2021. Patient data, including demographics, comorbidities, clinical symptoms, and hospital outcomes, were extracted from medical records. Statistical analyses were performed to determine associations between clinical variables and CT findings, with odds ratios (OR) and 95% confidence intervals (CI) calculated. Results: The diagnostic yield of brain CT was low, with a significant majority of scans (72.2%, n=210) revealing no acute pathology. Key clinical factors predicting abnormal CT findings included a history of diabetes mellitus, the presence of ataxic gait, and headache. Conversely, nausea and vomiting were significant predictors of normal findings, being associated with lower odds of central pathology. Conclusion: The diagnostic yield of routine brain CT in patients with acute dizziness is low. However, specific clinical indicators can effectively stratify risk. The presence of focal neurological signs like ataxia, headache, and certain comorbidities such as diabetes should heighten suspicion for central pathology and support the use of neuroimaging. In contrast, isolated vestibular symptoms like nausea and vomiting are associated with a lower probability of abnormal findings. These results could inform the development of clinical decision rules to optimize CT utilization, thereby reducing unnecessary radiation exposure and healthcare costs.

Aphasia diagnosis in Indonesia remains challenging due to limited culturally and linguistically appropriate instruments. Widely used tools such as the Boston Diagnostic Aphasia Examination (BDAE) and Western Aphasia Battery (WAB) are not adapted to the Indonesian context, while Tes Afasia untuk Diagnosis, Informasi, dan Rehabilitasi (TADIR) provides screening but lacks diagnostic accuracy. To address this gap, we developed the Instrumen Diagnosis dan Evaluasi Afasia (IDEA) for native Indonesian speakers and evaluated its validity, reliability, and normative cutoff values in cognitively healthy Indonesian adults. Eighty-three cognitively normal adults (screened using MoCA-Ina) with no history of neurological disease were assessed using IDEA, which evaluates six language domains. Items were adapted from existing tools and reviewed by experts. Content validity, internal consistency (Cronbachs alpha), and construct validity (Exploratory Factor Analysis) were analyzed using SPSS v25. A total of 83 participants were included (median age = 55.81 years, 54% secondary education). IDEA demonstrated good feasibility, with an average completion time of 45-60 minutes depending on participant engagement. Content validity was established by unanimous expert consensus. Construct validity showed meritorious sampling adequacy (KMO = .872) and significant sphericity (Bartletts test {chi}^2 (15) = 278.523, p<.001), supporting factor analysis. Internal consistency showed good reliability across six domains (Cronbachs = 0.896). IDEA is a valid and reliable tool for assessing aphasia in Indonesian natives. It is a culturally appropriate assessment tool which offers structured, domain-based evaluation and supports differential diagnosis of both classical and progressive aphasia syndromes. Keywords: Aphasia, Language Assessment, Indonesian, IDEA, Validity

Purpose: The purpose of this study was to identify subgroups of talkers with Parkinsons disease (PD) with shared tongue, lip, and jaw articulatory amplitude behaviors. The study also sought to identify demographic and clinical features that can distinguish the identified kinematic subgroups. Methods: 53 talkers with PD and 54 controls participated. Articulatory amplitudes of the tongue, lip, and jaw were measured during a paragraph reading task using three-dimensional electromagnetic articulography. Amplitude performance profiles of the tongue, lip, and jaw were established for each talker with PD by referencing their performance to that of controls. These profiles were submitted to a hierarchical cluster analysis to identify kinematic-based subgroups. Amplitude performances were compared across subgroups to determine between-group patterns. Demographic and clinical features (e.g., age, sex, disease duration, selected perceptual speech characteristics, dysarthria severity) were compared across the identified kinematic subgroups. Results: Four main kinematic subgroups with differing amplitude performance profiles were identified. One subgroup exhibited normal to mildly exaggerated or mildly reduced amplitudes and was labeled preclinical subgroup (n = 16). Three subgroups exhibited pronounced amplitude reductions of either the tongue (n = 10), the tongue and lips (n = 12), or the tongue, lips, and jaw (n = 10). In addition, there were five talkers with PD whose performance profiles did not align with the identified four subgroups. Their performance was characterized by either pronounced amplitude exaggerations or mildly reduced jaw and lip amplitudes and exaggerated tongue amplitudes. None of the demographic or clinical features differed significantly between the main four subgroups. Conclusion: Findings suggest that the extent to which hypokinesia manifests within the articulatory subsystem can vary in talkers with PD. Longitudinal studies are needed to determine if these subgroups represent different stages of disease progression or distinctly different manifestations of the disease within the articulatory subsystem.

Background/Objectives: Traumatic Brain Injuries (TBIs) affect more than 50 million individuals worldwide each year. Approximately 90% of individuals survive and experience persistent motor, cognitive, and emotional deficits, substantially contributing to a reduced quality of life and a global economic burden. TBI mechanisms are a foundational determinant of long-term recovery. The objective of this study was to examine long-term trends in functional locomotion ability over extended follow-up durations (>10 years) across distinct TBI mechanisms. The researchers hypothesized that TBIs caused by falls or violent mechanisms would be associated with poorer functional locomotor abilities and, subsequently, lower item scores than those sustained through automotive or recreational activities. Methods: Data were obtained from the Traumatic Brain Injury Model Systems (TBIMS) database at Craig Hospital in Englewood, Colorado, the largest longitudinal TBI data repository in the world. Functional locomotion was assessed using the Functional Independence Measure (FIM) Locomotion item as the primary outcome measure. To enhance measurement precision and ensure interval-level scaling, raw FIM scores were converted into logit-based estimates of latent functional ability using Rasch modeling. Longitudinal changes of these Rasch-transformed scores were analyzed using linear mixed-effects regression, accounting for individual-level variability and unbalanced follow-up data. Results: The findings demonstrated a clinically meaningful decline in functional ability among individuals with TBIs from violent mechanisms, particularly assault-related injuries and gunshot wounds, which were associated with chronic medical complications and limited functional independence. Conversely, TBIs from bicycling, unclassified vehicular incidents, and winter sports showed significant positive estimates, possibly reflecting higher premorbid physical fitness. Motor vehicle, motorcycle, pedestrian, and fall-related TBIs demonstrated steep early gains, followed by a period of recovery stabilization and plateau. In contrast, violence-related mechanisms were characterized by consistently low median scores, with minimal long-term improvement. Falls, gymnastics, track & field, and water sports did not exhibit meaningful changes in the context of the primary hypothesis. Conclusions: TBI mechanisms play a vital role in shaping long-term functional locomotion outcomes, with violence-related TBIs associated with poorer long-term functional independence. The results have clinically important implications, supporting earlier identification of high-risk populations and the development of targeted rehabilitation strategies during periods of heightened neuroplasticity. Rasch analysis integrated with linear mixed-effects modeling yields a robust analytic framework that uncovers subtle but meaningful differences in recovery trajectories across TBI mechanisms.

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.

A major obstacle for clinical trials is the lack of objective, sensitive, and reliable measures that can detect modest changes in disease progression. Here, we determine whether acoustic and linguistic digital speech measures automatically obtained during a functionally relevant passage-reading task capture multiple dimensions of disease in ataxia, including functional communication impairment, subclinical cerebellar dysfunction and disease progression. A total of 157 individuals with ataxia and 84 controls contributed cross-sectional data, and 54 individuals with ataxia and 43 controls contributed longitudinal data within the ongoing Neurobooth natural history study. Participants completed standardized speech recordings, patient-reported outcome measures (PROMs) and neurologist-rated clinical evaluations. A novel speech processing pipeline was developed to automatically transcribe audio recordings, identify word boundaries and extract a predefined set of linguistic and within-word acoustic features. Individuals with ataxia exhibited marked disruption of speech timing, coordination and articulatory control, including slowed speech (d=1.23), prolonged inter-word pauses (d=-0.91), higher/more variable vocal intensity (|d|=0.43-0.51) and altered spectral content (|d|=0.43-0.79) compared to healthy controls. Linguistic features (e.g. speaking rate and within-word pause duration) showed strong associations with clinician-rated severity and PROMs (|r|=0.23-68), indicating alignment with functional communication impairment and patient-perceived disease burden. In contrast, acoustic features derived from cepstral measures captured subtle abnormalities in speech motor control, differentiating not only individuals with ataxia (d=0.65) but also pre-ataxic individuals (d=0.56), and those without clinically evident dysarthria (d=0.45), from controls. These findings indicate that acoustic features reflect subclinical cerebellar motor dysfunction involving impaired temporal coordination and vocal control before overt clinical speech impairment emerges. Longitudinally, several acoustic measures were sensitive to disease progression (MSDR=0.19-0.68), even in cases where clinical scales showed no detectable change. Speech-derived changes correlated with changes in clinical scales and PROMs. Both acoustic and linguistic features exhibited strong intra-session reliability. During passage reading, acoustic and linguistic measures provide complementary but different clinical information in ataxias. Linguistic measures primarily reflect downstream functional consequences of ataxic dysarthria, whereas acoustic measures provide sensitive indicators of subclinical cerebellar motor dysfunction and progression. These findings demonstrate that natural speech analysis can produce digital measures for detecting subclinical disease, quantifying functional impairment, monitoring progression in ataxia, with strong potential for application in clinical trials and remote monitoring.

Traumatic brain injury (TBI) is a leading cause of death and long-term disability in children, with many experiencing persistent symptoms even after mild TBIs. Exposure to adverse childhood experiences (ACEs) can have physiological effects that may alter how the brain responds to injury, yet the effects of ACEs on white matter injury and recovery processes remain unclear. This study examined whether a history of ACEs is associated with patterns of longitudinal change in white matter microstructure in children with mTBI. Ninety-six concussed adolescents (mean age=14.9 years, range =11.4-17.9, 51% female) from the CARE4Kids consortium completed the Pediatric ACEs and Related Life-Events Screener and underwent diffusion-weighted MRI at baseline (7-35 days after injury) and follow-up (2 months later). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), orientation dispersion index (ODI), and intracellular volume fraction (ICVF) were estimated using tract-based spatial statistics and harmonized across sites. Differences in the magnitude and direction of change in diffusion metrics over time were examined in 15 tracts of interest. Higher ACE exposure was associated with smaller absolute change in AD, MD, ODI, and ICVF across several white matter tracts, including the corpus callosum, internal and external capsules, corona radiata, and posterior thalamic radiation. Groups did not differ in the direction of white matter change for any tract-metric combination. These findings suggest that ACE exposure may blunt white matter reactivity to injury and/or reorganization during recovery processes.

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: Motor neuron disease (MND) is a fatal neurodegenerative condition with significant clinical heterogeneity that is incompletely captured by existing phenotype classifications based on onset site. Electronic health records (EHRs) contain detailed symptom documentation in clinical narratives that may enable data-driven discovery of clinically meaningful patient subgroups. Methods: We developed a natural language processing (NLP) pipeline using MedCAT to extract symptoms from clinical notes of 2,361 people with a confirmed diagnosis of MND at a tertiary neurology center. MND cohort confirmation used three complementary methods: clinic attendance records, text-based diagnosis detection, and NLP extraction with negation detection. Extracted symptoms were filtered to Unified Medical Language System semantic type T184 (Sign or Symptom) with removal of negated concepts. Patients were clustered using latent class analysis on binary symptom profiles. Survival differences were assessed using Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards regression. Results: From the first clinical notes, we identified four clusters of symptoms among 872 patients and 76 symptoms: Motor-Bulbar (n=373), Motor-Tremor (n=154), Sensory-Pain (n=222), and Motor-Respiratory (n=123). When extended to all clinical notes (n=2,065; 184 symptoms), these reorganized into three clusters: Autonomic-Respiratory (n=472), Nocturnal-Respiratory (n=338), and Classic Motor (n=1,255). Survival differences were significant across all clusters in both the first notes and all notes analyses (log-rank p < 0.001). Conclusions: NLP-based symptom extraction from EHRs identifies clinically meaningful MND subgroups that extend beyond traditional onset-site classifications. Autonomic-respiratory symptom burden is associated with poorer survival while a newly identified Sensory-Pain subtype with a better prognosis. These data-driven phenotypes may improve prognostication and inform targeted supportive care.

Purpose DICER1-mutant primary intracranial sarcoma (PIS-DICER1) is a rare, recently defined high-grade intracranial tumor. This systematic review and meta-analysis aimed to comprehensively investigate its imaging characteristics to improve preoperative diagnostic accuracy and facilitate differential diagnosis. Methods A systematic literature search was conducted in PubMed and Web of Science for studies published up to December 31, 2025. Original studies with pathologically and molecularly confirmed PIS-DICER1 and detailed imaging data were included. Imaging features, including tumor location, margin definition, meningeal contact, intratumoral hemorrhage, enhancement pattern, cystic components, peritumoral edema, and advanced imaging findings (SWI, DWI, MRS, PWI), were extracted and analyzed. Pooled proportions with 95% confidence intervals (CIs) were calculated using a random-effects model. Results Twenty-four studies comprising 110 patients with detailed imaging data were included. The pooled mean age was 18.6 years (95% CI: 15.2-22.0), with a slight female predominance (53.3%, 96/180). Tumors were predominantly supratentorial (87%, 95% CI: 80%-93%). Substantial heterogeneity was observed across studies for location (I2 = 78%). Intratumoral hemorrhage was observed in 85% (95% CI: 78%-91%). Contrast-enhanced MRI demonstrated heterogeneous enhancement in all cases (100%, 95% CI: 96%-100%). Due to sparse data, advanced MRI features could not be quantitatively synthesized, underscoring a critical knowledge gap. Conclusion PIS-DICER1 exhibits imaging features including supratentorial location, intratumoral hemorrhage, heterogeneous enhancement, well-defined margins, and meningeal involvement. These features, particularly in children and young adults with hemorrhagic supratentorial masses, should prompt differential diagnosis. Definitive diagnosis requires molecular confirmation, but recognition of these characteristics facilitates diagnosis and preoperative planning.