BACKGROUND: Newly approved intravenous therapies for Duchenne muscular dystrophy (DMD) have led to unique challenges. Totally implantable venous access ports can be utilized to provide stable intravascular access but can...BACKGROUND: Newly approved intravenous therapies for Duchenne muscular dystrophy (DMD) have led to unique challenges. Totally implantable venous access ports can be utilized to provide stable intravascular access but can be associated with procedural complications and long-term issues. METHODS: Patients with DMD who underwent port placement between 2016 and 2024 were analyzed through chart review. RESULTS: Thirty DMD patients with a total of 46 ports were identified. Twenty-one (70%) patients experienced at least one long-term complication, the most common being port malfunction in 11 (37%) patients. There were no procedural complications, but one patient experienced rhabdomyolysis 2 days after placement. CONCLUSIONS: We found that surgical placement of ports was safe in our patients with DMD but requires specific monitoring.
BACKGROUND: Among the new cases of myasthenia gravis in China, the proportion of new childhood-onset myasthenia gravis (CMG) patients ranges from 10.3% to 12.6% and is increasing annually. Nevertheless, it remains a rare...BACKGROUND: Among the new cases of myasthenia gravis in China, the proportion of new childhood-onset myasthenia gravis (CMG) patients ranges from 10.3% to 12.6% and is increasing annually. Nevertheless, it remains a rare disease with limited extensive cohort studies. This study aimed to summarize and describe the clinical characteristics of CMG patients in China. METHODS: We reviewed the data from CMG patients treated at the Center for Myasthenia Gravis in Hebei Province between 2013 and 2023 and finally included data from 1031 patients. RESULTS: The gender ratio (male: female) was 1:1.4 and the median age of onset was 5 years, with a single peak at ages 1-3 years. Within the cohort, family history accounted for 1.7% (18/1031) of the patients. Furthermore, common cold was the most prevalent medical history factor in the cohort, accounting for 4.8% of the total patients. Overall, 62.4% (643/1031) and 0.5% (5/1031) of patients tested positive for acetylcholine receptor antibodies (AChR-Abs) and muscle-specific kinase antibodies (MuSK-Abs), respectively. In addition, the AChR-/MuSK-Ab-double positive rate was 0.1% (1/1031), whereas that for MuSK/AChR-Ab double negativity was 37.25% (384/1031). The Myasthenia Gravis Foundation of America (MGFA) I classification grade was high across all age groups, with the remaining classification grades increasing with age. In addition, ocular weakness as an initial symptom was high across all age groups, and as the age of the patients increased, the proportion of patients with weakness in the limbs, bulbar, and respiratory also increased. Finally, the AChR-Ab titer level was lowest in patients with MGFA I classification and may be related to prognosis. CONCLUSIONS: CMG has a peak incidence at ages 1-3 years, with some familial predisposition and a predominance of high MGFA I classification and AChR-Ab positivity. The complexity of the initial symptoms in CMG patients is related to increasing age. Interestingly, the AChR-Ab titer levels may be a potential factor in predicting patient prognosis.
BACKGROUND: There is very little published research on how life expectancy discussions are conducted when related to patients with Duchenne muscular dystrophy (DMD). As altered life expectancy plays a large role in overa...BACKGROUND: There is very little published research on how life expectancy discussions are conducted when related to patients with Duchenne muscular dystrophy (DMD). As altered life expectancy plays a large role in overall life planning in DMD patients and caregivers, understanding when/how these conversations originate is an important step in effectively meeting patients' needs. We aim to explore the common practices and approaches among physicians when discussing life expectancy with DMD patients and their caregivers. METHODS: A questionnaire with both quantitative and qualitative response fields was sent via email as a Research Electronic Data Capture (REDCap) link to physicians who work with DMD patients. They were identified from the parent project muscular dystrophy (PPMD) database. RESULTS: Fifty-five physicians completed the survey, with the majority being cardiologists and neuromuscular neurologists. Regarding the timing of life expectancy discussions, 23 (42.6%) endorse having them at the time of initial diagnosis, referencing the importance of providing all facts up front. On the contrary, 23 (42.6%) endorse having them sometime after diagnosis, pointing to the "emotional heaviness" at diagnosis that eases with time. Most providers (34, 61.8%) report initiating these conversations themselves, while others (8, 14.5%) wait for the parents to ask the question first. All report having 'multiple conversations over time' as opposed to 'a single conversation', noting that things grow easier with time and that parents often "don't hear everything" initially because of the shock and emotional weight of the diagnosis. Recurring themes on qualitative responses include the following: every family responds differently, limited access to palliative care, and families underestimating how long their DMD children will live in light of new medical advances. CONCLUSIONS: Overall, data suggest that the discussion surrounding life expectancy is a fluid process that is different for every family and should be revisited over time. Similarly, it appears there is a wide variety in how/when providers choose to discuss life expectancy - a process that may benefit from standardization across physicians, given parents' frequent underestimation of their children's life expectancy.
BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder in children. While serum myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) is a r...BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder in children. While serum myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) is a recognized biomarker, the role of cerebrospinal fluid (CSF) MOG-IgG remains unclear, particularly in Asian pediatric populations. This study aimed to assess the diagnostic and prognostic significance of CSF MOG-IgG in pediatric MOGAD patients in Asia. METHODS: In this retrospective multicenter study, 63 pediatric MOGAD patients were identified based on clinical and radiological features and underwent paired serum and CSF MOG-IgG testing between 2000 and 2023 at two Korean institutions using a flow-cytometry-based assay. RESULTS: MOG-IgG was detected in both serum and CSF in 44 (70%) patients, serum only in 17 (27%), and CSF only in 2 (3%). Most patients (65.1%) had a monophasic course, and both CSF-only cases remained monophasic during follow-up. CSF-positive patients exhibited significantly higher CSF white blood cell counts (P = 0.011) and more favorable long-term outcomes, as indicated by lower final Expanded Disability Status Scale scores (P < 0.001). CONCLUSIONS: This study highlights the clinical characteristics of CSF MOG-IgG in Asian pediatric MOGAD patients, suggesting a possible monophasic course in CSF-only cases and potential ethnic variations, though confirmation in larger prospective cohorts is warranted.
BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive neuromuscular condition requiring long-term multidisciplinary care. Endocrine management often includes pubertal induction with testosterone for delayed pube...BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive neuromuscular condition requiring long-term multidisciplinary care. Endocrine management often includes pubertal induction with testosterone for delayed puberty, which commonly occurs in individuals receiving chronic glucocorticoid therapy. Although gender diversity is increasingly recognized among adolescents, gender identity and gender-affirming care have not been well described among individuals with DMD. METHODS: We conducted a multi-institutional, retrospective case series across pediatric neuromuscular centers in the United States, Canada, and the United Kingdom. Providers submitted deidentified data via Research Electronic Data Capture on individuals with DMD who self-identified as transgender or gender diverse (TGD). Quantitative data were summarized descriptively, and qualitative provider narratives were analyzed thematically to characterize care approaches, barriers, and psychosocial outcomes. RESULTS: Ten TGD individuals with DMD were identified. Gender identity disclosure occurred between 13 and 25 years of age, most commonly in late adolescence or early adulthood. Distress related to testosterone therapy for pubertal induction was reported in half of the cases. All individuals received mental health support and seven pursued gender-affirming medical therapy, most commonly estrogen with antiandrogens. Providers described complex decision-making balancing gender-related goals with DMD-associated risks, including osteoporosis, cardiomyopathy, reduced mobility, and thromboembolic risk. Social affirmation and/or initiation of gender-affirming care were consistently associated with improvements in mood, emotional well-being, and engagement in care. System-level barriers included institutional variability in consent processes and interdisciplinary coordination. CONCLUSIONS: This international case series highlights delayed gender identity disclosure, complex hormonal decision-making, and the importance of coordinated, affirming, interdisciplinary care for TGD individuals with DMD. As survival in DMD improves, comprehensive neuromuscular care must address psychosocial well-being alongside physical health.
BACKGROUND: MIRAGE syndrome, an acronym for myelodysplasia, infections, restriction of growth, adrenal hypoplasia, genital abnormalities, and enteropathy, is a multisystem genetic condition due to variants in sterile alp...BACKGROUND: MIRAGE syndrome, an acronym for myelodysplasia, infections, restriction of growth, adrenal hypoplasia, genital abnormalities, and enteropathy, is a multisystem genetic condition due to variants in sterile alpha motif domain-containing protein 9. Neurodevelopmental features are infrequently documented with this condition. METHODS: Informed consent was obtained from families. A retrospective chart review was done to document the phenotype. A literature review was done to identify neurodevelopmental features and causes of death that have been documented. RESULTS: Three individuals with MIRAGE syndrome were included. A spectrum of neurological features were seen including hypotonia, seizures, cerebral and cerebellar hypoplasia, lenticulostriate vasculopathy, and ventriculomegaly, as well as early death from noninfectious processes. Additionally, we report a case of malignant hyperthermia. CONCLUSIONS: This report expands on the neurological phenotype and supports the need for further research to understand the neuropathologic process to provide more informed prognostic information to families.
BACKGROUND: Pediatric-onset multiple sclerosis (POMS) affects children's health-related quality of life (HRQOL). This study aimed to examine the role of parents' and children's perspectives on HRQOL. Since identification...BACKGROUND: Pediatric-onset multiple sclerosis (POMS) affects children's health-related quality of life (HRQOL). This study aimed to examine the role of parents' and children's perspectives on HRQOL. Since identification of predictors for HRQOL is crucial to intervention and patients' QOL, this study focused on identifying cognitive and emotional predictors of POMS patients' HRQOL. METHODS: A cross-sectional study assessing HRQOL predictors from child and parent reports in 30 children with POMS (mean age = 15.76 years, 63% female). Children were assessed for HRQOL, psychological, and cognitive functioning. HRQOL was measured using self- and parent-reports on the Pediatric Quality of Life Inventory, evaluating physical health, psychological, social, and school functioning. Predictors included cognitive functioning (processing speed, attention, memory), psychological functioning (depression, anxiety), and disease severity (Expanded Disability Status Scale). Multiple regressions identified predictors of child- and parent-reported HRQOL, and correlations examined relationships between significant predictors and HRQOL subdomains. RESULTS: School functioning was the most affected HRQOL domain, followed by physical health, emotional, and social functioning. Self-reported HRQOL was predicted solely by psychological functioning: anxiety and depression significantly predicted child-reported HRQOL, with anxiety having the strongest impact. Parent-reported HRQOL was predicted by processing speed, attention, and depression, with cognitive functioning relating to school, physical, and social domains, while depression was linked to psychological HRQOL. CONCLUSIONS: Children's HRQOL perceptions were strongly shaped by anxiety and depressive symptoms, whereas parents emphasized mainly cognitive functioning. Integrating both perspectives in clinical assessments is essential. Addressing anxiety and depression in children, alongside cognitive rehabilitation and parental education, may enhance HRQOL in POMS.
BACKGROUND: Electrographic seizures (ESzs) following status epilepticus (SE) occur in 26-57% of critically ill children, typically within 48 hours of onset, and are associated with adverse neurological outcomes. Although...BACKGROUND: Electrographic seizures (ESzs) following status epilepticus (SE) occur in 26-57% of critically ill children, typically within 48 hours of onset, and are associated with adverse neurological outcomes. Although SE with fever accounts for 40-49% of pediatric SE, few studies have focused on ESz in this subgroup. We conducted a single-center retrospective study to characterize the frequency, timing, and prognostic implications of ESz following SE with fever. METHODS: We retrospectively reviewed patients admitted to our pediatric intensive care unit with SE with fever between 2017 and 2023. Continuous electroencephalography (cEEG) was performed in accordance with American Clinical Neurophysiology Society guidelines. Univariate analysis identified factors associated with ESz and poor prognosis. A subgroup analysis was conducted for patients who met the criteria for febrile status epilepticus. RESULTS: In total, 83 patients were admitted with SE with fever; cEEG was recorded in 39. ESz were detected in seven patients (18%), including three detected more than 48 hours after onset. All seven patients with ESz had poor outcomes, whereas 25% (8/32) of those without ESz had poor outcomes (P < 0.01). Among the 15 patients meeting febrile status epilepticus criteria, ESz occurred in three (20%), all of whom had poor outcomes. CONCLUSIONS: In this cohort, ESz occurred in 18% of children following SE with fever and were associated with an unfavorable prognosis, including cases appearing more than 48 hours after onset. These findings suggest that prolonged cEEG monitoring may be useful for early detection and management of ESz in this population.
BACKGROUND: Movement disorders are prevalent in pediatric palliative care (PPC), complicating chronic neurological conditions. Comprehensive studies on their characteristics and management remain limited. This study char...BACKGROUND: Movement disorders are prevalent in pediatric palliative care (PPC), complicating chronic neurological conditions. Comprehensive studies on their characteristics and management remain limited. This study characterizes movement disorders and their management strategies in children receiving PPC and describes associated clinical and outcome patterns in this setting. METHODS: We conducted a retrospective study of 137 consecutive patients with chronic neurological disorders at the Pediatric Palliative Care Unit, Sant Joan de Déu Hospital, Barcelona (January 2023-December 2024). Data encompassed demographics, diagnoses, Gross Motor Function Classification System (GMFCS), seizures, spasticity, movement disorders, treatments, and outcomes, with neuroimaging and complications reviewed. Descriptive and comparative analyses were conducted. RESULTS: Of 137 patients (55.4% male, mean age 8.3 years), 46.7% had movement disorders, predominantly dystonia (59.4% of movement disorder patients) and generalized patterns (87.5%). GMFCS level V (81.7%) and total activity of daily living dependency (91.2%) were common. Baclofen was used in 35.0% (mean dose 1.5 mg/kg/day). Deceased patients (38.7% of 137) had significantly higher opioid use (50.9% vs. 11.9%, P < 0.001), more progressive disorders (49.0% vs. 22.5%, P < 0.001), and greater need for respiratory support (47.2% vs. 28.6%, P = 0.030) than survivors. Patients with movement disorders (n = 64) had a higher prevalence of mitochondrial disorders (14.1% vs. 4.1%, P = 0.035) and better gross motor function (14.3% GMFCS I-III vs. 1.4%, P = 0.006) compared to those without (n = 73). CONCLUSIONS: Movement disorders are common in PPC, with progressive disorders linked to mortality and respiratory complications. The observed association with mitochondrial disorders may help guide targeted screening and multidisciplinary management strategies.
BACKGROUND: Pediatric patients with Huntington disease (HD) present differently from adult-onset HD. In particular, the adult population experiences seizures at the same rate as the general public (∼1%), whereas seizures...BACKGROUND: Pediatric patients with Huntington disease (HD) present differently from adult-onset HD. In particular, the adult population experiences seizures at the same rate as the general public (∼1%), whereas seizures occur in approximately 30-50% of patients with juvenile-onset Huntington disease (JHD) and can be a presenting symptom. There have been many advances in epilepsy care including development of new antiseizure medications and expanded electroencephalography (EEG) modalities, but it is uncertain whether these advances are being utilized in the current care of patients with JHD. METHODS: An anonymous, caregiver-reported electronic survey was undertaken from January 2024 to September 2025. Patient advocacy groups, providers, and professional organizations aided in distribution through direct conversation, flyers, emails, and social media. RESULTS: There was a total of 12 respondents with JHD and seizures, of which 2 (16.7%) reported seizure as the presenting symptom. Types of seizures varied and multiple types could be present in the same individual. Staring spell seizures were the most reported. Valproic acid was the most commonly used antiseizure medication. Use of home ambulatory EEG and in-hospital long-term video EEG were reported. No child was being treated by an epileptologist. CONCLUSIONS: Despite advances in epilepsy management, older medications requiring lab monitoring and with greater side effect risks continue to be used most often in JHD. Long-term video EEG modalities were used, which for patients with JHD, can be informative for differentiating movement disorder from seizure. Future prospective longitudinal natural history studies of epilepsy in JHD will be needed to best inform clinical practice.
BACKGROUND: Reviewing the 'raw' electroencephalography (EEG) waveform when assessing suspected seizures on amplitude-integrated electroencephalography (aEEG) traces is important but can be time-consuming. Video and audio...BACKGROUND: Reviewing the 'raw' electroencephalography (EEG) waveform when assessing suspected seizures on amplitude-integrated electroencephalography (aEEG) traces is important but can be time-consuming. Video and audio fast playback of long EEG recordings was previously used for review of traces from analog EEG recording systems. This study aimed to develop and apply a system for rapid visual and audio review of digital neonatal EEGs from aEEG monitoring. METHODS: Two channels of aEEG with 'raw' EEG were monitored in newborns at risk of seizures. We developed software using MATLAB (The MathWorks Inc., USA) to generate sound and display traces from rapid EEG playback. RESULTS: Recordings of 3 hours duration from eight term newborn infants were played back at 60 times the recorded speed (at 60 times, 3 hours plays in 3 minutes); seizure activity was noted to have a distinct buzz-type sound differentiable from background activity. Of 170 combined EEG seizure events in the two channels, six were missed on audio, and there were four false positive events. The sensitivity and positive predictive value were 0.96 and 0.98, respectively. CONCLUSIONS: A computer system for rapid EEG review from neonatal aEEG recordings was developed and applied; the software generates EEG signal sound as well as simultaneously visually displaying the EEG traces. Audio generated from EEG traces can help identify seizure activity and aid background assessment.
Kulosik L, Schanze I, Zacher P
… +13 more, Al-Awam BS, Srinivasan VM, Gowda VK, Krey I, Fuchs A, Goldenberg A, Saugier-Veber P, Hashemi-Gorji F, Yassaee VR, Zenker M, Sticht H, Jamra RA, Neuser S
BACKGROUND: Distinct, recurrent missense variants in KIF5C have previously been described in a small number of patients with cortical dysplasia and severe intellectual disability. We aimed to further characterize the phe...BACKGROUND: Distinct, recurrent missense variants in KIF5C have previously been described in a small number of patients with cortical dysplasia and severe intellectual disability. We aimed to further characterize the phenotype associated with KIF5C variants, including truncating variants. METHODS: We analyzed ten newly identified individuals with disease-associated KIF5C variants and compared them to previously reported cases. The variant spectrum was evaluated in a multicenter case series, and a cross-sectional analysis of the phenotypic range was performed. Molecular modeling was used to identify variant clusters and to provide insights into their potential functional effects. RESULTS: In our cohort of 19 individuals (ten newly and nine previously reported), we identified eight distinct variants: three truncating, four missense, and one in-frame deletion. Individuals with missense variants consistently exhibited severe developmental delay, absence of speech, seizures, and malformations of cortical development. In contrast, individuals with truncating variants showed milder developmental delay, less severe speech impairment, and no malformations of cortical development. CONCLUSIONS: Our findings suggest a genotype-phenotype correlation in KIF5C, with truncating variants associated with a milder phenotype compared to missense variants.
McPherson TO, Bebin EM, Farach LS
… +22 more, Wulsin AC, Davis P, Au KS, Sahin M, Wu JY, Taub KS, Rajaraman R, Randle S, McClintock WM, Koenig MK, Frost MD, Northrup H, Werner K, Nolan D, Wong M, Krefting J, Peri K, Cutter G, Krueger D, Peters JM, Porter BE, PREVeNT Study Group
Pediatr Neurol
· 2026 Jun · PMID 41904855
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BACKGROUND: The PREVeNT trial enrolled 72 infants with tuberous sclerosis complex using the presence of interictal epileptiform discharges (IEDs) on a one-h electroencephalography (EEG) to randomize into a trial of place...BACKGROUND: The PREVeNT trial enrolled 72 infants with tuberous sclerosis complex using the presence of interictal epileptiform discharges (IEDs) on a one-h electroencephalography (EEG) to randomize into a trial of placebo versus early vigabatrin. Here, we ask if early vigabatrin impacts IED presence over the first 3 years of life. METHODS: Participants underwent an EEG every 6 weeks/first year of life, every 3 months/second year of life and once at age 36 months. EEGs were reviewed by two treatment blinded electrophysiologists; if they disagreed, a third reader adjudicated. RESULTS: Seven hundred ninety-three EEGs were recorded, with IEDs present in 33.5% and at a higher percentage in the placebo arm of the study (n = 27 participants, 45.9% of 296 EEGs) than in the early vigabatrin group (n = 29, 34.3% of 332 EEGs) P = 0.0496. Infantile spasm-free participants in the vigabatrin group drove this reduction: placebo n = 14/26 without spasms, 41.7% of EEGs had IEDs versus vigabatrin n = 23/29 without spasms, and 27.7% of EEGSs had IEDs, P = 0.0185. In contrast the placebo group with spasms n = 12/26 had 51.9% IED positive EEGs versus early vigabatrin n = 6/29 with spasms had 60.3% IED positive, P = 0.5182. Overall, participants with spasms n = 18 had a higher rate of EEGs with IEDs versus those without n = 37, 54.8% vs 33.0%, P = 0.0005. CONCLUSIONS: Early treatment with vigabatrin decreased by ∼20% the proportion of EEGs with IEDs over 3 years. Vigabatrin group participants who did not develop epileptic spasms drove this reduction. Participants who developed spasms in either group had IEDs in over half of their EEGs.
BACKGROUND: Hypoxic ischemic encephalopathy (HIE) leads to neonatal mortality and long-term morbidities. Clinical and histological chorioamnionitis is an additional risk factor for neonates with HIE, which could increase...BACKGROUND: Hypoxic ischemic encephalopathy (HIE) leads to neonatal mortality and long-term morbidities. Clinical and histological chorioamnionitis is an additional risk factor for neonates with HIE, which could increase morbidity and brain injury. We aimed to assess the short-term outcomes in neonates with HIE exposed to chorioamnionitis. METHODS: We conducted a retrospective cohort study using the Canadian Neonatal Network database. We included neonates with ≥35 weeks gestational age with HIE treated with therapeutic hypothermia (TH) born between January 2011 and December 2021. Chorioamnionitis was diagnosed either clinically or histologically. The primary outcome was a composite of mortality and/or brain injury on magnetic resonance imaging. We calculated odds ratios and 95% confidence intervals for the outcomes. RESULTS: Of the 6212 neonates included, 346 were exposed and 1813 neonates were not exposed to chorioamnionitis. The primary outcome was comparable in both the groups (odds ratio 1.07; confidence interval 0.83, 1.39). Individual components of the primary outcome and other in-hospital morbidities were also similar in both the groups. The primary outcome and neonatal morbidities were also not different in neonates who missed TH. Of note, there was no difference in the incidence of neonatal sepsis in both the groups. CONCLUSIONS: In our study, exposure to chorioamnionitis did not affect the short-term neonatal outcomes irrespective of enrollment in TH.
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a key therapy for stabilizing neurological function and improving survival in cerebral adrenoleukodystrophy (CALD). Identifying a suitable mat...BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a key therapy for stabilizing neurological function and improving survival in cerebral adrenoleukodystrophy (CALD). Identifying a suitable matched related donor (MRD) or unrelated donor remains challenging, especially in countries with limited donor registry representation. These barriers have increased the use of alternative donors, such as haploidentical or umbilical cord blood grafts. Early transplantation is associated with better outcomes. METHODS: We describe outcomes of seven consecutive children with rapidly progressive CALD who underwent allo-HSCT between January 2015 and December 2023 at a single institution in Colombia, including matched related donor and alternative donors (haploidentical related and umbilical cord blood). Clinical data, imaging, and transplant characteristics were collected retrospectively. RESULTS: Seven children underwent allo-HSCT at a median age of 8 years. The median (range) age at CALD diagnosis was 8 years (4-11), and the median interval from CALD diagnosis to allo-HSCT was 14 months (range, 6-36). Alternative donors were used in six of seven cases (86%). Neutrophil engraftment occurred in six patients (85%) at a median of 15 days (12-29), and platelet engraftment in all evaluable patients at a median of 18 days (12-27). The median follow-up duration after transplant was 24 months. Two patients experienced stable or preserved neurological function, while others showed progression or died from transplant or disease-related complications. CONCLUSIONS: This study highlights real-world outcomes of allo-HSCT for CALD in a resource-limited setting. The findings underscore the importance of early diagnosis and expedited donor access to optimize neurological outcomes.