BACKGROUND: Language impairments impact 72% of individuals with tuberous sclerosis complex (TSC). Nevertheless, evaluations are often delayed until children are 7 years old or older. Earlier prediction of language impair...BACKGROUND: Language impairments impact 72% of individuals with tuberous sclerosis complex (TSC). Nevertheless, evaluations are often delayed until children are 7 years old or older. Earlier prediction of language impairment is needed. Infant vocal behavior is a predictor of language development in typically developing children, but early vocal development had not been studied in TSC until recent research on 38 infants. In this study, the canonical babbling ratio (CBR) and volubility, key indicators of infant vocal behavior, were low. CBR reflects the proportion of syllables that are canonical and volubility reflects either production of utterances or syllables per minute. The present study has the following three goals: (1) To expand CBR and volubility characterization, (2) To evaluate predictiveness of CBR and volubility for autism spectrum disorder (ASD) and language outcomes, and (3) To determine if the contribution of CBR to prediction is independent of other known predictors. METHODS: We analyzed 202 recordings at 12 months for infants with TSC. Linear regression predicted language outcomes from vocal measures. Then, stepwise multiple regression compared the relative predictiveness for language outcomes of CBR and other measures known to predict language outcomes. Finally, logistic regression tested for ASD prediction. RESULTS: CBR and volubility were lower in TSC than in prior typically developing data. CBR was predictive of language outcomes at 24 months for infants with TSC even when competing against other known predictors, but neither CBR nor volubility predicted ASD. CONCLUSIONS: CBR may have utility for early identification of language impairments in TSC.
BACKGROUND: The International Classification of Functioning, Disability, and Health-Children and Youth Version (ICF-CY)-check list, is a free tool, used to quantify disability. World Health Organization Disability Assess...BACKGROUND: The International Classification of Functioning, Disability, and Health-Children and Youth Version (ICF-CY)-check list, is a free tool, used to quantify disability. World Health Organization Disability Assessment Schedule-Children and Youth version [WHODAS 2-Children and Youth (WHODAS-Child)] is a less time-consuming tool, to quantify disability, based on the ICF-frame work. We aimed to quantify the disability of a group of cognitively disabled children using ICF-CY-checklist, WHODAS-Child and Vineland Social Maturity Scale (VSMS) score. We compared scores obtained using ICF-CY and WHODAS-Child, with VSMS taken as reference and also compared ICF-CY and WHODAS-Child scores. We ascertained factors associated with greater disability. METHODS: A hospital based cross-sectional study with diagnostic test evaluation. RESULTS: Hundred cognitively disabled children were recruited (median age 6 years, 73% male). ICF-CY median 'b,' 'd,' and total scores were 8.8 (interquartile range [IQR]: 5.95, 15.4), 23.7 (IQR: 14.9, 36.7) and 16.8 (IQR: 10.7, 27.4). On multivariable-regression-analysis, age-at-first-concern below one-year, diagnosis of autism-spectrum-disorder, family history of developmental-cognitive-disability, prematurity, low-birth-weight, motor deficits and higher-maternal-age were associated with worse cognitive ability. There was a significant negative correlation (rho = -0.50, P < 0.001) on comparison of ICF-CY with VSMS, and WHODAS-Child in relation to VSMS (rho = -0.42, P < 0.001). A positive correlation was found between ICF-CY-d-score and WHODAS-Child score (rho = 0.79, P < 0.001). CONCLUSIONS: The impairment and disability of a group of children can be captured using ICF-CY-checklist. The easier to administer, WHODAS-Child, matches well with ICF-CY 'd' scores and VSMS, and can be used for quantification of disability. This quantification can help to assess burden-of-illness, in a geographic area or due to a particular etiology and would serve to assess the effect of an intervention on these children, uniformly across the globe.
BACKGROUND: To determine efficacy of early steroid therapy on outcomes in children with acute necrotizing encephalopathy. METHODS: We leveraged two 2023 systematic reviews to identify eligible publications, predefined as...BACKGROUND: To determine efficacy of early steroid therapy on outcomes in children with acute necrotizing encephalopathy. METHODS: We leveraged two 2023 systematic reviews to identify eligible publications, predefined as having ≥3 patients, objective study outcomes categorized as good or poor, and described according to steroid therapy. Data were combined by (i) adding raw data from included studies (as done in the previous systematic review) and (ii) random effects meta-analysis with relative risk (RR) and 95% confidence interval (CI). Sensitivity analysis used a more consistent definition of good outcome and excluded lower quality studies. P values ≤0.05 and ≤ 0.005 were considered statistically suggestive or significant. RESULTS: Nine retrospective observational studies were included, each with different definitions of good versus poor outcome. Combined numbers found a statistically suggestive effect for early steroids (RR 2.17 [95% CI 1.25, 3.76]; P = 0.006) and in the sensitivity analysis (RR 2.09 [95% CI 1.16, 3.93] P = 0.021) but not in subgroups with/without brainstem lesions. Meta-analysis found statistically suggestive effect for early steroids (RR 2.06 [95% CI 1.03, 4.09] P = 0.040); this was not statistically suggestive in sensitivity analysis (RR 2.03 [95% CI 0.99, 4.16] P = 0.052), in those without brainstem lesions, or for any steroids. CONCLUSIONS: Meta-analysis suggested that it may be premature to assert that early steroids, even in those without brainstem involvement, will improve neurologic outcomes in children with acute necrotizing encephalopathy. For a false positive rate 5%, the required prior probability of effect would be implausibly high. Good outcomes were not uncommon, questioning the label 'necrotizing' in all cases.
BACKGROUND: There is limited understanding of cerebral palsy (CP) in low-middle-income countries (LMICs). This retrospective cross-sectional study aims to describe and compare the phenotype, severity and etiologic profil...BACKGROUND: There is limited understanding of cerebral palsy (CP) in low-middle-income countries (LMICs). This retrospective cross-sectional study aims to describe and compare the phenotype, severity and etiologic profile of children with CP born either in a LMIC or high-income country (HIC) assessed in a single setting. METHODS: Data from consecutive children with CP initially assessed by a single neurologist over a 5-year interval (2020-2024 inclusive) were extracted from hospital records. Children were classified into one of two groups based on location at birth (HIC or LMIC). Pearson chi-square analyses compared the two CP populations along the following characteristics: CP subtype, etiology, magnetic resonance imaging finding, functional impairments, and comorbidities. RESULTS: Eighty-nine Canadian (HIC) born and 48 LMIC born children met inclusion criteria. LMIC children were significantly (P < 0.01) more likely to have spastic quadriparetic or dyskinetic CP, magnetic resonance imaging signs of deep gray matter injury, Gross Motor Function Classification System/Manual Ability Classification System level IV-V functional severity or cognitive disability and be nonverbal, deaf or cortically blind than a child born in a HIC. Intrapartum asphyxia or kernicterus was significantly (P < 0.01) more likely as an etiology in LMIC born children. CONCLUSIONS: Children from LMICs have a substantially different CP phenotype. This phenotype is markedly more severe with respect to functional impairments and comorbidities. This likely reflects a significantly greater degree of deep gray matter injury that is the consequence of an altered etiologic profile. These results provide greater insight into the profile of CP in LMICs offering specific targets for preventative strategies. Greater service needs for children with CP derived from migrant populations in HICs can be expected.
BACKGROUND: Migraine in childhood and adolescence is a common neurological disorder extending beyond headache attacks, often affecting cognitive, emotional, and behavioral functioning during the interictal phase. Althoug...BACKGROUND: Migraine in childhood and adolescence is a common neurological disorder extending beyond headache attacks, often affecting cognitive, emotional, and behavioral functioning during the interictal phase. Although migraine-related disability and school absenteeism are well recognized, comprehensive multidimensional assessments are limited, especially in non-Western populations. To examine the interictal burden of pediatric migraine by evaluating executive functions, emotional-behavioral symptoms, and attention-deficit/hyperactivity disorder (ADHD)-related features using standardized psychometric tools. METHODS: This cross-sectional study included 71 adolescents (mean age 14.6 ± 1.9 years; 70.4% female) diagnosed with migraine based on International Classification of Headache Disorders, 3rd edition criteria. Migraine-related disability and impact were measured with the Pediatric Migraine Disability Assessment (PedMIDAS) and Headache Impact Test (HIT-6). Executive functions were assessed using the Teenage Executive Functioning Inventory (TEXI), emotional-behavioral symptoms with the Strengths and Difficulties Questionnaire (SDQ), and ADHD-related features with the Conners Parent Rating Scale-Short Form. Correlation, group comparison, and multiple regression analyses explored associations between migraine severity, headache frequency, and psychometric outcomes. RESULTS: PedMIDAS and HIT-6 indicated moderate-to-severe migraine burden. HIT-6 correlated with TEXI inhibition, Conners total, ADHD index, and SDQ emotional symptoms. PedMIDAS correlated with SDQ emotional and hyperactivity subscales. Headache frequency was associated with TEXI total and SDQ total scores. Girls had higher PedMIDAS and TEXI inhibition, while boys scored higher on Conners hyperactivity. Regression analyses revealed directional but nonsignificant relationships after adjusting for confounders. CONCLUSIONS: Pediatric migraine imposes a considerable interictal burden, influencing executive, emotional, and behavioral domains. Multidimensional evaluation and integrated management approaches are essential to address both medical and psychosocial impacts.
BACKGROUND: In children with unilateral cerebral palsy (uCP), the relation between different factors (brain damage, prematurity, and cerebral palsy side) and visual impairments, which are common but often 'unseen,' is no...BACKGROUND: In children with unilateral cerebral palsy (uCP), the relation between different factors (brain damage, prematurity, and cerebral palsy side) and visual impairments, which are common but often 'unseen,' is not fully understood. METHODS: Visual functions and functional vision were assessed in 41 children with uCP (7-15 years, 21 left-sided, 19 preterm). Brain damage was scored on structural magnetic resonance imaging regarding lesion timing, location, and severity, and corpus callosum (CC) length and splenium thickness. With nonparametric statistics, we investigated the relation between visual outcomes and brain damage (r) and differences in visual outcomes and brain damage based on prematurity and uCP side (r). With elastic-net regularized regression models (area under the receiver operating characteristic curve [AUC]; d), we explored if gestational age and brain damage could predict impairments in visual functions. RESULTS: Damage to the lobes and CC was associated with reduced visual functions and functional vision (r = -0.402 to -0.611). Compared to children born at term, preterm children mainly showed reduced geniculostriate functions (r = 0.343-0.443) and damage to the parietal lobe (r = 0.353). No differences in brain damage were found between children with left- and right-sided uCP. In regression models, shorter CC length and parietal lobe lesion (d = -0.526 to 0.564) were the main predictors for impaired stereoacuity (AUC = 0.77), and occipital lobe lesion (d = 0.349) for impaired visuomotor integration (AUC = 0.81). Prediction models of visual perception showed poor predictive performance (AUC<0.70). CONCLUSIONS: Specific brain damage and prematurity are related to different visual impairments in children with uCP. Our results could guide clinicians in directing their attention to specific visual assessments and subsequent intervention in children with uCP.
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BACKGROUND: To assess the accuracy of the Generalized Anxiety Disorder-2 (GAD-2) Scale for screening anxiety symptoms in children with headache and epilepsy. METHODS: Single-center and large-scale assessment of the two-i...BACKGROUND: To assess the accuracy of the Generalized Anxiety Disorder-2 (GAD-2) Scale for screening anxiety symptoms in children with headache and epilepsy. METHODS: Single-center and large-scale assessment of the two-item GAD-2 as compared to the seven-item Generalized Anxiety Disorder-7 (GAD-7) to screen for moderate-severe anxiety symptoms in children undergoing follow-up neurology appointments. RESULTS: The GAD-7 was fully completed for 3960 of 6060 (65%) encounters. Anxiety symptoms were moderate in 534 (13%) encounters and severe in 337 (9%) encounters. The GAD-2 and GAD-7 were very strongly correlated (spearman's rho 0.91; P < 0.001). When assessing moderate-severe anxiety symptoms based on the GAD-7, a GAD-2 score of ≥3 yielded an area under the receiver operating characteristics curve of 0.96, sensitivity 89%, specificity 91%, positive predictive value 74%, and negative predictive value 97%. If assessment stopped with the GAD-2 at the ≥3 cutoff, then 74% of encounters would be considered not to have anxiety symptoms and would not complete additional questions, but 11% of encounters with moderate-severe anxiety symptoms would not be identified, including 0.6% of patients with severe anxiety symptoms. CONCLUSIONS: Anxiety symptoms were common. Use of the GAD-2 would reduce the number of questions needing completion compared to the GAD-7 for 74% of patients but would fail to identify 11% of patients with moderate-severe anxiety symptoms, including 0.6% of patients with severe anxiety symptoms. These data indicate that the use of the GAD-2 may be appropriate as a briefer alternative to the GAD-7 which may be ideal in clinical settings with a substantial questionnaire burden.
BACKGROUND: Motor function tests (MFTs) in Duchenne muscular dystrophy (DMD) are useful in the early stage but may miss subtle changes in the advanced stage due to floor effects. Conventional DMD-specific MFTs primarily...BACKGROUND: Motor function tests (MFTs) in Duchenne muscular dystrophy (DMD) are useful in the early stage but may miss subtle changes in the advanced stage due to floor effects. Conventional DMD-specific MFTs primarily assess proximal motor function and may not adequately detect distal motor function. Based on our clinical experience in spinal muscular atrophy (SMA), fine motor assessments such as the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) have been observed to be effective in detecting changes even in severely affected patients. Therefore, the aim of this study was to assess treatment response to viltolarsen in patients with DMD using both DMD-specific and SMA-based MFTs. METHODS: We retrospectively evaluated three patients with genetically confirmed DMD: two nonambulatory adolescents aged 17 and 19 years treated with viltolarsen for 36 months, and 1 ambulatory 6-year-old patient treated for 10 months, assessed at baseline and final visits using conventional DMD-specific MFTs, including time to stand from supine, 10-meter walk/run, Brooke upper extremity scale, and SMA-based MFTs such as CHOP-INTEND. RESULTS: In the ambulatory patient, the time to stand from supine showed a slight increase that did not reach the minimal clinically important difference, while the 10-meter walk/run test showed a slight decline. In contrast, both nonambulatory patients showed marked improvements in CHOP-INTEND scores, despite no change in conventional MFTs. CONCLUSIONS: These findings suggest that CHOP-INTEND may capture subtle but clinically meaningful improvements in advanced-stage DMD. In conclusion, selecting stage-appropriate MFTs based on disease severity is important when evaluating treatment-related changes in patients with DMD.
BACKGROUND: To identify the most common medication adherence barriers among pediatric patients with epilepsy, standardized screening was implemented in a child neurology division using the Barriers to Adherence Tool. MET...BACKGROUND: To identify the most common medication adherence barriers among pediatric patients with epilepsy, standardized screening was implemented in a child neurology division using the Barriers to Adherence Tool. METHODS: The Barriers to Adherence Tool was implemented as a standardized previsit questionnaire for follow-up encounters for seizures/epilepsy. Responses from July 2021 to March 2025 were analyzed. RESULTS: The questionnaire was completed for 12,466 of 16,808 (74%) follow-up encounters for 5251 patients. At least one barrier was reported at 4351 (35%) encounters with completed questionnaires. The most common barriers included side effects (1612 barriers endorsed; 25%), does not control seizures (1000; 16%), trouble remembering medication (792; 12%), dislike medication taste (684; 11%), other (592; 9%), run out of medication (363; 6%), and too many medications/doses (320; 5%). Barriers were more often reported among patients who self-reported as Black/African American, experienced frequent seizures, or took more than one antiseizure medication. Conversely, barriers were reported less often among patients who self-reported as White, were seizure free or experienced infrequent seizures, or took one antiseizure medication. Among the 1166 patients who completed the questionnaire multiple times and endorsed a barrier at the first encounter, reported barriers were fewer at the last encounter for 770 patients (66%), unchanged for 277 patients (24%), and increased for 119 patients (10%). CONCLUSIONS: Screening for medication barriers was feasible for a large cohort of patients in a sustainable and repeatable manner, and barriers were common. Future improvement initiatives may focus on improving common barriers.
BACKGROUND: This study aimed to evaluate electroclinical remission and long-term outcomes in children with infantile epileptic spasms syndrome (IESS) associated with trisomy 21 (T21). We hypothesized that initial treatme...BACKGROUND: This study aimed to evaluate electroclinical remission and long-term outcomes in children with infantile epileptic spasms syndrome (IESS) associated with trisomy 21 (T21). We hypothesized that initial treatment with hormone therapy would result in higher remission rates compared to treatment with vigabatrin. METHODS: A retrospective study of T21 and IESS patients was conducted across six North American tertiary pediatric centers. RESULTS: A total of 114 children with IESS were identified. Electroclinical remission without relapse occurred in 31.5% (17/54) of patients receiving hormone therapy as first-line treatment compared with 16.7% (6/36) treated with vigabatrin monotherapy (P = 0.114). Median time to remission was shorter with hormone therapy (41 days) than with vigabatrin (142 days; P < 0.001). Median age at last follow-up was 33 months (IQR 18-83) with a median follow-up duration of 25 months (IQR 11-74). At last follow-up, ongoing epilepsy was present in 30.7% (35/114) and autism spectrum disorder (ASD) in 25.4% (29/114), with similar rates across first-line treatment groups (ongoing epilepsy: hormonal 28.6% vs vigabatrin 30.6%; ASD: 21.4% vs 33.3%; all P > 0.05). CONCLUSIONS: Children with T21-associated IESS were approximately two times more likely to achieve electroclinical remission with hormone therapy as first treatment compared to vigabatrin, although this difference did not reach statistical significance. The median time to remission was significantly shorter in children who received hormone therapy as their first treatment compared to those treated with vigabatrin. The initial treatment did not impact long-term clinical outcomes, such as ongoing epilepsy or ASD.
BACKGROUND: Pediatric movement disorders (MDs) in Latin America are undercharacterized, limiting timely diagnosis and access to advanced therapies. Our aim is describe the clinical and etiological profile of pediatric MD...BACKGROUND: Pediatric movement disorders (MDs) in Latin America are undercharacterized, limiting timely diagnosis and access to advanced therapies. Our aim is describe the clinical and etiological profile of pediatric MDs at a Colombian tertiary referral center and identify factors associated with diagnostic delay. METHODS: We conducted a retrospective cohort study of 210 consecutive patients aged 0-18 years evaluated at a specialized pediatric MD clinic in Bogotá (January 2022-June 2025). All patients underwent standardized diagnostic protocols including comprehensive phenotyping, etiological workup, and treatment documentation. Multivariable logistic regression assessed predictors of diagnostic delay >12 months. RESULTS: Males comprised 57.6% (121/210). Median age at symptom onset was 18 months (interquartile range 6-82) and at first consultation 127 months (interquartile range 66-173). Primary phenotypes in this tertiary referral center were dystonia 33.3% (70/210), tics 14.3% (30/210), and tremor 10.9% (23/210); 33.3% (70/210) had mixed presentations. Etiologies included structural 27.6% (58/210), nonmetabolic genetic 14.8% (31/210), and unidentified 30.5% (64/210). Median diagnostic delay was 18.5 months with 64.9% (135/208) exceeding 12 months. Patients outside Bogotá experienced longer delays (36 vs 18 months, P < 0.001). Nonmetabolic genetic etiology independently predicted prolonged delay (odds ratio 6.36, 95% confidence interval 1.77-22.83). Intellectual disability affected 33.2% (69/208) and epilepsy 19.4% (40/206). CONCLUSIONS: This tertiary referral center data reveals high dystonia burden, substantial unidentified etiologies (30.5%), and prolonged diagnostic delays in Colombian pediatric MDs. Immediate priorities include expanding genomic testing access, establishing telemedicine networks for rural populations, and implementing fast-track diagnostic pathways to reduce delays and optimize therapeutic outcomes in middle-income settings.
BACKGROUND: Patient access is one of the greatest challenges in health care today. Pediatric neurology is a highly specialized field with a significant shortage of providers, resulting in appointment wait times that may...BACKGROUND: Patient access is one of the greatest challenges in health care today. Pediatric neurology is a highly specialized field with a significant shortage of providers, resulting in appointment wait times that may extend for several months. Missed appointments in which the patient does not cancel or reschedule in advance, referred to as "no-shows," contribute to further delays in access as those visit slots go unfilled. METHODS: We evaluated patient risk factors for appointment nonadherence in a pediatric neurology clinic and implemented an intervention for patients identified as being at highest risk for no-show. The intervention consisted of clinic schedulers directly calling the patient's parent or guardian to remind them of the upcoming appointment. Families were given the option to keep, cancel, or reschedule their appointment. RESULTS: Implementation of the targeted reminder intervention improved appointment show rates among high-risk patients, increased clinic access, and resulted in a 32% increase in clinic revenue. CONCLUSIONS: Targeted, direct phone reminders for high-risk pediatric neurology patients significantly reduced no-show rates, improved overall patient access, and increased clinic revenue. Longer-term implementation and further evaluation through multisite studies across diverse health care settings are warranted to confirm effectiveness and assess broader applicability of this intervention.
BACKGROUND: Intrathecal administration of Baclofen, a γ-aminobutyric acid agonist, is an established treatment for spasticity in both pediatric and adult populations, resulting in functional improvements in daily activit...BACKGROUND: Intrathecal administration of Baclofen, a γ-aminobutyric acid agonist, is an established treatment for spasticity in both pediatric and adult populations, resulting in functional improvements in daily activities. Treatment optimization requires multiple, gradual dose adjustments to achieve the optimal dose for each patient, tailored to individualized goals and the specific pathology. METHODS: We conducted a retrospective review of our experience from August 2021 to December 2024. A total of 43 pediatric patients were implanted with an intrathecal Baclofen pump. We analyzed the test dose, the dose-finding process and the complications we experienced. Subsequently, we conducted a subgroup analysis to identify any statistically significant differences between subgroups. RESULTS: Thirty-five patients underwent a bolus via lumbar puncture, while in 6 cases via a subcutaneous reservoir. The average dose at the implantation was 69 mcg of baclofen/day ± 37 mcg/day, with an average dose change during the follow-up of +52% ± 79%. The cumulative revision rates were 6.9%, 7.7%, and 11.8% at 30 days, 3 months, and 6 months, respectively. No statistically significant differences between subgroups were found. CONCLUSIONS: The dose-finding requires a long and multistep process. The high interindividual variability highlights the need for a highly personalized approach to dose titration.
BACKGROUND: Functional tic-like behaviors (FTLBs) are increasingly recognized as distinct from Tourette syndrome, characterized by abrupt onset, complex and atypical motor and vocal phenomena, and the absence of premonit...BACKGROUND: Functional tic-like behaviors (FTLBs) are increasingly recognized as distinct from Tourette syndrome, characterized by abrupt onset, complex and atypical motor and vocal phenomena, and the absence of premonitory urges or suppressibility. During the severe acute respiratory syndrome coronavirus 2 pandemic, there was a marked rise in FTLB cases, disproportionately affecting adolescents assigned female at birth and individuals with gender dysphoria. Data describing FTLBs in adolescents with coexisting gender dysphoria remain limited. METHODS: We conducted a retrospective review of patients younger than 18 years presenting to the Tourette Centers of Excellence at Arkansas Children's Hospital between January 2022 and December 2023 with sudden onset complex tic-like behaviors and coexisting gender dysphoria. Demographic characteristics, clinical phenomenology, psychiatric comorbidities, treatments, and outcomes were abstracted from the medical record. RESULTS: Nine patients met inclusion criteria (median age 15 years, range 9-18 years); 89% were assigned female at birth, and all were White/Caucasian. Tic onset occurred within six months before or after the diagnosis of gender dysphoria. FTLB phenomenology included context-dependent motor behaviors (self-injury, object throwing, copropraxia, freezing, and drop episodes) and socially inappropriate or situationally triggered vocalizations, with symptom fluctuation and frequent emergence of new movements or sounds. Psychiatric comorbidity was universal: anxiety and depression were present in 100%, attention-deficit/hyperactivity disorder in 44%, suicidal ideation in 44%, and prior suicide attempts in 33%. Additional diagnoses included post-traumatic stress disorder (22%), obsessive-compulsive disorder (22%), eating disorder (11%), and autism spectrum disorder (11%). All patients received psychotherapy, and 78% received pharmacologic treatment, most commonly selective serotonin reuptake inhibitors and alpha-2 agonists. At follow-up of at least 12 months, all patients demonstrated complete or near-complete resolution of FTLBs, accompanied by improved psychiatric stability and functional recovery. CONCLUSION: This case series highlights the intersection of FTLBs and gender dysphoria in adolescents and underscores the importance of multidisciplinary, integrated mental health care. Early recognition and comprehensive psychiatric treatment are associated with favorable long-term outcomes in this population.