BACKGROUND: The purpose of this research is to study the neurological consequences of infantile vitamin B12 deficiency on the developing brain. METHODS: A prospective cohort study was done in consecutive children with In...BACKGROUND: The purpose of this research is to study the neurological consequences of infantile vitamin B12 deficiency on the developing brain. METHODS: A prospective cohort study was done in consecutive children with Infantile B12 deficiency. Clinical evaluation, developmental assessment, blood investigations, and a magnetic resonance imaging (MRI) of the brain were performed at baseline and after therapy with injectable vitamin B12. RESULTS: Among 141 children (median age-13 months), developmental delay was observed in 131 (93%), and 79 (56%) had regression. Eighty (57%) babies had head circumference of < -2 Z score. At baseline, the MRI of the brain was abnormal in 137 (97.2%), showing thinning of corpus callosum (n = 133, 94.3%), cerebral cortical atrophy (n = 128, 90.8%), cerebellar atrophy (n = 126, 89.4%), atrophy of midbrain (n = 81, 57.4%) and pons (n = 78, 55.3%). A follow-up MRI done in 98 (69.5%) showed 66 (67%) had one or more residual abnormalities. The baseline full-scale developmental quotient was 22 (interquartile range: 13-30), while the follow-up full-scale developmental quotient score was 47.5 (interquartile range: 42.5-55). Seventy-nine (67.5%) had a follow-up developmental quotient of less than 50, implying moderate to severe developmental retardation. CONCLUSIONS: Despite therapy, children affected by the infantile B12 deficiency syndrome have significant lasting effects on the brain, evident as poor head growth, developmental deficits, and residual brain imaging changes.
Go S, Morishita N, Takeshita M
… +14 more, Murakami M, Minami S, Matsumoto W, Hayashi K, Takahashi R, Watanabe Y, Saito N, Ohno K, Kasuga A, Morichi S, Ishida Y, Ishii C, Kinjo N, Yamanaka G
BACKGROUND: Chronic daily headache (CDH) in youth is a functionally disabling and diagnostically heterogeneous condition that often requires multifaceted intervention. Real-world care is frequently fragmented-either limi...BACKGROUND: Chronic daily headache (CDH) in youth is a functionally disabling and diagnostically heterogeneous condition that often requires multifaceted intervention. Real-world care is frequently fragmented-either limited to pharmacologic management or constrained by limited access to behavioral services. We evaluated the effectiveness of a generalist-deliverable bio-psycho-social (BPS) management model for children and adolescents with CDH, addressing both pharmacologic and contextual factors in the absence of subspecialty mental health services. METHODS: This retrospective, single-center observational study included 37 pediatric patients diagnosed with CDH according to ICHD-3 criteria. All participants received a structured BPS model delivered by general pediatricians. The model comprised (1) feature-guided pharmacologic treatment, (2) narrative-based psychosocial dialog, and (3) gradual school reintegration. Headache frequency, school attendance, and Pediatric Migraine Disability Assessment-assessed disability were evaluated at baseline, 6 months, and 24 months. RESULTS: By 6 months, only 13.5% of patients met CDH criteria; by 24 months, this decreased to 5.4%. Headache frequency, school attendance, and disability scores improved significantly (P < 0.001 for all). Improvements occurred across diagnostic subtypes and were not solely dependent on pharmacologic treatment, underscoring the contribution of nonpharmacologic components. Functional recovery-particularly school attendance-often lagged behind symptom resolution. CONCLUSIONS: A generalist-deliverable BPS model was associated with sustained improvement in CDH outcomes, even in the absence of subspecialty resources. This pragmatic framework may support individualized, function-centered care for pediatric CDH in real-world settings.
BACKGROUND: Early infantile epileptic encephalopathy (EIEE) is a severe subtype of developmental and epileptic encephalopathies, characterized by early-onset, refractory seizures and associated with progressive psychomot...BACKGROUND: Early infantile epileptic encephalopathy (EIEE) is a severe subtype of developmental and epileptic encephalopathies, characterized by early-onset, refractory seizures and associated with progressive psychomotor impairment, intellectual disability, and increased early mortality. In this cohort study, we evaluated patients diagnosed with 34 distinct EIEE subtypes over a 3-year period. In addition, we identified novel founder variants in unrelated patients from the Khorasan Razavi region in northeastern Iran. METHODS: Clinical assessments were performed by specialists. All affected individuals experienced seizures with onset before one year of age. Global developmental delay and intellectual disability were diagnosed according to standard clinical criteria and evaluated by pediatric neurologists. Genomic DNA was extracted from peripheral blood samples for whole-exome sequencing, with candidate variants subsequently validated by Sanger sequencing. RESULTS: We identified a total of 61 genetic variants associated with 34 distinct EIEE subtypes in 65 unrelated families. Of these, 38 variants (62.3%) were novel, whereas 23 variants (37.7%) had been previously reported. Notably, recurrent founder variants were observed among patients originating from specific geographic regions. Overall, 44 variants (72.13%) were classified as pathogenic or likely pathogenic, while 17 variants (27.87%) were categorized as variant of uncertain significance. CONCLUSIONS: This study highlights the substantial genetic heterogeneity of EIEE in an underrepresented region, the Khorasan Razavi Province, with a high proportion of novel and founder variants. This study underscores the limitations of gene panels and supports the use of comprehensive genomic techniques, such as whole-exome sequencing, for early and accurate diagnosis.
BACKGROUND: Complex motor stereotypies (CMS) are repetitive movements classified into "primary" for typically developing individuals and "secondary" for those with other neurological or neurodevelopmental disorders. This...BACKGROUND: Complex motor stereotypies (CMS) are repetitive movements classified into "primary" for typically developing individuals and "secondary" for those with other neurological or neurodevelopmental disorders. This study evaluated children diagnosed with primary CMS to assess motor stereotypy outcomes, sex-related differences, and early neurodevelopmental histories that play a key role in diagnostic classification. METHODS: Sixty-five healthy participants diagnosed with pCMS (44 males, 21 females), mean age 9.1 ± 3.6 years (range 3-17 years), completed follow-up telephone interviews and questionnaires on symptom onset, medical history, and autism screens. Stereotypy severity was rated by both parents and affected children using the Stereotypy Severity Scale and Stereotypy Linear Analog Scale (SLAS). RESULTS: The mean stereotypy onset was 1.2 ± 1.1 years. Stereotypy Severity Scale Motor and Global Impairment scores were positively correlated and showed that the Impairment score was significantly influenced by the Motor Interference score. Stereotypy severity was reduced in older individuals, primarily due to decreased Motor Intensity scores. Females showed greater Global Impairment after adjusting for age. Comorbidities included anxiety disorders (35%), attention-deficit/hyperactivity disorder (35%), tics/Tourette syndrome (9%), and obsessive-compulsive disorder (6%). A history of motor and/or speech delays was reported in 58%. CONCLUSIONS: Although stereotypical symptoms were present in all subjects, there was an apparent age-related reduction in movement intensity. Stereotypies in females were associated with greater impairment in self-esteem, family life, school, and social acceptance. The presence of mild, early neurodevelopmental delays, and/or later appearing neuropsychiatric comorbidities is common among children with pCMS and should not be considered exclusionary for the diagnosis.
Damkjaer M, Morris JK, Ballardini E
… +15 more, Barrachina-Bonet L, Cavero-Carbonell C, Coi A, Gissler M, Given J, Heino A, Jordan S, Neville A, Santoro M, Tan J, Tucker D, Wellesley D, Urhoj SK, Garne E, Loane M
BACKGROUND: Children with congenital anomalies (CAs) are at an increased risk of developing epilepsy, but the relative risk (RR) for specific anomaly subtypes remains underexplored. This study aims to estimate the risk o...BACKGROUND: Children with congenital anomalies (CAs) are at an increased risk of developing epilepsy, but the relative risk (RR) for specific anomaly subtypes remains underexplored. This study aims to estimate the risk of epilepsy, as indicated by antiseizure medication (ASM) prescriptions, among children with various CAs compared to children without anomalies. METHODS: We utilized data from six European regions participating in the European network for surveillance of congenital anomalies registries, covering births from 2000 to 2015. Children with major CAs, classified by International Classification of Diseases codes, were compared to a reference population without anomalies. Epilepsy was identified based on >1 ASM prescription within a year. RRs were calculated using mixed-effects models to account for registry-specific variations. RESULTS: The study included 60,662 children with anomalies and 1,722,912 reference children, with a mean follow-up of 5.5 years. By age 5 years, ASM prevalence was 17.8 per 1000 in anomaly groups and 2.0 per 1000 in reference children. The highest RRs were observed in children with central nervous system anomalies, including anomalies of the corpus callosum, severe microcephaly, and hydrocephalus. Comparable RRs were found in children with severe congenital heart defects and gastrointestinal anomalies, primarily driven by diaphragmatic hernia. CONCLUSIONS: Children with CAs have a significantly higher risk of epilepsy, with central nervous system, chromosomal, severe congenital heart defect, and diaphragmatic hernia being key contributors. This study highlights the importance of tailored monitoring and early intervention for high-risk groups to improve neurological outcomes.
BACKGROUND: Limb-girdle muscular dystrophies (LGMDs) are a group of genetic disorders marked by progressive weakness and atrophy of proximal limb muscles. Calpainopathy is the most prevalent autosomal recessive form (LGM...BACKGROUND: Limb-girdle muscular dystrophies (LGMDs) are a group of genetic disorders marked by progressive weakness and atrophy of proximal limb muscles. Calpainopathy is the most prevalent autosomal recessive form (LGMD-R1), caused by biallelic variants in the CAPN3 gene, whereas the less common autosomal dominant (LGMD-D4) results from a heterozygous variation. METHODS: This retrospective study elaborates on the clinical and molecular characteristics of patients with CAPN3-related dystrophies in an Egyptian cohort of 48 LGMD patients. RESULTS: Exome sequencing identified 13 CAPN3 variants in 12 LGMD-R1 patients and one with LGMD-D4. Among these, two novel missense variants were described: c.581C>T (p.Ser194Phe) and c.1536G>C (p.Glu512Asp). More than half of the revealed variants were missense mutations, a finding that is consistent with previous studies in other populations. A genotype-phenotype correlation could not be established, particularly due to the presence of inter- and intrafamilial variability. This study supports the increased prevalence of (c.1343G>A, p.Arg448His) and (c.1027G>T, p.Glu343∗) variants in Egyptian patients. CONCLUSION: Given the high rate of consanguinity in Egypt, further extensive studies focusing on the genetic modifiers in the disease progression and the role of environmental factors are recommended.
BACKGROUND: The cyclin-dependent kinase-like 5 deficiency disorder (CDD) is an ultrarare X-linked disorder causing early-onset epileptic encephalopathy and severe developmental deficits. Few studies exist on its electroc...BACKGROUND: The cyclin-dependent kinase-like 5 deficiency disorder (CDD) is an ultrarare X-linked disorder causing early-onset epileptic encephalopathy and severe developmental deficits. Few studies exist on its electroclinical features, outcomes, sex differences, and neuroimaging, particularly from India. This study aims to describe the electroclinical syndrome, developmental profile, radiological findings, and outcomes in patients with CDD and to compare these factors between males and females. METHODS: This is a hospital-based observational study of patients diagnosed with CDD identified from a prospectively maintained registry of children with developmental and epileptic encephalopathy. Data on demographics, seizure types, epilepsy syndromes, antiseizure medications, electroencephalography findings, developmental assessments, genetic characteristics, brain magnetic resonance imaging, and outcomes were collected. RESULTS: We included 12 patients with pathogenic (9) and likely pathogenic (3) variants in cyclin-dependent kinase-like 5 (CDKL5), among whom seven were female. The mean age at onset of seizures was 5.95 ± 5.56 months and was higher for males than females (8.6 ± 7.23 vs 3.19 ± 2.47). The most common seizure types at onset were tonic seizures in 6 (50%) children and epileptic spasms in 4 (33.3%). Lennox-Gastaut syndrome and West syndrome were the most frequent epilepsy syndromes. The median number of seizures per person was 2.9, and the median number of antiseizure medications used was 6 during their lifetime. Magnetic resonance imaging revealed cerebral volume loss in 7 children and white matter lesions in 6. Severe developmental deficits, a Rett-like phenotype, and cortical visual impairment were observed in three-fourths of the children, and regression of milestones occurred in two-thirds. Repetitive motor behavior (P 0.0455) and regression (P 0.0101) were more common in females. CONCLUSIONS: CDD causes refractory epilepsy and severe developmental deficits irrespective of the sex of the patient, variant type, and treatment.
Sirchia F, Kalantari S, Carli D
… +18 more, Zadorozhna M, Bassanese F, Thorpe Venti E, Taft RJ, Kesari A, Sorasio L, Antona V, Guala A, Feresin A, Basile A, Licciardi F, Garau J, Gasparini P, Grosso E, Mussa A, Ferrero GB, Brusco A, Giorgio E
BACKGROUND: Many patients with rare genetic diseases remain undiagnosed or receive a molecular diagnosis only after years. In this study, we want to evaluate the usefulness of clinical genome sequencing (cGS) in a cohort...BACKGROUND: Many patients with rare genetic diseases remain undiagnosed or receive a molecular diagnosis only after years. In this study, we want to evaluate the usefulness of clinical genome sequencing (cGS) in a cohort of complex neuropediatric patients with undiagnosed rare genetic diseases. METHODS: Between 2018 and 2022, our Medical Genetics Units in Torino, Trieste and Pavia partnered with the iHope program, a philanthropic initiative by Illumina Inc., with the aim of offering family-based cGS within the Italian National Health Service (Servizio Sanitario Nazionale) diagnostic process. A multidisciplinary team of pediatricians, clinical geneticists, and molecular biologists selected 64 cases. Inclusion criteria consisted of suspicion of an ultra-rare monogenic disease and at least one negative result from a first-tier genetic test. RESULTS: A definitive molecular diagnosis was achieved in 57.8% of the patients. All patients and families underwent clinical re-evaluation to assess the diagnostic relevance of the laboratory findings, which led us to reclassify 10 variants of unknown significance as responsible for the probands' phenotypes. Diagnoses impacted patients' management, enabling palliative care referrals, avoiding unnecessary invasive tests, and guiding follow-up treatments. CONCLUSIONS: Our study confirms that the use of cGS in a rare disease setting increased the diagnostic yield even in complex cases where other methods had previously failed. We speculate that introducing cGS as first-tier test within the Italian Servizio Sanitario Nazionale might offer both diagnostic and economic advantages.
BACKGROUND: Previous work has shown pediatricians the neurological examination in newborn infants because they do not feel confident performing it. In a UK survey about the neurological examination in unwell newborns, 72...BACKGROUND: Previous work has shown pediatricians the neurological examination in newborn infants because they do not feel confident performing it. In a UK survey about the neurological examination in unwell newborns, 72% wanted a proforma to aid practice. Our aim was to develop a proforma to improve the neonatal neurological examination, alongside a flowchart to aid formulation of differential diagnoses and investigation plans. METHODS: Four perinatal neurologists and a graphic designer developed a proforma based on existing examinations and data on attitudes toward the examination in the unwell newborn. This was reviewed via qualitative focus groups and interviews with UK health professionals. Thematic analysis was used to gauge attitudes toward and improve the proforma. RESULTS: Two themes arose from the review and interviews: "Neurophobia" about the neurological assessment of the acutely unwell newborn, and ways of improving practice and confidence. Participants suggested improvements to the proforma. They reported it would allow the neurological examination to be performed consistently, and it would improve confidence, documentation, communication, and interpretation of findings. CONCLUSIONS: We have developed a proforma for documenting the neurological assessment of the unwell newborn, which participants report will improve reliable identification of abnormal signs, their neuroanatomical siting and significance, and confidence in assessing an unwell newborn neurologically. The proforma is not intended to replace current examinations for the stable term or preterm newborn, for whom appropriate validated tools should be chosen. We plan to undertake further validity testing, including interobserver agreement and data on the value of the interpretive flowchart.
BACKGROUND: In pediatric idiopathic intracranial hypertension (IIH) patients, 27-62% have been reported to have difficulties in one or more neurocognitive domains. Also higher rates of mental health issues have been repo...BACKGROUND: In pediatric idiopathic intracranial hypertension (IIH) patients, 27-62% have been reported to have difficulties in one or more neurocognitive domains. Also higher rates of mental health issues have been reported, further underscoring the importance of evaluating broader support needs. We aimed to investigate to what extent children and adolescents with newly diagnosed IIH received broad multidisciplinary assessments, as well as educational and weight-management support. METHODS: A population-based single center cohort study, included patients younger than 18 years of age when diagnosed with IIH according to the Friedman criteria, during 2000-2020. A cross-sectional interview survey and retrospective chart review were performed to investigate the frequency of broad multidisciplinary assessments at IIH diagnosis and need of educational support. RESULTS: Interviews were conducted with 61% (28 of 46) identified patients. According to medical records (N = 46), assessments were conducted by a psychologist in 7%, a physiotherapist in 4%, a social worker in 4%, and a special education teacher in 0%. Among patients with overweight or obesity, 67% were referred to a dietitian for weight management support. Dietitian involvement was more likely in obese than overweight patients, 86% versus 38% (P = 0.04). In addition, 64% of the interviewed patients reported a need for educational support, of whom half (32%) did not receive adequate support in school. CONCLUSIONS: Broad multidisciplinary assessments were uncommon among pediatric patients diagnosed with IIH. There was a high unmet need for educational support. Routine monitoring for neurocognitive impairments and educational needs should be part of pediatric IIH management. A broad multidisciplinary approach would best meet this need.
BACKGROUND: This study aims to clarify the natural course of Alexander disease and explore genotype‒phenotype correlations and prognostic factors. METHODS: This single-center, bidirectional cohort study included patients...BACKGROUND: This study aims to clarify the natural course of Alexander disease and explore genotype‒phenotype correlations and prognostic factors. METHODS: This single-center, bidirectional cohort study included patients genetically confirmed with Alexander disease, aged between 0 and 18 years. Survival curve analysis was conducted to evaluate the acquisition and loss of motor/cognitive skills to clarify the natural course of the disease. Statistical methods such as survival curve analysis and Cox regression analysis were used to analyze genotype‒phenotype correlations and prognostic factors. RESULTS: A total of 81 patients were included. A total of 27 types of gene variants were found among all the children, with 40.7% (11/27) in the 1A domain. At the last follow-up, 12.3% (10/81) of the patients had died. Survival curve analysis for the ability of "walking without support," "sitting down without support," "holding head upright," "understanding and following simple instructions," and "saying simple words" were lost at an average age of 15.2 ± 1.2 years, 17.3 ± 1.4 years, 17.2 ± 1.3 years, 18.8 ± 14.6 years, and 18.2 ± 1.3 years, respectively. Prognostic factor analysis via Cox single-factor and multifactor regression analysis found that patients with variants of R239 had a greater incidence of poor outcome than other variants did (hazard ratio: 2.597 [95% confidence interval: 1.052, 6.409], P = 0.038). CONCLUSIONS: The overall prognosis of Alexander disease is poor, with an average age at death of 18.6 ± 1.4 years and a high incidence of epilepsy (81.5%). Variants of R239 are potential prognostic factors for poor outcome.
Lamagrande-Casanova N, Romero-Adújar F, Lloris A
… +9 more, Sifontes K, González-Alguacil E, Cantarín V, Bascuas M, Benítez C, Ballará M, García-Peñas JJ, Duat-Rodríguez A, Soto-Insuga V
BACKGROUND: Obstructive sleep apnea (OSA) is a common condition in children with drug resistant epilepsy. Its association with vagus nerve stimulation (VNS) is well-documented in adults, but pediatric data remain scarce....BACKGROUND: Obstructive sleep apnea (OSA) is a common condition in children with drug resistant epilepsy. Its association with vagus nerve stimulation (VNS) is well-documented in adults, but pediatric data remain scarce. VNS-induced OSA may negatively impact seizure control and quality of life. This study aims to define the incidence, characteristic features, mechanistic underpinnings, and management strategies of VNS-associated OSA in children. METHODS: We conducted a retrospective case series of 14 children with drug resistant epilepsy who developed new-onset snoring following VNS implantation. All underwent polygraphy or polysomnography. We evaluated the temporal relationship between VNS stimulation and respiratory events, explored anatomical and functional mechanisms through drug-induced sleep endoscopy (DISE), and assessed therapeutic interventions including VNS parameter adjustments, Continuous Positive Airway Pressure, and surgical treatments. RESULTS: OSA was identified in 11 of 14 patients (79%) ranging from mild to severe. A highly characteristic respiratory pattern emerged, consisting of rhythmic obstructive events tightly synchronized with VNS active stimulation cycles. DISE identified vocal cord adduction during VNS activation in 3 patients, indicating an active obstructive mechanism. Nighttime VNS parameter adjustments effectively resolved OSA in 67% of patients without worsening seizure control. Continuous Positive Airway Pressure showed limited efficacy, likely due to active vocal cord adduction. CONCLUSIONS: VNS-associated OSA is a frequent and under-recognized complication in children with epilepsy. Its distinctive polysomnographic signature and demonstrable laryngeal mechanism highlight the need for systematic sleep evaluation in VNS-treated children. DISE provides high diagnostic yield, but when unavailable, targeted VNS adjustment-particularly overnight modulation-offers an effective and practical management strategy. Early identification and treatment of OSA may contribute to improved seizure outcomes and overall quality of life.
Hooper SR, Roem J, Schneider MF
… +5 more, Johnson RJ, Warady BA, Furth SL, Schwartz GJ, Chronic Kidney Disease in Children (CKiD) Study Investigators
Pediatr Neurol
· 2026 Mar · PMID 41576520
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BACKGROUND: Pediatric chronic kidney disease (CKD) is known to affect the neurocognitive functioning in children with CKD, even in those with mild to moderate CKD. What is not well understood is the underlying mechanisms...BACKGROUND: Pediatric chronic kidney disease (CKD) is known to affect the neurocognitive functioning in children with CKD, even in those with mild to moderate CKD. What is not well understood is the underlying mechanisms involved in this disruption of neurocognitive abilities. While serum uric acid (SUA) is a known factor in the disruption of neurocognition in adults with CKD, it has not been well studied in children. The primary purpose of this study was to address this gap in the literature by examining the association between both serum SUA level and change in SUA level with selected neurocognitive functions in children and adolescents with mild to moderate CKD. METHODS: The sample included 593 participants with mild to moderate CKD for the North American Chronic Kidney Disease in Children study. Assessment of neurocognition included measures of IQ, problem solving, selective attention, working memory, and parent ratings of executive functions. RESULTS: After statistical adjustment, findings did not reveal any clear patterns of association between SUA (cross-sectionally or annualized change) and any of the neurocognitive outcomes. The significant findings that were present for both verbal and visual working memory functions suggested that medium to high levels of SUA may be exerting some neuroprotective function on lessening risk for cognitive dysfunction (i.e., attention regulation). CONCLUSIONS: In one of the first studies to examine SUA and neurocognition in children with mild to moderate CKD, no clear associations were uncovered.
BACKGROUND: Surgical intervention has become an established treatment option for epilepsy, but its traditional indications are limited to drug resistant cases. This study compares outcomes of early surgery (predrug resis...BACKGROUND: Surgical intervention has become an established treatment option for epilepsy, but its traditional indications are limited to drug resistant cases. This study compares outcomes of early surgery (predrug resistance) with traditional surgery (postdrug resistance) in focal cortical dysplasia (FCD)-related epilepsy, providing clinical evidence for early surgical intervention. METHODS: Medical records of FCD-related epilepsy children who underwent 1.5 T or 3T brain magnetic resonance imaging at our center (Jan 2008-Dec 2022) were reviewed. Children were divided into early surgery and traditional surgery groups based on treatment pathway. Postoperative seizure outcomes, antiseizure medication (ASM) outcomes, seizure duration, and ASM usage were compared. RESULTS: Of the 195 children with magnetic resonance imaging-confirmed FCD who met the inclusion criteria, 167 (85.6%) were diagnosed with FCD-related epilepsy. Median follow-up duration was 61 months. Twenty-eight (16.7%) achieved seizure freedom with the first ASM, while 5.6% and 5.4% achieved seizure freedom with the second and third or more ASMs, respectively. Ninety-nine children received surgical treatment, with 45 undergoing early surgery and 54 receiving traditional surgery. At the last follow-up, significantly more children in the early surgery group (88.9%) achieved seizure freedom compared to the traditional surgery group (74.1%) (P = 0.033). CONCLUSIONS: Early surgical evaluation can help identify candidates who may benefit from early surgery while maintaining comparable perioperative risks to traditional surgery. Therefore, it is necessary to refine the timing and criteria for epilepsy surgery evaluation. For patients with noneloquent cortical brain lesions, early surgery is recommended to reduce the duration of living with seizure.
Kooper CC, Königs M, Steenweg ME
… +10 more, Hunfeld M, Scheurer NCD, Schippers HM, Peper W, Popma A, van Woensel JBM, Buis DR, Bruining H, Engelen M, Oosterlaan J
BACKGROUND: To investigate whether the heterogeneity in neurocognitive outcome following pediatric traumatic brain injury (TBI) can be reduced by distinguishing subgroups of children with distinct profiles of neurocognit...BACKGROUND: To investigate whether the heterogeneity in neurocognitive outcome following pediatric traumatic brain injury (TBI) can be reduced by distinguishing subgroups of children with distinct profiles of neurocognitive functioning, and to investigate whether these subgroups differ in demographic, premorbid, and clinical characteristics. METHODS: In this multicenter study, 113 children with TBI (mild [82%], moderate [7%], severe [11%]) and 113 demographically matched neurologically healthy (NH) children were assessed using comprehensive computerized neurocognitive testing at 6 months post-TBI. The TBI and NH groups were compared on neurocognitive domains, and the TBI group was subjected to cluster analysis to identify neurocognitive subgroups. Resulting subgroups were compared on demographic, premorbid, and clinical characteristics. RESULTS: Children with TBI had lower performance than NH children in Speed, Stability, Attention & Control, Verbal Working Memory, and Visual Working Memory (P < 0.05, d ≤ -0.42, small effect sizes). Cluster analysis identified four distinct subgroups: one had good outcome and three had adverse outcomes characterized by weak global outcome, weak visual-processing outcome, or weak executive functioning outcome. While subgroups did not differ in clinical characteristics including TBI severity, the weak global outcome subgroup had more premorbid behavioral problems, and the good outcome subgroup had higher socioeconomic status. CONCLUSIONS: This study indicates that children with mild to severe TBI exhibit neurocognitive deficits at 6 months post-TBI, among which subgroups of children with distinct neurocognitive outcome profiles exist. The neurocognitive outcome subgroups represent children with diverging severity and configuration of neurocognitive weaknesses. Clinical characteristics were not related to the outcome subgroups, highlighting the importance to consider other factors for the prognosis of neurocognitive outcome.
BACKGROUND: Transport protein particle complex 11 (TRAPPC11)-related disease, with autosomal recessive inheritance, exhibits a multisystemic involvement that goes widely beyond muscle weakness. Poor growth, psychomotor d...BACKGROUND: Transport protein particle complex 11 (TRAPPC11)-related disease, with autosomal recessive inheritance, exhibits a multisystemic involvement that goes widely beyond muscle weakness. Poor growth, psychomotor development delay, intellectual disability, microcephaly, ophthalmic involvement, and movement disorders are some of the typical features. Elevated serum creatine kinase levels are present in all previously reported TRAPPC11 c.1278+5G > A variant cases. METHODS: Clinical characterization of three siblings from a Roma family with TRAPPC11-related disease, all harboring a homozygous c.1287+5G > A variant. RESULTS: The older siblings presented typical features of the disease, including significant microcephaly, intellectual delay, and psychomotor regression precipitated by infections. Ataxia was consistently observed across all cases, albeit with varying severity. None of the cases had clinical signs compatible with muscular dystrophy. Notably, despite sharing the same mutation, the siblings exhibited remarkable phenotypic variability, with the youngest sibling displaying a milder phenotype. CONCLUSIONS: This case series elucidates the intricate presentation of TRAPPopathies and underscores its phenotypic diversity, emphasizing the influence of the implicated deleterious variant. This study contributes to our understanding of TRAPPC11-related disease and highlights the importance of recognizing and characterizing phenotypic variability in this genetic disorder.