Journal of Child Neurology

This study explores trends and potential risk factors among pediatric patients with drug-resistant epilepsy who were prescribed cenobamate by their epileptologist. Twenty-four patients (54.2% female) with drug-resistant (62.5% focal) epilepsy were administered cenobamate (mean = 13.27 years, standard deviation [SD] = 4.91 years) after failing multiple antiseizure medications (mean = 4.83, SD = 2.94). Fifty percent reported improved seizure frequency, although more than half the sample experienced physiological (n = 12, 50%) and/or psychiatric (n = 4, 16.7%) adverse events, with 39% rapidly discontinuing cenobamate (mean = 4.00 months, SD = 3.21) because of intolerable physiological (n = 4, 57.1%) and/or psychiatric adverse events (n = 3, 42.9%). Of those experiencing a psychiatric adverse event, all but 1 (75%) discontinued cenobamate, as compared to discontinuation by only 40% of those experiencing a physiological adverse event (n = 10). Psychiatric adverse events were significantly associated with sex (100% female), χ²(1, N = 24) = 4.06, P = .04. Preliminary analyses also suggest older age (adolescence) may increase risk for psychiatric adverse events of cenobamate among patients with pediatric epilepsy.

Infantile epileptic spasms syndrome carries high morbidity and mortality compared with other childhood epilepsy syndromes. High-dose prednisolone is considered the first-line option by many neurologists, with efficacy comparable to adrenocorticotropic hormone (ACTH).  The second-line therapy is debated if prednisolone fails to induce remission. The objective of this study was to evaluate the efficacy of adrenocorticotropic hormone versus vigabatrin as second-line antiseizure medication in patients with infantile epileptic spasms syndrome after high-dose prednisolone failure. Thirty-eight patients met the inclusion criteria. Seventeen patients (45%) took vigabatrin and 21 (55%) took adrenocorticotropic hormone. There were no significant differences regarding age of infantile spasms onset (P = .37) or sex between both groups (P = .32). Complete control of epileptic spasms was seen in 5 of 17 patients (29.5%) taking vigabatrin and in 4 of 21 (19%) taking adrenocorticotropic hormone (P = .70). Vigabatrin showed higher efficacy; however, it did not reach statistical significance, possibly because of our sample size. These results may help guide family counseling after the failure of high-dose prednisolone as first-line therapy.

Infantile neuroaxonal dystrophy (INAD) is an extremely rare neurodegenerative disorder affecting 1 in 1 000 000 children. The PLA2G6 gene mutation is associated with infantile neuroaxonal dystrophy. Symptoms typically begin between 6 and 18 months of age, leading to neurodegeneration, particularly impacting motor skills. This article presents 7 pediatric cases (aged 12 months to 11 years) clinically and radiologically diagnosed with infantile neuroaxonal dystrophy, with at least 1 variation in the PLA2G6 gene. All patients show neurodegeneration, particularly in the motor area, with normal laboratory test results and a high rate of consanguinity among parents (6/7 patients). Clinical findings included spasticity or hypotonia, nystagmus in 3 patients, and ataxia in 1 patient, but none of them showed extrapyramidal signs. Major brain magnetic resonance imaging (MRI) findings include cerebellar atrophy and claval hypertrophy, as well as alterations in cerebellar hemisphere density and drooping splenium of the corpus callosum. The patients exhibiting nystagmus, hypotonicity, absent deep tendon reflexes, and drooping of the splenium of the corpus callosum demonstrated early initial clinical findings and had a poor prognosis. Six of the 7 patients have a homozygous variant, whereas 1 has a compound heterozygous variant. All patients are bedridden, and their Gross Motor Function Classification System score is 5. We emphasize that a patient who experiences neurodegeneration after 1 year of age, with normal laboratory test results and cerebellar atrophy observed on brain MRI, should be considered for infantile neuroaxonal dystrophy. Furthermore, we believe that the drooping splenium of the corpus callosum is one of the radiologic indicators of infantile neuroaxonal dystrophy, and early recognition of this disease can lead to accurate diagnosis, effective treatment plans, and genetic counseling.

Background: Autoimmune encephalitis is a group of inflammatory brain diseases causing neuropsychiatric symptoms, seizures, and memory problems. If untreated, autoimmune encephalitis can lead to serious complications and even death. Therapeutic plasma exchange may improve outcomes in severe or treatment-resistant cases. Objective: This study aimed to describe the clinical characteristics and treatment outcomes among pediatric autoimmune encephalitis with therapeutic plasma exchange-containing regimen. Method: This retrospective case series conducted on children admitted with autoimmune encephalitis underwent therapeutic plasma exchange at Children's Hospital No.2 (Vietnam), from January 2019 to June 2022. Results: Thirty-six Vietnamese children with severe autoimmune encephalitis were included. The median age was 7.4 years, with 8.5 days from disease onset to hospitalization. 19.4% had preceding flu-like symptoms. Common manifestations included impaired consciousness (100%), cognitive impairment (91.7%), seizures (86.1%), and movement disorders (86.1%). Neurological abnormalities were assessed via cerebrospinal fluid, electroencephalography (EEG), and brain magnetic resonance imaging (MRI). Most patients had anti–N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, receiving intravenous methylprednisolone and therapeutic plasma exchange. Probable antibody-negative autoimmune encephalitis patients received therapeutic plasma exchange alone or with intravenous methylprednisolone. Additional treatments included antibiotics, mechanical ventilation, and vasopressors. Early therapeutic plasma exchange initiation (within 28 days) was associated with improvement. Whereas 54.5% of patients required antiepileptic drugs at discharge, only 24.2% experienced seizures at ≥1-year follow-up. Conclusions: In this study, anti-NMDAR encephalitis was the most common diagnosis among admitted patients. Although therapeutic plasma exchange requires special training and equipment and is only available in some tertiary hospitals, therapeutic plasma exchange did improve neuropsychiatric symptoms at discharge. Future research should focus on elucidating the factors that contribute to successful therapeutic plasma exchange outcomes.

Background: Schaaf-Yang syndrome is an ultra-rare neurodevelopmental disorder caused by pathogenic variants in the MAGEL2 gene, also implicated in Prader-Willi syndrome. With less than 1 case per 50 000 people, Schaaf-Yang syndrome remains underreported globally, and no previous cases have been documented in Brazil. Case description: This study presents a 4-year-old Brazilian girl clinically diagnosed with Prader-Willi syndrome, characterized by hypotonia, delayed neuropsychomotor development, and craniofacial dysmorphism. Initial assessments identified growth hormone deficiency and developmental delays, followed by genetic sequencing at 2 years of age, confirming a pathogenic MAGEL2 variant [NM_019066.5:c2821dup: p (Arg941Profs*10)]. The child was also diagnosed with autism spectrum disorder. Multidisciplinary interventions, including medical care, speech therapy, and psychological support, led to remarkable improvements in motor function, language, memory, and learning. Conclusions: This is the first documented Brazilian case of Schaaf-Yang syndrome, emphasizing the critical role of early diagnosis and personalized interventions in reducing the impact of the syndrome.

Valproate is known to have various adverse effects including hormonal dysfunction. There is debate in literature regarding the association between valproate therapy and subclinical hypothyroidism, with some studies suggesting a potential link. However, none of the studies on our review have noted overt hypothyroid symptoms with subclinical hypothyroidism. We present a pediatric patient with generalized epilepsy on long-term valproate therapy who developed subclinical hypothyroidism with overt hypothyroid symptoms. Our patient initially presented as a 3-year-old with absence epilepsy and was well-controlled with valproate monotherapy. After more than 2 years of seizure freedom, the patient developed symptoms of hypothyroidism, leading to a diagnosis of grade 2 subclinical hypothyroidism. Symptom resolution occurred with discontinuation of valproate and with initiation of levothyroxine. Ultimately, thyroid studies normalized, and levothyroxine was also discontinued. Although subclinical hypothyroidism is a known potential side effect of valproate therapy, this case demonstrates that overt hypothyroid symptoms are rare, but possible.

Developmental epileptic encephalopathy (DEE) in children presents significant diagnostic and management challenges. Advances in whole-exome sequencing (WES) have enabled the identification of rare genetic variants, offering new insights into these complex conditions. Here, we report a 2.5-year-old girl with refractory epilepsy and DEE, in whom WES revealed a novel homozygous SULT4A1 splice-site variant. Although the SULT4A1 variant likely contributed to her condition, the later emergence of motor and speech delay in a sibling with the same mutation suggests variable expressivity or age-dependent onset, rather than incomplete penetrance. The patient partially responded to immunotherapy but continued to experience breakthrough seizures and developmental delays, highlighting the challenges in managing such disorders. This case underscores the importance of genetic testing, functional studies, and genetic counseling in the diagnosis and treatment of rare neurodevelopmental disorders.

The Modified Mini-Mental State Examination for Children (MMSEc) is a screening tool for identifying intellectual disabilities in children. This study compares MMSEc scores with Full-Scale Intelligence Quotient (FSIQ) scores in 6-14-year-old children with epilepsy (n = 56) and controls with no neurologic disorders (n = 56). A positive correlation was observed between FSIQ and MMSEc scores (Spearman r = 0.873; P < .001). The MMSEc demonstrated a sensitivity of 77.08%, specificity of 100%, positive predictive value of 100%, negative predictive value of 42.11%, and an overall accuracy of 80.35% in identifying children with an FSIQ lower than 70. The area under the receiver operating characteristic curve was 0.993, with the optimal MMSEc threshold score being 22. MMSEc scores were low (<2 SD) for age-defined norms in 66.1% of children with epilepsy. The MMSEc could potentially be a quick and useful tool to screen for intellectual disability in children.

Background: Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative disorder caused by CLN2 gene mutations, leading to ceroid lipofuscin accumulation and progressive neurodegeneration. Cerliponase alfa, a recombinant tripeptidyl peptidase-1, may improve aspects of disease progression, but common hypersensitivity and infusion reactions, along with a limited number of studies and lack of controlled trials, constrain the generalizability of these findings. Purpose: This systematic review and single-arm meta-analysis aims to evaluate the efficacy and safety of cerliponase alfa in treating children with CLN2. Methods: Following Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, the protocol was registered in PROSPERO (CRD42024541000). We included prospective and retrospective cohorts of CLN2 patients treated with cerliponase alfa. A comprehensive search was conducted in PubMed, Embase, and Cochrane Central up to February 2024. Clinical outcomes and adverse effects were analyzed using a random effects model to compute pooled proportions with 95% CIs. Study quality was assessed with the Cochrane Risk of Bias tool for Non-randomized Studies. Results: From 318 records, 3 observational studies with 55 patients were included. A Clinical Rating Scale score of 0 or 1 was seen in 24% of patients. Generalized tonic-clonic seizures occurred in 41%, and dystonia in 15%. Adverse events included pyrexia (60%), hypersensitivity (82.6%), anaphylaxis (3%), and infusion-associated reactions (18.31%). Significant heterogeneity was observed. Conclusion: Cerliponase alfa may improve clinical outcomes in children with CLN2, though adverse effects might be prevalent.

Situational syncope refers to syncope that occurs in specific situations and is a special type of neurally mediated syncope. The etiologic composition of situational syncope varies between adults and children. In adults, it is more common during micturition and defecation, whereas in children, it is more frequently seen during flag-raising, micturition, and defecation. The clinical features and underlying mechanisms of various types of situational syncope also differ in terms of age and sex. The treatment of situational syncope mainly includes nonpharmacologic treatment, pharmacologic treatment, and surgical treatment. Adverse events related to situational syncope are rare, and the prognosis is generally good if there are no other systemic diseases. However, in patients with underlying cardiovascular diseases, situational syncope can lead to serious cardiovascular adverse events.