Journal of Child Neurology最新文献

In data from a multicenter prospective observational study, we assessed whether interictal epileptiform discharge metrics in the pre-seizure onset surveillance scalp electroencephalograms (EEGs) in children with tuberous sclerosis complex could predict seizure outcomes, specifically epileptic spasms. In 16 children with eligible EEG data (7 with epileptic spasms and 9 with other seizure types) and 16 controls, 2 spike metrics were calculated through automated detection followed by expert review: (1) spike rate (spikes per minute) and (2) number of unique spike foci. In patients who developed seizures, a combination of spike rate threshold of ≥2 per minute and ≥2 unique spike foci during sleep was highly predictive of impending epileptic spasms (100% positive predictive value, 2 false negatives). One control patient was falsely predicted to develop epileptic spasms, decreasing the overall positive predictive value to 83.3%. These findings suggest that EEG spike metrics could predict impending epileptic spasms in children with tuberous sclerosis complex, pending larger-scale validation.

Reversible cerebral vasoconstriction syndrome (RCVS) is uncommon in childhood. Although it usually has favorable outcomes, it still carries a risk of serious complications, including intracranial bleeding and ischemic stroke. RCVS may arise idiopathically, from vasoactive triggers or from daily activities such as defecation, urination, exertion, or sexual activity. Whole-body cryotherapy (WBC) is not officially recognized as a trigger for RCVS. We present a case of RCVS in an adolescent who underwent a WBC session preceding his symptoms and diagnosis. Although an association between cold weather exposure and stroke is recognized, the connection between cold weather and RCVS is less established. Furthermore, there is limited to no evidence linking WBC to stroke or RCVS. We aim to highlight a potential side effect of WBC, an increasingly popular intervention lacking evidence-based benefits and well-studied side effects.

Genetic testing based on family history and tumor type may miss numerous germline mutations. This case report describes an adolescent girl with a rare skull-base meningioma. Initial imaging suggested schwannoma but germline genetic testing with schwannomatosis panel (NF2, LZTR1, and SMARCB1) was negative. A stepwise surgical approach prioritized facial nerve preservation, followed by tumor removal. Histopathology identified the tumor as a meningothelial meningioma, WHO grade 1, rather than the initially suspected schwannoma. Comprehensive tumor-normal sequencing revealed a germline splice site variant in BAP1 (c.122G+1 G>T) and a tier 2 somatic variant in PBMR1 (c.3263_3269delinsA). This case highlights the value of combined somatic and germline genomic evaluations in complex diagnoses. Identifying the BAP1 mutation enabled preventive care, genetic testing for relatives, and tailored cancer screening. It underscores the need for thorough genomic assessments and multidisciplinary strategies to optimize outcomes in rare pediatric conditions.

Pyruvate dehydrogenase complex (PDC) deficiency is a rare mitochondrial disorder characterized by impaired oxidative metabolism, predominantly due to pathogenic variants in the PDHA1 gene. We present the clinical, biochemical, radiologic, and molecular characterization of 4 Argentine pediatric patients with PDHA1-related PDC deficiency, including a novel missense variant, c.260T>C p.(Ile87Thr). Clinical presentations ranged from severe neonatal encephalopathy with central apneas to a more slowly progressive neurodegenerative course in childhood. All patients exhibited lactic acidosis and structural brain abnormalities, with 3 fulfilling criteria for Leigh syndrome. Molecular studies identified 4 missense variants located in conserved regions of the E1α subunit. In silico analysis of the novel p.(Ile87Thr) variant suggested impaired thiamine pyrophosphate binding. All patients received thiamine and a ketogenic diet, with favorable outcomes in seizure control, neurodevelopment, and metabolic stability. Our findings expand the clinical and molecular spectrum of PDHA1-related PDC deficiency and underscore the importance of early diagnosis and targeted metabolic therapy. Furthermore, we report a previously undescribed radiologic pattern in one patient and propose potential structural implications of the novel variant based on protein modeling.

Trofinetide, a synthetic analog of glycine-proline-glutamate (GPE), is the first food and drug administration-approved treatment for Rett syndrome. Gastrointestinal side effects (primarily diarrhea) are common, but severe immune-mediated reactions have not been described. We report a case of a young girl with genetically confirmed Rett syndrome who developed emesis, pallor, and lethargy after 2 months of treatment with trofinetide. An attempt was made to restart the medication after being held for a week, but the patient again experienced adverse symptoms and the drug was held. After 3 months without the medication, she experienced recurrence of initial symptoms within hours of rechallenge, consistent with food protein-induced enterocolitis syndrome (FPIES). The medication was not continued after the re-challenge. The concept of drug-induced enterocolitis syndrome (DIES) has been reported with other agents; however, to our knowledge, this represents the first reported case of FPIES/DIES triggered by trofinetide. This case expands the spectrum of trofinetide-related adverse reactions and emphasizes the need to distinguish immune-mediated enterocolitis from dose-dependent osmotic diarrhea and highlights the importance of clinician vigilance when initiating similar therapies in children with complex neurodevelopmental disorders.

Fatigue is common in children with multiple sclerosis. This cross-sectional study aimed to determine the prevalence of fatigue, sleep disorders, and subjective sleep quality in children with multiple sclerosis, along with their relationships to mood, quality of life, physical activity, and multiple sclerosis disease characteristics. Validated questionnaires were completed, and objective sleep quality was evaluated with polysomnography. Of the 18 children recruited (median age 16.0 years), 72% reported fatigue and 61% experienced subjective sleep disturbance. Fourteen sleep studies were completed, from which 3 children (21%) were diagnosed with sleep disorders: 2 with periodic limb movement disorder and 1 with mild obstructive sleep apnea. Sleep architecture was fragmented in 13 children (93%). Fatigue correlated with subjective sleep disturbance measures. This study demonstrates an increased frequency of subjective and objective sleep disturbance in children with multiple sclerosis. Polysomnography should be considered in children with multiple sclerosis who report fatigue and subjective sleep disturbance.

Progressive neurodegeneration with the movement disorder can be challenging to diagnose. In this article, we present a 12-year-old female child with stroke and progressive neurocognitive decline that was followed by choreo-athetoid movements and worsening dystonia and epilepsy. There was diffuse cortical involvement with predominant frontal-parietal lobes involved, affecting speech and bladder bowel control. Despite no significant family history, the genetic evaluation helped us to diagnose the rare condition. We also discuss the various challenges faced while managing and diagnosing the patient and the role of surgical intervention for the management of difficult to control dystonias in such patients.