Journal of Child Neurology最新文献

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.

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.

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.

BackgroundFriedreich ataxia is a rare genetic disorder caused by mutations in the FXN gene, typically presenting with balance and coordination difficulties between ages 7 and 15 years. Neurologic symptoms are progressive and lead to loss of ambulation and especially in children other symptoms such as cardiomyopathy, scoliosis, and fatigue are common. The FACHILD natural history study aimed to expand knowledge about the disease course and evaluate clinical outcome assessments in children. We report on functional performance testing, clinical rating scales, and patient-reported outcomes as clinical outcome assessments for Friedreich ataxia. Over a 3-year period, all tests and assessments were conducted to evaluate their sensitivity to progression and correlate with established measures such as neurologic rating scales.MethodsIndividuals with genetically confirmed Friedreich ataxia, aged 7-18 years, were enrolled from October 2017 to November 2022. This analysis focused on ambulatory individuals, including timed walks (25-foot, 1 minute, and 6 minutes), the timed up and go, and the 9-hole pegboard test. Additionally, the Berg Balance Scale and FA-Activities of Daily Living were assessed. Progression data were analyzed using mixed models for repeated measures, with detailed analyses of intermittent missing data. Data from the Friedreich Ataxia Clinical Outcome Measures Study was used to augment analyses when available.Findings and InterpretationFunctional performance outcome measures are sensitive and clinically relevant tools for assessing disease progression in children with Friedreich ataxia. In early to moderately affected populations, the 1-Minute Walk demonstrated promising properties, showing comparable sensitivity to the modified Friedreich Ataxia Rating Scale and the Upright Stability Score.

ObjectiveThere has been limited research on carnitine levels, supplementation, and the ketogenic diet.MethodsOver 8 years, 150 consecutive children treated with the ketogenic diet at Johns Hopkins Hospital were evaluated and information about carnitine levels and use obtained.ResultsOne hundred five (70%) had carnitine levels checked. The mean total carnitine level at first follow-up was 56 µmol/L (standard deviation [SD] 32) (normal range 30-60 µmol/L) and free 26 (SD 19) µmol/L (normal range 22-52 µmol/L). In those not supplemented with carnitine, total carnitine was stable (46.2 [SD 12] to 44.9 [SD 19] µmol/L, P = .80), whereas free carnitine decreased (35.8 [SD 12] to 20.1 [SD 11] µmol/L, P < .001). Those on valproate had lower baseline total carnitine levels (40.7 [SD 20] vs 52.0 [SD 15] µmol/L, P = .02). At 3 months, 83% with normal total carnitine levels (>30 µmol/L) had >50% seizure reduction compared to 60% with hypocarnitinemia (P = .06). Carnitine was supplemented in 36 (24%), typically in those older, on higher ketogenic ratios, prior to 2020, and with longer ketogenic diet durations. Twelve (33%) had documented benefit from carnitine supplementation, but there was no group difference in seizure control or ketosis.ConclusionsIn this single-center study, hypocarnitinemia was seen at baseline in those on valproate and decreased free carnitine levels occurred over time. Those with higher total carnitine levels at 3 months were slightly more likely to be improved. Carnitine was supplemented in one-quarter of patients, with 1 of 3 showing modest benefit in ketosis and seizures.

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.

ObjectiveThe purpose of this study was to investigate the efficacy of transcutaneous vagus nerve stimulation in pediatric patients with drug-resistant epileptic encephalopathy with spike-and-wave activation in sleep.MethodsWe prospectively investigate seven drug-resistant epileptic encephalopathy with spike-and-wave activation in sleep children who underwent transcutaneous vagus nerve stimulation for 12 weeks. The Chinese Revised Wechsler Intelligence Scale for Children (C-WISC) was used to assess cognitive changes before and after stimulation. Microstate parameters (mean duration, occurrence, and coverage) were obtained by quantifying each patient's electroencephalography (EEG) findings. Correlation analyses were used to assess the association between microstate parameters and cognitive scores. We analyzed the brain dynamics of the patients based on 4 categories of classical microstates using weighted phase lag index to construct a whole brain dynamic network. Finally, the brain network was quantitatively analyzed based on graph theory metrics (including global efficiency, local efficiency, and strength).ResultsA 12-week transcutaneous vagus nerve stimulation resulted in a significant increase in M/CIQ (Memory/Concentration Intelligence Quotient) and in seizure cessation in 57.14% of patients. The mean duration of microstate C was significantly reduced and enlarged the bidirectional predominance of microstate A and B, while weakening the directional predominance of microstates A, B, and D to C. The global efficiency, local efficiency, and strength of the microstate-based functional subnetwork were significantly reduced. And M/CIQ showed a strong correlation with the mean duration.SignificanceThis study revealed the efficacy of transcutaneous vagus nerve stimulation in improving the cognitive state of drug-resistant epileptic encephalopathy with spike-and-wave activation in sleep pediatric patients.

BackgroundHemicrania continua and paroxysmal hemicrania are rare in the pediatric population. Recognizing these disorders characterized by unilateral headaches with autonomic features can reduce time to diagnosis, facilitate effective medical treatment, and reduce morbidity.ObjectiveTo review the diagnostic criteria and pathophysiology of hemicrania continua and paroxysmal hemicrania, analyze a retrospective cohort of adolescent patients with indomethacin-responsive headaches, and discuss the clinical features of these patients, both in how they follow the diagnostic criteria for these disorders and how they may deviate. We also examined time to diagnosis and prognosis for this cohort.MethodsA retrospective chart review was completed of patients 12-18 years old from 2014 to 2021 diagnosed with indomethacin-responsive headaches who presented to a tertiary pediatric headache clinic. Clinical headache characteristics, demographic features, medical diagnoses, and diagnostic testing were reviewed and collated.ResultsEight patients (7 female, 1 male) had indomethacin-responsive headaches. Six patients were diagnosed with hemicrania continua and 2 were diagnosed with paroxysmal hemicrania. The most common autonomic symptoms were unilateral nasal congestion and conjunctival injection/lacrimation. The median time to diagnosis was 15 months, and the median treatment length was 7 months.ConclusionPatients can have multiple headache phenotypes. Clinicians should ask headache patients of all ages about autonomic symptoms and unilateral headaches, specifically in fixed unilateral headaches. These headaches should be evaluated with imaging to rule out secondary intracranial causes. In those cases, with these features, an indomethacin trial is part of the diagnosis and should be considered early in the course.