Neuropediatrics最新文献

Background:  Non-selective sodium leak channel (NALCN) protein encoded by the NALCN gene is of key importance for neuronal cell excitability. Previous reports showed that biallelic NALCN pathogenic variants cause infantile hypotonia with psychomotor retardation and characteristic facies 1 (IHPRF1) while monoallelic variants lead to congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD). In our work, we aimed to expand the heterozygous NALCN-related clinical spectrum, presenting two affected individuals and a literature review.

Methods:  We describe two new unrelated subjects harboring monoallelic NALCN pathogenic variants identified through clinical exome sequencing and review the current literature of other heterozygous NALCN patients.

Results:  The c.3542G > A (p.Arg1181Gln) and the novel c.3423C > A (p.Phe1141Leu) heterozygous missense variants were disclosed in two subjects manifesting a similar phenotype characterized by congenital ataxia with progressive cerebellar atrophy, camptodactyly, and hypertrichosis of the arms (CAPCACH). Other NALCN subjects with overlapping features have already been reported. A combination of these clinical and neuroimaging findings suggests the definition of the new CAPCACH phenotype.

Conclusion:  We expand the heterozygous NALCN-related clinical spectrum from the more severe CLIFFAHDD to the milder CAPCACH phenotype. These conditions should be considered in the differential diagnosis of syndromic congenital ataxias, and the presence of camptodactyly and/or hypertrichosis may represent peculiar diagnostic clues.

Objective:  Infantile spasms (IS) are an age-specific epilepsy syndrome associated with poor outcomes. Sustained and early spasm control remains the main goal of therapy. We aimed to evaluate a unique pulsatile dexamethasone therapy regime in children with IS.

Methods:  Children with IS were treated with oral pulsatile-applied dexamethasone in the Children's Hospital Jena between 2002 and 2021, regardless of duration since IS onset or previous therapy (except ACTH). A prolonged initial pulse was given in case of insufficient response (standard: 5-7 days, prolonged: 10-14 days). We analyzed spasm reduction, electroencephalographic response, adverse reactions, neurodevelopmental status, and epileptic disorders at the last follow-up.

Results:  Included were 26 patients with a median age of 5.5 months (interquartile range 4-8) at IS onset and a mean follow-up of 6.2 years (standard deviation [SD] 3.99). Fifty percent had an unknown etiology. Patients received on average 10.8 pulses (SD 6.0); 69.2% achieved initial seizure freedom, however, 38.9% relapsed. Seventeen patients had an initial prolonged pulse, of those, 14 got initially seizure-free (82.4%). Sixty-four percent of the cases had a sustained spasm cessation after the third pulse. At the last follow-up, half of the patients had no persisting epileptic disorder; 22.2% had a favorable neurocognitive development. Patients with unknown etiology were more likely to achieve seizure freedom during therapy (p = 0.025), had a more favorable neurocognitive outcome (p = 0.049), and were less likely to suffer from epileptic disorders (p = 0.037). No serious adverse effects were observed.

Conclusion:  Our results show that our treatment is safe and leads to outcomes comparable to usually applied hormonal therapy regimes. Etiology remains the most influential factor.

Acute motor and sensory axonal neuropathy (AMSAN) is a rare and severe form of acute axonal injury caused by immune damage to the axonal membrane. AMSAN is an axonal variant of GBS. GBS occurs from immune injury to the myelin sheath, axonal variants of GBS (AMSAN and AMAN) differ in that insult is to the axonal membrane. AMSAN is seldom seen, especially in pediatric and adolescent patients. Unlike AMAN (acute motor axonal neuropathy), which has been well described in literature to be secondary to C. Jejuni infection, there is no known etiology of AMSAN. Here we present a case of an otherwise healthy 15-year-old female who presented with new onset facial and bulbar weakness that rapidly progressed to functional paralysis requiring intubation. With no clear diagnosis and after failure of improvement with high dose steroids, IVIG and plasma exchange transfusion, diagnosis was finally made with electromyography and nerve conduction study. In addition, extensive lab work was completed and was only notable for primary acute EBV infection. This case represents a new presenting symptom of AMSAN, a unique finding of concomitant primary EBV infection, the possibility of primary EBV infection as the triggering event in AMSAN and stresses the importance of electromyography and nerve conduction study when evaluating patients with weakness.

Background:  Infantile epileptic spasms syndrome (IESS) is the most common epileptic encephalopathy in infancy and early childhood. At present, adrenocorticotropic hormone (ACTH) and prednisolone are commonly used as drug treatment regimens for IESS. However, evidence of efficacy and economics remains controversial. This study aimed to evaluate the effectiveness, safety, and economy of ACTH and prednisolone of IESS.

Methods:  Seven literature databases and two clinical trial registration platforms were searched, and a meta-analysis was conducted. From the perspective of the health care system, a 14-day economic evaluation was conducted. The rate of spasm cessation on the 14th day was used as the effect index. The univariate sensitivity analysis was used to verify the robustness of the results.

Results:  Nine randomized controlled trials (RCTs) were included. Current clinical evidence is not sufficient to prove the difference in the rate of spasm cessation on the 14th day (risk ratio [RR] = 1.05, 95% CI 0.86-1.27, p = 0.64) and total adverse event rate (RR = 0.87, 95% CI 0.53-1.42, p = 0.57). ACTH had an advantage in improving electroclinical response on the 14th day (RR = 1.46, 95% CI 1.09-1.96, p = 0.01) and reducing the number of months taken for relapse (mean difference = 1.65, 95% CI 1.01-2.29, p < 0.01). The cost of ACTH and prednisolone was 5,629.19 yuan and 5.56 yuan, respectively. Univariate sensitivity analysis showed the most influential factor was the cost of ACTH.

Conclusions:  There is insufficient evidence to determine whether ACTH or prednisolone is better in the short-term regimen of IESS. ACTH may have more advantages in improving the long-term outcome of IESS. In China, a prednisolone regimen of IESS has a lower cost within 14 days.

X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy that commonly manifests with liver involvement. In most XLMTM cases, disease-causing variants have been identified in the myotubularin gene (MTM1) on chromosome Xq28, which encodes myotubularin protein (MTM1). The impairment of mitochondrial respiratory chain (MRC) enzyme activity in muscle has been observed in the XLMTM mouse model. Though several reports mentioned possible mechanisms of liver involvement in XLMTM patients and animal models, the precise underlying mechanisms remain unknown, and there is no report focused on mitochondrial functions in hepatocytes in XLMTM. We encountered two patients with XLMTM who had liver involvement. We measured MRC enzyme activities in two muscle biopsy specimens, and one liver specimen from our patients to investigate whether MTM1 variants cause MRC dysfunction and whether mitochondrial disturbance is associated with organ dysfunction. MRC enzyme activities decreased in skeletal muscles but were normal in the liver. In our patients, the impaired MRC enzyme activity found in muscle is consistent with previously reported mechanisms that the loss of MTM1-desmin intermediate filament and MTM1-IMMT (a mitochondrial membrane protein) interaction led to the mitochondrial dysfunction. However, our study showed that liver involvement in XLMTM may not be associated with mitochondrial dysfunction.

Background: Autism spectrum disorder (ASD) is often accompanied by comorbid conditions such as attention deficit hyperactivity disorder and epilepsy. In this context, patients are often treated with psychostimulants in an attempt to control behavioral symptoms. This study aims to understand the behavioral effects of psychostimulants in children with ASD and investigate if interictal epileptiform discharges on electroencephalogram (EEG) can act as a modifying factor in this behavior.

Methods: Sixty-eight patients with ASD who were being accompanied in the Department of Child and Adolescent Psychiatry of the Centro Hospitalar Universitário de São João and had previously done an EEG assessment answered a questionnaire regarding their behavioral response to psychostimulants.

Results: In total, 47.4% of patients reported improved agitation, 56.1% enhanced concentration, and 8.8% improved sleep. Conversely, 28.1% experienced worsened agitation, 15.8% worsened concentration, and 17.5% worsened sleep. The remaining reported no alterations. The age of diagnosis correlated significantly with improved agitation, with a higher diagnosis age being associated with a higher probability of improvement. Extended-release methylphenidate and genetic variations were significantly associated with worsening of agitation. Regarding speech, 86% exhibited no changes, while 14% showed alterations, mostly, 87.5%, characterized as negative. For other behavioral alterations, 45.6% reported negative changes, 3.5% reported positive changes, and 50.9% reported no additional alterations. Female gender was significantly associated with other negative behavioral changes. A significant correlation was found between treatment duration and the probability of improvement in agitation, concentration, and other behavioral changes.

Introduction: The Alsin Rho Guanine Nucleotide Exchange Factor (ALS2) gene encodes a protein alsin that functions as a guanine nucleotide exchange factor. The variations in ALS2 gene leads to degeneration of upper motor neurons of the corticospinal tract. The phenotypes resulting from variants in ALS2 gene are infantile-onset ascending hereditary spastic paralysis (IAHSP, OMIM # 607225), juvenile primary lateral sclerosis (JPLS, OMIM # 606353), and juvenile amyotrophic lateral sclerosis (JALS, OMIM # 205100). Our study objectives were to describe the clinical phenotype and genotype of children with an established diagnosis of ALS2 gene-related disorder.

Methods: The clinical details, laboratory data, and genotype findings of children with an established diagnosis of ALS2 gene-related disorder were collected from the hospital electronic database after obtaining institutional review board approval.

Results: One family with three affected siblings, a second family with a proband and an affected fetus, and a third family with two affected siblings with ALS2 gene variants were identified. IAHSP was diagnosed in all of our patients with variants in ALS2 gene. The clinical findings observed in our patients were insidious onset progressive spastic paraparesis, contractures, and dysarthria. Nonsense variants were observed in four patients while frameshift variant was observed in one family. Novel variants in ALS2 gene were identified in two unrelated families.

Conclusion: ALS2 mutation results in rare neurodegenerative disorders with the clinical spectrum encompassing IAHSP, JPLS, and JALS disorders. In view of allelic heterogeneity described in the literature, more research studies are needed for establishing genotype-phenotype correlation in patients with ALS2 gene-related disorder.