European Journal of Paediatric Neurology最新文献

Background: The study aimed to describe a new Ommaya reservoir implantation method in late-onset SMA patients, assessing its safety and effectiveness under standard clinical conditions.

Methods: Prospective observational study. Lumbar intrathecal access was unfeasible due to significant scoliosis and prior spinal surgeries with instrumentation. Patients were infused with Nusinersen through the Ommaya reservoir at Hospital Universitario La Paz (Spain) following the standard dosing protocol.

Results: The cohort was composed of 6 patients, 5 individuals with type 2 SMA (83.3 %), and 1 patient presenting with type 3 SMA. 4 of the patients were functionally sitters (66.7 %) and 2 had lost this ability prior to initiating treatment (non-sitters). Mean treatment was 34.7 months. Patient discharge was done in all the cases within 48 h post-admission; no significant postoperative complications or during administration of nusinersen were reported. Functional progress was observed in all patients. Hammersmith Functional Motor Scale Expanded (HFMSE) showed a low average increase (1.0), attributed to the severity of baseline functional impairments. Improvements in upper extremity motor function, measured by the Revised Upper Limb Module (RULM), were more pronounced, with an average improvement of 3.3. Disability levels as measured by the Egen Klassifikation 2 (EK2) scale, declined by 4.4.

Conclusion: the current study broadens knowledge regarding the efficacy and safety of using an Ommaya reservoir to administer nusinersen in patients with SMA Types 2 and 3. The technique demonstrated rapid, straightforward drug delivery through a subcutaneous needle, maintaining optimal sterility without radiation or the need for a multidisciplinary team.

Aim: To evaluate the efficacy of initial pharmacotherapy for infantile epileptic spasm syndrome (IESS) with electro-clinical outcome characteristics.

Method: A retrospective comparative cohort study with 280 IESS patients was designed; I. vigabatrin monotherapy (n = 129, 46 %); II. hormonotherapy (ACTH/oral prednisolone) (n = 73, 26 %); and III. vigabatrin plus early initiation of hormonotherapy in the first 14 days (n = 78, 28 %). Two types of outcomes were defined: (1) short-term outcome with spasm cessation time ≤42 days and resolution of hypsarrhythmia on the EEG on ≤3 months and (2) long-term outcome with spasm relapse rate or evolution to a new epileptic syndrome.

Results: The etiology-specific diagnoses of the IESS cohort were defined according to the ILAE classification: structural (n = 131, 46.8 %), genetic (n = 28, 10 %), metabolic (n = 13, 4.6 %), immune-infectious (n = 10, 3.6 %), and unknown (n = 98, 35 %). Each treatment modalities had similar short- and long-term outcome characteristics. However, hormonotherapy with steroids (ACTH/oral prednisolone) provided "early IESS resolution" with spasm cessation and resolution of hypsarrhythmia (p = 0.042). The relapse rates of IESS were significantly higher in the etiology well-defined group compared to the unknown group (p = 0.005). The genetic-etiology specific group was more likely to have evolved to a new electro-clinical syndrome with a rate of 83.3 % than the others (p = 0.039).

Conclusion: We observed that the early initiation of hormonotherapy with VGB (sequential therapy) should be investigated in etiology well-defined subgroup with short- and long-term outcome characteristics.

Objectives: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy that requires significant caregiver input across the lifespan. This predominantly falls on parents, who are faced with considerable challenges including physical demands, financial burdens, and sustained pressure on mental wellbeing leading to mental health difficulties. We aimed to develop a grounded theory model for the process of coping and adjustment that occurs when caring for a child who has a diagnosis of DS.

Methods: Using a Constructivist Grounded Theory methodology, we conducted five focus groups, each with 4-6 participants, and 24 in total. They were recruited via convenience sampling through a national Dravet syndrome patient advocacy group. Focus group dialogue was recorded, transcribed, and coded into themes to generate a theory of coping and adjustment that is grounded in the data.

Results: We developed a model of coping and adjustment for parents caring for a child with Dravet syndrome. The model includes contextual factors that impact on parents (loss and insufficient resource). We found a prominent theme of trauma and explored how parents responded to this trauma over time. All parents described a primary coping response reflecting the high levels of stress they had to contend with. Some parents were able to describe a secondary coping style that appeared to support healthier long-term coping and adjustment.

Significance: The study provides novel insight into the ways in which parents cope and adjust to caring for a child with DS, with a focus on adapting to trauma. These insights provide the foundation for the creation of targeted therapeutic interventions for parents of children with developmental and epileptic encephalopathies (DEEs), which we outline and discuss.

Background: Therapeutic apheresis (TA) are promising treatment option for neuroimmunological disorders. In paediatrics, the available data is limited, particularly for the use of IA. The aim of this study was to analyse the use of PE and IA in children and adolescents, with emphasis on outcome and neurological course after treatment as well as the safety of the two modalities.

Methods: Clinical data from paediatric patients with neuroimmunological disorders treated with TA in two German university children's hospitals between 2015 and 2022 were retrospectively analysed.

Results: In total, 39 patients underwent 322 sessions of TA, of which 184 were IA and 138 PE. The most common diagnosis was autoimmune encephalitis in 39 % (n = 15) of the patients. Other indications were central nervous system inflammatory demyelinating disorders in 21 % (n = 8), Guillain-Barré syndrome in 18 % (n = 7), Myelin Oligodendrocyte Glycopeptide-antibody associated syndromes in 8 % (n = 3), Myasthenia gravis in 5 % (n = 2) and other neurological disorders in 10 % (n = 4). Overall, there was an improvement in 76 % of patients (81 % with IA, 70 % with PE; p = 0.41) immediately after treatment and an improvement in 88 % of patients (90 % with IA, 85 % with PE; p = 0.63) one month after treatment. Complications occurred in 13 % of all sessions (13 % with IA and 13 % with PE; p = 1). Most complications were considered as moderate.

Conclusion: Both, IA and PE, are effective treatment options in the therapy of neuroimmunological disorders in children and adolescents, with no major differences in terms of efficiency or safety.

Objective: Early diagnosis and treatment of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) are crucial for a favorable prognosis. Detecting the causative autoantibodies can be challenging. Probable diagnostic criteria are useful in adults less so in children. We aimed to develop a novel diagnostic score for pediatric NMDARE using cohort data.

Methods: We retrospectively analyzed pediatric participants (0-18 years) with suspected autoimmune encephalitis who underwent cerebrospinal fluid analysis for antineuronal antibodies (Abs) between January 2015 and March 2023. Clinical data, including symptoms and laboratory findings, were analyzed. Symptoms were selected through univariate analysis and then analyzed with multivariate logistic regression model. Resulting odds ratios were used to calculate scores. Scoring systems were developed and evaluated with five-fold validation and univariate logistic regression. One scoring system was selected to create a diagnostic prediction score for pediatric NMDARE.

Results: Of the 504 patients, 264 met the inclusion criteria, and 39 tested positive for NMDAR Abs. Comparing clinical symptoms between cohorts and identified 15 variables significantly different (p < 0.05) to create a pediatric NMDARE prediction score. This score showed 82.1 % sensitivity and 82.2 % specificity, with an 8-point cutoff. The area under the curve was 0.888 (95 % confidence interval: 0.838-0.939). A five-fold cross-validation showed a sensitivity of 95.6 %, specificity of 71.4 %, and kappa coefficient of 0.670.

Conclusion: We developed a novel evidence-based diagnostic prediction score for pediatric NMDARE that incorporates specific clinical features and laboratory findings. This score may improve diagnostic accuracy and guide early therapy in children with suspected autoimmune encephalitis.

Childhood-onset mitochondrial disorders are rare genetic diseases that often manifest with neurological impairment due to altered mitochondrial structure or function. To date, pathogenic variants in 373 genes across the nuclear and mitochondrial genomes have been linked to mitochondrial disease, but the ensuing genetic and clinical complexity of these disorders poses considerable challenges to their diagnosis and management. Nevertheless, despite the current lack of curative treatment, recent advances in next generation sequencing and -omics technologies have laid the foundation for precision mitochondrial medicine through enhanced diagnostic accuracy and greater insight into pathomechanisms. This holds promise for the development of targeted treatments in this group of patients. Against a backdrop of inherent challenges and recent technological advances in mitochondrial medicine, this review discusses the current diagnostic approach to a child with suspected mitochondrial disease and outlines management considerations of particular relevance to paediatric neurologists. We highlight the importance of mitochondrial expertise centres in providing the laboratory infrastructure needed to supplement uninformative first line genomic testing with focused and/or further unbiased investigations where needed, as well as coordinating an integrated multidisciplinary model of care that is paramount to the management of patients affected by these conditions.

Background: Intra-thecal Nusinersen has been approved for the treatment of Spinal muscular atrophy (SMA). Limited data is available regarding the efficacy and safety of Nusinersen in children with SMA type 2 and 3 from North India.

Objective: To study the efficacy and safety of Nusinersen among children with SMA type 2 and 3 from North India compared to standard of care (SOC) over 12 months.

Methods: Children with a genetically confirmed diagnosis of SMA and ≥2 copies of the SMN2 gene were screened for enrolment in prospective study design. Revised Hammersmith score (RHS) and revised upper limb module (RULM) were assessed every three months. Compound muscle action potentials (CMAPs) at median and ulnar nerves and quality of life (QOL) were performed at baseline and 12 months. Intra-thecal procedure-related and treatment-emergent side effects in children receiving Nusinersen therapy were recorded. Outcome measures at 6 and 12 months were compared between the Nusinersen and SOC groups.

Results: Forty-two children with SMA, mean age of 85 ± 6 months, including 16 in the Nusinersen group and 26 in the SOC group, were enrolled. The mean RHS score in the Nusinersen group increased from the baseline of 35 ± 18 to 38.9 ± 19, and 39.9 ± 17 at 6 and 12 months (p value-0.001), in the SOC group increased from the baseline of 28.8 ± 15, to 29.6 ± 16, and 29.9 ± 17 at 6 and 12 months respectively (p value-0.35). The mean gain in the RHS score over 12 months in the Nusinersen group was significantly higher compared to the SOC group (p-value 0.02). RULM showed significant gain in the Nusinersen group compared to the SOC group over 12 months (p value 0.03). The median and ulnar nerve CMAPs, and QOL were similar in both the groups. A total of 119 intrathecal injections of Nusinersen were given. Most adverse events were mild and related to the intra-thecal procedure.

Conclusion: Intra-thecal Nusinersen therapy among children with late-onset SMA from North India over 12-month duration was associated with improvement in motor abilities as measured by RHS compared to SOC. Intra-thecal Nusinersen was safe and tolerated well.

A wide phenotypic spectrum exists among DMD patients, with genetic modifiers seen as a putative cause of this variability. The main aim was to evaluate the effect of 4 genetic modifiers and the location of DMD variants on disease severity in a DMD Argentine cohort. A secondary objective was to provide a summary of the current state of knowledge and association of the tested loci with DMD's phenotype. Two groups of patients with extreme phenotypes (Severe/Mild) were defined based on the age at loss of ambulation. SNVs in SPP1, LTBP4, CD40, and ACTN3 were genotyped, and their distribution was compared between groups using Chi-square or Fisher exact tests. Concurrent effects with glucocorticoids treatment, DMD mutation location (proximal/distal) and the other loci were evaluated by multivariate logistic regression. Additionally, we performed a systematic literature review to summarize and interpret the impact of modifiers on various DMD traits. ACTN3-rs1815739 was the only modifier loci of DMD progression in our cohort. A concurrent damaging effect between DMD mutation and ACTN3 was detected, identifying a possible interaction between distal variants and ACTN3 TT-genotype that need to be validated in a larger cohort. The systematic review showed agreement in the results when significant differences were reported. The employment of extreme DMD phenotypic groups was an innovative approach for identifying risk loci for disease severity. The interaction between DMD mutation location and ACTN3, if confirmed, could help to avoid confounding elements in assembling study cohorts for clinical trials. Finally, this report's major highlight is being the first study conducted on an Argentine and Latin-American population.