Guillain-Barré syndrome in children - High occurrence of Miller Fisher syndrome in East Asian region.

BACKGROUND: Guillain-Barré syndrome (GBS) is a rare acquired immune-mediated polyneuropathy. Updated population-based data concerning paediatric GBS is needed. METHODS: Paediatric patients aged below 18 years diagnosed with GBS between 2009 and 2018 in all 11 paediatric departments in Hong Kong were identified from the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System. The collected data from medical health records were reviewed by paediatric neurologist from each department. Estimated incidence of paediatric GBS was calculated. We also compared our findings with other paediatric GBS studies in Asia. RESULTS: 63 subjects of paediatric GBS were identified, giving an estimated annual incidence of 0.62 per 100,000 population. Half of the subjects had acute inflammatory demyelinating polyneuropathy (AIDP) (n = 31; 49.2%), one quarter had Miller Fisher Syndrome (MFS) (n = 16; 25.4%), one-fifth had axonal types of GBS (n = 12; 19.0%), and four were unclassified. Paediatric subjects with axonal subtypes of GBS compared to the other 2 subtypes, had significantly higher intensive care unit (ICU) admission rates (p = 0.001) and longest length of stay (p = 0.009). With immunomodulating therapy, complete recovery was highest in those with MFS (100%), followed by AIDP (87.1%) and axonal GBS (75%). Our study also confirms a higher MFS rate for paediatric GBS in East Asia region and our study has the highest MFS rate (25.4%). CONCLUSION: Our population-based 10-year paediatric GBS study provides updated evidence on estimated incidence, healthcare burden and motor outcome of each subtype of paediatric GBS and confirmed a higher occurrence of paediatric MFS in East Asia.

Exome sequencing identifies molecular diagnosis in children with drug-resistant epilepsy.

OBJECTIVE: Early onset drug-resistant epilepsy is a neurologic disorder in which 2 antiepileptic drugs fail to maintain the seizure-free status of the patient. Heterogeneous clinical presentations make the diagnosis challenging. We aim to identify the underlying genetic causes of a pediatric cohort with drug-resistant epilepsy and evaluate whether the findings can provide information on patient management. METHODS: We include patients with drug-resistant epilepsy onset before 18 years of age. Singleton clinical chromosomal microarray (CMA) followed by whole exome sequencing (WES) was performed using genomic DNA. In the first-tier analysis of the exome data, we aimed to identify disease-causing mutations in 546 genes known to cause, or to be associated with, epilepsy. For negative cases, we proceeded to exome-wide analysis. Rare coding variants were interrogated for pathogenicity based on the American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: We recruited 50 patients. We identified 6 pathogenic or likely pathogenic mutations, giving a diagnostic yield of 12%. Mutations were found in 6 different genes: SCN8A, SCN1A, MECP2, CDKL5, DEPDC5, and CHD2. The CDKL5 variant was found to be mosaic. One variant of unknown significance (VUS) in KCNT1 was found in a patient with compatible clinical features. Of note, a reported pathogenic SCN5A mutation known to contribute to Brugada syndrome, was also found in the patient with an SCN1A mutation. SIGNIFICANCE: Our study suggests that singleton WES is an effective diagnostic tool for drug-resistant epilepsy. Genetic diagnosis can help to consolidate the clinical diagnosis, to facilitate phenotypic expansion, and to influence treatment and management options for seizure control in our patients. In our study, a significant portion of the genetic findings are known to be associated with an increased risk of sudden unexpected death in epilepsy (SUDEP). These findings could assist with more appropriate management in patients with epilepsy.

Self-esteem in adolescents with epilepsy: Psychosocial and seizure-related correlates.

PURPOSE: This study evaluated self-esteem in adolescents with epilepsy and its association with psychosocial and disease-related variables. METHODS: This was a cross-sectional study with patients enrolled between January and June 2010. Culture-Free Self-Esteem Inventory for Children (CFSEI-2) was administered to 140 children with epilepsy and 50 children with asthma, aged 10-18years attending mainstream schools. RESULTS: Adolescents with epilepsy had a significantly lower overall self-esteem score when compared with those with asthma, 17±5.21 versus 19.4±3.83, respectively (P=0.005). Thirty-one (22.1%) children with epilepsy compared with 4 (8.3%) with asthma had overall self-esteem score below the cutoff (P=0.034). There was a significant correlation between overall self-esteem score and duration of epilepsy, Hospital Anxiety and Depression Scale (HADS) anxiety score, HADS depression score, and Strengths and Weaknesses of ADHD symptoms and Normal-Behaviors (SWAN) rating combined score. The impact of various correlates on individual domains was not identical. Independent factors associated with low overall self-esteem were HADS depression score (OR: 1.62; 95% CI: 1.2, 2.2; P=0.002), duration of epilepsy (OR: 1.4; 95% CI: 1.04, 1.88; P=0.024), and father employment status economically inactive (OR: 11.9; 95% CI: 1.07, 125; P=0.044). Seizure-free ≥12months was a favorable factor that was less likely to be associated with low self-esteem (OR: 0.14; 95% CI: 0.02, 0.81; P=0.028). CONCLUSION: Self-esteem was compromised in adolescents with epilepsy. A significant correlation between self-esteem and psychological comorbidities was demonstrated. Enhancing social support and education programs may improve the self-esteem and, ultimately, the lives of adolescents living with epilepsy.

Diagnostic yield of array CGH in patients with autism spectrum disorder in Hong Kong.

BACKGROUND: Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNV) and it is advocated to be the first tier genetic testing for patients with autism spectrum disorder (ASD). In this regard, diagnostic yield of array comparative genomic hybridization (CGH) for ASD patients is determined in a cohort of Chinese patients in Hong Kong. METHODS: A combined adult and paediatric cohort of 68 Chinese ASD patients (41 patients in adult group and 27 patients in paediatric group). The genomic DNA extracted from blood samples were analysed by array CGH using NimbleGen CGX-135K oligonucleotide array. RESULTS: We identified 15 CNV and eight of them were clinically significant. The overall diagnostic yield was 11.8 %. Five clinically significant CNV were detected in the adult group and three were in the paediatric group, providing diagnostic yields of 12.2 and 11.1 % respectively. The most frequently detected CNV was 16p13.11 duplications which were present in 4 patients (5.9 % of the cohort). CONCLUSIONS: In this study, a satisfactory diagnostic yield of array CGH was demonstrated in a Chinese ASD patient cohort which supported the clinical usefulness of array CGH as the first line testing of ASD in Hong Kong.

Anxiety and Depression in Adolescents With Epilepsy.

The present study examined anxiety and depression in adolescents with epilepsy and the association of these disorders with seizure-related and sociodemographic variables. The Hospital Anxiety and Depression Scale was administered to 140 children with epilepsy and 50 children with asthma aged 10 to 18 years attending mainstream schools. Adolescents with epilepsy had significantly higher scores on the depression subscale than those with asthma (5.2 ± 3.3 vs 4.2 ± 3.2, P = .032). Anxiety subscale scores and the frequency of anxiety and depression in both the epilepsy and asthma groups were not statistically significant. In the epilepsy group, 32.8% had anxiety and 22.1% had depression. Factors associated with anxiety were older age at the time of the study and polytherapy (2 or more antiepileptic drugs). Adolescents who had been seizure-free for 12 months or more at time of the study were less likely to experience anxiety. Factors associated with depression were medical comorbidities, female gender, frequent seizures, and younger age of seizure onset. A common risk factor for both anxiety and depression was the duration of epilepsy. Anxiety and depression were also highly associated with each other. Affective disorders are common in epilepsy and screening for psychiatric symptoms is required.