MATERIALS AND METHODS: Sixteen children with GDD underwent magnetic resonance imaging (MRI) and cross-sectional DTI. Formal developmental assessment of all GDD patients was performed using the Mullen Scales of Early Learning. An automated processing pipeline for the WMT assessment was implemented. The DTI-derived metrics of the children with GDD were compared to healthy children with normal development (ND).
RESULTS: Only two out of the 17 WMT demonstrated significant differences (p<0.05) in DTI parameters between the GDD and ND group. In the uncinate fasciculus (UF), the GDD group had lower mean values for fractional anisotropy (FA; 0.40 versus 0.44), higher values for mean diffusivity (0.96 versus 0.91×10-3 mm2/s) and radial diffusivity (0.75 versus 0.68×10-3 mm2/s) compared to the ND group. In the superior cerebellar peduncle (SCP), mean FA values were lower for the GDD group (0.38 versus 0.40). Normal myelination pattern of DTI parameters was deviated against age for GDD group for UF and SCP.
CONCLUSION: The UF and SCP WMT showed microstructural changes suggestive of compromised white matter maturation in children with GDD. The DTI metrics have potential as imaging markers for inadequate white matter maturation in GDD children.
METHODS: This prospective study includes parents of CWE aged 8-18 years old with no comorbidities. Epilepsy education was delivered using the IAEEP. Parents completed an AKA questionnaire before (time point 1 [TP1]), immediately after (TP2), and 4-6 months (TP3) after the provision of IAEEP. Parent proxy report of Health-Related Quality of Life Measurement for Children with Epilepsy (CHEQOL)-25 questionnaire and Depression, Anxiety, and Stress Scale (DASS)-21 questionnaire was completed at TP1 and TP3.
RESULTS: A total of 78 parents participated in the study. At baseline (TP1), parental responses were rated as "moderate" for awareness domain, "high" for knowledge domain, "very positive" for attitude domain, and "good" for total AKA score domain. No epilepsy or parental characteristics were associated with the low baseline parental AKA levels. After IAEEP intervention, there was a significant increase in all AKA subdomain scores. Post-IAEEP, the AKA of parents were rated as "very high" for awareness domain, "very high" for knowledge domain, "very positive" for attitude domain, and "excellent" for total AKA domain at both TP2 and TP3. Parent proxy CHEQOL-25 report showed significant increments in interpersonal/social and secrecy scale scores between TP1 and TP3. There were no significant differences in the DASS-21 scores between TP1 and TP3.
CONCLUSION: The IAEEP is an effective epilepsy educational tool to increase the levels of AKA among parents of CWE. Following the use of the IAEEP, parents of CWE also reported an improvement of their child's quality of life in the interpersonal/social and epilepsy secrecy CHEQOL-25 domains. There was no impact on parental mental health following exposure to the IAEEP.
METHOD: Retrospective study of children with ANE seen at University of Malaya Medical Centre from 2014 to 2019. All clinical details including ANE-severity score (ANE-SS), immunomodulation treatment and neurodevelopmental long-term outcome were collected.
RESULTS: Thirteen patients had ANE and brainstem death occurred in 5. In 10 patients (77%) viruses were isolated contributing to ANE: 8 influenza virus, 1 acute dengue infection, and 1 acute varicella zoster infection. The ANE-SS ranged 2-7: 9 were high risk and 4 were medium risk. Among the 8 survivors; 1 was lost to follow-up. Follow-up duration was 1-6 years (median 2.2). At follow-up among the 4 high-risk ANE-SS: 2 who were in a vegetative state, 1 remained unchanged and 1 improved to severe disability; the other 2 with severe disability improved to moderate and mild disability respectively. At follow-up all 3 medium-risk ANE-SS improved: 2 with severe disability improved to moderate and mild disability respectively, while 1 in a vegetative state improved to severe disability. Early treatment with immunomodulation did not affect outcome.
CONCLUSION: Our ANE series reiterates that ANE is a serious cause of encephalopathy with mortality of 38.5%. All survivors were in a vegetative state or had severe disability at discharge. Most of the survivors made a degree of recovery but good recovery was seen in 2. Follow-up of at least 12 months is recommended for accurate prognostication. Dengue virus infection needs to be considered in dengue endemic areas.
METHOD: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in a tertiary hospital in Malaysia from 2014 to 2015. Detailed assessment of anthropometric measurements; environmental lifestyle risk factors; serum vitamin D, calcium and parathyroid hormone levels; genotyping of single nucleotide polymorphisms of genes in vitamin D and calcium metabolism; and lumbar spine BMD were obtained. Low BMD was defined as BMD Z-score ≤ -2.0 SD.
RESULTS: Eighty-seven children with mean age of 11.9 years (56 males) participated in the study. The prevalence of low lumbar BMD was 21.8% (19 patients). Multivariate logistic regression analysis identified polytherapy >2 AEDs (OR: 7.86; 95% CI 1.03-59.96), small frame size with wrist breadth of <15th centile (OR 14.73; 95% CI 2.21-98.40), and body mass index Z-score 2 AEDs, underweight or with small frame size as they are at higher risk of having low BMD.
METHODS: Cross-sectional study of all CWE aged 8-18years old with at least 6months' duration of epilepsy, minimum reading level of primary school education Year 1, and attending mainstream education. Quality of life was measured using the parent-proxy and child self-report of Quality of Life Measurement for Children with Epilepsy (CHEQOL-25) questionnaire. Total and subscale CHEQOL-25 scores were obtained. The levels of parent-child agreement were determined using intraclass correlation coefficients (ICC). Family functioning was assessed using the General functioning subscale (GF-12).
RESULTS: A total of 115 CWE and their parents participated in the study. In general, Malaysian parents rated children's total CHEQOL-25 scores poorer than the children themselves [mean total parent score: 68.56 (SD: 10.86); mean total child score: 71.82 (SD: 9.55)]. Agreement between child and parent on the CHEQOL-25 was poor to moderate (ICC ranged from 0.31-0.54), with greatest discordance in the epilepsy secrecy domain (ICC=0.31, p=0.026). Parent and child were more likely to agree on more external domains: intrapersonal/social (ICC=0.54, p<0.001) and interpersonal/emotional (ICC=0.50, p<0.001). Malay ethnicity, focal seizure and high seizure frequency (≥1 seizure per month) were associated with lower CHEQOL-25 scores. There was a significant but weak correlation between GF-12 and parent-proxy CHEQOL-25 Total Scores (r=-0.186, p=0.046).
CONCLUSION: Our results emphasize the importance to have the child's perspective of their QOL as the level of agreement between the parent and child reported scores were poor to moderate. Malaysian CWE of Malay ethnicity, those with focal seizures or high seizure frequency are at risk of poorer QOL.
METHODS: Cross-sectional study of Malaysian ambulant CWE on antiseizure medication for >1 year. Sixteen SNPs in 8 genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1, CYP27A1, CYP3A4, NADSYN1/DHCR7) were genotyped. Linear and logistic regression models and co-variates adjusted analyses were used. SNPs with significant associations were further analysed in a group of ethnically-matched healthy Malaysian children.
RESULTS: 239 CWE were recruited (52.7% Malay, 24.3% Chinese and 23.0% Indian) with mean serum 25(OH)D of 58.8 nmol/L (SD 25.7). Prevalence of vitamin D deficiency (≤37.5 nmol/L) was 23.0%. Minor allele of GC-rs4588-A was associated with lower serum 25(OH)D in the meta-analysis of both CWE (β -8.11, P = 0.002) and Malaysian healthy children (β -5.08, P < 0.001), while VDR-rs7975232-A was significantly associated with reduced odds of vitamin D deficiency in Malay subgroup of CWE (OR: 0.16; 95% CI: 0.06-0.49; P = 0.001) and this association was not found in the healthy children group.
CONCLUSIONS: Our results suggest that GC-rs4588 is associated with lower serum 25(OH)D concentration in both Malaysian CWE and healthy children, while VDR-rs7975232A is associated with lower risk of vitamin D deficiency in Malaysian CWE of Malay ethnicity. Our findings may assist in the genetic risk stratification of low vitamin D status among CWE.
METHODS: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in three tertiary hospitals in Malaysia from April 2014 to April 2015. Detailed assessment of pubertal status, skin pigmentation, sunshine exposure behavior, physical activity, dietary vitamin D and calcium intake, anthropometric measurements and bone health blood tests (vitamin D, alkaline phosphatase, calcium, phosphate, and parathyroid hormone levels) were obtained on all patients. Vitamin D deficiency was defined as 25-hydroxy vitamin D [25(OH)D] levels ≤35 nmol/L and insufficiency as 25(OH)D levels of 36-50 nmol/L.
RESULTS: A total of 244 children (146 male) participated in the study. Ages ranged between 3.7 and 18.8 years (mean 12.3 years). 25(OH)D levels ranged between 7.5 and 140.9 nmol/L (mean 53.9 nmol/L). Vitamin D deficiency was identified in 55 patients (22.5%), and a further 48 (19.7%) had vitamin D insufficiency. Multivariate logistic regression analysis identified polytherapy >1 AED (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.07-4.36), age >12 years (OR 4.16, 95% CI 1.13-15.30), Indian ethnicity (OR 6.97, 95% CI 2.48-19.55), sun exposure time 30-60 min/day (OR 2.44, 95% CI 1.05-5.67), sun exposure time <30 min/day (OR 3.83, 95% CI 1.61-9.09), and female (OR 2.61, 95% CI 1.31-5.20) as statistically significant (p < 0.05) risk factors for vitamin D deficiency.
SIGNIFICANCE: Despite living in the tropics, a high proportion of Malaysian children with epilepsy are at risk of vitamin D deficiency. Targeted strategies including vitamin D supplementation and lifestyle advice of healthy sunlight exposure behavior should be implemented among children with epilepsy, particularly for those at high risk of having vitamin D deficiency.
METHOD: Cross-sectional study on 68 parents of Malaysian children aged 2-18 years with TSC. QOL was assessed using proxy-report Paediatric Quality of Life Inventory (PedsQL) V.4.0, and scores compared with those from a previous cohort of healthy children. Parents also completed questionnaires on child behaviour (child behaviour checklist (CBCL)) and parenting stress (parenting stress index-short form). Multiple regression analysis was used to determine sociodemographic, medical, parenting stress and behavioural factors that impacted on QOL.
RESULTS: The mean proxy-report PedsQL V.4.0 total scale score, physical health summary score and psychosocial health summary score of the patients were 60.6 (SD 20.11), 65.9 (SD 28.05) and 57.8 (SD 19.48), respectively. Compared with healthy children, TSC patients had significantly lower mean PedsQL V.4.0 total scale, physical health and psychosocial health summary scores (mean difference (95% CI): 24 (18-29), 20 (12-27) and 26 (21-31) respectively). Lower total scale scores were associated with clinically significant CBCL internalising behaviour scores, age 8-18 years and Chinese ethnicity. Lower psychosocial health summary scale scores were associated with clinically significant CBCL internalising behaviour scores, Chinese ethnicity or >1 antiepileptic drug (AED).
CONCLUSION: Parents of children with TSC reported lower PedsQL V.4.0 QOL scores in all domains, with psychosocial health most affected. Older children, those with internalising behaviour problems, of Chinese ethnicity or on >1 AED was at higher risk of lower QOL. Clinicians need to be vigilant of QOL needs among children with TSC particularly with these additional risk factors.
METHOD: Prospective cohort study on CWE age 7-18 years old with no comorbidities. Epilepsy education was delivered using Epigame. CWE completed AKA questionnaire before (time point 1 [TP1]), immediately after (TP2), 3 months (TP3) after provision of Epigame. Child self-report Health-Related Quality of Life Measurement for Children with Epilepsy (CHEQOL-25) questionnaire was completed at TP1 and TP3.
RESULTS: Total of 106 CWE participated in this study (mean age of 13.3 years). Baseline (TP1) AKA was rated "very low to moderate" for awareness domain in 95.3 %, "very low to moderate" for knowledge domain in 67 %, "negative to indifferent" for attitude domain in 54.7 %, and "very poor to moderate' for total AKA score domain in 84 %. "Positive to very positive" for child attitude domain was significantly associated with parents with "positive to very positive" for attitude domain (OR 10.6, 95 % CI 3.23-34.66). "Good to excellent" for total child AKA domain was significantly associated with parents with "Good to excellent" for total AKA domain (OR 5.2, 95 % CI 1.16-15.02) and with
METHODS: In May 2015, 15 epilepsy experts attended a Consensus Development Meeting to assess the clinical trial data for perampanel, specific to the adolescent age group (12-17 years) and develop consensus treatment recommendations.
RESULTS AND DISCUSSION: Analysis of the adolescent subgroup data of three pivotal placebo-controlled, double-blind, phase 3 trials investigating perampanel in patients with ongoing focal epileptic seizures despite receiving one to three antiepileptic drugs found that perampanel 4-12 mg was superior to placebo. The tolerability profile of perampanel was generally acceptable. Adolescent patients receiving long-term treatment with perampanel in an open-label extension study maintained improvements in seizure control compared with baseline, with a favorable risk-benefit profile. A phase 2 study showed that perampanel had no clinically important effects on cognitive function, growth, and development.
CONCLUSION: Perampanel is a welcome addition to the armamentarium of existing antiepileptic drugs as it represents a new approach in the management of epilepsy, with a novel mechanism of action, and the potential to have a considerable impact on the treatment of adolescents with epilepsy.
METHODS: A web-based survey was sent to clinicians involved in the management of SE, across all states and at all levels of healthcare services.
RESULTS: A total of 158 responses were received from 104 health facilities, including 23 tertiary government hospitals (95.8% of all government tertiary hospitals in Malaysia), 4 (80.0%) universities, 14 (6.7%) private, 15 (11.5%) district hospitals and 21 clinics. Intravenous (IV) diazepam was available in 14 (93.3%) district and 33 (80.5%) tertiary hospitals for prehospital management. Non-IV benzodiazepine (rectal diazepam and intramuscular midazolam) was not widely available in prehospital services (75.8% and 51.5%). Intramuscular midazolam was underutilised (60.0% in district and 65.9% in tertiary hospitals). IV sodium valproate and levetiracetam were only available in 66.7% and 53.3% of the district hospitals, respectively. Electroencephalogram (EEG) services were available in only 26.7% of the district hospitals. Non-pharmacological therapies such as ketogenic diet, electroconvulsive therapy, and therapeutic hypothermia were not available in most district and tertiary hospitals for refractory and super-refractory SE.
CONCLUSIONS: We identified several gaps in the current practice of SE management, including limited availability and underutilization of non-IV midazolam in prehospital services, underutilization of non-IV midazolam and other second-line ASMs, and lack of EEG monitoring in district hospitals and limited treatment options for refractory and super-refractory SE in tertiary hospitals.