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Role of inflammation in epilepsy and neurobehavioral comorbidities: Implication for therapy

Paudel YN, Shaikh MF, Shah S, Kumari Y, Othman I

Eur J Pharmacol, 2018 Oct 15;837:145-155.
PMID: 30125565 DOI: 10.1016/j.ejphar.2018.08.020

Epilepsy is a devastating condition affecting around 70 million people worldwide. Moreover, the quality of life of people with epilepsy (PWE) is worsened by a series of comorbidities. The neurobehavioral comorbidities discussed herein share a reciprocal and complex relationship with epilepsy, which ultimately complicates the treatment process in PWE. Understanding the mechanistic pathway by which these comorbidities are associated with epilepsy might be instrumental in developing therapeutic interventions. Inflammatory cytokine signaling in the brain regulates important brain functions including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, dopaminergic transmission, the kynurenine pathway, and affects neurogenesis as well as the neural circuitry of moods. In this review, we hypothesize that the complex relationship between epilepsy and its related comorbidities (cognitive impairment, depression, anxiety, autism, and schizophrenia) can be unraveled through the inflammatory mechanism that plays a prominent role in all these individual conditions. An ample amount of evidence is available reporting the role of inflammation in epilepsy and all individual comorbid condition but their complex relationship with epilepsy has not yet been explored through the prospective of inflammatory pathway. Our review suggests that epilepsy and its neurobehavioral comorbidities are associated with elevated levels of several key inflammatory markers. This review also sheds light on the mechanistic association between epilepsy and its neurobehavioral comorbidities. Moreover, we analyzed several anti-inflammatory therapies available for epilepsy and its neurobehavioral comorbidities. We suggest, these anti-inflammatory therapies might be a possible intervention and could be a promising strategy for preventing epileptogenesis and its related neurobehavioral comorbidities.

Matched MeSH terms: Autism Spectrum Disorder/etiology
The Potential Role of miRNAs as Predictive Biomarkers in Neurodevelopmental Disorders

Juvale IIA, Che Has AT

J Mol Neurosci, 2021 Jul;71(7):1338-1355.
PMID: 33774758 DOI: 10.1007/s12031-021-01825-7

Neurodevelopmental disorders are defined as a set of abnormal brain developmental conditions marked by the early childhood onset of cognitive, behavioral, and functional deficits leading to memory and learning problems, emotional instability, and impulsivity. Autism spectrum disorder, attention-deficit/hyperactivity disorder, Tourette syndrome, fragile X syndrome, and Down's syndrome are a few known examples of neurodevelopmental disorders. Although they are relatively common in both developed and developing countries, very little is currently known about their underlying molecular mechanisms. Both genetic and environmental factors are known to increase the risk of neurodevelopmental disorders. Current diagnostic and screening tests for neurodevelopmental disorders are not reliable; hence, individuals with neurodevelopmental disorders are often diagnosed in the later stages. This negatively affects their prognosis and quality of life, prompting the need for a better diagnostic biomarker. Recent studies on microRNAs and their altered regulation in diseases have shed some light on the possible role they could play in the development of the central nervous system. This review attempts to elucidate our current understanding of the role that microRNAs play in neurodevelopmental disorders with the hope of utilizing them as potential biomarkers in the future.

Matched MeSH terms: Autism Spectrum Disorder/diagnosis; Autism Spectrum Disorder/genetics
Factors associated with autism severity among Malaysian children with Autism Spectrum Disorder

Eow SY, Gan WY, Lim PY, Awang H, Mohd Shariff Z

Res Dev Disabil, 2020 May;100:103632.
PMID: 32179381 DOI: 10.1016/j.ridd.2020.103632

BACKGROUND: Children with Autism Spectrum Disorder (ASD) of different levels of symptom severity may exhibit a wide range of behaviours and characteristics. There is a limited nutrition-related study on children with ASD of different severity in Malaysia.
AIMS: This cross-sectional study aims to determine the association between sociodemographic factors, parental factors, and lifestyle factors with autism severity in children with ASD.
METHODS AND PROCEDURES: A total of 224 children with ASD were included in this study. Their mothers completed a self-administered questionnaire on sociodemographic characteristics, autism severity, parenting style, parental feeding practices, parenting stress, child's sleep habits and eating behaviours.
OUTCOMES AND RESULTS: As high as 78.1 % of the children with ASD demonstrated a high level of autism severity. Multiple linear regression showed that father's employment status (B = 6.970, 95 % CI = 3.172, 10.768, p autism severity.
CONCLUSIONS AND IMPLICATIONS: Children with ASD in this study had a high level of autism severity. Regular anthropometric measurements by healthcare professionals should be conducted at the autism intervention centres. It is important to have multidisciplinary collaboration in future research to develop customised guidelines for parents with autistic children.

Matched MeSH terms: Autism Spectrum Disorder/physiopathology
Fulltext The effectiveness and adverse effects of D-cycloserine compared with placebo on social and communication skills in individuals with autism spectrum disorder

Aye SZ, Ni H, Sein HH, Mon ST, Zheng Q, Wong YKY

Cochrane Database Syst Rev, 2021 02 14;2:CD013457.
PMID: 33583058 DOI: 10.1002/14651858.CD013457.pub2

BACKGROUND: Symptoms of autism spectrum disorder (ASD) have been associated, in part, with the dysfunction of N-methyl-D-aspartate (NMDA) glutamate receptors at excitatory synapses and glutamate abnormalities. Medications related to glutamatergic neurotransmission, such as D-cycloserine - which is a partial agonist of the NMDA glutamate receptor - are potential treatment options for the core features of ASD. However, the potential effect of D-cycloserine on the social and communication skills deficits of individuals with ASD has not been thoroughly explored and no systematic reviews of the evidence have been conducted.
OBJECTIVES: To assess the efficacy and adverse effects of D-cycloserine compared with placebo for social and communication skills in individuals with ASD.
SEARCH METHODS: In November 2020, we searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers. We also searched the reference lists of relevant publications and contacted the authors of the included study, Minshawi 2016, to identify any additional studies. In addition, we contacted pharmaceutical companies, searched manufacturers' websites and sources of reports of adverse events. SELECTION CRITERIA: All randomised controlled trials (RCTs) of any duration and dose of D-cycloserine, with or without adjunct treatment, compared to placebo in individuals with ASD.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted relevant data, assessed the risk of bias, graded the certainty of the evidence using the GRADE approach, and analysed and evaluated the data. We provide a narrative report of the findings as only one study is included in this review.
MAIN RESULTS: We included a single RCT (Minshawi 2016) funded by the United States Department of Defense. It was conducted at two sites in the USA: Indiana University School of Medicine and Cincinnati Children's Hospital Medical Centre. In the included study, 67 children with ASD aged between 5 and 11 years were randomised to receive either 10 weeks (10 doses) of (50 mg) D-cycloserine plus social skills training, or placebo plus social skills training. Randomisation was carried out 1:1 between D-cycloserine and placebo arms, and outcome measures were recorded at one-week post-treatment. The 'risk of bias' assessment for the included study was low for five domains and unclear for two domains. The study (67 participants) reported low certainty evidence of little to no difference between the two groups for all outcomes measured at one week post-treatment: social interaction impairment (mean difference (MD) 3.61 (assessed with the Social Responsiveness Scale), 95% confidence interval (CI) -5.60 to 12.82); social communication impairment (MD -1.08 (measured using the inappropriate speech subscale of the Aberrant Behavior Checklist (ABC)), 95% CI -2.34 to 0.18); restricted, repetitive, stereotyped patterns of behaviour (MD 0.12 (measured by the ABC stereotypy subscale), 95% CI -1.71 to 1.95); serious adverse events (risk ratio (RR) 1.11, 95% CI 0.94 to 1.31); non-core symptoms of ASD (RR 0.97 (measured by the Clinical Global Impression-Improvement scale), 95% CI 0.49 to 1.93); and tolerability of D-cycloserine (RR 0.32 (assessed by the number of dropouts), 95% CI 0.01 to 7.68). AUTHORS' CONCLUSIONS: We are unable to conclude with certainty whether D-cycloserine is effective for individuals with ASD. This review included low certainty data from only one study with methodological issues and imprecision. The added value of this review compared to the included study is we assessed the risk of bias and evaluated the certainty of evidence using the GRADE approach. Moreover, if we find new trials in future updates of this review, we could potentially pool the data, which may either strengthen or decrease the evidence for our findings.

Matched MeSH terms: Autism Spectrum Disorder/drug therapy*
Fulltext The effect of listening to Qur’anic recitation on social skills among children with Autism Spectrum Disorder (ASD)

Wan Fara Adila Wan Ahmad Kaspi, Kartini Ilias, Amir Muhriz Abdul Latiff, Mohd Zaid Daud

Malaysian Journal of Medicine and Health Sciences, 2019;15(104):101-101.
MyJurnal

Introduction: The number of children diagnosed with Autism Spectrum Disorder (ASD) keeps increasing every year. ASD is a neurodevelopmental disability that affects social communication and social interaction. They also demon-strate restricted, repetitive pattern of behaviour, interest or activities (RRB) that shows at an early developmental age. Due to this characteristic, ASD children are facing difficulties in social skills aspect such as eye contact, expression, and making friends. Studying and reciting the Quran are often used in Malaysia to ameliorate the symptoms, but there is no specific study in Malaysia that demonstrates the impact of these renditions on ASD’s children’s social skills. The objective of this study was to investigate the effect selected Qur’anic verses recitation on the social skills of the children with Autism Spectrum Disorder (ASD). Methods: This study will use the quasi-experimental research design. This study will be held at IDEAS Autism Centre, Rawang. The purposive sampling technique will be used and 14 ASD Muslim children aged 4-6 years old will be chosen. The ASD children will be divided into an experimental and control group. The experimental group will be listening to selected Qur’anic verses before the intervention. The Social Responsiveness Scale- Second Edition (SRS-2) will be used to assess the response. The scale consists of a 65-item questionnaire, with a 4-point Likert-scale. Results: The expected result for this study is the ASD children in the experimental group will have lower Total-scores of SRS-2 compared to control group. Conclusion: Listening to Qur’anic recitation provides a cost-effective complementary therapy to improve social skills among Muslim ASD children. Information from this study also can be used as a stepping stone in developing the teaching module to ASD children.

Matched MeSH terms: Autism Spectrum Disorder
Fulltext Sleep Disturbances in Children With Autism Spectrum Disorder at a Malaysian Tertiary Hospital

Koo HW, Ismail J, Yang WW, Syed Zakaria SZ

Front Pediatr, 2020;8:608242.
PMID: 33537265 DOI: 10.3389/fped.2020.608242

Introduction: Children with autism spectrum disorder (ASD) have a variety of co-morbid medical problems, including sleep disturbances. Prevalence of sleep disorders has been reported to be higher in this group as compared to the general population. Identifying sleep problems in children with ASD may help increase awareness and improve the overall quality of care for them. The aim of this study was to determine the prevalence of sleep problems and associated factors in a group of Malaysian children aged 6-16 years, with ASD. Method: This is a cross-sectional study at the Child Development Centre of UKM Medical Centre (UKM MC) on ASD children aged 6-16 years. Demographic data was obtained and the Sleep Disturbances Scale for Children (SDSC) questionnaire was completed by the main caregiver. Logistic regression analysis was used to determine factors related to higher total SDSC scores. Results: A total of 128 patients were recruited (111 boys) with a median age of 8 years 3 months (IQR: 2 years 10 months). Forty-seven (36.7%) of them obtained total SDSC scores in the pathological range with 19 (14.8%) scoring high for overall disturbances and 28 (21.9%) for at least one subtype of sleep disorders: 25 (19.5%) DIMS, 18 (14.1%) SBD, 10 (7.8%) DOES, 5 (3.9%) DOA, 6 (4.7%) SWTD, and 3 (2.3%) SHY. More than half of the children (57.8%) were reported to have sufficient sleep duration of 8-11 h, but longer sleep latency of at least 15 min (82.8%). Half of the ASD children also had co-morbidities in which one-third (34.4%) had attention-deficit hyperactivity disorder (ADHD). Using logistic regression analysis, four factors were significantly associated with higher total SDSC scores; female gender (p = 0.016), older age group (11-16 years old) (p = 0.039), shorter sleep length (p = 0.043), and longer sleep latency (p < 0.001). Conclusion: The prevalence of sleep disturbances is high among Malaysian children with ASD, especially DIMS. Female gender, older age group, shorter sleep length, and longer sleep latency were found to be associated with the sleep disturbances. Evaluation of sleep problems should form part of the comprehensive care of children with ASD.

Matched MeSH terms: Autism Spectrum Disorder
Fulltext Autism: awareness and perception among Malaysian Nursing Students in Sabah

Deena Clare Thomas, Julie C M, Helda A H, Nurhani Nadiah B, Ranita M

Malaysian Journal of Medicine and Health Sciences, 2020;16(105):71-0.
MyJurnal

Introduction: Autism spectrum disorder (ASD) is a developmental disability that can cause significant social, com- munication and behavioral challenges. According to the 2017 survey by the Ministry of Health Malaysia, children between the ages of 18 to 26 months showed ASD occurs approximately 1.6 in1000 children. In Sabah, 400 autistic children had been registered under Sabah Autism Society (SAS). The increasing prevalence of ASD had become a major concern not only to the parents but to the community. A correct understanding and perception about ASD are crucial especially to the nursing profession as they must be able to educate caregiver on how to manage patients with ASD. Methods: This is a quantitative study using a cross-sectional approach. The respondents are all nursing students in Sabah. The type of sampling is purposive, which is using snowball sampling methods. Research instruments were developed and distributed to all nursing colleges in Sabah. Results: A total of 115 students responded. The majority of age is within range of 18–20 years old and female students. Fifty percents (50%) respondents perceived that of autism is a socio-emotional and neuro-developmental disorder with a non-verbal behaviors’ impairment, curable disorder with proper treatment. More than fifty percent (50%) disagree that autistic child does not want friends and equivalent stand on the statement about autistic child can live independently. Ninety five percent (90%) agree that social media plays an important platform to deliver facts about autism, and health care provider remains as a key role to increase the level of awareness to the community. Conclusion: Results of this study revealed that nursing students in Sabah have a good awareness and perception towards autistic disorder. Nursing students in Sabah agree that social media plays a vital part to increase the level of awareness and perception.

Matched MeSH terms: Autism Spectrum Disorder
Parenting Stress and Resilience in Parents of Children With Autism Spectrum Disorder (ASD) in Southeast Asia: A Systematic Review

Ilias K, Cornish K, Kummar AS, Park MS, Golden KJ

Front Psychol, 2018;9:280.
PMID: 29686632 DOI: 10.3389/fpsyg.2018.00280

Background: This paper aimed to review the literature on the factors associated with parenting stress and resilience among parents of children with autism spectrum disorder (ASD) in the South East Asia (SEA) region. Methods: An extensive search of articles in multiple online databases (PsycNET, ProQuest, PudMed, EMBASE, CINAHL, Web of Science, and Google Scholar) resulted in 28 papers that met the inclusion criteria (i.e., conducted in the SEA region, specific to ASD only, published in a peer-reviewed journal, full text in English). Studies found were conducted in the following countries: Brunei, n = 1; Indonesia, n = 2; Malaysia, n = 12; Philippines, n = 5; Singapore, n = 5, Thailand, n = 2; and Vietnam, n = 1, but none from Cambodia, East Timor, Laos, and Myanmar were identified. Results: Across the studies, six main factors were found to be associated with parenting stress: social support, severity of autism symptoms, financial difficulty, parents' perception and understanding toward ASD, parents' anxiety and worries about their child's future, and religious beliefs. These six factors could also be categorized as either a source of parenting stress or a coping strategy/resilience mechanism that may attenuate parenting stress. Conclusion: The findings suggest that greater support services in Western countries may underlie the cultural differences observed in the SEA region. Limitations in the current review were identified. The limited number of studies yielded from the search suggests a need for expanded research on ASD and parenting stress, coping, and resilience in the SEA region especially in Cambodia, East Timor, Laos, and Myanmar. The identified stress and resilience factors may serve as sociocultural markers for clinicians, psychologists, and other professionals to consider when supporting parents of children with ASD.

Matched MeSH terms: Autism Spectrum Disorder
Fulltext Psychiatric disorders among new child and adolescent attendees in an outpatient setting of a Sungai Petani Hospital: a registry from January 2014 to December 2014

Nazariah Harun, Ravivarma Rao Panirselvam, Yusni Yusuff

Malaysian Journal of Psychiatry, 2016;25(1):0-0.
MyJurnal

Introduction: Children and adolescents requiring mental health services are increasing. This paper is a registry of new clients in the Child and Adolescent Mental Health (CAMH) outpatient clinic of Hospital Sultan Abdul Halim (HSAH), Sungai Petani, Kedah, Malaysia from January 2014 to December 2014.
Objectives: We aimed to determine the trends of different types of mental disorders in first contact clients at an outpatient CAMH clinic in HSAH. Thereafter, we sought to compare the differences in demographics with types of illness and treatments modalities. Method: We reviewed electronic case records retrospectively for the study period from January 2014 to December 2014 and universal sampling was done.
Results: During the study period, there were 160 new cases. The highest number of patients were from the primary school age group with a mean age of 9.98 years. The highest incidence was Attention Deficit Hyperactivity Disorder (23.8%), followed by Autism Spectrum Disorder (17.5%) and others at 15.6%. Out of those sampled, 61% were treated pharmacologically and 39% were receiving non-pharmacological treatment.
Conclusions: There is a need to enhance and expand services to enable the client and family to obtain the necessary intervention. With improved screening and empowerment of the family, better outcomes could be achieved for the client.

Study site: outpatient clinic of Hospital Sultan Abdul Halim (HSAH)

Matched MeSH terms: Autism Spectrum Disorder
Fulltext The Human Gut Microbiome - A Potential Controller of Wellness and Disease

Kho ZY, Lal SK

Front Microbiol, 2018;9:1835.
PMID: 30154767 DOI: 10.3389/fmicb.2018.01835

Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.

Matched MeSH terms: Autism Spectrum Disorder
Fulltext Clinical characteristics and demographic profile of children with Autism Spectrum Disorder (ASD) at child development clinic (CDC), Penang Hospital, Malaysia

Sathyabama R

Med J Malaysia, 2019 Oct;74(5):372-376.
PMID: 31649211

OBJECTIVE: To explore socio-demographics and clinical characteristics of children with Autism Spectrum Disorder (ASD) at Child Development Clinic (CDC), Penang Hospital.

STUDY DESIGN: A record review study of 331 children with ASD attending CDC, Penang Hospital from September 2013 to April 2017.

RESULTS: Out of 331 children with ASD, 82.5% were males, 17.5% females, with male to female ratio of 4.7:1. Mean age at consultation was 5 years and 6 months (SD 31.68 months) with age range from 19 months to 18 years and 4 months. 85.8% were term infants with normal birth weight. History of speech regression was noted in 14.8%, epilepsy and genetic disorders in 9.4% and 5.7% respectively. Sleep problems was reported in 29.3%, dietary issues 22.1%, challenging behaviour 24.2% and ADHD 14.2%. Mean age of the father and mother at birth was 33.6 and 31.6 years respectively.

CONCLUSION: In this study, we report a higher male to female ratio and mean age at referral with some similar rates of neurodevelopmental and medical comorbidities and relatively younger parental age with higher parental education levels.

Matched MeSH terms: Autism Spectrum Disorder

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