Publications by authors named "Vigneswari Ganesan"

7 Publications

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Congenital myasthenic syndrome with novel pathogenic variants in the COLQ gene associated with the presence of antibodies to acetylcholine receptors.

J Clin Neurosci 2020 Feb 10;72:468-471. Epub 2019 Dec 10.

Genetic Medicine Unit, Department of Paediatrics, University of Malaya Medical Centre, Kuala Lumpur, Malaysia. Electronic address:

Congenital myasthenic syndrome (CMS) is a heterogeneous group of inherited disorder which does not associate with anti-acetylcholine receptor (AChR) antibody. The presence of AChR autoantibody is pathogenic and highly sensitive and specific for autoimmune myasthenia gravis (MG). We describe 2 children from unrelated families who presented with hypotonia, ptosis and fatigability in early infancy with anti-AChR antibodies detected via ELISA on 2 separate occasions in the sera. Both were treated as refractory autoimmune MG due to poor clinical response to acetylcholinesterase inhibitor and immunotherapy. In view of the atypical clinical features, genetic studies of CMS were performed and both were confirmed to have novel pathogenic mutations in the COLQ gene. To the best of our knowledge, the presence of anti-AChR antibody in COLQ-related CMS has never been reported in the literature. The clinical presentation of early onset phenotype, and refractoriness to acetylcholinesterase inhibitor and immunotherapy should prompt CMS as a differential diagnosis.
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http://dx.doi.org/10.1016/j.jocn.2019.12.007DOI Listing
February 2020

Quality of life of children with tuberous sclerosis complex.

Arch Dis Child 2019 10 23;104(10):972-978. Epub 2019 May 23.

Paediatric Department, Hospital Raja Perempuan Zainab II, Kelantan, Malaysia.

Aim: Evaluation of impaired quality of life (QOL) of Malaysian children with tuberous sclerosis complex (TSC) and its possible risk factors.

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.
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http://dx.doi.org/10.1136/archdischild-2018-316394DOI Listing
October 2019

GRIN2D variants in three cases of developmental and epileptic encephalopathy.

Clin Genet 2018 12;94(6):538-547

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

N-methyl-d-aspartate (NMDA) receptors are glutamate-activated ion channels that are widely distributed in the central nervous system and essential for brain development and function. Dysfunction of NMDA receptors has been associated with various neurodevelopmental disorders. Recently, a de novo recurrent GRIN2D missense variant was found in two unrelated patients with developmental and epileptic encephalopathy. In this study, we identified by whole exome sequencing novel heterozygous GRIN2D missense variants in three unrelated patients with severe developmental delay and intractable epilepsy. All altered residues were highly conserved across vertebrates and among the four GluN2 subunits. Structural consideration indicated that all three variants are probably to impair GluN2D function, either by affecting intersubunit interaction or altering channel gating activity. We assessed the clinical features of our three cases and compared them to those of the two previously reported GRIN2D variant cases, and found that they all show similar clinical features. This study provides further evidence of GRIN2D variants being causal for epilepsy. Genetic diagnosis for GluN2-related disorders may be clinically useful when considering drug therapy targeting NMDA receptors.
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http://dx.doi.org/10.1111/cge.13454DOI Listing
December 2018

Characteristics of seizure frequency among Malaysian children diagnosed with structural-metabolic epilepsy.

J Neurosci Rural Pract 2012 Sep;3(3):244-50

College of Pharmacy, Al-Rashed University, Baghdad, Iraq.

Introduction: Seizure-free patients or substantial reduction in seizure frequency are the most important outcome measures in the management of epilepsy. The study aimed to evaluate the patterns of seizure frequency and its relationship with demographics, clinical characteristics, and outcomes.

Materials And Methods: A retrospective cohort study was conducted at the Pediatric Neurology Clinic, Hospital Pulau Pinang. Over a period of 6 months, the required data were extracted from the medical records using a pre-designed data collection form.

Results: Seizure frequency showed no significant association with patient's demographics and clinical characteristic. However, significant reduction in seizure frequency from the baseline to the last follow-up visit was only seen in certain subgroups of patients including Malays, females, patients <4 years of age, patients with global developmental delay/intellectual disability, and patients with focal seizure. There was no significant association between seizure frequency and rate of adverse events. Polytherapy visits were associated with higher seizure frequency than monotherapy visits (27.97 ± 56.66, 10.94 ± 30.96 attack per month, respectively) (P < 0.001). There was a clear tendency to get antiepileptic drugs used at doses above the recommended range in polytherapy (8.4%) rather than in monotherapy (1.4%) visits (P < 0.001). A significant correlation was found between seizure frequency and number of visits per patient per year (r = 0.450, P < 0.001).

Conclusion: Among children with structural-metabolic epilepsy, Malays, females, patients <4 years of age, patients with global developmental delay/intellectual disability and patients manifested with focal seizure are more responsive antiepileptic drug therapy than the other subgroups of patients.
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http://dx.doi.org/10.4103/0976-3147.102596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505308PMC
September 2012

Cost-effectiveness analysis for the use of serum antiepileptic drug level monitoring in children diagnosed with structural-metabolic epilepsy.

Epilepsy Res 2013 Mar 25;104(1-2):151-7. Epub 2012 Oct 25.

College of Pharmacy, Al-Rasheed University, Baghdad, Iraq.

Treatment with antiepileptic drugs is commonly guided by serum level monitoring. Such monitoring requires expensive laboratory equipment and products. However, well-conducted studies on the cost-effectiveness of therapeutic drug monitoring for antiepileptic drugs are lacking particularly in patients with structural-metabolic epilepsy. The study aims to assess the cost-effectiveness of serum level monitoring services in the management of children with structural-metabolic epilepsy during the first year of diagnosis. A retrospective cost-effectiveness analysis was conducted from the provider perspective. It included patients attended a paediatric neurology clinic. The effectiveness measures used in this analysis were the number of patients that achieved ≥50% reduction in seizure frequency, and the number of patients with 3-month seizure free. Medical records of the patients were reviewed for the required information. Medical chart/billing data obtained from the hospital were collected to estimate the resources used (One Malaysian Ringgit MYR is equivalent to 0.31 USD). The recruited children were followed for one year following their first visit. The average cost effectiveness ratio for the monitored patients (MYR 2735 per patient that achieved a ≥50% reduction in seizure frequency) was lower than that for non-monitored patients (MYR 2921 per patients that achieved a ≥50% reduction in seizure frequency), with incremental cost-effectiveness ratio of MYR 2357 per one additional patient that achieved a ≥50% reduction in seizure frequency. The average cost effectiveness ratios for monitored and non-monitored group were MYR 8279 and MYR 6433 per patient with a 3-month seizure-free period, respectively, with incremental cost-effectiveness ratio of MYR 29,666 per one additional patient with a 3-month seizure-free period. In terms of the effectiveness measures used, serum level monitoring of antiepileptic drugs was found to be cost-effective. However, the incremental cost-effectiveness ratio was found to be sensitive to the cost of management.
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http://dx.doi.org/10.1016/j.eplepsyres.2012.09.012DOI Listing
March 2013

Medical care costs of newly diagnosed children with structural-metabolic epilepsy: a one year prevalence-based approached.

Seizure 2012 Dec 29;21(10):764-9. Epub 2012 Aug 29.

College of Pharmacy, Al-Rashed University, Baghdad, Iraq.

Purpose: Aims of this study were to estimate the first-year medical care costs of newly diagnosed children with structural-metabolic epilepsy and to determine the cost-driving factors in the selected population.

Method: This was a prevalence-based retrospective chart review that included patients who attended a pediatric neurology clinic in a tertiary referral center in Malaysia. The total first-year medical care costs were estimated from the provider (i.e., hospital) perspective, using a bottom-up, microcosting analysis. Medical chart/billing data (i.e., case reports) obtained from the hospital (i.e., provider) were collected to determine the resources used. Prices or cost data were standardized for the year 2010 (One Malaysian Ringgit MYR is equivalent to 0.26 Euro or 0.32 USD).

Results: The most expensive item in the costs list was antiepileptic drugs, whereas ultrasound examination represented the cheapest item. Hospitalization and the use of non-antiepileptic drugs were the second and third most costly items, respectively. The cost of therapeutic drug monitoring comprised only a small proportion of the total annual expenditure. None of the demographic variables (i.e., gender, race, and age) significantly impacted the first-year medical care costs. Similarly, child development, seizure type, therapy type (i.e., polytherapy versus monotherapy), and therapeutic drug monitoring utilization were also not associated with the cost of management. The first-year medical care costs positively correlated with seizure frequency (r(s)=0.294, p=0.001). However, the only variable that significantly predict the first-year medical care costs was the type of antiepileptic drugs (R(2)=0.292, F=7.772, p<0.001).

Conclusion: This investigation was the first cost analysis study of epilepsy in Malaysia. The total first-year medical care costs for 120 patients with structural-metabolic epilepsy were MYR 202,816 (i.e., MYR 1690.13 per patient per year). The study findings highlight the importance of optimizing seizure control in reducing the cost of management.
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http://dx.doi.org/10.1016/j.seizure.2012.08.005DOI Listing
December 2012

Practices associated with serum antiepileptic drug level monitoring at a pediatric neurology clinic: a Malaysian experience.

J Pharm Pract 2013 Jun 13;26(3):192-7. Epub 2012 Jul 13.

College of Pharmacy, Al-Rashed University, Baghdad, Iraq.

Objectives: To assess the practices associated with the application of therapeutic drug monitoring (TDM) for antiepileptic drugs (AEDs) in the management of children with structural-metabolic epilepsy.

Methods: It was a retrospective chart review and included children aged ≥2 years old with structural-metabolic epilepsy, treated with AEDs, and received TDM. The data were extracted from the medical records.

Results: Thirty-two patients were identified with 50 TDM assays. In two thirds of the assays, "check level" and "recheck level" were the reasons behind the requesting of serum level monitoring of AEDs. Knowledge of serum AED levels led to alterations in the management in 60% of the assays. Thirty-two (76%) pediatrician's actions were consistent with the recommendation of TDM pharmacist. Forty-nine (98%) levels were appropriately indicated. In relation to the appropriateness of sampling time, 9 (18%) levels were not assessed due to missing data. Twenty-seven (54%) levels were appropriately sampled.

Conclusions: More studies should be designed to improve the component of the current TDM request form, especially in the reason section. By the same token, the number of pointless assays and the costs to the health care system can be reduced both by enhancing and improving the educational standards of the requesting neurologists.
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http://dx.doi.org/10.1177/0897190012451926DOI Listing
June 2013