Displaying publications 201 - 220 of 236 in total

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  1. Haerian BS, Baum L, Kwan P, Cherny SS, Shin JG, Kim SE, et al.
    Mol Neurobiol, 2016 10;53(8):5457-67.
    PMID: 26452361 DOI: 10.1007/s12035-015-9457-y
    Gamma-aminobutyric acid receptor (GABA-A) is the most common receptor of fast synaptic inhibition in the human brain. Gamma protein encoded by the GABRG2 gene is one of the subunits of the GABA-A receptor, which plays an essential role in the function of this receptor. Several studies have identified various febrile seizure (FS) and epilepsy risk variants of GABRG2 gene in different populations, but some others did not support these results. The aim of this case-control study is to investigate whether GABRG2 polymorphisms contribute to susceptibility for FS and epilepsy in pooled data of three cohorts, from Malaysia (composed of Malay, Chinese, and Indian), Hong Kong, and Korea. Furthermore, the pooled dataset of these cohorts with previous reports were meta-analyzed for determining the risk effect size of the rs211037 polymorphism on FS and symptomatic epilepsy (SE). The rs211037, rs210987, rs440218, rs2422106, rs211014, and rs401750 polymorphisms were genotyped in the 6442 subjects (1729 epilepsy and 4713 controls). Results of the case-control study showed associations between rs211037 and the risk of SE in the pooled data from all cohorts (T vs. C, p = 3 × 10(-5), and TT vs. CC, p = 2 × 10(-5)) and the risk of partial seizure in the combined data of Malaysia and Hong Kong (both T vs. C and TT vs. CC, p = 2 × 10(-6)). The rs211037-rs210987 and rs2422106-rs211014-rs401750 haplotypes were also associated with susceptibility to SE in Chinese. Meta-analysis of all Asians identified association between rs211037 and FS and SE (T vs. C, p = 4 × 10(-4), and p = 4 × 10(-3), respectively). In conclusion, rs211037 alone may be a risk factor for FS, partial seizure, and SE, and in linkage disequilibrium with rs210987 can contribute to FS and SE in Asians, particularly in Chinese.
    Matched MeSH terms: Epilepsy/genetics*
  2. Sha'ari HM, Haerian BS, Baum L, Tan HJ, Rafia MH, Kwan P, et al.
    Mol Neurobiol, 2016 07;53(5):2869-2877.
    PMID: 25876511 DOI: 10.1007/s12035-015-9150-1
    Epilepsy is a common neurological disease characterized by recurrent unprovoked seizures. Evidence suggested that abnormal activity of brain-derived neurotrophic factor (BDNF) contributes to the pathogenesis of epilepsy. Some previous studies identified association between genetic variants of BDNF and risk of epilepsy. In this study, this association has been examined in the Hong Kong and Malaysian epilepsy cohorts. Genomic DNA of 6047 subjects (1640 patients with epilepsy and 4407 healthy individuals) was genotyped for rs6265, rs11030104, rs7103411, and rs7127507 polymorphisms by using Sequenom MassArray and Illumina HumanHap 610-Quad or 550-Duo BeadChip arrays techniques. Results showed significant association between rs6265 T, rs7103411 C, and rs7127507 T and cryptgenic epilepsy risk (p = 0.00003, p = 0.0002, and p = 0.002, respectively) or between rs6265 and rs7103411 and symptomatic epilepsy risk in Malaysian Indians (TT vs. CC, p = 0.004 and T vs. C, p = 0.0002, respectively) as well as between rs6265 T and risk of cryptogenic epilepsy in Malaysian Chinese (p = 0.005). The Trs6265-Crs7103411-Trs7127507 was significantly associated with cryptogenic epilepsy in Malaysian Indians (p = 0.00005). In conclusion, our results suggest that BDNF polymorphisms might contribute to the risk of epilepsy in Malaysian Indians and Chinese.
    Matched MeSH terms: Epilepsy/genetics*
  3. Lai ST, Tan WY, Wo MC, Lim KS, Ahmad SB, Tan CT
    Seizure, 2019 Oct;71:132-139.
    PMID: 31325820 DOI: 10.1016/j.seizure.2019.07.008
    PURPOSE: The literature on caregiver burden tends to focus on children and teenagers with epilepsy and less on adults. As caregiving is a dynamic, complex process across the trajectories, this study aims to examine the factors associated with caregiving burden in those caring for adults with epilepsy.

    METHOD: This is a cross-sectional, survey-based study in which participants responded to questionnairesregarding perceived burden (ZBI), quality of life (IEQoL), psychological distress (DASS-21), family functioning (FAD) and perceived social support (MSPSS). Additional measures include socio-demographics and clinical characteristics of the care-recipient.

    RESULTS: A total of 111 caregivers participated, of whom 72.1% were females, 55% parents, 59.5% Chinese, 51.4% unemployed and 46.0% with tertiary education.Approximately half (42.3%) reported mild-to-moderate levels of burden (mean ZBI score 29.93, SD 16.09).Furthermore, multiple regression analysisidentified10 predictors of caregiver burden, namely family functioning, weekly caregiving hours, number of caregivers per family, attitude towards epilepsy, family support, caregivers' gender, personal income and as well as care-recipients' age of onset, seizure frequency and ADL dependency (F(10, 85) = 11.37, p 

    Matched MeSH terms: Epilepsy/nursing*
  4. Mohamed Y, Alias NN, Shuaib IL, Tharakan J, Abdullah J, Munawir AH, et al.
    PMID: 17333778
    Advances in neuroimaging techniques, particularly Magnetic Resonance Imaging (MRI), have proved invaluable in detecting structural brain lesions in patients with epilepsy in developed countries. In Malaysia, a few electroencephalography facilities available in rural district hospitals run by trained physician assistants have Internet connections to a government neurological center in Kuala Lumpur. These facilities are more commonly available than MRI machines, which require radiological expertise and helium replacement, which may problematic in Southeast Asian countries where radiologists are found in mainly big cities or towns. We conducted a cross-sectional study over a two year period begining January 2001 on rural patients, correlating EEG reports and MRI images with a clinical diagnosis of epilepsy to set guidelines for which rural patients need to be referred to a hospital with MRI facilities. The patients referred by different hospitals without neurological services were classified as having generalized, partial or unclassified seizures based on the International Classification of Epileptic Seizures proposed by the International League Against Epilepsy (ILAE). The clinical parameters studied were seizure type, seizure frequency, status epilepticus and duration of seizure. EEG reports were reviewed for localized and generalized abnormalities and epileptiform changes. Statistical analysis was performed using logistic regression and area under the curve. The association between clinical and radiological abnormalities was evaluated for sensitivity and specificity. Twenty-six males and 18 females were evaluated. The mean age was 20.7 +/- 13.3 years. Nineteen (43.2%) had generalized seizures, 22 (50.0%) had partial seizures and 3 (6.8%) presented with unclassified seizures. The EEG was abnormal in 30 patients (20 with generalized abnormalities and 10 localized abnormalities). The MRI was abnormal in 17 patients (38.6%); the abnormalities observed were cerebral atrophy (5), hippocampal sclerosis (4), infarct/gliosis (3), cortical dysgenesis (2) and tumors (2). One patient had an arachnoid cyst in the right occipital region. Of the 17 patients with an abnormal MRI, 14 had an abnormal EEG, this difference was not statistically significant. There was no significant associaton between epileptographic changes and MRI findings (p = 0.078). EEG findings were associated with MRI findings (p = 0.004). The association between an abnormal EEG and an abnormal MRI had a specificity of 82.4%, while epileptogenic changes had a specificity of 64.7% in relation to abnormal MRI findings. This meants that those patients in rural hospitals with abnormal EEGs should be referred to a neurology center for further workup and an MRI to detect causes with an epileptic focus.
    Matched MeSH terms: Epilepsy/diagnosis*
  5. Swamy M, Yusof WR, Sirajudeen KN, Mustapha Z, Govindasamy C
    J Physiol Biochem, 2011 Mar;67(1):105-13.
    PMID: 20960085 DOI: 10.1007/s13105-010-0054-2
    To understand their role in epilepsy, the nitric oxide synthetase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS), and total antioxidant status (TAS), were estimated in different regions of brain in rats subjected to experimental epilepsy induced by subcutaneous administration of kainic acid (KA). The short-term (acute) group animals were killed after 2 h and the long term (chronic) group animals were killed after 5 days of single injection of KA (15 mg/kg body weight). After decapitation of rats, the brain regions were separated and in their homogenates, the concentration of NOx, TBARS and TAS and the activities of NOS, AS, AL, arginase and glutamine synthetase were assayed by colorimetric methods. The results of the study demonstrated the increased activity of NOS and formation of NO in acute and chronic groups epilepsy. The activities of AS and AL were increased and indicate the effective recycling of citrulline to arginine. The activity of glutamine synthetase was decreased in acute and chronic groups of epilepsy compared to control group and indicate the modulation of its activity by NO in epilepsy. The activity of arginase was not changed in acute group; however it was decreased in chronic group and may favor increased production of NO in this condition. The concentration TBARS were increased and TAS decreased in acute and chronic groups of epilepsy and supports the oxidative stress in epilepsy.
    Matched MeSH terms: Epilepsy/chemically induced; Epilepsy/metabolism*
  6. Salih MR, Bahari MB, Hassali MA, Shafie AA, Al-Lela OQ, Abd AY, et al.
    J Pharm Pract, 2013 Jun;26(3):192-7.
    PMID: 22797836 DOI: 10.1177/0897190012451926
    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.
    KEYWORDS: Malaysia; epilepsy; neurology; pediatrics; therapeutic drug monitoring
    Study site: Paediatric Neurology Clinic, Hospital Pulau Pinang, Malaysia
    Matched MeSH terms: Epilepsy/drug therapy*
  7. Then SM, Rani ZZ, Raymond AA, Ratnaningrum S, Jamal R
    Asian Pac J Allergy Immunol, 2011 Sep;29(3):290-3.
    PMID: 22053601
    We describe the association of the HLA-B*1502 allele in 27 epilepsy patients (19 Malays, 8 Chinese) treated with carbamazepine (CBZ) at the UKM Medical Center (UKMMC), 6 with CBZ-Steven Johnson Syndrome (CBZ-SJS), 11 with CBZ-induced rash, 2 with suspected phenytoin-induced rash and 8 negative controls. Our study showed that 10 (6 Malay, 4 Chinese) patients were positive for HLA-B*1502. Out of the 10 patients, six were confirmed to have CBZ-SJS (p = 0.0006), while four patients developed a skin rash. However there were 6 Malay patients and 1 Chinese patient that developed a skin rash after CBZ administration who were not positive for the allele, indicating that there might be more that one allele associated with CBZ-induced hypersensitivity. Another 2 patients were suspected of having phenytoin-induced rash, instead of CBZ, and these patients did not have HLA-B*1502. In conclusion, this study confirmed the association of HLA-B*1502 with CBZ-SJS among Malaysian epilepsy patients, however there might be other genes that could be responsible for the CBZ-induced rash.
    Matched MeSH terms: Epilepsy/drug therapy
  8. Yeap LL, Lim KS, Ng CC, Hui-Ping Khor A, Lo YL
    Ther Drug Monit, 2014 Feb;36(1):3-9.
    PMID: 24342894 DOI: 10.1097/FTD.0000000000000024
    The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control. At the same time, the patient was diagnosed with hyperthyroidism and was given carbimazole and propranolol. Hyperthyroidism and the concurrent use of these antihyperthyroid agents may have further slowed down the metabolism of carbamazepine. Therapeutic drug monitoring of carbamazepine was carried out, and a slow carbamazepine clearance of 1.45 L·h⁻¹ per 70 kg was observed. Genotyping of selected genetic variants in CYP3A4, CYP3A5, EPHX1, ABCB1, and ABCC2 revealed that she has CYP3A5*3/*3 and ABCB1 3435-CC genotypes. Both genotypes have been shown to be associated with higher adjusted mean serum carbamazepine concentration in Chinese and Korean patients with epilepsy. Physicians should be vigilant about the risk of adverse effects among patients with a slow carbamazepine clearance, especially in Malays. Simulations of carbamazepine dosing regimen based on the pharmacokinetic parameters of this patient were performed to allow individualization of drug therapy.
    Matched MeSH terms: Epilepsy/drug therapy*
  9. Walker JD, Spiro G, Loewen K, Jacklin K
    J Alzheimers Dis, 2020;78(4):1439-1451.
    PMID: 33185601 DOI: 10.3233/JAD-200704
    BACKGROUND: There remains a lack of information and understanding of the prevalence and incidence of Alzheimer's disease and related dementia in Indigenous populations. Little evidence available suggests that Indigenous peoples may have disproportionately high rates of Alzheimer's disease and related dementia (ADRD).

    OBJECTIVE: Given this information, this study systematically explores what risk factors may be associated with ADRD in Indigenous populations.

    METHODS: A search of all published literature was conducted in October 2016, March 2018, and July 2019 using Medline, Embase, and PsychINFO. Subject headings explored were inclusive of all terms related to Indigenous persons, dementia, and risk. All relevant words, phrases, and combinations were used. To be included in this systematic review, articles had to display an association of a risk factor and ADRD. Only studies that reported a quantifiable measure of risk, involved human subjects, and were published in English were included.

    RESULTS: Of 237 articles originally identified through database searches, 45 were duplicates and 179 did not meet a priori inclusion criteria, resulting in 13 studies eligible for inclusion in this systematic review.

    CONCLUSION: The large number of potentially modifiable risk factors reported relative to non-modifiable risk factors illustrates the importance of socioeconomic context in the pathogenesis of ADRD in Indigenous populations. The tendency to prioritize genetic over social explanations when encountering disproportionately high disease rates in Indigenous populations can distract from modifiable proximal, intermediate, and distal determinants of health.

    Matched MeSH terms: Epilepsy/epidemiology
  10. Sasongko TH, Ismail NF, Nik Mohd Ariff NA, Zabidi-Hussin ZA
    Jpn J Clin Oncol, 2014 Nov;44(11):1130.
    PMID: 25320338 DOI: 10.1093/jjco/hyu157
    Matched MeSH terms: Epilepsy
  11. Tan EH, Yusoff AA, Abdullah JM, Razak SA
    J Pediatr Neurosci, 2012 May;7(2):123-5.
    PMID: 23248692 DOI: 10.4103/1817-1745.102575
    In this report, we describe a 15-year-old Malaysian male patient with a de novo SCN1A mutation who experienced prolonged febrile seizures after his first seizure at 6 months of age. This boy had generalized tonic clonic seizure (GTCS) which occurred with and without fever. Sequencing analysis of voltage-gated sodium channel a1-subunit gene, SCN1A, confirmed a homozygous A to G change at nucleotide 5197 (c.5197A > G) in exon 26 resulting in amino acid substitution of asparagines to aspartate at codon 1733 of sodium channel. The mutation identified in this patient is located in the pore-forming loop of SCN1A and this case report suggests missense mutation in pore-forming loop causes generalized epilepsy with febrile seizure plus (GEFS+) with clinically more severe neurologic phenotype including intellectual disabilities (mental retardation and autism features) and neuropsychiatric disease (anxiety disorder).
    Matched MeSH terms: Epilepsy, Generalized
  12. Chia ZJ, Lim KS, Lee SR, Lai WW, Chan PQ, Ng SJ, et al.
    Epilepsy Behav, 2021 Apr;117:107798.
    PMID: 33582391 DOI: 10.1016/j.yebeh.2021.107798
    BACKGROUND: In epilepsy stigma, certain perceptions are culturally dependent and greatly influence a person's attitudes. Hence, we aimed to explore the perceptions associated with attitudes toward epilepsy in various urban subpopulations.

    METHOD: This is a mixed-method study employing the Public Attitude Toward Epilepsy (PATE) scale as the quantitative measure, followed by a semi-structured interview. The qualitative data were then counted and analyzed concurrently with the quantitative data.

    RESULT: A total of 410 respondents (104 people with epilepsy [PWE]; 104 family members [FM]; 100 medical students [MS]; 102 public [Pb]) aged 37 years (IQR 23-55) were recruited. They were mostly female (57.3%), Chinese (52.0%), and highly educated (63.7%). The attitudes toward epilepsy among medical students are the best, followed by the PWE and their family members, and the worst among the public. The qualitative results revealed 4 main themes, which were "general social values", "epilepsy severity and control", "PWE's abilities", and "harms and burdens to the respondents and others". A two-dimensional perception model was constructed based on these themes, which consisted of general-personal and universal-specific dimensions. Generally, the PWE/FM subgroup focused more on PWE's abilities, whereas the MS/Pb subgroup more on general social values, and harms and burden. In the education aspect, most attitudes were related to the epilepsy severity and PWE's abilities, whereas in employment, the main consideration was the PWE's abilities. Burden to life and concern about inheritance were major considerations in the marital relationship. Those with positive attitudes tend to highlight the importance of general social values, while negative attitudes associated more with epilepsy severity. In general domain, general social values were the main considering factor but in personal domain, most participants will consider epilepsy severity and control, harms and burden to themselves.

    CONCLUSION: The perceptions underlying attitudes toward epilepsy were complex and varied between subpopulations, attitude levels, domains, and aspects of life. (304 words).

    Matched MeSH terms: Epilepsy
  13. Nor Haizura Abd Rani, Fadhli Mustaffa, Chuan Wui Teoh, Flora Li Tze Chong, Nornazirah Azizan, Firdaus Hayati, et al.
    MyJurnal
    Introduction:Gliosarcoma is a rare malignant brain tumor. The clinical presentation is acute with rapid progression of symptoms. Commonly affecting the elderly, it is rare to happen in youngsters. Case description: A 28-year-old radiographer presented to us with two episodes of unprovoked seizure. He denied any medical illnesses, or trauma, fall, motor vehicle accident and fever prior to these attacks. The computed tomography (CT) of brain was normal. He was managed as epilepsy and remained symptom-free for 3 years until the unprovoked seizure recurred. Another CT of brain performed and revealed a right parietal intracranial mass. This finding was supported by magnetic reso-nance imaging scan. The histologic examination showed a biphasic pattern of glial with predominant sarcomatous component giving a diagnosis of gliosarcoma of the brain. He had completed six cycles of adjuvant chemotherapy and was asymptomatic during clinic follow up with no tumor recurrence. Conclusion: Individuals with high risk of radiation exposure particularly radiographer as in our case requires a special attention when it comes to the diagnosis of malignancy. Despite of indolent clinical presentations, a close monitoring is needed to avoid mismanagement and subsequent morbidities.
    Matched MeSH terms: Epilepsy
  14. Tan, Kenny, Luen, Leong Wei, Ong, Yi Ping, Khai, H’ng Kee, Tan, Li May, Siti Nur Fatihah Abd Rahman, et al.
    MyJurnal
    Phenytoin follows Michaelis-Menten, a non-linear pharmacokinetics that occurs when drug molecules saturates the enzymes ability to metabolise the drug. When this occurs, steady state phenytoin serum concentration increases in a disproportionate manner after a dosage increase. General population data are usually used for the phenytoin dose calculation. However, many studies show that population pharmacokinetic parameters of phenytoin have high variations. Thus, use of specific local pharmacokinetic parameters for each population group in estimating individualised phenytoin dose can reduce phenytoin toxicity cases. This prospective, observational study was conducted to estimate a local Vmax and Km of phenytoin for adult epileptic patients in neurological ward and clinic at Hospital Pulau Pinang, Malaysia. All therapeutic drug monitoring of oral capsule phenytoin were studied in a three-month data collection period. Out of the 17 subjects in our study, there are 13 male subjects (76.47%) and 4 female subjects (23.53%). A total 11 Malay subjects (64.71%), 4 Chinese subjects (23.53%) and 2 Indian subjects (11.76%) were included. Median Vmax and Km were found to be 8.25 mg/kg/day and 3.80 mg/l. Male subjects have a higher Vmax (8.30 mg/kg/day) but a lower Km (3.3 mg/l). Chinese population has the highest Vmax (8.80 mg/kg/day). For Km, Indian population is the highest, with a value of 5.5 mg/l. From our study, gender does not correlate with Vmax and Km of phenytoin (p-value > 0.05). Ethnicity was also found to have no association with Vmax and Km (p-value > 0.05). Local Vmax (8.25 mg/kg/day) is higher and Km (3.8 mg/l) is lower when compared with standard Vmax (7 mg/kg/day) and Km (4 mg/l) obtained from Caucasian population.
    Matched MeSH terms: Epilepsy
  15. Yousuf, R.M., Shahar, M.A., Marzuki, O.A., Azarisman, S.M.S., Rosle, C., Tin, M.H.
    MyJurnal
    Introduction: Epilepsy remains a stigmatised disease across geographical and temporal boundaries. Very little is known about epileptic stigma (ES) in cross-cultural settings. The aim of this study was to assess the prevalence of perceived stigma and factors associated with it, among patients with epilepsy (PWE) at a tertiary care referral hospital in East Coast of Malaysia. Methods: A cross sectional survey among 132 consenting PWE using pre-tested, semi-structured questionnaire in Malay/English language to assess their knowledge, attitude and practices (KAPs). Results: Among 132 respondents, 51.5% were male and 48.5 % were female. Their age ranged from 14 to 70 years (mean=31.6±13.41). Majority (53.8%) of them were aged 30 years or younger. The median number of years they had epilepsy was 8.0 (IQR 4.0-18.8) years and average duration of seizure prior to seeking medical attention was 1.0 (IQR 0.3 - 4.5) year. Most of them (90.9%) did not know the cause of epilepsy; however nearly all (91.7%) believed that it was a disease of the
    brain. Higher education level respondents possessed significantly higher KAP scores compared to lower education level respondents (p
    Matched MeSH terms: Epilepsy
  16. Akyuz E, Doganyigit Z, Paudel YN, Koklu B, Kaymak E, Villa C, et al.
    Life (Basel), 2021 Mar 26;11(4).
    PMID: 33810231 DOI: 10.3390/life11040276
    Epilepsy is characterized by an imbalance in neurotransmitter activity; an increased excitatory to an inhibitory activity. Acetylcholine (ACh), serotonin, and norepinephrine (NE) may modulate neural activity via several mechanisms, mainly through its receptors/transporter activity and alterations in the extracellular potassium (K+) concentration via K+ ion channels. Seizures may disrupt the regulation of inwardly rectifying K+ (Kir) channels and alter the receptor/transporter activity. However, there are limited data present on the immunoreactivity pattern of these neurotransmitter receptors/transporters and K+ channels in chronic models of epilepsy, which therefore was the aim of this study. Changes in the immunoreactivity of epileptogenesis-related neurotransmitter receptors/transporters (M2, 5-HT2B, and NE transporter) as well as Kir channels (Kir3.1 and Kir6.2) were determined in the cortex, hippocampus and medulla of adult Wistar rats by utilizing a Pentylenetetrazol (PTZ)-kindling chronic epilepsy model. Increased immunoreactivity of the NE transporter, M2, and 5-HT2B receptors was witnessed in the cortex and medulla. While the immunoreactivity of the 5-HT2B receptor was found increased in the cortex and medulla, it was decreased in the hippocampus, with no changes observed in the M2 receptor in this region. Kir3.1 and Kir6.2 staining showed increase immunoreactivity in the cerebral cortex, but channel contrasting findings in the hippocampus and medulla. Our results suggest that seizure kindling may result in significant changes in the neurotransmitter system which may contribute or propagate to future epileptogenesis, brain damage and potentially towards sudden unexpected death in epilepsy (SUDEP). Further studies on the pathogenic role of these changes in neurotransmitter receptors/transporters and K+ channel immunoreactivity may identify newer possible targets to treat seizures or prevent epilepsy-related comorbidities.
    Matched MeSH terms: Epilepsy
  17. Paudel YN, Angelopoulou E, Piperi C, Gnatkovsky V, Othman I, Shaikh MF
    Curr Neuropharmacol, 2020;18(11):1126-1137.
    PMID: 32310049 DOI: 10.2174/1570159X18666200420125017
    Epilepsy is a devastating neurological condition characterized by long-term tendency to generate unprovoked seizures, affecting around 1-2 % of the population worldwide. Epilepsy is a serious health concern which often associates with other neurobehavioral comorbidities that further worsen disease conditions. Despite tremendous research, the mainstream anti-epileptic drugs (AEDs) exert only symptomatic relief leading to 30% of untreatable patients. This reflects the complexity of the disease pathogenesis and urges the precise understanding of underlying mechanisms in order to explore novel therapeutic strategies that might alter the disease progression as well as minimize the epilepsy-associated comorbidities. Unfortunately, the development of novel AEDs might be a difficult process engaging huge funds, tremendous scientific efforts and stringent regulatory compliance with a possible chance of end-stage drug failure. Hence, an alternate strategy is drug repurposing, where anti-epileptic effects are elicited from drugs that are already used to treat non-epileptic disorders. Herein, we provide evidence of the anti-epileptic effects of Fingolimod (FTY720), a modulator of sphingosine-1-phosphate (S1P) receptor, USFDA approved already for Relapsing-Remitting Multiple Sclerosis (RRMS). Emerging experimental findings suggest that Fingolimod treatment exerts disease-modifying anti-epileptic effects based on its anti-neuroinflammatory properties, potent neuroprotection, anti-gliotic effects, myelin protection, reduction of mTOR signaling pathway and activation of microglia and astrocytes. We further discuss the underlying molecular crosstalk associated with the anti-epileptic effects of Fingolimod and provide evidence for repurposing Fingolimod to overcome the limitations of current AEDs.
    Matched MeSH terms: Epilepsy
  18. Teh KX, Henien NPB, Wong LS, Wong ZKH, Raja Ismail RZ, Achok HN, et al.
    PLoS One, 2020;15(7):e0235674.
    PMID: 32649723 DOI: 10.1371/journal.pone.0235674
    BACKGROUND: Non-adherence to anti-seizure medication (ASM) therapy is an important contributing factor to the higher mortality rate and treatment failure of epilepsy. This study aimed to determine the rate and factors associated with non-adherence to ASM therapy through the WHO five dimensions of medication adherence framework.

    METHODS: We conducted a cross-sectional study at an outpatient Neurology Clinic of a tertiary government hospital in Malaysia. Between March and July 2019, we identified 217 patients with a confirmed diagnosis of epilepsy, receiving oral ASM therapy and able to administer their medications. We performed a semi-structured interview to gather information on sociodemographic background, clinical and medication history, and perceptions on healthcare services. Adherence to ASM therapy was evaluated using the Medication Compliance Questionnaire (MCQ). Patient's illness perception was assessed by the Brief Illness Perception Questionnaire (B-IPQ).

    RESULTS: 208 patients participated in this study. The median age of the study participants was 35 years (IQR 26-44). 58.2% were females and majority, 55.8%, were from the Malay ethnic group. Based on the MCQ scoring, 89 patients (42.8%) were non-adherent. Multiple logistic regression demonstrated that being employed or students (adjusted odds ratio [aOR] 2.26, 95%CI: 1.19-4.29 p = 0.012) and having an average or below average perceived access to pharmacy services (aOR 2.94, 95%CI: 1.38-6.24, p = 0.005) were significant contributors to non-adherence.

    CONCLUSION: Being employed or students and having an average or below average perceived access to pharmacy services were associated with ASM non-adherence Efforts to improve ASM adherence should adopt a comprehensive approach considering the success of adherence is contingent on the interrelationship of multiple dimensions.

    Matched MeSH terms: Epilepsy
  19. Then, Sue-Mian, Azman Ali Raymond
    MyJurnal
    Epilepsy is a common neurological disorder affecting approximately 50 million people worldwide. Antiepileptic drugs (AEDs) are commonly used to treat the disease depending, mainlyon the type of seizure. However, the useof AEDs mayalso lead to cutaneous adverse drug reactions (cADR) such as toxic epidermal necrolysis (TEN), Stevens-Johnsonsyndrome (SJS), exfoliative dermatitis (ED) and drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), which are unwanted comorbidities in epilepsy. It was first discoveredthat the HLA-B*15:02 allele was strongly associatedwith carbamazepine(CBZ)-induced SJS/TEN amongHan Chinese and this ledto the discovery of other HLAallelesand cytochrome P450 (CYP) genes that were significantly associatedwith various AED-inducedcADRsacross variouspopulations. This mini-reviewis an update on the latest findings ofthe involvement of various HLA alleles and CYP alleles in cADRs caused by CBZ, phenytoin (PHT), oxcarbazepine (OXC) and lamotrigine(LTG) in different case-control studies around the world. From our review, we found that CBZ-and PHT-induced cADRsweremore commonly reportedthan the other AEDs.Therefore,there were morerobust pharmacogenetics studies related to these AEDs. OXC-and LTG-induced cADRswereless commonly reported,and somore studies are needed to validate the reported association of the newer reported HLA alleles with theseAEDs. It is also importantto considerthe allelic frequency within a given population before concludingthe use of thesealleles as genetic markers to prevent AED-induced cADR. Overall, the current body of research pointto a combination of alleles as a better pharmacogenetic marker comparedto the use of a single gene as a genetic marker for AED-induced cADR.
    Matched MeSH terms: Epilepsy
  20. Ayipo YO, Mordi MN, Mustapha M, Damodaran T
    Eur J Pharmacol, 2021 Feb 15;893:173837.
    PMID: 33359647 DOI: 10.1016/j.ejphar.2020.173837
    Neuropsychiatric disorders are diseases of the central nervous system (CNS) which are characterised by complex pathomechanisms that including homeostatic failure, malfunction, atrophy, pathology remodelling and reactivity anomaly of the neuronal system where treatment options remain challenging. β-Carboline (βC) alkaloids are scaffolds of structurally diverse tricyclic pyrido[3,4-b]indole alkaloid with vast occurrence in nature. Their unique structural features which favour interactions with enzymes and protein receptor targets account for their potent neuropharmacological properties. However, our current understanding of their biological mechanisms for these beneficial effects, especially for neuropsychiatric disorders is sparse. Therefore, we present a comprehensive review of the scientific progress in the last two decades on the prospective pharmacology and physiology of the βC alkaloids in the treatment of some neuropsychiatric conditions such as depression, anxiety, Alzheimer's disease, Parkinson's disease, brain tumour, essential tremor, epilepsy and seizure, licking behaviour, dystonia, agnosia, spasm, positive ingestive response as demonstrated in non-clinical models. The current evidence supports that βC alkaloids offer potential therapeutic agents against most of these disorders and amenable for further drug design.
    Matched MeSH terms: Epilepsy
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