How many more seizure remission can we achieve with epilepsy surgeries in a general epilepsy population?

@#Background & Objective: We knew that 63.6% of the epilepsy population can be seizure free with the use of anti-epileptic drugs (AED), but are unsure how many more with epilepsy surgeries. We aimed to determine the additional remission rate achieved with epilepsy surgeries in addition to AED. Methods: We analysed the seizure outcome among epilepsy patients seen retrospectively over oneyear period in University Malaya Medical Centre, Malaysia, which provides all levels (level 1-4) of epilepsy cares, in response to anti-epileptic drug (AED) and epilepsy surgeries. The seizure outcome was categorised into remission and drug-resistant, according to ILAE definition of drug resistance. Results: There were 909 patients seen during the study period, majority with focal epilepsy (63.3%), and Chinese (37.4%). Of those, 409 (45.0%) were in seizure remission, 238 (26.2%) had drug-resistant epilepsy and 262 (28.8%) uncertain. Only the remission and drug-resistant groups (N=647) were included in subsequent analysis. The mean age of onset in drug-resistant group was 14.8±12.3 years old, which was significantly younger than the remission group (20.8±16.8, p<0.05). There were 40 (54.8%) patients who underwent resective epilepsy surgeries (10 were lesion-negative cases). The seizure freedom rate with epilepsy surgery was 60.0% (n=24). Overall, a total of 59.5% of patients were in seizure remission with AED, with an additional 3.7% with epilepsy surgery. Conclusion: There were 3.7% of epilepsy patients achieved seizure remission with epilepsy surgeries in a general epilepsy cohort in addition to AEDs.

Epilepsy in Southeast Asia, how much have we closed the management gap in past two decades?

@#The last review on epilepsy in Southeast Asian (SEA) countries was reported in 1997. This review aimed to update the understanding of epilepsy management in this region over the past 23 years. There has been significant increase in the epidemiological studies which reported a prevalence of 4.3-7.7 per 1,000 populations in this region. Reversible aetiologies of epilepsy such as head injury, birth trauma, cerebrovascular disease, and intracranial infections (neurocysticercosis or meningoencephalitis) are still prevalent, with a surge in autoimmune encephalitis. There was a surge in genetic studies which suggest ethnic variation. Treatment gap is still high especially in the rural and less developed areas, and the availability and affordability of newer anti-epileptic drugs (AEDs) is still a major challenge in SEA. Alternative medicine is a common practice but varies among different ethnic groups. AEDs hypersensitivity especially on the association between HLA-B*1502 and carbamazepine-related severe cutaneous reaction had been extensively studied and proven in nearly all SEA countries. However, HLA-B*1502 screening is not widely available in SEA and the cost-effectiveness of the screening is questionable. Stigma and its psychosocial consequences are still a major concern despite enormous efforts to study the public attitudes towards epilepsy and change of epilepsy naming in a few countries. The number and complexity of epilepsy surgery are progressing, but it is still under-utilized in many SEA countries, related to cost, cultural perception and lack of facilities. More resources should also be channelled in training adequate number of epileptologists who can spearhead epilepsy care around the region, as well as public education and research in epilepsy. In conclusion, there is an increase in epilepsy research in this region, gradual increase in trained neurologists and facilities, and efforts to reduce the knowledge and treatment gap, but the epilepsy management gap is still a battle to fight.

Epilepsy research output in Southeast Asian countries: A systematic review

@#Objective: Epilepsy is understudied in Southeast Asian (SEA) countries. This systematic review aimed to determine the number of epilepsy publications performed in SEA and identify factors associated with research output in this region. Methods: Existing academic journal article searches were performed using PubMed, Scopus, Medline and Web of Science till 1st March 2018. Openness is determined by the use of English in medical school and overseas epilepsy fellowship. Results: A total of 702 epilepsy articles have been published in the last 50 years in the SEA region, with an exponential increase of publications after the year 1997, with the cumulative number doubled every 5 years. Only half (54%) were published in the journals with impact factor (IF) ≥1. Majority of the publications (48.2%) employed cross sectional design, followed by animal or laboratory studies (21.1%), with few randomized controlled trials and systematic review/meta-analysis studies (1.7% and 2.3%, respectively). Half (52.9%) of the publications were clinical studies. The number of papers with IF≥1 correlated positively with openness to international standard (R=0.720, p<0.05), and knowledge-based economy (p=0.01). Conclusion: Epilepsy research output in SEA is low in quantity and quality. The output is mainly related to the type of economy (knowledge-based or non-knowledge-based) and openness to international ideas and standard.

Disseminated Takayasu arteritis with neurovascular small and medium vessel involvement

@#Takayasu arteritis is a rare granulomatous vasculitis that is commonly classified as a large vessel disease. Small and medium vessel involvement are extremely rare, with only a few case reports describing neurovascular, ocular and cutaneous involvement. We describe a 21 year old Malaysian woman with pre-existing Takayasu arteritis confined to the large vessels, presenting one year later to our centre with status epilepticus. Extensive radiologic studies revealed diffuse encephalopathic changes and multifocal neurovascular involvement, with the vasculitis progressing to encompass the large, medium and small vessels. The patient was treated with high dose steroid therapy and discharged well with long term steroid and immunosuppressive therapy. Follow up MRI with vessel wall imaging sequence (VW-MR) and arterial spin labelling (ASL) perfusion imaging demonstrated intra and extracranial vessel wall inflammation, with generalized reduction in left sided cerebral blood flow. This case demonstrates that Takayasu arteritis is not exclusively a large vessel vasculitis, and that small and medium vessel involvement does not preclude its diagnosis.

Phenytoin toxicity presenting with acute visual loss and acute delirium, a case report

@#Phenytoin is a widely prescribed antiepileptic agent for both focal and generalized seizure. We report a case of a 20-year-old man with focal epilepsy presented with acute bilateral visual loss, and delirium. His random phenytoin serum concentration on admission was 43.6 mg/L, well above the recommended therapeutic range of 10-20 mg/L. Extensive investigations have ruled out other vascular or demyelinating causes. His visual symptoms completely resolved after discontinuing phenytoin for 84 hours. This case shows that acute phenytoin toxicity can result in reversible visual failure.

Level 4 comprehensive epilepsy program in Malaysia, a resource-limited country

Background and Objective: There is a great challenge to establish a level 4 epilepsy care offeringcomplete evaluation for epilepsy surgery including invasive monitoring in a resource-limited country.This study aimed to report the setup of a level 4 comprehensive epilepsy program in Malaysia and theoutcome of epilepsy surgery over the past 4 years. Methods: This is a retrospective study analyzingcases with intractable epilepsy in a comprehensive epilepsy program in University Malaya MedicalCenter (UMMC), Kuala Lumpur, from January 2012 to August 2016. Results: A total of 92 caseshad comprehensive epilepsy evaluation from January 2012 till August 2016. The mean age was 35.57years old (range 15-59) and 54 (58.7%) were male. There were 17 cases having epilepsy surgeryafter stage-1 evaluation. Eleven cases had mesial temporal sclerosis and 81% achieved Engel classI surgical outcome. Six cases had lesionectomy and 60% had Engel class I outcome. A total of 16surgeries were performed after stage-2 evaluation, including invasive EEG monitoring in 9 cases.Among those with surgery performed more than 12 months from the time of data collection, 5/10(50%) achieved Engel I outcome, whereas 2 (20%) had worthwhile improvement (Engel class III)with 75% and 90% seizure reduction.Conclusion: Level 4 epilepsy care has an important role and is possible with joint multidisciplinaryeffort in a middle-income country like Malaysia despite resource limitation.

HLA-B*1502 and carbamazepine induced StevensJohnson syndrome/toxic epidermal necrolysis in Indonesia

Background & Objective: Association between HLA-B*1502 and carbamazepine-induced StevenJohnson syndrome/toxic epidermal necrolysis (CBZ-SJS/TEN) was reported in many Southeast Asian populations but not in Indonesian. The purpose of this study was to evaluate the association between HLA-B*1502 andCBZ-SJS/TEN in an Indonesian population. Methods: Patients with history of CBZ-SJS/TEN are recruited as cases and those who tolerated CBZ as controls. HLA-B typing was performed. Results: We recruited 14 cases with CBZ-SJS/TEN and 53 controls. Positive HLA-B*1502 was found in 8 (57.1%) cases and 14 (26.4%) controls (OR 3.7, 95% CI 1.09-12.61, p=0.035). Conclusion: HLA-B*1502 is associated with CBZ-SJS/TEN patients in Indonesian.

Bilateral thalamic internal medullary lamina involvement in a case of dengue encephalitis

There are 50-100 million dengue infections each year, but dengue encephalitis is relatively uncommon. The aetiology of neuronal injury is proposed to be due to direct viral neurotropism or host immune response-mediated inflammation causing neuronal damage. We report a case of severe dengue encephalitis, presenting during the acute viraemic phase of the disease. This was associated with inflammation and haemorrhage of the internal medullary lamina of both thalami which, to our knowledge, has not yet been reported in other infections of the central nervous system.

Validity and reliability of the Chinese parent proxy and child self-report health related quality of life measure for children with epilepsy (CHEQOL-25) in Malaysia

Objective: To determine the validity and reliability of the Chinese parent proxy and child self-report health related quality of life measure for children with epilepsy (CHEQOL-25) in Malaysia. Methods: Face and content validity of the Chinese parent proxy and child self-report CHEQOL-25 was verified by an expert panel, and piloted in five children with epilepsy (CWE). The Chinese CHEQOL-25 was then administered to 40 parent proxies and their CWE (aged 8-18 years), from two tertiary hospitals, at baseline and 2 weeks later. Results: Forty parents and their CWE were recruited. Cronbach’s alpha for each subscale ranged from 0.56-0.83. At test-retest, the interclass correlation for all items ranged from 0.68-0.97. Items 8 and 25 were removed as their corrected item-total correlation values were <0.3. Epilepsy severity, the number of anti-epileptic drugs taken daily, number of close friends and number of time spent with friends were found to be associated with the parent proxy CHEQOL-25 score. Duration of epilepsy, child’s cognitive ability, number of close friends and number of time spent with friends were associated with child self-report CHEQOL-25. The parent proxy and the child selfreport showed high to fair agreement on the “interpersonal/social” [Intraclass correlation coefficient (ICC)=0.670, p<0.001] and “epilepsy secrecy” subscale (ICC=0.417, p=0.048). Conclusions: Our small study found that the Chinese CHEQOL-25 was a valid and reliable questionnaire to assess the quality of life of children with epilepsy from the parent prospective and child self-report when items 8 and 25 were removed.

Efficacy of repetitive transcranial magnetic stimulation on refractory epilepsy in Malaysia

Background & Objective: Modulation of cortical excitability by low frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic use in epilepsy. This study aimed to evaluate the efficacy of low-frequency rTMS on refractory epilepsy in a group of Malaysian subjects. Methods: Nine patients with refractory epilepsy completed the study. All patients received 10 sessions of 1Hz rTMS (1000 pulses per session) at 90% of resting motor threshold. Outcome measures included seizure frequency, Symptom Checklist-90 (SCL-90), Beck Depression Inventory II (BDI II) and Quality of Life in Epilepsy-31 (QOLIE-31). Responders were defined as having ≥ 50% seizure reduction. Results: The mean age was 33.8 years (SD 11.7), with 4 male. Three patients had mesial temporal sclerosis (MTS); 4 with focal cortical dysplasia (FCD) and two lesion-negative. Three patients achieved >50% seizure reduction at 8 weeks post-treatment, with 2 of them had improvement in the number of IED. All of the responders had FCD. The responders were younger (mean 24.7 vs. 38.3 years old), had shorter duration of illness (mean 15.7 vs. 30.5 years) and had less frequent seizure frequency prior to treatment (mean 5.5 vs. 10.8 attacks per week), as compared to the non-responders. Six patients had improvement in BDI-II scores, two in QOLIE-31 and four in SCL-90 post treatment, irrespective of seizure control. The mean scores in BDI-II improved significantly with treatment (p<0.01). Conclusion: rTMS is a potentially promising treatment for epilepsy, esp

Spontaneous remission without progression to limbic encephalitis in a patient with LGi1 seropositive faciobrachial dystonic seizure

Faciobrachial dystonic seizures are pathognomonic of leucine-rich glioma inactivated-1 (LGi1) antibody, non-paraneoplastic limbic encephalitis. Faciobrachial dystonic seizures usually precede limbic encephalitis by about a month. It is unknown whether, if untreated, faciobrachial dystonic seizures inevitably progress to limbic encephalitis. We present an LGi1 seropositive patient with a year’s history of faciobrachial dystonic seizures, who achieved remission spontaneously without immunotherapy or antiepileptic drug treatment, and did not develop evidence of limbic encephalitis over a three-year follow-up.

EEG is sensitive in early diagnosis of anti NMDAR encephalitis and useful in monitoring disease progress

Background& Objective: Investigation modalities, such as MRI and CSF examination, are neither sensitive nor specific in the early phase of anti-NMDAR encephalitis. Nuclear imaging may be useful to monitor the response to treatment but limited by the availability.We aimed to determine the role of EEG as a tool for early diagnosis as well as a tool to assess disease progression and response to treatment. Methods: A total of 99 EEGsdone in 16 patients diagnosed with anti-NMDAR encephalitis throughout the course of illness, were reviewed retrospectively. The EEG changes were correlated with the clinical presentations and response to treatment. Sixteen EEGs of patients with schizophrenia and mood disorder, and 10 EEGs of patients with infective encephalitis were included as control. Results: EEGs performed during the psychiatric and cognitive dysfunctionphase in patient with anti-NMDAR encephalitis, showed diffuse background slowing in the delta-theta range in all the patients. Serial EEGs showed that the dominant background frequency improved with improvement in cognitive status. Nine patients had complete recovery with normalisation of the EEG abnormalities. Eight patients had their typical clinical seizure recorded during EEG monitoring, but only 2 (25.0%) with EEG correlation. Ten patients had status epilepticus (62.5%), 5 had EEG recorded during their status epilepticus, of which only one with EEG correlation (20.0%). Eleven patients had asymmetric background (68.8%), but only 1 has correlation with focal changes in the MRI brain (9.1%). Even though the EEGs of patients with infective encephalitis also showed background slowing, their CSF analysis was supportive of an infective cause. EEGs of patients with established psychiatric disorder were within normal limits. Conclusion: EEG abnormality has a good correlation with the degree of psychiatric and cognitive dysfunction in patient with anti-NMDAR encephalitis, and is useful in early diagnosis, monitoring the progress and the response to treatment. However, it has poor correlation with clinical seizures.

Epilepsy stigma in Asia: the meaning and impact of stigma

Stigma is conceptually broad and culturally variable. Understanding stigma from the conceptual theories, culturally application based on the word stigma in other languages, the definition of stigma and its synonyms, as well as the medical implications in other stigmatized disease such as AIDS, will help us to understand the complexity of stigma in epilepsy. This review investigated the meaning and types of stigma from different perspectives, leading to staging stigma into 5 levels, i.e. social identity, stereotype, prejudice, discrimination and social disability. In addition to the conventional categorization of stigma into social, felt, self-perceived or internalized stigma, new categories of stigma i.e. personal and general attitudes towards epilepsy based on a newly developed Public Attitudes Toward Epilepsy (PATE) scale was introduced. Courtesy stigma was further elaborated in related to Asian culture. Based on well-established and recently developed theories, the causation and impact of epilepsy stigma was discussed in an Asian context, especially from the aspects of language and society values which are culturally specific. Integrating these theories of causation, illness and stereotype perceptions were proposed to be the mediating mechanism of stigma, which led to the development of a practical and multi-dimensional stigmatization model, aiming to guide, widen and deepen the scope of future stigma research in epilepsy. Using the established model, together with review of related studies, research priorities in epilepsy stigma research especially in Asia focusing on five aspects, i.e. expanding population studies especially on significant others, understanding stigma from personal attitude perspective, investigating the cultural and social causation of stigma, and the impacts of stigma on patients as well as the family members, were proposed.

Chinese Public Attitudes Toward Epilepsy (PATE) scale: translation and psychometric evaluation

Introduction: None of the quantitative scale for public attitudes toward epilepsy was translated to Chinese language. This study aimed to translate and test the validity and reliability of a Chinese version of the Public Attitudes Toward Epilepsy (PATE) scale. Methods: The translation was performed according to standard principles and tested in 140 Chinese-speaking adults aged more than 18 years for psychometric validation. Results: The items in each domain had similar standard deviations (equal item variance), ranged from 0.85-0.95 in personal domain and 0.75-1.04 in general domain. The correlation between an item and its domain was 0.4 and above for all, and higher than the correlation with the other domain. Multitrait analysis showed the Chinese PATE had a similar variance, floor and ceiling effects, and relative relationship between the domains, as the original PATE. The Chinese PATE scale showed a similar correlation with almost all demographic variable except age. Item means were generally clustered in the factor analysis as hypothesized. The Cronbach’s α values was within acceptable range (0.773) in the personal domain and satisfactory range (0.693) in the general domain. Conclusion: The Chinese PATE scale is a validated and reliable translated version in measuring the public attitudes toward epilepsy.

Only certain aspects of knowledge have impact on attitudes toward epilepsy

Introduction: None of the identified studies employed quantitative scales correlating the knowledge and attitudes toward epilepsy. Method: This study aimed to study the relationship between the knowledge and attitudes toward epilepsy, using the Epilepsy Knowledge Questionnaire (EKQ) and the Public Attitudes Toward Epilepsy (PATE) scale. Results: A total of 279 publics with a mean age of 36.6±14.7 years (ranged from 15-77 years), 50.8% female with majority (63.0%) Chinese, and 49.5% with tertiary education level, were recruited. The mean score of epilepsy knowledge questionnaire (EKQ) was 21.05±3.92 (95% CI: 20.57-21.48). Higher score in EKQ was associated with higher education level (p<0.01). The total score in the EKQ correlated negatively with the mean scores in the PATE scale, as well as the mean scores in both the personal domain and general domains in the PATE scale (p<0.05). Only 8 out of 34 items in EKQ were associated significantly with the mean scores in the personal domain, and 4 other items were with the general domain of the PATE scale. Conclusion: This study showed that although the overall knowledge in epilepsy is significantly associated with better attitudes toward epilepsy, only certain aspects of knowledge in the scale contributed to this association.

Name of epilepsy, does it matter?

Names of epilepsy may refl ect misconception and contribute to stigma in epilepsy. Epilepsy in Chinese (dian xian, madness; yang dian feng, goat madness) is associated with insanity and animals. Because of the infl uence of Traditional Chinese Medicine, the names of epilepsy in certain East and Southeast Asian languages also convey the image of insanity and associated with animals. In the case of Malay who are mainly Muslim, it is also religiously unclean (gila babi, mad pig disease), contributing to stigma of the epilepsy patients. Of the East and South East Asian languages, epilepsy in Chinese, Japanese, Korean, Malay, Lao, Thai, Burmese, and Khmer (Cambodia) has the connotation of madness. The names of epilepsy have been replaced by a neutral terminology in Malay in Malaysia, and recently also for Chinese in Hong Kong, and Korean in South Korea.

Attitudes toward epilepsy, a systematic review

Surveys about attitudes towards those with epilepsy have been performed since 1949, in order to understand the social stigma toward epilepsy. This review aims to demonstrate the variation in public attitudes towards epilepsy and its associated factors, with a critical review of the methodology used to examine attitudes towards epilepsy. There was marked variation of attitudes between Western and non-Western populations, and these attitudes were positively correlated with the standard of living. Besides the general public, studies were also performed within specifi c groups, particularly teachers and students. However absence of a standardized questionnaire makes direct comparison diffi cult. A few quantitative methods were developed but these were limited by cultural variations and thus lack of global acceptance. Short-term intervention studies demonstrate an improvement of attitude with knowledge. Nonetheless, the cultural and social reasons underlying the attitudes, and how this affects the life of people with epilepsy, are understudied. Therefore, surveys on attitudes should continue to be carried out, particularly in populations prone to have negative attitudes with emphasis on underlying reasons, and such progress should be monitored longitudinally. Attitudes of people such as parents, teachers, school counselors, health care professionals, and employers, which have a direct impact on people with epilepsy, should be more extensively studied.

Variability of plantar response in normal population

Background: There is lack of normality data in the literature on the plantar response. Objective: To determine the variability of plantar response in normal population and factors that might contribute to the variability. Methods: We conducted a study of plantar response in healthy subjects aged 19-21 in two phases. First phase was plantar examination with hard strike. Subjects with big toe extension in the fi rst phase were re-examined with light and hard strike in the second phase. Results: 100 subjects recruited in fi rst phase, 19 subjects in second phase. Out of 600 attempts (3 attempts for each foot) with hard strike, responses of the big toe were fl exion (48.3%), extension (11.3%), no movement (39.8%); other toes were fl exion (55.0%), extension (13.0%), no movement (32.0%); ankle was dorsifl exion (30.8%), no movement (59.3%); knee were fl exion (15.7%), no movement (84.3%); hip were fl exion (15.2%), no movement (84.8%). Of those with big toe extension, signifi cantly less had persistent big toe extension with light strike. More (41%) among those with extensor big toe has withdrawal response (with fl exion of the hip and knee) as compared to those with fl exor big toe (18.5%, p<0.05). Interfoot asymmetry was seen in 27% (kappa 0.54). Plantar responses of sequential strikes were mostly consistent, with only 3.5% inter-attempt variability. Conclusion: Plantar response with extensor great toe is seen in about 10% of normal adults, less with lighter strike. Withdrawal response can be a partial explanation to the big toe extensor response in normal adults.

Sports and safety in epilepsy

Sport is important not only in normal healthy populations, but also in persons with medical illness, physical or mental disabilities. Active participation in sports is benefi cial physically and psychologically. The main concern in sports for persons with epilepsy is safety. This results in sedentary lifestyles, overprotective attitudes of caregivers and friends. Despite the benefi ts of sports, with the various reassuring studies showing non-signifi cant impact of sports in seizures frequency, physiological changes, EEG, and physical injury, people with epilepsy continue to be less active in sports. This is related to various barriers in sports include epilepsy-specifi c fear, personal barriers, social barrier. Understanding and overcoming these barriers is the key in promoting sports among people with epilepsy.

Traumatic vertebral artery dissection mimicking central pontine myelinolysis: A case report

A 27 year-old Chinese man, involved in a motor vehicle accident, presented with rapidly progressive pseudobulbar palsy and spastic tetraplegia. Magnetic resonance imaging (MRI) of the brain showed central pontine T2 hyperintensity with an unaffected outer rim, consistent with central pontine myelinolysis. There was no hyponatraemia before MRI and he was neither an alcoholic nor malnourished. Cerebral angiogram confi rmed the diagnosis of right vertebral artery dissection. Vertebral artery dissection should be considered in a case with imaging suggestive of central pontine myelinolysis.