A quality of care assessment for women of childbearing potential with epilepsy in Bhutan: An observational study.

BACKGROUND & OBJECTIVE: In lower-middle income countries such as Bhutan, the treatment gap for epilepsy is over 50% as compared to a treatment gap of less than 10% in high-income countries. We aim to analyze the quality of epilepsy care for women of childbearing potential in Bhutan using the Quality Indicators in Epilepsy Treatment (QUIET) tool, and to assess the usefulness of the tool's section for women with active epilepsy (WWE) in the Bhutanese setting. METHODS: A prospective convenience cohort was enrolled in Thimphu, Paro, Punakha, and Wangdue, Kingdom of Bhutan, in 2022. Bhutanese women of childbearing potential at the time of enrollment (18-44 years old) were evaluated for the diagnosis of active epilepsy and underwent a structured survey-based interview with Bhutanese staff. Participants were surveyed on their epilepsy, pregnancy, and antiseizure medicine (ASM) histories. The clinical history and quality of epilepsy care of adult WWE were assessed using a section of the QUIET tool for women, an instrument originally developed by the U.S. Department of Veterans Affairs to analyze the quality of epilepsy care for American adults. RESULTS: There were 82 Bhutanese WWE of childbearing potential, with mean age of 30.6 years at enrollment (range 18-44, standard deviation (SD) 6.6) and mean age of 20.3 years at epilepsy diagnosis (range 3-40, SD 8.0)). 39 % (n = 32) had a high school or above level of education, and 42 % (n = 34) were employed. 35 % (n = 29) reported a seizure within the prior week, and 88 % (n = 72) reported a seizure within the prior year. 49 % (n = 40) of participants experienced > 100 lifetime seizures. All but one participant took antiseizure medications (ASMs). At enrollment, participants presently took no (n = 1), one (n = 3), two (n = 37), three (n = 25), four (n = 11), or over five (n = 5) ASMs. The most common ASMs taken were levetiracetam (n = 40), phenytoin (n = 27), carbamazepine (n = 23), phenobarbital (n = 22), and sodium valproate (n = 20). 61 % of all WWE took folic acid. Of the 40 previously pregnant WWE, eight (20 %) took folic acid during any time of their pregnancy. 35 % (n = 29) used betel nut (doma, quid) and 53 % (n = 21) of pregnant WWE used betel nut during pregnancy. CONCLUSIONS: Based on data about WWE participants' ASM, supplement, and substance use, our study identified the high use of first generation ASMs (including valproate), frequently in polytherapy, and betel nut use as treatment gaps in women of childbearing potential age with active epilepsy in Bhutan. To address these gaps for locations such as Bhutan, we propose modifications to the QUIET tool's "Chronic Epilepsy Care for Women" section.

Depression, sleep quality, and social isolation among people with epilepsy in Bhutan: A cross-sectional study.

PURPOSE: The aim of this study was to analyze the possible contributions of seizure burden, sleep quality, and social integration to depression among people with epilepsy (PWE) in Bhutan. METHODS: Bhutan is a lower-middle-income country in Southeast Asia with a public healthcare system without neurologists. People with epilepsy were prospectively recruited from psychiatrist-run epilepsy clinics at the National Referral Hospital in the capital city of Thimphu. Adult participants with epilepsy were interviewed for clinical history, sleep quality using the Pittsburgh Sleep Quality Index, social networks using the Berkman-Syme Social Network Index, and depressive symptoms using the Patient Health Questionnaire - 9 (PHQ-9). A multivariable regression model was built to assess the relationship between depression as an outcome and the possible contributors of sleep quality, sex, and seizure in the prior month. RESULTS: Out of 80 participants (39 women, mean age: 29.4 years old, range: 18-56 years, 58 [73%] with a seizure in the previous month), 33% had poor sleep quality, 68% were socially isolated, 30% had a mild depressive symptom burden or more, and 18% reported suicidal ideation at the time of their interview. Women had a higher average PHQ-9 score versus men, which showed a trend towards statistical significance (5.6 versus 3.3 PHQ-9 points, p = 0.07), and on average met criteria for mild depression. Social integration was not significantly associated with sleep quality and had no relationship with depressive burden. There was a small positive correlation between poorer sleep quality and depressive symptoms which showed a trend towards statistical significance (r = 0.21, p = 0.06). In a multivariable regression, poor sleep quality was associated with higher depressive symptom burden, adjusting for participant sex and having a seizure in the previous month (p = 0.01). CONCLUSIONS: Our exploratory study disentangles the multilayered psychosocial burden of disease experienced by PWE in Bhutan, a lower-middle-income country with access to antiseizure medications and psychiatrists but not expert epilepsy services or human resources. Further investigation into the interrelationships among social isolation, poor sleep quality, depression, and seizure burden could identify preventable and remediable constituents of this burden.

The economic burden of epilepsy in Bhutan.

OBJECTIVE: To assess the economic impact of epilepsy in Bhutan, a lower-middle-income country with a universal health care system, but with limited access to neurological care. METHODS: A cross-sectional survey was conducted of patients with epilepsy at the Jigme Dorji Wangchuk National Referral Hospital from January to August 2016. Data were collected on clinical features, cost of care, impact of epilepsy on school or work and household economic status of participants and matched comparisons (a sibling or neighbour from a household without epilepsy). RESULTS: A total of 172 individuals were included in the study (130 adults and 42 children). One-third of adults and 20 (48%) children had seizures at least once per month. Mean direct out-of-pocket cost for epilepsy care was 6054 Bhutanese Ngultrum (BTN; 91 USD) per year, of which transportation formed the greatest portion (53%). Direct costs of epilepsy were an average of 3.2% of annual household income. Adults missed 6.8 (standard deviation [SD]: 9.0) days of work or school per year on average, and children missed 18.6 (SD: 34.7) days of school. Among adults, 23 (18%) abandoned employment or school because of epilepsy; seven children (18%) stopped school because of epilepsy. Households with a person with epilepsy had a lower monthly per-person income (6434 BTN) than comparison households without epilepsy (8892 BTN; P = 0.027). CONCLUSIONS: In Bhutan, despite universal health care services, households of people with epilepsy face a significant economic burden. With many adults and children unable to attend school or work, epilepsy causes a major disruption to individuals' livelihoods.

Areca catechu (palm tree) nut chewing and seizures: An observational study.

OBJECTIVE: The objective of this study was to report the impact of chronic abuse of Areca catechu nut wrapped in leaf (also known as doma, quid, paan), the fourth most commonly abused psychoactive substance worldwide, on the frequency of seizures among people with epilepsy. METHODS: People with clinically diagnosed epilepsy (>14years old) residing in the Kingdom of Bhutan were surveyed for self-reported Areca catechu use, demographic variables, epilepsy characteristics, and seizure frequency. The relationship between seizure frequency in the prior month and chewing Areca catechu, adjusted for various confounders, was analyzed using multivariable regression models. RESULTS: There were 152 people with epilepsy, including 50 chewers (33%) and 102 (67%) nonchewers. The median duration of chewing A. catechu was 62months (25th, 75th percentiles: 24, 120months). Chewers consumed an average of three nuts daily. There was no significant difference between chewers and nonchewers in the mean age, proportion of male vs. female, age at first epileptic seizure, or number of antiepileptic drugs presently taken; chewers were more likely to be rural dwellers (p=0.042). After adjustment for all of the above variables, on average, chewers had 58.7% fewer [95%CI: (-79.4, -17.0)] seizures in the prior month, equating to 2.1 fewer [95% CI: (-3.9, -0.3)] seizures. CONCLUSIONS: Our observational study suggests that the social custom of chewing Areca catechu nut is associated with reduced seizure frequency among people with epilepsy. This association may be due to its natural stimulant properties, a novel antiepileptic property of the nut, or has another, yet unknown explanation.

Medication prescribing and patient-reported outcome measures in people with epilepsy in Bhutan.

OBJECTIVE: The aim of this study was to assess medication prescribing and patient-reported outcomes among people with epilepsy (PWE) in Bhutan and introduce criteria for evaluating unmet epilepsy care needs, particularly in resource-limited settings. METHODS: People with epilepsy in Bhutan (National Referral Hospital, 2014-2015) completed a questionnaire, the Quality of Life in Epilepsy Inventory (QOLIE-31), and an electroencephalogram (EEG). Management gap was the proportion of participants meeting any of six prespecified criteria based on best practices and the National Institute for Health and Care Excellence (NICE) guidelines. RESULTS: Among 253 participants (53% female, median: 24years), 93% (n=235) were treated with antiepileptic drugs (AEDs). Seventy-two percent (n=183) had active epilepsy (≥1 seizure in the prior year). At least one criterion was met by 55% (n=138) of participants, whereas the treatment gap encompassed only 5% (n=13). The criteria were the following: 1. Among 18 participants taking no AED, 72% (n=13) had active epilepsy. 2. Among 26 adults on subtherapeutic monotherapy, 46% (n=12) had active epilepsy. 3. Among 48 participants reporting staring spells, 56% (n=27) were treated with carbamazepine or phenytoin. 4. Among 101 female participants aged 14-40years, 23% (n=23) were treated with sodium valproate. 5. Among 67 participants reporting seizure-related injuries, 87% (n=58) had active epilepsy. 6. Among 111 participants with a QOLIE-31 score below 50/100, 77% (n=86) had active epilepsy. Years since first AED treatment (odds ratio: 1.07, 95% CI: 1.03, 1.12) and epileptiform discharges on EEG (odds ratio: 1.95, 95% CI: 1.15, 3.29) were significantly associated with more criteria met. CONCLUSIONS: By defining the management gap, subpopulations at greatest need for targeted interventions may be prioritized, including those already taking AEDs.

Aversive Reaction Between Disulfiram and Betel Quid Among Inpatients With Alcohol Use Disorder in Bhutan: A Preliminary Study.

Betel quid (BQ) is commonly used in the Asia-Pacific region. Disulfiram is prescribed for people with alcohol use disorders (PwAUDs) after the completion of detoxification as an alternative to rehabilitation. This prospective observational study reported the aversive reactions and common symptoms of disulfiram and BQ in PwAUDs. Participants included PwAUDs admitted to the psychiatric ward at the Jigme Dorji Wangchuck National Referral Hospital for detoxification, who were on Disulfiram and using BQ at the same time. Aversive reactions between disulfiram and BQ were observed for 100 patients over a year. Twenty participants showed aversive reactions between BQ and disulfiram. Common symptoms included sweating, diarrhea, dizziness, tremors, palpitations, shortness of breath, nausea and vomiting, and headache. Since PwAUDs in Bhutan are inducted on disulfiram after detoxification, and most use BQ simultaneously, this study will help inform health care providers to educate people about the aversive reactions of disulfiram and BQ.

Missed opportunities for epilepsy surgery referrals in Bhutan: A cohort study.

OBJECTIVE: To quantify the missed opportunities for epilepsy surgery referral and operationalize the Canadian Appropriateness of Epilepsy Surgery (CASES) tool for use in a lower income country without neurologists. METHODS: People with epilepsy were recruited from the Jigme Dorji Wangchuck National Referral Hospital from 2014-2016. Each participant was clinically evaluated, underwent at least one standard EEG, and was invited to undergo a free 1.5 T brain MRI. Clinical variables required for CASES were operationalized for use in lower-income populations and entered into the free, anonymous website tool. FINDINGS: There were 209 eligible participants (mean age 28.4 years, 56 % female, 179 with brain MRI data). Of the 179 participants with brain MRI, 43 (24.0 %) were appropriate for an epilepsy surgery referral, 21 (11.7 %) were uncertain, and 115 (64.3 %) were inappropriate for referral. Among the 43 appropriate referral cases, 36 (83.7 %) were "very high" and 7 (16.3 %) were "high" priorities for referral. For every unit increase in surgical appropriateness, quality of life (QoL) dropped by 2.3 points (p-value <0.001). Among the 68 patients who took >1 antiepileptic drug prior to enrollment, 42 (61.8 %) were appropriate referrals, 14 (20.6 %) were uncertain, and 12 (17.6 %) were inappropriate. CONCLUSION: Approximately a quarter of Bhutanese epilepsy patients who completed evaluation in this national referral-based hospital should have been evaluated for epilepsy surgery, sometimes urgently. Surgical services for epilepsy are an emerging priority for improving global epilepsy care and should be scaled up through international partnerships and clinician support algorithms like CASES to avoid missed opportunities.

Contraception, pregnancy, and peripartum experiences among women with epilepsy in Bhutan.

INTRODUCTION: Reports on the reproductive health of women with epilepsy (WWE) in low- and middle-income countries (LMICs) are limited. Bhutan is a lower income country with a high estimated prevalence of epilepsy and no out-of-pocket payment requirements for health visits or medications. METHODS: We developed a 10-category survey to interview WWE ages 20-59 years in the Kingdom of Bhutan to understand their contraceptive use and peripartum experiences. WWE were recruited from 2016-2017 from an existing epilepsy cohort and their reproductive health data were merged with epilepsy and socioeconomic data obtained from initial clinical evaluations performed between 2014 and 2016. RESULTS: Of the 134 WWE eligible for the study, 94 were reachable and there was 1 refusal to participate (response rate 99% among reachable WWE; 69% of all WWE in the cohort). Of the 93 WWE (median age 27 years, range 20-52), 50 (54%) reported prior pregnancies. Of the entire cohort, 55 women responded on contraception: 26 (47%) WWE had never used contraception in their lifetime. Of the 29 WWE who had ever used contraception, the most commonly reported form was male condoms (14/29, 48%), followed by depot medroxyprogesterone acetate injections (13/29, 45%), and intrauterine devices (5/29, 17%). Sixty-three percent of WWE recalled receiving information on family planning (31 of 49). Of the 50 WWE with prior pregnancies, 37 of 46 (80%) used folic acid; 6 WWE reported commencing it in the first trimester while 29 WWE began supplementation in the second trimester. Primary school education or higher was associated with folic acid supplementation during pregnancy (26/29 vs. 11/17, p=0.040). Epilepsy affected at least one of the pregnancies in 38 of the cases (76%) with an average of 2.3 pregnancies per woman). There was a total of 86 pregnancies and an average inter-pregnancy interval of 3.5 years. Ninety-five percent of women attended prenatal care (36/38), 22% had at least one miscarriage (8/37), 14% had at least one pre-term delivery (5/36), and 21% had Caesarean sections (8/38). Seventeen of 38 (45%) of WWE had seizures during pregnancy. A majority of WWE (97%, 37 of 38) with a prior pregnancy reported breastfeeding their infant. CONCLUSIONS: Nearly half of Bhutanese WWE did not use contraception; among those who used it, male condoms were most common but 11% were at risk of potential drug-drug interactions between oral contraception and enzyme-inducing antiepileptic drugs. Bhutanese WWE had a high rate of prenatal visits. Folic acid was prescribed in most pregnant WWE but the majority began supplementation in the second trimester. The number of pregnancies in WWE in Bhutan (2.3 per woman) was comparable to the number of children per women in Bhutan (2.3). Breastfeeding was practiced almost universally. Points of intervention may include pre-conception initiation of folic acid, optimization of dosing of AEDs with contraceptives, guidelines for peripartum seizure treatment, and establishment of a prospective registry for WWE and their offspring.

Yield of Brain MRI in Clinically Diagnosed Epilepsy in the Kingdom of Bhutan: A Prospective Study.

BACKGROUND: People with epilepsy (PWE) in low- and middle-income countries may not access the health resources that are considered optimal for epilepsy diagnosis. The diagnostic yield of magnetic resonance imaging (MRI) has not been well studied in these settings. OBJECTIVES: To report the diagnostic yield of brain MRI and identify clinical associations of abnormal MRI findings among PWE in a neurocysticercosis-endemic, resource-limited setting and to identify the proportion and putative structural brain causes of drug-resistant epilepsy. METHODS: PWE were prospectively enrolled at the Jigme Dorji Wangchuck National Referral Hospital in Bhutan (2014-2015). Each participant completed clinical questionnaires and a 1.5-Tesla brain MRI. Each MRI was reviewed by at least 1 radiologist and neurologist in Bhutan and the United States. A working definition of drug-resistant epilepsy for resource-limited settings was given as (a) seizures for >1 year, (b) at least 1 seizure in the prior year, and (c) presently taking 2 or more antiepileptic drugs (AEDs). Logistic regression models were constructed to test the cross-sectional association of an abnormal brain MRI with clinical variables. FINDINGS: A total of 217 participants (125 [57%] female; 54 [25%] < 18 years old; 199 [92%] taking AEDs; 154 [71%] with a seizure in the prior year) were enrolled. There was a high prevalence of abnormal brain MRIs (176/217, 81%). Mesial temporal sclerosis was the most common finding (n = 115, 53%, including 24 children), exceeding the number of PWE with neurocysticercosis (n = 26, 12%, including 1 child) and congenital/perinatal abnormalities (n = 29, 14%, including 14 children). The number of AEDs (odds ratio = .59, P = .03) and duration of epilepsy (odds ratio = 1.11, P = .02) were significantly associated with an abnormal MRI. Seizure in the prior month was associated with the presence of mesial temporal sclerosis (odds ratio = .47, P = .01). A total of 25 (12%) participants met our definition of drug-resistant epilepsy, with mesial temporal sclerosis (n = 10), congenital malformations (n = 5), and neurocysticercosis (n = 4) being the more common findings. CONCLUSIONS: The prevalence of abnormalities on brain MRI for PWE in resource-limited settings is high as a result of a diffuse range of etiologies, most commonly mesial temporal sclerosis. Drug-resistant epilepsy accounted for 12% of the referral population in a conservative estimation.

Validation of a smartphone-based EEG among people with epilepsy: A prospective study.

Our objective was to assess the ability of a smartphone-based electroencephalography (EEG) application, the Smartphone Brain Scanner-2 (SBS2), to detect epileptiform abnormalities compared to standard clinical EEG. The SBS2 system consists of an Android tablet wirelessly connected to a 14-electrode EasyCap headset (cost ~ 300 USD). SBS2 and standard EEG were performed in people with suspected epilepsy in Bhutan (2014-2015), and recordings were interpreted by neurologists. Among 205 participants (54% female, median age 24 years), epileptiform discharges were detected on 14% of SBS2 and 25% of standard EEGs. The SBS2 had 39.2% sensitivity (95% confidence interval (CI) 25.8%, 53.9%) and 94.8% specificity (95% CI 90.0%, 97.7%) for epileptiform discharges with positive and negative predictive values of 0.71 (95% CI 0.51, 0.87) and 0.82 (95% CI 0.76, 0.89) respectively. 31% of focal and 82% of generalized abnormalities were identified on SBS2 recordings. Cohen's kappa (κ) for the SBS2 EEG and standard EEG for the epileptiform versus non-epileptiform outcome was κ = 0.40 (95% CI 0.25, 0.55). No safety or tolerability concerns were reported. Despite limitations in sensitivity, the SBS2 may become a viable supportive test for the capture of epileptiform abnormalities, and extend EEG access to new, especially resource-limited, populations at a reduced cost.

Knowledge, attitudes and practices regarding epilepsy in the Kingdom of Bhutan.

OBJECTIVE: To assess the knowledge, attitudes and practices of epilepsy among healthcare workers (HCWs) and people with epilepsy (PWE) living in Bhutan. METHODS: A survey with similar questions was distributed to HCWs and PWE (2014-2015). Responses were compared between the two groups. A Stigma Scale in Epilepsy Score was tested for an independent association with patient age, sex, years of education and presence of seizure freedom using regression models. RESULTS: PWE (n=177), when compared to HCWs (n=75), were more likely to believe that epilepsy is contagious; epilepsy results from karma or past actions; PWE need help in school; and people with epilepsy have spiritual powers (p<0.05 for each comparison). Among people with epilepsy, a higher stigma score was independently associated with lower educational attainment (p=0.006) and presence of a seizure in the prior year (p=0.013), but not age, sex or anti-epileptic drug side effects. CONCLUSIONS: While knowledge of epilepsy was overall fairly high, PWE more often held certain stigmatizing beliefs, including theories of contagion and a relationship between seizures and spiritual powers. Higher educational level and seizure freedom were associated with lower stigma, underscoring their importance in stigma reduction.

Neurocysticercosis in Bhutan: a cross-sectional study in people with epilepsy.

BACKGROUND: We sought to provide an assessment of the burden of neurocysticercosis among people with epilepsy (PWE) in Bhutan and evaluate the yield of various tests for Taenia solium. METHODS: PWE were enrolled at the National Referral Hospital in Thimphu (2014-2015). Serum was tested for anti-Taenia solium IgG using ELISA (Ab-ELISA), enzyme-linked immunoelectrotransfer blot (EITB), and parasite antigen. Results were compared to brain MRI. Participants were categorized as definite neurocysticercosis (MRI and EITB positive), probable neurocysticercosis (MRI or EITB positive), or without neurocysticercosis. Logistic regression models were constructed to explore clinicodemographic associations. RESULTS: There were 12/205 (6%, 95% CI 2%, 9%) definite and 40/205 (20%, 95% CI 14%, 25%) probable neurocysticercosis cases. 25/205 (12%) with positive EITB did not have neurocysticercosis on MRI, and 15/205 (7%) participants with positive MRI had negative EITB. Participants with neurocysticercosis-suggestive lesions on MRI had an average of 1.2 cysts (parenchymal 26/27; nodular/calcified stage 21/27). In a multivariable analysis, present age (OR 1.05, 95% CI 1.01,1.09, p=0.025) was positively associated with (combined probable or definite) neurocysticercosis while mesial temporal sclerosis on MRI (OR 0.294, 95% CI 0.144, 0.598, p=0.001) was negatively associated. CONCLUSIONS: Neurocysticercosis was associated with 6-25% of epilepsy in a Bhutanese cohort. Combining EITB and MRI would aid the diagnosis of neurocysticercosis among PWE since no test identified all cases.