Factors correlating to decisions for prescribing pharmacological treatment and referrals in suspected peripheral neuropathy cases in chat consultation-based application.

Introduction: Since the COVID-19 pandemic, there has been increasing use ofchat-based telemedicine, including for patients with neuropathy complaints. It is imperative to learn how to effectively use telemedicine. This study describes the characteristics of patients with neuropathy complaints in chat-based telemedicine services in Indonesia and their influence on treatment decisions and referrals. Methods: This is a retrospective cross-sectional study during the COVID-19 pandemic era (March 2020 to December 2021) using anonymous secondary data from patient chat databases on Indonesian application-based telemedicine services (Halodoc, Alodokter, Good Doctor, and Milvik). We applied bivariate and multivariate analysis. Results: We obtained 1051 patients with suspected peripheral nerve complaints (4 per 10,000) from a total of 2,199,527 user consultations, with the majority being 40-64 years old females and diabetes mellitus was the leading comorbid (90.7%). Most patients received treatment (90.7%) and only 11.4% patients were referred. Multivariate analysis showed that treatment was more likely to be given by a neurologist (p < 0.01). Chronic symptoms (p < 0.01) and previous laboratory/other tests (p = 0.01) decreased the likelihood of medication prescription. Referrals were more likely to be given to chronic onset (p = 0.02), hypertension and heart disease (p < 0.01), and previous laboratory/other tests (p = 0.02). The opposite was true for age≥65 years, female (p = 0.04), and neurologists or other specialists as responders (p < 0.01). Conclusion: We identified several factors that influence the treatment decision such as female patients and onset. Meanwhile, age, sex, chronic symptoms, history of hypertension and heart disease, and previous laboratory/other tests may influence the referral decisions. General practitioners were more likely to refer the patients whereas neurologists or other specialists were more likely to give treatment. Chat-based telemedicine services can still be developed in the future to be better.

The Impact of Post-COVID-19 Conditions on Sleep and Quality of Life in Indonesia: A Nationwide Cross-Sectional Study.

Background: Sleep disturbances are included in the six most commonly cited complaints in post-COVID-19 conditions. In order to find the optimal management approach and enhance Quality of Life (QoL), we intend to explore sleep disturbances that occur in post-COVID-19 conditions. Methods: This was a cross-sectional study conducted with interviews and questionnaires using the Pittsburgh Sleep Quality Index (PSQI) for assessing sleep quality, Insomnia Severity Index (ISI) for assessing insomnia, Epworth Sleepiness Scale (ESS) for assessing Excessive Daytime Sleepiness (EDS), STOP-BANG questionnaire for assessing Obstructive Sleep Apnea (OSA), and Short Form 36 (SF-36) for assessing QoL. We recruited respondents from several cities in Indonesia and performed an analysis to find the relationship between sleep disturbance and its association with QoL. Results: This study involved 757 respondents. They were predominantly female, with a median age of 39 years, no comorbidities, and had exhibited mild COVID-19 severity. Subjects with post-COVID-19 conditions experienced insomnia, poor sleep quality, normal sleepiness, and low risk of OSA. Sleep quality caused role limitations due to decreased physical and mental health. Insomnia caused role limitations due to emotional and social functioning problems. Meanwhile, OSA only affected physical functioning. Conclusion: Numerous aspects of patients' QoL are affected by sleep disturbance in post-COVID-19 conditions. A comprehensive approach and coordinated care pathways must be effectively managed to improve QoL among individuals experiencing sleep disturbance.

Screening of Major Depression Disorder in Patients With Epilepsy in Indonesian National Referral Hospital.

Background and Objectives: Major depressive disorder (MDD) is a common psychiatric disorder in patients with epilepsy (PWE). The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is one of the MDD screening tools used in PWE. This study aims to determine the accuracy of the valid and reliable NDDI-E Indonesian version as an MDD screening tool in PWE and investigate the prevalence and risk factors for the development of MDD in PWE. Methods: A diagnostic cross-sectional study was conducted at Cipto Mangunkusumo National Referral Hospital, Indonesia. Patients were PWE aged 18 years or older who visited the epilepsy outpatient clinic. The valid and reliable NDDI-E Indonesian version and Mini International Neuropsychiatric Interview (MINI) International Classification of Disease, 10th Revision (ICD-10) were used to diagnose MDD. In phase II of the study, diagnostic accuracy was evaluated using the receiver operative characteristic (ROC) curve method to obtain the area under the curve (AUC) and diagnostic 2 x 2 table to determine the cutoff point, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). During phase III of the study, eligible individuals were screened for MDD using the NDDI-E Indonesian version. Demographic and clinical data were collected. Data analysis was performed using the χ2 test, Mann-Whitney test, and multivariate logistic regression analysis. Results: A total of 105 individuals were involved, and only 23 of them were found to experience MDD based on MINI ICD-10. The best cutoff point for the NDDI-E Indonesian version was ≥11, with a sensitivity of 91.3%, specificity 89%, PPV 70%, and NPV 97.3%. The AUC obtained from ROC analysis was 97.5% (95% CI 95-99%, p < 0.001). Then, the survey was completed by 79 individuals, predominantly male, mostly within the age range of 26-45 years. The prevalence of MDD in PWE was 50.6%, and the significant risk factors were seizure frequency ≥8 times a year and the presence of chronic diseases (p < 0.001). Discussion: The NDDI-E Indonesian version was a screening tool with a high diagnostic accuracy to detect MDD in PWE at a cutoff point of 11. Poor seizure control and the presence of other chronic diseases were the risk factors correlated with MDD development in PWE.

Investigation of Correlation between Resistance to Diazepam and Expression of Inflammatory Markers in The Peripheral Blood of Patients with Status Epilepticus.

OBJECTIVE: This study investigated several inflammatory markers' gene and protein expression in status epilepticus (SE) and their correlation with diazepam resistance. MATERIALS AND METHODS: Peripheral blood samples were collected from 18 adult patients with SE in Cipto Mangunkusumo Central Hospital, consisting of 12 diazepam-responsive and six diazepam-resistant samples, within 72 hours of the onset of the seizure. We collected baseline demographic and clinical data from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, stimulated with lipopolysaccharide (LPS) 1 mg/ml, and harvested for RNA isolation. The RNA was used to determine the expression of Human Mobility Group Box 1 (HMGB1), Interleukin- 6 (IL-6), IL-10, Toll-like Receptor 4 (TLR4), and Glial fibrillary acidic protein (GFAP). In addition, we performed serum protein assay of HMGB1, IL-6, IL-10, TLR4, and GFAP to compare with gene expression. RESULTS: We found a significant difference between the responsive and resistant groups for serum HMGB1 and IL-6 concentration. The mRNA expression of HMGB1 and IL-6 was significantly higher in LPS-stimulated samples in the responsive but not in the resistant groups. The ratio of IL-6 to IL-10 showed a significant difference between LPS and control in the responsive group. Diazepam response was significantly correlated with seizure duration and serum protein concentration of HMGB1. CONCLUSION: HMGB1 was highly expressed in the resistant group and strongly correlated with diazepam response, and there was a significant increase in HMGB1 mRNA expression in response to LPS stimulation. These findings suggest that targeting HMGB1 may be a promising therapeutic strategy and that HMGB1 levels could be a valuable biomarker for predicting diazepam resistance in SE.

Multidrug Resistance-1 C3435T Polymorphism and Carbamazepine Plasma Level in Indonesian Temporal Lobe Epilepsy Patients.

BACKGROUND: Temporal lobe epilepsy (TLE) has the highest probability of becoming resistant. One of the causes was Polymorphism in multidrug resistant-1 (MDR1) C3435T. In Dr. Cipto Mangunkusumo Hospital, potential drug-resistant epilepsy prevalence was 84.51%; 66.6% of them used carbamazepine (CBZ) as antiseizure medication. This comparative cross-sectional study aimed to investigate MDR1 C3435T polymorphism and CBZ plasma level (plCBZ) in Indonesian TLE patients. METHODS: TLE patient was selected consecutively; divided into drug-responsive (DRV) and drugresistant (DRE) groups. Healthy subjects were included as a control for the gene polymorphism comparison. MDR1 was identified using the restriction fragment length polymorphism PCR technique; C allele at 159 and 57bp while T allele at 216bp. High-performance liquid chromatography was used to determine plCBZ. RESULTS: There were 86 subjects; 61 in the study group and 25 controls. The genotype distribution between them was 0.58 vs 0.42, x2=0.54, p=0.000. In the study group, CBZ within therapeutic doses (dCBZ) had outreached the therapeutic plCBZ and found similar in all genotypes. DRE criteria were found in 37 subjects. Distribution of C and T in DRV was 0.63 vs 0.37, x2=10.4; and DRE 0.55 vs 0.45 x2=6.17 (p=0.019). In Tukey's multiple comparison post hoc test, CT in DRV had significantly lower dCBZ (330,36 ± 174,91 mg) and plCBZ (7.15 ± 2.64 mcg/mL) compared to all genotypes in DRE. Whereas mean dCBZ was around 800mg and plCBZ outreached the toxic level; TT was the highest. CONCLUSION: The genotype MDR1 distribution was similar in the normal population and DRE. Therapeutic plCBZ was achieved using the low dose. CT genotype responds to lower dCBZ, while TT genotype outreached the highest toxic plCBZ.

Characteristics of menstrual disorders and reproductive hormones in women with epilepsy at an Indonesian national referral hospital.

Objective: Menstrual disorders are more common in women with epilepsy than in those without epilepsy. This study aimed to examine the characteristics of reproductive function in women with epilepsy at an Indonesian national referral hospital. Methods: A case-control study was conducted from March 2020 to March 2021. Women with and without epilepsy aged ≥18 years were enrolled. All women were premenopausal before epilepsy diagnosis. Data on demographic characteristics, menstrual profiles, epileptic syndrome, seizure type, seizure frequency, etiology, localization, and anticonvulsant medication were collected. Hormone levels (follicle stimulating hormone, luteinizing hormone, prolactin, and estradiol) were measured. Results: A total of 72 women with and 50 without epilepsy (controls) were included. Dysmenorrhea was more common in women with epilepsy than in those without (59.7 vs. 20%, p < 0.001; odds ratio: 5.931 [95% confidence interval: 2.566-13.709]). Marriage rates were higher in women without epilepsy (82 vs. 45.8%, p < 0.001). No difference was found in hormone levels between the groups. The frequency of seizures was associated with prolactin and estradiol levels (p < 0.001). Polytherapy with clobazam was associated with menstrual cycle regularity. In women with epilepsy with menstrual disorders, valproic acid was associated with higher estradiol levels (p = 0.001) and lamotrigine with lower follicle stimulating hormone levels (p = 0.008). Significance: Women with epilepsy experienced more dysmenorrhea. A higher frequency of seizures associated with lower prolactin and estradiol levels. Polytherapy with clobazam was associated with irregular menstrual cycles, while valproic acid and lamotrigine was associated with estradiol and follicle stimulating hormone levels.

Sleep disturbance in post COVID-19 conditions: Prevalence and quality of life.

Post COVID-19 conditions are complaints and symptoms in patients with a history of probable or confirmed COVID-19 after 3 months of the onset of COVID-19 and last at least 2 months. About 10-20% of people may experience post COVID-19 conditions, one of which is sleep disturbance. There is a wide range of prevalence of sleep disturbances from 6% to more than 70%. An online survey of the post COVID-19 conditions in various countries showed that 78.58% of subjects had sleep disturbances, including insomnia, sleep-disordered breathing, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, parasomnias, and sleep-related movement disorders. Sleep disturbance can be found starting from 2 weeks until 48 weeks or more after discharge or after having a negative COVID-19 test results. Women aged < 50 years old with severe COVID-19 infection reported a worse outcome. Several mechanisms may cause sleep disturbance in post COVID-19 condition, namely persistent viral infection and inflammation, immunity dysregulation, and mitochondrial dysfunction. Several studies discovered sleep disturbance was a major problem that affected different domains of QoL in post COVID-19 conditions. Significant correlation was found between several dimensions of SF-36 with moderate-to-severe insomnia in post COVID-19 conditions. Therefore, sleep disturbance is a major problem in post COVID-19 conditions and may affect patients' QoL, and the existence of sleep disturbance should be a concern in post COVID-19 conditions period. Further research is required to determine the prevalence based on agreed definition as well as methods to assess this condition and its impact on QoL.

The stigma paradox: Perception of quality-of-life in people with epilepsy among themselves, the family, and the general population in Indonesian urban areas.

OBJECTIVE: To understand quality of life (QoL) perceptions of people with epilepsy (PWE) through knowledge, attitude, and behavior (KAB); PWE; their families (PWEf); and the general population (GPop). METHODS: This descriptive study was conducted in Jakarta and its surrounding cities from January to December 2019. PWE were recruited from outpatient clinics. PWEf were caregivers who lived with PWE. GPop were age matched, randomly selected, and interviewed for public events. The perception of QoL was scaled from 1 to 5 (1 =very poor to 5 =very good). KAB was obtained from open- and closed-ended questionnaires, scaled from 1 to 5 (1 =strongly disagree to 5 =strongly agree). The differences in each group were analyzed using t-tests and analysis of variance. RESULTS: We interviewed 371 participants, predominantly female and senior high school graduates. Unemployment and singlehood were higher in PWEs. QoL perception in PWE was similar to GPop (3.01 [0.75] vs. 3.07 [0.76], p = 0.49), yet lower in PWEf (2.78 [0.76]; p < 0.05). According to PWE and PWEf, not being stigmatized and support from family were essential, while GPop emphasized the medical perspective. Overall, the knowledge section had the lowest score and behavior had the highest. The GPop was uncertain about the cause of epilepsy in K2 (3.73 [1.05]), K4 (3.35 [1.24]), and K7 (2.93 [1.08]); p < 0.001. Despite positive behavior, GPop were unwilling to marry (B4) nor had PWE as their in-laws (B5); (2.83 [0.73] and 2.78 [0.77]; p < 0.001). Moreover, PWEf were still doubtful about GPop's acceptance (B1) (3.86 [0.38] vs 4.00 [0.40]; p < 0.05). CONCLUSION: The perception of QoL in PWE did not seem to be directly associated with KAB. Despite similar knowledge of PWE and PWEf, better perceptions came from PWE and GPop. The reluctance to form deeper bonds between GPop and PWE, along with PWEf's skepticism, could lead to low self-esteem, unemployment, and unmarried rates. Further studies are required to elaborate on these issues.

Altered mental status in moderate-severe traumatic brain injury in Indonesia: the clinical manifestation and EEG features of non-convulsive status epilepticus.

INTRODUCTION: Moderate-to-severe traumatic brain injury (msTBI) can cause non-convulsive status epilepticus (NCSE). Electroencephalography (EEG) is employed as a diagnostic tool due to the non-specificity of clinical symptoms. This study aimed to identify clinical and EEG features related to NCSE in patients with msTBI. METHODS: This was a cross-sectional study. Suspected NCSE in msTBI was examined using EEG data collected in consecutive patients from January 2017 to December 2019 at Dr. Cipto Mangunkusumo Hospital, Jakarta. Diagnoses of NCSE were made based on clinical manifestations and EEG features using the modified Salzburg Consensus Criteria for NCSE (mSCNC). RESULTS: Of the 39 msTBI patients, 19 were diagnosed with NCSE; only two fulfilled the definitive criteria, and the remaining were possible NCSE. Delirium and perceptual impairment were only found in NCSE, while psychomotor agitation was higher (12.8% vs. 5.1% in NCSE vs. non-NCSE). The most common EEG feature was rhythmic activity (>0.5 Hz) without fluctuation, which improved with anti-epileptic drug administration. The Glasgow Coma Scale (GCS) score at onset and at hospitalisation discharge was significantly lower in patients with NCSE. The lesions in NCSE mostly originated from the temporal lobe. Injury to the temporal lobe had a significant relationship with NCSE occurrence (p = 0.036, odds ratio 11.45 [95% confidence interval 1.17-111.6]). DISCUSSION: Post-traumatic NCSE can manifest as an alteration in mental status that could lead to missed diagnosis. In this study, delirium, perceptual impairment, and psychomotor agitation were confirmed as NCSE using EEG. The most common discharge originated from the injured temporal lobe, and this site was a significant factor associated with NCSE in patients with msTBI. CONCLUSION: NCSE can be found in msTBI cases with clinical manifestations of altered mental status, psychomotor agitation, and hallucination. An injured temporal lobe was a susceptible site for the development of NCSE.

Nonconvulsive Status Epilepticus in Metabolic Encephalopathy in Indonesia Referral Hospital.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is often underdiagnosed in patients with metabolic encephalopathy (ME). The diagnosis of ME should be made specifically to recognize the underlying etiology. Delay in seizure identification and making a diagnosis of NCSE contributed to the poor outcome. OBJECTIVE: This study aimed to find the incidence and outcome of NCSE in patients with ME. METHODS AND MATERIAL: This was an observational prospective cross-sectional study in patients with ME in emergency and critical care units in Cipto Mangunkusumo General Hospital. The diagnosis of NCSE was based on EEG using Salzburg Criteria for Nonconvulsive Status Epilepticus (SCNC). The outcome was assessed within 30 days after the NCSE diagnosis has been made. RESULTS: A total of 50 patients with ME were involved in this study. NCSE was confirmed in 32 subjects (64%). The most common etiology of ME was sepsis (58%). The mortality rate in the NCSE and non-NCSE group was 40.6% vs 44.4%. Multiple aetiologies were risk factors to poor outcome in the NCSE group. CONCLUSIONS: The incidence of NCSE among patients with ME at our hospital was high. Despite the anti-epileptic treatment of the NCSE group, the underlying cause of ME is still the main factor that affected the outcome. Therefore, aggressive treatment of anti-epileptic drug (AED) should be very carefully considered knowing the possible side-effect that might worsen the outcome of patients with ME.

Screening of Generalized Anxiety Disorder in Patients with Epilepsy: Using a Valid and Reliable Indonesian Version of Generalized Anxiety Disorder-7 (GAD-7).

INTRODUCTION: Generalized anxiety disorder (GAD) is one of the most common types of anxiety disorder in epilepsy population, comprising 21.9%, that would further impair patients' quality of life. Generalized Anxiety Disorder-7 (GAD-7) is the only screening tool for GAD that has been validated in patients with epilepsy (PWE). It is a self-reporting instrument that can be completed in less than three minutes; hence, its usage is appropriate in primary healthcare and neurology outpatient clinic. This study aimed to obtain a valid and reliable Indonesian version of GAD-7, assess its accuracy, and finally evaluate the prevalence of GAD in Indonesian PWE along with its contributing factors. METHODS: A cross-sectional study was conducted in Cipto Mangunkusumo General Hospital, Jakarta. The GAD-7 was translated and adapted using World Health Organization (WHO) steps. Validity, reliability, test-retest reliability, and diagnostic accuracy were evaluated. Then, epilepsy outpatients were screened for GAD using the Indonesian version of GAD-7. RESULTS: Internal validity and reliability for Indonesian version of GAD-7 were satisfactory with validity coefficient of 0.648 to 0.800 (p<0.01) and Cronbach's alpha value of 0.867. The best cutoff value to detect GAD in Indonesian PWE was >6 with the sensitivity, specificity, negative predictive value, and positive predictive value of 100%, 84.4%, 100%, and 55.8%, respectively. ROC analysis showed the area under the curve of 0.98 (95% CI: 0.96-0.99). The total subjects screened with the validated Indonesian version of GAD-7 were 146, and 49% were screened as having GAD. Sociodemographic and clinical characteristics had no statistically significant association with the presence of GAD. CONCLUSION: The Indonesian version of GAD-7 was a valuable screening tool to detect GAD in PWE. GAD was screened in a quite high proportion of PWE. Sociodemographic and clinical characteristics were not proven to play role in its development.

Adverse Events of Antiepileptic Drugs Using Indonesian Version of Liverpool Adverse Events Profile.

INTRODUCTION: Adverse events (AEs) associated with antiepileptic drugs (AEDs) affect people with epilepsy's (PWE) quality of life. A study conducted in 15 European countries showed that the AEs prevalence of AEDs in PWE was up to 80%. To date, there are no validated screening instruments to detect AEs of AEDs in Indonesian PWE. Therefore its epidemiology is currently unknown. This study aimed to validate the Indonesian version of Liverpool Adverse Events Profile (LAEP), consequently increasing physicians' awareness toward the probability of AEs and its necessary evaluation. Furthermore, this study was intended to determine the AEs prevalence of AEDs in Indonesian PWE. METHODS: The questionnaire was translated from English into Indonesian version. The validity and reliability were tested using Spearman correlation and Cronbach's alpha measurement. An observational cross-sectional study was carried out on consecutive PWE in outpatient clinic, Cipto Mangunkusumo Hospital. We analyzed duration of epilepsy, onset of epilepsy, seizure frequency, type of epilepsy, etiology and epilepsy syndrome, number of AEDs, duration of AED use, and comorbidity. RESULTS: All of the 19 items in the questionnaire were valid, with correlation coefficient ranging from 0.465 to 0.690 (moderate-strong correlation). Cronbach's alpha value was 0.846 (good consistency). The total of 90 subjects were enrolled with 91% screened as having AEs using LAEP questionnaire. The most common AEs were tiredness (67.8%), sleepiness (66.7%), memory problems (62.2%), and difficulty in concentrating (56.7%). The only clinical variable that influenced AEs was polytherapy. CONCLUSION: The Indonesian version of LAEP was a valid and reliable instrument to screen AE of AEDs in PWE. Almost all the subjects in this study were suspected having AEs. Polytherapy was the independent factor of AE.