Scoliocorrector Fatma-UI for correction of adolescent idiopathic scoliosis: Development, effectivity, safety and functional outcome.

BACKGROUND: Adolescent idiopathic scoliosis remains a major problem due to its high incidence, high risk, and high cost. One of the aims of the management in scoliosis is to correct the deformity. Many techniques are available to correct scoliosis deformity; however, they are all far from ideal to achieve three-dimensional correction in scoliosis. AIM: To develop a set of tools named Scoliocorrector Fatma-UI (SCFUI) to aid three-dimensional correction and to evaluate the efficacy, safety, and functional outcome. METHODS: This study consists of two stages. In the first stage, we developed the SCFUI and tested it in finite element and biomechanical tests. The second stage was a single-blinded randomized clinical trial to evaluate the SCFUI compared to direct vertebral rotation (DVR). Forty-four subjects with adolescent idiopathic scoliosis were randomly allocated into the DVR group (n = 23) and SCFUI group (n = 21). Radiological, neurological, and functional outcome was compared between the groups. RESULTS: Finite element revealed the maximum stress of the SCFUI components to be between 31.2 - 252 MPa. Biomechanical analysis revealed the modulus elasticity of SCFUI was 9561324 ± 633277 MPa. Both groups showed improvement in Cobb angle and sagittal profile, however the rotation angle was lower in the SCFUI group (11.59 ± 7.46 vs 18.23 ± 6.39, P = 0.001). Neurological and functional outcome were comparable in both groups. CONCLUSION: We concluded that SCFUI developed in this study resulted in similar coronal and sagittal but better rotational correction compared to DVR. The safety and functional outcomes were also similar to DVR.

Pulmonary Function Assessment in Myasthenia Gravis Patients in a National Referral Hospital in Indonesia.

Purpose: Myasthenia gravis (MG) can cause respiratory muscle weakness and the need of ventilator support. Spirometry as the gold standard for pulmonary function examination has limited availability, especially in our hospital which is only available in outpatient clinic during work hours (not in emergency room or patient room). Furthermore, all primary healthcare in Indonesia do not have spirometry equipment, thus other alternatives are required. This study aimed to analyze the relationship between a single breath counting test (SBCT), peak flow meter (PFM), and spirometry to assess pulmonary function in MG patients in a national referral hospital in Indonesia. Patients and Methods: A single-center, cross-sectional study was conducted and SBCT, PFM, and spirometry examination were performed in MG patients and healthy controls. Results: Seventy patients, aged 47.7 ± 13.4 years old, participated in this study. SBCT, forced vital capacity first second (FVC1), and forced expiratory volume first second (FEV1) value between MG patients and healthy controls showed a significant difference, in which healthy controls have higher SBCT, FVC1, and FEV1 values (p = 0.000, p = 0.000 and p = 0.001 respectively). There was a significant difference between PFM with SBCT and FVC1 value in MG patients. Strong correlation was found between SBCT and FVC1 in MG patients. Conclusion: MG patients had worse pulmonary function compared to healthy controls. SBCT and PFM examination have a significant correlation with FVC1 in MG patients. Therefore, SBCT and PFM can be used as a bedside tool to detect respiratory impairment in MG patients.

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.

Expression in skin biopsies supports genetic evidence linking CAMKK2, P2X7R and P2X4R with HIV-associated sensory neuropathy.

HIV-associated sensory neuropathy (HIV-SN) affects 14-38% of HIV+ individuals stable on therapy with no neurotoxic drugs. Polymorphisms in CAMKK2, P2X7R and P2X4R associated with altered risk of HIV-SN in Indonesian and South African patients. The role of CaMKK2 in neuronal repair makes this an attractive candidate, but a direct role for any protein is predicated on expression in affected tissues. Here, we describe expression of CaMKK2, P2X7R and P2X4R proteins in skin biopsies from the lower legs of HIV+ Indonesians with and without HIV-SN, and healthy controls (HC). HIV-SN was diagnosed using the Brief Peripheral Neuropathy Screen. Biopsies were stained to detect protein gene product 9.5 on nerve fibres and CaMKK2, P2X7R or P2X4R, and were examined using 3-colour sequential scanning confocal microscopy. Intraepidermal nerve fibre densities (IENFD) were lower in HIV+ donors than HC and correlated directly with nadir CD4 T-cell counts (r = 0.69, p = 0.004). However, IENFD counts were similar in HIV-SN+ and HIV-SN- donors (p = 0.19) and so did not define neuropathy. CaMKK2+ cells were located close to dermal and epidermal nerve fibres and were rare in HC and HIV-SN- donors, consistent with a role for the protein in nerve damage and/or repair. P2X7R was expressed by cells in blood vessels of HIV-SN- donors, but rarely in HC or HIV-SN+ donors. P2X4R expression by cells in the epidermal basal layer appeared greatest in HIV-SN+ donors. Overall, the differential expression of CaMKK2, P2X7R and P2X4R supports the genetic evidence of a role for these proteins in HIV-SN.

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.

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.

Radiological Outcomes of Reduction Surgery for Degenerative Lumbar Spondylolisthesis Using Long Arm Pedicle Screws.

Objective: Until now, the spondylolisthesis reduction technique has relied on posterior instrumentation using long arm pedicle screws. In this way, the segments will be brought into alignment with the other vertebrae with the pedicle mats being tightened. The aim of this study is to acknowledge whether reduction surgery for degenerative lumbar spondylolisthesis (DLS) using long arm pedicle screws is able to correct the listhesis and spinopelvic parameters. Methods: We carried out a retrospective study of patients with degenerative lumbar spondylolisthesis who went through reduction surgery using long arm pedicle screws in our institutions from January 2019 to March 2022. Preoperative and postoperative radiological outcomes consisting of listhesis and spinopelvic parameters were assessed. Results: We found a statistical difference between the magnitude of listhesis immediately after surgery and preoperatively (p<0.001), with a successful correction of 85.85%. There was significant decrease in the value of pelvic tilt (p=0.044) and increase in the value of sacral slope (p=0.008) after surgery. Conclusion: Reduction surgery using long arm pedicle screws for DLS was able to reduce the listhesis effectively up to 85.5%, and also to restore the parts of spinopelvic parameters, the pelvic tilt and sacral slope, approaching normal values.

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.

Encephalomyelitis associated with coronavirus disease 2019: a case report.

BACKGROUND: Despite a considerable number of articles regarding neurological manifestations associated with severe acute respiratory syndrome coronavirus 2 infection, reports on transverse myelitis and encephalitis are scarce. CASE PRESENTATION: We report a 35-year-old Asian Arab female presenting with longitudinally extensive transverse myelitis within 3 weeks after being diagnosed with mild coronavirus disease 2019 infection. Administration of high-dose methylprednisolone led to significant clinical improvement. However, 2 days after discharge, the patient was readmitted with encephalitis manifestations, consisting of fever and loss of consciousness, along with deterioration in myelitis symptoms. Severe acute respiratory syndrome coronavirus 2 antibody was detected in cerebrospinal fluid, but DNA of severe acute respiratory syndrome coronavirus 2 was not found. Clinical recovery was achieved after the administration of intravenous immunoglobulin. CONCLUSION: Longitudinally extensive transverse myelitis can be a neurological manifestation of coronavirus disease 2019 and can be followed by encephalomyelitis episodes. High-dose steroids and intravenous immunoglobulin as an immunomodulator are possible effective treatment options.

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.

Case series: COVID-19 in patients with mild to moderate myasthenia gravis in a National Referral Hospital in Indonesia.

BACKGROUND: During the COVID-19 pandemic, patients with myasthenia gravis (MG) are most likely to be affected by this situation. Corticosteroids and immunosuppressant agents increase the risk of severe infection. Furthermore, viral infection and some medications in COVID-19 may exacerbate MG symptoms. CASE DESCRIPTION: We presented three patients with MG who contracted COVID-19. All of the patients had a favourable outcome. Only one patient who was not treated with corticosteroids or immunosuppressant therapy experienced deterioration of MG symptoms, while the other patients who received immunosuppressant therapy did not develop MG exacerbation. Surprisingly, azithromycin did not provoke myasthenic crisis (MC) in patients with normal MGFA classification. CONCLUSION: Using immunosuppressant agents may not lead to MG deterioration and may not be related to unfavourable outcomes.

Brief Report: Demographic and Genetic Associations With Markers of Small and Large Fiber Sensory Neuropathy in HIV Patients Treated Without Stavudine.

Neurotoxic antiretroviral therapy (ART) such as stavudine has been now replaced with safer therapies, reducing the prevalence of neuropathy from 34% to 15% in HIV+ Indonesians. However, it is unclear whether the residual cases display damage to small or large nerve fibers and whether both are influenced by known risk factors, including alleles of CAMKK2 associated with neuropathy in HIV patients. The encoded protein influences the growth and repair of nerve fibers. HIV-positive adults on ART for >12 months without exposure to stavudine were screened for neuropathy using the AIDS Clinical Trials Group Brief Peripheral Neuropathy Screen (BPNS). Large fiber neuropathy was assessed by nerve conduction (NC) and small fiber neuropathy using stimulated skin wrinkling (SSW) applied to the fingers. CAMKK2 alleles were assessed by TaqMan OpenArray technology. Neuropathy diagnoses were more common with SSW than BPNS (49/173 vs 26/185, χ; P = 0.0009), with poor alignment between these outcomes (P = 0.60). NC and BPNS diagnosed neuropathy at similar frequencies (29/151 vs 26/185; P = 0.12) and were aligned (P < 0.0001). In bivariate analyses, all diagnoses were associated with patients' age and persistent HIV replication, with minor effects from CD4 T-cell counts and time on ART. CAMKK2 alleles associated with neuropathy diagnosed with BPNS and SSW but not NC. Multivariable analyses confirmed the importance of age and HIV replication, with distinct CAMKK2 polymorphisms affecting BPNS and SSW. Paradoxically, height was protective against skin wrinkling. Overall the data link CAMKK2 genotypes with small rather than large fiber damage. SSW may reflect pathology distinct from that identified using BPNS.

TNF-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans.

HIV-associated sensory neuropathy (HIV-SN) is a disabling complication of HIV disease and antiretroviral therapies (ART). Since stavudine was removed from recommended treatment schedules, the prevalence of HIV-SN has declined and associated risk factors have changed. With stavudine, rs1799964*C (TNF-1031) associated with HIV-SN in Caucasians and Indonesians but not in South Africans. Here, we investigate associations between HIV-SN and rs1799964*C and 12 other polymorphisms spanning TNF and seven neighboring genes (the TNF-block) in Indonesians (n = 202; 34/168 cases) and South Africans (n = 75; 29/75 cases) treated without stavudine. Haplotypes were derived using fastPHASE and haplotype networks built with PopART. There were no associations with rs1799964*C in either population. However, rs9281523*C in intron 10 of BAT1 (alternatively DDX39B) independently associated with HIV-SN in Indonesians after correcting for lower CD4 T-cell counts and >500 copies of HIV RNA/mL (model p = 0.0011, Pseudo R2 = 0.09). rs4947324*T (between NFKBIL1 and LTA) independently associated with reduced risk of HIV-SN and African haplotype 1 (containing no minor alleles) associated with increased risk of HIV-SN after correcting for greater body weight, a history of tuberculosis and nadir CD4 T-cell counts (model: p = 0.0003, Pseudo R2 = 0.23). These results confirm TNF-block genotypes influence susceptibility of HIV-SN. However, critical genotypes differ between ethnicities and with stavudine use.

Polymorphisms in CAMKK2 associate with susceptibility to sensory neuropathy in HIV patients treated without stavudine.

HIV-associated sensory neuropathy (HIV-SN) is a debilitating neurological complication of HIV infection potentiated by the antiretroviral drug stavudine. While stavudine is no longer used, HIV-SN now affects around 15% of HIV+ Indonesians. Here, we investigate whether polymorphisms within the P2X-block (P2X4R, P2X7R, CAMKK2) and/or ANAPC5 mark susceptibility to HIV-SN in this setting. As polymorphisms in these genes associated with HIV-SN in African HIV patients receiving stavudine, the comparison can identify mechanisms independent of stavudine. HIV patients who had never used stavudine (n = 202) attending clinics in Jakarta were screened for neuropathy using the AIDS Clinical Trials Group Brief Peripheral Neuropathy Screen. Open-array technology was used to type 48 polymorphisms spanning the four genes. Haplotypes were derived for each gene using fastPHASE. Haplogroups were constructed with median-joining methods. Multivariable models optimally predicting HIV-SN were based on factors achieving p < 0.2 in bivariate analyses. Minor alleles of three co-inherited polymorphisms in CAMKK2 (rs7975295*C, rs1560568*A, rs1132780*T) associated with a reduced prevalence of HIV-SN individually and after adjusting for lower CD4 T cell count and viremia (p = 0.0002, pseudo R2 = 0.11). The optimal model for haplotypes linked HIV-SN with viremia and lower current CD4 T cell count, plus CAMKK2 haplotypes 6 and 11 and P2X7R haplotypes 2 and 12 (p = 0.0002; pseudo R2 = 0.11). CAMKK2 haplogroup A (includes 16 haplotypes and all instances of rs7975295*C, rs1560568*A, rs1132780*T) associated with reduced rates of HIV-SN (p = 0.02, OR = 0.43 CI = 0.21-0.88). These findings support a protective role for these three alleles, suggesting a role in the pathogenesis of HIV-SN that is independent of stavudine.

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.

Neuropathic pain in HIV patients receiving ART without stavudine in an Indonesia Referral Hospital.

Lower limb neuropathic pain in HIV patients is a common manifestation of sensory neuropathy (HIV-SN), but can be seen in patients who do not meet standard definitions of HIV-SN. The drug stavudine is a risk factor for HIV-SN, but some patients treated without stavudine experience HIV-SN, and the prevalence and risk factors influencing neuropathic pain in this setting are unknown. A cross sectional study at Cipto Mangunkusumo Hospital Jakarta tested 197 HIV patients treated for >12 months without stavudine. HIV-SN was defined using the AIDS Clinical Trial Group Brief Peripheral Neuropathy Screening Test (ACTG-BPNST). A validated Indonesia translation of Douleur Neuropathique en 4 (DN4) questionnaire was used to assess lower limb neuropathic pain. Nerve conduction studies assessed large nerve fiber function and Stimulated Skin Wrinkle (SSW) tests were performed to assess small nerve fibers. The prevalence of neuropathic pain was 6.6%. BPNST+HIV-SN was diagnosed in 14.2% of the cohort and 38.5% of patients with pain. Use of protease inhibitors and ART duration <2 years associated with neuropathic pain in univariate (p = .036, p = .002, resp.) and multivariable analyses (model p < .001). SSW tests were abnormal in 53.8% of subjects with neuropathic pain and only 25.5% without pain (p = .05). Patients with pain without BPNST+HIV-SN had begun ART more recently than those with both diagnoses. Overall this preliminary study showed that neuropathic pain associated with protease inhibitors and a shorter duration of ART in Indonesian HIV patients, and may be an early symptom of small fiber neuropathy in this context.

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.