The association between abcb1 gene polymorphism and clopidogrel response variability in stroke ischemic: a cross sectional study.

BACKGROUND: Clopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency. METHODS: A cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020 and 2023 in RSUI/RSCM. All subjects were assessed for ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (> 208 PRU), responsive (95-208 PRU), and bleeding risk (< 95 PRU). RESULTS: 124 subjects enrolled in this study, with 12,9% of subjects classified as non-responsive/resistant, 49,5% as responsive, and 41,9% as bleeding risk. ABCB1 C1236T homozygote wildtype (CC) was associated with 3,76 times higher bleeding risk than other variants (p = 0,008; 95%CI 1,41 - 10,07). Genotype frequency of ABCB1 C3435T homozygote wildtype, heterozygote, and homozygote variants were 35,9%, 43,5% and 16,9%, respectively; while the genotype frequency of ABCB1 C1236T were 17,8%, 39,5%, and 42,7%, respectively. CONCLUSION: ABCB1 C1236T homozygote wildtype was associated with 3,76 times higher bleeding risk than other variants. The most common genotype frequency of ABCB1 C1236T was homozygote variant; while for ABCB1 C3435T was heterozygote.

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.

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.

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.

Factors Related to Knowledge, Perception, and Practices Towards COVID-19 Among Patients with Autoimmune Diseases: A Multicenter Online Survey.

BACKGROUND: autoimmune patients can be more susceptible to infection. Proper knowledge, perception, and practices towards COVID-19 are essential for these patients during pandemic. This study aimed to know their knowledge, perception, and practices regarding COVID-19. METHODS: cross sectional study using online survey was conducted from April to May 2020. Patients with autoimmune disease were asked about demographic characteristics, diagnosis, history of treatment, knowledge, perception, and practice regarding COVID-19. RESULTS: there were 685 respondents. Most of them were female and had systemic lupus erythematosus with median age of 37 years old. Almost all respondents had good knowledge regarding transmission of COVID-19 and did proper prevention practices. Adequacy of information and steroid or mycophenolate mofetil/mycophenolic acid (MMF/MPA) use were related to perception of the effect of pandemic to their own health. Visiting private clinic and receiving hydroxychloroquine/chloroquine sulfate or sulfasalazine were related to perception that autoimmune conditions would make them more prone to COVID-19. Work from home was related to perception that when contracting COVID-19, the symptoms would be more severe. Living in Sumatra region and getting hydroxychloroquine/chloroquine sulfate or MMF/MPA were related to perception that autoimmune medications could reduce risk of getting COVID-19. Adequate information, university education, private clinic visit, and hydroxychloroquine/chloroquine sulfate use were related to perception that COVID-19 pandemic would cause difficulties in getting medications. CONCLUSION: almost all respondents had good knowledge and practices regarding COVID-19. Adequacy of information, autoimmune treatment, work from home, educational background, area of living, and health care facilities contributed to perception regarding COVID-19 pandemic.

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.

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.

Pedicle screw position changing policy for nerve injury problems during screw insertion on thoracolumbar compression fractures.

INTRODUCTION: Intraoperative neurophysiologic monitoring (IONM) had important role related to the complications in spinal surgery. Somatosensory Evoked Potential (SSEP), Transcranial electric Muscle Evoked Potentials (tceMEPs), and free run EMG are parameters used to asses functional integrity of the nervous system during surgical procedures. Once warning signal was recognized, surgeon have to make a precise decision to overcome that problem. PRESENTATION OF CASE: We present a 47-year old male with back pain due to compression fracture of thoracic vertebra T12 and lumbar vertebrae L1. While stabilizing through the posterior approach on the T11 and 12 as well as L2 and L3, the SSEP monitor showed 50% reduction in the waveform as the pedicle screw was inserted at the left side of T12. The instrumentation was changed into vertebra thoracal T10, T11, and vertebrae lumbar L2, L3. The SSEP normalized and post operatively pain decreased. After surgery there was no neurological deficit. DISCUSSION: Acute trauma as a result of spine instrumentation may provoke significant edema, with mass effect causing neurophysiological dysfunction. Administration of intravenous steroid would do at this stage, followed by constant infusion for following 24-48h, may help ameliorating the mass effect and improving the neurologic outcome. Alternatively, immediate pedicle screw changing policy showed absolute recovery of nerve injury. CONCLUSION: Insertion of pedicle screw in spinal surgery has a risk of complication that could be treated by pedicle screw changing policy.

Preservation and Tissue Handling Technique on Iatrogenic Dural Tear with Herniated Nerve Root at Cauda Equina Level.

Iatrogenic or incidental dural tear is a relatively common complication in lumbar decompression surgery. Although mostly there are no changes that occurred in long-term result following an incidental durotomy, the sequelae are not always benign especially when the herniated nerve root is involved. Preservation and tissue handling is paramount in order to prevent further injury. Two cases of dural tear with herniated nerve root complicating the lumbar decompression surgery are presented. Direct watertight repair was performed using the preservation and tissue handling concept. Assessing the relative size between the dural tear and the root mass is the key in determining whether enlargement of tear is needed. Whenever feasible, the tear will not be enlarged. Opening the vent by using a suture anchor and manually repositioning the nerve root with a fine instrument is the key for an atraumatic handling of the herniated nerve root. Clinical and neurophysiology examination was performed postoperatively and no further neurologic deficit occurred despite the iatrogenic injury. Although some debate on a few intraoperative and postoperative details still persists, tissue handling and preservation concept should be applied in all cases.

Intradural Intramedullary Mixed Type Hemangioma: Optimizing the Surgical Management through Intraoperative Neurophysiological Monitoring.

Intradural intramedullary mixed type hemangioma is a rare histotype of primary spinal cord tumors, though it can carry a severe clinical burden leading to limb dysfunction or motor and sensory disturbances. Timely intervention with radical resection is the hallmark of treatment but achieving it is not an easy task even for experienced neurosurgeons. We herein present an exemplificative case presenting with sudden paraplegia in which total resection was achieved under intraoperative neurophysiology monitoring. A thorough discussion on the operative technique and the role of neuromonitoring in allowing a safe surgical management of primary spinal cord tumors is presented.