Immunohistochemical Expression of IDH1, ATRX, Ki67, GFAP, and Prognosis in Indonesian Glioma Patients.

Background: The current World Health Organization (WHO) 2021 classification of human glioma is based on key molecular biomarkers to define neoplastic entities. This review further delineates mutant IDH (isocitrate dehydrogenase) from wild-type IDH disease, a necessity given the large survival gap between mutant IDH and wild-type IDH tumors. In Indonesia, there are currently few reports on the distribution and significance of these mutations. Therefore, this research aims to determine the relationship between IDH mutations, as well as clinicopathological and prognostic factors in patients with gliomas. Other immunohistochemical markers including ATRX (alpha-thalassemia/mental retardation, X-linked), Ki67 and GFAP (glial fibrillary acidic protein) expression were also evaluated. Methods: Forty-two glioma samples were collected from patients who underwent surgery at Dr. Kariadi General Hospital in Semarang, Central Java, Indonesia. Fresh and paraffin-embedded, formalin-fixed tissue samples were removed and sectioned for hematoxylin and eosin staining, immunohistochemistry, and IDH analysis of mutation. Medical records were used to collect clinicopathological and survival data. Results: IDH1 mutations were discovered in 32 (76,1%) patients, and those with IDH1 mutation had longer overall survival when corresponded to patients with IDH1-wild-type. Lower expression of Ki67 was discovered to be very associated with a better prognosis. Conclusion: IDH1 mutations status showed a significant relationship with prognosis in patients with glioma. Meanwhile, other markers (ATRX, Ki67, and GFAP) did not correlate with the prognosis.

Bibliometric Analysis of the Neurosurgery Publication Productivity of Southeast Asia in 2011-2020.

BACKGROUND: There is a large disparity between the quality of neurosurgical research in developed and developing nations, including the Association of Southeast Asian Nations (ASEAN). Bibliometric analysis is an appropriate method for evaluating the quality of research in a geographic region. We analyzed the neurosurgery reports published by the ASEAN countries to highlight regional productivity in neurosurgery research. METHODS: We performed a bibliometric analysis of neurosurgery reports from the ASEAN countries between 2011 and 2020. We described the publication number, study type, and field of study of the publication articles. In addition, we assessed the correlations between the neurosurgery research productivity of these countries and the neurosurgeon ratio, medical doctor ratio, per capita gross domestic product, and health expenditure per capita. RESULTS: We identified 1939 neurosurgeons in the ASEAN region; 570 articles were published by neurosurgeons in the region between 2011 and 2020. Singaporean neurosurgeons were the most productive, with 177 articles, accounting for 31% of the total ASEAN neurosurgeon publications in the study period. However, there has been a rapid recent increase in the number of articles. Case reports and tumors were the dominant type and field of the articles, respectively. There was no significant correlation between the neurosurgical research productivity of the ASEAN countries and the neurosurgeon ratio, medical doctor ratio, per capita gross domestic product, and health expenditure per capita. CONCLUSIONS: By analyzing the neurosurgery publications from ASEAN countries over the previous decade, we highlight the status of neurosurgical research in these countries.

Posttraumatic epilepsy: A single institution case series in Indonesia.

Background: Posttraumatic epilepsy (PTE) is a debilitating sequelae following traumatic brain injury (TBI). Risk of developing PTE is higher in the first 6 months following head trauma and remains increased for 10 years. Many cases of PTE developed into drug-resistant epilepsy in which need surgical treatment. Case Description: Fourteen patients were identified from 1998 until 2021. Mean age at onset was 21.00 ± 6.13 years, mean age of surgery was 29.50 ± 6.83 years. All patients had partial complex seizure with more than half of cases (n = 10, 71.4%) reported with focal impaired awareness seizure and focal to bilateral tonic-clonic type of seizure which were observed in the remained cases (n = 4, 28.6%). Abnormal magnetic resonance imaging findings were observed in 12 patients: mesial temporal sclerosis (n = 7), encephalomalacia (n = 4), brain atrophy (n = 4), and focal cortical dysplasia (n = 2). More than half of cases presented with mesial temporal lobe epilepsy despite site and type of brain injury. Most patients who undergone epileptogenic focus resection were free of seizure, but two patients remained to have seizure with worthwhile improvement. Conclusion: This study emphasizes the clinical characteristic of PTE cases in our center in Indonesia. While encephalomalacia is a typical finding following TBI and often responsible for epilepsy, electroencephalogram recording remains critical in determining epileptic focus. Most of PTE patients presented with temporal lobe epilepsy had excellent outcomes after surgical resection of epileptogenic focus.

Difference in GFAP Levels in POCD and Non-POCD Patients After on Pump CABG.

Introduction: On-pump, coronary artery bypass grafting (CABG) is the most common cause of postoperative cognitive dysfunction (POCD) after cardiac surgery. Previous studies showed that the incidence of POCD after cardiac surgery was 60%, higher than non-cardiac surgery with 11.7%. Glial fibrillary acid protein (GFAP) is one of the sensitive biomarkers of brain damage. Previous studies have found that elevated GFAP serum is associated with cognitive impairment. This study aims to measure the difference in GFAP levels in POCD and non-POCD patients after CABG on-pump surgery. Methods: This study is a retrospective cohort design study. The data were obtained from 56 subjects undergoing elective CABG on the pump surgery enrolled into two groups consisting of 28 POCD as a case group and 28 non-POCD as a control group. In this study, the ELISA method measured the levels of GFAP biomarkers within 24 hours after surgery. After 72 hours, the patient received a MoCA-INA examination to determine cognitive impairment. Data analysis was carried out by SPSS 23.00 software. Results: The mean age of patients in both groups was 60 years and was dominated by males (>85%). POCD patients were found to have a significantly longer duration of cardiopulmonary bypass (CPB) and cross-clamp surgery than non-POCD patients (p = 0.002 and p = 0.004). Postoperative GFAP levels in POCD patients were significantly higher than in non-POCD patients (12.95 ± 7.47 vs 3.80 ± 2.77, p < 0.001). There was a significant increase in GFAP levels compared with non-POCD (8.28 ± 7.24 vs -1.5 ± 3.03, p < 0.001). The area under the curve (AUC) value of GFAP against POCD was 0.887, cut-off GFAP 4.750 with a sensitivity of 92.9% and a specificity of 71.4%. Conclusion: POCD patients had higher GFAP levels than non-POCD patients. There are differences in GFAP levels in patients with POCD and non-POCD post-CABG surgery.

An Association Between C-Reactive Protein Levels and the Occurrence of Cognitive Dysfunction After Heart Valve Replacement.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is defined as cognitive dysfunction related to inflammation after surgical procedures, which is common following cardiac surgery. Cognitive deficits are thought to result from a systemic inflammatory response. C-reactive protein (CRP) and other proinflammatory cytokines, which are released in response to inflammation, disrupt the blood-brain barrier and neurotransmission, resulting in POCD. This study aimed to determine the correlation between POCD and increased levels of CRP in patients who had undergone heart valve replacement. METHODS: This study comprised 32 patients with normal cognitive function undergoing heart valve replacement. The CRP levels were measured before surgery and on the second postoperative day, and cognitive function was examined via the Indonesian-adapted Montreal Cognitive Assessment (MOCA-INA) on the third postoperative day. Data were analyzed using Spearman correlation test. RESULTS: Of the 32 patients, 28 (87.5%) experienced POCD. The median level of CRP was 6.6 mg/dL (interquartile range: 4.0, 8.3 g/dL). According to Spearman correlation test, increased levels of CRP were significantly related to POCD following heart valve replacement (p = 0.003, r = 0.501). The receiver operating characteristic curve indicated that the CRP cutoff level was 3.345 mg/dL, and the sensitivity and specificity were 89.3% and 75%, respectively. CONCLUSION: High expression level of CRP was correlated with POCD following heart valve replacement.

Postoperative Evaluation of the Quality of Life, Depression, and Anxiety of Temporal Lobe Epilepsy Cohort: A Single Institute Experience in Indonesia.

Background: Besides seizure control, quality of life (QoL) should be considered as an equally important outcome for epilepsy surgery service providers. The paucity of QoL reports from developing countries has enlarged the representation gap between wealthy countries and countries with fewer resources. In this study, we evaluated postoperative QoL in the Indonesian drug-resistant epilepsy cohort where the epilepsy surgery service faces limited resource availability. Methods: We evaluated the QoL in patients with temporal lobe epilepsy who underwent surgery in our epilepsy surgery center in Semarang, Indonesia, from 2001 until 2015. The follow-up period started in 2018 through 2019. Postoperative QoL, depression, and anxiety were evaluated with self-reporting questionnaires including the Quality of Life in Epilepsy Inventory-31, Beck Depression Inventory-II, and Zung Self-Rating Anxiety Scales. Results: Forty returned questionnaires were included in the analysis (male 25, 62.5%; mean age 27.6 ± 9.05 years). The seizure-free cohort (n = 22, 55.0%) reported higher scores in most QoL dimensions particularly adjustment, overall QoL, and seizure worry compared to those with persistent seizures. The overall QoL level was correlated with seizure freedom and surgery type. QoL dimensions were negatively correlated with anxiety and depression levels. Conclusions: Postoperative seizure freedom was a major factor of postoperative QoL level. Besides seizure freedom, anxiety and depression levels were also negatively correlated with QoL levels in the Indonesian population.

Initiating an epilepsy surgery program with limited resources in Indonesia.

To share the experiences of organizing the epilepsy surgery program in Indonesia. This study was divided into two periods based on the presurgical evaluation method: the first period (1999-2004), when interictal electroencephalogram (EEG) and magnetic resonance imaging (MRI) were used mainly for confirmation, and the second period (2005-2017), when long-term non-invasive and invasive video-EEG was involved in the evaluation. Long-term outcomes were recorded up to December 2019 based on the Engel scale. All 65 surgical recruits in the first period possessed temporal lobe epilepsy (TLE), while 524 patients were treated in the second period. In the first period, 76.8%, 16.1%, and 7.1% of patients with TLE achieved Classes I, II, and III, respectively, and in the second period, 89.4%, 5.5%, and 4.9% achieved Classes I, II, and III, respectively, alongside Class IV, at 0.3%. The overall median survival times for patients with focal impaired awareness seizures (FIAS), focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures were 9, 11 and 11 years (95% CI: 8.170-9.830, 10.170-11.830, and 7.265-14.735), respectively, with p = 0.04. The utilization of stringent and selective criteria to reserve surgeries is important for a successful epilepsy program with limited resources.

Challenges in intradural disc herniation diagnosis and surgery: A case report.

INTRODUCTION: Intradural disc herniation (IDH) is a rare complication which comprises 0.27% of all herniated intervertebral discs. We are reporting a case of lumbar intradural disc herniation at the L4-L5 levels highlighting challenges in establishing clinical diagnosis and surgical approach involving a transdural microsurgery approach. PRESENTATION OF CASE: A 38-year-old gentleman was presented with left radicular low back pain without motoric and autonomic involvement admitted to our neurosurgical service. Spine MRI showed an intradural, extra-axial spinal mass. DISCUSSION: Lumbar IDH is a rare pathology thus often initially diagnosed as other more common conditions. In our case, the IDH diagnosis was confirmed during surgery as the radiological examination results mimic intradural extra-axial tumor. During surgery, a hard irregular white mass was found shortly after dural incision. Histopathological results showed chondrocytes, fibrotic and necrotic appearances consistent with the diagnosis of disc herniation. Postoperatively, the patient showed improvement and pain alleviation. CONCLUSION: We observed the beak sign which is one of the important features of IDH imaging. Surgery-wise, the challenge of dissecting the anterolateral part of the duramater from the annulus fibrosus of the intervertebral disc should be noted by the performing surgeon.

Preoperative sensory aura predicts risk for seizure in temporal lobe epilepsy surgery.

BACKGROUND: Patients with temporal lobe epilepsy (TLE) often report viscerosensory and experiential auras, with substantial epilepsy localization. However, few previous studies have investigated the epileptic preoperative aura, particularly with regard to its effect on surgical outcomes in patients with drug-resistant epilepsy. OBJECTIVE: This study investigated the potential role of preoperative aura in predicting outcomes after surgery for TLE. MATERIAL AND METHODS: This study included consecutive patients diagnosed with TLE who underwent anterior temporal lobectomy (ATL) for drug-resistant TLE during the period from January 1999 to December 2017. Data pertaining to patient age at the time of surgery, sex, age at initial seizure onset, duration of epilepsy, presence of preoperative aura, comprehensive clinical semiology, side of surgery, and type of pathology were analyzed. Preoperative auras were classified as autonomic, sensory, mental and affective, or multiple manifestations. Patients were followed at 3 and 12 months after surgery and at regular intervals thereafter. RESULTS AND CONCLUSIONS: A total of 498 patients were included in the study. Positive preoperative aura was observed in 386 patients (77.51%). The correlation of each variable with seizure outcomes was analyzed, and the only variable found to correlate with seizure outcome was the presence of preoperative aura. Compared with those with negative preoperative aura, those with positive preoperative aura were 1.74-fold more likely to be seizure-free after surgery for TLE. The analysis of patient data suggested a later onset of initial seizure in those with positive preoperative aura, compared with those without (p = 0.04, 95% confidence interval (CI): 0.55-3.24). Patients with a shorter duration of disease prior to TLE surgery were more likely to achieve seizure-free status postoperatively. Preoperative sensory aura was a good predictor that a patient would be seizure-free during follow-up (p = 0.022).

Surgery for Radiologically Normal-Appearing Temporal Lobe Epilepsy in a Centre with Limited Resources.

Approximately 26-30% of temporal lobe epilepsy (TLE) cases display a normal-appearing magnetic resonance image (MRI) leading to difficulty in determining the epileptogenic focus. This causes challenges in surgical management, especially in countries with limited resources. The medical records of 154 patients with normal-appearing MRI TLE who underwent epilepsy surgery between July 1999 and July 2019 in our epilepsy centre in Indonesia were examined. The primary outcome was the Engel classification of seizures. Anterior temporal lobectomy was performed in 85.1% of the 154 patients, followed by selective amygdalo-hippocampectomy and resection surgery. Of 82 patients (53.2%), Engel Class I result was reported in 69.5% and Class II in 25.6%. The median seizure-free period was 13 (95% CI,12.550-13.450) years, while the seizure-free rate at 5 and 12 years follow-up was 96.3% and 69.0%, respectively. Patients with a sensory aura had better seizure-free outcome 15 (11.575-18.425) years. Anterior temporal lobectomy and selective amygdala-hippocampectomy gave the same favourable outcome. Despite the challenges of surgical procedures for normal MRI TLE, our outcome has been favourable. This study suggests that epilepsy surgery in normal MRI TLE can be performed in centres with limited resources.

Seizure Outcomes in Patients with Complete versus Anterior Corpus Callosotomy: Analysis of Outcome.

INTRODUCTION: Corpus callosotomy (CCT) is a palliative procedure to treat injurious drop attacks or multifocal/generalized seizures in which resection of the epileptogenic focus is not feasible. We are presenting our experience in treating intractable epilepsy patients by CCT procedures. METHODS: We observed 16 patients who underwent callosotomy (male to female ratio 7:9; adult to pediatric ratio 3:13). Initial seizure frequency was reported ranged from 1 to 2 attacks daily to very often (more than 20 episodes daily). RESULTS: Our observation showed that among patients with drop attacks, complete and >90% seizure freedom was reported by 4 and 6 of 13 patients, respectively (76.9% combined). CONCLUSION: Our observation showed that corpus callosotomy yielded good outcome in patients with intractable epilepsy in Indonesia. Our observation showed total callosotomy achieved complete seizure freedom better compared to partial callosotomy patients.

Hemispherotomy for drug-resistant epilepsy in an Indonesian population.

Hemispherotomy is a surgical treatment indicated in patients with drug-resistant epilepsy due to unilateral hemispheric pathology. Hemispherotomy is less invasive compared with hemispherectomy. We reviewed our experience performing 24 hemispherotomy and report the results of 16 patients with prolonged follow-up of this relatively uncommon procedure in two centers in Indonesia. This is a retrospective observational study conducted from 1999 to July 2019 in two epilepsy neurosurgical centers in Semarang, Indonesia. Surgical techniques included vertical parasagittal hemispherotomy (VPH), peri-insular hemispherotomy (PIH), and modified PIH called the Shimizu approach (SA). The postoperative assessment was carried out using the Engel classification system of seizure outcome. Seizure freedom (Engel class I) outcome was achieved in 10 patients (62.5%), class II in 3 patients (18.7%), class III in 2 patients (12.5%), and class IV in 1 patient (6.3%) with follow-up duration spanning from 24 to 160 months. To the best of our knowledge, this series is the most extensive documentation of hemispherotomy in an Indonesian population.