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.

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.

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.

Improvement in treatment results of glioblastoma over the last three decades and beneficial factors.

BACKGROUND: The purpose of this study is to elucidate the trend of glioblastoma outcome and scrutinize the factors contributing to better outcome over three decades. METHODS: Survival time and the influencing factors were retrospectively analyzed in 223 newly diagnosed primary glioblastoma patients during 1980-2010. Appraised factors included age, sex, tumor site, year of surgery, extent of resections, use of surgery supporting system, Karnofsky Performance Status (KPS), chemotherapy, conventional external beam radiotherapy (EBRT), and CyberKnife stereotactic radiotherapy (CK-SRT) use. RESULTS: The median survival time (MST) in all patients was 13.6 months. The MSTs for 4 periods were 9.8 (1980-1990), 13.7 (1991-2000), 12.9 (2001-2005), and 15.8 months (2006-2010), respectively (p=0.0047). Total resection, subtotal resection, partial resection, and biopsy had MSTs of 31.8, 13.9, 11.4, and 7.0 months, respectively (p<0.0001). Regarding chemotherapy, MSTs of the temozolomide base group and nimustine hydrochloride (ACNU) base group were 16.9 and 14.6 months, respectively, whereas the MST of patients without chemotherapy was only 9.8 months (p<0.0001). The MSTs for 40-Gy EBRT plus CK-SRT and 60-Gy EBRT were 19.1 and 10.7 months, respectively (p<0.0001). But in sub-selected patients, treated during 2001-2010, whose resection rate was total resection or subtotal resection, EBRT was completed and postoperative KPS was greater than or equal to 70, the MST with and without CK-SRT was 26.6 and 18.3 months, respectively (p=0.1529). According to the Cox proportional hazards model, degree of resection, KPS, ACNU use, temozolomide use, bevacizumab use, EBRT dose, and CK-SRT use were good prognostic factors. Use of neuronavigation and use of intraoperative magnetic resonance imaging were related to higher resection rate, but not determined as prognostic factors. CONCLUSIONS: We observed a gradual improvement in glioblastoma outcome, presumably because of improvements in therapeutic modalities for surgery, anticancer agents, and radiation, but the efficacy of CK-SRT remains unclear.

Geometric survey on magnetic resonance imaging of growth hormone producing pituitary adenoma.

Apart from the radiologic features regarding size and invasiveness, we had noticed some differences in morphology among types of pituitary adenomas. We conducted this study to verify the differences in radiologic morphology between growth hormone producing pituitary adenomas (GHoma) and nonfunctioning pituitary adenomas (NFoma). Pre-surgical magnetic resonance images (MRIs) were assessed in 50 cases of GHoma and 50 cases of NFoma. Geometric parameters on MRI were set in accordance with sellar anatomy. Intensity of T1-weighted image was not different between the two groups, but hypo-intensity of T2-weighted image was more frequently seen in GHoma. Predominant inferior extension of tumor was seen mostly in GHoma (88 vs. 38%). Extension of the tumor to the superior compartment of cavernous sinus was more frequent in NFoma. Pituitary gland was generally located superior to GHoma and postero-superior to NFoma. Growth characteristics of pituitary adenoma were confirmed to differ between GHoma and NFoma.

Mature posterior fossa teratoma mimicking dermoid cyst.

We describe a very rare case of mature posterior fossa teratoma in an adult who presented with clinico-radiological findings consistent with a dermoid cyst. A computed tomography scan showed a hypodense mass in the cistern magna with calcification and a sinus tract in the occipital bone. Magnetic resonance imaging revealed a hypo- to hyperintense mass without contrast enhancement. The intraoperative picture showed a dermal sinus and a cyst containing lipid, keratin and hair. Histopathological examination showed a tumor with components of all the three germ layers; thereby, a diagnosis of mature teratoma was made. The histopathological differentiation between teratoma and dermoid cyst is very valuable for ruling out the presence of immature/malignant or germinomatous components that would require further adjuvant therapies. Thus, we here present a rare case of posterior fossa teratoma mimicking dermoid cyst and emphasize the importance of histopathological differentiation between these entities.

Posterior fossa immature teratoma in an infant with trisomy 21: A case report and review of the literature.

BACKGROUND: Intracranial teratoma associated with Down syndrome is rare. With only three previously reported cases, our case is the first one presenting an immature component. CASE DESCRIPTION: A 2-month-old boy with trisomy 21 presented with lethargy and head enlargement. A magnetic resonance imaging (MRI) study showed an obstructive hydrocephalus with 0.5 cm posterior fossa tumor compressing the cerebellum. The tumor revealed a mixed intensity on T1- and T2-weighted MRI images and was surrounded by peritumoral cysts. It was heterogeneously enhancing and showed multinodular mass. The tumor was gross totally removed via suboccipital craniotomy and histologically diagnosed as immature teratoma. Four cycles of chemotherapy consisting of cisplatin and etoposide followed the surgery. The radiotherapy was withheld due to infancy. Recurrent lesions in the tumor bed were noted 10 months later. They were removed in the second surgery and histologically identified as mature teratoma. CONCLUSION: Maturation of immature teratoma may be a result of natural conversion of multipotent embryonal cells into mature tissues and following chemotherapy.

Prolactin-producing pituitary adenoma with abundant spherical amyloid deposition masquerading as extensive calcification.

A 53-year-old male presented with a case of prolactin-producing pituitary adenoma with abundant spherical amyloid depositions masquerading as extensive calcification and manifesting as visual disturbance. Computed tomography revealed a large high density mass suggesting calcified tumor in the intra- and supra-sellar regions. Magnetic resonance imaging revealed a heterogeneously enhanced large pituitary tumor reaching lateral ventricle. Blood prolactin level was elevated to 5971 ng/ml. Cabergoline treatment for 3 months provided considerable shrinkage of the tumor but failed to improve the visual symptoms. Transcranial surgery revealed that the tumor was fibrous and included abundant grayish translucent spherical granules with diameter of 0.5-1.5 mm. Immunohistochemically, the tumor was strongly positive for prolactin. Congo red stain and polarized light showed that these spherical bodies were amyloid depositions. No calcification was noted.

Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae.

OBJECTIVE: Somatotropinomae are classified as densely and sparsely granulated adenomae, which typically exhibit a perinuclear pattern (PP) and a dot pattern (DP) in cytokeratin (CK) immunostaining respectively. Some exhibit a mixed pattern (MP). We studied the relationship between these somatotropinoma subtypes and their clinico-pathological features. METHODS: The study population consisted of 141 Japanese acromegalic patients. We evaluated their clinical presentation and their response to provocation tests with TRH and LHRH and to suppression (octreotide) test. Tumour tissues were subjected to immunostaining for CAM-5.2, MIB-1, CD34, E-cadherin (CDH1) and p53 (TP53). In 43 cases (30 non-DP and 13 DP), we analysed gsp mutations (constitutively activating mutations of the G(s)α protein that is encoded by GNAS gene). RESULTS: The 141 adenomae were categorised into three subtypes based on their CK staining patterns; 30 (21.3%) exhibited DP, 83 (58.9%) exhibited PP, and 28 (19.9%) exhibited MP. Compared with the other subtypes, DP adenomae were significantly larger, and their E-cadherin expression and response to TRH, LHRH and octreotide challenge were lower. The postoperative cure rate tended to be lower in DP adenomae. gsp mutations were detected in 25 of 43 cases examined (58.1%); 20 of the 30 non-DP (66.7%) and 5 of the 13 DP tumours (38.5%) were affected by the mutation. CONCLUSION: DP somatotropinomae exhibit characteristic features. Compared with the non-DP subtypes, DP adenomae manifested a larger tumour size, a lower incidence of abnormal responses to TRH and LHRH challenge, a poor response to octreotide test and a lower expression of E-cadherin. gsp mutation was not exclusive for non-DP somatotropinomae.