Making a decision to withdraw antiepileptic drugs (AEDs) in patients with epilepsy in remission requires a careful assessment of many patient and disease related factors and the associated risks and benefits. Although unnecessary continuation of AEDs exposes the patients to unwarranted side-effects, a premature withdrawal with subsequent seizure recurrence may be distressing for the patient who otherwise considers himself as cured. Although the final decision needs to be individualized, there are certain guidelines which can help us in making evidence based decision. In this article, we intend to review the current evidence on this subject with an aim of providing a framework of the best clinical practice in this field.

Background: Migraine has a complex etiology determined by genetic and environmental factors, but the molecular mechanisms and genetics of this disease have not yet been fully clarified. Aim: This case/control study was designed to analyze the genotype distributions and allele frequencies for the Rho-kinase 2 (ROCK2) gene Thr431Asn polymorphism among the migraine patients. Materials and Methods: A total of 155 migraine patients and 155 healthy age and sex matched controls were included in this study. Genomic deoxyribonucleic acid from migraine patients and controls was analyzed by real-time polymerase chain reaction. Results: Neither genotype distributions nor the allele frequencies for the Thr431Asn polymorphism showed a significant difference between the groups. In addition, there were no marked differences in genotype and allele frequencies for the migraine without aura and migraine with aura subgroups when compared with control group. Conclusion: This is the first study to show that the ROCK2 gene Thr431Asn polymorphism is not a risk factor for the migraine in the Turkish population.

Objective: This study is designed to evaluate the long-term outcome of trapping vertebral artery-posterior inferior cerebellar artery (VA-PICA) dissecting aneurysms after revascularization. Materials and Methods: Five patients with VA-PICA dissecting aneurysms were treated surgically between 2007 and 2010. All the aneurysms were trapped through a far-lateral approach after revascularization of the PICAs by occipital artery-posterior inferior cerebellar artery (OA-PICA) bypass. All patients were scheduled for clinical follow-up in the out-patient department at 3 months, 6 months, then annually. Computed tomography (CT) scan and CT angiography, or magnetic resonance (MR) imaging and MR angiography were performed to assess the anastomosis and cerebral blood supply. Results: Among the five patients, two of them did not have any neurological deficit after surgery, the other three had post-operative lower cranial nerve palsy but recovered completely within 6 months. Post-operative cerebral angiography (received by two patients) and CT angiography (received by the other three patients) showed patent bypasses in all patients and there was no reappearance of the aneurysms. After following-up from 47 to 74 months (61 month is the median follow-up period), all patients showed excellent outcomes. Conclusion: Trapping the aneurysms after revascularization of PICAs by OA-PICA bypass is a safe method to treat the VA-PICA dissecting aneurysms.

Background: Epidemiology of primary central nervous system lymphoma (PCNSL) world-wide shows an increase in incidence linked to human immunodeficiency virus (HIV) pandemic. Materials and Methods: This retrospective review of case records analyzed the trends of hospital-based incidence of PCNSL over two decades (1991-2010), relation to immune status and effect of steroids on yield of stereotactic biopsy (STB). Results: A total of 76 cases of PCNSL were diagnosed over a period of two decades. Incidence of lymphomas amongst all biopsied lesions showed a gradual increase from 0.18% at the beginning of study period to 0.41% at the end of study period. Only 8.6% (3 of 35 tested) of the PCNSL patients were positive for HIV. The mean age of patients with HIV infection (31.3 ± 3.5 years) was significantly lower compared with those without HIV infection (44.7 ± 10.9 years) (P = 0.033). Diagnosis was obtained by open biopsy in 32 patients (42.1%) and STB in 44 patients (57.9%). Open biopsy yielded a histological confirmation of PCNSL in all cases. Among those who underwent STB, the incidence of negative biopsy with short duration of steroids (≤1 week) was 33.3% and increased to 57.1% with increasing duration of steroid treatment (>1 week). Conclusions: This study documented an increase in hospital based incidence of PCNSL in our institute, independent of HIV association. Steroid intake administration for more than a week prior to biopsy adversely affected the yield of STB in PCNSL.

Background: Malignant middle cerebral artery (MCA) infarction is associated with high mortality and morbidity. Decompressive hemicraniectomy (DH) reduces mortality significantly but evidence for long-term functional benefit is sparse and contradictory. Materials and Methods: A total of 60 patients with malignant MCA infarction were prospectively enrolled. 36 (60%) patients underwent DH and 24 (40%) patients received best medical therapy alone. Both groups were followed-up for 1 year for improvement in disability and aphasia using modified Rankin score (mRS) and Western Aphasia Battery respectively. Good outcome was defined as mRS ≤ 3. Secondary analysis using mRS ≤ 4 was also performed. Results: An absolute risk reduction of 45% was observed in mortality at 1 year; 38% (14/36) in the surgical group died versus 83% (20/24) in the medical group. Good outcome at 1 year was achieved in 20% (7/35) patients in the surgical group compared with none in the medical group (P = 0.025). Repeated measures regression suggested increased proportion of patients improving over time (discharge, 3, 6 and 12 months). Surgery reduced the odds of moderate to severe disability (mRS ≥ 4) by 93.5% (odds ratio: 0.064, 95% confidence interval: 0.01-0.045, P = 0.006). Conclusions: DH in malignant MCA infarction not only reduces mortality but also increases chances of a better functional outcome. The benefit of surgery in motor and aphasia recovery is progressive and sustained until 1 year.

Objective: The objective of the following study is to determine 1p, 19q status in a cohort of glial neoplasms. Materials and Methods: Fluorescence in situ hybridization for determination of 1p, 19q deletions in 100 glial neoplasms diagnosed between January 2007 and March 2011, was performed using Vysis dual color probes localizing to 1p36/1q25; 19q13/19p13. Results: Out of the 100 tumors, 78 tumors were either pure oligodendroglial (OD) neoplasms or had an OD component. 1p and 19q codeletions were seen in 72.7% of oligodendrogliomas (World Health Organization [WHO] Grade II), 90.9% of anaplastic oligodendrogliomas (WHO Grade III), 22.2% of mixed oligoastrocytomas (WHO Grade II) and 42.9% of the anaplastic oligoastrocytomas (WHO Grade III). Of the 29 tumors that were diagnosed as glioblastoma multiforme (GBM), 11 had an OD component of which four showed codeletions of 1p and 19q (36.4%) and two tumors showed epidermal growth factor receptor (EGFR) amplification (20%) without 1p19q codeletions. Amongst the remaining 18 GBMs without an OD component, three cases showed EGFR amplification (16.7%), one case showed isolated deletion of 1p and none showed 1p19q codeletions. Polysomies involving 1p and/or 19q with or without deletions were seen in 76.9% of mixed oligoastrocytic tumors, 7.7% of pure OD tumors and one glioblastoma. Conclusions: 1p19q codeletion is an early molecular change in the genesis of OD tumors, which is retained at the time of progression. Mixed tumors more frequently show polysomies of 1p and 19q. The presence of codeletion in a third of the GBMs with an OD component with its absence in GBMs without an OD component, justifies categorization of these tumors as a separate entity.

Background: Meningiomas represent about 30% of primary adult central nervous system tumors. Though slow growing, they recur, causing significant morbidity and mortality. Objective: The objective of the following study is to grade meningiomas according to World Health Organization (WHO) 2007 criteria and to correlate the grade with degree of expression of epidermal growth factor receptor (EGFR) and p53. Materials and Methods: Meningiomas diagnosed in the year 2010 in the Department of Pathology of our institute, were included in the study. Clinical and radiological findings were noted from medical records. The histopathology slides were reviewed and the tumors were graded according to WHO 2007 criteria. Tissue microarrays (TMA) were prepared and immunohistochemical analysis with epithelial membrane antigen, Vimentin, Ki67, EGFR and p53 was performed on the TMA slides. Results: A total of 79 meningiomas diagnosed during the study period included 30 male and 49 female patients with an age range of 10-75 years. There was a female preponderance with M:F ratio of 1:1.63. EGFR was found to be higher in grade I (82.93%) compared with grade II (35.71%) and grade III tumors (20%) with an overall positivity of 60.81%. Mean p53 indices were higher in grade III (50%) compared with grade II (39.29%) and grade I tumors (38.46%) with an overall positivity of 39.44%. Ki67 labeling index (LI) was significantly high in grade III (16.4%) compared with grade II (6.46%) and grade I tumors (3.13%). Conclusion: EGFR expression and Ki67 LI correlated with grade of meningioma P < 0.0001 and P < 0.0001 respectively which were statistically significant whereas p53 expression did not correlate (P - 0.90).

Background: A recent phase 1/2 clinical trial argued for caution for the use of sulfasalazine in progressive glioblastoma (GBM). However, the study enrolled patients with recurrent or progressive high-grade glioma indicating that patients recruited probably had severe disease. Thus, the study may not accurately reflect the effectiveness of sulfasalazine for GBM and we hypothesized that earlier sulfasalazine administration may lead to anticancer effects. Aim: The aim of this study was to investigate whether sulfasalazine can improve the outcomes of patients with newly diagnosed GBM. Subjects and Methods: A total of 12 patients were treated with temozolomide and sulfasalazine with radiation therapy after surgery. Twelve patients with primary GBM treated with temozolomide and radiation therapy formed the control group. Progression-free survival (PFS), overall survival (OS) and seizure-free survival (SFS) curves were obtained using the Kaplan-Meier method. The survival curves were compared using the log-rank test. Results: The median OS, PFS and SFS did not differ between the groups. Grade 3 or 4 adverse events occurred over the duration of the study in nine (75%) patients. The median SFS was 12 months in nine patients who received sulfasalazine administration for more than 21 days, which was strongly but not significantly longer than the 3 months observed in the control group (P = 0.078). Conclusions: Sulfasalazine treatment with temozolomide plus radiotherapy for newly diagnosed primary GBM is associated with a high rate of discontinuation due to hematologic toxic effects. This treatment may have no effect on OS or PFS, although it may improve seizure control if an adequate dose can be administered.

Background: Given the importance of intracranial stenosis as a cause of recurrent ischemic stroke and the lack of evidence supporting a clear choice for prevention of recurrent ischemic events, a computer simulation model for prognostic prediction could be used to improve decision making. Aims: The aim of the following study is to compare the long-term effect of aspirin, clopidogrel and clopidogrel plus aspirin for prevention of recurrent stroke due to atherosclerotic intracranial artery stenosis. Setting and Design: The cohort consisted of 206 patients from 2006 to 2011. Materials and Methods: A two-state Markov model was used to predict the prognosis of patients with stroke or transient ischemic attack (TIA) caused by angiographically verified 50-99% stenosis of a major intracranial artery to receive aspirin, clopidogrel, or dual therapy. Statistical Analysis: Two tests were used: Pearson Chi-square test or Fisher's exact test (for percentages) and Kruskal Wallis test (for rank order data). Results: In the 10-year Markov cohort analysis, 36.24% of patients who were treated with clopidogrel plus aspirin developed to recurrent stroke while the probability for patients in the aspirin group and clopidogrel group was 42.60% and 48.39% respectively. Patients with clopidogrel plus aspirin had the highest quality-adjusted life years, followed by aspirin and clopidogrel. Conclusion: To prevent recurrent stroke in patients with intracranial artery stenosis, especially in those patients with a history of TIA or coronary artery disease, medical therapy with clopidogrel plus aspirin should be considered in preference to aspirin alone.

Background: Craniopharyngioma is a benign tumor, but recurrences are common and prognosis is poor. The pathologic mechanism underlying the high recurrence is still unknown. Aims: We hypothesized that there are hypoxic microenvironments within craniopharyngiomas and hypoxia inducible factor-1 alpha (HIF-1α) and its related genes are largely expressed in recurrent craniopharyngiomas. Materials and Methods: A total of 19 patients with craniopharyngiomas have been identified. The relative quantitative expressions of HIF-1α, vascular endothelial growth factor (VEGF) and carbonic adhydrase 9 (CA9) messenger ribonucleic acid (mRNA) of craniopharyngioma tissues were detected by real time reverse transcription polymerase chain reaction. Results: HIF-1α and VEGF mRNA was significantly up-regulated in recurrent craniopharyngiomas. Mean expression levels (recurrent craniopharyngiomas compared with non-recurrent craniopharyngiomas, as normalized to expression of β-actin) were 3.09 versus 0.75 (P = 0.001) for HIF-1α, 1.07 versus 0.32 (P = 0.000) for VEGF, 1.21 versus 1.93 (P = 0.503) for CA9. In craniopharyngiomas, the expression of VEGF showed a significant correlation with HIF-1α (r = 0.836, P = 0.000). Conclusion: There were hypoxic microenvironments within craniopharyngiomas. Therefore, preventing the tumor cells from adapting to the hypoxic conditions may be an effective way to obviate the relapse of craniopharyngioma.

Aims: Disabled-2 (Dab2) is frequently down-regulated in several types of cancers. We examined the expression level of Dab2 in human meningiomas and meningioma cells, aimed to investigate its role in the oncogenesis and development of meningiomas. Materials and Methods: Western blot analysis was employed to detect Dab2 expression in 90 fresh tissues of meningiomas, 10 leptomeninges and two kinds of human malignant meningioma cell lines. Independent samples t-test, analysis of variance, Pearson Chi-square test and likelihood ratio test were used to analyze the expression level of Dab2 and its relations to clinic-pathological characteristics of meningiomas. Results: Dab2 was significantly down-regulated in classic meningiomas than the atypical or anaplastic meningiomas. The reduced or loss of expression of Dab2 were significantly correlated with the lower classification of meningiomas and negatively correlated with the invasive ability of adjacent tissues. Furthermore, it was reduced or lost in malignant meningioma cell lines (IOMM-Lee and KT21-MG1). The lower classification of meningiomas correlated with previous comorbidities; not with the gender, age of patients and smoking. Conclusions: Dab2 is expressed at variable level in meningiomas with different grade of malignancy and probably plays a pivotal role in the early stage of oncogenesis of malignant meningiomas.

Objectives: The objective of the following study is to determine the effect of continuous insonation using 2-MHz transcranial Doppler-ultrasound (TCD-US) on the recanalization rate and the short-term outcome in subjects with acute ischemic stroke due to middle cerebral artery (MCA) occlusion. Materials and Methods: A total of 42 patients with acute ischemic stroke due to MCA occlusion within 24 h were recruited and randomly allotted to two groups (21 patients in each group). Group 1 included patients who received 1 h continuous TCD-US for MCA and Group 2 included patients who did not receive 1 h continuous TCD-US. Patients in both groups were received MCA insonation and TCD study to measure mean flow velocity (MFV) in MCA one after the initial study at 20 and 60 min. All patients received aspirin (150-325 mg). The clinical course during hospital stay was assessed before and after 1 h of US insonation, at 24 h after symptom onset using the National Institutes of Health Stroke Scale. Results: Change in MFV after insonation for Group 1 in comparison to Group 2 at 3 time points was significantly high (P < 0.001). Conclusion: Sonothrombolysis is a therapeutic option to improve the outcomes in patients with acute ischemic stroke due to MCA occlusion.