Vitamin D receptor regulates transcription of mitochondrial DNA and directly interacts with mitochondrial DNA and TFAM.

Vitamin D receptor (VDR) is an essential transcription factor (TF) synthesized in different cell types. We hypothesized that VDR might also act as a mitochondrial TF. We conducted the experiments in primary cortical neurons, PC12, HEK293T, SH-SY5Y cell lines, human peripheral blood mononuclear cells (PBMC) and human brain. We showed that vitamin D/VDR affects the expression of mitochondrial DNA (mtDNA) encoded oxidative phosphorylation (OXPHOS) subunits. We observed the co-localization of VDR with mitochondria and the mtDNA with confocal microscopy. mtDNA-chromatin-immunoprecipitation and electrophoretic mobility shift assays indicated that VDR was able to bind to the mtDNA D-loop site in several locations, with a consensus sequence "MMHKCA." We also reported the possible interaction between VDR and mitochondrial transcription factor A (TFAM) and their binding sites located in close proximity in mtDNA. Consequently, our results showed for the first time that VDR was able to bind and regulate mtDNA transcription and interact with TFAM even in the human brain. These results not only revealed a novel function of VDR, but also showed that VDR is indispensable for energy demanded cells.

Outcome Predictors of Lesional Posterior Cortex Epilepsy Surgery.

BACKGROUND: Lesional posterior cortex epilepsy (PCE) is often drug resistant and may benefit from surgical intervention. In this study, we aimed to identify potential predictive factors associated with seizure recurrence after epilepsy surgery in lesional PCE. METHODS: We retrospectively reviewed patients with PCE who underwent surgery between 1998 and 2021. They were divided into 2 groups according to seizure outcome; the seizure-free group (group 1) and the non-seizure-free group (group 2). The relationship among clinical factors, electroencephalography (EEG) or cranial magnetic resonance imaging findings, disease, and seizure outcome was investigated. RESULTS: A total of 60 patients, with a mean age of 27.26 ± 12.35 years (range, 9-61 years), were included in the study. There were 31 patients (51.66%) in group 1 (Engel class I) and 29 patients (48.33%) in group 2 (13 [21.66%], 10 [16.66%], and 6 [10%] patients in Engel class II, III, and IV, respectively), with a mean follow-up of 8.95 ± 6.96 years (range, 1-24 years). No difference was observed regarding age, gender, age at seizure onset, operation type, treatment gap, and presence of bilateral lesions between the groups (P > 0.05). However, bilateral findings on interictal EEG and gliosis as the underlying disease were predictors of seizure recurrence (P < 0.05). CONCLUSIONS: More than half of the patients (including 2 with bilateral magnetic resonance imaging lesions) were seizure free at long-term follow-up. However, patients with bilateral findings on interictal EEG and gliosis were more likely to have recurrent seizures after surgery. Because lesional PCE is almost always drug resistant and has a potential for favorable outcomes, epilepsy surgery should be considered early.

Vagus Nerve Stimulation in Intractable Epilepsy.

AIM: To investigate and compare the efficacy and safety of vagus nerve stimulation (VNS) therapy in different types of epilepsy. MATERIAL AND METHODS: Patients, who were implanted with VNS between the years 2005 and 2020, were retrospectively included in the study. Age, gender, age at seizure onset, epilepsy types, VNS implantation year, replacement year, pre and post-VNS seizure frequency, number of responders, number of antiseizure medication and adverse events were recorded. RESULTS: In total, 41 patients were included in the study. The number of patients with focal epilepsy was 21 (51.2%). 10 patients (24.4%) had generalized epilepsy and 10 patients (24.4%) had ?combined generalized and focal epilepsy? (Lennox-Gastaut, Dravet syndrome). The Pre-VNS median seizure frequency was 1.5/day in the focal group, 0.6/day in the generalized group and 6/day in the combined group. Seizure frequencies dropped to 0.3/day in the focal group, 0.2/day in the generalized group and 3.0/day in the combined group at the 12th month after VNS (p < 0.001, p=0.004, p < 0.001). The response rate was found to be 68.3% at the 12th month after VNS. The number of antiseizure medications was decreased from 3.6/day to 3.1/day at the 12th months after VNS (p < 0.001). Two patients? (4.9%) VNS therapy was discontinued due to adverse events. CONCLUSION: The study indicates that VNS therapy is safe and effective in focal, generalized and combined epilepsy types. Despite having a low seizure freedom rate, VNS is a good alternative treatment option for patients who for any reason are not candidates for resective surgery.

Factors Affecting Seizure Outcomes After Surgery for Cavernoma Related Epilepsy.

AIM: To present one of the largest retrospective cavernoma related epilepsy (CRE) studies which include divergent supratentorial locations operated and followed up at least 2 years. We also investigated the factors affecting the seizure outcome. MATERIAL AND METHODS: This study includes a total of 56 patients with drug-responsive (n=40) and drug-resistant (n=16) CRE who underwent resective surgery. Age at seizure onset, age at surgery, gender, duration of epilepsy, seizure frequencies/type before and after treatment, EEG and brain MRI findings, prescribed AEDs, preoperative and post-operative neurological status, histopathological diagnosis, post-operative seizure outcomes and surgical information were documented. RESULTS: The average follow-up period was 69.6 months (range 24-216 months). The seizure outcome was assessed according to Engel?s classification at the last follow-up. Engel class I was achieved in 53 patients (95%); there was one patient at class II and two patients at class III. All patients in the drug-responsive group were at Engel class I after the surgery, while all patients at Engel classes II and III were in the drug-resistant patient group. This clearly shows that there were better outcomes in DRP group (p < 0.01). Neither the locations of cavernomas nor the duration of epilepsy had any impact on seizure outcome (p > 0.05). CONCLUSION: An earlier surgical intervention may prevent the patients from becoming drug-resistant such that their chances of being seizure free after surgery increase.

Ultrastructural investigation of synaptic alterations in the rat hippocampus after irradiation and hyperthermia.

This study aimed to investigate ultrastructural synaptic alterations in rat hippocampus after in utero exposure to irradiation (IR) and postnatal exposure to hyperthermia (HT). There were four groups in each of the time points (3rd and 6th months). IR group: Pregnant rats were exposed to radiation on the 17th gestational day. HT group: Hyperthermia was applied to the rat pups on the 10th day after their birth. IR+HT group: Both IR and HT were applied at the same time periods. Control group: No IR or HT was applied. Rat pups were sacrificed after 3 and 6 months. Thin sections from the dentate gyrus (DG) and the CA3 of hippocampus were evaluated for synapse numbers by electron microscopy. Synapses were counted, and statistical analysis was performed. Abnormalities in myelin sheath, mossy terminals and neuropil were observed in the CA3 and DG of all groups. The synapses in the CA3 region were significantly increased in the IR-3rd month, IR-6th month, and IR+HT-3rd month groups vs control group. Synapses were significantly increased in the DG of HT-3rd month group. A trend for an increase in synapse numbers was seen in the CA3 and DG. Increased number of synapses in the rat hippocampus may be due to mossy fiber sprouting, possibly caused by in utero irradiation and/or postnatal hyperthermia.

Evaluation of Ideal Extent of Corpus Callosotomy Based on the Location of Intracallosal Motor Fibers.

BACKGROUND: The corpus callosotomy (CCT) has been reported as an effective procedure to alleviate drop attacks. However, the extent of CCT remains debatable. Classical studies suggest that motor fibers traverse mainly through the anterior half of the corpus callosum (CC), although recent diffusion tensor imaging studies described that motor fibers crossed the CC in a more posterior location, emphasizing the posterior midbody and the isthmus. METHODS: Cortical and subcortical structures were examined in 30 hemispheres prepared for white matter fiber dissection. Dissections were carried out under surgical magnification to trace fibers originating from the primary motor cortex and their course through the CC. The distance of the most anterior and posterior motor fibers to the tip of the genu were measured, and the extent of CCT enabling disconnection of all motor fibers was calculated. RESULTS: Motor fibers coursed through the posterior half of the CC in the majority of hemispheres, mainly locating in posterior midbody and the isthmus. Callosal fibers should be interrupted to an average of 61% ± 0.07% point of the CC to reach the anterior limit of motor fibers and to an average of 69% ± 0.07% point to include posterior limit of motor fibers. Motor fibers were extending until the posterior one third of the CC in 22 specimens. CONCLUSIONS: Anterior-half CCT did not include all motor fibers in any specimen. Anterior two thirds CCT disrupted all motor fibers in one fourth of the cases. Our findings suggest that an ideal CCT should extend to the posterior midbody and isthmus of the CC.

68Ga PSMA PET/MR in the differentiation of low and high grade gliomas: Is 68Ga PSMA PET/MRI useful to detect brain gliomas?

BACKGROUND: Magnetic resonance imaging (MRI) is the most important imaging modality in the diagnosis and follow-up of glial brain tumors. OBJECTIVE: The aim of our study is to determine the correlation between tumor grade, determined with postoperative pathological examination, and standard uptake value (SUV), a semi-quantitative parameter, in patients who underwent imaging 68Ga-PSMA with using PET/MR. MATERIAL-METHOD: Thirty-five out of 38 patients' images whose pathology was consistent with glial tumor, 42 lesions from separate anatomic localizations or with higher activity uptake than the rest of the tumor were evaluated. SUV values measured on PET images and grade relationship were evaluated based on each lesion while mitosis, Ki-67 were evaluated for each patient. RESULTS: Grade, Ki-67, mitosis, necrosis and SUVmax/mean/peak were found statistically significant with moderate/high correlation. The parameter with the highest correlation coefficient was mitosis. (For SUVmax r = 0.64, p = 0). When Grade II and III were considered as the first group and IV as the second group, the cutoff values were found to be 2.3 for SUVmax, 0.21 for SUVmean and 0.63 for SUVpeak. In the diagnosis of HGG, PET's sensitivity is higher than MRI but no statistically difference was found between specificities. CONCLUSION: 68Ga PSMA PET imaging is found to be particularly useful in differentiating Grade IV glial tumors from other grades. This finding is thought to be important in the differentiation the relapse with postoperative tissue changes, which is an important problem in the follow-up.

Accelerated long-term forgetting after amygdalohippocampectomy in temporal lobe epilepsy.

AIM OF THE STUDY: Temporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF). In this study, we aimed to demonstrate the effect of surgery on the ALF phenomena thus contributing to potential explanation of the causal mechanism. MATERIALS AND METHODS: We evaluated 51 patients with TLE related to hippocampal sclerosis who had amygdalohippocampectomy and had remained seizure-free after surgery. A control group consisted of 24 healthy individuals. All were given a verbal learning test assessing recall after 30 min, 1 week and 6 weeks. RESULTS: In our study, the Left-TLE (L-TLE) group showed a statistically significant reduction in the performance at all assessment intervals from 30 min to 1 week compared to the Right-TLE and control groups regarding verbal learning memory test (VLMT) as well as for logical memory. The forgetting rates in the VLMT from 30 min to 1 week were not statistically significantly different between all 3 groups. The logical memory test results equally showed no statistically significant difference in the forgetting rates for the 3 groups between 30 min and 1 week. CONCLUSIONS AND CLINICAL IMPLICATIONS: These results may support ongoing debates assuming the initial low performance in the memory of L-TLE patients to be directly related with left hippocampal-temporal tissue loss irrespective of epileptic activity. The discovery of the ALF phenomenon explains that standard memory tests are unable to detect memory loss in some patients who are experiencing a significant level of problems with forgetfulness in their daily lives.

Evaluation of olfactory and gustatory changes in patients with mesial temporal lobe epilepsy.

PURPOSE: The temporal lobe plays an important role in the perception of odors. Another important anatomical structure involved in the perception of smell is the olfactory bulb. The relationship between olfactory bulb volume (OBV) and olfactory function is unclear, however. In our study, we aimed to evaluate the relationship between OBV and olfactory function in patients with mesial temporal lobe epilepsy (MTLE). METHOD: Forty-eight patients with MTLE who were managed in the Cerrahpasa Medical Faculty Neurology Department's epilepsy outpatient clinic were recruited for the study. Tests with Sniffin' Sticks and Taste Strips were performed and OBV measured in all patients. Two control groups were recruited, one for the Sniffin' Sticks and Taste Strip tests and one for OBV measurement. RESULTS: In the smell tests; the threshold, discrimination and identification scores were significantly lower in the MTLE group than in the control group. The mean taste test scores did not differ significantly between the MTLE and control groups. In the MTLE group, the mean right OBV was 40.2 ± 12.54 and the left OBV was 39.3 ± 10.54, both of which were significantly lower those in the control group. The mean OBVs of patients with hyposmia were significantly smaller bilaterally than the OBVs of those with normosmia. There was no correlation between the gustatory scores and OBV. CONCLUSIONS: Olfactory function was significantly impaired in patients with MTLE compared with healthy controls in all domains, namely threshold, discrimination, and identification. In addition, olfactory bulbus volume was smaller in patients with olfactory dysfunction.

Variations in Toll-like receptor and nuclear factor-kappa B genes and the risk of glioma.

PURPOSE: Glioblastoma (GBM) is the most aggressive primary brain tumour in the adult nervous system and is associated with a poor prognosis. NF-KB activation is an important driver of the malignant phenotype that confers a negative prognosis in patients with GBM. NF-KB plays a role in Toll-like Receptors (TLR)-induced tumourigenesis. The aim of the present study was to investigate the association of a promoter region polymorphism of NFKB1 gene encoding the p50 subunit of NF-KB, namely -94ins/del ATTG, the most widely discussed the TLR2 Arg753Gln, TLR4Asp299Gly and TLR4Thr399Ile polymorphisms, their combined effects, and the glioma risk. METHODS: A group of 120 Glioma patients and 225 control subjects were screened for these four polymorphisms using the PCR-RFLP method. RESULTS: Statistical analysis indicates that the ins/ins genotype of NFKB -94ins/delATTG (p=0.003), and the AA genotype of TLR4Asp299Gly (p < 0.001) are risk factors for glioma and people carrying the ins allele have an approximately 1.47 times susceptibility risk of glioma whereas GG genotype of TLR2Arg753Gln seems to be protective against glioma (p = 0.002). Combined genotype analysis showed that del/ins-GG genotype of TLR2Arg753Gln-NFKB1, del/ins + GG genotype of TLR4Asp299Gly-NFKB1, del/ins-CC genotype of TLR4Thr399Ile-NFKB1 were risk factors for glioma development. CONCLUSION: NFKB1 -94ins/delATTG and TLR4Asp299Gly polymorphisms are associated with increased glioma cancer risk in a Turkish population.

Role of mesial temporal lobe structures in sensory processing in humans: a prepulse modulation study in temporal lobe epilepsy.

Prepulse modulation (PPM) is an electrophysiological method which enables to assess sensory processing in vivo. Reflex responses may be facilitated or inhibited (prepulse inhibition, PPI) after a weak stimulus. Theoretically, in animal studies, the generator of PPI involves pedunculopontine nucleus which is modulated by various structures, including amygdala. We aimed to investigate whether or not there was a role of limbic structures in the generation of PPM in humans. For this purpose, we studied PPM of the blink reflex (BR) in 10 patients with mesial temporal lobe epilepsy (MTLE group) and in nine patients who had previously undergone amygdala resection for medically resistant MTLE (surgery group). A control group including 19 healthy volunteers was formed. Blink reflex, BR-PPM and BR excitability recovery were recorded in all participants. Two components of BR, first early ipsilateral component (R1) and second late bilateral components (R2 and R2c) were identified. All BR parameters after single stimulation were normal in all groups. Compared to healthy subjects, R2-PPI was more pronounced in the surgery group whereas there was a R2-PPI deficit in the MTLE group. R2-PPI deficit in the MTLE group was more prominent on the lesion side. Ipsilesional R1 facilitation was more evident at ISI of 100 ms in both MTLE and surgery groups compared to healthy subjects. BR excitability recovery was not different between groups. MTLE in humans leads to a PPI deficit. Interestingly, removal of amygdala in humans with MTLE probably provides more efficient functioning of PPI network. Amygdala and hippocampus play roles in the human R2-PPI circuit. Modulation of R1 facilitation is unilateral whereas the modulation of R2-PPI is bilateral, though asymmetric.

An Exceptional Neurosurgical Presentation of a Patient with Osteopetrosis.

BACKGROUND: Osteopetrosis (OP) is a varied clinical condition caused by malfunction or insufficient development of osteoclasts, or both. Neurologic findings can occur because of osteopetrotic conditions restricting neural foramina through which the spinal cord, cranial nerves, or major vascular structures traverse the skull. Renal tubular acidosis (RTA) is a well-documented condition with OP. However, Chiari I malformation is rarely reported concomitantly with OP. CASE DESCRIPTION: We present a patient with a known RTA who was admitted with a rapid progressive tetraparesis within 24 hours. Clinical and radiologic evaluation of the patient revealed OP with RTA together with Chiari I malformation and holocord hydromyelia. Management of the patient was started with correction of severe hypokalemia (K: 1.4 mEq/L), which resulted in dramatic improvement in tetraparesis. Two days later, a posterior fossa bone decompression with ventriculoperitoneal shunt placement during the same session led to prominent decrease in size of the ventricles and the hydromyelia on long-term follow-up. CONCLUSIONS: Patients with OP can exhibit many clinical conditions. However, our case involved an unusual and rapid progressive tetraparesis, which could confuse the management as necessitating an emergent posterior fossa decompression. Stabilizing the metabolic status of the patient facilitated elective surgery, which further improved patient's neurologic findings and diminished hydromyelia on long-term follow-up.

Dysembryoplastic neuroepithelial tumours: clinical, radiological, pathological features and outcome.

OBJECT: To analyse the clinical, imaging and histopathological data of patients who were diagnosed to have Dysembrioplastic Neuroepithelial Tumour (DNET) and underwent surgery between 1995-2015. MATERIALS AND METHODS: Age at seizure onset, age at surgery, gender, disease duration, seizure outcome of 44 patients were analysed together with Magnetic Resonance Imaging (MRI) of 21 patients. MRI types were classified as type 1 (cystic/polycystic-like, well-delineated, strongly hypointense T1), type 2 (nodularlike,heterogeneous), type 3 (dysplastic-like, iso/hyposignal T1, poor delineation, gray-white matter blurring). RESULTS: Histopathological classification revealed simple form in 19, complex in 14 and non-specific in 11 patients. Lobar distribution of the lesions was as follows: 21 Temporal (47.7%), 12 parietal (27.3%), 8 frontal (18.2%) and 3 occipital (6.8%). Type 1 MRI was observed in 10, type 2 was in 7, and type 3 in 4 patients on radiological evaluation. All cases with type 1 MRI corresponded to either simple or complex forms and all cases with type 3 MRI corresponded to nonspecific form. The histopathological distribution of cases with type 2 MRI was 4 as non-specific, 2 as simple, 1 as complex. There was no significant difference in the age of onset, age at operation and duration of epilepsy between the patients with different MRI subtypes. The majority of patients (N:36) had Engel I outcome (81,8%). In groups with Engel II and III outcome, duration of epilepsy was significantly higher (p:0,014) and simple form of DNET has significantly higher seizure freedom after surgery compared to complex and nonspecific forms of DNET (p:0,002). CONCLUSION: Patients with DNET constitute a group with favorable outcomes after epilepsy surgery especially with early referral to surgery. Longer duration of epilepsy was associated with worse seizure outcome for DNET patients. There was significant correlation between radiological and histopathological types of DNET especially in type 1 and 3.

Comparison of clinical features and surgical outcome in focal cortical dysplasia type 1 and type 2.

INTRODUCTION: Recent ILAE classification defined focal cortical dysplasia (FCD) patients with accompanying epileptic lesions as a separate group. We investigated data of patients with sole FCD lesions regarding long-term seizure outcome and different characteristics of FCD type 1 and type 2 patients. METHODS: Eighty children and adult patients underwent surgery for FCD were included to the analysis of factors differentiating FCD type 1 and type 2 groups and their effect on long-term outcome. RESULTS: FCD type 2 patients had earlier epilepsy onset (8.1 vs. 6.1 years. p=0.019) and underwent surgery younger than type 1 (18.2 vs. 23.7 years. p=0.034). FCD type 2 patients were more prominently MR positive (77.8% vs. 53.8%. p=0.029), which increased within FCD type 2 group as patients become younger (p=0.028). FCD Type 1 lesions showed mostly multilobar extension and FCD type 2 mostly located in frontal lobe. Seizure freedom was achieved in 65.4% of FCD type 1 patients and 70.4% of FCD type 2 patients. Seven patients had permanent de novo neurological deficits. Mean follow-up time was 5.5 years (Range: 1-11 years). CONCLUSION: Surgical intervention in carefully selected patients may facilitate favorable seizure outcome leading to better quality of life. FCD type 1 and type 2 groups present with evident differences, which may promote medical and surgical management of these pathologies.

Seizure Outcome of Patients with Magnetic Resonance Imaging-Negative Epilepsies: Still An Ongoing Debate.

BACKGROUND: Surgical results regarding MRI-negative epilepsy were presented and related clinical and histopathological parameters were discussed. METHODS: Thirty-six MRI-negative epilepsy patients were retrospectively analyzed. Histopathological specimens were re-reviewed by 2 blind neuropathologists and re-classified based on the current classifications. RESULTS: The mean age at surgery and seizure onset was 24.5 years and 9.3 years, respectively. Eight patients were younger than 18 years. Mean duration of seizures was 15.3 years. All but 2 underwent invasive monitorization. Eighteen patients had hypometabolism on FDG-PET with temporal lobe involvement in majority (66.7%). Hypometabolism was found in all patients with hippocampal sclerosis (HS), which was present in 50% and 66.7% of focal cortical dysplasia (FCD) type I and II patients, respectively. The frontal lobe resection was the most frequent type of operation followed by resections in temporal, parietal and occipital lobes. In 7 patients, multilobar resection was performed. Histopathological diagnosis was FCD type I, II, III, HS, and gliosis in 14, 12, 2, 3 and 2 patients, respectively. The mean follow-up was 5.8 years. Seventeen patients were seizure free and favorable outcome (Engel's I and II) was found in 69.7%. FCD type I tend to have more favorable seizure outcome. Duration of epilepsy and hypometabolism on FDG-PET was significantly related to outcome, whereas involved lobe was not. CONCLUSIONS: Our results suggest it is worth pursuing resective surgery in adults as well as in children with drug-resistant epilepsy with normal MRI.

Tissue Expressions of Soluble Human Epoxide Hydrolase-2 Enzyme in Patients with Temporal Lobe Epilepsy.

OBJECTIVE: We sought to simply demonstrate how levels of soluble human epoxide hydrolase-2 show changes in both temporal the cortex and hippocampal complex in patients with temporal lobe epilepsy. METHODS: A total of 20 patients underwent anterior temporal lobe resection due to temporal lobe epilepsy. The control group comprised 15 people who died in traffic accidents or by falling from a height, and their autopsy findings were included. Adequately sized temporal cortex and hippocampal samples were removed from each patient during surgery, and the same anatomic structures were removed from the control subjects during the autopsy procedures. Each sample was stored at -80°C as rapidly as possible until the enzyme assay. RESULTS: The temporal cortex in the epilepsy patients had a significantly higher enzyme level than did the temporal cortex of the control group (P = 0.03). Correlation analysis showed that as the enzyme level increases in the temporal cortex, it also increases in the hippocampal complex (r2 = 0.06, P = 0.00001). More important, enzyme tissue levels showed positive correlations with seizure frequency in both the temporal cortex and hippocampal complex in patients (r2 = 0.7, P = 0.00001 and r2 = 0.4, P = 0.003, respectively). The duration of epilepsy was also positively correlated with the hippocampal enzyme level (r2 = 0.06, P = 0.00001). CONCLUSIONS: Soluble human epoxy hydrolase enzyme-2 is increased in both lateral and medial temporal tissues in temporal lobe epilepsy. Further studies should be conducted as inhibition of this enzyme has resulted in a significant decrease in or stopping of seizures and attenuated neuroinflammation in experimental epilepsy models in the current literature.

Epilepsy-related brain tumors.

Seizures are among the most common presentations of brain tumors. Several tumor types can cause seizures in varying rates; neuroglial tumors and the gliomas are the most common ones. Brain tumors are the second most common cause of focal intractable epilepsy in epilepsy surgery series, with the highest frequency being dysembryoplastic neuroepithelial tumors and gangliogliomas. Seizure management is an important part of the treatment of patients with brain tumors. This review discusses clinical features and management of seizures in patients with brain tumors, including, neuroglial tumors, gliomas, meningioma and metastases; with the help of recent literature data. Tumor-related seizures are focal seizures with or without secondary generalization. Seizures may occur either as initial symptom or during the course of the disease. Brain tumors related epilepsy tends to be resistant to antiepileptic drugs and treatment of tumor is main step also for the seizure treatment. Early surgery and extent of the tumor removal are important factors for achieving seizure freedom particularly in neuroglial tumors and low grade gliomas. During selection of the appropriate antiepileptic drug, the general approach to partial epilepsies can be followed. There are several factors influencing epileptogenesis in brain tumor-related epilepsy which also explains clinical heterogeneity of epilepsy among tumor types. Identification of molecular markers may guide future therapeutic approaches and further studies are needed to prove antitumor effects of different antiepileptic drugs.

Cytokine Polymorphism and HLA Genotyping in Patients with Temporal Lobe Epilepsy Related to Hippocampal Sclerosis.

OBJECTIVE: Hippocampal sclerosis (HS) is the most common pathological substrate associated with mesial temporal lobe epilepsy (MTLE), where inflammatory processes are known to play an increasingly important role in the pathogenesis. To further investigate the role of the immune system, both cytokine gene polymorphisms and human leukocyte antigen (HLA) genotyping in patients with MTLE-HS were investigated. METHODS: The DNA samples of 100 patients with MTLE-HS and 201 healthy individuals were genotyped for cytokines (IL-6,IL-10, TNF-α, TGF-ß1 and IFN-γ) and HLA using polymerase chain reaction (PCR)-SSP and SSO methods. The results were statistically analyzed in patient and healthy control groups and then according to the presence of febrile seizures (FS) in the patient group. RESULTS: Analysis of cytokine genotyping did not reveal any significant difference between patients with MTLE-HS and controls and patients with or without FS. However, the HLA DRB1*13 allele was found to be more frequent in the patient population after Bonferroni correction. CONCLUSION: This study suggests the possible role of HLA in the pathogenesis of MTLE-HS, although it failed to show any relationship with the cytokine system. However, data regarding the role of HLA are still lacking, and further studies are necessary to verify our results.

Compatibility of MRI and FDG-PET findings with histopathological results in patients with focal cortical dysplasia.

PURPOSE: The present study aimed to determine if the specific characteristics of fluorodeoxyglucose-positron emission tomography (FDG-PET) analyses of the FCD subgroups were compatible with the magnetic resonance imaging (MRI) and clinical findings of the patients in these subgroups. METHODS: This study included 71 patients who had a presurgical evaluation workup performed due to drug-resistant seizures, who underwent epilepsy surgery, and who were histopathologically diagnosed with FCD. Relationships involving MRI and FDG-PET findings and clinical data from pathological subgroups and patients were assessed. RESULTS: According to the International League Against Epilepsy (ILAE) classifications of FCD, 28 of the patients were type I and 43 were type II. FCD was visible on the MRI scans of 53 patients, and a majority of this group was classified as type II FCD (n=34). Of these 53 patients, FCD was located in the temporal area of 21 patients, the extratemporal area of 29 patients. Of the patients who exhibited FDG-PET hypometabolism (PET-positive), 23 were classified as temporal, 17 as frontal, 11 showed involvement of the posterior cortex. The age of seizure onset was younger in PET-positive patients (p=0.032), and histopathological analyses revealed that 23 patients had type I FCD and 30 patients had type II FCD. CONCLUSION: PET scans reveal a lesion by showing hypometabolism in patients who have refractory epilepsy and an early age of onset with FCD. The lesions of MRI-negative/PET-positive FCD patients tend to be localized in the temporal lobe and that FCD may be localized in the frontal lobe of MRI-negative/PET-negative patients. However, the histopathological examinations of MRI-positive/PET-positive, MRI-negative/PET-positive, and MRI-negative/PET-negative patients did not exhibit a particular histopathological subtype.