Emin Ozyurt

Surgical outcome of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis

Seizure outcome in mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE‐HS) that was evaluated according to a noninvasive protocol was assessed in 165 patients and reported using both Engels and ILAE classifications. The mean postoperative follow‐up was 5.0 ± 2.7 years. At the end of first year, 77.1% of patients were in Engel‐I, and 52.7% were in ILAE‐I. Antiepileptic drugs (AEDs) were discontinued in 41 patients (42.7%), all remained seizure‐free for >2 years that could be accepted as “cure.” Thirty‐six patients had recurrences, 19 had running‐down phenomena. Anterior temporal lobectomy (ATL) was performed in 27 patients with a better outcome when compared to patients operated by selective anterior hippocampectomy. Clinical risk factors for better and worse outcome, which show some similarity in different reports, seem to veil the main reason, which is the accurate delineation of epileptogenic zone considering the presence of different subgroups and underlying developmental pathologies.

Prostaglandin E2 levels in human brain tumor tissues and arachidonic acid levels in the plasma membrane of human brain tumors

Arachidonic acid is stored in the cell membrane and released when the cell is activated by appropriate stimuli. It is the substrate for prostaglandins. Both experimental and human tumors often synthesize high levels of prostaglandins, most notably prostaglandin E2 (PGE2). Some experiments suggest that these compounds increase tumor growth through their actions on host immunocytes. In this study, 22 patients with various brain tumors and 12 control brain tissues were studied. PGE2 levels in tissue samples were measured by ELISA. Arachidonic acid levels in the plasma membrane of tissue samples were analyzed by capillary gas chromatography. The levels of PGE2 were significantly higher in gliomas (n = 10) and meningiomas (n = 7) compared with control tissues (P = 0.000 and P = 0.000, respectively). Also, PGE2 levels in meningiomas were significantly higher than in gliomas (P = 0.000). Arachidonic acid levels in the plasma membrane of gliomas (n = 9) and meningiomas (n = 6) were significantly higher than in the control tissues (P = 0.000 and P = 0.000, respectively). These results suggest that the increased production of PGE2 may suppress the immune system and play an important role in tumor growth.

Expression and cellular distribution of multidrug resistance-related proteins in patients with focal cortical dysplasia

Recent arouse of interest indicated that drug resistant proteins are markedly over-expressed in the epileptogenic tissue and they may be responsible for the one-third of the epileptic patients who were refractory to anti-epileptic drugs (AEDs). Since several AEDs may act as substrates for these drug resistant proteins, the enhanced function of such proteins may increase drug extrusion, resulting in inadequate response to drug therapy in patients with epilepsy. We studied expression of the multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) in the epileptic tissues resected surgically in 28 patients with focal cortical dysplasia (FCD) by immunohistochemistry. The results were compared with 10 normal necropsy brain tissues. Normal brain showed no MDR1 expression in neurons and astrocytes, while MRP1 expression was very weak, which were encountered in a few samples. MDR1 expression was mainly localized on the vascular endothelial cells. In contrast to normal brain, we found intense MDR1 and MRP1 expression in both neurons and reactive astrocytes in the vast majority of dysplastic tissues. The majority of the dysplastic neurons demonstrated moderate to strong MRP1 immunoreactivity. Endothelial cells showed both MDR1 and MRP1 expression in the majority of the specimens studied. Multidrug transporters are over-expressed in the epileptogenic zone in patients with FCD. These results are concordant with previous studies, in which over-expression of multidrug proteins were shown in epileptogenic brain tissue in patients with FCD, that the over-expression of drug transport proteins in tissue from patients with refractory epilepsy may explain one possible mechanism for drug resistant in these pathologies.

Visual field defects in selective amygdalohippocampectomy for hippocampal sclerosis: the fate of Meyer's loop during the transsylvian approach to the temporal horn.

OBJECTIVEMeyers loop, the most vulnerable part of the optic radiations during approaches to the temporomedial region, extends to the tip of the temporal horn and is often encountered in epilepsy surgery. The risk of damaging Meyers loop during transsylvian selective amygdalohippocampectomy peaks while accessing the temporal horn through its roof by opening the inferior limiting sulcus of the insula. In this prospective study, we sought to evaluate and identify the incidence of visual field deficits in a homogeneous group of patients who had temporal lobe epilepsy with hippocampal sclerosis and who underwent transsylvian selective amygdalohippocampectomy. METHODSWe studied 30 patients who were referred for epilepsy surgery for intractable complex partial and/or secondary generalized seizures and evaluated according to a noninvasive protocol. All patients underwent selective amygdalohippocampectomy for temporal lobe epilepsy with hippocampal sclerosis using the standard transsylvian approach. Visual field deficits were examined preoperatively in 30 patients, by either a confrontation method (n = 18) or standard Goldmann perimetry (n = 12) and postoperatively in all patients using standard Humphrey digital perimetry. RESULTSVisual field examination was normal in all patients before surgery. Humphrey perimetric measurement revealed visual field deficits in 11 patients (36.6%) after surgery. CONCLUSIONWe have shown that there is a considerable risk of having visual field deficits after standard transsylvian selective amygdalohippocampectomy owing to the interruption of the anterior bundle of the optic radiation fibers, which most likely occurs while opening the temporal horn through the inferior limiting sulcus of the insula.

Excessive masturbation after epilepsy surgery

Sexual behavior changes as well as depression, anxiety, and organic mood/personality disorders have been reported in temporal lobe epilepsy (TLE) patients before and after epilepsy surgery. The authors describe a 14-year-old girl with symptoms of excessive masturbation in inappropriate places, social withdrawal, irritability, aggressive behavior, and crying spells after selective amygdalohippocampectomy for medically intractable TLE with hippocampal sclerosis. Since the family members felt extremely embarrassed, they were upset and angry with the patient which, in turn, increased her depressive symptoms. Both her excessive masturbation behavior and depressive symptoms remitted within 2 months of psychoeducative intervention and treatment with citalopram 20mg/day. Excessive masturbation is proposed to be related to the psychosocial changes due to seizure-free status after surgery as well as other possible mechanisms such as Kluver-Bucy syndrome features and neurophysiologic changes associated with the cessation of epileptic discharges. This case demonstrates that psychiatric problems and sexual changes encountered after epilepsy surgery are possibly multifactorial and in adolescence hypersexuality may be manifested as excessive masturbation behavior.

Association between APOE polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis.

To evaluate the hypothetical link between apolipoprotein E (APOE) polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) and whether presence of APOE epsilon4 allele shortens the latent period between febrile seizures and epilepsy. A further interest is whether presence of APOE epsilon4 allele has an impact on severity of the disease. Forty‐seven patients with MTLE‐HS were compared with 62 controls. APOE polymorphisms were determined from lymphocytes by standard methods. Eight patients (17%) and 10 controls (16.1%) were demonstrated to have one APOE epsilon4 allele. There was not any statistically significant difference in APOE epsilon4 frequency between patients and controls (P > 0.05). There was not any difference statistically according to onset age of epilepsy and the presence of APOE epsilon4 allele within patient group. APOE epsilon4 polymorphisms did not influence the severity of epilepsy. APOE epsilon4 polymorphisms had no impact on outcome after surgery. Patients with bilateral memory deficits, bilateral hippocampal atrophy and with bilateral epileptiform interictal EEG transients, were independently compared with patients having unilateral features and there were not any statistically significant differences. This study has found no association between APOE epsilon4 polymorphisms and presentation of MTLE‐HS in a group of Turkish patients.

Surgical Outcome of Epilepsy Patients Evaluated with a Noninvasive Protocol

Summary: Surgery is now an accepted treatment for some medically intractable epilepsies. Presurgical evaluation is particularly important for the localization of the epileptogenic zone, which may necessitate sophisticated imaging techniques and intracranial electroencephalogram (EEG) recordings. If patients are carefully selected, however, successful results can be achieved with noninvasive evaluation methods. Seventy‐seven patients were operated on for intractable seizures. All patients underwent EEG, neuropsychological, psychiatric, and magnetic resonance imaging investigations. Ictal EEG‐video recording was performed in all nonlesional and in some lesional cases that had discordant data. Selective amygdalo‐hippocampectomy was performed on patients with mesial temporal lobe epilepsy (MTLE), an extended or a limited lesionectomy was performed on patients with structural lesions, and a lesionectomy with deafferentation was performed on two patients with West syndrome. Electrocorticography was not used. Temporal lobe directed surgery was performed in 63·6% of the cases. The pathological examinations of all cases showed hippocampal sclerosis (HS) in 43%, tumor or tumor‐like lesions in 36%, and cortical dysplasia in 5% of patients. After a mean follow‐up of 17 months (range, 2–53), 75% of the patients were seizure‐free with or without aura and 15% had a marked improvement, whereas 10% did not benefit from surgery. Neuropsychological outcome of patients with MTLE and HS also showed worthwhile results. Our patients, who were evaluated without pre‐ and perioperative intracranial recordings and other sophisticated techniques, had an outcome comparable to those in other series from more experienced centers. Our experience indicates that successful results, especially for patients with MTLE‐HS and lesion‐related epilepsies, can be obtained at centers with limited resources if the diagnoses and evaluation procedures are performed carefully.

An association between mesial temporal lobe epilepsy with hippocampal sclerosis and human leukocyte antigens.

Summary:  Purpose: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) is one of the medically intractable epilepsies that may be remediable with surgery. Although the pathogenesis of HS still remains obscure, genetics may play a role as a predisposing factor, with the genetically controlled immune system as one of its aspects. Our aim in this study was to investigate whether there is any association between human leukocyte antigens (HLAs) that are related to chromosome 6 and this specific type of epilepsy.

Correlation between 1H MRS and Memory before and after Surgery in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis

Summary:  Purpose: Proton magnetic resonance spectroscopy (1H MRS), which can demonstrate neuronal loss and gliosis, may be used as a sensitive tool for lateralization of temporal lobe epilepsy (TLE). Although the correlation between the memory functions and 1H MRS has been investigated, its predictive value after surgery has not been studied previously. This study evaluated memory and 1H MRS values of medically intractable patients with mesial TLE and hippocampal sclerosis (MTLE‐HS) before and after selective amygdalohippocampectomy (SAH).

The expression of astroglial glutamate transporters in patients with focal cortical dysplasia: an immunohistochemical study

PurposeAn abnormal increase in the extracellular glutamate is thought to play a crucial role in the initiation, spread, and maintenance of seizure activity.In normal conditions, the majority of this excess glutamate is cleared via glial glutamate transporters (EAAT-1 and EAAT-2). We aimed to examine the immunohistochemical expression of these transporters in the dysplastic tissues of patients with focal cortical dysplasia (FCD).MethodsThe parafin-embedded dysplastic tissues of 33 patients who were operated on due to medically intractable epilepsy and histopathologically diagnosed with FCD between 2001 and 2006 were stained immunohistochemically with appropriate antibodies, and the distribution and intensity of immunoreactivity (IR) of EAAT-1 and EAAT-2 were examined.The findings were compared with the histologically normal tissues of five patients who underwent temporal lobectomy for epilepsy surgery and 10 fresh postmortem cases.ResultsIn the majority of the patients, the EAAT-1 and EAAT-2 IR were decreased, their astrocytic expression were lower, and the pattern of distribution were more diffused when compared to the control groups.Analyzing these findings according to the types of FCD revealed that as the severity of the dysplasia increased, the IR and astrocytic expression of both transporters are decreased and their distribution tend to be more “diffused.”ConclusionThe results of this study suggest a relationship between the decreased glutamate transporter expressions in dysplastic tissues which,in turn, may cause increased extracellular concentrations of glutamate and FCD pathophysiology.Further studies with larger patient populations,investigating the expression of glutamate transporters at mRNA and protein levels, are required to clarify their roles in the pathophysiology of FCD.