Buge Oz

International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: A Task Force report from the ILAE Commission on Diagnostic Methods

Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug‐resistant temporal lobe epilepsy (TLE). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. A task force reviewed previous classification schemes and proposes a system based on semiquantitative hippocampal cell loss patterns that can be applied in any histopathology laboratory. Interobserver and intraobserver agreement studies reached consensus to classify three types in anatomically well‐preserved hippocampal specimens: HS International League Against Epilepsy (ILAE) type 1 refers always to severe neuronal cell loss and gliosis predominantly in CA1 and CA4 regions, compared to CA1 predominant neuronal cell loss and gliosis (HS ILAE type 2), or CA4 predominant neuronal cell loss and gliosis (HS ILAE type 3). Surgical hippocampus specimens obtained from patients with TLE may also show normal content of neurons with reactive gliosis only (no‐HS). HS ILAE type 1 is more often associated with a history of initial precipitating injuries before age 5 years, with early seizure onset, and favorable postsurgical seizure control. CA1 predominant HS ILAE type 2 and CA4 predominant HS ILAE type 3 have been studied less systematically so far, but some reports point to less favorable outcome, and to differences regarding epilepsy history, including age of seizure onset. The proposed international consensus classification will aid in the characterization of specific clinicopathologic syndromes, and explore variability in imaging and electrophysiology findings, and in postsurgical seizure control.

Pulmonary Artery Involvement and Associated Lung Disease in Behçet Disease: A Series of 47 Patients

AbstractPulmonary artery aneurysms (PAAs) are well known causes of mortality and morbidity in Behçet disease (BD). However, pulmonary artery involvement in BD is not limited to PAA; the other main type of pulmonary artery involvement is pulmonary artery thrombus (PAT), with or without associated PAA. In addition, other types of lung disease like nodules and cavities in the lung parenchyma are frequently associated with pulmonary artery involvement, and can be misinterpreted as being due to infection. We surveyed the clinical, radiologic, and laboratory characteristics and outcome of 47 BD patients with pulmonary artery involvement and the associated findings, all seen and followed at a single dedicated tertiary care center.We identified 47 (41 male, 6 female) patients in whom pulmonary artery involvement was diagnosed, who were registered in the multidisciplinary clinic at Cerrahpasa Medical Faculty between January 2000 and December 2007. Mean age at diagnosis was 29 ± 8 years, and mean disease duration to the onset of pulmonary artery involvement was 3.6 ± 4.8 years. Hemoptysis was the most common presenting symptom (79%) followed by cough, fever, dyspnea, and pleuritic chest pain. Thirty-four of 47 patients (72%) presented with PAA, including 8 with associated PAT. The remaining 13 patients (28%) had isolated PAT. Patients with isolated PAT in general have clinical features similar to patients with PAA. However, hemoptysis was less frequent and voluminous in patients with isolated PAT. Most (91%) of the patients had active disease outside the lungs when they presented with pulmonary artery involvement.Forty (85%) patients had nodules and 6 (13%) had cavities when first seen. Peripheral venous thrombosis was present in 36 of 47 (77%) patients, and intracardiac thrombi in 12 of the 36 (33%) patients. Nodules, cavities, and intracardiac thrombi were mainly present in the acute stages of pulmonary artery involvement.Pulmonary artery involvement is usually multiple, and involves mostly descending branches of the pulmonary artery. Pulmonary artery involvement may disappear, but arterial stenosis or occlusions usually develop at the same location. After a mean follow-up of 7 years, 12 of 47 (26%) patients were dead; patients with larger aneurysms were more likely to die. Sixteen of 47 (34%) patients were symptom free, and the remaining 40% had mild dyspnea (13/47) and/or small bouts of hemoptysis (8/47).Pulmonary artery pressure may be elevated, and may indicate a poor prognosis. Mediastinal lymphadenopathy and mild pleural and pericardial effusions may also be observed. Corticosteroids and immunosuppressive agents are the mainstays of treatment; however, refractory cases may require embolization, lobectomy, cavitectomy, and decortication.

Good interobserver and intraobserver agreement in the evaluation of the new ILAE classification of focal cortical dysplasias

Purpose:  An International League Against Epilepsy (ILAE) consensus classification system for focal cortical dysplasias (FCDs) has been published in 2011 specifying clinicopathologic FCD variants. The aim of the present work was to microscopically assess interobserver agreement and intraobserver reproducibility for FCD categories among an international group of neuropathologists with different levels of experience and access to epilepsy surgery tissue.

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.

High cholesterol diet supplemented with sunflower seed oil but not olive oil stimulates lipid peroxidation in plasma, liver, and aorta of rats

Abstract To determine the effect of a high cholesterol diet supplemented with sunflower seed oil or olive oil on plasma, liver, and aorta lipid peroxidation, rats were fed a basal diet, a high cholesterol diet (basal diet containing 2% cholesterol and 0.5% cholic acid), or a high cholesterol diet supplemented with 10% ( wt wt ) sunflower seed oil or 10% ( wt wt ) olive oil for 4 months. In rats fed the high cholesterol diet supplemented with sunflower seed oil, plasma, liver, and aorta lipid peroxide levels and the aorta cholesterol to phospholipid ratio were greater than in rats fed the high cholesterol diet. In contrast, no change was observed in plasma, liver, and aorta lipid peroxidation and the cholesterol to phospholipid ratio in rats fed the high cholesterol diet containing olive oil as compared with the high cholesterol diet. In addition, atherosclerotic lesions were not detected in the aorta of all groups. We concluded that a high cholesterol diet supplemented with polyunsaturated fats, but not with monounsaturated fats, seems to have a tendency to exaggerate lipid peroxidation.

Acute ethanol intoxication in a model of traumatic brain injury: the protective role of moderate doses demonstrated by immunoreactivity of synaptophysin in hippocampal neurons.

Abstract Although ethanol intoxication is reported to be a complicating factor in traumatic brain injury, some recent studies are indicating its possible protective role especially at lower doses. Ethanol inhibition of NMDA-mediated excitotoxicity which predominates at lower doses is believed to be responsible for this protection. The aim of this study was to demonstrate this neuroprotective role of alcohol using immunoreactivity for synaptophysin as an indirect marker for severity of injury. Acute ethanol intoxication at moderate doses was performed 2 h prior to trauma. Severe traumatic brain injury was administrated using an impact acceleration model in Sprague–Dawley rats. At post-traumatic 48th hour, immunorectivity for synapthophysin in the rat hippocampi was evaluated under light microscopy. According to our results there were slight increases in immunoreactivity for synaptophysin in the stratum oriens and striatum radiatum of CA1 subfield of hippocampus when ethanol was administered prior to trauma comparing to moderate increase in the trauma-only group. On the other hand vacuolar degeneration and red neuron formation was more prominent in the pyramidal cell layer of CA1 and CA3 when ethanol was not administered. Ethanol may have a neuroprotective role when administered at moderate doses prior to traumatic brain injury. This effect of ethanol may primarily be due to inhibition of NMDA receptors.

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.

Intramedullary tuberculous abscess: a case report.

Study Design This case report shows an intramedullary thoracic spinal cord abscess secondary to Mycobacterium tuberculosis in a 7‐year‐old boy with chronic progressive paraparesis and hypesthesia below T10. Objectives The treatment of this patient involved drainage of pus followed by appropriate chemotherapy. Summary of Background Data Abscess and tuberculomas of the spinal cord are rare entities. They are indistinguishable from neoplasms. The possibility of tubercular abscess or granuloma should be kept in mind when an intraspinal mass is found, provided that the clinical history is unusual for tumor. Methods A left T7‐T8 hemilaminectomy was performed. A quantity of pus was drained through a small myelotomy. A small specimen was taken, and antituberculosis treatment was given after surgery. Results Excellent clinical outcome was obtained with a combination of medical and surgical management. Conclusion The treatment of intramedullary abscess consists of surgical evacuation of the pus. Appropriate treatment offers a favorable prognosis even in cases with severe deficits.

The distribution of extracellular matrix proteins and CD44S expression in human astrocytomas

Aims of the study were: 1. to establish the prevalence of CD44 protein expression in human astrocytomas; 2. to compare the distribution of the extracellular matrix in these tumors; 3. to investigate the relation between CD 44, the extracellular matrix proteins and the histological grade of the tumor. CD44, Type IV Collagen (Col IV), Laminin (LN), Fibronectin (FN), and Tenascin (TN) expression were detected by immunohistochemistry in formalin fixed paraffin embedded tissue samples of 52 astrocytic tumors: 35 glioblastomas (GB), 7 Anaplastic astrocytomas (AA) and 10 astrocytomas (A). The localization of Col IV was observed in the basement membrane of the vessel walls in most of the astrocytomas (88.4%) with a similar pattern obtained with LN staining. 7 of 10 A (70%), 2 of 7 AA (28%) and 9 of 35 GB (25.7%) showed LN positivity. There was a negative correlation between LN expression and tumor grade (p=0.03). FN was either localized in the basement membrane or showed thick multi-layered immunoreactivity of the vessel walls. FN expression was seen in 6 A (60%), 4 AA (57%) and all of 35 GB (100%). The FN distribution was not uniform and its staining intensity showed decrease in GB. 3A (30%), 3 AA (42%), 27 GB (77.1%) showed TN expression in the vessel walls and in some tumor cells of 19 GBs. TN expression was positively correlated with the degree of vascular endothelial proliferation in GB (p<0.05). The expression of CD44s was seen as plasma membrane positivity of glioma cells in 5 of 10A (50%), 3 of 7AA (42.3%) and 29 of 35 GB (82.8%). The intensity of immunoreaction was quite strong especially near the vessels. There was a good correlation between TN and CD44s expression in human astrocytic tumors (p=0.005). No relationship was observed between GFAP, ECM proteins and CD44s expression. Both CD44s and TN expression showed increase with malignancy in astrocytomas. These findings indicated that the histological malignancy of the astrocytomas was correlated with expression of TN and CD44s. It was suggested that in astrocytomas there was a biological relationship only between CD44 and TN, but none with the other ECM proteins. TN may play a role in angiogenesis in human astrocytic tumors.

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.