Zsolt Horváth

Survival of mossy cells of the hippocampal dentate gyrus in humans with mesial temporal lobe epilepsy.

OBJECT Hippocampal sclerosis can be identified in most patients with mesial temporal lobe epilepsy (TLE). Surgical removal of the sclerotic hippocampus is widely performed to treat patients with drug-resistant mesial TLE. In general, both epilepsy-prone and epilepsy-resistant neurons are believed to be in the hippocampal formation. The hilar mossy cells of the hippocampal dentate gyrus are usually considered one of the most vulnerable types of neurons. The aim of this study was to clarify the fate of mossy cells in the hippocampus in epileptic humans. METHODS Of the 19 patients included in this study, 15 underwent temporal lobe resection because of drug-resistant TLE. Four patients were used as controls because they harbored tumors that had not invaded the hippocampus and they had experienced no seizures. Histological evaluation of resected hippocampal tissues was performed using immunohistochemistry. RESULTS Mossy cells were identified in the control as well as the epileptic hippocampi by using cocaine- and amphetamine-regulated transcript peptide immunohistochemistry. In most cases the number of mossy cells was reduced and thorny excrescences were smaller in the epileptic hippocampi than in controls; however, there was a significant loss of pyramidal cells and a partial loss of granule cells in the same epileptic hippocampi in which mossy cell loss was apparent. The loss of mossy cells could be correlated with the extent of hippocampal sclerosis, patient age at seizure onset, duration of epilepsy, and frequency of seizures. CONCLUSIONS In many cases large numbers of mossy cells were present in the hilus of the dentate gyrus when most pyramidal neurons of the CA1 and CA3 areas of the Ammons horn were lost, suggesting that mossy cells may not be more vulnerable to epileptic seizures than the hippocampal pyramidal neurons.

Transcranial Doppler-determined pulsatility index in the evaluation of endoscopic third ventriculostomy (preliminary data).

Objective. Endoscopic 3rd ventriculostomy has become the method of choice in the management of occlusive hydrocephalus. The treatment is accompanied by significantly less peri-operative complications than the cerebrospinal fluid shunting procedures previously employed. Close surveillance of patients, however, is necessary to avoid the consequences of raised intracranial pressure that may develop in case of obstruction of the artificial outlet of the 3rd ventricle. The aim of this study was to confirm the value of transcranial Doppler-determined pulsatility index (pI) in the assessment of the patency of endoscopic 3rd ventriculostomy and to elucidate its usefulness in early postoperative recognition of increased intracranial pressure. Methods. In twenty-two patients suffering from occlusive hydrocephalus, transcranial Doppler sonography (TCD) was performed before, immediately after, and five days after endoscopic fenestration of the floor of the 3rd ventricle. PI was defined with fast Fourier transformation. Mean PI values were determined in both middle cerebral arteries (MCA), over five cardiac cycles. Results. In nineteen cases, PI values showed a significant decrease immediately as well as five days after the intervention as compared to the pre-operative values, and flow-sensitive MRI confirmed the patency of the fenestration in all cases. In one patient the operation failed to produce an effective diversion of cerebrospinal fluid as shown by flow-sensitive MRI, and the pulsatility index was unchanged. In two patients, a significant immediate postfenestration drop in PI was followed by a recurrence of PI to pre-operative levels without any clinical deterioration. Conclusions. Preliminary results suggest that the transcranial Doppler-determined pulsatility index is a useful non-invasive tool for the evaluation of the patency of the fenestration in the early follow-up of patients who underwent endoscopic third ventriculostomy.

Complete Removal of Colloid Cyst via CT-Guided Stereotactic Biportal Neuroendoscopy

Summary¶ Four patients harbouring a colloid cyst of the 3rd ventricle were operated on endoscopically. With the “classical” monoportal technique, through a precoronal burr hole only partial removal could be achieved in the first case. As the crucial point of the procedure is the safe dissection of the cyst from the thela chorioidea and from the internal cerebral veins, adequate control of the posterior rim of the foramen of Monro and the roof of the 3rd ventricle is mandatory. Accordingly in other three cases a CT-guided biportal endoscopic technique was applied, which permitted radical removal of the entire cyst with maximum safety. CT-guidance is essential for optimal planning after careful study of the individual anatomy. In this way the rigid scopes are moved exclusively along their own axes throughout the procedure, the resulting brain damage thereby being minimal. With regard to all circumstances of the procedure, the use of flexible endoscopes appears to be inappropriate and biportal endoscopy offers itself as the method of choice.

Correlation between calbindin expression in granule cells of the resected hippocampal dentate gyrus and verbal memory in temporal lobe epilepsy

Calbindin expression of granule cells of the dentate gyrus is decreased in temporal lobe epilepsy (TLE) regardless of its etiology. In this study, we examined the relation between reduction of calbindin immunoreactivity and the verbal and visuo-spatial memory function of patients with TLE of different etiologies. Significant linear correlation was shown between calbindin expression and short-term and long-term percent retention and retroactive interference in auditory verbal learning test (AVLT) of patients including those with hippocampal sclerosis. In addition, we found significant linear regression between calbindin expression and short-term and long-term percent retention of AVLT in patients whose epilepsy was caused by malformation of cortical development or tumor and when no hippocampal sclerosis and substantial neuronal loss were detected. Together with the role of calbindin in memory established in previous studies on calbindin knock-out mice, our results suggest that reduction of calbindin expression may contribute to memory impairments of patients with TLE, particularly, when neuronal loss is not significant.

Degree and pattern of calbindin immunoreactivity in granule cells of the dentate gyrus differ in mesial temporal sclerosis, cortical malformation- and tumor-related epilepsies

A loss of calbindin immunoreactivity in granule cells of the hippocampal dentate gyrus is a characteristic feature of temporal lobe epilepsy with hippocampal sclerosis. Whether decreased calbindin expression is unique to the hippocampal sclerosis associated with cryptogenic temporal lobe epilepsy, or also occurs in tumor- or malformation-related epilepsy, is unknown. We show that calbindin immunoreactivity in granule cells has been decreased in epilepsy regardless of its etiology. In cases of cortical malformations or hippocampal sclerosis, calbindin immunoreactivity was undetectable in most granule cells. In tumor-related resections, in patients who had a long history of epileptic seizures, calbindin was detected only in one-third of granule cells. Regardless of etiology, calbindin expression correlated with age of onset and with duration of the epilepsy. In contrast to tumor-induced epilepsy, where calbindin-immunoreactive granule cells were equally distributed in the granule cell layer, in hippocampal sclerosis and malformation-related epilepsy, two-thirds of calbindin-immunoreactive granule cells were located in the outer half and only one-third in the inner half of the layer. Developmentally, granule cells at the border of the molecular layer are ontogenetically the oldest, and those at the border of the hilus are the youngest. The reduction of calbindin immunoreactivity in ontogenetically younger granule cells highlights the deleterious effect of early occurring epilepsy and initial early precipitating injury, including febrile seizures that may substantially affect developing immature granule cells, but less the earlier born matured ones.

Comparison of CT characteristics of extravertebral cement leakages after vertebroplasty performed by different navigation and injection techniques

SummaryObjective. This study was intended to assess the results of post-operative CT scans in three groups of patients following percutaneous vertebroplasty (VP) using different navigation and injection methods, in an attempt to explain the radiological characteristics of extravertebral cement leakage with relation to needle placement and focused on the ventral epidural accumulation of bone cement. Furthermore, we have suggested a morphological (and functional) classification of the types of cement leakage. Methods. Between July 2001 and February 2005, 123 percutaneous VP procedures were performed during 75 sessions in 65 patients for treatment of painful osteoporotic vertebral body compression fractures. These included:- Group I: 28 patients, 33 sessions; 50 right sided unilateral VP under fluoroscopic control with central position of the tip of the needle within the bone marrow. Group II: 27 patients, 28 sessions; 50 bilateral VP under fluoroscopic control with separate cement injections into both “hemivertebrae”. Group III: 14 patients, 14 sessions; 23 bilateral VP navigated by frameless stereotaxy (neuronavigation). Needles were positioned strictly into the lateral thirds of the vertebral bodies. Leakages were classified as epidural, foraminal, intradiscal, venous paravertebral, compact extravertebral on the post-operative CT scans, and their frequency was compared in relation to the navigation method and the position of the tip of the needle. Results.Group I: extravertebral cement was detected in 23 patients (82%), and in 35 (70%) of the 50 vertebrae treated (ventral epidural: 23 vertebrae = 46%; intradiscal: 12 vertebrae = 24%; venous paravertebral: 8 vertebrae = 16%; intraforaminal: 7 vertebrae = 14%; and compact extravertebral: 3 vertebrae = 6%). Group II: extravertebral cement was detected in 20 patients (74%), and in 38 (76%) of the 50 vertebrae treated (ventral epidural: 12 vertebrae = 24%; intradiscal: 12 vertebrae = 24%; venous paravertebral: 9 vertebrae = 18%; and foraminal: 1 vertebra = 2%). Group III: extravertebral cement could be detected in 10 patients (71%), and in 10 (43%) of the 23 vertebrae treated (ventral epidural: 3 vertebrae = 13%; intradiscal: 8 vertebrae = 34%; venous paravertebral: 4 vertebrae = 17%). Conclusion. The incidence of epidural accumulation of bone cement may be concluded to be closely correlated with the position of the tip of the needle. Centrally injected bone cement may easily invade into the basivertebral system, and the material can then be transferred via these veins toward the ventral epidural space, and result in canal compromise and/or compression of the neural elements. The results of statistical analysis (Chi-square test) revealed that injection of bone cement into the lateral third of the vertebral body significantly decreases the extent of ventral epidural leakage. Therefore, a strictly lateral injection is advised, when the tip of the needle is placed into the lateral third of the vertebral body. Frameless stereotaxy navigation improves achievement of accurate needle placement and decreases the frequency of ventral epidural leakage. It is a safe and very accurate method for positioning of the injecting needles.

Characterization of neurons in the cortical white matter in human temporal lobe epilepsy.

The aim of the present work was to characterize neurons in the archi- and neocortical white matter, and to investigate their distribution in mesial temporal sclerosis. Immunohistochemistry and quantification of neurons were performed on surgically resected tissue sections of patients with therapy-resistant temporal lobe epilepsy. Temporal lobe tissues of patients with tumor but without epilepsy and that from autopsy were used as controls. Neurons were identified with immunohistochemistry using antibodies against NeuN, calcium-binding proteins, transcription factor Tbr1 and neurofilaments. We found significantly higher density of neurons in the archi- and neocortical white matter of patients with temporal lobe epilepsy than in that of controls. Based on their morphology and neurochemical content, both excitatory and inhibitory cells were present among these neurons. A subset of neurons in the white matter was Tbr-1-immunoreactive and these neurons coexpressed NeuN and neurofilament marker SMI311R. No colocalization of Tbr1 was observed with the inhibitory neuronal markers, calcium-binding proteins. We suggest that a large population of white matter neurons comprises remnants of the subplate. Furthermore, we propose that a subset of white matter neurons was arrested during migration, highlighting the role of cortical maldevelopment in epilepsy associated with mesial temporal sclerosis.

Biexponential diffusion alterations in the normal-appearing white matter of glioma patients might indicate the presence of global vasogenic edema

To investigate normal‐appearing white matter (NAWM) microstructure of glioma patients with biexponential diffusion analysis in order to reveal the nature of diffusion abnormalities and to assess whether they are region‐specific or global.

Occlusive hydrocephalus complicating tuberous sclerosis: report of two cases.

Two patients—6 and 14 years old—with tuberous sclerosis are presented. Both developed a subependymal giant cell astrocytoma from nodules located near to the foramen of Monro. They caused obstruction of the cerebrospinal fluid pathways. Signs of raised intracranial pressure were detected in both patients, and one of them had also developed infantile spasm—Blitz‐Nick‐Salaam seizures. Cutaneous stigmata being characteristic for this entity were observed in both cases, but their mental development was unaffected. Diagnosis was based on computed tomography. Angiography did not reveal pathological vessels. The tumours were completely excised through transcallosal exposure in both cases. The patients have been symptom‐free during the follow‐up time of 1 and 2 years. Although the incidence of malignant transformation of tuberous sclerosis is less than 15% the disease generally has a poor prognosis which can be ascribed to sudden increase of intracranial pressure caused by obstruction of cerebrospinal fluid pathways by paraventricular tumours. However, regular follow‐up of paraventricular nodules and maintenance of patency of cerebrospinal fluid pathways by microsurgical methods in patients suffering from mild cerebral disorders offers a better chance of survival.