Kost Elisevich

A direct brain interface based on event-related potentials

Cross-correlation between a trigger-averaged event-related potential (ERP) template and continuous electrocorticogram was used to detect movement-related ERPs. The accuracy of ERP detection for the five best subjects (of 17 studied), had hit percentages >90% and false positive percentages <10%. These cases were considered appropriate for operation of a direct brain interface.

SPARC: A Signal of Astrocytic Neoplastic Transformation and Reactive Response in Human Primary and Xenograft Gliomas

In an attempt to identify genetic alterations occurring early in astrocytoma progression, we performed subtractive hybridization between astrocytoma and glioblastoma cDNA libraries. We identified secreted protein acidic and rich in cysteine (SPARC), a protein implicated in cell-matrix interactions, as a gene overexpressed early in progression. Northern blot and immunohistochemical analyses indicated that transcript and protein were both elevated in all tumor specimens (grades II-IV) examined when compared with levels in normal brain. The level of SPARC expression was found to be tumor-dependent rather than grade-related. Immunohistochemically, SPARC protein was found to be overexpressed in 1) cells in the less cellularly dense regions within the tumor mass, 2) histomorphologically neoplastic-looking cells in adjacent normal brain at the tumor/brain interface, 3) neovessel endothelial cells in both the tumor and adjacent normal brain, and 4) reactive astrocytes in normal brain adjacent to tumor. Using a combination of DNA in situ hybridization and protein immunohistochemical analyses of the human/rat xenograft, SPARC expression was observed in the human glioma cells within the tumor mass, and in cells that invaded along vascular basement membranes and individually into the rat brain parenchyma, suggesting it may be an invasion-related gene. While it remains to be determined whether SPARC functionally contributes to tumor cell invasion, these data suggest that the early onset of increased SPARC expression, though complex, may serve as a signal indicative of neoplastic astrocytic transformation and reactive response to tumor-induced stress.

Auditory cortex stimulation for tinnitus.

Functional imaging techniques have demonstrated a relationship between the intensity of tinnitus and the degree of reorganization of the primary auditory cortex. Studies in experimental animals and humans have revealed that tinnitus is associated with a synchronized hyperactivity in the auditory cortex and proposed that the underlying pathophysiological mechanism is thalamocortical dysrhythmia; hence, decreased auditory stimulation results in decreased firing rate, and decreased lateral inhibition. Consequently, the surrounding brain area becomes hyperactive, firing at gamma band rates; this is considered a necessary precondition of auditory consciousness, and also tinnitus. Synchronization of the gamma band activity could possibly induce a topographical reorganization based on Hebbian mechanisms. Therefore, it seems logical to try to suppress tinnitus by modifying the tinnitus-related auditory cortex reorganization and hyperactivity. This can be achieved using neuronavigation-guided transcranial magnetic stimulation (TMS), which is capable of modulating cortical activity. If TMS is capable of suppressing tinnitus, the effect should be maintained by implanting electrodes over the area of electrophysiological signal abnormality on the auditory cortex. The results in the first patients treated by auditory cortex stimulation demonstrate a statistically significant tinnitus suppression in cases of unilateral pure tone tinnitus without suppression of white or narrow band noise. Hence, auditory cortex stimulation could become a physiologically guided treatment for a selected category of patients with severe tinnitus.

Morbidity and infection in combined subdural grid and strip electrode investigation for intractable epilepsy

The coverage of large surface areas of the brain for electrographic monitoring purposes necessitates a craniotomy to achieve comprehensive sampling. We undertook a review and prospective analysis over 3 years of 38 patients undergoing craniotomy for electrode implantation. The indication for invasive monitoring was to determine candidacy for resective surgery in patients whose seizure focus was not well localized by scalp electroencephalography and other noninvasive testing. Prophylactic cultures from the epidural space were obtained at electrode removal. There were five positive epidural cultures. All five patients went on to seizure-free status. Two positive cultures occurred in patients without obvious infection and who were not treated with antibiotics. Other complications included individual cases of atrial fibrillation, pulmonary edema, postoperative fever, and epidural hematoma. There was no mortality or permanent neurologic morbidity related to craniotomy for electrode placement. There was a 7.9% rate of clinical infection per patient and a 5.7% rate per craniotomy side. This study has identified several factors that significantly correlate with positive epidural culture results: > 100 electrodes, more than ten cables, more than 14 days of implantation, and more than one cable exit site.

Effect of Ionizing Radiation on Partial Seizures Attributable to Malignant Cerebral Tumors

Empirical evidence in the clinical literature suggests that ionizing radiation influences human epileptic behavior. A group of patients with tumor-associated epilepsy, biopsy-proven malignancy, and primary antineoplastic treatment with ionizing radiation was selected to evaluate this observation. The antiepileptic effect of ionizing radiation was examined in 9 patients presenting with malignant cerebral tumor and medically refractory partial seizures during at least 2 months. Tissue diagnosis was obtained by stereotactic biopsy without further surgery. Histological categories included anaplastic astrocytoma (5 cases), glioblastoma (2), lymphoma (1), and metastatic non-small cell carcinoma of the lung (1). All patients had medically refractory simple partial seizures with or without secondary generalization with frequencies of 3/week to 8/day for 2-7 months before completion of therapy. Fractionated radiation therapy by parallel opposed fields was delivered with a cumulative dose range of 3,000-6,600 cGy. One patient also had 125I brachytherapy with implant removal after 6 months. Five patients had a seizure-free outcome for periods lasting 2-12 months, whereas the remainder experienced a reduction in frequency of greater than 75% during a follow-up period of 3 months to 6 years. One patient with a glioblastoma remained seizure-free for 3 months and experienced 2 generalized seizures during tumor progression and clinical deterioration but otherwise remained under good anticonvulsant control until his death after 1 year. This review of cases of partial seizures attributable to an unresected malignant cerebral tumor indicates that ionizing radiation may have a favorable effect upon medically refractory partial seizures with significant reduction or elimination of seizures. Moreover, the effect lasts beyond the immediate and early postradiation period. The therapy may thus also lessen the propensity for cerebral tissue towards later epileptogenicity that gives rise to a partial seizure disorder.

Hippocampal volumetry for lateralization of temporal lobe epilepsy: automated versus manual methods.

The hippocampus has been the primary region of interest in the preoperative imaging investigations of mesial temporal lobe epilepsy (mTLE). Hippocampal imaging and electroencephalographic features may be sufficient in several cases to declare the epileptogenic focus. In particular, hippocampal atrophy, as appreciated on T1-weighted (T1W) magnetic resonance (MR) images, may suggest a mesial temporal sclerosis. Qualitative visual assessment of hippocampal volume, however, is influenced by head position in the magnet and the amount of atrophy in different parts of the hippocampus. An entropy-based segmentation algorithm for subcortical brain structures (LocalInfo) was developed and supplemented by both a new multiple atlas strategy and a free-form deformation step to capture structural variability. Manually segmented T1-weighted magnetic resonance (MR) images of 10 non-epileptic subjects were used as atlases for the proposed automatic segmentation protocol which was applied to a cohort of 46 mTLE patients. The segmentation and lateralization accuracies of the proposed technique were compared with those of two other available programs, HAMMER and FreeSurfer, in addition to the manual method. The Dice coefficient for the proposed method was 11% (p<10(-5)) and 14% (p<10(-4)) higher in comparison with the HAMMER and FreeSurfer, respectively. Mean and Hausdorff distances in the proposed method were also 14% (p<0.2) and 26% (p<10(-3)) lower in comparison with HAMMER and 8% (p<0.8) and 48% (p<10(-5)) lower in comparison with FreeSurfer, respectively. LocalInfo proved to have higher concordance (87%) with the manual segmentation method than either HAMMER (85%) or FreeSurfer (83%). The accuracy of lateralization by volumetry in this study with LocalInfo was 74% compared to 78% with the manual segmentation method. LocalInfo yields a closer approximation to that of manual segmentation and may therefore prove to be more reliable than currently published automatic segmentation algorithms.

Direct electrical stimulation of Heschl's gyrus for tinnitus treatment.

Objectives/Hypothesis: The purpose of the study was to determine the effect of electrical stimulation of the auditory cortex in patients with tinnitus.

Hippocampal connexin 43 expression in human complex partial seizure disorder

An increase in the cellular production of gap junction proteins and increased numbers of gap junctions in the neuronoglial syncytium of an epileptic focus have been proposed as a possible mechanism underlying synchronization of discharge. To study this issue, both Northern and Western blot analyses of the gap junction protein connexin 43 mRNA and protein abundance were performed on hippocampal tissue resected from patients presenting with a complex partial seizure disorder arising from the medial temporal area and the hippocampus in particular. Samples from 15 patients with medically intractable seizures were compared to those from 5 nonepileptic patients requiring temporal lobectomy in life-threatening situations. Six of the 15 epileptic patients underwent noninvasive electrographic recording, whereas the remaining 9 patients required intracerebral electrodes for extraoperative recording and therefore showed a more discrete focality than the noninvasive recordings. A decline in the mean levels of connexin 43 mRNA expressed predominantly in astrocytes was noted in the epileptic patient groups, particularly for those cases requiring intracranial electrode placement where ictal onset was more clearly established to be intrahippocampal. Quantitation of connexin 43 protein in both epileptogenic and nonepileptogenic hippocampal tissues showed no significant differences in expression. Although mean values for mRNA showed a decline, clinical outcomes postoperatively showed no correlation with either mRNA or protein expression individually in our epileptic population. The findings indicate that there is effectively no upregulation of mRNA and no increased production of connexin 43 protein in response to the development of epileptogenicity. Rather it appears the influence of gap junctions as a substrate of epileptogenicity in any mechanism(s) underlying synchrony or electrical propagation may be a function of the dynamic state (open versus closed) of the membrane-bound gap junction.

An Assessment of MEG Coherence Imaging in the Study of Temporal Lobe Epilepsy

Purpose:  This study examines whether magnetoencephalographic (MEG) coherence imaging is more sensitive than the standard single equivalent dipole (ECD) model in lateralizing the site of epileptogenicity in patients with drug‐resistant temporal lobe epilepsy (TLE).

FLAIR signal and texture analysis for lateralizing mesial temporal lobe epilepsy

Standard magnetic resonance (MR) imaging analysis in several cases of mesial temporal lobe epilepsy (mTLE) either fail to show an identifiable hippocampal asymmetry or provide only subtle distinguishing features that remain inconclusive. A retrospective analysis of hippocampal fluid-attenuated inversion recovery (FLAIR) MR images was performed in cases of mTLE addressing, particularly, the mean and standard deviation of the signal and its texture. Preoperative T1-weighted and FLAIR MR images of 25 nonepileptic control subjects and 36 mTLE patients with Engel class Ia outcomes were analyzed. Patients requiring extraoperative electrocorticography (ECoG) with intracranial electrodes and thus judged to be more challenging were studied as a separate cohort. Hippocampi were manually segmented on T1-weighted images and their outlines were transposed onto FLAIR studies using an affine registration. Image intensity features including mean and standard deviation and wavelet-based texture features were determined for the hippocampal body. The right/left ratios of these features were used with a linear classifier to establish laterality. Whole hippocampal within-subject volume ratios were assessed for comparison. Mean and standard deviation of FLAIR signal intensities lateralized the site of epileptogenicity in 98% of all cases, whereas analysis of wavelet texture features and hippocampal volumetry each yielded correct lateralization in 94% and 83% of cases, respectively. Of patients requiring more intensive study with extraoperative ECoG, 17/18 were lateralized effectively by the combination of mean and standard deviation ratios despite a ratio of mean signal intensity near one in some. The analysis of mean and standard deviation of FLAIR signal intensities provides a highly sensitive method for lateralizing the epileptic focus in mTLE over that of volumetry or texture analysis of the hippocampal body.