Dirk Van Roost

Human temporal lobe potentials in verbal learning and memory processes

Animal experiments and lesion studies have shown the importance of temporal lobe structures for language and memory. We recorded intracranial cognitive potentials from the human lateral and medial temporal lobe in 26 patients with temporal lobe epilepsy undergoing presurgical evaluation, using a word- and a picture-recognition paradigm. Neuropsychological testing included word fluency, verbal reasoning, sustained attention and a verbal learning memory test (VLMT), which was an adapted version of the Rey auditory verbal learning test. Word-specific N400-potentials elicited in the middle temporal gyrus of the dominant left hemisphere (LTL-N400) predicted immediate recall performance after learning, whereas N400s, elicited by words but not pictures in the left anterior medial temporal lobe (AMTL-N400), predicted delayed recall. The number of words that were learned but forgotten after a 30-min delay correlated only with N400s elicited by words in the left anterior medial temporal lobe. Thus, intracranial recordings indicated that different electrophysiological responses in different temporal lobe structures were linked to memory scores from specific neuropsychological tests.

Primary central nervous system lymphomas are derived from germinal-center B cells and show a preferential usage of the V4-34 gene segment

Primary central nervous system lymphomas (PCNSLs) have recently received considerable clinical attention due to their increasing incidence. To clarify the histogenetic origin of these intriguing neoplasms, PCNSLs from 10 HIV-negative patients were analyzed for immunoglobulin (Ig) gene rearrangements. All tumors exhibited clonal IgH gene rearrangements. Of the 10 cases, 5 used the V4-34 gene segment, and all of these lymphomas shared an amino acid exchange from glycine to aspartate due to a mutation in the first codon of the complementarity-determining region 1. No preferential usage of D(H), J(H), V(kappa), J(kappa), V(lambda), or J(lambda) gene segments was observed. All potentially functional rearrangements exhibited somatic mutations. The pattern of somatic mutations indicated selection of the tumor cells (or their precursors) for expression of a functional antibody. Mean mutation frequencies of 13. 2% and 8.3% were detected for the heavy and light chains, respectively, thereby exceeding other lymphoma entities. Cloning experiments of three tumors showed ongoing mutation in at least one case. These data suggest that PCNSLs are derived from highly mutated germinal-center B cells. The frequent usage of the V4-34 gene and the presence of a shared replacement mutation may indicate that the tumor precursors recognized a shared (super) antigen.

Depth electrode implantation in the length axis of the hippocampus for the presurgical evaluation of medial temporal lobe epilepsy: a computed tomography-based stereotactic insertion technique and its accuracy.

OBJECTIVEnAn individualized computed tomography-based stereotactic technique for the longitudinal insertion of intrahippocampal electrodes is presented and its accuracy described.nnnMETHODSnThe technique makes use of one well reproducible target in the hippocampal head and of the approximate inclination of the anteroposterior length axis of the hippocampus, for which the orbital floor is taken as an auxiliary landmark. It was used in 141 patients with medically intractable complex partial seizures. In 106 patients, magnetic resonance imaging (MRI) was available for assessment of implantation accuracy. Each of the 212 electrodes was plotted on topographic drawings and its goodness of fit rated.nnnRESULTSnWhereas hippocampal head and body were hit by 97 and 96% of the electrodes, respectively, the amygdala was hit by only 75% of the electrodes and mainly at its basal margin. For 93% of the electrodes, the inclination in a sagittal plane corresponded exactly to that of the hippocampus. The implantation morbidity amounted to 5.7%, whereas permanent neurological deficit occurred in one (0.7%) of the 141 patients.nnnCONCLUSIONnThis computed tomography-based protocol proved to be reliable and hence can be considered as an adequate alternative to MRI-based stereotactic implantation if MRI is not available or if a single MRI-based stereotactic set-up is unreliable because of intolerable distortions.

Safety of Intrahippocampal Depth Electrodes for Presurgical Evaluation of Patients with Intractable Epilepsy

: Purpose: Intracerebral depth electrodes are used in preoperative evaluation of selected patients with intractable epilepsies. In spite of their usefulness, safety of depth electrodes is disputed, and the number of insertions is decreasing. This study examined retrospectively possible deleterious effects such as perioperative complications, induction of epileptogenesis, and neuropsychologic deficits.

Pseudohypoxic brain swelling: a newly defined complication after uneventful brain surgery, probably related to suction drainage.

OBJECTIVEThis is the first description of a severe and sometimes fatal complication after uneventful intracranial surgery. The clinical presentation and imaging features mimic those of global cerebral hypoxia. Extensive investigations were performed to discover the pathogenesis. METHODSSeventeen cases of pseudohypoxic brain swelling (PHBS) were collected from our institution and from various other neurosurgical departments and were studied for common features. PHBS can occur in a mild, moderate, or severe degree. It is characterized by a very early postoperative onset of clinical deterioration (clouded or lost consciousness and pupillary abnormalities), in association with typical bilateral computed tomographic or magnetic resonance imaging changes (hypodensities or altered intensities in the basal ganglia and/or thalamus). The following variables were considered: age, primary pathological lesion and intracranial location, previous cranial surgery, anesthetic risk, type of anesthesia, approach and duration of surgery, intraoperative observations, technical monitoring results, and blood gas analyses. The results of postoperative computed tomography and various other imaging studies, intracranial pressure measurements, transcranial Doppler sonography, toxicological analyses, brain and muscle biopsies, and autopsies were also considered in the investigation. Several countermeasures were instituted and evaluated. RESULTSAnoxemic and ischemic hypoxia was excluded as a cause of PHBS. No evidence was found for inhibition of the respiratory chain, mitochondriopathy, poisoning, or adverse effects of drugs. CONCLUSIONIndications of intracranial hypotension, induced by suction drainage, being the main pathomechanism of PHBS are discussed. A serious warning is issued regarding the use of suction drainage after intracranial surgery.

Cellular pathology of amygdala neurons in human temporal lobe epilepsy.

The amygdala complex substantially contributes to the generation and propagation of focal seizures in patients suffering from temporal lobe epilepsy (TLE). A cellular substrate for increased excitability in the human amygdala, however, remains to be identified. Here, we analyzed the three-dimensional morphology of 264 neurons from different subregions of the amygdaloid complex obtained from 17 en bloc resected surgical specimens using intracellular Lucifer Yellow (LY) injection and confocal laser scanning microscopy. Autopsy samples from unaffected individuals (n=3, 20 neurons) served as controls. We have identified spine-laden, spine-sparse and aspinous cells in the lateral, basal, accessory basal and granular nuclei. Semiquantitative analysis points to significant changes in neuronal soma size, number of dendrites and spine densities in specimens from epilepsy patients compared to controls. Neuronal somata in the epilepsy group were smaller compared to controls (P<0.01), neurons had fewer first-order dendrites (P<0.01), whereas the maximum density of spines per dendritic segment in these cells was increased in TLE patients (P<0.01). There were also dendritic alterations such as focal constrictions or spine bifurcations. These changes were consistent between amygdaloid subregions. The dendritic morphology of amygdaloid neurons in TLE patients points to substantial changes in synaptic connectivity and would be compatible with altered neuronal circuitries operating in the epileptic human amygdala. Although the morphological alterations differ from those described in hippocampal subregions of a similar cohort of TLE patients, they appear to reflect a characteristic pathological substrate associated with seizure activity/propagation within the amygdaloid complex.

Inferior temporal stream for word processing with integrated mnemonic function.

The participation of the inferior temporal cortex in visual word perception and recognition raises several questions: Is there a directed processing stream proceeding anteriorly by continuous cortical processing? How fast are words processed within such an inferior temporal stream? Does this stream support implicit or explicit memory? To answer these questions, we analyzed the spatio‐temporal relationship of event‐related potentials, recorded directly from the inferior temporal cortex in epilepsy patients performing a continuous visual word recognition paradigm. Event‐related potentials elicited an inferior temporal positivity in a strip along the left collateral sulcus. This potential exhibited a linear (r = 0.74) peak latency progression from posterior to anterior inferior temporal regions (≈15 cm/sec), indicating a directed, intracortical processing stream. Peak amplitudes and latencies showed reliable old/new effects with smaller amplitudes and shorter latencies for old as opposed to new words. Although the amplitude‐old/new‐effect occurred for all repeated words (e.g., implicit memory), the latency‐old/new‐effect occurred for correctly recognized old words only (e.g., explicit recognition). These results seem to dissociate two distinct mnemonic processes. The graded decrease of mean ITP peak amplitudes and latencies, however, does not allow us to exclude a single trace model as assumed for explicit recognition memory based on familiarity (Mandler [ 1980 ]: Psychol Rev 87:252–271). Regardless whether there is a dissociation between implicit and explicit memory in inferior temporal cortex or not, our findings are in accordance with an integrated inferior temporal processing stream for words that performs continuously semantic and mnemonic operations supporting both implicit and explicit memory. Hum. Brain Mapping 14:251–260, 2001.

Prediction of Postoperative Seizure Control by Hippocampal Event‐Related Potentials

Summary: Purpose: In spite of unequivocal results of the presurgical evaluation, between 10 and 30% of patients with medial temporal lobe epilepsy (MTLE) do not become seizure free by temporal lobe surgery. Because event‐related potentials (ERPs) recorded within the hippocampal formation have been shown to be sensitive to the epileptogenic process, we examined whether ERPs can help to improve the prediction of postoperative seizure control.

Surgical management of brain-stem cavernomas

We present a series of seven patients who were operated on for symptomatic brain-stem cavernomas. The following approaches were used: medial suboccipital (N = 4), lateral suboccipital (N = 1), subtemporal-transtentorial (N = 1), and frontal transcortical-transventricular-subchorioidaltrans velum interpositum (N = 1). Intraoperative motor (N = 4) and somatosensory (N = 1) evoked potential monitoring revealed temporary changes in 3 patients. Immediately postoperatively, the following additional deficits were observed in 6 patients: oculomotor nerve paresis (N = 2), abducens nerve paresis (N = 3), facial nerve paresis (N = 2), deafness (N = 1), and increased ataxia (N = 3). One patient died due to septic complications not related to surgery. After a mean observation time of 2 years, 2 patients had improved, 3 were unchanged, and 1 patient deteriorated as compared to his preoperative status. In conclusion, surgical treatment of brain-stem cavernomas, although carrying a significant risk of temporary neurological deterioration is recommended in symptomatic patients in whom the cavernoma seems to reach the surface of the brain-stem. Intraoperative functional topographic mapping and monitoring have proven useful tools lowering the surgical risks in these patients.

Heterotopias, cortical dysplasias and glioneural tumors participate in cognitive processing in patients with temporal lobe epilepsy.

Focal brain lesions such as cortical dysplasia and glioneural tumors generate epileptic activity and thus may be synaptically connected with normal cortex. To test this hypothesis, we compared event-related potentials recorded directly from the medial temporal lobe (MTL) and a dysplastic lesion in eight patients with intractable temporal lobe epilepsy. The P3 component, related to visual target detection, showed different peak latencies in four patients and a larger intralesional amplitude compared to established anterior-MTL-generators in two patients. Semantic processing was identified by the N400 component and showed a different latency in four patients and larger intralesional amplitudes in two patients. These results are compatible with the hypothesis that cortical lesions interact with synaptic pathways related to cognitive functions such as visual target detection, and verbal processing.