Search

This review traces the evolution of epilepsy surgery from its early beginnings in the 20th century with the development of neurophysiology, and later the identification of pathology in surgical specimens, to the tremendous boost given by direct brain imaging in the late 20th century. This resulted in the sophisticated methods of presurgical investigation, surgical techniques, and postsurgery care available from the millennium. In parallel, functional surgery, which modifies the nervous system's behaviour, available throughout, has attained a greater place by the use of stimulation.

We assessed performance on selected tests of verbal memory in 48 patients who had undergone either anterior temporal lobectomy or selective amygdalo-hippocampectomy for the relief of pharmacologically intractable epilepsy. We related performance both to the side of surgical excision and to the presence or absence of abnormalities in the contralateral, unoperated, temporal lobe, as revealed by proton magnetic resonance spectroscopy (1H MRS) or T2 relaxometry. There were abnormalities on the unoperated side detected by 1H MRS in 50% of the 34 patients who successfully underwent spectroscopy, and by T2 relaxometry in 33% of the complete series of 48 patients. There was no systematic relationship between seizure outcome and the presence or absence of abnormalities on the unoperated side. Verbal memory deficits were present in patients with left-sided excision, regardless of whether there were abnormalities on the unoperated side. The patients with right-sided excision also had verbal memory deficits, but only in the group with magnetic resonance abnormalities on the contralateral (ie, left) side and only on delayed recall. The study extends previous findings on the role of the temporal lobes in memory and highlights the role of these new magnetic resonance techniques in relating cognitive processes to brain structures.

Three groups of patients with Parkinson's disease (PD) - mild, unmedicated (UPD), mild, medicated (MPD) and severe, medicated (SPD) - and patients with lesions of the frontal lobe (FLL) or temporal lobe (TLL) were compared with matched controls on the learning and reversal of probabilistic and two-pair concurrent colour discriminations. Both of the cortical lesion groups showed reversal deficits, with no increase in perseverative responding. The UPD group, although impaired on a spatial recognition task, showed intact discrimination learning and reversal; the MPD and SPD patients showed non-perseverative reversal impairments on both reversal tasks. Two hypotheses - based on disease severity and possible deleterious effects of medication - are offered to explain the reversal impairments of the PD patients and the results are discussed in terms of the role of dopamine in reward-based learning.

Neurophysiological studies in primates and neuroimaging studies in humans suggest that the orbito-frontal cortex is involved in representing the reward value of stimuli and in the rapid learning and relearning of associations between visual stimuli and rewarding or punishing outcomes. In the present study, we tested patients with circumscribed surgical lesions in different regions of the frontal lobe on a new visual discrimination reversal test, which, in an fMRI study (O'Doherty, Kringelbach, Rolls, Hornak, & Andrews, 2001), produced bilateral orbito-frontal cortex activation in normal subjects. In this task, touching one of two simultaneously presented patterns produced reward or loss of imaginary money delivered on a probabilistic basis to minimize the usefulness of verbal strategies. A number of types of feedback were present on the screen. The main result was that the group of patients with bilateral orbito-frontal cortex lesions were severely impaired at the reversal task, in that they accumulated less money. These patients often failed to switch their choice of stimulus after a large loss and often did switch their choice although they had just received a reward. The investigation showed that bilateral lesions were required for this deficit, since patients with unilateral orbito-frontal cortex (or medial prefrontal cortex) lesions were not impaired in the probabilistic reversal task. The task ruled out a simple motor disinhibition as an explanation of the deficit in the bilateral orbito-frontal cortex patients, in that the patients were required to choose one of two stimuli on each trial. A comparison group of patients with dorsolateral prefrontal cortex lesions was in some cases able to do the task, and in other cases, was impaired. Posttest debriefing showed that all the dorsolateral prefrontal patients who were impaired at the task had failed to pay attention to the crucial feedback provided on the screen after each trial about the amount won or lost on each trial. In contrast, all dorsolateral patients who paid attention to this crucial feedback performed normally on the reversal task. Further, it was confirmed that the bilateral orbito-frontal cortex patients had also paid attention to this crucial feedback, but in contrast had still performed poorly at the task. The results thus show that the orbital prefrontal cortex is required bilaterally for monitoring changes in the reward value of stimuli and using this to guide behavior in the task; whereas the dorsolateral prefrontal cortex, if it produces deficits in the task, does so for reasons related to executive functions, such as the control of attention. Thus, the ability to determine which information is relevant when making a choice of pattern can be disrupted by a dorsolateral lesion on either side, whereas the ability to use this information to guide behavior is not disrupted by a unilateral lesion in either the left or the right orbito-frontal cortex, but is severely impaired by a bilateral lesion in this region. Because both abilities are important in many of the tasks and decisions that arise in the course of daily life, the present results are relevant to understanding the difficulties faced by patients after surgical excisions in different frontal brain regions.

Summary To analyse the functions of different parts of the prefrontal cortex in emotion, patients with different prefrontal surgical excisions were compared on four measures of emotion: voice and face emotional expression identification, social behaviour, and the subjective experience of emotion. Some patients with bilateral lesions of the orbitofrontal cortex (OFC) had deficits in voice and face expression identification, and the group had impairments in social behaviour and significant changes in their subjective emotional state. Some patients with unilateral damage restricted to the OFC also had deficits in voice expression identification, and the group did not have significant changes in social behaviour or in their subjective emotional state. Patients with unilateral lesions of the antero-ventral part of the anterior cingulate cortex (ACC) and/or medial Brodmann area (BA) 9 were, in some cases, impaired on voice and face expression identification, had some change in social behaviour, and had significant changes in their subjective emotional state. Patients with unilateral lesions of the OFC and of the ACC and/or medial BA 9 were, in some cases, impaired on voice and face expression identification, had some changes in social behaviour, and had significant changes in their subjective emotional state. Patients with dorsolateral prefrontal cortex lesions or with medial lesions outside ACC and medial BA 9 areas (dorsolateral/other medial group) were unimpaired on any of these measures of emotion. In all cases in which voice expression identification was impaired, there were no deficits in control tests of the discrimination of unfamiliar voices and the recognition of environmental sounds. Thus bilateral or unilateral lesions circumscribed surgically within the OFC can impair emotional voice and/or face expression identification, but significant changes in social behaviour and in subjective emotional state are related to bilateral lesions. Importantly, unilateral lesions of the ACC (including some of medial BA 9) can produce voice and/or face expression identification deficits, and marked changes in subjective emotional state. These findings with surgically circumscribed lesions show that within the prefrontal cortex, both the OFC and the ACC/medial BA 9 region are involved in a number of aspects of emotion in humans including emotion identification, social behaviour and subjective emotional state, and that the dorsolateral prefrontal areas are not involved in emotion in these ways.

Objectives - To assess the prognostic factors determining seizure remission after temporal lobectomy for intractable epilepsy associated with mesial temporal sclerosis (MTS) at pathology. Methods - The clinical and investigative features of 116 consecutive patients who had temporal lobe surgery for drug-resistant epilepsy and MTS at pathology were assessed using actuarial statistics and logistic regression analysis. Results - At a median follow-up of 63 months the probability of achieving at least a 1-year period of continuous seizure freedom was 67%. Factors contributing to a favourable outcome were interictal EEG localization to the operated lobe and the absence of secondarily generalized seizures. These were also selected in the multivariate analysis, although at lower statistical significance (P=0.08 and 0.09, respectively). Perinatal complications were associated with a significantly worse outcome but overall, complicated febrile convulsions and congruent neuropsychological deficits were not significantly predictive variables. Conclusions - The present findings may aid in the non-invasive presurgical assessment of patients with intractable TLE and clinical and neuroimaging evidence of MTS.

Objectives: To investigate the relationship between recognition memory and metabolite levels in medial structures of the temporal lobes in the living human brain. Methods: Proton MRS ( 1 H MRS) and the intracarotid amobarbital test were performed in 16 epileptic patients found suitable for temporal lobectomy. All patients had mesial temporal sclerosis. Metabolite ratios between N -acetylaspartate (NAA), creatine and phosphocreatine (Cr + PCr), and choline-containing compounds (Cho) [NAA/(Cr + PCr), NAA/Cho, and NAA/(Cr + PCr + Cho)] were calculated for 1 H MRS voxels that included the amygdala, anterior half of the hippocampus, and underlying subiculum. Metabolite ratios were correlated with unilateral memory scores estimated by the intracarotid amobarbital test for words, objects, faces, and total score. Results: The total memory score, memory for objects and faces, and NAA/(Cr + PCr) were significantly lower for the hemisphere ipsilateral to the resection. The asymmetry indexes for NAA/(Cr + PCr) correlated with asymmetry indexes for words (ρ = 0.82, p = 0.0001) and total memory (ρ = 0.72, p = 0.002). Analysis of memory scores and metabolite ratios from all 32 hemispheres revealed a correlation between NAA/(Cr + PCr) and memory for words (ρ = 0.45, p = 0.009). A correlation between memory for words and NAA/(Cr + PCr) existed in the contralateral (ρ = 0.58, p = 0.019) and in the right (ρ = 0.51, p = 0.045) hemispheres, and a trend was found in the left hemispheres (ρ = 0.48, p = 0.06). Conclusion: There is a correlation between memory for words and the NAA/(Cr + PCr) ratio from medial temporal structures in patients with mesial temporal sclerosis. The findings suggest that medial temporal structures and adjacent neocortex play a significant role in recognition memory in humans, particularly for words.

OBJECTIVES—To study the variability, topography, polarity, duration, and incidence of interictal epileptiform discharges (EDs) in the scalp EEG and electrocorticogram (ECoG) from 16 patients with temporal lobe epilepsy who underwent surgical treatment. METHODS—Preoperative scalp EEGs during quinalbarbitone induced sleep were compared with preresection ECoGs obtained under general anaesthesia. The analysis was based on the initial ECoG record obtained before activation by intravenous thiopentone, and the EEG during stages I and II of sleep. RESULTS—On the scalp, 15 patients had a single discharge pattern, spikes were predominantly negative, EDs were of largest amplitude at the anterior temporal electrode in 13 patients and mean discharge incidence was 4.0 (SD 4.2) discharges/min. In ECoG recordings, nine patients had two independent ECoG patterns, the polarity of spikes was negative, positive-negative, or positive, the site of maximal amplitude varied greatly between subjects, discharge incidence was 7.3 (SD 3.9) discharges/min. There was no relation between the topography of the largest spikes on the scalp and in the ECoG. In 14 patients, scalp spikes showed statistically significant longer duration on the scalp than in the ECoG. In seven patients who had frequent widespread ECoG discharges, averaging spikes across ECoG channels generated spiky patterns of duration similar to that of scalp spikes. CONCLUSION—It seems that, in temporal lobe epilepsy, scalp discharges originate from widespread ECoG discharges and tend to produce a stereotyped pattern on the scalp with largest amplitudes at the anterior temporal electrodes. This is probably due to local anatomical peculiarities in the brain coverings, such as skull discontinuities, rather than to the location of neuronal generators within the temporal lobe. Due to spatiotemporal averaging, widespread cortical discharges which become asynchronous during propagation appear with increased duration and blunted waveform in the EEG, whereas sharply localised phenomena such as positive focal spikes are not recorded from the scalp.

Aims In a retrospective study of resected specimens from 416 patients being treated for long-standing epilepsy, 74 cases of dysembryoplastic neuroepithelial tumour (DNT) were encountered that were all characteristically composed of small round oligodendroglia-like cells (OLC), astrocytes and mature neurones in varying proportions. The architectural patterns, histological, immunohistochemical and ultrastructural features and results of cell proliferation studies and postoperative follow-up are described to facilitate the identification of DNT and to differentiate it from other intrinsic neoplasms that commonly present with seizures. Methods and results The tumours presented with early onset of seizures, at a median age of 7 years, without the signs of raised intracranial pressure. A majority of the lesions were located in the temporal lobe (n = 59), with fewer cases in the frontal (n = 8), parietal (n = 6) and occipital lobes (n = 1), and ranged in size from 10 to 70 mm; 33 were cystic. Histologically three types could be distinguished, multinodular, solitary nodular and diffuse. The first type (37.8%) had the features of a typical DNT with multinodular architecture and mixed cellular composition. The second type (33.8%) consisted of a solitary nodule, while the third (28.4%) was a diffuse tumour, both composed of a similar mixture of cells as the multinodular DNT. The lesions were seen in the neocortex and white matter and tumours in the temporal lobe often involved the amygdala and hippocampus. The presence of myxoid matrix, microcystic change, calcification and leptomeningeal involvement were common. Dysplastic neurones at the periphery of the tumour and abnormalities in cortical lamination in the adjacent neocortex were found in about one-third of the resections. Rare mitotic figures were encountered in eight of the tumours and necrosis was found in two. Immunocytochemistry for glial fibrillary acidic protein (GFAP) and neuronal markers neuron-specific enolase, synaptophysin and neurofilament (RT 97) assists in establishing the diagnosis, highlighting the astrocytic and neuronal components, and the OLC, by the absence of expression of GFAP. Electron microscopy showed that in some cases OLC show neuronal differentiation. Although the proliferating cell nuclear antigen labelling index varied between 0 and 45.5%, 20 of the 51 tumours stained failed to express the antigen, in keeping with the indolent nature of this neoplasm. The response to surgery was excellent; none of the tumours have recurred, and the control of seizures remained good. Conclusions Despite some histological heterogeneity, the clinical and pathological features and indolent biological behaviour indicate that these tumours constitute a single distinct entity. The spectrum of morphological appearances of DNT is broader than has been previously reported, the recognition of which is needed to avoid unnecessary neoadjuvant therapy.

OBJECTIVES To determine predictors for surgical outcome in the presurgical assessment of frontal lobe epilepsy. METHODS Thirty seven patients were operated on for frontal lobe epilepsy between 1975 and 1996. Their medical records were reviewed for ictal semiology, age at onset, duration of the epilepsy, age at operation, preoperative interictal and ictal encephalographic findings, and abnormalities on neuroimaging and neuropsychological testing. In addition, type of resection and pathology were compared with surgical outcome. RESULTS Univariate statistical analysis showed that the presence of a focal abnormality on neuroimaging was associated with favourable outcome. The presence of the following ictal findings was associated with poor outcome: autonomic manifestations, eye deviation, head version contralateral to the operated side, and bilateral or multifocal ictal onset. Fifteen patients had secondarily generalised interictal discharges and, interestingly, their presence was not associated with poor outcome. Multivariate logistic regression showed that the presence of a focal abnormality on neuroimaging was significantly associated with a favourable outcome while contralateral head version was the only variable significantly associated with poor surgical outcome. CONCLUSIONS A focal abnormality on neuroimaging was the only variable which was significantly associated with a favourable surgical outcome, whereas contralateral head version was the most significant predictor for a poor outcome. The presence of generalised discharges before surgery was not associated with poor outcome.

Memory for stories was investigated in 25 patients with frontal lobe excisions and 25 control subjects. The subjects were presented with three different story types that either conformed to a well-known script, contained the same elements as a script but in a randomised order, or described a novel event. Subjects were asked to perform a test of recognition memory and memory for order on words presented in each story. The frontal lobe patients were unimpaired on the recognition memory test for salient words taken from each story. However, an impairment was observed in the frontal patients when they were asked to order the words taken from the novel story only. This deficit was no longer seen when the subjects were required to order sentences describing the key events in the story. These findings help to elucidate the role of the frontal lobes in memory for order information.

Although acute electrocorticography (ECoG) is routinely performed during epilepsy surgery there is little evidence that the extent of the discharging regions is a useful guide to tailoring the resection or that the findings are predictive of outcome or pathology. Patterns of discharge propagation have, however, rarely been considered in assessing the ECoG. We hypothesize that regions where discharges show earliest peaks ('leading regions') are located in the epileptogenic zone, whereas sites in which late, secondary, propagated activity occurs have less epileptogenic potential and do not need to be excised. To allow intraoperative topographic ECoG analysis, a computer program has been developed to identify leading regions and the sites showing greatest rates or amplitudes of spikes. Their topography has been compared retrospectively with pathology and seizure control in 42 consecutive patients following temporal lobe surgery. Leading regions were most often found in the hippocampus, the subtemporal cortex and the superior temporal gyrus. The most common propagation patterns were from hippocampus to subtemporal cortex and vice versa. There was no association between seizure outcome and the location of regions with greatest incidence or amplitude of spikes or location of leading regions. There was, however, a strong and significant association between poor outcome and non-removal of leading regions other than those in the posterior subtemporal cortex. All leading regions (other than posterior subtemporal) were resected in 27 patients of whom 25 had a favourable outcome. Leading regions (other than posterior subtemporal) remained in 14 patients of whom only four had a good outcome. One patient had no epileptiform activity in the ECoG and good outcome. Persistent posterior subtemporal leading regions remained in nine subjects; all had favourable outcome (Grades I or II) but only three were seizure free. These results suggest that: (i) interictal epileptiform discharges may originate from a complex interaction between separate regions, resulting in propagation and recruitment of neuronal activity along specific neural pathways; (ii) removal of all discharging areas appears unnecessary to achieve seizure control provided that leading regions (other than posterior subtemporal) are removed; and (iii) identification of such leading regions could be used to tailor resections in order to improve seizure control and reduce neurological, neuropsychological and psychiatric post-surgical morbidity.

An 11-channel multiplexed stimulator of nerves and muscles in the left forearm was implanted for hand control in January 1986 in a 21 year old woman who, after sustaining a C6 spinal lesion 7 years earlier, had voluntary shoulder and elbow movement but paralysed hands, trunk and legs. The patient controls the stimulation via a microcomputer control box and an RF transdermal link. We have investigated the control of her stimulated hand with a joystick under her contralateral hand which she moves from the shoulder and elbow. Since 1986, we have tried a variety of joystick control schemes involving power and key grips. Currently, for grip adjustment, forward and backward joystick movements correspond to thumb extension and abduction, respectively giving in addition both finger and wrist extension, whereas right and left joystick movements yield first closure and thumb opposition/adduction and flexion, respectively. Useful grasps are available by moving the joystick forward and then left (key grip), by moving the joystick backward and left (pinch grip), or by moving the joystick back and right (power grip). Thus, three distinct grips may be selected using these three quadrants of joystick movement. An additional control mode was found to be desirable to augment the patient's limited voluntary wrist positioning and provide wrist stability while adjusting finger grip.

Alterations in emotional and social functioning such as impaired ability to recognize emotions in others, a lack of empathy and poor insight have commonly been reported following prefrontal cortex damage. This study sought to investigate the subtleties of such difficulties in 34 individuals with discrete unilateral and bilateral neurosurgical lesions encroaching on the orbitofrontal, medial, and dorsolateral regions of the prefrontal cortex. A specifically devised self- and informant report measure, the social-emotional questionnaire was used to examine five factors of functioning: emotion recognition; empathy; social conformity; antisocial behaviour; and sociability. There were some specific significant differences between the clinical and control groups' informant-ratings in certain domains of social and emotional functioning. Individuals with damage involving the orbitofrontal region were reported to display elevated levels of antisocial behaviour. Individuals with bilateral orbitofrontal lesions were rated as showing significantly reduced social and emotional functioning in comparison with individuals with unilateral lesions and controls. In addition, individuals with bilateral lesions had significantly less insight overall regarding their social-emotional abilities. The right unilateral lesion group showed significantly less insight into their abilities to recognize emotion in others in comparison with the left unilateral group. In conclusion, these results suggest that specific social-emotional and insight deficits may form separate constellations of impairment. The findings also indicate that marked changes in social and emotional functioning are more likely following bilateral damage, and unilateral lesions do not inevitably lead to impairments.

The preresection and postresection intraoperative electrocorticograms of 76 consecutive patients undergoing resective surgery for intractable epilepsy were analyzed to see if location, configuration, and discharge rate of epileptiform activity correlated with type and location of pathology of the resected specimens and outcome in regard to seizure control. The location of the predominant spike focus did not correlate with either type of location of pathology or with seizure outcome from temporal lobe surgery (n = 58). The presence of spontaneous or activated spikes outside the resected area did not correlate with outcome from any surgery type. Positive spikes recorded from the amygdala and anterior hippocampus (n = 37) were not associated with type or location of pathology, but bursts of fast repetitive spikes on these needle recordings tended to associate with mesiotemporal pathology (p = less than 0.02) and with mesial temporal sclerosis (p = less than 0.04). A preresection spike discharge rate of 1 per 4 minutes or less was associated with a poor outcome in 5 of 6 patients (p = 0.03), whereas a rate of 18 or more per minute was associated with a good outcome in 15 of 18 patients (p less than 0.06). Persistence of 50% or more of the preresection epileptiform activity in the postresection electrocorticogram after temporal lobectomy correlated with poor outcome in 80% (p = less than 0.03), although the absolute amount of epileptiform activity remaining in the postresection electrocorticogram did not correlate with outcome. Further studies are needed to define the role of intraoperative electrocorticograms in resective epilepsy surgery.

A technique for extradural deafferentation of the S2 to S5 segments and extradural implantation of stimulating electrodes is described, and its application to twelve patients with spinal cord lesions is reported. Nine patients use their implants for micturition, and seven are fully continent. The advantages and disadvantages of this technique compared with the more usual intrathecal procedure are discussed.

A method of direct stereotactic placement of recording depth electrodes in the temporal lobe structures is described. The advantages of this approach, namely its simplicity, accuracy and flexibility, are discussed.

Objective: To assess the value of single-pulse electrical stimulation (SPES) to identify frontal epileptogenic cortex during presurgical assessment. Methods: SPES (1-millisecond pulses, 4 to 8 mA, 0.1 Hz) has been used during chronic recordings in 30 patients with intracranial electrodes in the frontal lobes. As a result of presurgical assessment, 17 patients were considered to have frontal epilepsy and 13 extrafrontal epilepsy. Results: Two types of responses to SPES were seen: 1) early responses: starting immediately after the stimulus and considered as normal responses; 2) late responses: two types of responses seen in some areas after the initial early response: a) delayed responses: spikes or sharp waves occurring between 100 milliseconds and 1 second after stimulation. Frontal delayed responses were seen in 11 frontal patients and 1 extrafrontal patient, whereas extrafrontal delayed responses were seen in 1 frontal and 10 extrafrontal patients. b) Repetitive responses: two or more consecutive sharp-and-slow-wave complexes, each resembling the initial early response. Repetitive responses were seen only when stimulating the frontal lobes of 10 frontal patients. Among the 17 frontal patients, 13 had late responses exclusively in the epileptogenic frontal lobe, whereas only 3 showed them in both frontal lobes. Frontal late responses were associated with neuropathologic abnormalities, and complete resection of abnormal SPES areas was associated with good postsurgical seizure outcome. Conclusions: Single-pulse electrical stimulation (SPES) could be an important additional investigation during presurgical assessment to identify frontal epileptogenicity. SPES can be useful in patients who have widespread or multiple epileptogenic areas, normal neuroimaging, or few seizures during telemetry.

Summary: Purpose: To determine the characteristics and the clinical significance of focal slow activity and its association with focal epileptogenesis in patients with temporal lobe epilepsy (TLE). Methods: We analyzed the interictal EEGs of 141 patients who had temporal lobe resections for intractable focal seizures and correlated the findings with pathologic changes and outcome. The pathologic changes were categorized into medial temporal sclerosis, tumors, and nonspecific changes. Results: Lateralized slow activity was found in 66% of the patients, and it was mainly temporal, of delta frequency and irregular morphology. None of its characteristics, including quantity and reactivity to eye opening, was substrate specific. It was highly concordant with temporal spiking (60%), without any difference across the three groups, but provided additional information in 19 (15%) patients who had no lateralizing spikes. The effect of sleep also was similar in all three groups and included transition of slow waves into spikes. Lateralized slow activity to the side of the operation was significantly associated with favorable outcome only in the group with nonspecific pathology (p = 0.008), regardless of the presence, laterality, or topography of spikes. Conclusions: Our findings suggest that in patients with TLE whose brain magnetic resonance imaging (MRI) is either normal or suggestive of medial temporal sclerosis, interictal temporal slow activity has a lateralizing value similar to that of temporal spiking. Its association with a favorable outcome in patients with nonspecific pathology also suggests that candidates with lateralizing temporal delta and normal MRI should not be barred from further preoperative assessment.

There is a burgeoning interest in the neural basis of the ability to attribute mental states to others; a capacity referred to as 'theory of mind' (ToM). We examined the effects of lesions of the amygdala which arise at different stages of development on this key aspect of social cognition. Tests of ToM, executive and general neuropsychological function were given to subjects with lesions of the amygdala arising congenitally or in early childhood ('early damage', n = 15), subjects who acquired damage to the amygdala in adulthood ('late damage' n = 11) and matched clinical (n = 14) and healthy comparison groups (n = 38). Subjects with early damage to the amygdala, particularly if the lesion was associated with childhood onset of seizures, were impaired relative to all other groups on more advanced tests of ToM reasoning, such as detecting tactless or ironic comments or interpreting non-literal utterances. These deficits held for subjects with either left or right early amygdala damage and encompassed the understanding of both the beliefs and emotional states of others. In contrast, subjects who acquired damage to the amygdala in adulthood (usually as part of an anterior temporal lobectomy) were not impaired in ToM reasoning relative to both clinical and healthy controls, supporting the position that the amygdala is not part of the neural circuitry mediating the 'on-line' performance of ToM reasoning. In line with theories which claim that ToM is an independent faculty of cognition, we found that the pattern of results held after co-varying for measures of executive function, memory and general intellectual functioning. We discuss the results in the light of recent theories which link early developmental insults to the amygdala with the ToM impairments which are thought to be a core neurocognitive deficit found in disorders such as autism. We conclude that the amygdala may play an important role in the neural systems supporting the normal development of ToM reasoning.

To assess the efficacy of vagus nerve stimulation (VNS) in patients with medically and surgically intractable complex partial seizures (CPS).Sixteen patients with previous temporal [15] and frontal [one] resections were treated with VNS between 1994 and 1999 at King's College Hospital, London, UK. Post-operative video-electroencephalogram telemetry had shown that CPS started from the operated side in 12 patients, contralaterally in three and bilaterally independently in one.Three patients (18.75%) had 50% or more reduction in seizure frequency, but one showed severe worsening of epilepsy, which remitted upon VNS discontinuation. The antiepileptic effect of VNS was not different with respect to the type of operation (anterior temporal lobectomy vs amygdalohippocampectomy), the side of operation, or the side of seizure onset. We observed psychotropic effects in two patients with post-ictal psychosis, in two others with depression, and in a child with severe behavioral disorder.VNS may have a rather limited antiepileptic role to play in patients with persistent seizures following epilepsy surgery, but may independently possess useful antipsychotic and mood-stabilizing properties.

Three of 282 consecutive patients who had temporal resections for intractable epilepsy developed postoperative postictal psychosis. These three patients had seizure recurrence contralateral to the resection, whereas none of the patients with ipsilateral seizure recurrence developed any psychiatric symptoms after surgery. Two had left amygdalo-hippocampectomy and one right temporal lobectomy. The de novo occurrence of postoperative postictal psychosis is a well-defined complication of surgery for temporal lobe epilepsy, and may relate to contralateral epileptogenesis.

The aim of the present study was to investigate in vivo cortical excitability in the human brain. We studied 45 consecutive patients with refractory epilepsy in whom subdural or intracerebral electrodes were implanted for assessment prior to epilepsy surgery. We compared cortical responses to single pulse stimulation (up to 8 mA, 1 ms duration) in areas where seizure onset occurred, with responses recorded elsewhere. Two main types of responses were seen: (i) 'early responses', spikes and/or slow waves starting within 100 ms after the stimulus which were observed in most regions in all patients; and (ii) 'delayed responses', spikes or sharp waves occurring between 100 ms and 1 s after stimulation which were seen in some regions in 27 patients. The distributions of early and delayed responses were compared with the topography of seizure onset. Whereas early responses were seen in most regions and seem to be a normal response of the cortex to single pulse stimulation, the distributions of delayed responses were significantly associated with the regions where seizure onset occurred. We conclude that the presence of delayed responses can identify regions of hyperexcitable cortex in the human brain. The study of delayed responses may improve our understanding of the physiology and dynamics of neuronal circuits in epileptic tissue and may have an immediate clinical application in assessment of candidates for surgical treatment of epilepsy.

To assess the prognostic factors determining seizure remission after temporal lobectomy for intractable epilepsy associated with mesial temporal sclerosis (MTS) at pathology.The clinical and investigative features of 116 consecutive patients who had temporal lobe surgery for drug-resistant epilepsy and MTS at pathology were assessed using actuarial statistics and logistic regression analysis.At a median follow-up of 63 months the probability of achieving at least a 1-year period of continuous seizure freedom was 67%. Factors contributing to a favourable outcome were interictal EEG localization to the operated lobe and the absence of secondarily generalized seizures. These were also selected in the multivariate analysis, although at lower statistical significance (P=0.08 and 0.09, respectively). Perinatal complications were associated with a significantly worse outcome but overall, complicated febrile convulsions and congruent neuropsychological deficits were not significantly predictive variables.The present findings may aid in the non-invasive presurgical assessment of patients with intractable TLE and clinical and neuroimaging evidence of MTS.

Urgent CT scanning of critically ill neurosurgical patients is costly, labour intensive and associated with some risk. A study of urgent postoperative CT scans was carried out to assess the proportion that changed patient management. A further study evaluated the accuracy of predicting a haematoma. A retrospective analysis was carried out over a 6-month period of all scans performed within 48 h of craniotomy. This was followed by a prospective comparison between the surgeon's estimate of the chance of a haematoma on the scan and the scan result. Of 184 patient undergoing craniotomy, 40 patients (22%) were scanned within 48 h. Five patients were re-operated for haematoma formation. Prospective assessment showed that surgeons consistently over-estimated the risk at haematoma (mean prescan estimate 63%, actual risk 8%, p = 2.5 2 10 -12 ). Less than 1 in 10 postoperative scans show a neurosurgical target. Other changes in management following scanning were slight.

OBJECTIVES To evaluate the influence of clinical, investigative, and pathological factors on seizure remission after temporal lobectomy for medically intractable epilepsy associated with focal lesions other than hippocampal sclerosis. METHODS From a series of 234 consecutive “en bloc” temporal resections for medically intractable epilepsy performed between 1976 and 1995, neuropathological examination disclosed a focal lesion in 80. The preoperative clinical, neuropsychological, interictal EEG, and neuroimaging characteristics of these patients were assembled in a computerised database. The original neuropathological material was re-examined for lesion classification and completeness of removal. The presence of additional cortical dysplasia and mesial temporal sclerosis was also noted. Survival analysis was performed using Kaplein-Meier curves and actuarial statistics. Logistic regression analysis was used to establish the independent significance of the clinical variables. RESULTS The probability of achieving a 1 year seizure remission was 71% by 5 years of follow up. Factors predicting a poor outcome on multivariate analysis included the need for special schooling and a long duration of epilepsy. Generalised tonic-clonic seizures, interictal EEG discharges confined to the resected lobe, demonstration of the lesion preoperatively on CT, and complete histological resection of the lesion were not predictive of outcome. Neuropsychological tests correctly predicted outcome in left sided cases but apparently congruent findings in right sided resections were associated with a poor outcome. Pathological reclassification established the dysembryoplastic neuroepithelial tumour as the commonest neoplasm (87%) in this series, with a significantly better seizure outcome than for developmental lesions, such as focal cortical dysplasia. CONCLUSIONS The findings highlight the importance of dysembryoplastic neuroepithelial tumour in the pathogenesis of medically refractory lesional temporal lobe epilepsy and the prognostic significance of preoperative duration of epilepsy emphasises the need for early recognition and surgical treatment. Cognitive and behavioural dysfunction, however, is associated with a lower seizure remission rate, independent of duration of epilepsy.

The authors report two adult patients with chronic temporal lobe epilepsy and pathologic features consistent with Rasmussen’s encephalitis. Although seizures persisted after temporal lobe surgery no progressive cognitive or neurologic deficit has emerged. Prominent auditory auras in each suggested a persisting epileptogenic focus in the superior temporal gyrus. The current findings expand the clinical spectrum of Rasmussen’s encephalitis and suggest that chronic nonprogressive encephalitis may serve as the pathologic substrate of medically intractable temporal lobe epilepsy.

Surgical procedures used to treat chronic drug-resistant epilepsy fall into two groups. The first group, resective surgery, comprises procedures in which cerebral tissue is removed on the basis that the patient’s epilepsy arises within that area, which can be safely removed. It is necessary to show that the seizure semiology, any structural abnormality demonstrated by brain imaging, usually MRI, and the results of appropriate neurophysiological investigations are all concordant and indicate that the epilepsy originates from an epileptogenic zone within the area. In these circumstances up to 80% of patients will have a significant reduction in the seizure frequency, with a high proportion free of seizures, and a concomitant improvement in other areas such as education, employment and quality of life. The second group of surgical procedures, functional surgery, is made up of operations which aim to modify the way in which the brain deals with the pathophysiology associated with chronic epilepsy. In various ways these operations try to modify the effect of the epileptic discharges so as to reduce this activity and thus reduce the clinical seizure manifestations in the patient. Whereas the rationale behind resective surgery is fairly simple, namely, that an epileptogenic zone is identified which can be safely resected, that underlying functional surgery is more complex.

In a retrospective study of resected specimens from 416 patients being treated for long-standing epilepsy, 74 cases of dysembryoplastic neuroepithelial tumour (DNT) were encountered that were all characteristically composed of small round oligodendroglia-like cells (OLC), astrocytes and mature neurones in varying proportions. The architectural patterns, histological, immunohistochemical and ultrastructural features and results of cell proliferation studies and postoperative follow-up are described to facilitate the identification of DNT and to differentiate it from other intrinsic neoplasms that commonly present with seizures.The tumours presented with early onset of seizures, at a median age of 7 years, without the signs of raised intracranial pressure. A majority of the lesions were located in the temporal lobe (n = 59), with fewer cases in the frontal (n = 8), parietal (n = 6) and occipital lobes (n = 1), and ranged in size from 10 to 70 mm; 33 were cystic. Histologically three types could be distinguished, multinodular, solitary nodular and diffuse. The first type (37.8%) had the features of a typical DNT with multinodular architecture and mixed cellular composition. The second type (33.8%) consisted of a solitary nodule, while the third (28.4%) was a diffuse tumour, both composed of a similar mixture of cells as the multinodular DNT. The lesions were seen in the neocortex and white matter and tumours in the temporal lobe often involved the amygdala and hippocampus. The presence of myxoid matrix, microcystic change, calcification and leptomeningeal involvement were common. Dysplastic neurones at the periphery of the tumour and abnormalities in cortical lamination in the adjacent neocortex were found in about one-third of the resections. Rare mitotic figures were encountered in eight of the tumours and necrosis was found in two. Immunocytochemistry for glial fibrillary acidic protein (GFAP) and neuronal markers neuron-specific enolase, synaptophysin and neurofilament (RT 97) assists in establishing the diagnosis, highlighting the astrocytic and neuronal components, and the OLC, by the absence of expression of GFAP. Electron microscopy showed that in some cases OLC show neuronal differentiation. Although the proliferating cell nuclear antigen labelling index varied between 0 and 45.5%, 20 of the 51 tumours stained failed to express the antigen, in keeping with the indolent nature of this neoplasm. The response to surgery was excellent; none of the tumours have recurred, and the control of seizures remained good.Despite some histological heterogeneity, the clinical and pathological features and indolent biological behaviour indicate that these tumours constitute a single distinct entity. The spectrum of morphological appearances of DNT is broader than has been previously reported, the recognition of which is needed to avoid unnecessary neoadjuvant therapy.

This paper discusses the place of non-invasive and invasive methods of investigation in the selection of patients for temporal lobe resection. Two series from the same department are compared and the relationship of the outcome to pathology is also discussed.

A retrospective study was made of the postoperative course of 90 patients submitted to "en bloc" temporal lobectomy for intractable epilepsy. Particular attention was paid to the pattern of recurrent seizures after operation. Follow-up periods of at least 5 years were available for 60 patients and a further 47 patients were followed up for periods of between 5 and 12 years after surgery. Three postoperative courses were observed, failure of the treatment in which the seizure frequency was changed by less than 75% (21% of the total), a partial relief of seizures in an intermediate group (21%) and a successful result in the remainder (58%) although only 25% of the total remained constantly fit-free. The recurrence of fits after a long fit-free interval is described and discussed.

This review of the effects of hemidecortication in humans has been limited to studies of cognitive outcome published during the last 20 years. More directly than in the case of split-brain patients, the patients reviewed here attest to the remarkable ability of a single hemisphere, whether left or right, to support at least at modest levels a wide range of cognitive functions--from visual perception, through memory and intellectual processes, to language and even speech. In some cases, as has been indicated, the surgical removal of a diseased hemisphere has resulted in improvement of cognitive function. This positive outcome has occurred more frequently in patients with early (i.e. congenital or perinatal) onset of seizure disorders than in those with late onset (e.g. Rasmussen's disease). But even for the latter patients, the cognitive costs of the surgery per se have rarely been severe. And in both types of case, the incidence of either complete or substantial postoperative relief from intractable seizures has been high, ranging around 80-90%. Although the therapeutic efficacy and small cognitive costs of the surgery are now quite well established, little is known yet regarding the specific cognitive defects that arise from the loss of one as opposed to the other cerebral hemisphere. Intelligence levels have been found to be equally low, averaging in the mid-60s and almost never rising above 100 in patients with either left or right hemidecortications, and memory quotients have most often appeared to fall in line with the IQ scores, again without clear evidence of any difference in the effects of left and right removals. Even in the case of visual spatial perception, considered to be a hallmark of right hemisphere function, the evidence is unclear, one study reporting selective impairment on difficult visuospatial tasks in right hemispherectomised patients, but another not. Only in regard to language processes is there a consensus regarding the differential effects of left and right hemidecortication, and here the differences are apparent only in the relatively subtler aspects of language. Thus, the isolated right hemisphere is at a significant disadvantage compared with the left in the comprehension of abstract, low frequency words, in phonetic feature analysis, and in the subtleties of grammar, such as the comprehension of passive negative constructions and the correct use of morphological markers in unfamiliar contexts (e.g. application of comparative and superlative forms of an adjective to nonwords.(ABSTRACT TRUNCATED AT 400 WORDS)

Left and right temporal lobectomy patients, patients with frontal lobe lesions, and healthy control subjects participated in an eyelid conditioning study based on conditional discrimination learning. All groups acquired the first conditioned response at a similar time during learning, but both temporal lobectomy groups showed poorer discrimination than control subjects. The results support models that relate hippocampal function to operation of if-then rules.

The principles underlying such surgery are reviewed, together with details of the necessary investigation, and a review of long term results from the literature. Cortical Resection for epilepsy remains a useful treatment for drug resistant epilepsy when a cortical focus can be identified by neurophysiological or radiological means. Such a resection has a reasonable chance of relieving or ameliorating the epilepsy with only a small chance of producing or worsening any neurological deficit.

The results of hemispherectomy are very satisfactory but depend upon the technique used. Recent reports from a number of centres confirm that 73% of patients are fit free following hemispherectomy. Delayed pressure complications of hemispherectomy are discussed, together with the modified techniques required to cope with such problems.