The evolution of epilepsy surgery.

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.

Social and emotional functioning following bilateral and unilateral neurosurgical prefrontal cortex lesions.

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.

Long-term clinical and positron emission tomography outcome of fetal striatal transplantation in Huntington's disease.

Two patients with moderate Huntington's disease (HD) received bilateral fetal striatal allografts. One patient demonstrated, for the first time, increased striatal D2 receptor binding, evident with 11C-raclopride positron emission tomography, and prolonged clinical improvement over 5 years, suggesting long term survival and efficacy of the graft. The other patient did not improve clinically or radiologically. Our results indicate that striatal transplantation in HD may be beneficial but further studies are needed to confirm this.

Ipsilesional and contralesional sensorimotor function after hemispherectomy: differences between distal and proximal function.

Previous studies have reported mainly on contralesional somatosensory and motor function after hemispherectomy. So far, ipsilesional impairments have received little attention even though these have been reported in patients with less extensive lesions. In the current study we assessed ipsilesional and contralesional sensorimotor function in a group of 12 patients with hemispherectomy. In addition, we focused on differences between distal and proximal function and investigated several factors that may have contributed to individual differences between patients. The tests included tapping, force production, tactile double simultaneous stimulation, pressure sensitivity, passive joint movement sense and sensitivity to hot and cold. Ipsilesional impairments were found on all tests, except passive joint movement sense. Unexpectedly, no significant ipsilateral distal-proximal gradient was found for any of the measures. Both the removal of the diseased cerebral hemisphere and possible changes to the remaining brain structures may have affected ipsilesional sensorimotor function. Contralesional performance was impaired on all tests except for passive joint movement in the shoulder. The contralesional impairments were characterized by a distal-proximal gradient measured on all tests, except that of sensitivity to hot and cold. Distal function was always most impaired. The difference between distal and proximal motor function is in agreement with the established concepts of the motor pathways, with the motoneurons innervating proximal muscles receiving bilateral cortical and subcortical input. Age at onset of original brain damage correlated significantly with passive joint movement sense. Patients with known abnormalities to the remaining brain structures performed inferior on the tapping test only. No effect was found of the hemispheric side of removal.

Is it worth pursuing surgery for epilepsy in patients with normal neuroimaging?

OBJECTIVE: To determine whether it is worth pursuing surgery for the treatment of epilepsy in patients with normal neuroimaging. METHODS: Two patient populations were studied: (1) 136 consecutive patients who were surgically treated; (2) 105 consecutive patients assessed with chronically implanted intracranial electrodes within the same period. Sixty patients belonged to both groups, and included all 21 patients who had normal neuroimaging. RESULTS: There were no differences in the proportion of patients with favourable outcome between those with normal and those with abnormal neuroimaging, irrespective of whether intracranial recordings were required. Among the 19 operated patients with normal neuroimaging, 74% had a favourable outcome (Engel's seizure outcome grades I and II), and among the 93 patients with abnormal neuroimaging, 73% had favourable outcome (p = 0.96). In patients with temporal resections, 92% of the 13 patients with normal neuroimaging had a favourable outcome, whereas among the 70 patients with abnormal neuroimaging, 80% had a favourable outcome (p = 0.44). In patients with extratemporal resections, two of the six patients with normal neuroimaging had a favourable outcome, while 12 of the 23 patients with abnormal neuroimaging had a favourable outcome (p = 0.65). Among the 105 patients studied with intracranial electrodes, five suffered transitory deficits as a result of implantation, and two suffered permanent deficits (one hemiplegia caused by haematoma and one mild dysphasia resulting from haemorrhage). CONCLUSIONS: It is worth pursuing surgery in patients with normal neuroimaging because it results in good seizure control and the incidence of permanent deficits associated with intracranial studies is low.

Impaired dimensional selection but intact use of reward feedback during visual discrimination learning in Parkinson's disease.

It has been suggested that Parkinson's disease (PD) impairs the ability to learn on the basis of reward or reinforcing feedback i.e., by trial-and-error. In many learning tasks, particular 'dimensions' of stimulus information are relevant whilst others are irrelevant; therefore, efficient performance depends on identifying the dimensions of these 'compound' stimuli and selecting the relevant dimension for further processing. We investigated the ability of patients with PD, as well as patients with Huntington's disease and patients with frontal or temporal lobe lesions, to learn visual discriminations which required either a number of associations to be learned concurrently (the 'eight-pair' task) or the selection of information from compound stimuli (the 'five-dimension' task), both tasks being learned by trial-and-error. None of the basal ganglia disorder patient groups was impaired on the eight-pair task, militating against a crucial role for these brain structures in trial-and-error learning per se. Patients with mild, medicated PD, but not unmedicated PD patients, were impaired at identifying all five feature dimensions in the five-dimension task, implying dopaminergic 'overdosing' of the ability to analyse compound stimuli in terms of their component dimensions. Temporal lobe lesion patients performed similarly, suggesting that the temporal lobe may be the site of the medication overdose effect. Patients with severe, medicated PD were impaired at compound discrimination learning on the five-dimension task in the absence of an underlying impairment in identifying component stimulus dimensions; this pattern resembled that seen in Huntington's disease and frontal lobe lesion patients, implying that fronto-striatal circuitry is involved in the formation of rules based upon selected stimulus dimensions.

Single-pulse electrical stimulation identifies epileptogenic frontal cortex in the human brain.

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.

The impact of early and late damage to the human amygdala on 'theory of mind' reasoning.

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.

Reward-related reversal learning after surgical excisions in orbito-frontal or dorsolateral prefrontal cortex in humans.

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.

Neuropsychological effects associated with temporal lobectomy and amygdalohippocampectomy depending on Wada test failure.

OBJECTIVE: To compare the neuropsychological effects of temporal lobectomy (TL) and amygdalohippocampectomy (AH), depending on whether the patients had passed or failed the Wada test. METHODS: We compared changes in neuropsychological scores in patients who underwent TL (n = 91) or AH (n = 15), and had passed or failed the Wada test. Comparisons were carried out in all 106 patients and among the 20 patients who failed the Wada test (12 who had TL and 8 who had AH). RESULTS: No patient became globally amnesic after surgery. Among all patients, no differences were found in pre-surgical or change scores (percentage of change after surgery compared with preoperative values) of neuropsychological tests between patients who underwent TL or AH. Among patients who failed the Wada test, those in the TL group showed higher visual memory impairment (p<0.05). There was a strong trend suggesting that TL is associated with higher verbal memory deficits than AH (p = 0.07). Of those TL patients who failed the Wada test, the contralateral Wada score correlated with change scores in verbal intelligence quotient (p<0.01), and there was a strong trend towards a correlation with the logical memory immediate recall version subtest of the Wechsler Memory Scale (p = 0.06). CONCLUSIONS: No profound changes in intelligence quotient or memory scores were found after TL or AH. Nevertheless, patients who underwent TL and failed the Wada test showed more deficits than those who passed the test or those who had AH. The presence of a correlation between contralateral Wada scores and verbal deficits in TL patients who failed the Wada test but not among AH patients suggests that, if temporal surgery is required, AH might be preferred to TL in patients who fail the Wada test.

Changes in emotion after circumscribed surgical lesions of the orbitofrontal and cingulate cortices.

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.

VNS in patients with previous unsuccessful resective epilepsy surgery: antiepileptic and psychotropic effects.

OBJECTIVES: To assess the efficacy of vagus nerve stimulation (VNS) in patients with medically and surgically intractable complex partial seizures (CPS). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Postictal psychosis after temporal lobectomy.

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.

Responses to single pulse electrical stimulation identify epileptogenesis in the human brain in vivo.

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.

Relevance of residual histologic and electrocorticographic abnormalities for surgical outcome in frontal lobe epilepsy.

PURPOSE: To estimate the significance of residual electrocorticographic and neuropathologic abnormalities on seizure control after surgery for frontal lobe epilepsy with the purpose of determining their relevance in deciding the extent of the surgical procedure. METHODS: The presence of epileptiform discharges in intraoperative electrocorticograms (ECoGs) and the nature and extent of neuropathologic abnormalities were reviewed for 35 patients who underwent frontal lobe resections for the treatment of epilepsy at our institution. The relations between surgical outcome and presence of the following features were studied: (a) presence of abnormal tissue at the limits of the resection; (b) presence of sporadic spikes and seizure patterns in the preresection ECoG; (c) their abolition in the postresection ECoG; and (d) the topography of residual discharges with respect to the margins of the resection. RESULTS: On neuropathologic examination, 18 patients showed focal cortical dysplasia (CD), and 17 showed other abnormalities (non-CD). Ten CD patients and 11 non-CD patients experienced a favourable outcome. Seizure patterns were significantly more common in patients with focal cortical dysplasia than in those without, with a sensitivity of 94% and a specificity of 75%. Abolition of seizure patterns was associated with a favourable surgical outcome (p = 0.031). Abolition of sporadic spikes or their presence in the postresection ECoG did not influence outcome. There was no clear relation between outcome and location of residual sporadic discharges. Seizure patterns persisted in the postresection ECoG in three CD patients, were located at the margins of the resection in all three, and these patients had a poor outcome. Incomplete removal of abnormal tissue was not associated with a poorer outcome in either patient group or in the complete sample. CONCLUSIONS: Seizure patterns were significantly more common in patients with cortical dysplasia, and their abolition on postresection ECoG recordings was associated with a favourable surgical outcome. Persistence of sporadic ECoG spikes and incomplete removal of histologic abnormalities did not affect outcome significantly.

Prognostic factors in the surgical treatment of medically intractable epilepsy associated with mesial temporal sclerosis.

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.

The urgent postoperative CT scan: a critical appraisal of its impact.

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 x 10(-12)). Less than 1 in 10 postoperative scans show a neurosurgical target. Other changes in management following scanning were slight.

Predictors of outcome and pathological considerations in the surgical treatment of intractable epilepsy associated with temporal lobe lesions.

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 Kaplan-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.