Focal cortical dysplasia: long term seizure outcome after surgical treatment.

BACKGROUND: Studies of long term outcome after epilepsy surgery for cortical malformations are rare. In this study, we report our experience with surgical treatment and year to year long term outcome for a subgroup of patients with focal cortical dysplasia (FCD). METHODS: We retrospectively analysed the records of 49 patients (females n = 26; males n = 23; mean age 25 (11) years) with a mean duration of epilepsy of 18 years (range 1-45). Preoperative MRI, histological results based on the Palmini classification and clinical year to year follow-up according to the International League Against Epilepsy (ILAE) classification were available in all patients. RESULTS: 98% of patients had a lesion on preoperative MRI. In addition to lobectomy (n = 9) or lesionectomy (n = 40), 14 patients had multiple subpial transections of the eloquent cortex. The resected tissue was classified as FCD type II b in 41 cases with an extratemporal (88%) and FCD type II a in 8 cases with a temporal localisation (100%). After a mean follow-up of 8.1 (4.5) years, 37 patients (76%) were seizure free, a subgroup of 23 patients (47%) had been completely seizure free since surgery (ILAE class 1a) and 4 patients (8%) had only auras (ILAE class 2). Over a 10 year follow-up, the proportion of satisfactory outcomes decreased, mainly within the first 3 years. During long term follow-up, 48% stopped antiepileptic drug treatment, 34% received a driver's license and 57% found a job or training. CONCLUSION: Surgical treatment of epilepsy with FCD is not only successful in the short term but also has a satisfying long term outcome which remains constant after 3 years of follow-up but is not associated with better employment status or improvement in daily living.

Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement.

Rasmussen encephalitis (RE) is a rare but severe immune-mediated brain disorder leading to unilateral hemispheric atrophy, associated progressive neurological dysfunction and intractable seizures. Recent data on the pathogenesis of the disease, its clinical and paraclinical presentation, and therapeutic approaches are summarized. Based on these data, we propose formal diagnostic criteria and a therapeutic pathway for the management of RE patients.

Will there be a neuroscientific theory of consciousness?

Neuroscientists and philosophers nowadays claim that the problem of phenomenal consciousness is a scientific problem. Increasing knowledge of the neural correlates of consciousness is expected to yield an explanation of consciousness in neuroscientific terms. On the other hand, it is sometimes argued that even complete knowledge of brain function will leave unanswered the question of why cerebral processes are accompanied by consciousness at all. Proponents of this view assume an unbridgeable `explanatory gap' between the brain and the whole realm of phenomenal consciousness. Here, it is argued that this `explanatory gap' problem can not adequately be met by current neuroscientific approaches to consciousness, while purely philosophical approaches remain controversial because they inevitably reach a level of contradictory intuitions that do not seem to be resolvable by further argument. However, the problem may be resolved once one accepts that the features of consciousness itself might change with our judgments and descriptions of consciousness inspired by neuroscience. Such a `change of consciousness' becomes realistic when consciousness is construed as a description-dependent, `non-intrinsic' property[1]. Hence, it is argued that neuroscientists are right not to try to refute the explanatory gap argument, but that they should continue research on the neural correlates of consciousness, thus preparing new descriptions of phenomenal consciousness.

Sensory gating in the human hippocampal and rhinal regions.

OBJECTIVE: The objective of this work was to ascertain if sensory gating can be demonstrated within the human medial temporal lobe. METHODS: Eight patients with intractable epilepsy with depth electrodes implanted in the medial temporal lobe for pre-surgery evaluation underwent evoked response recording to auditory paired-stimuli (S1-S2). Each of the eight subjects had a diagnosis of left medial temporal lobe epilepsy (MTLE). RESULTS: Data from the non-focal right hippocampi revealed a large negative response on S1 (starting at about 190 ms and lasting for approximately 300 ms from stimulus onset). Rhinal region recordings revealed a positive response (starting at about 240 ms with a rapid incline, followed by a long-lasting decline). A significant attenuation of both responses to S2 stimuli was observed. CONCLUSIONS: Data are suggestive of an involvement of the human medial temporal lobe in the processing of simple auditory information which occurs in a time frame later than the neocortical auditory evoked components. The exact role of these anatomical structures in the sensory gating process remains to be defined. SIGNIFICANCE: This study provides the first evidence of an activation of the rhinal cortex after simple auditory stimulation and provides new evidence that the activation of the medial temporal lobe structures occurs at a later stage than that of the neocortex.

Amobarbital effects on the posterior hippocampus during the intracarotid amobarbital test.

OBJECTIVE: To relate functional effects on the hippocampus during the intracarotid amobarbital test (IAT) to its direct perfusion with amobarbital. METHODS: In 17 patients with intractable temporal lobe epilepsy, 28 hemispheres were perfused with 2.3 mL of 10% solution of 200 mg amobarbital and 37 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO). For evaluation of amobarbital effects, data were combined from stereo-EEG (S-EEG) recordings from intrahippocampal depth electrodes and high-resolution SPECT after intracarotid injection of HMPAO. RESULTS: Perfusion of the entire hippocampus was observed only in hemispheres with a fetal origin of the posterior cerebral artery (PCA). In 10 hemispheres, S-EEG recordings could not unequivocally be assigned to either the anterior or the posterior part of the hippocampus. In the remaining 18 hemispheres, only the two with a fetal type of PCA showed perfusion of the entire hippocampus. In both, hippocampal electrical activity changed under the influence of amobarbital but did not differ in anterior and posterior contacts. In 15 of 16 hemispheres in which SPECT demonstrated perfusion of the anterior hippocampus only, amobarbital injection resulted in significant S-EEG activity change in both the anterior and the posterior parts of the hippocampus. CONCLUSION: S-EEG effects on the posterior hippocampus during the IAT can occur without direct perfusion of those brain areas.

Technetium-99m HM-PAO brain SPECT in epileptic patients before and during unilateral hemispheric anesthesia (Wada test): report of three cases.

The lipophilic brain SPECT agent [99mTc]hexamethyl propylene amine oxime (HM-PAO) was used in three cases before and during unilateral anesthesia of one hemisphere for lateralization of speech dominance (Wada test). This procedure led to a decrease of regional cerebral blood flow (rCBF) in each of the hemispheres to 55 and 90%, respectively. Diminution of rCBF was significantly more pronounced in the dominant hemisphere. A second phenomenon observed during the Wada test was crossed cerebellar diaschisis. These findings support the assumption that HM-PAO allows monitoring of brain perfusion, as rapid changes of rCBF due to decreased neuronal activity cause respective alterations of cerebral and cerebellar uptake of this new brain agent.

Evidence of very fast memory consolidation: an intracarotid amytal study.

This study provides evidence from intracarotid amobarbital tests (IAT) in patients with epilepsy that complete suppression of the electrophysiological activity of the left language-dominant hemisphere through left IAT does not impair memory for verbal information given 1 min or immediately before the injection of the barbiturate. Although language functions were completely disrupted and patients were unable to encode new information during the left IAT, pre/post memory was as good as in the right IAT. This lack of retrograde amnesia leads to the conclusion that a relatively stable representation of events is achieved within seconds after encoding. The results contradict models which assume that short-term memory is based on purely electrophysiological processes.

Limbic ERPs predict verbal memory after left-sided hippocampectomy.

Surgical removal of the dominant medial temporal lobe regions runs a considerable risk of verbal memory deficits which may be compensated for postoperatively by corresponding regions in the non-dominant medial temporal lobe. We examined this possibility by recording event-related potentials (ERPs) to words from the medial temporal lobes of patients with left-sided temporal lobe epilepsy (TLE) undergoing presurgical evaluation. N400 amplitudes in the right anterior medial temporal lobe predicted the postoperative verbal recall performance of individual patients with surprising accuracy, indicating that intracranial recordings can be used to quantify the functional capacities of the right hemisphere that can compensate for the verbal memory deficits after loss of medial temporal lobe structures in the left hemisphere.

Cortical activation in patients with functional hemispherectomy.

Functional hemispherectomy, a safe and effective therapeutical procedure in medically intractable epilepsy, offers the chance to investigate a strictly unilateral cortical activation in ipsilateral limb movement. We assessed the pattern of cortical activation in a group of patients following functional hemispherectomy. We measured regional cerebral blood flow (rCBF) in 6 patients postoperatively and 6 normal subjects with positron emission tomography using 15[O]H2O as a tracer. Brain activation was achieved by passive elbow movements of the affected arm. Analysis of group results and between-group comparisons were performed with statistical parametric mapping, (SPM96). In normal subjects brain activation was found contralaterally in the cranial sensorimotor cortex and the supplementary motor area and ipsilaterally in the inferior parietal cortex. In patients significant rCBF increases were found in the inferior parietal cortex, caudal sensorimotor cortex and the supplementary motor area ipsilaterally. The activation was weaker than in normal subjects. Compared with normal subjects patients showed additional activation in the premotor cortex, caudal sensorimotor cortex and the inferior parietal cortex of the remaining hemisphere. Less activation compared with normal subjects was found in the cranial sensorimotor cortex and the supplementary motor area. A functional network connecting the inferior parietal cortex, premotor cortex and the supplementary motor area as well as the existence of ipsilateral projections originating from these regions may explain why these areas are predominantly involved in reorganization confined to a single hemisphere.

Cortical motor reorganization following early brain damage and hemispherectomy demonstrated by transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) was utilized to study 7 patients who had undergone hemispherectomy for control of longstanding intractable epilepsy to assess cortical motor reorganization and MEP (motor evoked potentials) ipsilateral to the remaining hemisphere. Five patients were seizure-free post-operatively. All patients displayed a spastic hemiparesis, were able to walk, raise and bend the paretic arm and use the paretic hand to different degrees. METHODS: We examined MEP threshold, site of maximal response to TMS, and latency to the biceps brachii, abductor pollicis brevis and the anterior tibial muscles using a 7 and 12 cm diameter round coil. RESULTS: The following results were obtained: (1) No MEP could be induced to either side by use of the small coil. (2) When using the large coil MEP-threshold was elevated also when stimulating the non-affected hemisphere in comparison to normal controls. (3) Ipsilateral MEP were found to: be non-inducible in two patients, demonstrate largely increased latencies in 3 and be identical to contralateral MEP in two patients. (4) Ipsilateral MEP could be evoked more often in distal than proximal muscles. (5) The site of maximal ipsilateral MEP response was found approximately 2 cm anteriorly to that of the contralateral MEP to the non-affected side of the body (6) No correlation was found between the degree of hemiparesis and inducability of MEP. CONCLUSIONS: The pattern of reorganization of ipsilateral motor control following early brain damage and hemispherectomy appears to be extremely diverse and does not correlate with the degree of neurological impairment.

Linguistic perseveration in dominant-side intracarotid amobarbital tests.

148 patients with medically intractable complex-partial seizures received bilateral intracarotid amobarbital tests. In 21 patients (14.2%), there were inappropriate responses (intrusions: N = 10; perseverations: N = 11) to a series repetition task (counting backwards) given immediately before amobarbital injection. Five cases from the perseveration subgroup are discussed in detail. In these patients, linguistic perseveration occurred with left-sided amobarbital injection, although they were all found to have left hemispheric speech dominance according to language testing during the amobarbital procedure. It is argued that these perseverations are best explained as a right hemispheric continuation of a speech motor program previously initiated by the left hemisphere.

Severe negative emotional reactions in intracarotid sodium amytal procedures: further evidence for hemispheric asymmetries?

Intracarotid sodium amytal (ISA) procedures are commonly used to determine the lateralization of language and memory functions in presurgical evaluation of epileptic patients. Besides, they provide a means for studying putative hemispheric asymmetries in the organization of emotional behavior. In this study, we report the incidence of negative emotional reactions in eighty epileptic patients undergoing ISA procedures as a part of presurgical evaluation. There were only four such reactions in a total of 159 tests (2.5%), all in right-handed patients with left cerebral dominance for language functions. In one case, emotional outbursts occurred with barbiturization of the nondominant hemisphere. This observation invalidates the hypothesis that a loss of left-hemispheric functions generally leads to negative emotional reactions due to a right hemisphere specialization for the processing of negative emotions. Rather than pointing to fixed hemispheric asymmetries, our findings suggest that severe negative emotional reactions result from a flexible cognitive evaluation of the organism's overall situation.

[MR tomography following craniocerebral trauma: comparison with computed tomography, electroencephalography and neurologic status]. / MR-Tomographie nach Schädel-Hirn-Trauma: Vergleich mit Computertomographie, Elektroenzephalographie und neurologischem Status.

56 patients with head and brain trauma and in coma were studied prospectively by means of MRT, CT, EEG and neurological examination. All patients had initial CT and EEG admission. MRT showed that in our patients morphological return to normal was the exception. Patients with head and brain injuries should be examined by MRT during the course of their illness. The use of special sequences, such as gradient-echo sequences for the diagnosis of haemorrhagic contusions, is indicated. CT should be retained for evaluating bone injury and cerebral damage during the acute stage.

Quantitative and qualitative evaluation of patterns of cerebral language dominance. An amobarbital study.

As a part of presurgical evaluation, 173 patients received bilateral intracarotid amobarbital tests for determination of cerebral language dominance. Language testing during intracarotid amobarbital procedures (IAP) consisted of the following tasks: automatic speech, sentence comprehension, body commands, naming, repetition, reading, and spontaneous speech. Patterns of cerebral language dominance were evaluated and discussed on five levels of analysis: (1) quantification of language dominance on the basis of a lateralization index derived from the total language scores in each IAP; (2) determination of five dominance subpatterns (left or right dominant, strongly bilateral, and incomplete left or right dominant) according to quantification performed on level (1) and clinical judgement; (3) qualitative differentiation of three kinds of bilaterality (positive, negative, and general) according to total language performance in left and right IAP; (4) analysis of grouped linguistic subfunctions extracted from performance in specific IAP subtests; (5) extraordinary individual case histories. The distribution of lateralization indices revealed only partially continuous degrees of lateralization, especially between the left-dominant and bilateral subgroups. As for the clinically oriented classification, incomplete left dominance is frequent (16.2%), while incomplete right dominance does not occur at all. Atypical dominance patterns are mostly correlated to bilateral and/or extratemporal foci. Concerning grouped subfunctions, a rotated factor matrix statistic yields an analysis of clusters of IAP subtests, where functions involving expressive language capacities are separated from those that are purely receptive. Further analyses of bilaterality subpatterns suggest that there are mainly four bilaterality phenomena, namely interhemispheric dissociation, double representation, unilateral representation of subfunctions, and partial representation of subfunctions in either hemisphere. Application of these differentiations to individual cases yields additional evidence that can be used in patient selection for operation in order to avoid postoperative neuropsychological deficits, especially in candidates for extratemporal surgery. In conclusion, a multilevel analysis of IAP language data is recommended since it permits a detailed account of varieties of language dominance patterns and contributes to more adequate presurgical decision-making in planned operations in cognitively relevant brain areas.

Interhemispheric dissociation of expressive and receptive language functions in patients with complex-partial seizures: an amobarbital study.

Bilateral intracarotid amobarbital procedures (IAP) were performed in 144 patients with medically intractable complex-partial seizures. As a result of language testing, 29 patients (20.1%) were found to have bilateral language representation to different degrees. In four (2.8%) of these patients--all right-handers with early onset of epilepsy and/or evidence of early brain damage--there was strong evidence of an interhemispheric dissociation of expressive and receptive language functions. Two of these patients had circumscribed temporal foci (one left, one right), and receptive language functions were represented in the hemisphere contralateral to the focus. One patient with a right frontal focus showed left-hemisphere dominance for expressive functions, while the fourth patient exhibited left-hemisphere dominance for receptive functions associated with a right temporo-parietal focus. It is argued that in these four cases the circumscribed functional and/or structural impairments have led to a shift of the anatomically associated language functions to the opposite hemisphere (rather than to neighboring regions of the same hemisphere). These findings substantiate the hypothesis that in special circumstances the anterior (expressive) language area can be located in one hemisphere and the posterior (receptive) area in the other.

Consciousness in non-epileptic attack disorder.

Non-epileptic attack disorder (NEAD) is one of the most important differential diagnoses of epilepsy. Impairment of consciousness is the key feature of non-epileptic attacks (NEAs). The first half of this review summarises the clinical research literature featuring observations relating to consciousness in NEAD. The second half places this evidence in the wider context of the recent discourse on consciousness in neuroscience and the philosophy of mind. We argue that studies of consciousness should not only distinguish between the 'level' and `content' of consciousness but also between 'phenomenal consciousness' (consciousness of states it somehow "feels to be like") and 'access consciousness' (having certain 'higher' cognitive processes at one's disposal). The existing evidence shows that there is a great intra- and interindividual variability of NEA experience. However, in most NEAs phenomenal experience - and, as a precondition for that experience, vigilance or wakefulness - is reduced to a lesser degree than in those epileptic seizures involving impairment of consciousness. In fact, complete loss of "consciousness" is the exception rather than the rule in NEAs. Patients, as well as external observers, may have a tendency to overestimate impairments of consciousness during the seizures.

Association between structural abnormalities and fMRI response in the amygdala in patients with temporal lobe epilepsy.

OBJECTIVE: The goal of this study was to investigate whether dysplastic amygdalae show an impaired response as revealed by functional MRI (fMRI). METHODS: A fearful face fMRI paradigm using video sequences, as we have recently applied, was used in 25 patients with temporal lobe epilepsy (TLE): 24 had mesial TLE (14 right-, nine left-sided, one bilateral); one left lateral neocortical TLE. T1-, T2-weighted and fluid attenuated inversion recovery (FLAIR) MRI sequences were assessed for the detection and categorisation of structural amygdalar abnormalities according to size and MR signal intensity. Of the 25 patients, five patients had probable dysplastic amygdala (pDA): two right- and three left-sided. RESULTS: A fearful face paradigm led to significant amygdalar activation in all but one patient (p<0.05). In 15 (60%) of the patients amygdalar activation was found contralateral and in four (16%) ipsilateral to the side of seizure onset. Bilateral amygdalar activation was registered in five (20%) patients. In two patients with right-sided and one with left-sided pDA, fMRI activation was observed only in the contralateral amygdala. In two out of three patients with left-sided pDA we found significant ipsilateral amygdalar fMRI-responses. CONCLUSION: Unilateral pDA does not necessarily affect the amygdalar fMRI BOLD-response.

Transient splenium lesions in presurgical epilepsy patients: incidence and pathogenesis.

INTRODUCTION: Transient splenium corporis callosi (SCC) lesions are related to rapid reduction of antiepileptic drugs (AEDs). The range of substances with predilection for SCC changes, their pathophysiology and their occurrence are still unknown. METHODS: In a prospective 2-year study an epilepsy-dedicated MRI protocol supplemented by DWI and ADC maps was performed after AED withdrawal for diagnostic seizure provocation in all patients with pharmacoresistant seizures locally admitted to the Department of Epileptology. RESULTS: Of 891 presurgical epilepsy patients, 6 (0.7%) had SCC lesions with cytotoxic edema on DWI. Carbamazepine combined with other AEDs was administered in five of those patients. In the study period we observed identical lesions in a schizophrenic patient treated with olanzapine and citalopram, in a patient with oropharyngeal carcinoma treated with alkylating agents, and in a hypernatremic patient following neurohypophyseal granular cell tumor surgery. CONCLUSION: Transient SCC lesions are related to rapid AED reduction but may occur in similar conditions with fluid balance alterations. We contribute further clinical data in this field to better classify the pharmaceuticals that are prone to the described cerebral cytotoxic side effects in the SCC and to clarify their incidence among presurgical epilepsy patients.