SUMMARYPurpose: Deep brain stimulation (DBS) of the thalamus is an emerging surgical option for people with medically refractory epilepsy that is not suitable for resective surgery, or in whom surgery has failed. Our main aim was to evaluate the efficacy of bilateral centromedian thalamic nucleus (CMN) DBS for seizure control in generalized epilepsy and frontal lobe epilepsy with a two-center, single-blind, controlled trial. Methods: Participants were adults with refractory generalized or frontal lobe epilepsy. Seizure diaries were kept by patients/carers prospectively from enrollment. The baseline preimplantation period was followed by a control period consisting of a blind stimulation-OFF phase of at least 3 months, a 3-month blind stimulation-ON phase, and a 6-month unblinded stimulation-ON phase. The control period was followed by an unblinded long-term extension phase with stimulation-ON in those patients in whom stimulation was thought to be effective. Key Findings: Eleven patients were recruited at King's College Hospital (London, United Kingdom United Kingdom) and at University Hospital La Princesa (Madrid, Spain). Among the five patients with frontal lobe epilepsy, only one patient had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, two patients with frontal lobe epilepsy had >50% improvement in seizure frequency. All six patients with generalized epilepsy had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, five of the six patients showed >50% improvement in the frequency of major seizures (one became seizure free, one had >99% improvement, and three had 60-95% reduction in seizure frequency). Among patients with generalized epilepsy, the DBS implantation itself appears to be effective, as two patients remained seizure free during 12 and 50 months with DBS OFF, and the remaining four had 50-91% improvement in the initial 3 months with DBS OFF. Significance: DBS implantation and stimulation of the CMN appears to be a safe and efficacious treatment, particularly in patients with refractory generalized epilepsy. CMN stimulation was not as effective in frontal lobe epilepsy, which requires further studies. DBS of the CMN should be considered as a treatment option, particularly in patients with refractory generalized epilepsy syndromes.

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.

The hypothesis that focal scalp EEG and MEG interictal epileptiform activity can be modelled by single dipoles or by a limited number of dipoles was examined. The time course and spatial distribution of interictal activity recorded simultaneously by surface electrodes and by electrodes next to mesial temporal structures in 12 patients being assessed for epilepsy surgery have been studied to estimate the degree of confinement of neural activity present during interictal paroxysms, and the degree to which volume conduction and neural propagation take part in the diffusion of interictal activity. Also, intrapatient topographical correlations of ictal onset zone and deep interictal activity have been studied. Correlations between the amplitudes of deep and surface recordings, together with previous reports on the amplitude of scalp signals produced by artificially implanted dipoles suggest that the ratio of deep to surface activity recorded during interictal epileptiform activity on the scalp is around 1:2000. This implies that most such activity recorded on the scalp does not arise from volume conduction from deep structures but is generated in the underlying neocortex. Also, time delays of up to 220 ms recorded between interictal paroxysms at different recording sites show that interictal epileptiform activity can propagate neuronally within several milliseconds to relatively remote cortex. Large areas of archicortex and neocortex can then be simultaneously or sequentially active via three possible mechanisms: (1) by fast association fibres directly, (2) by fast association fibres that trigger local phenomena which in turn give rise to sharp/slow waves or spikes, and (3) propagation along the neocortex. The low ratio of deep-to-surface signal on the scalp and the simultaneous activation of large neocortical areas can yield spurious equivalent dipoles localised in deeper structures. Frequent interictal spike activities can also take place independently in areas other than the ictal onset zone and their interictal propagation to the surface is independent of their capacity to trigger seizures. It is concluded that: (1) the deep-to-surface ratios of electromagnetic fields from deep sources are extremely low on the scalp; (2) single dipoles or a limited number of dipoles are not adequate models for interictal activity for surgical assessment; (3) the correct localisation of the onset of interictal activity does not necessarily imply the onset of seizures in the region or in the same hemisphere. It is suggested that, until volume conduction and neurophysiological propagation can be distinguished, semiempirical correlations between symptomatology, surgical outcome, and detailed presurgical modelling of the neocortical projection patterns by combined MEG, EEG, and MRI could be more fruitfil than source localisation with unrealistic source models. (JNeurolNeurosurg Psychiatry 1994;57:435-449)

No abstract

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.

No abstract

Connections between human temporal and frontal cortices were investigated by intracranial electroencephalographic responses to electrical stimulation with 1-ms single pulses in 51 patients assessed for surgery for treatment of epilepsy. The areas studied were medial temporal, entorhinal, lateral temporal, medial frontal, lateral frontal and orbital frontal cortices. Findings were assumed to be representative of human brain as no differences were found between epileptogenic and non-epileptogenic hemispheres. Connections between intralobar temporal and frontal regions were common (43-95%). Connections from temporal to ipsilateral frontal regions were relatively uncommon (seen in 0-25% of hemispheres). Connections from frontal to ipsilateral temporal cortices were more common, particularly from orbital to ipsilateral medial temporal regions (40%). Contralateral temporal connections were rare (< 9%) whereas contralateral frontal connections were frequent and faster, particularly from medial frontal to contralateral medial frontal (61%) and orbital frontal cortices (57%), and between both orbital cortices (67%). Orbital cortex receives profuse connections from the ipsilateral medial (78%) and lateral (88%) frontal cortices, and from the contralateral medial (57%) and orbital (67%) frontal cortices. The high incidence of intralobar temporal connections supports the presence of temporal reverberating circuits. Frontal cortex projects within the lobe and beyond, to ipsilateral and contralateral structures.

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.