Medial temporal lobe functional connectivity predicts stimulation-induced theta power.

Focal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked increases in theta (5-8 Hz) power, particularly when stimulation was applied in or adjacent to white matter. Stimulation tended to decrease power in the high-frequency broadband (HFB; 50-200 Hz) range, and these modulations were correlated with HFB-based networks in a subset of subjects. Our results demonstrate that functional connectivity is predictive of causal changes in the brain, capturing evoked activity across brain regions and frequency bands.

Widespread theta synchrony and high-frequency desynchronization underlies enhanced cognition.

The idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30-100 Hz) and slow theta (3-8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, gamma power rises as that region desynchronizes with gamma activity elsewhere in the brain, establishing gamma as a largely asynchronous phenomenon. The abundant phenomenon of theta synchrony is positively correlated with a brain region's gamma power, suggesting a predominant low-frequency mechanism for inter-regional communication.

The implantation effect: delay in seizure occurrence with implantation of intracranial electrodes.

OBJECTIVE: A transient decrease in seizure frequency has been identified during therapeutic brain stimulation trials with stimulator in patients in the inactive sham group. This study was performed to examine whether the implantation of intracranial electrodes decreases seizure occurrence and explores factors that may be associated. METHODS: A retrospective review of 193 patients was performed, all evaluated with both scalp video EEG monitoring and intracranial EEG (iEEG) monitoring. Data about the number of seizures per day during the monitoring period, the number of days until the first seizure, anti-epileptic drugs (AEDs), pain medications, types of implanted electrodes, and anesthetic agents were reviewed. We conducted a repeated measure analysis for counted data using generalized estimating equations with a log-link function and adjustment for number of days and anti-epileptic medication load on the previous day to compare seizure frequencies between scalp and iEEG monitoring. RESULTS: The time to the first seizure was significantly prolonged during iEEG monitoring as compared to scalp monitoring after correction for AED withdrawal (hazard ratio: 0.81, CI 0.69-0.96). During scalp video EEG monitoring, patients experienced an average of 1.09 seizures/day vs 1.27 seizures/day during iEEG monitoring (P=.066). There was no significant difference in seizure frequency in patients that received craniotomy vs burr holes only for intracranial implantation. An increasing number of electrodes implanted increased the delay to seizures (P=.01). Of all anesthetic agents used, desflurane seemed to have an anticonvulsive effect compared to other anesthetics (P=.006). Pain medication did not influence delay to seizures. SIGNIFICANCE: Seizures are delayed during iEEG as opposed to scalp monitoring illustrating the "implantation effect" previously observed. Surgical planning should account for longer monitoring periods, particularly when using larger intracranial arrays.

Secondarily generalized seizures in mesial temporal epilepsy: clinical characteristics, lateralizing signs, and association with sleep-wake cycle.

PURPOSE: Secondarily generalized seizures (SGSs) are often considered to be stereotyped, presumably sharing a common electrical pathway. We examined whether SGSs are uniform in a homogeneous group of patients with mesial temporal epilepsy, and whether certain clinical signs associated with generalization are lateralizing with regard to seizure origin. METHODS: A comprehensive, standardized video/EEG analysis was performed of the clinical characteristics of 29 patients (69 SGSs) with mesial temporal seizure onset. RESULTS: The sequence of tonic postures, as well as the sequence of tonic and clonic activity, was variable in SGSs of mesial temporal origin. The sequence of tonic activity, followed by vibratory and then clonic activity alone, was seen only in 51.7% of patients. Tonic and clonic activity could occur simultaneously. The most common clinical signs were forced head deviation (89.7%) and vocalization (75.9%). The most common tonic posture was bilateral arm extension (72.4%). All other clinical signs occurred in <60% of patients. Among these, early forced head deviation, asymmetric tonic facial contraction, tonic arm abduction with elbow flexion, and tonic arm extension combined with opposite arm flexion had lateralizing significance. The preceding partial seizure in SGSs (mean, 43.6 s) was significantly shorter than partial seizures without generalization (mean, 105.2 s; p < 0.001). SGSs occurred more often out of sleep (p < 0.01). CONCLUSION: Secondarily generalized seizures of mesial temporal origin are not uniform in their clinical presentation. The final phases of SGSs are more stereotyped than the initial clinical signs of generalization. This suggests variable electrical spread patterns, which may end in a common pathway. Some asymmetric motor signs have lateralizing significance. SGSs were associated with sleep and abbreviated partial seizures.

Medically intractable, localization-related epilepsy with normal MRI: presurgical evaluation and surgical outcome in 43 patients.

PURPOSE: High-resolution magnetic resonance imaging (MRI) plays a crucial role in the presurgical evaluation of patients with medically refractory partial epilepsy. Although MRI detects a morphologic abnormality as the cause of the epilepsy in the majority of patients, some patients have a normal MRI. This study was undertaken to explore the hypothesis that in patients with normal MRI, invasive monitoring can lead to localization of the seizure-onset zone and successful epilepsy surgery. METHODS: A series of 115 patients with partial epilepsy who had undergone intracranial electrode evaluation (subdural strip, subdural grid, and/or depth electrodes) between February 1992 and February 1999 was analyzed retrospectively. Of these, 43 patients (37%) had a normal MRI. RESULTS: Invasive monitoring detected a focal seizure onset in 25 (58%) patients, multifocal seizure origin in 12 (28%) patients, and in six patients, no focal seizure origin was found. Of the 25 patients with a focal seizure origin, cortical resection was performed in 24, of whom 20 (83%) had a good surgical outcome with respect to seizure control. Six of the 12 patients with multifocal seizure origin underwent other forms of epilepsy surgery (palliative cortical resection in two, anterior callosotomy in two, and vagal nerve stimulator placement in two). CONCLUSIONS: Successful epilepsy surgery is possible in patients with normal MRIs, but appropriate presurgical evaluations are necessary. In patients with evidence of multifocal seizure origin during noninvasive evaluation, invasive monitoring should generally be avoided.

Investigation of extra-temporal epilepsy.

Medically intractable epilepsy of extra-temporal origin can represent a difficult therapeutic challenge. Our Epilepsy Service has managed these patients using standard investigative methods as well as ictal SPECT and intracranial electrode recording. In the present series of patients, image-guided surgery was used for all electrode implantation and resective surgery. Seizure localization and successful resection were achieved in 70-80% of 42 patients with follow-up of at least one year. Normal MRI and previous failed intracranial investigation were not associated with poorer outcome.

Intractable seizures of frontal lobe origin: clinical characteristics, localizing signs, and results of surgery.

PURPOSE: We analyzed the clinical characteristics of seizures of frontal lobe (FL) origin with particular emphasis on establishing different categories and determining if these categories had any localizing or lateralizing value. In addition, results of surgery are reported. METHODS: Seizure characteristics were established by historical review and electroencephalographic/videotape analysis of 449 seizures in 26 adult patients with refractory seizures of FL origin. RESULTS: No outstanding risk factor was identified for seizures of FL origin. Seizures were frequent (7.1 per week), brief (mean duration, 48.3 seconds), and had a nocturnal preponderance in 58% of the patients. Status epilepticus was reported in 54%, and generalized convulsions as a prominent seizure type were reported in 26% of patients. The most common reported aura was a nonspecific sensation, often localized to the head (35%). Early forced head and eye deviation was not a consistent lateralizing sign, whereas late head and eye deviation always occurred contralateral to the site of seizure origin. Early asymmetric tonic posturing occurred consistently contralateral to the side of seizure origin. Clinical seizure patterns did not consistently localize to specific regions of the frontal lobe, although there were some noticeable trends: focal clonic seizures were associated with seizure origin in the frontal convexity; tonic seizures were most often associated with origin in the supplementary motor area but also occurred with origin in other parts of the frontal lobe; seizures resembling typical temporal lobe seizures with oroalimentary automatisms were observed with seizure origin in the orbitofrontal region; and seizures with hyperactive, frenetic automatisms were not associated with any specific region within the frontal lobes. Eighty percent of patients had favorable seizure outcome after surgery (class I/II). CONCLUSION: Although certain clinical features are characteristic for seizures of frontal lobe origin and some have lateralizing value, they do not localize to specific areas within the FL. After careful presurgical evaluation, both lesional and nonlesional patients benefit from epilepsy surgery.

Epilepsy surgery in developing countries.

Epilepsy surgery (ES) is a well-accepted treatment for medically intractable epilepsy patients in developed countries, but it is highly technology dependent. Such technology is not usually available in developing countries. For presurgical evaluation, magnetic resonance imaging (MRI) and electroencephalogram recording while videotaping the patient have been important. High technology equipment will, in conjunction with MRI, identify approximately 70% of ES candidates. Introducing ES into developing countries will require determining the candidates that are appropriate for the existing medical infrastructure. This article reviews ES and its possible introduction into conditions existing in developing countries. The authors address (a) the types of patients to be considered for resective ES (some patients require a fairly standard series of noninvasive studies: others will require extensive invasive studies), (b) ways to determine which patients might be appropriate for the existing situation (unilateral mesial temporal lobe epilepsy detected with MRI, epilepsy with a circumscribed MRI lesion, hemispheric lesions, circumscribed MRI detected neuronal migration, and development disorders), (c) surgical procedures (local resection, functional hemispherectomy, multiple subpial transections, corpus callosotomy, and implantation of a vagal nerve stimulator), (d) special considerations for introducing ES into developing countries (medical infrastructure, technology, seizure monitoring systems, selective intracarotid/carotid Amytal testing, and surgical equipment), and (e) the limitations, realistic expectations, personnel requirements, and educational function for selected professionals. Delivery of the technology and expertise to perform ES in developing regions of the world is a realizable project, but it would be limited by available technology and existing medical infrastructure. It should be possible in most areas to train local personnel and thereby leave a lasting legacy.

An unusual complication of intracranial electrodes.

This report describes two patients who developed persistent neurologic deficits during intracranial EEG recording without clear evidence of intracranial edema or infarction. Both patients had previously received high-dose brain radiation therapy and chemotherapy. Because of this experience, we strongly caution the use of intracranial electrodes in patients with similar profiles.

The role of intracranial electrode reevaluation in epilepsy patients after failed initial invasive monitoring.

PURPOSE: Intracranial electrode recording often provides localization of the site of seizure onset to allow epilepsy surgery. In patients whose invasive evaluation fails to localize seizure origin, the utility of further invasive monitoring is unknown. This study was undertaken to explore the hypothesis that a second intracranial investigation is selected patients warrants consideration and can lead to successful epilepsy surgery. METHODS: A series of 110 consecutive patients with partial epilepsy who had undergone intracranial electrode evaluation (by subdural strip, subdural grid, and/or depth electrodes) between February 1992 and October 1998 was retrospectively analyzed. Of these, failed localization of seizure origin was thought to be due to sampling error in 13 patients. Nine of these 13 patients underwent a second intracranial investigation. RESULTS: Reevaluation with intracranial electrodes resulted in satisfactory seizure-onset localization in seven of nine patients, and these seven had epilepsy surgery. Three frontal, two temporal, and one occipital resection as well as one multiple subpial transection were performed. Six patients have become seizure free, and one was not significantly improved. The mean follow-up is 2.8 years. There was no permanent morbidity. CONCLUSIONS: In selected patients in whom invasive monitoring fails to identify the site of seizure origin, reinvestigation with intracranial electrodes can achieve localization of the region of seizure onset and allow successful surgical treatment.