Search

Epilepsies are debilitating neurological disorders characterized by repeated episodes of pathological seizure activity. Absence epilepsy (AE) is a poorly understood type of seizure with an estimated 30% of affected patients failing to respond to antiepileptic drugs. Thus, novel therapies are needed for the treatment of AE. A promising cell-based therapeutic strategy is centered on transplantation of embryonic neural stem cells from the medial ganglionic eminence (MGE), which give rise to gamma-aminobutyric acidergic (GABAergic) interneurons during embyronic development. Here, we used the Stargazer (Stg) mouse model of AE to map affected loci using c-Fos immunohistochemistry, which revealed intense seizure-induce activity in visual and somatosensory cortices. We report that transplantation of MGE cells into the primary visual cortex (V1) of Stg mice significantly reduces AE episodes and lowers mortality. Electrophysiological analysis in acute cortical slices of visual cortex demonstrated that Stg V1 neurons exhibit more pronounced increases in activity in response to a potassium-mediated excitability challenge than wildtypes (WT). The defective network activity in V1 was significantly altered following WT MGE transplantation, associating it with behavioral rescue of seizures in Stgs. Taken together, these findings present MGE grafting in the V1 as a possible clinical approach in the treatment of AE., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Research Question: Recent discoveries have challenged the traditional view that the thalamus is the primary source driving spike-and-wave discharges (SWDs). At odds, SWDs in genetic absence models have a cortical focal origin in the deep layers of the perioral region of the somatosensory cortex. The present study examines the effect of unilateral and bilateral surgical resection of the assumed focal cortical region on the occurrence of SWDs in anesthetized WAG/Rij rats, a well described and validated genetic absence model., Methods: Male WAG/Rij rats were used: 9 in the resected and 6 in the control group. EEG recordings were made before and after craniectomy, after unilateral and after bilateral removal of the focal region., Results: SWDs decreased after unilateral cortical resection, while SWDs were no longer noticed after bilateral resection. This was also the case when the resected areas were restricted to layers I-IV with layers V and VI intact., Conclusions: These results suggest that SWDs are completely abolished after bilateral removal of the focal region, most likely by interference with an intracortical columnar circuit. The evidence suggests that absence epilepsy is a network type of epilepsy since interference with only the local cortical network abolishes all seizures.

Neurophysiological and neuroimaging studies including both patients with disorders of consciousness and healthy subjects with modified states of consciousness suggest a crucial role of the medial posteroparietal cortex in conscious information processing. However no direct neuropsychological evidence supports this hypothesis and studies including patients with restricted lesions of this brain region are almost non-existent. Using direct intraoperative electrostimulations, we showed in a rare patient that disrupting the subcortical connectivity of the left posterior cingulate cortex (PCC) reliably induced a breakdown in conscious experience. This acute phenomenon was mainly characterized by a transient behavioral unresponsiveness with loss of external connectedness. In all cases, when he regained consciousness, the patient described himself as in dream, outside the operating room. This finding suggests that functional integrity of the PPC connectivity is necessary for maintaining consciousness of external environment., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: We analyzed clinical and electroencephalography (EEG) outcomes of 13 patients with pharmacoresistant encephalopathy with electrical status epilepticus during sleep (ESES) following epilepsy surgery., Methods: All patients had symptomatic etiology of ESES and preoperative neuropsychological deterioration. Ten patients had daily atypical absences. Clinical outcome was assessed at 6 months and at 2 years after surgery. Clinical and EEG data were reviewed retrospectively. The spike propagation pattern and area and source strength in source montage were analyzed from preoperative and postoperative EEG studies., Key Findings: Preoperative sleep EEG showed electrical status epilepticus during sleep (SES) with one-way interhemispheric propagation in nine patients and with two-way interhemispheric propagation in four. The age of the patients at the time of surgery ranged from 3.6-9.9 years. Focal resection (two patients) or hemispherotomy (one patient with postoperative EEG) either terminated SES or restricted the discharge to one region. Either reduced SES propagation area or source strength was found in four of eight callosotomy patients with postoperative EEG. Of patients who had seizures preoperatively, Engel class I-II seizure outcome was observed in two of three children after focal resection or hemispherotomy and in two of eight children after callosotomy. None of these patients with Engel class I-II outcome had SES with two-way interhemispheric propagation on preoperative EEG. Cognitive deterioration was halted postoperatively in all except one patient. Cognitive catch-up of more than 10 IQ points was seen in three patients, all of whom had shown a first measured IQ of >75., Significance: Patients with pharmacoresistant ESES based on symptomatic etiology may benefit from resective surgery or corpus callosotomy regarding both seizure outcome and cognitive prognosis., (Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.)

The substantia nigra pars reticulata (SNpr) is involved in controlling a variety of seizure phenomena. Intranigral transplants of GABAergic cells have been shown to decrease the severity of already established epileptic seizures, but the effects observed have been short-lived. This study evaluated the ability of intranigral transplants of GABA-producing cells to reduce spontaneous absence seizures in a genetic animal model for periods up to 3 months after transplantation. Intranigral transplants did not induce any behavioral deficits in the animals, and they did not form tumors; however, the transplants failed to decrease absence seizures in the genetic model. The assumed increase in intranigral levels of GABA after the transplants may be insufficient to counteract all the factors involved in generating the absence seizures; in this animal model, it may be necessary to further decrease nigral activity by implanting GABAergic cells in another area. These results bear down on the fact that cell transplants need to be tailored for each type of convulsive disorder in terms of the type of cells delivered and the location of the transplants., (Copyright 2010 Elsevier Inc. All rights reserved.)

Dense array EEG is a method of recording electroencephalography (EEG) with many more electrodes (up to 256) than is utilized with standard techniques that typically employ 19-21 scalp electrodes. The rationale for this approach is to enhance the spatial resolution of scalp EEG. In our research, dense array EEG is used in conjunction with a realistic model of head tissue conductivity and methods of electrographic source analysis to determine cerebral cortical localization of epileptiform discharges. In studies of patients with absence seizures, only localized cortical regions are involved during the attack. Typically, absences are accompanied by "wave-spike" complexes that show, both at the beginning and throughout the ictus, repetitive cycles of stereotyped, localized involvement of mainly mesial and orbital frontal cortex. Dense array EEG can also be used for long-term EEG video monitoring (LTM). We have used dense array EEG LTM to capture seizures in over 40 patients with medically refractory localization-related epilepsy, including both temporal and extra temporal cases, where standard LTM failed to reveal reliable ictal localization. One research goal is to test the validity of dense array LTM findings by comparison with invasive LTM and surgical outcome. Collection of a prospective series of surgical candidates who undergo both procedures is currently underway. Analysis of subjects with either generalized or localization-related seizures suggest that all seizures, including those traditionally classified as "generalized," propagate through discrete cortical networks. Furthermore, based on initial review of propagation patterns, we hypothesize that all epileptic seizures may be fundamentally corticothalamic or corticolimbic in nature. Dense array EEG may prove useful in noninvasive ictal localization, when standard methods fail. Future research will determine if the method will reduce the need for invasive EEG recordings, or assist in the appropriate placement of novel treatment devices.

Objective: The purpose of this study was to evaluate seizure outcome in children with intractable secondary generalized epilepsy without a resectable focus who underwent complete corpus callosotomy and compare these results to those of anterior two-third callosotomy., Method: Data were obtained for all patients who underwent a corpus callosotomy from 2000 to 2005. The study involved 37 patients. Eleven patients had anterior two-third corpus callosotomy compared with 28 patients who underwent complete corpus callosotomy. Two of these patients had completion of their callosotomy following initial partial callosotomy. Seizure type, seizure frequency, and family satisfaction were evaluated for all patients pre- and postoperatively., Results: A reduction of >or=75% in seizures occurred in 75% of the total-callosotomy patients compared to 55% of the partial-callosotomy patients. Family satisfaction for complete and partial callosotomy was 89 and 73%, respectively. No prolonged neurologic deficits were observed in either group., Conclusion: Complete corpus callosotomy is the most effective treatment for secondary generalized intractable seizures not amenable to focal resection in children.

The authors present the case of a 6-year-old girl with typical absence epilepsy induced by hyperventilation associated with moyamoya disease (MMD). A diffuse 3-Hz spike-and-wave complex induced by hyperventilation was apparent on an electroencephalogram, and her seizures were intractable to medication. Significant ischemia in the bilateral frontal lobes was present. The epilepsy disappeared after superficial temporal artery-middle cerebral artery anastomosis with encephalomyosynangiosis on both sides. In the treatment of children with intractable absence epilepsy, the possibility of underlying MMD and indications that revascularization surgery may be needed should be taken into consideration.

A tonic or "drop" attacks--often seen in Lennox-Gastaut syndrome--are some of the most feared childhood seizures, since they may lead to head injuries. Corpus callosum division will often control atonic seizures, and other types of generalized seizure.

The mesiofrontal cortex comprises a number of distinct anatomic and functional areas. Structural lesions and cortical dysgenesis are recognized causes of mesial frontal epilepsy, but a specific gene defect may also be important, as seen in some forms of familial frontal lobe epilepsy. The predominant seizure manifestations, which are not necessarily strictly correlated with a specific ictal onset zone, are absence, hypermotor, and postural tonic seizures. Other seizure types also occur. The task of localization of the epileptogenic zone can be challenging, whether EEG or imaging methods are used. Successful localization can lead to a rewarding outcome after epilepsy surgery, particularly in those with an imaged lesion.

There are no reports of an association between obsessive-compulsive disorder and cingulate epilepsy in childhood. We report the behavioral, cognitive, and EEG findings in a young girl with medically resistant seizures and severe obsessive-compulsive symptomatology. Her scalp EEG and neuropsychological test scores suggested right frontal lobe dysfunction. The intractability of her seizures and progressive intellectual and psychosocial deterioration prompted evaluation for excisional surgery. Intracranial EEG recording demonstrated a focal seizure origin in the right anterior cingulate gyrus. Cingulotomy resulted in freedom from seizures and significant improvement in her obsessive-compulsive symptoms.

We studied the effectiveness of anterior callosotomy in 43 patients whose follow-up period averaged 39 months. These patients had intractable generalized seizures, characterized by a combination of seizure patterns, most frequently drop attacks with generalized tonic-clonic, generalized tonic, and absence seizures. Overall, drop attacks were the most frequent (31/43 or 72%) and the most disabling seizure pattern (27/43 or 63%); they were also the most likely to benefit from anterior callosotomy (70%). Patients with lateralized changes tended to have a better result than did those without lateralization, but patients with synchronous and symmetrical spike and wave discharges also benefited. The preoperative intelligence quotient and the etiological factors were not predictors of outcome. There was a correlation between the extent of section and the results; patients with section of the anterior two thirds had a better result, compared with those who had section of the anterior half.

A 32 years old woman who had postural limbic and primarily generalized tonic-clonic seizures since the age of 11 presented to us with a CT image strongly suggestive of a mesial meningioma near the right cingulum. Her ictal EEG pattern was characterized by regular 1.5-2.0 Hz sharp and slow wave complexes. A right craniotomy was performed under general anesthesia and intraoperative electroencephalographic and electrocorticographic recordings were obtained by means of scalp steel electrodes and modified cerebellar stimulation electrodes, respectively. These recordings demonstrated that surface spikes were often independent from the electrocorticographically recorded ones. Before tumor excision, electrical stimulation of the peritumoral mesial cortex resulted in an increase in the epileptic activity. The stimulation of the cavity left after tumor excision led to a prolonged electrographic seizure and neurophysiological procedures were stopped. Post-operatively, the patient has remained seizure free for 6 months and her EEG was normal. The pre-, intra- and postoperative findings in this case suggest that the gliotic peritumoral mesial cortex was at least involved in the epileptogenic process.

Using the 2-[F-18]fluorodeoxyglucose method, 213 positron emission tomographic (PET) studies of local brain glucose metabolism (CMRglu) were performed in 124 patients with various forms of epilepsy. Interictal PET scans of primary epileptics typically showed some global metabolic depression and decreased functional activity of insular, basal and anterior temporal cortex. Epilepsia partialis continua Kozevnikov was characterized by hypo- or hyper-metabolism of perirolandic cortex. Tuberous sclerosis was distinguished by neocortical foci of significantly decreased glucose consumption. Even in the interictal resting state, with regard to sensitivity (greater than 90%) and accuracy of focus localization. PET was superior to other diagnostic methods in typical temporal lobe epilepsy. Averaging 23% below normal CMRglu, the majority of hypometabolic foci were found in mesial temporal structures. Improved distinction between the epileptogenic area and the surrounding tissue showing comparatively normal functional responsiveness, was achieved by psychophysical activation using emotional speech or continuous visual recognition during PET scanning. In patients who had undergone total cerebral hemispherectomy because of uncontrolled epilepsy, remarkable recruitment of association areas was observed on both motor and speech activation.

We report a case of Lennox-Gastaut-type epilepsy that was followed for 3 years. The patient showed typical EEG findings and later a parietotemporal astrocytoma (type II) on the left. Removal of the tumor was followed by recovery of the child and disappearance of EEG epileptic elements.

6 patients undergoing anterior corpus callosotomy for intractable epilepsy have been studied with depth electroencephalography (EEG). Recording before, during and after surgery has confirmed the ability of depth EEG to demonstrate and identify lateralized, focal and often multifocal disturbances. Callosal section has an immediate and lasting effect on clinical seizures and is accompanied by EEG changes with loss of generalization and synchrony following commissurotomy. Depth electrodes within the corpus callosal radiations variably reflect preoperative epileptiform activity recorded from the temporal and frontal regions and postoperatively confirm loss of a potential route of propagation through the commissure.

Types of seizures, age at onset of epilepsy, preoperative duration of epilepsy, and age at operation were studied in the literature and in 74 patients who underwent unilateral temporal lobe resection in 1960-1969 in Denmark. The medical and surgical series were compared. The age at onset was significantly lower in the surgical series. Prognostically favourable factors were: i) preoperative presence of a single type of seizure; ii) duration of epilepsy of less than 4 years, and in grand mal epilepsy of less than 1 year; iii) operation for epilepsy in or before early adulthood. Prognostically unfavourable factors were i) preoperative presence of grand mal; ii) age at onset of epilepsy or of the first grand mal seizure between 5 and 20 years; iii) preoperative duration of psychomotor epilepsy over 10 years.

Cerebral commissurotomy is a well established procedure in the treatment of epileptics refractory to drug therapy. Breeching of the ventricles in complete commissurotomy carries a certain morbidity. This has led others to perform operations in which the entire corpus callosum or only its anterior portion with or without the anterior commissure were sectioned. Sectioning of the anterior corpus callosum alone is justified by: a) frequent appearance in patients of seizures attributable to a frontal focus, b) clinical and experimental evidence that frontal discharges spread across the corpus callosum leading to subsequent generalized its, c) the attempt to understand the mechanisms involved in generalized seizures, d) even further reduced surgical morbidity and neuropsychological disability. Five epileptics were submitted to anterior callosotomy. The seizures in all of them suggested a frontal focus and consisted of absences, adversive, tonic, atonic, and tonic-clonic attacks. All patients were incapacitated by the frequency of seizures. Their EEGs showed paroxysms of bilateral synchronous slow spike and wave with uni-, or multiple (including bilateral symmetrical) focal accentuation. In two patients there were additional independent temporal lobe discharges. Neuropsychological evaluation showed cognitive deficits caused by inattention paroxysms and absences. After anterior callosotomy there was marked reduction in frequency of all types of seizures, the greatest improvement being in the reduction of frequency of absences. There was a marked decrease in physical, social and neuropsychological disabilities.

Stereotactic Forel-H-Tomy has been performed in 20 cases of epilepsy refractory to medication of which 15 have been followed from 2 to 7 years. The outcome of operation in 7 cases is judged as 'markedly effective' or 'effective'. In 3 cases the operation was ineffective. Effectiveness was greater in bilateral operation. Improvement of EEG was indicated by disappearance or marked reduction of spikes (or sharp waves) or spike and wave complex. Grand mal seizures alone or cases of minor seizure alone have responded more favorably than other clinical types. Six cases demonstrated improvement of personality and emotions.

Heterotopia of the cerebral cortex, a disorder of neuronal migration, may be associated with medically intractable seizures. We report on a patient with bihemispheric cortical heterotopia who had medically intractable atonic seizures that were successfully treated by corpus callosotomy. The clinical and radiographic aspects of cortical heterotopia and the surgical management of seizures associated with heterotopia are discussed.

A group of 15 children aged 13 months to 15 years and operated upon for focal epilepsy has been analyzed. Hemispherectomy was performed in 3 cases, lobectomy in 6 cases, and cortical excision of different extents in another 6 cases. Within a period of 5 months to 7 years from the surgical intervention 60% of the patients were practically restored to health, 20% improved, and 20% virtually unimproved. The authors discuss the problems of indication in connection with age as well as the therapeutical failures. In cases where conservative therapy failed the intervention prevented the epileptic process from encroaching upon the centrencephalic system. It is essential that the intervention be made before the occurrence of irreversible psychic changes, as these may then no longer be influenced by the intervention. There are no age limits to a surgical intervention. An accurate analysis of the functional capability of the brain tissue is absolutely necessary; what is also important, however, is specific care, in order to avoid postoperative complications.