Arthur Cukiert

Extended, One-stage Callosal Section for Treatment of Refractory Secondarily Generalized Epilepsy in Patients with Lennox–Gastaut and Lennox-like Syndromes

Summary:  Purpose: We report on the efficacy and safety of extended one‐stage callosal section performed in a large and homogeneous series of patients.

Results of surgery in patients with refractory extratemporal epilepsy with normal or nonlocalizing magnetic resonance findings investigated with subdural grids.

Summary:  Purpose: To study the efficacy of extensive coverage of the brain surface with subdural grids in defining extratemporal cortical areas amenable for resection in patients with refractory extratemporal epilepy (R‐ExTE) and normal or nonlocalizing magnetic resonance imaging (MRI) scans.

Seizure outcome after hippocampal deep brain stimulation in a prospective cohort of patients with refractory temporal lobe epilepsy

PURPOSE In this study, we present the results obtained from a series of patients with refractory temporal lobe epilepsy (r-TLE) who underwent hippocampal deep brain stimulation (Hip-DBS). METHODS Nine consecutive adult patients were studied. Low-frequency and high-frequency stimulation was carried out immediately after the insertion of each electrode. Chronic continuous high-frequency stimulation was used during treatment. The mean follow-up time was 30.1 months. The mean age of the patients was 37.2 years. The MRI scan was normal in three patients; four patients had bilateral mesial temporal sclerosis (MTS), and two had unilateral MTS. RESULTS The patients with unilateral MTS received unilateral implantation and experienced a 76% and an 80% reduction in seizure frequency after Hip-DBS. All patients with normal MRI scans were implanted bilaterally. Two of these patients received unilateral activation of the electrodes and experienced a 97% and an 80% reduction in seizure frequency; the third patient had bilateral activation of the device and was a non-responder. All patients with bilateral MTS were implanted bilaterally. Three of these patients received unilateral activation of the device and experienced a 66%, a 66% and a 100% reduction in seizure frequency after Hip-DBS; one patient had bilateral electrode activation, and was a non-responder. Whenever present, generalised tonic-clonic seizures disappeared completely after Hip-DBS. CONCLUSIONS Although performed on a relatively small number of patients, Hip-DBS was safe and effective in our patients with r-TLE. Seven of the nine patients were considered responders. Hip-DBS might represent a useful therapeutic option in patients with refractory temporal lobe epilepsy who were not candidates for resective surgery or have had previous failed procedures.

Insular epilepsy: similarities to temporal lobe epilepsy case report

Insular epilepsy has been rarely reported and its clinical and electrographic features are poorly understood. The electrographic study of the insula is difficult since it is hidden from the brain surface by the frontal and temporal lobe. A 48 years-old woman started having simple partial autonomic and complex partial seizures with automatisms and ictal left arm paresis 8 years prior to admission. Seizures frequency was 1 per week. Pre-operative EEG showed a right temporal lobe focus. Neuropsychological testing disclosed right fronto-temporal dysfunction. MRI showed a right anterior insular cavernous angioma. Intraoperative ECoG obtained after splitting of the sylvian fissure showed independent spiking from the insula and temporal lobe and insular spikes that spread to the temporal lobe. The cavernous angioma and the surrounding gliotic tissue were removed and the temporal lobe was left in place. Post-resection ECoG still disclosed independent temporal and insular spiking with a lower frequency. The patient has been seizure-free since surgery. Insular epilepsy may share many clinical and electroencephalographic features with temporal lobe epilepsy.

Aspectos epidemiológicos da epilepsia em São Paulo: um estudo da prevalência

Several studies on epidemiology of epilepsy were carried out in different parts of the world. However, the majority of their data was collected from hospitals, clinics, individual physicians and or small communities. Although these studies have contributed to our knowledge as to the risk factors of epilepsy, some of them have prevented us from further generalization, since the prevalence rates of the phenomena were not known for the entire population where from they were derived. Latin America has remained without epidemiological data, specially prevalence rates, for many years. A house-to-house survey was programmed by the Brazilian League of Epilepsy in the urban area of S. Paulo City the third largest cosmopolitan city in the world: 13 million inhabitants in 1980. A significant sample of 2011 houses was chosen by statistical means. A total of 7603 interviews were performed by 50 senior medical students and nurses, and 388 persons were considered suspect and further referred to our University Hospital for other studies; 348 of these were examined, and in 91 the diagnosis of epilepsy was confirmed, thus producing a prevalence rate 11.9 per 1000.

Centro-median stimulation yields additional seizure frequency and attention improvement in patients previously submitted to callosotomy

RATIONALE Deep brain stimulation (DBS) has been increasingly used in the treatment of refractory epilepsy over the last decade. We report on the outcome after thalamic centro-median (CM) DBS in patients with generalized epilepsy who had been previously treated with extended callosal section. METHODS Four consecutive patients with generalized epilepsy who were previously submitted to callosal section and had at least 1 year of follow-up after deep brain implantation were studied. Age ranged from 19 to 44 years. All patients were submitted to bilateral CM thalamic DBS. Post-operative CT scans documented the electrode position in all patients. All patients had pre- and post-stimulation prolonged interictal scalp EEG recordings, including spike counts. Attention level was evaluated by means of the SNAP-IV questionnaire. The pre-implantation anti-epileptic drug regimen was maintained post-operatively in all patients. RESULTS Post-operative CT documented that all electrodes were correctly located. There was no morbidity or mortality. Seizure frequency reduction ranging from 65 to 95% and increased attention level was seen in all patients. Interictal spiking frequency was reduced from 25 to 95%, but their morphology remained the same. There was re-synchronization of interictal discharges during slow-wave sleep in 2 patients. CONCLUSION All patients benefit from the procedure. The CM seems to play a role in modulating the epileptic discharges and attention in these patients. On the other hand, it is not the generator of the epileptic abnormality and appeared not to be involved in non-REM sleep-related interictal spiking modulation.

Congruence of the topography of intracranial calcifications and epileptic foci

Nodular intracranial calcifications (NIC) are frequent findings in CT scans of epileptic patients in countries where granulomatous central nervous disease such as neurocysticercosis is endemic. In 34 consecutive epileptic patients with NIC submitted to EEG, CT and CSF analysis, the correlation between the electroclinical localization of the focus and the topography of the NIC was studied. Twenty-nine patients had partial (Group I) and 5 had primarily generalized seizures (Group II). Twenty group I and 1 group II patients showed abnormal EEGs. CSF abnormalities consisted of increased protein content (n = 3) and positive Weinbergs reaction (n = 2). In 2 cases, viable neurocysticercotic vesicles were seen. Twenty-one patients had single NICs. No correlation could be established in group II patients. Within group I, 15 patients had a positive and 14 a negative correlation. Sixty-six percent of the patients with single NICs had negative correlations. These findings strongly suggest that the calcifications themselves are not the epileptogenic lesions in at least 50% of the studied cases.

Double pathology in Rasmussen's encephalitis : Etiologic considerations

In a 7‐year‐old girl with epilepsia partialis continua (EPC) involving the left face, arm, and leg for 1 year, serial neuroimaging studies showed progressive, brain atrophy. Because medical treatment was ineffective, she underwent a large fronto‐temporal surgical resection. Neuropathological examination showed loss of lamination and dysplastic neurons, gliosis, microglial nodules, and perivascular cuffing. Such “double pathology” (dysgenesia and a chronic inflammatory process) may have implications for the pathophysiology of Rasmussens syndrome.

Long-term outcome after callosotomy or vagus nerve stimulation in consecutive prospective cohorts of children with Lennox-Gastaut or Lennox-like syndrome and non-specific MRI findings

PURPOSE There is currently no resective (potentially curative) surgical option that is useful in patients with Lennox-Gastaut syndrome. Palliative procedures such as callosotomy (Cx), vagus nerve stimulation (VNS) or deep brain stimulation have been offered. We compared the outcomes after Cx or VNS in two consecutive prospective cohorts of patients with generalised epilepsy. METHODS Twenty-four patients underwent callosotomy from 2006 to 2007 (Group 1); 20 additional patients were submitted to VNS from 2008 to 2009 (Group 2). They had generalised epilepsy of the Lennox-Gastaut or Lennox-like type. They were submitted to a neurological interview and examination, interictal and ictal video-EEG, high resolution 1.5T MRI, and cognitive and quality of life evaluations. The two-year post-operative follow-up results were evaluated for each patient. RESULTS The final mean stimuli intensity was 3.0 mA in the Group 2 patients. Seizure-free patients accounted for 10% in Group 1 and none in Group 2. Ten and sixteen percent of the Group 1 and 2 patients, respectively, were non-responders. Improvements in attention and quality of life were noted in 85% of both Group 1 and 2 patients. Rupture of the secondary bilateral synchrony was noted in 85% of Group 1 patients; there was no EEG modification after VNS in Group 2. Both procedures were effective regarding the control of atypical absences and generalised tonic-clonic seizures. Both procedures were not effective in controlling tonic seizures. Callosotomy was very effective in reducing the frequency of atonic seizures, but VNS was ineffective. In contrast, callosotomy was not effective in reducing myoclonic seizures, whereas VNS was. DISCUSSION Callosotomy might be preferred as the primary treatment in children with Lennox-Gastaut syndrome, and no specific findings on MRI if atonic seizures prevail in the patients clinical picture; when myoclonic seizures prevail, the same might hold true in favour of VNS. When atypical absence or generalised tonic-clonic seizures are the main concern, although both procedures carry similar effectiveness, VNS might be considered a good option as an initial approach, taking into account the adverse event profile. Patients should be advised that both procedures are not very effective in the treatment of tonic seizures.

Intraoperative neurophysiological responses in epileptic patients submitted to hippocampal and thalamic deep brain stimulation.

PURPOSE Deep brain stimulation (DBS) has been used in an increasing frequency for treatment of refractory epilepsy. Acute deep brain macrostimulation intraoperative findings were sparsely published in the literature. We report on our intraoperative macrostimulation findings during thalamic and hippocampal DBS implantation. METHODS Eighteen patients were studied. All patients underwent routine pre-operative evaluation that included clinical history, neurological examination, interictal and ictal EEG, high resolution 1.5T MRI and neuropsychological testing. Six patients with temporal lobe epilepsy were submitted to hippocampal DBS (Hip-DBS); 6 patients with focal epilepsy were submitted to anterior thalamic nucleus DBS (AN-DBS) and 6 patients with generalized epilepsy were submitted to centro-median thalamic nucleus DBS (CM-DBS). Age ranged from 9 to 40 years (11 males). All patients were submitted to bilateral quadripolar DBS electrode implantation in a single procedure, under general anesthesia, and intraoperative scalp EEG monitoring. Final electrodes position was checked postoperatively using volumetric CT scanning. Bipolar stimulation using the more proximal and distal electrodes was performed. Final standard stimulation parameters were 6Hz, 4V, 300μs (low frequency range: LF) or 130Hz, 4V, 300μs (high frequency range: HF). KEY FINDINGS Bilateral recruiting response (RR) was obtained after unilateral stimulation in all patients submitted to AN and CM-DBS using LF stimulation. RR was widespread but prevailed over the fronto-temporal region bilaterally, and over the stimulated hemisphere. HF stimulation led to background slowing and a DC shift. The mean voltage for the appearance of RR was 4V (CM) and 3V (AN). CM and AN-DBS did not alter inter-ictal spiking frequency or morphology. RR obtained after LF Hip-DBS was restricted to the stimulated temporal lobe and no contralateral activation was noted. HF stimulation yielded no visually recognizable EEG modification. Mean intensity for initial appearance of RR was 3V. In 5 of the 6 patients submitted to Hip-DBS, an increase in inter-ictal spiking was noted unilaterally immediately after electrode insertion. Intraoperative LF stimulation did not modify temporal lobe spiking; on the other hand, HF was effective in abolishing inter-ictal spiking in 4 of the 6 patients studied. There was no immediate morbidity or mortality in this series. SIGNIFICANCE Macrostimulation might be used to confirm that the hardware was working properly. There was no typical RR derived from each studied thalamic nuclei after LF stimulation. On the other hand, absence of such RRs was highly suggestive of hardware malfunction or inadequate targeting. Thalamic-DBS (Th-DBS) RR was always bilateral after unilateral stimulation, although they somehow prevailed over the stimulated hemisphere. Contrary to Th-DBS, Hip-DBS gave rise to localized RR over the ipsolateral temporal neocortex, and absence of this response might very likely be related to inadequate targeting or hardware failure. Increased spiking was seen over temporal neocortex during hippocampal electrode insertion; this might point to the more epileptogenic hippocampal region in each individual patient. We did not notice any intraoperative response difference among patients with temporal lobe epilepsy with or without MTS. The relationship between these intraoperative findings and seizure outcome is not yet clear and should be further evaluated.