Vagus Nerve Stimulation Electrode Impedance Over Time in Children With Lennox-Gastaut Syndrome.

OBJECTIVE: This manuscript describes the behavior of impedance of vagus nerve stimulation (VNS) electrode over time in a cohort of children with Lennox-Gastaut syndrome. MATERIALS AND METHODS: Nineteen consecutive pediatric patients with Lennox-Gastaut syndrome submitted to VNS were studied. All patients had at least four years of follow-up. Serial impedance measurements were carried out during every out-patient visit. A baseline value was obtained one month after surgery, before generator activation and yearly values were recorded for the next four years. Outcome regarding seizures was obtained through analysis of standardized seizure diaries filled out by the patient, relatives, or caregivers. RESULTS: There were 12 boys. Age ranged from four to 14 years (mean = 7.2). Mean impedance value was 2635 Ω at baseline, 2576 Ω after one year, 2418 Ω after two years, 2340 Ω after three years, and 2241 Ω after four years. There was a mean impedance decrease of 17% after four years. This decrease was statistically significant compared with baseline by the second year of follow-up: p = 0.342 after one year, p = 0.007 after two years, p = 0.001 after three years, and p = 0.001 after four years. There was no significant relationship between impedance values and seizure outcome at any time point. CONCLUSIONS: VNS electrode impedance significantly decreased during long-term follow-up in children with Lennox-Gastaut syndrome. To our knowledge, this is the first report on such findings regarding VNS in the literature. These findings suggest that the electrode/nerve interface is stable during long-term follow-up of VNS therapy and that this preserved anatomical relationship might be related to our ability to safely stimulate and review/explant the system whenever needed.

Combined Neuromodulation (Vagus Nerve Stimulation and Deep Brain Stimulation) in Patients With Refractory Generalized Epilepsy: An Observational Study.

INTRODUCTION: This article describes our findings while treating patients with refractory generalized epilepsy with combined vagus nerve stimulation (VNS) and centro-median deep brain stimulation (CMDBS). MATERIALS AND METHODS: A total of 11 consecutive patients with refractory generalized epilepsy (ten with Lennox-Gastaut syndrome) previously submitted to VNS and who subsequently underwent CMDBS were retrospectively studied. The VNS final parameters were 2 to 2.5 mA, 30 Hz, and 500 µs, cycling mode, 30 seconds "on" and 5 minutes "off" for all patients. The CMDBS final parameters were 4 to 5 V, 130 Hz, and 300 µs, bipolar, continuous stimulation in all patients. RESULTS: There were eight male participants, ranging in age from eight to 49 years (mean 19 years). Follow-up time after VNS ranged from 18 to 132 months (mean 52 months) and from an additional 18 to 164 months (mean 42 months) during combined VNS-CMDBS. All patients had daily seizures. Atypical absences were noted in eight patients, tonic seizures in seven, bilateral tonic-clonic seizures in four, atonic seizures in three, and myoclonic seizures in two patients. Four patients were initially considered responders to VNS. All these patients also had an additional >50% seizure frequency reduction during combined VNS-CMDBS. Seven patients were not responders to VNS, and of those, four had an additional >50% seizure frequency reduction during combined VNS-CMDBS. Eight patients had an additional >50% reduction in seizure frequency when moved from VNS alone to VNS-CMDBS therapy. There were two nonresponders during combined VNS-CMDBS therapy, and both were nonresponders to VNS alone. Nine patients were considered responders during VNS-CMDBS combined therapy compared with baseline. DISCUSSION: This study showed that combined VNS-CMDBS therapy was able to double the number of responders compared with VNS alone in a cohort of patients with refractory generalized epilepsy. We believe these data represent the first evidence that combined neuromodulation may be useful in this quite homogeneous patient population.

Impact of Cardiac-Based Vagus Nerve Stimulation Closed-Loop Stimulation on the Seizure Outcome of Patients With Generalized Epilepsy: A Prospective, Individual-Control Study.

OBJECTIVES: We designed a prospective, individual-controlled study to evaluate the effect of cardiac-based VNS (cbVNS) in a cohort of patients with generalized epilepsy (GE). MATERIALS AND METHODS: Twenty patients were included. They were followed up for six months under regular VNS (rVNS) and subsequently for six months during cbVNS. Stimulation parameters were 500 µsec, 30 Hz, and up to 2.5 mA. Seizure frequency was documented after two, four, and six months during the rVNS and cbVNS phases. Patients with at least 50% seizure frequency reduction were considered responders. The total and relative amount of stimulation cycles generated by both rVNS and cbVNS activation were documented. Findings during rVNS were compared to baseline and cbVNS data were compared to those during rVNS. RESULTS: There was a significant decrease in mean seizure frequency (61% [95% CI, 48-74]; p < 0.001) during the rVNS phase compared to baseline. There was no additional significant (16% [95% CI, 4-35]; p = 0.097) mean seizure frequency reduction during cbVNS compared to the rVNS phase. Fifteen patients (75%) were considered responders after rVNS. Four patients (20%) were considered responders after six months of cbVNS. During the cbVNS phase, the mean total number of cycles/day was 346, 354, and 333 for months two, four, and six, respectively; the cycles generated by rVNS were 142, 138, and 146 for months two, four, and six, respectively; and cycles generated by cbVNS were 204, 215, and 186 for months two, four, and six, respectively. There was no relationship between the mean total number of cycles (-6[95% CI, -85 to 72]; p = 0.431), the mean number of auto-stimulation cycles (27[95% CI,-112 to 166]; p = 0.139), the mean number of regular cycles (-33[95% CI,-123 to 57]; p = 0.122), or the mean percentage of auto-stimulation cycles (13[95% CI,19- 45]; p = 0.109) and outcome during the cbVNS phase. Eight patients showed some decrease in seizure frequency during cbVNS. CONCLUSIONS: rVNS was effective in reducing seizure frequency in patients with generalized epilepsy, but activation of the cbVNS feature did not add significantly to rVNS efficacy. On the other hand, although not statistically significant, 40% of the patients showed some reduction in seizure frequency, which might prove useful at an individual level.

Long-term seizure outcome during continuous bipolar hippocampal deep brain stimulation in patients with temporal lobe epilepsy with or without mesial temporal sclerosis: An observational, open-label study.

OBJECTIVE: We present the findings related to seizure outcome during hippocampal deep brain stimulation (Hip-DBS) in patients with refractory temporal lobe epilepsy. METHODS: Twenty-five patients submitted to Hip-DBS were studied. All patients were evaluated with interictal and ictal electroencephalography (EEG) and high-resolution 1.5 T magnetic resonance imaging (MRI). The hippocampus was targeted directly on MRI using a posterior occipital burr hole approach. Bipolar continuous stimulation was ramped up until 3.0 V (300 µs, 130 Hz). Patients were considered responders if at least 50% seizure frequency reduction was obtained. RESULTS: Median age was 39 years; median follow-up time was 57 months (16 women). All patients had focal with impaired awareness seizure (FIAS) and 23 patients had focal aware seizure (FAS). Baseline median FAS and FIAS frequency was 8. Ictal EEG showed unilateral (n = 10) or bilateral (n = 15) seizure onset. MRI showed unilateral (n = 11) or bilateral (n = 8) mesial temporal sclerosis (MTS) and was normal in six6 patients. Fifteen patients were submitted to bilateral and 10 patients to unilateral Hip-DBS. Median reduction in FAS frequency was 66%. Eighteen patients with FAS were considered responders and five (21%) were free of FAS. Median FIAS frequency (n = 25) reduction was 91%. Twenty-two patients were considered responders and eight (32%) were free of FIAS. FIAS were significantly more reduced then FAS (P = .017). There was no relation between any contact's position within the hippocampus and outcome for either FAS (P = .727) or FIAS (P = .410). There was no difference in outcome in patients submitted to either unilateral or bilateral Hip-DBS regarding FAS (P = .978) or FIAS (P = .693). SIGNIFICANCE: Hip-DBS significantly reduced the frequency of both FAS and FIAS in this cohort of patients with refractory temporal lobe epilepsy. Hip-DBS might represent a good therapeutic option in such patients not amenable to resective surgery.

Hippocampal deep brain stimulation: a therapeutic option in patients with extensive bilateral periventricular nodular heterotopia: a case report.

A female adult patient with extensive bilateral periventricular nodular heterotopia (PNH), who was referred for bilateral hippocampal deep brain stimulation (Hip-DBS), was investigated. She presented with daily focal aware and impaired-awareness seizures with automatism and weekly generalized tonic-clonic seizures. Her EEG showed bilateral independent ictal and interictal neocortical temporal lobe discharges and her MRI showed extensive, symmetric PNH. She was treated with bilateral Hip-DBS which led to a major decrease in her seizure frequency (one seizure per trimester). The outcome was stable over three years, and there was no additional neuropsychological deficits or device-related adverse effects. This is the first reported patient to be undergo long-term continuous Hip-DBS to treat bilateral PNH. DBS, a non-lesional, reversible, neuromodulatory technique, may prove to be a good therapeutic option in patients with extensive bilateral epileptogenic networks who present with temporal lobe epilepsy and who are usually considered poor candidates for resective surgery.

Seizure outcome during bilateral, continuous, thalamic centromedian nuclei deep brain stimulation in patients with generalized epilepsy: a prospective, open-label study.

OBJECTIVE: We report on the seizure frequency and attention outcome during thalamic centromedian stimulation (CM-DBS) in patients with refractory generalized epilepsy (GE). METHODS: Twenty consecutive patients with GE who were submitted to CM-DBS and had at least one year of follow-up were prospectively studied. The CM was targeted bilaterally. Stimulation intensity was ramped up (bipolar, continuous, 130 Hz; 300µsec) until 4.5 V or until side effects developed. Contacts` position was determined on postoperative volumetric MRI scans. Attention was qualitatively evaluated using the SNAP-IV (Swanson, Nolan, and Pelham) questionnaire. Patients were considered responders during CM-DBS if an at least 50% seizure frequency reduction was obtained compared to baseline. RESULTS: Median age was 15.5 years (13 males). Median follow-up time was 2.55 years. EEG disclosed generalized spike-and wave discharges in all patients. MRI was normal in 10 patients, showed diffuse atrophy in 6 patients, and showed abnormalities in 4 patients (3 patients had bilateral cortical development abnormalities and one had unilateral hemispheric atrophy). Patients presented with daily multiple seizure types (8 to 66 per day; median: 37), including tonic, atonic, myoclonic, atypical absence and generalized tonic-clonic seizures. Mean DBS intensity was 4.3 V. An insertional effect was noted in 14 patients. CM-DBS was able to significantly reduce the frequency of tonic (p < 0.001), atypical absence seizures (p < 0.001), atonic seizures (p = 0.001) and bilateral generalized tonic-clonic seizures (p = 0.004). One patient became seizure-free. Ninety percent of the patients were considered responders (>50% seizure frequency reduction). All patients showed some improvement in attention. The mean number of items in which improvement was noted in the SNAP-IV questionnaire was 4.8. There was a significant relationship between overall seizure frequency reduction and improvement of attention (p = 0.033). DISCUSSION: This prospective, open label study included a large, homogeneous cohort and provided evidence on the efficacy of CM-DBS in reducing the seizure burden and increasing attention in patients with refractory generalized epilepsy.

Seizure outcome after hippocampal deep brain stimulation in patients with refractory temporal lobe epilepsy: A prospective, controlled, randomized, double-blind study.

OBJECTIVE: We designed a prospective, randomized, controlled, double-blind study to evaluate the efficacy of hippocampal deep brain stimulation (Hip-DBS) in patients with refractory temporary lobe epilepsy (TLE). METHODS: Sixteen adult patients with refractory TLE were studied. Patient's workup included medical history, interictal and ictal electroencephalography (EEG), and high-resolution 1.5T magnetic resonance imaging (MRI). Patients were randomized on a 1:1 proportion to an active (stimulation on) or to a control (no stimulation) arm. After implantation, patients were allowed to recover for 1 month, which was followed by a 1-month titration (or sham) period. The 6-month blinded phase started immediately afterward. A postoperative MRI confirmed the electrode's position in all patients. All patients received bipolar continuous stimulation. Stimulus duration was 300 µs and frequency was 130 Hz; final intensity was 2 V. Patients were considered responders when they had at least 50% seizure frequency reduction. RESULTS: All patients had focal impaired awareness seizures (FIAS, complex partial seizures), and 87% had focal aware seizures (FAS, simple partial seizures). Mean preoperative seizure frequency was 12.5 ± 9.4 (mean ± standard deviation) per month. MRI findings were normal in two patients, disclosed bilateral mesial temporal sclerosis (MTS) in three, left MTS in five, and right MTS in six patients. An insertional effect could be noted in both control and active patients. In the active group (n = 8), four patients became seizure-free; seven of eight were considered responders and one was a nonresponder. There was a significant difference regarding FIAS frequency between the two groups from the first month of full stimulation (p < 0.001) until the end of the blinded phase (p < 0.001). This was also true for FAS, except for the third month of the blinded phase. SIGNIFICANCE: Hip-DBS was effective in significantly reducing seizure frequency in patients with refractory TLE in the active group, as compared to the control group. Fifty-percent of the patients in the active group became seizure-free. The present study is the larger prospective, controlled, double-blind study to evaluate the effects of Hip-DBS published to date.

Seizure Outcome After Battery Depletion in Epileptic Patients Submitted to Deep Brain Stimulation.

OBJECTIVE: We studied patients treated with chronic DBS in whom there was depletion of the generator's battery, in order to get insight on the modulatory potential of chronic DBS in refractory epilepsy. MATERIAL: Nine adult patients with refractory epilepsy treated with at least three years of deep brain stimulation (DBS), and who were followed up for at least six months after battery depletion were studied. One patient was treated with hippocampal DBS (Hip-DBS), two to centro-median DBS (CM-DBS) and six to anterior nucleus stimulation (AN-DBS). RESULTS: Two patients did not have seizure's frequency modification after battery depletion; the other seven patients had seizure frequency increase, including those three patients that were seizure-free. Five of those seven patients who had seizure frequency increase after battery's depletion had seizure's frequency lower than their pre-DBS baseline seizure frequency; two of such patients returned to their pre-DBS baseline seizure frequency. CONCLUSIONS: In the majority of the patients, three years of chronic DBS did not show a permanent effect on epileptogenesis. On the other hand, the post-battery depletion seizure's frequency was usually much lower than the baseline (pre-DBS) seizure's frequency, suggesting that there was actual network neuromodulation.

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.

Speech preservation using a non-linear paradigm for determination of the extent of neocortical resection in patients with mesial temporal sclerosis submitted to cortico-amygdalo-hippocampectomy (CAH).

RATIONALE: The rationale for using a non-linear (proportional) paradigm for determining the extent of the neocortex to be removed in temporal lobe resection was based on anatomical and intra-operative cortical mapping findings. We present our results regarding speech preservation in patients submitted to CAH using the central artery as an anatomical landmark for determining the posterior border of neocortical resection. METHODS: Two hundred and fifty consecutive right-handed patients with left unilateral mesial sclerosis were studied. All patients were submitted to CAH under general anesthesia and without intraoperative electrocorticography. The posterior border of the lateral neocortical resection was defined by a line perpendicular to the temporal axis at the level of the central artery. RESULTS: Seven patients had transient (1-3 weeks; mean=9 days) receptive speech disturbance. There was no permanent speech deficit. Imaging documented edema or contusion at the posterior temporal cortical border in all patients who had transient speech deficits. The mean extent of cortical resection was 3.9 cm in adults and 3.1cm in kids. DISCUSSION: This is the first report in the literature discussing the use of a non-linear paradigm to determine the extent of lateral neocortical removal in this patient population. We found no permanent speech disturbances in this series. The non-linear approach used in this series proved to be safe and effective to avoid post-operative speech disorders. It was able to compensate for different brain and head sizes, and allowed smaller neocortical removal when compared to traditional linear approaches.

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 electrode's 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.

Outcome after cortico-amygdalo-hippocampectomy in patients with temporal lobe epilepsy and normal MRI.

RATIONALE: We describe seizure and neuropsychological outcome obtained after CAH in patients with TLE and normal MRI evaluated in the modern imaging era. METHODS: Forty-five adult consecutive patients with TLE and normal MRI were studied. All patients had neuropsychological testing, interictal and ictal EEG recordings and MRI. They were divided into two groups: Group 1 (n=18), included patients in whom non-invasive neurophysiological evaluation was lateralizing and Group 2 (n=27) included patients with non-lateralizing neurophysiological data who were submitted to invasive recordings. RESULTS: Seventy-seven percent of the Group 1 patients were rated as Engel I; 11% were rated as Engel II and 11% as Engel III. In Group 2, there were 57% of patients seizure-free, 26% in Engel II and 14% in Engel III. Pre-operatively, mean general IQ was 82 and 78 in Groups 1 and 2, respectively; post-operatively, mean general IQ was respectively 86 and 71. Some degree of verbal memory decline was noted in all patients submitted to dominant temporal lobe resection in both Groups 1 and 2. At last follow-up visit, 22% of Group 1 and 11% of Group 2 patients were receiving no antiepileptic drugs (AED). CONCLUSIONS: Our data showed that patients with TLE and normal MRI could get good surgical results after CAH although 60% of them would need invasive recordings and their results regarding seizure control and cognition were worse than those obtained in patients with MRI defined temporal lobe lesions. Caution should be taken in offering dominant temporal lobe resection to this subset of patients.

Vagus nerve stimulation might have a unique effect in reflex eating seizures.

We studied the effects of vagus nerve stimulation (VNS) on eating seizures, which theoretically would be triggered by neural activity and signaling from organs innervated by the vagus nerve. Three adult patients with daily nonreflex and reflex eating seizures were studied; one patient also had hot-water seizures. One patient had bilateral polymicrogyria and two had normal magnetic resonance imaging (MRI) findings. All patients were submitted to VNS implantation and had at least 2 years of postimplantation follow-up. Final stimulation parameters were 2.0-2.5 mA, 500 micros, and 30 Hz. Eating seizures decreased 70-95% and nonreflex seizures decreased 0-40% after VNS. There was no improvement in hot-water seizures. VNS seems to be an especially useful treatment modality in patients with reflex eating seizures not amenable to resective surgery.

Parkinsonism induced by VNS in a child with double-cortex syndrome.

We describe a child with epilepsy associated with double-cortex syndrome in whom vagus nerve stimulation (VNS) generated parkinsonian symptoms. A 13-year-old girl presented with refractory secondary generalized epilepsy from the age of 6 years and mental retardation. Her electroencephalography (EEG) showed diffuse polyspike and wave discharges. Magnetic resonance imaging (MRI) showed double-cortex syndrome. She was submitted to extended callosal section at the age of 10 years, which yielded 50% seizure frequency reduction. She was submitted to VNS by the age of 12 years. As stimulation intensity was increased, there was appearance of extrapyramidal symptoms: She developed bilateral tremor and rigidity, and gait and postural disturbance. All symptoms disappeared 7-10 days after VNS was turned off. Several attempts to reactivate VNS led to the same results. During the periods when VNS was on she presented with marked seizure frequency reduction. This is the first report of a clinically evident direct effect of VNS on the basal ganglia.

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.

Outcome after cortico-amygdalo-hippocampectomy in patients with severe bilateral mesial temporal sclerosis submitted to invasive recording.

INTRODUCTION: Although some degree of bilateral hippocampal involvement might be frequent in patients with temporal lobe epilepsy, severe bilateral mesial temporal sclerosis (MTS) is very rare. We present our experience while treating patients with severe bilateral MTS submitted to invasive recordings. METHODS: Nine adult patients were studied. All patients had simple and complex partial seizures. All patients had bilateral independent interictal temporal lobe spiking and non-lateralizing video-EEG findings. MRI showed severe bilateral MTS and no other brain lesion. All patients had severe verbal and non-verbal memory deficits. All patients were submitted to invasive recordings after bilateral subdural grids implantation. Cortico-amygdalo-hippocampectomy (CAH) was performed in all patients on the side suggested by invasive recording. Follow-up time ranged from 5 to 10 years. RESULTS: Invasive video-EEG showed exclusively unilateral seizure onset in seven patients; in two patients, seizures originating from both temporal lobes were found (80% of them originated from one side). Five patients were submitted to left and four to right CAH. Seven patients were rendered seizure-free after surgery (Engel I); the other two were rated as Engel II. There was no additional memory decline. There was no surgical morbidity or mortality. Pathological examination showed MTS in all patients. DISCUSSION: Good surgical outcome (77% seizure-free patients) could be obtained even in this apparently unsuitable group of patients. All patients benefit from the procedure. We did not see any cognitive decline in our patients with severe bilateral MTS. Patients with severe bilateral MTS would need invasive recordings despite any findings during surface video-EEG.

Outcome after hemispherectomy in hemiplegic adult patients with refractory epilepsy associated with early middle cerebral artery infarcts.

PURPOSE: To study the outcome after hemispherectomy (HP) in a homogeneous adult patient population with refractory hemispheric epilepsy. METHODS: Fourteen adult patients submitted to HP were studied. Patients had to be at least 18 years old, and have refractory epilepsy, clearly focal lateralized seizures and unilateral porencephalus consistent with early middle cerebral artery infarct on magnetic resonance imaging (MRI). All patients were submitted to functional hemispherectomy. We analyzed age of seizure onset, age by the time of surgery, gender, seizure type and frequency, interictal and ictal electroencephalography (EEG) findings, MRI and IQ scores preoperatively; seizure frequency, drug regimen, and IQ outcome were studied postoperatively. RESULTS: Mean follow-up was 64 months. All patients had frequent daily seizures preoperatively. All patients had unilateral simple partial motor seizures (SPS); 11 patients had secondarily generalized tonic-clonic (GTC) seizures and five patients had complex partial seizures (CPS), preoperatively. All patients had hemiplegia and hemianopsia. Twelve patients had unilateral EEG findings, and in two epileptic discharges were seen exclusively over the apparently normal hemisphere. Twelve patients were seizure-free after surgery and two patients had at least 90% improvement in seizure frequency. Pre- and postoperative mean general IQ was 84 and 88, respectively. Five of the twelve Engel I patients were receiving no drugs at last follow-up. There was no mortality or major morbidity. CONCLUSIONS: Our results suggest that well-selected adult patients might also get good results after HP. Although good results were obtained in our adult series, the same procedure yielded a much more striking result if performed earlier in life.

Outcome after extended callosal section in patients with primary idiopathic generalized epilepsy.

PURPOSE: We report the outcome of patients with refractory idiopathic generalized epilepsy (IGE) who were submitted to extended one-stage callosal section. METHODS: Eleven patients with IGE who were submitted to extended one-stage callosal section were studied. Preoperative workup included history and neurologic examination, interictal, and ictal electroencephalography (EEG) recording, high resolution 1.5T magnetic resonance imaging (MRI) and intelligence quotient (IQ) testing. All patients were submitted to extended one-stage microsurgical callosal section, leaving only the splenium intact. RESULTS: Preoperative ictal patterns included repetitive spike and wave or polyspike and wave discharges or fast epileptic recruiting rhythm. MRI showed no focal lesions. Preoperatively, mean general IQ was 85. Postoperatively, at least a 75% reduction in the frequency of generalized tonic-clonic seizures was noted in all patients. In three patients absences disappeared completely, and the others had at least 90% reduction in seizure frequency. Only one patient had myoclonic seizures preoperatively, and these seizures disappeared after callosal section. After surgery, mean general IQ was 89. A very clear increase in attention level was noted in all patients. Postoperative interictal EEG recordings showed rupture of bilateral synchrony in all patients. DISCUSSION: This article reports on a large and homogeneous series of patients with refractory IGE submitted for callosal section. There was a marked decrease in generalized seizure frequency and increase in the attention level in this patient population. Our results suggest that corticocortical interaction might have a role in IGE pathogenesis. Callosotomy is a safe, effective, and underused palliative procedure in these well-selected patients with refractory IGE.

Outcome after corticoamygdalohippocampectomy in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis without preoperative ictal recording.

PURPOSE: We report on the surgical outcome obtained in patients with refractory temporal lobe epilepsy with mesial temporal sclerosis (MTS) who were evaluated preoperatively without ictal recording and were submitted to corticoamygdalohippocampectomy. METHODS: Two hundred twelve patients with refractory temporal lobe epilepsy were evaluated by means of clinical history, neurological examination, interictal electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychological testing. MRI disclosed unilateral MTS in all patients. All patients were submitted to corticoamygdalohippocampectomy at the side determined by MRI. RESULTS: Interictal EEG showed unilateral temporal lobe spiking in 176 patients; in 36 patients, bilateral discharges were found. Mean follow-up time was 2.7 years. One hundred ninety-four patients (92%) were classified as Engel's class I. Eighteen patients (8%) were rated as Engel's class II. Thirty-two out of 36 patients, in whom bilateral discharges were found, were in Engel's class I. Sixty percent of the patients had an improvement in memory function related to the nonoperated temporal lobe. Fifty-nine percent of the patients had a 10-point increase in general IQ postoperatively. Verbal memory decline was noted in three patients. Pathological examination showed MTS in all patients. CONCLUSIONS: It is possible to adequately select good surgical candidates for temporal lobe resection using MRI and interictal EEG alone. In patients with MRI-defined MTS, we should expect a 90% postoperative remission rate. Cognitive decline was very rarely seen in this patient population. The finding of MTS on MRI is the single most important prognostic factor for good outcome after temporal lobe surgery.

Surgical outcome in patients with refractory epilepsy associated to MRI-defined unilateral mesial temporal sclerosis.

INTRODUCTION: Several pre-operative work-up protocols have been used while selecting epileptic patients for surgery among different centers. The relative value of the different available pre-operative tests is still under discussion. OBJECTIVE: We report on the surgical outcome obtained in patients with refractory temporal lobe epilepsy associated to mesial temporal sclerosis (MTS) and who were evaluated pre-operatively by interictal EEG and MRI alone. METHOD: Forty one patients with refractory unilateral temporal lobe epilepsy were evaluated using interictal EEG and MRI. MRI disclosed unilateral MTS in all patients. All patients had at least 4 interictal EEG recordings. All patients were submitted to cortico-amygdalo-hippocampectomy at the side determined by MRI. RESULTS: Interictal EEG showed unilateral epileptiform discharges compatible with MRI findings in 37 patients; in four out of the 41 patients, bilateral discharges were found. Mean follow-up time was 4.3+/-1.1 years. Thirty-nine patients (95.1%) were classified as Engels Class I (70.6% Engel I-A). Two patients (4.9%) were rated as Engel's Class II. All patients in whom bilateral discharges were found were in Engels Class I. Pathological examination showed MTS in all patients. CONCLUSION: It is possible to adequately select good surgical candidates for temporal lobe resection using MRI and interictal EEG alone. In patients with MRI-defined MTS we should expect a postoperative remission rate higher then 90%. The finding of MTS on MRI is the most important good prognostic factor after temporal lobe resection.