Global modified-Delphi consensus on comorbidities and prognosis of SCN8A-related epilepsy and/or neurodevelopmental disorders.

OBJECTIVES: We aimed to develop consensus on comorbidities (frequency, severity, and prognosis) and overall outcomes in epilepsy, development, and cognition for the five phenotypes of SCN8A-related disorders. METHODS: A core panel consisting of 13 clinicians, 1 researcher, and 6 caregivers was formed and split into three workgroups. One group focused on comorbidities and prognosis. All groups performed a literature review and developed questions for use in a modified-Delphi process. Twenty-eight clinicians, one researcher, and 13 caregivers from 16 countries participated in three rounds of the modified-Delphi process. Consensus was defined as follows: strong consensus ≥80% fully agree; moderate consensus ≥80% fully or partially agree, <10% disagree; and modest consensus 67%-79% fully or partially agree, <10% disagree. RESULTS: Consensus was reached on the presence of 14 comorbidities in patients with Severe Developmental and Epileptic Encephalopathy (Severe DEE) spanning non-seizure neurological disorders and other organ systems; impacts were mostly severe and unlikely to improve or resolve. Across Mild/Moderate Developmental and Epileptic Encephalopathy (Mild/Moderate DEE), Neurodevelopmental Delay with Generalized Epilepsy (NDDwGE), and NDD without Epilepsy (NDDwoE) phenotypes, cognitive and sleep-related comorbidities as well as fine and gross motor delays may be present but are less severe and more likely to improve compared to Severe DEE. There was no consensus on comorbidities in the SeL(F)IE phenotype but strong conesensus that seizures would largely resolve. Seizure freedom is rare in patients with Severe DEE but may occur in some with Mild/Moderate DEE and NDDwGE. SIGNIFICANCE: Significant comorbidities are present in most phenotypes of SCN8A-related disorders but are most severe and pervasive in the Severe DEE phenotype. We hope that this work will improve recognition, early intervention, and long-term management for patients with these comorbidities and provide the basis for future evidence-based studies on optimal treatments of SCN8A-related disorders. Identifying the prognosis of patients with SCN8A-related disorders will also improve care and quality-of-life for patients and their caregivers.

Global modified Delphi consensus on diagnosis, phenotypes, and treatment of SCN8A-related epilepsy and/or neurodevelopmental disorders.

OBJECTIVE: We aimed to develop consensus for diagnosis/management of SCN8A-related disorders. Utilizing a modified Delphi process, a global cohort of experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, and management of SCN8A-related disorders. METHODS: A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty-eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, <10% disagree; and modest consensus, 67%-79% fully/partially agree, <10% disagree. RESULTS: Early diagnosis is important for long-term clinical outcomes in SCN8A-related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self-limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first-line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first-line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First-line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients. SIGNIFICANCE: This is the first-ever global consensus for the diagnosis and treatment of SCN8A-related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence-based care and empowers SCN8A families to advocate for their children.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

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.

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.

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.

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.

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.

A prospective long-term study on the outcome after vagus nerve stimulation at maximally tolerated current intensity in a cohort of children with refractory secondary generalized epilepsy.

INTRODUCTION: We report the outcome after vagus nerve stimulation (VNS) in children with secondary generalized epilepsy. METHODS: Twenty-four consecutive children with Lennox-Gastaut or Lennox-like syndrome under the age of 12 years by the time of surgery, who were implanted with a vagus nerve stimulator and had at least two years of postimplantation follow-up, were prospectively included in the study. The generator was turned on using 0.25 mA, 30 Hz, 500 µsec, 30 sec "on," 5 min "off" stimuli parameters; current was then increased by 0.25 mA every two weeks, until 3.5 mA was reached or adverse effects were noted. RESULTS: Magnetic resonance imaging was normal or showed atrophy in 13 children. Six children got an end-of-study (24 months) postimplantation video-electroencephalogram, and their findings were similar to those before VNS. Quality of life and health measures improved in up to 50% (mean = 25%) in 20 children. Attention was noted to improve in 21 out of the 24 children. Final intensity parameters ranged from 2 to 3.5 mA (mean = 3.1 mA). An implantation effect was noted in 14 out of the 24 children, and lasted a mean of 20.2 days. There were 47 seizure types among the 24 children. An at least 50% seizure frequency reduction was noted in 35 seizure types and 17 seizure types disappeared after VNS. Atypical absence, myoclonic and generalized tonic-clonic seizures were significantly reduced by VNS; tonic and atonic seizures did not improve. Transient seizure frequency worsening was noted in ten of the 24 children, at a mean of 3.1 mA. DISCUSSION: Our study showed that VNS was effective in reducing atypical absence, generalized tonic-clonic, and myoclonic seizures (but not atonic or tonic seizures) in children with Lennox-Gastaut or Lennox-like syndrome. A concomitant improvement in attention level and quality of life and health also was noted. Secondary generalized epilepsy represents a subset of good candidates for VNS.

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.

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.

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.

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.

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.

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 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.

Outcomes of pregnant women with refractory epilepsy.

PURPOSE: Epilepsy is the most common neurological disorder requiring medical treatment during pregnancy. However, very few studies are specially dedicated to pregnant women with refractory epilepsy. This study was carried out with the aim of describing obstetrical and neurological outcomes of pregnant women with refractory epilepsy in Brazil. METHODS: Pregnant women with refractory epilepsy were enrolled in longitudinal cohort study between January 2005 and January 2018. They were regularly followed by a neurologist until the end of pregnancy. Neurological outcomes included seizure control, status epilepticus and adherence to antiepileptic medications. Obstetrical outcomes included major congenital malformations and obstetrical complications. RESULTS: A total of eighty two patients with a mean age of 24.5 ± 5.5 were included in our study. A significant number of women experienced an increase in seizure frequency and the prevalence of status epilepticus was 8.5%. More than half were non-adherent to antiepileptic drugs. Most of patients required treatment changes during pregnancy, in dose and/or in number of antiepileptic drugs. Cesarean section was the preferred way of delivery and five cases of major congenital malformations were detected. Obstetrical complications were significantly associated with polytherapy, multiple comorbidities, poor adherence to treatment and seizure deterioration during pregnancy (p < 0.05). CONCLUSIONS: Women with refractory epilepsy can have a significant risk of obstetric and neurological complications during pregnancy. Treatment of refractory epilepsy in pregnancy is a real challenge for neurologists.

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.