Vagus nerve stimulation for medically refractory absence epilepsy

PurposeA proportion of patients with childhood and juvenile absence epilepsies (CAE, JAE) are likely to be classified as medically refractory. In view of evidence gap for the treatment of such patients, this series is reported to generate estimate for efficacy of vagus nerve stimulation (VNS) in this patient population.MethodsPatients were identified by a chart review of all VNS recipients between January 1, 2006 and December 31, 2011. The diagnosis of CAE and JAE was based on conventional criteria. Details of demography, epilepsy phenomenology, management and outcomes were extracted. The outcome measures included reduction in daily seizure frequency measured as a percentage of pre-VNS seizure frequency and classified on International League Against Epilepsy (ILAE) outcome scale.ResultsNine patients (7 CAE, 2 JAE) with a mean age of seizure onset of 5.4 years (±3.9) were identified. Mean duration of epilepsy prior to VNS implant was found to be 3.9 years (±1.4). These patients had failed a median of 5 anti-epileptic drugs before being referred for consideration of surgical treatment. After a mean follow-up of 33.9 months (±25.5, minimum 4 months), 1 patient attained complete seizure freedom (ILAE class 1), 6 had ILAE class 4 and 2 had ILAE class 5 outcomes, respectively. Mean reduction in daily seizure frequency was found to be 53.5 ± 60.3% (1-sided p-value for paired t-test = 0.04), with a 50% responder rate of 55.6%.ConclusionVNS may be considered as a therapeutic option in patients with medically refractory absence epilepsy.     

Lamotrigine–valproic acid combination therapy for medically refractory epilepsy

Purpose:   A retrospective study of lamotrigine (LTG)–valproic acid (VPA) combination therapy in medically refractory epilepsy.
Methods:   Patients were identified with an adult epilepsy clinic database and were included if they had been on LTG–VPA combination therapy for at least 6 months. Patient demographics and information about epilepsy type, severity, and degree of medical intractability were obtained by retrospective chart review. The primary outcome measure was change in baseline seizure frequency, and patients were stratified into three groups: (i) seizure-free, (ii) improved (at least 50% reduction in baseline seizure frequency), and (iii) not improved.
Results:   Thirty-five patients met all inclusion–exclusion criteria. Epilepsy type was generalized in 25 patients (71%) and partial in 10 patients (29%). Before LTG–VPA treatment, 27 of 35 (77%) experienced disabling seizures on a monthly basis, and 17 of 35 (49%) of patients had at least one disabling seizure per week. Patients had previously failed treatment with a median of five antiepileptic drugs (AEDs), alone or in combination. With LTG–VPA therapy, 18 (51.4%) remained completely seizure-free, four (11.4%) were improved, and 13 (37.1%) were unimproved. Median follow-up was 42 months. Of the 22 patients who improved, 11 had previously failed LTG and VPA monotherapy. There was no significant difference between improved and unimproved patients with respect to demographics, epilepsy type or severity, or number of previously failed AEDs.
Discussion:   The combination of LTG and VPA should be considered in patients with medically refractory epilepsy. The effectiveness of this combination appears to be independent of epilepsy type or patient demographics.     

Endoscopic surgery for hypothalamic hamartomas causing medically refractory gelastic epilepsy

Introduction There is increasing evidence that removal or disconnection of hypothalamic hamartomas can lead to seizure control and improvement in behavior. The purpose of this study is to report our experiences with endoscopic removal of these hamartomas.Methods This is a prospective review of the early outcome of 44 patients undergoing endoscopic resection utilizing frameless stereotaxis and a micromanipulator.Results All patients had normal-sized ventricles. Complete removal was possible in 14 patients, 13 of whom were seizure free at follow-up. Four patients suffered complications that have persisted for more than 3 months: One had significant hemiparesis and three had persistent difficulties with short-term memory. Postoperatively, no patient suffered a permanent hormonal deficiency. In one patient who had undergone a previous attempt at transcallosal resection, the procedure was abandoned because of the lack of internal anatomic landmarks. In a second patient, insufficient mass could be removed due to the size of the lesion and the distorted anatomy. Consequently, 1 week later, the patient underwent a transcallosal approach.Conclusion In appropriately selected patients, sessile hypothalamic hamartomas can be removed completely or they can be completely disconnected from the hypothalamus with an acceptable risk. At least a year after surgery is needed to evaluate the efficacy of the procedure in terms of control of seizures and improvements in behavior and emotional ability.     

Surgical treatment of medically refractory epilepsy in childhood

Twenty five percent of children with epilepsy continue to seize despite best medical management and may be defined as medically refractory. Many children with medically refractory localization-related epilepsy, i.e. seizures which originate in a particular area of brain and secondarily spread to involve other brain regions, may benefit from a variety of surgical treatments including hemispherectomy, corpus callosotomy, focal cortical resection of the temporal lobe, focal cortical resection of extratemporal regions of brain, and multiple subpial resections. A successful outcome from epilepsy surgery is generally defined as a seizure-free state with no imposition of neurologic deficit. In order to achieve these twin goals two criteria must be fulfilled. First, precise localization of the epileptogenic zone in the brain is necessary. The epileptogenic zone may be defined as the region of epileptogenic cerebral cortex whose removal will result in a seizure-free state. Second, one must determine the anatomic localization of eloquent cortex in brain in order to spare these areas during any planned cortical excision of epileptogenic cortex. Several diagnostic measures may be used to achieve a successful surgical outcome. A clinical history to ascertain the earliest symptom in the clinical progression of the seizure (semiology) is imperative as is ictal and interictal scalp EEG, neuropsychological testing, magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computerized tomography (SPECT), interictal magnetoencephalography (MEG). In the typical child undergoing evaluation for epilepsy surgery, if the clinical, neuropsychological, EEG, and radiological data are all concordant and point to the same area of epileptogenicity in brain, cortical excision of the suspected epileptogenic zone is undertaken. However, if the data are discordant, and/or the epileptogenic zone resides wholly or in part within eloquent cortex, invasive intracranial monitoring from depth and/or subdural electrodes during a seizure is required to map out the areas of epileptogenicity in brain. The assessment of potential risks and benefits for this type of epilepsy surgery in children involve complex age-related issues, including the possible impact of uncontrolled seizures, medication, or surgery, on learning and development.     

Surgical treatment of medically refractory epilepsy in childhood

Twenty-five percent of children with epilepsy continue to seize despite the best medical management and may be defined as medically refractory. Many children with medically refractory localization-related epilepsy, i.e. seizures which originate in a particular area of the brain and secondarily spread to involve other brain regions, may benefit from a variety of surgical treatments including hemispherectomy, corpus callosotomy, focal cortical resection of the temporal lobe, focal cortical resection of extratemporal regions of the brain, and multiple subpial resections. A successful outcome from epilepsy surgery is generally defined as a seizure-free state with no imposition of neurologic deficit. In order to achieve these twin goals two criteria must be fulfilled. First, precise localization of the epileptogenic zone in the brain is necessary. The epileptogenic zone may be defined as the region of epileptogenic cerebral cortex whose removal will result in a seizure-free state. Second, one must determine the anatomic localization of eloquent cortex in the brain in order to spare these areas during any planned cortical excision of epileptogenic cortex. Several diagnostic measures may be used to achieve a successful surgical outcome. A clinical history to ascertain the earliest symptom in the clinical progression of the seizure (semiology) is imperative as is ictal and interictal scalp EEG, neuropsychological testing, magnetic resonance imaging, positron emission tomography, single photon emission computerized tomography, and interictal magnetoencephalography. In the typical child undergoing evaluation for epilepsy surgery, if the clinical, neuropsychological, EEG, and radiological data are all concordant and point to the same area of epileptogenicity in the brain, cortical excision of the suspected epileptogenic zone is undertaken. However, if the data are discordant, and/or the epileptogenic zone resides wholly or in part within eloquent cortex, invasive intracranial monitoring from depth and/or subdural electrodes during a seizure is required to map out the areas of epileptogenicity in the brain. The assessment of potential risks and benefits for this type of epilepsy surgery in children involves complex age-related issues, including the possible impact of uncontrolled seizures, medication, or surgery on learning and development.     

Neuropsychology and psychopathology: cognitive analysis during medically refractory epilepsy surgery

In psychopathology, few studies have been focused on the psychiatric complications of medically refractory mesial temporal lobe epilepsy (MTLE). The aim of the present study was to study NG's capacities, who presented emotional change after right temporal epilepsy surgery with phobias and empathy disorders. NG was examined in two emotional judgment tasks: one explicit and another implicit. For negative stimuli, NG had attraction in the explicit task and dependency in the implicit task. This study suggests that surgical intervention might be one of the causes of postoperative psychiatric disorders in patients with MTLE. MTLE patients have to be explored with neuropsychological paradigms.     

Psychological profiles in patients with medically refractory epilepsy.

The aim of this study was to explore whether patients with epilepsy show characteristic psychological profiles which might be risk factors for epileptic seizures. The instruments used in the case-control study were the Millon Behavioural Health Inventory (MBHI) and the Arnett Inventory of Sensation Seeking (AISS). A sample of hospitalized patients with medically refractory epilepsy (n = 15) and a sample of healthy controls (n = 15) matched on age and gender. Compared to the controls, the patients with epilepsy showed different psychological profiles. The patients with epilepsy showed significantly higher scores on the basic coping styles MBHI Inhibition style and MBHI Sensitivity style, and lower scores on the MBHI Sociability and the MBHI Confidence. The epilepsy group also exhibited elevated scores on the MBHI psychogenic attitude scales Chronic tension, Recent stress, Pre-morbid pessimism, Social alienation and Somatic anxiety. The patient group had lower sensation-seeking scores on the AISS Novelty scale, the AISS Intensity scale and in AISS Total scores. Some patients with medically refractory epilepsy show dysfunctional coping styles. These factors should be taken into consideration in treatment and rehabilitation planning. The findings point to psychological risk factors for eliciting epileptic seizures.     

Robot-assisted versus stereotactic frame-based stereoelectroencephalography in medically refractory epilepsy

AimTo explore the difference between robot assisted (RA) and stereotactic frame based (SF) stereoelectroencephalography (SEEG) in patients with medically refractory epilepsy.MethodsWe undertook a retrospective review of 33 SEEG cases at our center, of which 14 were SF performed from March to October 2018 and 19 were RA performed from November 2018 to December 2019. Detailed review of medical histories and operative records as well as imaging and trajectory plans was carried out for each patient, and the results related to each technique compared. A multiple linear regression model was used to test for variables that significantly influenced placement error.ResultsCompared to the SF group, the RA group had a higher mean number of electrodes per patient (10.7 ± 2.8 versus 6.4 ± 0.8, P < 0.0001) and a significantly shorter mean operative time (127.3 ± 40.7 versus 152.7 ± 13.6 min, P = 0.033). For the RA group, the intracranial implantation length was positively correlated with target point error (p = 0.000), depth error (p = 0.043), and two-dimensional (2D) radial error (p = 0.041). Conversely, skull thickness was negatively correlated with the TP error (p = 0.004), depth error (p = 0.037) and 2D radial error (p = 0.000). We also analyzed the mean entry point, target point, depth and 2D radial errors, the complication rates, and the results of epileptogenic zone (EZ) localization and Engel class. The results showed no difference in these aspects between the SF group and the RA group.ConclusionThis study suggests that, compared to stereotactic frame based SEEG, robot assisted SEEG is significantly more efficient and comparable in safety and effectiveness.     

Long-term outcome of nonsurgical candidates with medically refractory localization-related epilepsy

PURPOSE: Epilepsy surgery can result in complete seizure remission rates of upto 80% in patients with mesial temporal sclerosis and unilateral seizures. The seizure-free rate after surgery for patients with extratemporal nonlesional epilepsy has ranged between 30% and 40%. Some patients with medically refractory localization-related epilepsy cannot be offered surgical resection because of inadequate localization of the epileptogenic zone, documentation of bilateral ictal onsets, or functionally important areas of cortex that prohibit resection. The short-term rate of complete remission with medications in temporal lobe epilepsy is poor. Less is known about remission rates in patients who are not surgical candidates. In this study, we evaluated the outcome of medical treatment in patients with medically refractory partial epilepsy who were evaluated for possible epilepsy surgery but deemed to be inadequate surgical candidates. METHODS: A retrospective chart review and telephone survey with a self-rating questionnaire were completed for all patients who underwent epilepsy surgery evaluation but were not ultimately offered surgical treatment at the University of Michigan from 1990 through 1998. We assessed changes in seizure frequency and type, imaging characteristics, ictal recordings, interim medication history, and subjective changes in quality of life. RESULTS: Thirty-four subjects were available for follow-up study, at an average of >4 years after surgical evaluation. A significant reduction in seizure frequency was noted at the time of follow-up compared with that at the time of surgical evaluation. Of patients, 21% achieved seizure remission and remained seizure free for an average of 2.5 years. Four of the seven seizure-free patients attributed their remission to new antiepileptic drugs (AEDs). On a global self-rating item, 15 of 34, or 44%, felt more or much more satisfied with their lives, and 41% felt their quality of life was stable. CONCLUSIONS: A surprisingly large number of patients we surveyed, with refractory partial epilepsy not eligible for surgical management, reported reduced seizure frequency at follow-up, and 21% were seizure free. Our findings suggest that the long-term prognosis in patients with refractory partial epilepsy who are not surgical candidates may be more positive than might be generally expected.     

Obstructive sleep apnea is common in medically refractory epilepsy patients

BACKGROUND: Previous reports have documented the coexistence of obstructive sleep apnea (OSA) and epilepsy and the therapeutic effects of treatment on seizure frequency and daytime sleepiness. The authors' objective was to determine the prevalence of OSA and its association with survey items in a group of patients with medically refractory epilepsy undergoing polysomnography (PSG). METHODS: Thirty-nine candidates for epilepsy surgery without a history of OSA underwent PSG as part of a research protocol examining the relationship of interictal epileptiform discharges to sleep state. Subjects also completed questionnaires about their sleep, including validated measures of sleep-related breathing disorders (Sleep Apnea Scale of the Sleep Disorders Questionnaire [SA/SDQ]) and subjective daytime sleepiness (Epworth Sleepiness Scale [ESS]). RESULTS: One-third of subjects had OSA, defined by a respiratory disturbance index (RDI) > or = 5. Five subjects (13%) had moderate to severe OSA (RDI > 20). Subjects with OSA were more likely to be older, male, have a higher SA/SDQ score, and more likely to have seizures during sleep than those without OSA (p < 0.05). Seizure frequency per month, the number or type of antiepileptic drugs (AED) prescribed, the localization of seizures (temporal versus extratemporal), and the ESS were not statistically different between the two groups. CONCLUSIONS: In our sample, previously undiagnosed obstructive sleep apnea was common, especially among men, older subjects, and those with seizures during sleep. The impact of treating OSA on seizure frequency and daytime sleepiness in medically refractory epilepsy patients warrants further controlled study.     

Tailored cortical resection following image guided subdural grid implantation for medically refractory epilepsy

The aim of this study was to report the safety and efficacy of tailored cortical resection based on image guided subdural electrode implantations in eight patients with medically refractory epilepsy. The patients were selected for multimodality image guided subdural grid implantation, inpatient invasive electroencephalography video monitoring and surgical resection of epileptogenic foci. All patients had frequent disabling, medically refractory seizures pre-operatively. At a minimum of 10 months post-resection all patients had a worthwhile improvement in seizure frequency, with 7 of the 8 (87.5%) having an excellent outcome (Engel Class I). Short-term complications of grid implantation were: one patient with a post-operative subdural haemorrhage and one patient with a transient fluctuating dysphasia. The only long-term complication was a mild, non-disabling dysarthria following resection near eloquent speech cortex in one patient. We conclude that tailored cortical resection following image-guided insertion of subdural grids is a reliable, safe and highly effective method for the treatment of medically refractory epilepsy in carefully selected patients.     

Cost-utility analysis of vagus nerve stimulators for adults with medically refractory epilepsy.

INTRODUCTION: The cost-utility of vagus nerve stimulator (VNS) devices for medically refractory epilepsy has yet to be estimated. METHODS: Using a meta-analysis of randomised controlled trials of VNS, we estimate that six people require implantation in order for one person to experience a 50% reduction in seizure frequency. Costs averted from improved epilepsy control were ascertained from published literature. Values for health states were obtained from a series of 42 seizure clinic attenders using time trade-off techniques and the EQ-5D health status instrument. The cost per quality adjusted life year gained was estimated and the values obtained were tested in a sensitivity analysis. RESULTS: Improved epilepsy control averted, on average, 745 pounds sterling health care costs per annum. People with epilepsy had great difficulty performing the time trade-off experiment, but those who managed to complete the task valued a 50% reduction in their own seizure frequency at 0.285 units. For a programme of six implants, the baseline model estimated the cost per quality adjusted life year gained at 28,849 pounds sterling. The most favourable estimate was equal to 4785 pounds sterling per quality adjusted life year gained, assuming that the number needed to treat was similar to published series in which one response was obtained for every three implants. The least favourable estimate was equal to 63,000 pounds sterling per quality adjusted life year gained, when EQ-5D utility values were used. The cost per quality adjusted life year gained was not sensitive to changes in length of stay, nor complication rates, but was significantly influenced by cost of device and device battery life expectancy. CONCLUSION: There is not a strong economic argument against a programme of VNS implantation, although care should be taken to try and identify and treat those most likely to benefit.     

2005 AES Annual Course: Evidence Used to Treat Women with Epilepsy

Summary:  Although most female-specific considerations for treatment of epilepsy cannot be answered by Class I evidence, significant progress in our knowledge base has occurred in the past few years. Open-label studies of progesterone supplementation showed promising results; an ongoing randomized trial may provide definitive evidence for therapeutic use of progesterone in women. A randomized trial of hormone replacement therapy demonstrated a dose-related increase in seizure frequency in postmenopausal women with epilepsy. The use of different AED regimens during pregnancy cannot be explored with randomized, controlled trials; we must rely on the best available evidence from ongoing observational studies. The consistent findings of large prospective pregnancy registries reveal a consistent pattern of amplified risk for major congenital malformations in pregnancies exposed to valproate. These registries have also highlighted the concern for the effect of shifting hormones on AED concentrations. An increased frequency of seizures during pregnancy has been noted with lamotrigine (LTG) and oxcarabazepine, both of which undergo glucuronidation. Other studies have demonstrated an increased clearance of LTG during pregnancy and with exogenous estrogen use. It may be prudent to closely monitor serum concentrations of these AEDs with hormonal changes. An increased risk for neurodevelopmental consequences has been demonstrated for the fetus exposed to AED polytherapy, valproic acid, or frequent maternal convulsive seizures. Preliminary information about breastfeeding with LTG and levetiracetam is available. These newly released findings provide the tools to begin to practice evidence-based medicine when treating our female patients during their reproductive and postmenopausal years.     

From the American Epilepsy Society 2009 Annual Course. Non-substrate-directed epilepsy and surgery: PRO and CON

The surgical treatment of epilepsy is the most efficacious therapeutic modality for patients with a medically refractory partial seizure disorder. Epilepsy surgery has been demonstrated to be both effective and well tolerated in individuals with medial temporal lobe epilepsy associated with mesial temporal sclerosis. The identification of an MRI pathological substrate may be useful in identifying the epileptogenic zone and the appropriate operative strategy, and is predictive of the long-term seizure outcome. Patients with a non-substrate-directed partial epilepsy often require a more rigorous presurgical evaluation because of issues regarding the lateralization and localization of the epileptic brain tissue. The surgical outcome may be most disappointing in individuals with localization-related epilepsy of extratemporal origin associated with a normal MRI study. The present discussion focuses on the selection of patients with extratemporal non-substrate-directed epilepsy for a presurgical evaluation. The important factors associated with an improved quality of life subsequent to epilepsy surgery include seizure remission and avoidance of operation-induced adverse effects.     

涉及中央区难治性癫(癎)的外科治疗

目的 探讨涉及中央区难治性癫(癎)的手术治疗.方法 3例患者术前除常规致癫(癎)灶评估外,还应用fMRI作皮质功能区定位.术中通过皮层EEG(ECoG)对致癫(癎)灶定位,通过皮层诱发电位(SEP)及皮质电刺激定位脑功能区,对位于功能区以外的致疒间灶行切除性手术,功能区内的致疒间灶行软脑膜下横行纤维切断术.结果 术后无神经功能障碍,术后3月,2例病人无癫(癎)发作,1例偶有部分性发作;术后8月,1例无发作,1例偶有部分性发作,1例减少75%发作. 结论术前功能区评估、术中电生理监测有助于保护皮质重要功能和提高手术癫(癎)控制率.     

Interictal brain SPECT in patients with medically refractory temporal lobe epilepsy

The objective of this study was to evaluate the utility of interictal brain SPECT in localizing the epileptogenic focus in a population of patients of Epilepsy Clinic of Hospital Universitário Clementino Fraga Filho (HUCFF/UFRJ), with medically refractory temporal lobe epilepsy (TLE) and normal computed tomography (CT) scans, studying the correlation between SPECT, electroencephalogram (EEG) and, in 11 cases, brain magnetic resonance imaging (MRI), and to compare the results to the other six literature series. Twelve (52.2%) patients presented abnormal SPECT. Among these, five (41.6% of abnormal SPECTs) presented unilateral SPECT changes at the same side of EEG (hypoperfusion in four and hyperperfusion in one), three (25% of abnormal SPECTs) presented bilateral hypoperfusion and bilateral EEG changes too, and four (33.3%) presented unilateral hypoperfusion and bilateral EEG changes. The statistical analysis was based on fuzzy logic. The correlation index among SPECT X EEG, SPECT X MRI and SPECT X EEG X MRI were highly significant, with significance levels at 0.01, p < 0.0005 and trust interval at 99% in all correlations. The correlation studies between the series presented similar results.