Seizure-alerting behavior in dogs owned by people experiencing seizures.

INTRODUCTION: The unpredictability of epileptic seizures is considered an important threat to the quality of life of a person with epilepsy. Currently, however, there are no tools for seizure prediction that can be applied to the domestic setting. Although the information about seizure-alert dogs - dogs that display changes in behavior before a seizure that are interpreted by the owner as an alert - is mostly anecdotal; living with an alerting dog (AD) has been reported to improve quality of life of the owner by reducing the stress originating from the unpredictability of epileptic seizures and, sometimes, diminishing the seizure frequency. AIM OF THE STUDY: The aim of the study was to investigate, at an international level, the behaviors displayed by trained and untrained dogs that are able to anticipate seizures and to identify patient- and dog-related factors associated with the presence or absence of alerting behavior. METHODOLOGY: An online questionnaire for dog owners with seizures was designed. Information about the participants (demographics, seizure type, presence of preictal symptoms) and their dogs (demographics, behavior around the time of seizures) was collected. In addition, two validated scales were included to measure the human-dog relationship (Monash Dog-Owner Relationship scale (MDORS)) and five different traits of the dogs' personality (Monash Canine Personality Questionnaire refined (MCPQ-R)). RESULTS: Two hundred and twenty-seven responses of people experiencing seizures were received from six participant countries: 132 from people with dogs that had started alerting spontaneously, 10 from owners of trained AD, and the rest from owners of dogs that did not display any alerting behavior (nonalerting dog (NAD)). Individuals' gender, age, or seizure type did not predict the presence of alerting behavior in their dogs. People who indicated that they experience preictal symptoms were more likely to have a spontaneously AD. The owner-dog bond was significantly higher with ADs compared with NADs, and ADs scored significantly higher than NADs in the personality traits "Amicability", "Motivation", and "Training focus". CONCLUSION: This study collected a large group of dog owners with seizures reporting behavioral changes in their dogs before their seizures occurred. This was associated with the presence of preictal symptoms. The seizure-alerting behavior of the dog may have a positive influence on the bond between the owner and the dog.

Investigating social cognition in epilepsy using a naturalistic task.

OBJECTIVE: The primary objective for this study was to assess social cognition in patients with focal epilepsy using a naturalistic task, which accurately models complex real-world social interaction. METHODS: We conducted an observational study of social cognition in 43 patients with focal epilepsy and in 22 controls. Patients and controls completed The Awareness of Social Inference Test, which measures both basic and advanced social cognition in a realistic video-based format. Patient and controls also completed standard measures of cognitive functioning and measures of depression. RESULTS: Compared to controls, we found that patients with epilepsy (PWEs) had no difficulty identifying positively valenced emotional states (happiness) yet had difficulty identifying most negatively valenced emotional states (anger, fear, and disgust). In addition, PWEs were able to identify sincere exchanges correctly but could not identify sarcastic and insincere exchanges. We found that basic social cognition significantly correlated with standard generalized cognitive measures, whereas advanced social cognition did not. Finally, age at onset had significant impact on social cognition, whereas other epilepsy characteristics did not. SIGNIFICANCE: PWEs have deficits in social cognition when measured using a naturalistic video-based task. Advanced social cognition may be an independent cognitive domain in PWEs that is not adequately measured using standard psychometric instruments. Problems with social cognition may arise as a consequence of epilepsy during the periods of robust social development in childhood and adolescence.

Migraine and epilepsy: review of the literature.

Migraine and epilepsy are disorders that are common, paroxysmal, and chronic. In many ways they are clearly different diseases, yet there are some pathophysiological overlaps, and overlaps in clinical symptomatology, particularly with regard to visual and other sensory disturbances, pain, and alterations of consciousness. Epidemiological studies have revealed that the two diseases are comorbid in a number of individuals. Both are now recognized as originating from electrical disturbances in the brain, although their wider manifestations involve the recruitment of multiple pathogenic mechanisms. An initial excess of neuronal activity in migraine leads to cortical spreading depression and aura, with the subsequent recruitment of the trigeminal nucleus leading to central sensitization and pain. In epilepsy, neuronal overactivity leads to the recruitment of larger populations of neurons firing in a rhythmic manner that constitutes an epileptic seizure. Migraine aura and headaches may act as a trigger for epileptic seizures. Epilepsy is not infrequently accompanied by preictal, ictal, and postictal headaches that often have migrainous features. Genetic links are also apparent between the two disorders, and are particularly evident in the familial hemiplegic migraine syndromes where different mutations can produce either migraine, epilepsy, or both. Also, various medications are found to be effective for both migraine and epilepsy, again pointing to a commonality and overlap between the two disorders.

Reducing severity of comorbid psychiatric symptoms in an epilepsy clinic using a colocation model: results of a pilot intervention.

RATIONALE: Patients with epilepsy (PWEs) and patients with nonepileptic seizures (PWNESs) constitute particularly vulnerable patient populations and have high rates of psychiatric comorbidities. This potentially decreases quality of life and increases health-care utilization and expenditures. However, lack of access to care or concern of stigma may preclude referral to outpatient psychiatric clinics. Furthermore, the optimal treatment for NESs includes longitudinal psychiatric management. No published literature has assessed the impact of colocated psychiatric services within outpatient epilepsy clinics. We, therefore, evaluated the colocation of psychiatric services within a level 4 epilepsy center. METHODS: From July 2013 to June 2014, we piloted an intervention to colocate a psychiatrist in the Dartmouth-Hitchcock Epilepsy Center outpatient clinic one afternoon a week (0.1 FTE) to provide medication management and time-limited structural psychotherapeutic interventions to all patients who scored greater than 15 on the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and who agreed to referral. Psychiatric symptom severity was assessed at baseline and follow-up visits using validated scales including NDDI-E, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and cognitive subscale items from Quality of Life in Epilepsy-31 (QOLIE-31) scores. RESULTS: Forty-three patients (18 males; 25 females) were referred to the clinic over a one-year interval; 27 (64.3%) were seen in follow-up with a median of 3 follow-up visits (range: 1 to 7). Thirty-seven percent of the patients had NESs exclusive of epilepsy, and 11% of the patients had dual diagnosis of epilepsy and NESs. Psychiatric symptom severity decreased in 84% of the patients, with PHQ-9 and GAD-7 scores improving significantly from baseline (4.6±0.4 SD improvement in PHQ-9 and 4.0±0.4 SD improvement in GAD-7, p-values<0.001). Cognitive subitem scores for NDDI-E and QOLIE-31 at their most recent visit were significantly improved compared with nadir scores (3.3±0.6 SD improvement in NDDI-E and 1.5±0.2 SD improvement in QOLIE-31, p-values<0.001). These results are, moreover, clinically significant-defined as improvement by 4-5 points on PHQ-9 and GAD-7 instruments-and are correlated with overall improvement as measured by NDDI-E and cognitive subscale QOLIE-31 items. CONCLUSION: A colocated psychiatrist demonstrated reduction in psychiatric symptoms of PWEs and PWNESs, improving psychiatric access and streamlining their care. Epileptologists were able to dedicate more time to managing epilepsy as opposed to psychiatric comorbidities. As integrated models of collaborative and colocated care are becoming more widespread, mental health-care providers located in outpatient neurology clinics may benefit both patients and providers.

A comparison of continuous video-EEG monitoring and 30-minute EEG in an ICU.

AIM: To determine whether there is added benefit in detecting electrographic abnormalities from 16-24 hours of continuous video-EEG in adult medical/surgical ICU patients, compared to a 30-minute EEG. METHODS: This was a prospectively enroled non-randomized study of 130 consecutive ICU patients for whom EEG was requested. For 117 patients, a 30-minute EEG was requested for altered mental state and/or suspected seizures; 83 patients continued with continuous video-EEG for 16-24 hours and 34 patients had only the 30-minute EEG. For 13 patients with prior seizures, continuous video-EEG was requested and was carried out for 16-24 hours. We gathered EEG data prospectively, and reviewed the medical records retrospectively to assess the impact of continuous video-EEG. RESULTS: A total of 83 continuous video-EEG recordings were performed for 16-24 hours beyond 30 minutes of routine EEG. All were slow, and 34% showed epileptiform findings in the first 30 minutes, including 2% with seizures. Over 16-24 hours, 14% developed new or additional epileptiform abnormalities, including 6% with seizures. In 8%, treatment was changed based on continuous video-EEG. Among the 34 EEGs limited to 30 minutes, almost all were slow and 18% showed epileptiform activity, including 3% with seizures. Among the 13 patients with known seizures, continuous video-EEG was slow in all and 69% had epileptiform abnormalities in the first 30 minutes, including 31% with seizures. An additional 8% developed epileptiform abnormalities over 16-24 hours. In 46%, treatment was changed based on continuous video-EEG. CONCLUSION: This study indicates that if continuous video-EEG is not available, a 30-minute EEG in the ICU has a substantial diagnostic yield and will lead to the detection of the majority of epileptiform abnormalities. In a small percentage of patients, continuous video-EEG will lead to the detection of additional epileptiform abnormalities. In a sub-population, with a history of seizures prior to the initiation of EEG recording, the benefits of continuous video-EEG in monitoring seizure activity and influencing treatment may be greater.

Interictal PET and ictal subtraction SPECT: sensitivity in the detection of seizure foci in patients with medically intractable epilepsy.

PURPOSE: Interictal positron emission tomography (PET) and ictal subtraction single photon emission computed tomography (SPECT) of the brain have been shown to be valuable tests in the presurgical evaluation of epilepsy. To determine the relative utility of these methods in the localization of seizure foci, we compared interictal PET and ictal subtraction SPECT to subdural and depth electrode recordings in patients with medically intractable epilepsy. METHODS: Between 2003 and 2009, clinical information on all patients at our institution undergoing intracranial electroencephalography (EEG) monitoring was charted in a prospectively recorded database. Patients who underwent preoperative interictal PET and ictal subtraction SPECT were selected from this database. Patient characteristics and the findings on preoperative interictal PET and ictal subtraction SPECT were analyzed. Sensitivity of detection of seizure foci for each modality, as compared to intracranial EEG monitoring, was calculated. KEY FINDINGS: Fifty-three patients underwent intracranial EEG monitoring with preoperative interictal PET and ictal subtraction SPECT scans. The average patient age was 32.7 years (median 32 years, range 1-60 years). Twenty-seven patients had findings of reduced metabolism on interictal PET scan, whereas all 53 patients studied demonstrated a region of relative hyperperfusion on ictal subtraction SPECT suggestive of an epileptogenic zone. Intracranial EEG monitoring identified a single seizure focus in 45 patients, with 39 eventually undergoing resective surgery. Of the 45 patients in whom a seizure focus was localized, PET scan identified the same region in 25 cases (56% sensitivity) and SPECT in 39 cases (87% sensitivity). Intracranial EEG was concordant with at least one study in 41 cases (91%) and both studies in 23 cases (51%). In 16 (80%) of 20 cases where PET did not correlate with intracranial EEG, the SPECT study was concordant. Conversely, PET and intracranial EEG were concordant in two (33%) of the six cases where the SPECT did not demonstrate the seizure focus outlined by intracranial EEG. Thirty-three patients had surgical resection and >2 years of follow-up, and 21 of these (64%) had Engel class 1 outcome. No significant effect of imaging concordance on seizure outcome was seen. SIGNIFICANCE: Interictal PET and ictal subtraction SPECT studies can provide important information in the preoperative evaluation of medically intractable epilepsy. Of the two studies, ictal subtraction SPECT appears to be the more sensitive. When both studies are used together, however, they can provide complementary information.

Outcome of frontal lobe epilepsy surgery.

PURPOSE: There is still controversy in deciding which patients with frontal lobe epilepsy (FLE) should undergo resective surgery, even though it is a well-established therapy. The aim of this study is to define multiple outcome measures and determine whether there are certain subpopulations of preferred surgical candidates that have a more favorable seizure prognosis. METHODS: Fifty-eight patients underwent resective FLE surgery with a mean follow-up period of 79.3 months (range 12-208 months). Patient demographics, clinical seizure characteristics, seizure-onset zone within the frontal lobes, and diagnostic tests were tabulated. Engel class, International League Against Epilepsy (ILAE) class, postoperative seizure patterns, time to first recurrent seizure, and seizures and employment during the last year of follow-up were used as outcome measures. Neuropsychological performance and Beck Depression Inventory (BDI) scores were used to define neuropsychological outcome and examined as predictors of seizure outcome. KEY FINDINGS: Thirty-three (57%) patients with resective surgery had an Engel class I outcome and 29 (50%) had an ILAE class I outcome. Mean time to first seizure after surgery was 33.3 months (range 0-208). Only 14 patients (24%) were completely seizure-free without auras (Engel IA) throughout the entire follow-up period. The most common pattern of seizure recurrence was mixed, with prolonged periods of seizure freedom intermixed with recurrences. In addition, 32% of patients made gains in employment and 52% were able to reduce use of antiepileptic drugs (AEDs), although only 9% discontinued AEDs. No significant association was found between class I or class IA outcome and the presence of a focal magnetic resonance imaging (MRI) abnormality, any specific localization of seizure focus within the frontal lobe, or neuropsychological change. SIGNIFICANCE: Findings indicate that that long-term outcome is generally favorable in FLE resective surgery, and support the need for considering multiple outcome measures to more fully characterize clinically relevant postsurgical changes. Outcome can be favorable even in MRI-negative patients.

Brain stimulation for the treatment of epilepsy.

Direct brain stimulation is an emerging treatment of epilepsy. Scheduled or responsive stimulation has been applied. The most explored targets for scheduled stimulation are the anterior nucleus of the thalamus and the hippocampus. The anterior nucleus of the thalamus was studied in a large multicenter trial. There was a significant seizure reduction with the stimulator "on" versus "off" during several months after stimulator implantation. The hippocampus as stimulation target has not yet been studied in a large randomized trial. Responsive stimulation applies a stimulus whenever epileptiform activity occurs. It requires on-line detection of epileptiform activity. This concept is based on the observation that epileptiform activity during functional mapping can be aborted by brief pulses of cortical stimulation. Current technology is able to detect seizure activity intracranially on-line and delivers a high frequency stimulus if epileptiform activity is detected. A large randomized multicenter trial has been conducted testing this system for focal epilepsy.

Intractable occipital lobe epilepsy: clinical characteristics and surgical treatment.

Intractable occipital lobe epilepsy remains a surgical challenge. Clinical characteristics of 14 patients were analyzed. Twelve patients had surgery, seven patients had visual auras (50%) and only eight patients (57%) had posterior scalp EEG changes. Ictal single-proton emission computed tomography (SPECT) incorrectly localized in 7 of 10 patients. Six patients (50%) had Engel's class I outcome. Patients with inferior occipital seizure onset appeared to fare better (three of four class I) than patients with lateral or medial occipital seizure onset (three of eight class I). Patients who had all three occipital surfaces covered with electrodes had a better outcome (four of five class I) than patients who had limited electroencephalography (EEG) coverage (two of seven class I). Magnetic resonance imaging (MRI) lesions did not guarantee a seizure free outcome. In conclusion, visual auras, scalp EEG, and imaging findings are not reliable for correct identification of occipital onset. Occipital seizure onset can be easily missed in nonlesional epilepsy. Comprehensive intracranial EEG coverage of all three occipital surfaces leads to better outcomes.

New-onset obsessive-compulsive disorder following neurosurgery for medication-refractory seizure disorder.

A 31-year-old man with medication-refractory seizures in the context of right mesial temporal lobe sclerosis and right occipital encephalomalacia is described. He experienced the onset of obsessive-compulsive symptoms following resection of the right hippocampus and right occipital pole. Semistructured psychiatric evaluation was conducted 16 months after surgery. Results indicated that he fulfilled diagnostic criteria for obsessive-compulsive disorder (OCD) and that he was not depressed at the time of the evaluation. Total score on the Yale-Brown Obsessive Compulsive Scale was 24, indicating moderate symptom severity, and he had prominent symptoms related to contamination, washing, checking, repeating rituals, and ordering. He also reported significant problems with "not just right" experiences. Treatment with sertraline resulted in apathy. To our knowledge, the present case is only the fourth reported of de novo onset OCD following neurosurgery for seizure disorder, and the first in a patient without either preexisting obsessive traits or an OCD spectrum disorder.

A pilot trial with modified Atkins' diet in adult patients with refractory epilepsy.

OBJECTIVES: At Ghent University Hospital, the feasibility and efficacy of the modified Atkins' diet was evaluated in adult patients with refractory epilepsy. The Atkins' diet restricts carbohydrate intake and was originally designed for weight loss. PATIENTS AND METHODS: During a 6-month trial period, a carbohydrate restriction of 20 g/day was in place. During a 36 h hospital admission, patients were instructed about the diet. Patients underwent clinical neurological testing, EEG, ECG, blood and urine analyses and mood evaluation before and during the trial. Seizure frequency and side effects were recorded in seizure diaries and followed up at monthly clinic visits. RESULTS: Eight patients were included in the study. Three out of eight patients followed the diet for 6 months. One out of three patients showed a >50% seizure reduction, 1/3>30%, and 1/3<30%. Side effects such as constipation and diarrhoea were mild and occurred mainly during the initial week of the diet. Patients reported improved concentration and well being. This was confirmed by improved scores on the Beck Depression Inventory Scale. CONCLUSION: This pilot study shows that the modified Atkins' diet is feasible in an adult population, and that seizure frequency reduction is possible. The results need to be confirmed in larger prospective, controlled studies with comparison groups.

Mesial temporal sclerosis after status epilepticus due to milk alkali syndrome.

Seizures induced by hypercalcemia are rare. A few case reports of seizures associated with hypercalcemia have been published, but none due to the milk alkali syndrome. This is the first report regarding seizures associated with calcium carbonate overuse. The two patients described in this article, who had no risk factors for developing epilepsy, suffered from status epilepticus probably induced by hypercalcemia. Subsequently, they both developed complex partial seizures, and were later found to have mesial temporal sclerosis on MRI. There are no reports linking hypercalcemia to mesial temporal sclerosis. While this may be a coincidence, there is reason to suspect that the development of persistent epilepsy, possibly due to mesial temporal sclerosis, was caused by prolonged seizures induced by hypercalcemia.

Robotic image-guided depth electrode implantation in the evaluation of medically intractable epilepsy.

OBJECT: The authors describe their experience with a technique for robotic implantation of depth electrodes in patients concurrently undergoing craniotomy and placement of subdural monitoring electrodes for the evaluation of intractable epilepsy. METHODS: Patients included in this study underwent evaluation in the Dartmouth Surgical Epilepsy Program and were recommended for invasive seizure monitoring with depth electrodes between 2006 and the present. In all cases an image-guided robotic system was used during craniotomy for concurrent subdural grid electrode placement. A total of 7 electrodes were placed in 4 patients within the time period. RESULTS: Three of 4 patients had successful localization of seizure onset, and 2 underwent subsequent resection. Of the patients who underwent resection, 1 is now seizure free, and the second has only auras. There was 1 complication after subpial grid placement but no complications related to the depth electrodes. CONCLUSIONS: Robotic image-guided placement of depth electrodes with concurrent craniotomy is feasible, and the technique is safe, accurate, and efficient.

Efficacy and safety of corpus callosotomy after vagal nerve stimulation in patients with drug-resistant epilepsy.

OBJECTIVE Vagal nerve stimulation (VNS) and corpus callosotomy (CC) have both been shown to be of benefit in the treatment of medically refractory epilepsy. Recent case series have reviewed the efficacy of VNS in patients who have undergone CC, with encouraging results. There are few data, however, on the use of CC following VNS therapy. METHODS The records of all patients at the authors' center who underwent CC following VNS between 1998 and 2015 were reviewed. Patient baseline characteristics, operative details, and postoperative outcomes were analyzed. RESULTS Ten patients met inclusion criteria. The median follow-up was 72 months, with a minimum follow-up of 12 months (range 12-109 months). The mean time between VNS and CC was 53.7 months. The most common reason for CC was progression of seizures after VNS. Seven patients had anterior CC, and 3 patients returned to the operating room for a completion of the procedure. All patients had a decrease in the rate of falls and drop seizures; 7 patients experienced elimination of drop seizures. Nine patients had an Engel Class III outcome, and 1 patient had a Class IV outcome. There were 3 immediate postoperative complications and 1 delayed complication. One patient developed pneumonia, 1 developed transient mutism, and 1 had persistent weakness in the nondominant foot. One patient presented with a wound infection. CONCLUSIONS The authors demonstrate that CC can help reduce seizures in patients with medically refractory epilepsy following VNS, particularly with respect to drop attacks.

Generator replacement in epilepsy patients treated with vagus nerve stimulation.

PURPOSE: In epilepsy patients treated with vagus nerve stimulation (VNS), the occurrence of end of battery life (EOBL), when the generator will no longer deliver any stimulation, was investigated with regard to seizure control. EOBL is preceeded by end of effective stimulation (EOES) when irregular stimulation may occur. METHODS: In 14/78 patients, treated with VNS at Ghent University Hospital, generators were replaced at different times following EOES or EOBL. We retrospectively analysed the time of occurrence of EOES and EOBL and seizure control before and after generator replacement. RESULTS: EOES or EOBL was indicated by loss of seizure control, decreased perception of stimulation and recurrence of depression in 3, 3 and 1/14 patient(s), respectively. In 2 and 1/14 patient(s), EOBL and premature generator failure, respectively, were detected during routine check-up at the epilepsy clinic. In 4/14 patients, generator replacement was performed before estimated EOES. Pre-replacement seizure control could not be regained in 2/14 patients in whom replacement had been postponed for several months. Estimation of EOES and EOBL occurrence proved difficult in individual patients. CONCLUSION: EOES or EOBL may be indicated by loss of seizure control, decreased or irregular perception of stimulation by the patient and loss of other VNS-induced effects. Postponing generator replacement may result into permanent loss of seizure control. In responders we suggest generator replacement before EOBL. Our results call for performance of prospective studies in larger patient groups that may eventually lead to general guidelines on the indication and timing of generator replacement.

Does asymmetric basal ganglia or thalamic activation aid in seizure foci lateralization on ictal SPECT studies?

UNLABELLED: Basal ganglia or thalamic activation has been reported in ictal SPECT studies of patients with intractable epilepsy. We hypothesized that lateralization of activation of these subcortical structures may aid in the lateralization of seizure foci in patients in whom the cortical focus is subtle or equivocal. METHODS: This was a retrospective analysis of 72 ictal (99m)Tc-ethylcysteinate dimer SPECT studies in 43 patients with intractable epilepsy in whom seizure laterality could be eventually determined. All patients underwent video-electroencephalography (EEG) monitoring, MRI, and one or more ictal SPECT scans as well as an interictal SPECT scan. Intracranial electrode EEG monitoring and surgery were performed as clinically indicated. Ictal and interictal studies were coregistered with patients' MRI scans using automated software, and ictal minus interictal subtraction images were obtained. The presence of asymmetric basal ganglia or thalamic activation was determined by 2 experienced observers who were unaware of clinical information. The final seizure focus was determined by surgical cure in 37 patients. In patients in whom surgery was not indicated or initial surgery was performed at another institution (n = 6), a consistent focus detected by intracranial electrode monitoring or repeated stereotypical seizures all originating from the same site on video-surface EEG monitoring was considered to indicate the final seizure focus. RESULTS: Thirty-five patients had neocortical seizures and 8 had mesial temporal lobe seizures. Asymmetric basal ganglia activation was seen in 22 (30.6%) studies. This activation was ipsilateral to the final determined seizure focus in 17 of 22 of these studies (77.3%) and contralateral in 5 of 22 (21.7%). Asymmetric thalamic activation was seen in 15 studies (20.8%), of which 12 of 15 (80%) were ipsilateral to the final seizure focus, whereas 3 of 15 (20%) were contralateral. In 3 of 5 studies with contralateral basal ganglia activation and 1 of 3 studies with contralateral thalamic activation, the SPECT study as a whole was found to be falsely localizing. In another 2 cases of contralateral subcortical activation, the SPECT study as a whole was considered nonlocalizing. Worse outcome was not observed in patients with false ictal SPECT subcortical lateralization; however, the presence of asymmetric subcortical uptake, regardless of relationship to seizure focus, was associated with decreased incidence of seizures at 1 y after surgery. CONCLUSION: Although asymmetric basal ganglia or thalamic activation is common, it is rarely the sole indicator of seizure localization. However, it may be a useful confirmatory sign in subtle cases of cortical localization. In cases of false ictal SPECT subcortical lateralization, the basal ganglia appear to follow cortical activation pattern. Furthermore, there appears to be a correlation between lateralizing uptake in subcortical structures on ictal SPECT and postsurgical outcome in intractable epilepsy patients.

Tolerability and effects on quality of life of twice-daily extended-release carbamazepine in adults with seizure disorders: an open-label, 12- to 36-month continuation study.

BACKGROUND: An earlier 6-month, multicenter, open-label study in patients with complex partial seizures found that a switch from multiple daily doses of conventional carbamazepine (CBZ) to twice-daily CBZ extended-release capsules(CBZ-ERC) was well tolerated, with maintenance of seizure control over the study period and significant improvements in quality of life (P < 0.001). OBJECTIVE: The goal of the present study was to assess the tolerability and effects on quality of life of twice-daily CBZ-ERC over the longer term in patients with seizure disorders. METHODS: This was a multicenter, open-label assessment of the long-term(12-36 months) tolerability and quality-of-life effects of twice-daily CBZ-ERC given at a daily dose equivalent to the daily dose of CBZ taken before study en-try. The regimen could be adjusted as clinically indicated up to a daily dose of 1600 mg. Patients could receive up to 2 other antiepileptic drugs during the study. RESULTS: One hundred eighteen patients were enrolled. In patients completing>12 months of study therapy, a significant decrease in the highest mean 2-day frequency of generalized tonic-clonic seizures was observed over the first 12 months (P = 0.005). The significant improvements in quality of life achieved in the earlier study were maintained during the present study. Of 37 patients who were discontinued from the study, 9 met criteria mandating withdrawal from the study due to exacerbation of seizures. Three patients were discontinued from the study for adverse events judged to be unrelated to study drug. Low incidences of rash (3.4%) and weight gain (0.8%) were reported. CONCLUSIONS: In this population of adults with seizure disorders, CBZ-ERC twice daily was well tolerated during 12 to 36 months of open-label treatment,with no increase in seizure frequency or decrease in quality of life.

Vagus nerve stimulation for refractory epilepsy: a transatlantic experience.

Vagus nerve stimulation (VNS) is an alternative treatment for medically or surgically refractory epilepsy. The long-term efficacy and safety of VNS were evaluated in a large patient series at Ghent University Hospital and Dartmouth-Hitchcock Medical Center. Between March 1995 and February 2003, seizure frequency and type as well as prescribed antiepileptic drugs and side effects were prospectively assessed in 131 patients treated with VNS in either center. Patients with a minimum follow-up duration of 6 months were included in the efficacy and safety analysis. A total of 118 of 131 implanted patients had a minimum postimplantation follow-up period of 6 months (mean, 33 months). The mean age of these patients was 32 years and the mean duration of refractory epilepsy was 22 years. The mean reduction in monthly seizure frequency in all patients was 55% (range, 0-100; SD = 31.6). Seven percent of patients were free of seizures with impaired consciousness, 50% of patients had a seizure frequency reduction of more than 50%, and 21% of patients were nonresponders. Fifteen patients reported stimulation-related side effects such as hoarseness or gagging. In a large patient series from two geographically distinct epilepsy centers located in two different continents, VNS proved to be efficacious and safe during long-term follow-up.