Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy.

OBJECTIVE: Pharmacoresistant bilateral mesial temporal lobe epilepsy often implies poor resective surgical candidacy. Low-frequency stimulation of a fiber tract connected to bilateral hippocampi, the fornicodorsocommissural tract, has been shown to be safe and efficacious in reducing seizures in a previous short-term study. Here, we report a single-blinded, within-subject control, long-term deep-brain stimulation trial of low-frequency stimulation of the fornicodorsocommissural tract in bilateral mesial temporal lobe epilepsy. Outcomes of interest included safety with respect to verbal memory scores and reduction of seizure frequency. METHODS: Our enrollment goal was 16 adult subjects to be randomized to 2-Hz or 5-Hz low-frequency stimulation of the fornicodorsocommissural tract starting at 2 mA. The study design consisted of four two-month blocks of stimulation with a 50%-duty cycle, alternating with two-month blocks of no stimulation. RESULTS: We terminated the study after enrollment of five subjects due to slow accrual. Fornicodorsocommissural tract stimulation elicited bilateral hippocampal evoked responses in all subjects. Three subjects underwent implantation of pulse generators and long-term low-frequency stimulation with mean monthly seizures of 3.14 ±â€¯2.67 (median 3.0 [IQR 1-4.0]) during stimulation-off blocks, compared with 0.96 ±â€¯1.23 (median 1.0 [IQR 0-1.0]) during stimulation-on blocks (p = 0.0005) during the blinded phase. Generalized Estimating Equations showed that low-frequency stimulation reduced monthly seizure-frequency by 0.71 per mA (p < 0.001). Verbal memory scores were stable with no psychiatric complications or other adverse events. SIGNIFICANCE: The results demonstrate feasibility of stimulating both hippocampi using a single deep-brain stimulation electrode in the fornicodorsocommissural tract, efficacy of low-frequency stimulation in reducing seizures, and safety as regards verbal memory.

Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome.

PURPOSE: The purpose of this study was to evaluate the seizure outcomes after transverse multiple hippocampal transections (MHTs) in 13 patients with intractable TLE. METHODS: Thirteen patients with normal memory scores, including 8 with nonlesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. After confirming hippocampal seizure onset, they underwent MHT. Intraoperative monitoring was done with 5-6 hippocampal electrodes spaced at approximately 1-cm intervals and spike counting for 5-8min before each cut. The number of transections ranged between 4 and 7. Neuropsychological assessment was completed preoperatively and postoperatively for all patients and will be reported separately. RESULTS: Duration of epilepsy ranged between 5 and 55years. There were no complications. Intraoperatively, MHT resulted in marked spike reduction (p=0.003, paired t-test). Ten patients (77%) are seizure-free (average follow-up was 33months, range 20-65months) without medication changes. One of the 3 patients with persistent seizures had an MRI revealing incomplete transections, another had an additional neocortical seizure focus (as suggested by pure aphasic seizures), and the third had only 2 seizures in 4years, one of which occurred during antiseizure medication withdrawal. Verbal and visual memory outcomes will be reported separately. Right and left hippocampal volumes were not different preoperatively (n=12, p=0.64, Wilcoxon signed-rank test), but the transected hippocampal volume decreased postoperatively (p=0.0173). CONCLUSIONS: Multiple hippocampal transections provide an effective intervention and a safe alternative to temporal lobectomy in patients with hippocampal epilepsy.

Low-frequency electrical stimulation of a fiber tract in temporal lobe epilepsy.

OBJECTIVE: Surgical resection of the temporal lobe is an effective treatment for medically intractable temporal lobe epilepsy, but can cause memory impairment. Deep brain stimulation in epilepsy has targeted gray matter structures using high frequencies, but achieved limited success. We tested the hypothesis that low-frequency stimulation of the fornix reduces interictal epileptiform discharges and seizures in patients with intractable mesial temporal lobe epilepsy, without affecting memory. METHODS: We implanted depth electrodes in 11 patients for surgical evaluation of intractable epilepsy. Low-frequency stimulation of the fornix occurred in 4-hour sessions in the video-electroencephalography unit. Mental status assessment was performed at baseline and during stimulation. We studied the effect of stimulation on hippocampal spikes and seizures. RESULTS: There were no complications, and the patients were unaware of the stimulation. Fornix stimulation elicited evoked responses in the hippocampus and the posterior cingulate gyrus. Hourly Mini-Mental Status Examination (MMSE) scores showed an increase during stimulation when compared to prestimulation MMSE, largely due to improvement in recall, possibly representing a practice effect. Hippocampal spikes were significantly reduced during and outlasting each stimulation session. Seizure odds (n = 7) were reduced by 92% in the 2 days that followed stimulation. INTERPRETATION: Low-frequency stimulation of the fornix activates the hippocampus and other areas of the declarative memory circuit. The results of this preliminary study suggest that low-frequency stimulation is tolerable and reduces epileptiform discharges and seizures in patients with intractable mesial temporal lobe epilepsy. A controlled clinical trial may be warranted.

Accuracy of frame-based stereotactic depth electrode implantation during craniotomy for subdural grid placement.

BACKGROUND: Frame-based stereotaxy and open craniotomy may seem mutually exclusive, but invasive electrophysiological monitoring can require broad sampling of the cortex and precise targeting of deeper structures. OBJECTIVES: The purpose of this study is to describe simultaneous frame-based insertion of depth electrodes and craniotomy for placement of subdural grids through a single surgical field and to determine the accuracy of depth electrodes placed using this technique. METHODS: A total of 6 patients with intractable epilepsy underwent placement of a stereotactic frame with the center of the planned cranial flap equidistant from the fixation posts. After volumetric imaging, craniotomy for placement of subdural grids was performed. Depth electrodes were placed using frame-based stereotaxy. Postoperative CT determined the accuracy of electrode placement. RESULTS: A total of 31 depth electrodes were placed. Mean distance of distal electrode contact from the target was 1.0 ± 0.15 mm. Error was correlated to distance to target, with an additional 0.35 mm error for each centimeter (r = 0.635, p < 0.001); when corrected, there was no difference in accuracy based on target structure or method of placement (prior to craniotomy vs. through grid, p = 0.23). CONCLUSION: The described technique for craniotomy through a stereotactic frame allows placement of subdural grids and depth electrodes without sacrificing the accuracy of a frame or requiring staged procedures.

Can semiology predict psychogenic nonepileptic seizures? A prospective study.

OBJECTIVE: Reducing health and economic burdens from diagnostic delay of psychogenic nonepileptic seizures (PNES) requires prompt referral for video electroencephalography (VEEG) monitoring, the diagnostic gold standard. Practitioners make VEEG referrals when semiology suggests PNES, although few semiological signs are supported by well-designed studies, and most VEEG studies neglect to concurrently measure how accurately seizure witnesses can ascertain semiology. In this study, we estimate the value of eyewitness-reported and video-documented semiology for predicting PNES, and we measure accuracy of eyewitness reports. METHODS: We prospectively interviewed eyewitnesses of seizures in patients referred for VEEG monitoring, to inquire about 48 putative PNES and ES signs. Multiple, EEG-blinded, epileptologists independently evaluated seizure videos and documented the presence/absence of signs. We used generalized estimating equations to identify reliable video-documented PNES and ES signs, and we compared eyewitness reports with video findings to assess how accurately signs are reported. We used logistic regression to determine whether eyewitness reports could predict VEEG-ascertained seizure type. RESULTS: We analyzed 120 seizures (36 PNES, 84 ES) from 35 consecutive subjects. Of 45 video-documented signs, only 3 PNES signs ("preserved awareness," "eye flutter," and "bystanders can intensify or alleviate") and 3 ES signs ("abrupt onset," "eye-opening/widening," and postictal "confusion/sleep") were significant and reliable indicators of seizure type. Eyewitness reports of these 6 signs were inaccurate and not statistically different from guessing. Consequentially, eyewitness reports of signs did not predict VEEG-ascertained diagnosis. We validated our findings in a second, prospective cohort of 36 consecutive subjects. INTERPRETATION: We identified 6 semiological signs that reliably distinguish PNES and ES, and found that eyewitness reports of these signs are unreliable. We offer suggestions to improve the accuracy of eyewitness reports.

Modern technology calls for a modern approach to classification of epileptic seizures and the epilepsies.

In the last 10-15 years the ILAE Commission on Classification and Terminology has been presenting proposals to modernize the current ILAE Classification of Epileptic Seizures and Epilepsies. These proposals were discussed extensively in a series of articles published recently in Epilepsia and Epilepsy Currents. There is almost universal consensus that the availability of new diagnostic techniques as also of a modern understanding of epilepsy calls for a complete revision of the Classification of Epileptic Seizures and Epilepsies. Unfortunately, however, the Commission is still not prepared to take a bold step ahead and completely revisit our approach to classification of epileptic seizures and epilepsies. In this manuscript we critically analyze the current proposals of the Commission and make suggestions for a classification system that reflects modern diagnostic techniques and our current understanding of epilepsy.

Psychogenic nonepileptic seizures.

This review by three established clinicians/researchers and two 'rising stars' in the field of psychogenic nonepileptic seizures (PNES) describes recent progress in this area and highlights priorities for future research. Empirically testable models of PNES are emerging but many questions about the aetiology of PNES remain unanswered at present. Video-EEG has made it possible for doctors to make secured diagnoses of PNES in more cases. However, unacceptable diagnostic delays and misdiagnoses are still common. Non-specific EEG changes are often misinterpreted as evidence of epilepsy. A better understanding of the symptomatology of PNES may allow earlier and more accurate diagnoses using self-report questionnaires. The communication of the diagnosis and the engagement of patient in psychological treatment can be difficult. A recent pilot RCT has demonstrated the effectiveness of a psychological treatment in reducing seizures in the short term, but longer-term effectiveness is yet to be demonstrated.

Transection of CA3 does not affect memory performance in rats.

Longitudinal hippocampal pathways are needed for seizure synchronization, and there is evidence that their transection may abolish seizures. However, the effect of such transection on memory is unknown. In this study, we investigated the effect of transverse CA3 transections on memory function in Sprague-Dawley rats. With a stereotactic knife, a single CA3 transection was made unilaterally (n=5) or bilaterally (n=5). Sham surgery was done in another group (n=4). Morris water maze and novel object recognition tests were started 18 days later and revealed no significant differences between transected animals and controls. Cresyl-violet brain staining confirmed the locations of transections in the CA3 region. We conclude that normal performances in Morris water maze and novel object recognition tests do not appear to require intact transmission throughout the whole length of CA3, supporting the hypothesis that CA3 transections may be used in temporal lobe epilepsy to interrupt seizure circuitry while preserving memory.

National Institutes of Health stroke scale assists in predicting the need for percutaneous endoscopic gastrostomy tube placement in acute ischemic stroke.

Percutaneous endoscopic gastrostomy (PEG) tubes are commonly needed for early nutrition in patients with acute ischemic stroke. We evaluated the relationship between the NIH Stroke Scale (NIHSS) score and the need for PEG tube placement. Patients with acute ischemic stroke were included in this study. We collected information on patient demographics, stroke severity as indicated by the NIHSS, and risk factors for vascular disease. We ascertained the swallowing evaluation and PEG tube placement during the same hospitalization. A hierarchical optimal classification tree was determined for the best predictors. A total of 187 patients (mean age, 67.2 years) were included, only 33 (17.6%) of whom had a PEG tube placed during the course of hospitalization. Those who had the PEG were slightly older (73.8 vs 65.8 years), had severe stroke (median NIHSS score, 18 vs 4), and a longer hospital stay (median 12 vs 4 days). Independent predictors for PEG placement included bulbar symptoms at onset, higher NIHSS score, stroke in the middle cerebral artery distribution, and aspiration pneumonia. Hierarchical analysis showed that patients with aspiration pneumonia and NIHSS score >or=12 had the highest likelihood (relative risk [RR] = 4.67; P < .0001) of requiring a PEG tube. In the absence of pneumonia, NIHSS score >or=16 yielded a moderate likelihood of requiring PEG (RR = 1.80; P < .0001). Our findings indicate that the presence of pneumonia and high NIHSS score are the best predictors for requiring PEG tube insertion in patients with ischemic stroke. These findings may have benefits in terms of early decision making, shorter hospitalization, and possible cost savings.

Seizure symptoms and ambulatory EEG findings: incidence of epileptiform discharges.

AIMS: Ambulatory video-EEG monitoring has been utilized as a cost-effective alternative to inpatient video-EEG monitoring for non-surgical diagnostic evaluation of symptoms suggestive of epileptic seizures. We aimed to assess incidence of epileptiform discharges in ambulatory video-EEG recordings according to seizure symptom history obtained during clinical evaluation. METHODS: This was a retrospective cohort study. We queried seizure symptoms from 9,221 consecutive ambulatory video-EEG studies in 35 states over one calendar year. We assessed incidence of epileptiform discharges for each symptom, including symptoms that conformed to a category heading, even if not included in the ILAE 2017 symptom list. We report incidences, odds ratios, and corresponding p values using Fisher's exact test and univariate logistic regression. We applied multivariable logistic regression to generate odds ratios for the six symptom categories that are controlled for the presence of other symptoms. RESULTS: History that included motor symptoms (OR=1.53) or automatisms (OR=1.42) was associated with increased occurrence of epileptiform discharges, whereas history of sensory symptoms (OR=0.76) predicted lack of epileptiform discharges. Patient-reported symptoms that were associated with increased occurrence of epileptiform discharges included lip-smacking, moaning, verbal automatism, aggression, eye-blinking, déjà vu, muscle pain, urinary incontinence, choking and jerking. On the other hand, auditory hallucination memory deficits, lightheadedness, syncope, giddiness, fibromyalgia and chronic pain predicted absence of epileptiform discharges. The majority of epileptiform discharges consisted only of interictal sharp waves or spikes. CONCLUSIONS: Our study shows that the use of ILAE 2017 symptom categories may help guide ambulatory video-EEG studies.

Outcome of ambulatory video-EEG monitoring in a ˜10,000 patient nationwide cohort.

PURPOSE: We evaluate outcome of in-home diagnostic ambulatory video-EEG monitoring (AVEM) performed on a nationwide cohort of patients over one calendar year, and we compare our findings with outcomes of inpatient adult and pediatric VEM performed during the same year at two academic epilepsy centers. METHODS: This is a retrospective cohort study. We obtained AVEM outcome data from an independent ambulatory-EEG testing facility. Inpatient VEM data from a 4-bed adult epilepsy center and an 8-bed pediatric epilepsy center were also included. Primary outcome measure was composite percentage of VEM records with epileptiform activity on EEG tracings or at least one video-recorded pushbutton event. We assessed patient-reported symptoms documented in AVEM event diaries. RESULTS: Of 9221 AVEM recordings performed across 28 states, 62.5% attained primary outcome. At least one patient-activated pushbutton event was captured on video in 54% of AVEM recordings (53.6% in adults, 56.1% in children). Epileptiform activity was reported in 1657 (18.0%) AVEM recordings (1473 [88.9%] only interictal, 9 [0.5%] only ictal, 175 [10.6%] both interictal and ictal). Most common patient-reported symptomatology during AVEM pushbutton events was behavioral/autonomic/emotional in adults and children. Compared to AVEM, inpatient VEM captured more confirmed representative events in adult and pediatric samples. CONCLUSIONS: AVEM is useful for non-urgent diagnostic evaluation of events.

Visual evoked potentials.

Pattern reversal evoked potentials (PVEPs) are a noninvasive procedure that are useful for detecting lesions of the visual pathways. This article reviews anatomy of the visual pathway and the testing protocols for fullfield and hemifield PVEP and flash (goggle) visual evoked potentials (FVEP). Criteria for evaluation of normal and abnormal responses and clinical correlates are discussed. We conclude with a brief discussion of recording visual evoked potentials (VEPs) from subdural or depth electrodes to localize primary visual cortex in patients, with a parieto-occipital seizure focus, who are undergoing evaluation for epilepsy surgery.

A pilot study of the role of the claustrum in attention and seizures in rats.

OBJECTIVE: The claustrum has been implicated in consciousness, and MRIs of patients with status epilepticus have shown increased claustral signal intensity. In an attempt to investigate the role of claustrum in cognition and seizures, we (1) assessed the effect of high-frequency stimulation (HFS) of the claustrum on performance in the operant chamber; (2) studied interclaustral and claustrohippocampal connectivity through cerebro-cerebral evoked potentials (CCEPs); and (3) investigated the role of claustrum in kainate-induced (KA) seizures. METHODS: Adult male Sprague-Dawley rats were trained in operant conditioning and implanted with electrodes in bilateral claustra and hippocampi. Claustrum HFS (50 Hz) was delivered bilaterally and unilaterally with increasing intensities from 50 to 1000 µA, and performance scores were assessed. CCEPs were studied by averaging the responses to bipolar stimulations, 1-ms wide pulses at 0.1 Hz to the claustrum. KA seizures were analyzed on video-EEG recordings. RESULTS: Generalized Estimating Equations analysis revealed that claustral stimulation reduced task performance scores relative to rest sessions (bilateral: -15.8 percentage points, p < 0.0001; unilateral: -15.2, p < 0.0001). With some stimulations, the rats showed a stimulus-locked decrease in attentiveness and, occasionally, an inability to complete the operant task. CCEPs demonstrated interclaustral and claustrohippocampal connectivity. Some KA seizures appeared to originate from the claustrum. CONCLUSIONS: Findings from the operant conditioning task suggest stimulation of the claustrum can alter attention or awareness. CCEPs demonstrated connectivity between the two claustra and between the claustrum and the hippocampi. Such connectivity may be part of the circuitry that underlies the alteration of awareness in limbic seizures. Lastly, KA seizures showed early involvement of the claustrum, a finding that also supports a possible role of the claustrum in the alteration of consciousness that accompanies dyscognitive seizures.

Lateralization of interictal EEG findings.

Several reports indicate that interictal epileptiform discharges (IED) may be more likely to occur over the left cerebral hemisphere than over the right. The objective of our study was to determine the frequency and type of IED on routine and multihour EEGs in a tertiary epilepsy center to estimate the frequency of left-sided versus right-sided IED and to determine interictal spike distribution pattern differences between adult and pediatric epilepsy patients. The current study retrospectively reviewed 31,207 EEGs (25,793 routine EEGs and 5414 multihour EEGs) recorded on 24,003 patients during the period from 1993 to 2003. All EEGs were read according to a systematic EEG classification system. Every patient was considered only once by including the first abnormal EEG. Regional unilateral or bilateral IEDs were recorded in 1707 patients (7%). Regional unilateral or bilateral slow was recorded in 2297 patients (9.6%). Left-sided regional IED were seen in 828 patients and accounted for 58% of all unilateral IED. Left-sided slow was seen in 1389 patients and accounted for 65% of all unilateral slow. Lateralization of slow was due to intermittent slow, whereas continuous slow involved both hemispheres equally. There was no lateralization difference in benign focal epileptiform discharges of childhood. Lateralization shows a tendency toward greater left-sided lateralization of interictal findings with aging. Benign focal epileptiform discharges were only seen under the age of 20 years old. Regional IEDs were seen in approximately 7% of patients and slowing occurs in 10% of patients. Both abnormalities were seen more frequently in the left hemisphere. Age adjusted analysis of the data revealed that this left-sided predominance was mildly increased in adults as compared with pediatric patients.

The safety of controlled hypotension for shoulder arthroscopy in the beach-chair position.

BACKGROUND: The safety of controlled hypotension during arthroscopic shoulder procedures with the patient in the beach-chair position is controversial. Current practice for the management of intraoperative blood pressure is derived from expert opinion among anesthesiologists, but there is a paucity of clinical data validating their practice. The purpose of this study was to evaluate the effect of controlled hypotension on cerebral perfusion with use of continuous electroencephalographic monitoring in patients undergoing shoulder arthroscopy in the beach-chair position. METHODS: Fifty-two consecutive patients who had undergone shoulder arthroscopy in the beach-chair position were enrolled prospectively in this study. All patients underwent preoperative blood pressure measurements, assignment of an American Society of Anesthesiologists (ASA) grade, and a preoperative and postoperative neurological and Mini-Mental State Examination (MMSE). The target systolic blood pressure for all patients was 90 to 100 mm Hg during surgery. Continuous intraoperative monitoring was performed with standard ASA monitors and a ten-lead portable electroencephalography monitor. Real-time electroencephalographic monitoring was performed by an attending-level neurophysiologist. RESULTS: All patients violated at least one recommended limit for blood pressure reduction. The average decrease in systolic blood pressure and mean arterial pressure from baseline was 36% and 42%, respectively. Three patients demonstrated ischemic changes on electroencephalography that resolved with an increase in blood pressure. No adverse neurological sequelae were observed in any patient on the basis of the MMSE. CONCLUSIONS: This study provides the first prospective data on global cerebral perfusion during shoulder arthroscopy in the beach-chair position with use of controlled hypotension. Our study suggests that patients may be able to safely tolerate a reduction in blood pressure greater than current recommendations. In the future, intraoperative cerebral monitoring may play a role in preventing neurological injury in patients undergoing shoulder arthroscopy in the beach-chair position.

Risk factors associated with death in in-hospital pediatric convulsive status epilepticus.

OBJECTIVE: To evaluate in-patient mortality and predictors of death associated with convulsive status epilepticus (SE) in a large, multi-center, pediatric cohort. PATIENTS AND METHODS: We identified our cohort from the KID Inpatient Database for the years 1997, 2000, 2003 and 2006. We queried the database for convulsive SE, associated diagnoses, and for inpatient death. Univariate logistic testing was used to screen for potential risk factors. These risk factors were then entered into a stepwise backwards conditional multivariable logistic regression procedure. P-values less than 0.05 were taken as significant. RESULTS: We identified 12,365 (5,541 female) patients with convulsive SE aged 0-20 years (mean age 6.2 years, standard deviation 5.5 years, median 5 years) among 14,965,571 pediatric inpatients (0.08%). Of these, 117 died while in the hospital (0.9%). The most frequent additional admission ICD-9 code diagnoses in addition to SE were cerebral palsy, pneumonia, and respiratory failure. Independent risk factors for death in patients with SE, assessed by multivariate calculation, included near drowning (Odds ratio [OR] 43.2; Confidence Interval [CI] 4.4-426.8), hemorrhagic shock (OR 17.83; CI 6.5-49.1), sepsis (OR 10.14; CI 4.0-25.6), massive aspiration (OR 9.1; CI 1.8-47), mechanical ventilation >96 hours (OR9; 5.6-14.6), transfusion (OR 8.25; CI 4.3-15.8), structural brain lesion (OR7.0; CI 3.1-16), hypoglycemia (OR5.8; CI 1.75-19.2), sepsis with liver failure (OR 14.4; CI 5-41.9), and admission in December (OR3.4; CI 1.6-4.1). African American ethnicity (OR 0.4; CI 0.2-0.8) was associated with a decreased risk of death in SE. CONCLUSION: Pediatric convulsive SE occurs in up to 0.08% of pediatric inpatient admissions with a mortality of up to 1%. There appear to be several risk factors that can predict mortality. These may warrant additional monitoring and aggressive management.

Sleep-wake patterns of seizures in children with lesional epilepsy.

This study examined diurnal patterns of seizures and their occurrence during wakefulness and sleep in children with lesional focal epilepsy. We reviewed 332 consecutive children with lesional focal epilepsy and video-electroencephalogram monitoring during a 3-year period. Data were analyzed in relationship to clock time, wakefulness/sleep, and seizure localization. The distribution of lesions in 66 children (259 seizures) included mesial temporal, 29%; neocortical temporal, 18%; frontal, 29%; parietal, 13.5%; and occipital, 12%. Seizures in patients with frontal lesions occurred mostly during sleep (72%). Seizures in mesial temporal (64%), neocortical temporal (71%), and occipital (66%) lesional epilepsy occurred mostly during wakefulness. Temporal lobe seizures occurred more frequently during wakefulness (66%), compared with extratemporal seizures (32%) (odds ratio, 2.67; 95% confidence interval, 1.61-4.42). Temporal lobe seizures peaked between 9:00 am and noon and 3:00-6:00 pm, whereas extratemporal seizures peaked between 6:00-9:00 am. Sleep, not clock time, provides a more robust stimulus for seizure onset, especially for frontal lobe seizures. Temporal lobe seizures are more frequent during wakefulness than are extratemporal seizures. Circadian patterns of seizures may provide additional diagnostic and treatment options, such as differential medication dosing and sleep-schedule adjustments.

Extended-release lamotrigine in the treatment of patients with epilepsy.

IMPORTANCE TO THE FIELD: Epilepsy is a neurological disorder primarily characterized by recurrent, unprovoked seizures resulting from excessive or synchronous neuronal activity in the brain. Depending on the case definition and population studied, the lifetime prevalence of epilepsy in the USA is estimated to be 1.2 - 2.9%. In general, epilepsy is related to a significant increased risk of mortality and injury. A cornerstone of epilepsy management is use of antiepileptic drugs (AEDs). This review focuses on the AED lamotrigine, with particular emphasis on the extended-release formulation, in the management of patients with epilepsy, and the significant clinical issues that may be relevant with once-daily AED therapy. AREAS COVERED IN THIS REVIEW: An introductory section overviews the prevalence of epilepsy, current treatment recommendations for patients with epilepsy, and unmet needs in epilepsy management. This is followed by an overview of the AED market with currently available and developing compounds, a summary of lamotrigine and extended-release lamotrigine, clinical efficacy and tolerability studies with extended-release lamotrigine, and regulatory issues. The review concludes with an expert opinion summary on the important issue of treatment adherence, the possible role of extended-release lamotrigine in adherence enhancement, and additional research and areas which need further focus for optimal epilepsy outcomes. WHAT THE READER WILL GAIN: The reader will gain familiarity with extended-release (once-daily) lamotrigine and clinical issues that may be relevant to once-daily use. Once-daily AED use might be one way to simplify the epilepsy treatment regimen and can pave the way for other approaches that can maximize adherence, such as a frank discussion of risks, benefits, and attitudes towards treatment - all critical components of a strong and positive doctor-patient relationship. TAKE HOME MESSAGE: The AED lamotrigine is widely used in clinical settings and has become available in a once-daily extended-release version, which may minimize serum concentration fluctuation and presumably would both reduce patient burden and maximize treatment adherence as opposed to the immediate-release version of the compound. Adverse effects and safety concerns between the immediate- and extended-release versions of lamotrigine seem similar based upon interpretation of the limited literature.

Triple pathology in epilepsy: coexistence of cavernous angiomas and cortical dysplasias with other lesions.

Coexistence of cortical dysplasias (CD) with cavernomas has rarely been reported. We reviewed our surgical specimens from patients who underwent surgery for pharmacoresistant epilepsy between 2003 and 2008, and identified seven cases with cavernoma, of whom two had overlying CD. In addition, each of these patients had a third form of a potentially epileptogenic lesion: hippocampal sclerosis in one, and venous angioma in the other. We conclude that CD is heterogeneous, with milder forms appearing to co-exist with other pathologies, including vascular abnormalities and hippocampal sclerosis.