Major depressive disorder as a predictor of a worse seizure outcome one year after surgery in patients with temporal lobe epilepsy and mesial temporal sclerosis

PurposeThe association between pre-surgical psychiatric disorders (PDs) and worse seizure outcome in patients with refractory epilepsy submitted to surgery has been increasingly recognized in the literature. The present study aimed to verify the impact of pre- and post-surgical PD on seizure outcome in a series of patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE–MTS).MethodData from 115 TLE–MTS patients (65 females; 56.5%) who underwent cortico-amygdalohippocampectomy (CAH) were analyzed. Pre- and post-surgical psychiatric evaluations were performed using DSM-IV and ILAE criteria. The outcome subcategory Engel IA was considered as corresponding to a favorable prognosis. A multivariate logistic regression model was applied to identify possible risk factors associated with a worse seizure outcome.ResultsPre-surgical PDs, particularly major depressive disorder (MDD), anxiety and psychotic disorders, were common, being found in 47 patients (40.8%). Fifty-six patients (48.7%) were classified as having achieved an Engel IA one year after CAH. According to the logistic regression model, the presence of pre-surgical MDD (OR = 5.23; p = 0.003) appeared as the most important risk factor associated with a non-favorable seizure outcome.ConclusionAlthough epilepsy surgery may be the best treatment option for patients with refractory TLE–MTS, our findings emphasize the importance of performing a detailed psychiatric examination as part of the pre-surgical evaluation protocol.     

Psychiatric disorders as “hidden” contraindications for presurgical VEEG in patients with refractory epilepsy: A retrospective cohort study in a tertiary center

Given the high frequency of psychiatric disorders (PDs) observed among patients with epilepsy, studies have highlighted the necessity of psychiatric evaluation for these patients, especially for those with refractory temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS) who are surgical candidates. Current evidence highlights the safety of video-electroencephalography (VEEG) as a means of investigation in patients with TLE-MTS and PDs. However, the presence of such disorders has still been seen as a contraindication for presurgical evaluation with VEEG in some epilepsy centers mainly because of the risk of negative behavioral events. The present retrospective cohort study performed in a Brazilian tertiary epilepsy center aimed to identify whether the presence of a PD remains a contraindication for presurgical VEEG. Clinical, sociodemographic, and psychiatric data from 41 patients who underwent VEEG as part of their presurgical evaluation were compared to data from 32 patients with refractory TLE-MTS who had not undergone VEEG. Psychiatric diagnoses were determined using the DSM-IV and ILAE criteria. Psychiatric disorders were diagnosed in 34 patients (46.6%). Major depressive disorder was the most frequent PD and was observed in 22 patients (30.1%). Anxiety disorders were observed in 14 patients (19.2%). Of the 41 patients (56.2%) who underwent presurgical VEEG, only 12 (29.2%) were found to have a PD during the presurgical psychiatric evaluation compared to 22 of the 32 (68.7%) who did not undergo VEEG (p = 0.001; RR = 2.35). The present findings suggest that the presence of a PD alone should not be a contraindication for VEEG monitoring and epilepsy surgery.     

Short-term efficacy and safety of zonisamide as adjunctive treatment for refractory partial seizures: a multicenter open-label single-arm trial in Korean patients

ObjectiveTo evaluate the efficacy and safety of adjunctive zonisamide (ZNS) therapy in Korean adults with uncontrolled partial epilepsy.MethodsStudy patients had an average of at least one seizure per 4-week (averaged over a 12-week historical baseline) despite the use of one to three antiepileptic drugs. The starting dose of ZNS was 100 mg/day, and was increased to 200 mg/day after 2 weeks. During the 12-week maintenance period, the dose of ZNS was adjusted to 200–400 mg/day based on the physicians’ discretion. The global evaluation scale (GES) and quality of life (QOLIE-31) were also evaluated.ResultsA total of 121 patients were enrolled, of which 88 patients completed the study. The median percent reduction in weekly seizure frequency over the treatment period was 59.0%. The ≥50% and ≥75% responder rates were 57.3% and 38.5%, respectively. Seizure freedom over the treatment period was observed in 25 patients, but seizure freedom throughout the 16-week treatment period was attained in only 16 patients. On investigator's GES, 84 patients were considered improved, with 33 patients showing marked improvement. In QOLIE-31 scale, seizure worry improved significantly but emotional well-being deteriorated. Treatment-emergent adverse events (AEs) were reported in 80 patients. The most common AEs were dizziness (28.1%), somnolence (24.0%), anorexia (18.2%), headache (14.0%), nausea (13.2%), and weight loss (10.7%). Twenty-two patients discontinued the trial due to drug-related AEs.ConclusionsOur results suggest that adjunctive ZNS therapy for the treatment of refractory partial epilepsy, though efficacious, is associated with significant tolerability problems.     

Sleep before and after temporal lobe epilepsy surgery

PurposePatients with epilepsy often complain of non-restorative sleep. This is the consequence of the acute effect of seizures and the chronic effect of epilepsy responsible for disrupting sleep architecture. Other factors such as antiepileptic drugs (AEDs), also play a role in the alteration of sleep organization. The aim of this study was to evaluate the specific effect of seizures and interictal epileptiform abnormalities (IEAs) on sleep, in particular to see whether reducing seizure frequency by epilepsy surgery might improve sleep organization in these patients.MethodsEleven patients with refractory mesial temporal lobe epilepsy, who underwent surgical treatment and who were seizure free at the follow-up, were included in the study. Treatment with AEDs was not significantly modified before the second year of follow-up. Patients were evaluated before surgery, at 1-year and 2-year follow-up visits with a videoEEG monitoring (24 h/24). At each follow-up visit, interictal epileptiform abnormalities and sleep macrostructure parameters were assessed.ResultsAll patients showed a reduction of their IEAs. At 1-year follow-up, total sleep time and REM sleep increased significantly (p = 0.032 and p = 0.006, respectively). At 2-year follow-up, an important increase of REM sleep was observed (p = 0.028). Most significant variations were noted 1 year after surgery. No significant variations were observed between the first and the second year after surgery.ConclusionsSurgical treatment of temporal lobe epilepsy may improve sleep macrostructure by reducing the number of seizures and of IEAs. These results indirectly confirm the role of epilepsy in disrupting sleep organization chronically.     

Detecting health disparities among Caucasians and African-Americans with epilepsy

ObjectiveThe aim of the study was to determine whether African-Americans and Caucasians who receive care at a tertiary epilepsy center can be distinguished on a variety of demographic, clinical, and psychosocial variables.MethodsWe surveyed 111 consecutive patients followed at a tertiary epilepsy center.ResultsOn univariate analysis, African-Americans had significantly more seizures (P = 0.03), lower scores on the Beliefs About Medicines Questionnaire—Specific (Necessity minus Concerns) (BMQ-S) (P = 0.01), and higher scores on the BMQ—General (BMQ-G) (P = 0.02). In binary logistic regression with race as the target variable, higher seizure frequency remained significantly associated with being African-American (P = 0.04). After ordinal regression with seizure frequency as the target variable, being African-American (P = 0.04) and higher BMQ-G scores (P = 0.02) remained significantly associated with increased seizure frequency.ConclusionCompared with Caucasians, African-Americans have higher seizure frequency and scores on the BMQ indicating a higher mistrust of medications. Aside from race, attitudes toward medications are also independently associated with seizure control.     

Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data

ObjectiveDrug-resistant epilepsy is a devastating disorder associated with diminished quality of life (QOL). Surgical resection leads to seizure freedom and improved QOL in many epilepsy patients, but not all individuals are candidates for resection. In these cases, neuromodulation-based therapies such as vagus nerve stimulation (VNS) are often used, but most VNS studies focus exclusively on reduction of seizure frequency. QOL changes and predictors with VNS remain poorly understood.MethodUsing the VNS Therapy Patient Outcome Registry, we examined 7 metrics related to QOL after VNS for epilepsy in over 5000 patients (including over 3000 with ≥ 12 months follow-up), as subjectively assessed by treating physicians. Trends and predictors of QOL changes were examined and related to post-operative seizure outcome and likelihood of VNS generator replacement.ResultsAfter VNS therapy, physicians reported patient improvement in alertness (58–63%, range over follow-up period), post-ictal state (55–62%), cluster seizures (48–56%), mood change (43–49%), verbal communication (38–45%), school/professional achievements (29–39%), and memory (29–38%). Predictors of net QOL improvement included shorter time to implant (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1–1.6), generalized seizure type (OR, 1.2; 95% CI, 1.0–1.4), female gender (OR, 1.2; 95% CI, 1.0–1.4), and Caucasian ethnicity (OR, 1.3; 95% CI, 1.0–1.5). No significant trends were observed over time. Patients with net QOL improvement were more likely to have favorable seizure outcomes (chi square [χ²] = 148.1, p < 0.001) and more likely to undergo VNS generator replacement (χ² = 68.9, p < 0.001) than those with worsened/unchanged QOL.SignificanceVNS for drug-resistant epilepsy is associated with improvement on various QOL metrics subjectively rated by physicians. QOL improvement is associated with favorable seizure outcome and a higher likelihood of generator replacement, suggesting satisfaction with therapy. It is important to consider QOL metrics in neuromodulation for epilepsy, given the deleterious effects of seizures on patient QOL.     

Seizure frequency in children with epilepsy: Factors influencing accuracy and parental awareness

RationaleThe objective of this study was to ascertain the accuracy of clinical reports to determine the seizure frequency in children diagnosed with epilepsy.MethodsWe reviewed the clinical record of 78 children (January–May of 2006) admitted to the EEG–video monitoring with epilepsy diagnosis. Clinical reports of parents and the files of EEG–video monitoring were reviewed to determine parents’ awareness for seizures.ResultsDuring video–EEG monitoring, 1244 were recorded on 78 children. Seizures were confirmed in 1095 of which 472 were correctly reported (38%) by parents whereas 623 remained under-reported (50%). Parents’ report thus had a sensitivity of 43%, positive predictive value of 76% to identify seizures. Based on the EEG–video monitoring, seizures were reported accurately in 22 (28%) and under-reported in 38 (49%) children. In the under-reported group, none of the seizures were recognized in 10 (13%), only a portion identified in 28 children. The parents’ report describing seizure frequency has limited value for young children (p = 0.01) and children with absence seizures (p = 0.03). However, clinical reports were accurate for the children with developmental delay (p < 0.06) or not being on any anticonvulsant drug (AED) therapy (p = 0.02).ConclusionOur results indicate that a significant number of seizures remain under-reported by parents of children with epilepsy. The current study underscores that the seizure frequency should be interpreted with caution for young children and children with absence seizures. Video–EEG recording has a complimentary role to the clinical observation for the accurate assessment of seizure frequency in children.     

Safety in the epilepsy monitoring unit: A retrospective study of 524 consecutive admissions

The yield of monitoring patients at an epilepsy monitoring unit (EMU) depends on the recording of paroxysmal events in a timely fashion, however, increasing the risk of safety adverse events (AEs). We aimed to retrospectively study the frequency and risk factors for AE occurrences in all consecutive admissions to an adult EMU in a tertiary medical center. We also compared our findings with published data from other centers.Between January 2011 and June 2014, there were 524 consecutive admissions to the adult EMU at the Tel Aviv Sourasky Medical Center. Adverse events were recorded in 47 (9.0%) admissions. The most common AE was 4-hour seizure cluster (58.7% of AEs) and, in decreasing frequency, AEs related to antiepileptic drugs (AEDs, 11.1%), falls and traumatic injuries (9.5%), intravenous line complications (9.5%), electrode-related (4.8%), status epilepticus (SE, 3.2%), and cardiac (1.6%) and psychiatric (1.6%) complications.There were significantly more AEs among patients with a younger age at disease onset (p = 0.005), a history of temporal lobe epilepsy (p = 0.046), a history of focal seizures with altered consciousness (p = 0.008), a history of SE (p = 0.022), use of a vagal nerve stimulator (p = 0.039), and intellectual disability (p = 0.016) and when the indication for EMU monitoring was noninvasive or invasive presurgical evaluation (p = 0.001). Adverse events occurred more frequently when patients had more events in the EMU (p = 0.001) and among those administered carbamazepine (p = 0.037), levetiracetam (p = 0.004), clobazam (p = 0.008), and sulthiame (p = 0.016). Patients with a history of psychogenic nonepileptic seizures (PNESs) had significantly fewer AEs (p = 0.013).Adverse events were not associated with the age, gender, duration of hospitalization or monitoring, AED withdrawal and renewal, seizure frequency by history, presence of major psychiatric comorbidities, abnormal neurological exam, or the presence of a lesion as on brain magnetic resonance imaging.In conclusion, this study reveals that AEs are not unusual in the EMU and that seizure clustering is the most common among them. Adverse events occur more frequently in patients with more severe epilepsy and intellectual disability and in patients undergoing presurgical evaluations and less frequently in patients with PNESs.     

A retrospective study comparing preoperative evaluations and postoperative outcomes in paediatric and adult patients undergoing surgical resection for refractory epilepsy

PurposeTo review and compare the preoperative characteristics and postsurgical outcomes in paediatric and adult patients who underwent surgical resections from 2001 to 2009.MethodsCombined data from noninvasive measures such as ictal semiology, interictal/ictal scalp EEGs, MRI and SPECT were utilised to identify the epileptogenic zones (EZ). When noninvasive investigations produced inconclusive or inconsistent findings, patients underwent intracranial EEG monitoring. Resective micro-surgical procedures were conducted according to the results of the anatomo-electro-clinical investigations and were carried out to remove the EZ. We then followed up 222 paediatric (≤18 years old) and 100 adult patients (≥19 years old) for 1–9 years postoperatively.ResultsThe mean age of seizure onset in paediatric group was significantly lower than that in adult group. 95 (43%) of the paediatric and 42 (42%) of the adult patients required long-term intracranial EEG recording. 54 (24.3%) of the paediatric and 62 (62%) of the adult patients were found to have temporal lobe epilepsy (TLE), while 149 (67.1%) of the paediatric and 37 (37.0%) of the adult patients had extra-temporal lobe epilepsy (ETLE) (p = 0.000). 19 (8.6%) of the paediatric patients and 1 (1%) adult patient had hemispheric lesions (p = 0.009). 148 (66.7%) of the paediatric and 61 (61.0%) of the adult patients were seizure-free during the follow-up period. 17 of 19 (89.5%) children who underwent hemispherectomy were seizure-free. In both paediatric and adult groups, the surgical outcome for patients with TLE was significantly better than that of patients with ETLE (p = 0.018 in children, p = 0.029 in adults). Both the location of EZs and seizure-free ratio were significantly different (p < 0.001) between the preadolescent (≤12 years old) and adolescent (13–18 years old) group. Hippocampal sclerosis was the most common pathologic finding in patients with TLE in both groups, and was followed by focal cortical dysplasia. In patients with TLE, the proportion of tumour was significantly higher in the paediatric than the adult group (25.9% vs. 10%, p = 0.021).ConclusionPaediatric patients with refractory seizures had more extratemporal or hemispheric resectable epileptogenic foci and fewer temporal foci than adults. Our study demonstrates that resective surgery is an effective and safe early intervention in strictly selected paediatric patients with refractory epilepsy.     

Is reoperation an option for patients with temporal lobe epilepsy after failure of surgery?

PurposeEpilepsy surgery is the most efficacious therapeutic modality for patients with medically refractory focal epilepsies, but surgical failures remain a challenge to the epilepsy treatment team. The aim of present study was to evaluate the postoperative outcome of patients who underwent reoperation after a failed epilepsy surgery on the temporal lobe.MethodsWe systematically analyzed the results of comprehensive preoperative evaluations before the first surgery, and before and after reoperation in 17 patients with drug resistant temporal lobe epilepsies.ResultsOverall, 13 of 17 patients (76.5%) improved after reoperation: five patients (29.4%) were completely seizure free after reoperation (median duration 60 months, range 12–72); six patients (35.3%) were seizure free at least 12 month before observation points (median duration 120.5 months, range 35–155) and two patients (11.8%) had a decrease in seizure frequency. Four patients (23.5%) remained unchanged with respect to seizure frequency and severity. There was no correlation between the improvement in seizure outcome after reoperation and other clinical data except of the history of traumatic brain injury (TBI). The patients who had no history of TBI improved after reoperation, compared to patients with TBI (p = 0.044). The postoperative seizure outcome of patients with incongruent Video-EEG results before the first surgery (p = 0.116) and before reoperation (p = 0.622) was not poorer compared to patients with congruent Video-EEG results.ConclusionsReoperation can considerably improve the operative outcome of the first failed epilepsy surgery in patients with drug resistant temporal lobe epilepsies. Epilepsy centres should be encouraged to report the results of failed epilepsy surgeries.     

Characteristics of refractory vs. medically controlled epilepsy patients with obstructive sleep apnea and their response to CPAP treatment

Obstructive sleep apnea (OSA) commonly coexists with epilepsy, and treatment of OSA may decrease seizure frequency. However, it is unclear whether patients with medically refractory epilepsy have a higher incidence of OSA compared with well-controlled epilepsy patients and whether the two groups carry different risk factors.PurposeThis study aimed to investigate the presence of OSA in patients with refractory vs. well-controlled epilepsy and their associated risk factors. We also assessed the benefits of treatment of OSA with continuous positive airway pressure (CPAP) in refractory epilepsy patients.MethodsWe retrospectively reviewed data from patients who presented to the Jacobs Neurological Institute Comprehensive Epilepsy Center of University at Buffalo from 2007 to 2010.ResultsThere is a tendency for much higher incidence of OSA in our epilepsy population compared with the general population (15.2% vs. 4.41%). For patients with well-controlled epilepsy, older age, male gender, and higher seizure frequency were predictors of a diagnosis of OSA. However, in medically refractory epilepsy patients, diabetes and snoring predicted a diagnosis of OSA. Treatment of OSA with CPAP in refractory epilepsy patients improved their seizure control (p < 0.02).ConclusionThis study confirms that OSA is common in epilepsy patients and treatment of OSA can improve seizure control in medically refractory cases. Patients with refractory epilepsy who have diabetes are more likely to have OSA.     

Effect of successful epilepsy surgery on subjective and objective sleep parameters – a prospective study

ObjectiveTo evaluate the effect of surgery on subjective and objective measures of sleep quality among patients with medically refractory focal epilepsy.MethodsIn a prospective cohort study, patients with medically refractory epilepsy undergoing epilepsy surgery were recruited. All patients were assessed seven days pre- and three months post-surgery in terms of history pertaining to epilepsy and sleep, Epworth sleepiness score (ESS), one week sleep log and over night polysomnography (PSG).ResultsAmong 17 patients (mean age 18, 11 males), seizure frequency had reduced (p = 0.04) and self reported sleep parameters had significantly improved (reduced total duration of night time sleep, regularity on one week sleep log and ESS (p < 0.05)) three months following epilepsy surgery. Patients with good surgical outcome (n = 12) showed reduced seizure frequency (p = 0.01) and reduced ESS with corresponding reduction in arousal index (AI) (p = 0.02) and increase in total sleep time (p = 0.03), postoperatively. Three patients in the good surgical outcome group showed reduction in apnea–hypopnea index (AHI) from more than five to less than five. There was no significant change either in seizure frequency, self reported clinical parameters or PSG parameters among patients with poor surgical outcome.ConclusionEpilepsy surgery improves subjective sleep parameters in patients with medically refractory epilepsy during the early post operative period. Successful epilepsy surgery may improve objective (PSG documented) sleep quality, sleep architecture and obstructive sleep apnea with resultant reduction in excessive daytime sleepiness.     

Specific adverse effects of antiepileptic drugs — A true-to-life monotherapy study

BackgroundIn patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy.MethodsAll patients ≥ 16 years of age with epilepsy for ≥ 12 months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database.ResultsOut of 841 patients, 438 (61% female, mean age: 44.7 ± 17.1 years) on monotherapy were included in this study. Levetiracetam (n = 151), lamotrigine (n = 167), valproic acid (n = 73), or controlled-release carbamazepine (n = 47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score ≥ 45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands.ConclusionIndividual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence.     

The effect of vitamin B supplementation on homocysteine metabolism and clinical state of patients with chronic epilepsy treated with carbamazepine and valproic acid

PurposeTo investigate the influence of vitamin B supplementation on the plasma total homocysteine (p-tHcy), serum folate (s-FA), serum B12 (s-B12), and clinical state of patients with chronic epilepsy.MethodsBeck Depression Inventory (BDI) scores and p-tHcy, s-B12, and s-FA levels were assessed at baseline, after 1 year of supplementation (G1), and before and after 1 year of VPA or CBZ therapy (G2).ResultsEighty-one patients participated in the study: 51 patients with chronic epilepsy (G1) treated with carbamazepine (CBZ) or valproic acid (VPA), and 30 patients with newly diagnosed epilepsy (G2). At baseline, mean p-tHcy level was significantly higher in G1 than G2 (p = 0.0001) with no significant differences in s-FA or s-B12 levels. p-tHcy level significantly decreased in CBZ-treated G1 patients (p = 0.00002) after 1 year of supplementation and increased in G2 after 1 year of anti-epileptic drug (AED) therapy without supplementation. BDI scores in G1 decreased significantly after 1 year of supplementation (p = 0.0001) and increased significantly in VPA-treated G2 patients after 1 year of AED therapy (p = 0.02). The number of hyperhomocysteinemic patients significantly decreased in G1 after vitamin B supplementation (p = 0.01) and increased in G2 (p = 0.002). We also observed improved BDI scores and reduced seizure frequency in patients with chronic epilepsy.ConclusionsThese data support the hypothesis that AEDs play a major role in hyperhomocysteinemia development in patients with epilepsy. Adding folate and vitamin B12 to AED therapy is a safe and inexpensive way to reduce the risk of hyperhomocysteinemia.     

Surgical versus conservative treatment in patients with cerebral cavernomas and non refractory epilepsy

PurposeThe optimal therapy of patients with cerebral cavernoma (CCs) and new onset epilepsy, sporadic seizures, or non well established refractory epilepsy is still not clear. The aim of this study was to compare the incidence of seizures in patients with CCs both operated and non operated, in order to obtain more information on the correct management of these patients.Materials and methodsWe studied retrospectively 43 patients with non refractory epilepsy secondary to CCs. Twenty-six of them (60.5%) underwent surgery and made up the surgical group, and 17 patients were treated medically and constituted the medical group. Seizure frequency and other clinical variables were compared between both groups.ResultsAt two years, out of the 26 operated patients, 19 (73%) remained seizure free, 4 (15%) had less than a seizure per month, and one patient (4%) had more than one seizure per month. At five years, 15 patients of the surgical group remained for analysis. Of them, 11 (73.3%) were seizure free, and 4 (26.7%) had less than one seizure a month. In the medical group, 12 out of 17 patients were seizure free (70.6%). There were no significant differences between the two groups (p = 0.2 and p = 0.3, respectively). Seven patients had postoperative neurological sequelae.ConclusionSurgical treatment of patients with non refractory epilepsy due to CCs did not significantly reduce the likelihood of seizures when compared to medical treatment. It must also be considered that surgery carries serious risks. A prospective and randomized study must be carried out to further clarify our findings.     

Levetiracetam in children with refractory epilepsy: Lack of correlation between plasma concentration and efficacy

PurposeThe goals of this study are to evaluate the efficacy and tolerability of levetiracetam (LEV) as add-on therapy in children with refractory epilepsies and to determine the value of LEV blood level monitoring in this population.MethodsSixty-nine children (39 males and 30 females) treated with LEV between 2006 and 2007 were selected. Their medical files were reviewed for LEV efficacy and tolerability. In a subgroup of children currently taking LEV, plasma concentrations were determined by high performance liquid chromatography by ultraviolet detection (HPLC-UV) method and correlated with the given dose per kilo as well as clinical response.ResultsFifty-one patients (74%) had a more than 50% reduction in seizure frequency with 16 patients (23%) becoming seizure free on LEV. Eighteen (26%) patients had a less than 50% reduction in seizure frequency. Adverse events due to LEV ranged from mild to moderate in only 18 patients (26%). The most frequently observed were drowsiness, behavioral difficulties, increase in seizure frequency and headaches. The majority (60.5%) of the responders received doses between 10 and 50 mg/kg/day and had a plasma concentration (PC) between 5 and 40 μg/ml. However, we found no clear correlation between PC and efficacy.ConclusionLevetiracetam given twice a day in children with refractory epilepsy reduces seizure frequency in all types of epilepsy. In children, LEV is a broad spectrum anticonvulsant with a favourable safety profile.     

Circadian patterns of generalized tonic-clonic evolutions in pediatric epilepsy patients

ObjectiveTo investigate the sleep/wake, day/night, and 24-h periodicity of pediatric evolution to generalized tonic–clonic seizures (GTC).MethodsCharts of 407 consecutive patients aged 0–21 years undergoing continuous video-EEG monitoring for epilepsy were reviewed for the presence of GTC evolution. Seizures were characterized according to 2001 ILAE terminology. Charts were reviewed for EEG seizure localization, MRI lesion, and for seizure occurrence in 3-h time blocks, out of sleep or wakefulness, and during the day (6 AM–6 PM) or night. Analysis was done with binomial testing. Regression models were fitted using generalized estimating equations with patients as the cluster level variable.Results71 patients (32 girls, mean age 12.63 ± 5.3 years) had 223 seizures with GTC evolution. Sleep/wake seizure distribution predicted tonic–clonic evolution better than time of day, with more occurring during sleep (p < 0.001). Tonic–clonic evolution occurred most frequently between 12–3 AM and 6–9 AM (p < 0.05). Patients with generalized EEG onset had more tonic–clonic evolution between 9 AM and 12 PM (p < 0.05). Patients with extratemporal focal seizures were more likely to evolve during sleep (p < 0.001); this pattern was not found in patients with temporal or generalized seizure onset on EEG. Patients without MRI lesions were more likely to evolve between 12 AM and 3 AM (p < 0.05), in the sleeping state (p < 0.001), and at night (p < 0.05). Logistic regression revealed that sleep and older patient age were the most important predictors of GTC evolution.ConclusionGTC evolution occurs most frequently out of sleep and in older patients. Our results may assist in seizure prediction, individualized treatment patterns, and potentially complication and SUDEP prevention.     

Health concerns predicts poor quality of life in well-controlled epilepsy

PurposeMost studies of quality of life (QOL) in seizure-free epilepsy patients suggest normal or near-normal function. Previous studies on QOL in well-controlled epilepsy have not investigated determinants for QOL from a database that includes a wide range of health related and epilepsy related variables, as well as demographical data, neuropsychological data, data from a comprehensive personality inventory and results from a QOL-questionnaire. Thus, the aim of this study was to analyze predictors of QOL based on such a range of variables.MethodsAdults with epilepsy on antiepileptic (AED) monotherapy and without epileptic seizures for at least 2 years (n = 158) were assessed with the QOLIE-89.ResultsThe main findings were that QOL in well-controlled epilepsy patients was in the normal range and that presence of substantial health related concerns was a significant predictor of poor QOL.DiscussionThe findings that substantial health concerns predict poor QOL may have clinical implications, as seizure-free epilepsy is a relatively benign condition, and careful information and counselling about this may alleviate health concerns and improve quality of life.     

Diagnostic yield of inpatient video-electroencephalographic monitoring: Experience from a Chinese comprehensive epilepsy center

Video-electroencephalographic monitoring (VEEG) is useful in the diagnosis of seizure disorders; however, its diagnostic yield in developing countries is not well known. The current study retrospectively reviewed the charts of 484 consecutive patients who were admitted to our center between July 2012 and September 2013. Of these patients, 298 (61.6%) were admitted for diagnostic clarification and underwent VEEG for a mean duration of 1.3 days (range = 1–9 days). The patients were divided into two groups: those whose diagnosis was changed and those whose diagnosis was not changed as a result of VEEG. A patient with a preadmission diagnosis of epilepsy who was discharged with a diagnosis of nonepileptic events (NEEs) or who was further classified as focal/generalized epilepsy on discharge was included in the “change in diagnosis” group. A patient admitted with an uncertain diagnosis and discharged with a diagnosis of NEEs or epilepsy (including focal epilepsy and generalized epilepsy) was also included in the “change in diagnosis” group. Video-electroencephalographic monitoring recorded typical ictal events (epileptic events or nonepileptic events) in 147 (49.3%) of the patients admitted for diagnostic clarification. In total, 181 (60.7%) patients had a change in diagnosis after VEEG. Among them, 103 (56.9%) patients had a preadmission diagnosis of epilepsy, which was further classified as focal epilepsy (88 patients) or generalized epilepsy (15 patients); the diagnosis of NEEs and epilepsy was clarified in 78 (43.1%) patients. The number of patients diagnosed with NEEs increased from 31 (10.4%) on admission to 88 (29.5%) on discharge. Among all the patients admitted for diagnostic clarification, therapeutic plans were changed for 104 (57.5%) patients. In 117 (39.3%) patients with no diagnostic change, VEEG evaluation provided confirmative diagnostic information in 47 (15.8%) patients and no additional diagnostic information in 70 (23.5%) patients. The study indicates that VEEG is useful in terms of clarifying seizure diagnoses and evaluating seizure frequency. In our cohort study, VEEG of a relatively short mean duration produced a comparable diagnostic yield as that reported in other studies.     

Ictal high-gamma oscillation (60-99 Hz) in intracranial electroencephalography and postoperative seizure outcome in neocortical epilepsy

ObjectiveHigh-gamma oscillations (HGOs) (60–99 Hz) have been suggested to correlate with seizure onset zones and seizure outcomes. We investigated the correlation between the extent of removal of ictal HGO generating areas and postoperative seizure outcome in neocortical epilepsy (NE).MethodsTwenty three patients with medically intractable NE underwent chronic intracranial electroencephalography (iEEG) using subdural electrodes. Ictal HGOs and superimposed undersampled ripples within ±3 s of video-iEEG ictal onset were extracted by wavelet clustering and thresholding. Cluster epileptogenicity indices (CEIs) were calculated. The temporal analysis window was locked to the timing of the maximum CEI wavecluster. Root mean square amplitudes, cross-correlation synchronies and the local focus indices within the temporal window were calculated.ResultsPercentages of resected maximum CEI waveclusters and HGO zones with high standardised amplitudes (>3), high cross-correlation synchronies (>0.9) and high local focus indices (>2) were significantly higher in the seizure-free group compared to the not seizure-free group (p = 0.036, p = 0.018, and p = 0.026, respectively).ConclusionsThe automatic quantitative ictal HGO analysis may be effective in delineating the epileptogenic zone.SignificanceHGO analysis may be helpful for improving post-resection seizure outcome in NE in the future.