Prospective audits with newer antiepileptic drugs in focal epilepsy: Insights into population responses?

Despite the availability of a wide range of new antiepileptic drugs (AEDs), there is little evidence that their introduction has substantially altered outcomes. This paper reviews data from 5 consecutive prospective audits with new AEDs using similar methodology. Prospective audits with topiramate (TPM; n = 135), levetiracetam (LEV; n = 136), zonisamide (ZNS; n = 141), pregabalin (PGB; n = 135), and lacosamide (LCM; n = 160) were undertaken in treated patients with uncontrolled partial-onset seizures. Follow-up continued until one of four endpoints was reached: seizure freedom for ≥ 6 months on unchanged dosing; ≥ 50% reduction (responder) in seizure frequency on the highest tolerated dose compared with baseline; < 50% seizure frequency reduction (marginal response) compared with baseline in patients wishing to continue treatment with the new AED; or withdrawal due to lack of efficacy, side effects, or both. A greater proportion of seizure-free patients occurred with LEV (23.5%), LCM (21.9%), and TPM (20.7%) than with ZNS (12.8%) and PGB (10.4%). A higher percentage discontinued treatment with ZNS (41.8%) and PGB (50.4%) than with LEV (32.4%), TPM (31.1%), and LCM (22.5%). Most seizure-free patients responded to the new agent as first or second add-on (TPM 96%; LEV 97%; ZNS 89%; PGB 86%; LCM 97%) often at modest or moderate dosing (TPM 68%, ≤ 200 mg/day; LEV 63%, ≤ 1000 mg/day; ZNS 61%, ≤ 100 mg/day; PGB 86%, ≤ 300 mg/day; LCM 74%, ≤ 200 mg/day). With < 10% of patients discontinuing all AEDs due to lack of efficacy, tolerability was the major factor influencing the number of patients remaining on treatment. Lacosamide was the best (77% patients continued treatment), while PGB was the worst (50% continued treatment) tolerated AED. Overall, seizure freedom was achieved in < 25% of patients in each audit, mainly as a first or second add-on, with best tolerated AEDs producing a higher number of good outcomes. Seizures in very few patients with drug-resistant epilepsy, as defined by the International League Against Epilepsy task force, responded to any of the 5 newer AEDs. These data support the suggestion that the introduction of modern agents has not importantly impacted the outcomes in refractory epilepsy.     

Quality of life,mood and seizure control in patients with brain tumor related epilepsy treated with lacosamide as add-on therapy: A prospective explorative study with a historical control group

ObjectiveBrain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated.Therefore it represents a possible therapeutic choice for patients with BTRE. We propose a prospective study with a historical control group to evaluate the effect of LCM as add-on therapy on seizure control and quality of life in patients with BTRE. This study has been designed to test the superiority of Lacosamide over Levetiracetam as an add-on. We compared a prospective cohort of 25 patients treated with Lacosamide with a historical control group (n = 19) treated with Levetiracetam as an add-on.MethodsWe recruited 25 adult patients (M 18, F 7; mean age 41.9) affected by BTRE with uncontrolled partial-onset seizures treated with AED polytherapy. We added LCM as an add-on. Patients were evaluated at baseline, after 3 months and at 6 months.This population has been compared with a historical control group of 19 BTRE adult patients (M 13, F 6; median age 48.0, range: 28–70) with uncontrolled partial-onset seizures treated with LEV as add-on.The patients underwent QoL, mood and adverse events tests (Adverse Event Profile-AEP) and evaluation of seizure frequency.ResultsTwelve patients had high grade gliomas, and thirteen had low grade gliomas. During follow-up, thirteen patients underwent chemotherapy, three radiotherapy and five patients had disease progression. Nine patients had simple partial seizures, eight had complex partial seizures, and eight had secondary generalized seizures. Fifteen patients were in monotherapy and ten in polytherapy with AEDs. LCM was added up to reach the maximum dosage of 400 mg/die (mean final dose 300 mg/die). Four patients dropped out due to poor compliance and 1 for inefficacy.In the historical control group treated with LEV (mean final dose 2000 mg/die) 12 patients had high-grade gliomas, and 7 had low grade gliomas. Thirteen patients were in monotherapy and 6 in polytherapy with AEDs.In the 22 patients evaluable of 25 patients treated with LCM, we observed at final follow-up 7 patients seizure free, 12 with a significant reduction of seizures ≥ 50%, 2 stable and 1 patient with number of seizures increased.Mean seizure frequency at baseline compared with baseline period: the mean number of seizures significantly decreased from baseline (9.4) to final follow-up (1.2) (P = 0.005). The Responder Rate was 86.4%.Comparing responder rate of 22 evaluable patients with LCM with responder rate of 19 patients with LEV we didn't observe significant differences (p = 0.31).In our patients treated with LCM we didn't observe significant difference at 3 and 6 months in QoL tests results; we observe a significant reduction in the mean score of Karnofsky Performance Status (KPS) and Barthel Index (BI) between baseline and 6 months of follow-up (KPS p = 0.003; BI p = 0.007).No clinical side effects were observed.ConclusionComparing the LCM with the historical group treated with LEV in add-on, we observed that LCM seems to have a higher clinical efficacy than LEV.In our patients, we did not observe any significant changes in QoL tests, indicating stability in all quality of life domains explored, despite the objective worsening in their functional status. Although this is a small series with a relatively short follow-up, our data indicates that LCM in add-on in patients with BTRE appears to be as effective as LEV in add-on, without impact on mood and quality of life.     

Clinical management of elderly patients with epilepsy; the use of lacosamide in a single center setting

IntroductionLacosamide (LCM) is a third-generation antiepileptic drug (AED) for which there is limited experience in the treatment of elderly patients with epilepsy. This study was performed to evaluate the use of LCM in this particular patient group, focusing on its tolerability and effectiveness. This is a retrospective, single-center study, in patients over 60 years old treated with LCM between 1/2010 and 5/2015. Altogether, 233 elderly patients receiving LCM were identified; of these, 67 fulfilled the inclusion criteria, i.e., LCM administered for at least 2 weeks.ResultsLacosamide was initiated for acute seizure disorders (prolonged complex partial seizures, recurrent seizures, or status epilepticus) in 54 patients (81%) and for chronic epilepsy in 13 patients in an outpatient setting. The mean follow-up period for LCM treatment was 14 months. The mean daily dose of LCM at the end of follow-up was 368 mg (range: 100–600) for those 57 patients that continued treatment. Ten patients (15%) stopped LCM treatment but none because of lack of efficacy and only three patients (4%) because of side effects. The most frequent side effects were dizziness, fatigue, and tremor.ConclusionsLacosamide was well tolerated even at relatively high doses and in combination therapy.     

Vagus nerve stimulation in pediatric patients: Is it really worthwhile?

Vagus nerve stimulation (VNS) seems to be effective in the management of selected cases of pharmacoresistant epilepsy in children. This was a case–control prospective study of children with refractory epilepsy submitted to vagal nerve stimulator implantation and a control group with epilepsy treated with antiepileptic drugs. Patients under 18 years of age who underwent clinical or surgical treatment because of pharmacoresistant epilepsy from January 2009 to January 2012 were followed and compared with an age-matched control group at final evaluation. Statistically significant differences were observed considering age at epilepsy onset (VNS group — 1.33 ± 1.45 years; controls — 3.23 ± 3.11; p = 0.0001), abnormal findings in neurological examination (p = 0.01), history of previous ineffective epilepsy surgery (p = 0.03), and baseline seizure frequency (p = 0.0001). At long-term follow-up, 55.4% of the patients in the VNS group had at least 50% reduction of seizure frequency, with 11.1% of the patients presenting 95% reduction on seizure frequency. Also, a decrease in traumas and hospitalization due to seizures and a subjective improvement in mood and alertness were observed. The control group did not show a significant modification in seizure frequency during the study. In this series, VNS patients evolved with a statistically significant reduction of the number of seizures, a decreased morbidity of the seizures, and the number of days in inpatient care. In accordance with the current literature, VNS has been proven to be an effective alternative in the treatment of pediatric patients with drug-resistant epilepsy.     

Lacosamide in patients with temporal lobe epilepsy: An observational multicentric open-label study

PurposeThe aim of this study was to evaluate the efficacy and tolerability of lacosamide (LCM) both as add-on therapy and monotherapy in patients with temporal lobe epilepsy (TLE) based on an observational, prospective, multicenter study.MethodsWe enrolled 100 patients (mean age: 43.4 ± 12.53 years, 57 females) with nonlesional TLE and TLE with hippocampal sclerosis (HS) that did not respond to the first drug and who were referred to epilepsy centers of the University of Catanzaro, University of Palermo, IRCSS Neuromed of Pozzilli, and Otto-von-Guericke University of Magdeburg. In this open-label, multicenter trial, patients were initiated on oral LCM as add-on therapy to first AED monotherapy or as a later add-on to two concomitant AEDs. Seizure frequency changes and adverse events were recorded for at least six months after LCM was added.ResultsFourteen patients dropped out because of positive MRI findings other than HS. Patients received LCM at 200–400 mg/day. Fifty-eight out of these 86 patients with seizures that were previously drug-resistant had reduced seizure frequency after introduction of LCM. Forty-five out of 86 patients were classified as responders (12 were seizure-free, 33 achieved a reduction > 50%). Interestingly, five patients out of 86 achieved seizure freedom for at least one year and progressively switched to monotherapy with LCM, and all five remained seizure-free at follow-up (6–48 months).ConclusionsOur results may suggest that LCM at doses of 200 to 400 mg/day reduces seizure frequency in adults with TLE regardless of the presence of HS, and that it may be considered as a first add-on treatment for patients with pharmacoresistant TLE.     

Seizure recurrence in patients with solitary cystic granuloma or single parenchymal cerebral calcification: A comparative evaluation

BackgroundSolitary cysticercus granuloma and single parenchymal calcified lesion are two common neuroimaging abnormalities in Indian patients with epilepsy. In this study, we evaluated the frequency and predictors of seizure recurrence in patients presenting with new onset epilepsy or single epileptic seizures and these two different imaging findings.Materials and methodsWe enrolled 115 patients with newly diagnosed epilepsy. All patients were clinically evaluated and were treated with oxcarbazepine. No anti-helminthic treatment was prescribed. The patients were followed up for 6 months. In the solitary cystic granuloma group, repeat computed tomography was done after 6 months.ResultsThe study included 80 patients with solitary cysticercus granuloma and 35 patients with a single calcified lesion. Twenty (25%) patients with solitary cysticercus granuloma and 12 (34.3%) patients with parenchymal calcified lesion had a seizure recurrence during the study period (p = 0.307). After 6 months, 57 (71.3%) patients in the solitary cysticercus granuloma group demonstrated complete resolution of the granuloma and in 21 (26.2%) patients the granuloma transformed into a calcified lesion. In the solitary cysticercus granuloma group, a family history of seizure, serial seizures and calcification on follow-up neuroimaging (p < 0.05) were significantly associated with recurrence of seizures. In patients with a single parenchymal calcified lesions, electroencephalographic abnormalities and serial seizures (p = <0.05) were significant predictors of recurrence. Kaplan–Meier statistics revealed that the seizure recurrence rate was insignificantly higher in patients with calcified lesions than in patients with solitary cysticercosis granulomas.ConclusionIn conclusion, in patients with solitary cysticercus granuloma, a family history of seizures, serial seizures and calcification of the granuloma, and in patients with a calcified brain lesion, electroencephalographic abnormalities, family history of epilepsy and serial seizures were associated with an increased risk of seizure recurrence.     

Evaluation of health-care utilization in patients with Dravet syndrome and on adjunctive treatment with stiripentol and clobazam

Dravet syndrome (DS) is a rare, severe childhood epilepsy syndrome that imposes a substantial burden on patients and their caregivers. This study evaluated health-care utilization over a 2-year period in patients with DS at an outpatient clinic of a German epilepsy center. Data on the course of epilepsy, anticonvulsant treatment, and direct costs were recorded using the electronic seizure diary Epivista® and patients' files.We enrolled 13 patients with DS (6 females, mean age: 12.3 ± 7.5 years) between 2007 and 2010 and evaluated them during a 1-year baseline. All patients had drug-resistant epilepsy and their seizures failed to improve with a mean number of 6.7 ± 3.4 anticonvulsants. They had an overall mean seizure frequency of 102.1 seizures per year (median: 31, range: 3–538) with 43.2 GTCSs per year (median: 14, range: 0–228). We estimated the annual total direct costs at €6506 ± 3974 (range: €1174–11,783) per patient with hospitalization (68.9% of total direct costs) as the major cost factor ahead of costs for anticonvulsants (24.0%). For the 1-year follow-up period, less severely affected patients were continued on conventional anticonvulsants (n = 4) or switched to adjunctive treatment with stiripentol and clobazam (n = 9). In the latter group, six patients (67%) were long-term responders, with between 25% and 100% seizure reduction with respect to either GTCSs or the overall seizure frequency. This reduction in seizure frequency was associated with a shift in the distribution of cost components towards higher medication costs and decreased hospitalization costs. The total direct costs increased by 42.7%, mainly due to the newly introduced stiripentol, with an annual cost of €6610.This study showed that direct costs of patients with DS were above the average European costs of drug-resistant epilepsy in children. Treatment with new anticonvulsants resulted in reduction of seizures and inpatient admissions.     

Effects of adjunctive lacosamide on mood and quality of life in patients with epilepsy

We examined the effects of adjunctive lacosamide (LCM) on mood and quality of life (QOL) in adult patients with partial-onset seizures in a prospective, controlled, single-blind study. Patients in whom LCM was added to their AED regimen for clinical indications comprised the LCM group (n = 18), while the control group (n = 32) comprised patients on ≥ 2 AEDs with anticipated stable dosing for the duration of the study. Profile of Mood States (POMS) and QOLIE-89 were used to assess mood and QOL at enrollment and 12–16 weeks later. Adherence to LCM was measured electronically with the Medication Event Monitoring System (MEMS) and using a self-report measure. There were no significant between-group differences in age, AED load, side-effects (A–B Neurotoxicity Scale), MoCA mental status, or seizure-related factors. LCM adherence (measured by MEMS) was 70.7%. There was a significant decrease in negative mood states in the LCM group (estimated marginal mean at baseline = 49.4, at follow-up = 29.7; p = 0.02), after controlling for seizure freedom. Based on previously reported benchmarks, clinically significant change on the POMS occurred in 7 (38%) LCM patients. The effect of LCM on the overall QOL was not significant (p = 0.078). Correlation between POMS Total Mood Distress and Emotional-Wellbeing on the QOLIE-89 was significant (r = − 0.783; p = 0.01). These results suggest that LCM may have a favorable impact on mood.     

Marijuana use in adults admitted to a Canadian epilepsy monitoring unit

ObjectivesEpidemiologic evidence supporting antiseizure properties of cannabis is limited and controversial. We determined the prevalence of marijuana use and its perceived effects in patients with and without epilepsy.MethodsInformation was collected over 14 months from consecutive adult patients admitted to an epilepsy monitoring unit using a 27-item anonymous questionnaire. Patients with cognitive impairment unable to understand the questions or give informed consent and readmissions were not recruited. Subjects were divided into 4 groups, those with epileptic seizures, those with psychogenic nonepileptic seizures (PNES), those with both epileptic and PNES, and those with other nonepileptic events. Patients with exclusively epileptic seizures were compared with those with exclusively PNES.ResultsFrom 310 patients, 18 undiagnosed cases were excluded leaving a cohort of 292 patients with median age 35 (range: 27–49) years; 57.2% female. Epilepsy was documented in 190 (65.1%), PNES in 64 (21.9%), and both types of seizures in 26 (8.9%). Median duration of seizure disorder was longer (2 [1–9] vs. 13 [5.7–25] years; p < 0.001) and seizure frequency lower (daily or weekly in 62.3% vs. 44.9%; p = 0.03) in patients with epilepsy compared with those in patients with PNES. Overall, 166 (57%) had tried marijuana, and 36.2% used it over the past year. Utilization was 57.1% in sole epilepsy and 64.1% in sole PNES, but daily use was more likely in epilepsy (59% vs. 33.3%). Estimated mean dose was 1 g/day. Marijuana use was associated with tobacco smoking (p < 0.001) but not alcohol use. Eight patients used other street drugs. Improvement in seizures was perceived by 84% in those with epilepsy and 72.7% in those with PNES. In the 2 groups, stress was decreased in 84.9% and 88%, sleep improved in 77.3% and 88%, and memory/concentration was better in 32% and 28%, respectively. Antiepileptic drug side effects were decreased in 53.2% of marijuana users. Perceived effect on epileptic seizures correlated with effect on stress (r = 0.35, p = 0.004). Adverse effects of marijuana were mild and reported in 30.7% but included possible seizure precipitation in 5 patients with epilepsy.SignificancePatients with uncontrolled epilepsy or nonepileptic events had a high rate of marijuana use with associated perceived improvements in seizure control, stress, sleep, and drug side effects. Stress reduction may contribute to the perceived impact of marijuana on seizures and nonepileptic events in adults.     

Initial response to antiepileptic drugs in patients with newly diagnosed epilepsy

This study aimed to identify factors predicting the response to antiepileptic drugs in patients with newly diagnosed epilepsy. We prospectively studied 176 patients with newly diagnosed epilepsy. Patients were included if they had a history of two or more clinically definite unprovoked seizures, or had a definite epileptic focus on MRI or epileptiform discharges on electroencephalography if they had suffered only one seizure. The primary endpoint was seizure freedom during the initial 6 months of antiepileptic drug treatment. The secondary endpoint was the time to the first seizure during the maintenance period of antiepileptic drug treatment. A total of 100 patients were included, and seizure freedom for 6 months was achieved in 73 patients. The response to antiepileptic drugs was significantly lower in patients with early age at seizure onset (⩽16 versus >16 years old, odds ratio = 4; 95% confidence interval [CI] 1.5–12.9; relative risk = 1.4; 95% CI 1.1–1.8). In addition, the time to the first seizure during the maintenance period was significantly earlier in patients with age at seizure onset ⩽16 years compared with those with age at seizure onset >16 years on the Kaplan–Meier survival analysis (p = 0.011). Early age at seizure onset is an important factor influencing the response to antiepileptic drugs in patients with newly diagnosed epilepsy.     

Efficacy,tolerability, and retention rates of zonisamide in older adult patients with focal-onset epilepsy: Experiences from two tertiary epilepsy centers

ObjectiveThe objective of this study was to evaluate the efficacy, tolerability, and retention rates for zonisamide (ZNS) in older adult patients with focal-onset epilepsy.Patients and methodsChart reviews of patients aged 60 years and older with focal-onset epilepsy treated with ZNS in two tertiary epilepsy centers were analyzed retrospectively.ResultsEighty-five patients (41 males, 44 females) aged over 60 years (range: 60–81) with focal-onset epilepsy treated with ZNS were identified; 55.3% of the patients (n = 47) were on monotherapy. The median and average doses of ZNS doses were 200 mg/day (range: 100–400) and 212.9 ± 84.2 mg/day, respectively. With ZNS treatment, 67.1% of the patients (n = 57) were seizure-free for a median of 28 months (range: 10–56) whereas 20% (n = 17) of the patients had seizures that were unresponsive to ZNS treatment. Best seizure control was achieved in patients with poststroke epilepsy; seizure freedom was 80% in this subgroup.Overall retention rate was found to be 83.5%. There was no significant relation between receiving poly- or monotherapy and discontinuation of ZNS (p = 0.18).Thirty-two of the patients (37.6%) lost weight. Median weight loss was 8 kg (range: 2–16). There was no significant correlation between weight loss and the administered doses of ZNS (r = 0.34; p = 0.12).ConclusionDespite limitations due to the retrospective design of the study, the results show that ZNS is a well-retained drug with high efficacy in older adult patients with epilepsy.     

Skin conductance biofeedback training in adults with drug-resistant temporal lobe epilepsy and stress-triggered seizures: A proof-of-concept study

The present proof-of-concept study investigated the feasibility of skin conductance biofeedback training in reducing seizures in adults with drug-resistant temporal lobe epilepsy (TLE), whose seizures are triggered by stress. Skin conductance biofeedback aims to increase levels of peripheral sympathetic arousal in order to reduce cortical excitability. This might seem somewhat counterintuitive, since such autonomic arousal may also be associated with increased stress and anxiety. Thus, this sought to verify that patients with TLE and stress-triggered seizures are not worsened in terms of stress, anxiety, and negative emotional response to this nonpharmacological treatment. Eleven patients with drug-resistant TLE with seizures triggered by stress were treated with 12 sessions of biofeedback. Patients did not worsen on cognitive evaluation of attentional biases towards negative emotional stimuli (P > .05) or on psychometric evaluation with state anxiety inventory (P = .059); in addition, a significant improvement was found in the Negative Affect Schedule (P = .014) and in the Beck Depression Inventory (P = .009). Biofeedback training significantly reduced seizure frequency with a mean reduction of − 48.61% (SD = 27.79) (P = .005). There was a correlation between the mean change in skin conductance activity over the biofeedback treatment and the reduction of seizure frequency (r(11) = .62, P = .042). Thus, the skin conductance biofeedback used in the present study, which teaches patients to achieve an increased level of peripheral sympathetic arousal, was a well-tolerated nonpharmacological treatment. Further, well-controlled studies are needed to confirm the therapeutic value of this nonpharmacological treatment in reducing seizures in adults with drug-resistant TLE with seizures triggered by stress.     

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.     

Cross-reactivity of skin rashes with current antiepileptic drugs in Chinese population

ObjectiveDue to less experience with the cross-reactivity of antiepileptic drugs (AEDs) in Chinese population, we surveyed the rates of cross- reactivity of rash among commonly used AEDs in Chinese patients with epilepsy, particularly between the traditional and the new compounds.MethodsWe have retrospectively reviewed the medical records concerning all antiepileptic drug treatment in consecutive Chinese patients with epilepsy in our center. The incidence of AED-related rash was determined in 3793 outpatients, taking at least one of the AEDs-carbamazepine (CBZ), valproic acid (VPA), phenytoin (PHT), phenobarbital (PB), clonazepam (CZP), oxcarbazepine (OXC), lamotrigine (LTG), gabapentin (GBP), topiramate (TPM), levetiracetam (LEV) and traditional Chinese medicine (TCM). We have performed telephone interviews among all patients with AEDs-related rash. We described the clinical characteristics of the 18 patients with cross-reactivity involving the AEDs, and the cross- reactivity pattern for CBZ, PHT, OXC, and LTG.ResultsA total of 3.61% (137/3793) of patients experienced a skin rash to at least one AEDs, of these patients, 73 (53.28%) were female and 64 were males (46.72%). While 18 patients had a rash to two or more AEDs. Of patients who had a rash to CBZ and were also prescribed PHT (n = 17), 52.9% had a rash to PHT (abbreviated as CBZ → PHT: 52.9%); of patients who had a rash to PHT and were also prescribed CBZ (n = 13), rate of rash was 69.2% (i.e., PHT → CBZ: 69.2%). Other results: CBZ → LTG: 25% (n = 16); LTG  → CBZ: 44.4% (n = 9); CBZ → OXC: 40% (n = 10); OXC → CBZ: 66.7% (n = 6); LTG → PHT: 20% (n = 5); PHT → LTG: 16.7% (n = 6); OXC → LTG: 25% (n = 4); LTG → OXC: 33.3% (n = 3); OXC → PHT: 25% (n = 4); PHT → OXC: 16.7% (n = 6). There was a highly significant mutual risk for cross- reactivity for CBZ and PHT, and OXC, and LTG (p < 0.001), mutual risk reached statistical significance for LTG and CBZ (p = 0.01).ConclusionCross-reactivity rates between certain AEDs are high, especially when involving carbamazepine and phenytoin. There were also too few patients with rash to reach definitely conclusions about possible cross-reactivity. Larger numbers of patients would be needed to assess this and the mechanism. Caution should be exercised when prescribing certain AEDs (especially CBZ and PHT, but also OXC, and LTG).     

Prevalence and correlates of major depressive disorder (MDD) among adolescent patients with epilepsy attending a Nigerian neuropsychiatric hospital

BackgroundA high prevalence of mood disorders exists in patients with epilepsy. In most cases, this is not detected and, consequently, not treated. This study aimed to determine the prevalence and correlates of major depressive disorder (MDD) among adolescents with epilepsy attending a child and adolescent clinic in Nigeria.MethodsWe recruited 156 participants consecutively for the study. Adherence was assessed using the 8-item Morisky Medication Adherence Questionnaire, while the K-SADS was used to assess the presence of major depressive disorder. Seizure control was evaluated by the frequency of seizures within a year.ResultsMajor depressive disorder (DSM-IV criteria) was diagnosed in 28.2% of the participants. The age of participants (p = 0.013), seizure control (p = 0.03), medication adherence (p = 0.045), frequency of seizures in the preceding 4 weeks (p < 0.001), and duration of illness (p < 0.001) were all significantly associated with the presence of MDD. Participants with seizures occurring more than once weekly in the preceding 4 weeks were 16 times more likely to have a MDD compared with those with no seizures in the preceding 4 weeks (p < 0.001, 95% C.I. [4.13, 65.43]), while participants with a duration of illness more than 10 years were more than four times likely to have MDD compared with those with an illness duration of 5–10 years (p < 0.01, 95% C.I. [0.07, 0.70]).ConclusionThe prevalence of MDD among patients with epilepsy was high. Poor seizure control, poor medication adherence, and long duration of illness were associated with the presence of MDD among such patients. Intervention should focus on ensuring good seizure control and optimal adherence in order to mitigate the impact of MDD in patients with epilepsy.     

Disparities in injury death location for people with epilepsy/seizures

ObjectiveWide variation has been reported in the proportion of injury deaths occurring during the prehospital phase. Potential disparities in where injured people with epilepsy and seizure disorders die have not been examined. We compared location of death between injured patients with epilepsy and seizure disorders and similar patients without epilepsy/seizures and tested the hypothesis that injured people with epilepsy/seizures are more likely to die outside of a hospital or health care setting.MethodsU.S. vital statistics (mortality) data from the multiple cause of death files of the National Center for Health Statistics were analyzed. Patients less than 65 years of age at death who had injury as the underlying cause of death were included. Multinomial logistic regression was used to assess location of death, controlling for patient and injury characteristics.ResultsControlling for potential confounders, people with epilepsy/seizures were more likely to die at home from unintentional injuries (relative risk ratio [RRR] = 1.51, P < 0.001) and less likely to die in public places (RRR = 0.27, P < 0.001). People with epilepsy/seizures were less likely to die at home or in public places from suicide, but significantly more likely to die at home from homicide (RRR = 2.29, P < 0.001). By mechanism of injury, people with epilepsy/seizures were more likely to die at home from drowning (RRR = 2.35, P < 0.001).DiscussionDisparities in where injured people with epilepsy/seizures die deserve further attention. Identifying the underlying causes of these disparities will allow for the development of targeted prevention interventions.     

Comparing stimulant effects in youth with ADHD symptoms and epilepsy

To retrospectively examine response to stimulant treatment in patients with epilepsy and ADHD symptoms as predicted by seizure freedom for six months, use of methylphenidate (MPH) versus amphetamine (AMP) preparations, cognitive level, and medical records were searched for patients under the age of 18 with epilepsy and ADHD symptoms treated with MPH or AMP (n = 36, age = 10.4 ± 3.5; male = 67%). “Responders” had a CGI-improvement score of ≤ 2 and did not stop medication because of adverse effects. “Worsened” patients discontinued medication because of agitation/emotional lability. Seizure freedom did not predict treatment response. Lower cognitive level was associated with increased rate of worsening (p = 0.048). No patients who were seizure-free at the start of the medication trial experienced an increase in seizures. Of the patients having seizures at the start of trial, one patient on MPH and two patients on AMP had increased seizures during the trial. Seizures returned to baseline frequency or less after stimulant discontinuation or anticonvulsant adjustment. Methylphenidate was associated with a higher response rate, with 12 of 19 given MPH (0.62 ± 0.28 mg/kg/day) compared with 4 of 17 given AMP (0.37 ± 0.26 mg/kg/day) responding (p = 0.03). Methylphenidate treatment and higher cognitive level were associated with improved treatment outcome, while seizure freedom had no clear effect. Confidence in these findings is limited by the study's small, open-label, and uncontrolled design.     

Gender and age influence in daytime and nighttime seizure occurrence in epilepsy associated with mesial temporal sclerosis

ObjectivesThe aim of this study was to analyze the daytime and nighttime seizure distribution during video-EEG monitoring in patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS) and the role of gender, age, and lesion side on 24-hour seizure distribution.MethodsWe studied 167 consecutive adult (age ≥ 16 years) patients with epilepsy associated with unilateral mesial temporal sclerosis that had three or more recorded seizures during continuous video-EEG monitoring with a minimum recording time period of 24 h. Seizure onset time was classified according to occurrence in six 4-hour periods.ResultsSeven hundred thirty-five seizures were evaluated. We observed two higher seizure occurrence periods: 08:01–12:00 (p = 0.001) and 16:01–20:00 (p = 0.03). Significantly fewer seizures were observed between 0:01 and 4:00 (p = 0.01). Nonuniform seizure distribution was noted in women (p < 0.0001), in young patients (less than 45 years of age) (p < 0.0001), and in both patients with left (p = 0.03) and patients with right mesial temporal sclerosis (p = 0.008). Men presented uniform seizure occurrence distribution (p = 0.15). Women had fewer seizures than expected and fewer seizures than men between 0:01–04:00 (p < 0.0001 and p = 0.0015, respectively) and 04:01–08:00 (p = 0.01 and p = 0.03, respectively). Young patients (age < 45 years) had two seizure occurrence peaks, 08:01–12:00 (p = 0.016) and 16:01–20:00 (p = 0.004). Middle-aged/old patients (≥ 45 years) had only one seizure occurrence peak, 08:01–12:00 (p = 0.012). Young patients had more seizures than middle-aged/old patients between 16:01–20:00 (p = 0.04). No differences were noted between left and right MTS.SignificanceWe observed two seizure occurrence peaks: morning and late afternoon/evening. We encountered variations in daytime and nighttime seizure distribution according to gender and age, but not according to side of MTS. Future studies are needed to confirm these findings and to unravel the neurobiological substrate underlying daytime and nighttime variations of seizure occurrence in different age groups and between genders.