Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Evaluate efficacy, safety, and tolerability of adjunctive brivaracetam (BRV) in adult Asian patients with focal-onset seizures (FOS). METHODS: Phase III, randomized, double-blind, placebo-controlled study (EP0083; NCT03083665) evaluating BRV 50 mg/day and 200 mg/day in patients (≥16-80 years) with FOS with/without secondary generalization (focal to bilateral tonic-clonic seizures) despite current treatment with 1 or 2 concomitant antiseizure medications. Following an 8-week baseline, patients were randomized 1:1:1 to placebo, BRV 50 mg/day, or BRV 200 mg/day, and entered a 12-week treatment period. Efficacy outcomes: percent reduction over placebo in 28-day FOS frequency (primary); 50% responder rate in FOS frequency; median percent reduction in FOS frequency from baseline; seizure freedom during treatment period (secondary). Primary safety endpoints: incidences of treatment-emergent adverse events (TEAEs); TEAEs leading to discontinuation; serious TEAEs. RESULTS: In this study, 448/449 randomized patients (mean age, 34.5 years; 53.8% female) received ≥1 dose of study medication (placebo/BRV 50 mg/BRV 200 mg/day: n = 149/151/148). Percent reduction over placebo in 28-day adjusted FOS frequency was 24.5% (p = 0.0005) and 33.4% (p < 0.0001) with BRV 50 mg/day and 200 mg/day, respectively, 50% responder rate was 19.0%, 41.1%, and 49.3% with placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p < 0.0001 for both BRV groups vs. placebo). Median percent reduction in FOS frequency from baseline was 21.3%/38.9%/46.7% in patients on placebo/BRV 50 mg/BRV 200 mg/day, respectively. Overall, 0, 7 (4.6%), and 10 (6.8%) patients were classified as seizure-free during the treatment period on placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p = 0.0146/p = 0.0017 for BRV 50 mg/200 mg/day vs. placebo, respectively). TEAE incidences were similar between patients on placebo (58.4%) and all patients receiving BRV (58.5%); TEAE incidences for BRV 50 mg/day and BRV 200 mg/day were 57.0% and 60.1%, respectively. Overall, 0.7% of patients on placebo and 2.0% of all patients on BRV reported serious TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 1.3% and 2.7%, respectively), 20.1% of patients on placebo and 33.1% of all patients on BRV reported drug-related TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 26.5% and 39.9%, respectively), and 4.7% of patients on placebo and 3.0% of all patients on BRV discontinued due to TEAEs (discontinuation incidences for BRV 50 mg/day and BRV 200 mg/day were 2.6% and 3.4%, respectively). SIGNIFICANCE: Adjunctive BRV was efficacious and well tolerated in adult Asian patients with FOS. Efficacy and safety profiles were consistent with BRV studies in predominantly non-Asian populations. PLAIN LANGUAGE SUMMARY: Brivaracetam is used to treat partial or focal seizures in people with epilepsy. Most studies with brivaracetam tablets have involved people from non-Asian racial backgrounds. In this study, 449 Asian adults with epilepsy took part. One third took 50 mg of brivaracetam, one third took 200 mg of brivaracetam, and one third took a placebo each day for 12 weeks. On average, those who took brivaracetam had fewer seizures than those given the placebo. Most of the side effects were mild and the number and type of side effects seen were as expected for this medication.

Effectiveness and safety of Lacosamide therapy for children with focal epilepsy: a real world study.

Objectives: To compare the effectiveness and safety of the new antiepileptic drug, lacosamide (LCM) with Levetiracetam, for the treatment of focal epilepsy in children. Methods: This study was a cohort study. Children with focal epilepsy who received LCM or Levetiracetam treatment in West China Second Hospital of Sichuan University were recruited and followed up for 12 months. Changes in the frequency of epilepsy, 50% and 75% responder rates, and seizure freedom rates from baseline to the maintenance period and adherence score were assessed. In addition, adverse events (AEs) were recorded. Results: 92 patients completed the study, and were divided into two groups: LCM (n = 46) and Levetiracetam (n = 46). Participants were aged from 2 to 16.3 years, with a mean epilepsy duration of 2.57 years. The average maintenance dose of LCM was 5.03 ± 1.91 mg/kg/d after the titration period. There was no significant difference between the two groups in terms of the mean seizure frequency during subsequent visits at 1, 3,6, 9, 12 months. There was significant difference between the two groups in terms of the 50% responder rate at 6 months. No serious AEs were reported in both groups. The vast majority of patients had good adherence (adherence score = 4) in the LCM group. Conclusion: LCM is effective as adjunctive therapy in children with epilepsy and has good safety, tolerability and adherence. Large sample size studies with long-term follow-up are needed in the future to comprehensively evaluate the use of LCM in children. Clinical Trial Registration: [https://www.chictr.org.cn/showproj.html?proj=41041], identifier [ChiCTR1900024507].

Alice in wonderland syndrome "through the looking-glass" in a rare presentation of non-convulsive status epilepticus in cerebral venous sinus thrombosis and COVID-19.

Alice in Wonderland Syndrome (AIWS) is a rare perceptual disorder, rarely associated with epileptic etiology. We report the case of a 23-year-old man with subacute onset of right peri-orbital headache and visual misperceptions consistent with AIWS Type B, who underwent laboratory tests, brain CT with venography, ophthalmic examination, and neurological assessment that turned out to be normal except for visuospatial difficulties and constructional apraxia. A nasopharyngeal SARS-CoV2 swab taken as screening protocol was positive. The EEG performed because of the persistence of AIWS showed a focal right temporo-occipital non-convulsive status epilepticus; a slow resolution of clinical and EEG alterations was achieved with anti-seizure medications. Brain MRI showed right cortical temporo-occipital signal abnormalities consistent with peri-ictal changes and post-contrast T1 revealed a superior sagittal sinus thrombosis, thus anticoagulant therapy was initiated. AIWS is associated with temporo-parieto-occipital carrefour abnormalities, where visual and somatosensory inputs are integrated to generate the representation of body schema. In this patient, AIWS is caused by temporo-occipital status epilepticus without anatomical and electroencephalographic involvement of the parietal region, consistent with the absence of somatosensory symptoms of the syndrome. Status epilepticus can be the presenting symptom of cerebral venous sinus thrombosis (CVST) which, in this case, is possibly due to the hypercoagulable state associated with COVID-19.

Graph Theory-Based Electroencephalographic Connectivity via Phase-Locking Value and Its Association with Ketogenic Diet Responsiveness in Patients with Focal Onset Seizures.

Ketogenic diets (KDs) are a promising alternative therapy for pediatric refractory epilepsy. Several predictors of KD responsiveness have been identified, including biochemical parameters, seizure types, and electroencephalography (EEG) examinations. We hypothesized that graph theory-based EEG functional connectivity could explain KD responses in patients presenting focal onset seizure (FOS). A total of 17 patients aged 0-30 years old with focal onset seizures (FOS) were recruited as a study group between January 2015 and July 2021. Twenty age-matched children presenting headache with no intracranial complications nor other medical issues were enrolled as a control group. Data were obtained at baseline and at 12 months after initiating KD therapy (KDT) using the child behavior checklist (CBCL) and brain functional connectivity parameters based on phase-locking value from 19 scalp EEG signals, including nodal strength, global efficiency, clustering coefficient, and betweenness centrality. Compared with age-matched controls, patients presenting FOS with right or bilateral EEG lateralization presented higher baseline functional connectivity, including parameters such as global efficiency, mean cluster coefficient and mean nodal strength in the delta and beta frequency bands. In patients presenting FOS with right or bilateral EEG lateralization, the global efficiency of functional connectivity parameters in the delta and theta frequency bands was significantly lower at 12 months after KDT treatment than before KDT. Those patients also presented a significantly lower mean clustering coefficient and mean nodal strength in the theta frequency band at 12 months after KDT treatment. Changes in brain functional connectivity were positively correlated with social problems, attention, and behavioral scores based on CBCL assessments completed by parents. This study provides evidence that KDT might be beneficial in the treatment of patients with FOS. Graph theoretic analysis revealed that the observed effects were related to decreased functional connectivity, particularly in terms of global efficiency. Our findings related to brain connectivity revealed lateralization to the right (non-dominant) hemisphere; however, we were unable to define the underlying mechanism. Our data revealed that in addition to altered brain connectivity, KDT improved the patient's behavior and emotional state.

Adjunctive Treatment With Eslicarbazepine Acetate for Adults and Children With Focal-Onset Epilepsy: A Meta-Analysis.

Background: The efficacy and tolerability of eslicarbazepine acetate (ESL) in adults and children with focal-onset epilepsy (FOE) according to the dose remain to be validated. A meta-analysis based on randomized controlled trials (RCTs) was therefore conducted as a summary. Methods: Relevant RCTs were collected by systematic searching the electronic databases of PubMed, Cochrane's Library, Embase, Wanfang and CNKI from inception to May 16, 2022. The random-effect model was adopted to pool the results by incorporating the possible heterogeneity. Efficacy outcomes including responsive rate and effective rate, defined as cases with 50 and ≥75% reduction in seizure frequency compared to baseline, were determined, respectively. Incidence of severe adverse events (AE) leading to drug discontinuation was also evaluated. Results: Ten studies including 2,565 people with epilepsy contributed to the meta-analysis. For adults, ESL 400 mg/d did not improve the response rate or the effective rate; ESL 800 mg/d was associated with improved response rate (odds ratio [OR] 2.16, 95% confidence interval [CI]: 1.65-2.83, p < 0.001) and effective rate (OR 2.16, 95% CI: 1.41-3.30, p < 0.001) without significantly increased severe AE (OR 1.58, 95% CI: 0.90-2.78, p = 0.11); ESL 1,200 mg/d improved response rate (OR 2.49, p < 0.001) and effective rate (OR 3.09, p = 0.04), but significantly increased severe AE (OR 3.72, p < 0.001). For children, ESL also did not significantly improve the response rate (OR 1.76, p = 0.22) or the effective rate (OR 2.17, p = 0.13). Conclusion: ESL 800 mg/d is effective and well-tolerated as adjuvants for adults with FOE. Efficacy of ESL in children with FOE should be further evaluated.

Endovascular Electroencephalogram Records Simultaneous Subdural Electrode-Detectable, Scalp Electrode-Undetectable Interictal Epileptiform Discharges.

INTRODUCTION: We hypothesized that an endovascular electroencephalogram (eEEG) can detect subdural electrode (SDE)-detectable, scalp EEG-undetectable epileptiform discharges. The purpose of this study is, therefore, to measure SDE-detectable, scalp EEG-undetectable epileptiform discharges by an eEEG on a pig. METHODS: A pig under general anesthesia was utilized to measure an artificially generated epileptic field by an eEEG that was able to be detected by an SDE, but not a scalp EEG as a primary outcome. We also compared the phase lag of each epileptiform discharge that was detected by the eEEG and SDE as a secondary outcome. RESULTS: The eEEG electrode detected 113 (97%) epileptiform discharges (97% sensitivity). Epileptiform discharges that were localized within the three contacts (contacts two, three and four), but not spread to other parts, were detected by the eEEG with a 92% sensitivity. The latency between peaks of the eEEG and right SDE earliest epileptiform discharge ranged from 0 to 48 ms (mean, 13.3 ms; median, 11 ms; standard deviation, 9.0 ms). CONCLUSION: In a pig, an eEEG could detect epileptiform discharges that an SDE could detect, but that a scalp EEG could not.

High prevalence of pathological alertness and wakefulness on maintenance of wakefulness test in adults with focal-onset epilepsy.

BACKGROUND: Excessive daytime sleepiness (EDS) is a common complaint in adults with epilepsy (AWE), but objective evaluation is lacking. We used the maintenance of wakefulness test (MWT) to objectively measure the ability of adults with focal-onset epilepsy to maintain wakefulness in soporific conditions. METHODS: Adults with epilepsy participating in a study investigating the effects of lacosamide on sleep and wakefulness underwent baseline ambulatory polysomnography (PSG)/EEG followed by MWT. Mean sleep latency (MSL) and mean percent sleep time (MST, mean percentage of non-wake EEG scored in 3-sec bins from lights out to sleep onset averaged over the 4 MWT trials) were quantified. Subjective sleepiness was assessed by the Epworth Sleepiness Scale (ESS). Spearman correlation and linear regression assessed relationships between MWT parameters, ESS and relevant sleep and epilepsy-related variables. RESULTS: Maintenance of wakefulness test MSL in 51 AWE (mean age 43.5 ±â€¯13 years, 69% female, mean BMI 24.6 ±â€¯11.2 kg/m2) was 21.7 ±â€¯11.9 min; 45.1% had an abnormally short MSL <19.4 min and 15.7% <8 min. MST was 9.3% [3.3, 19.1]. Mean ESS score was 8.8 ±â€¯5.7; 39% had elevated ESS (>10). No correlation between subjective ESS and objective MSL (p = 0.67) or MST (p = 0.61) was found. MSL was significantly shorter in subjects with focal to bilateral tonic-clonic seizures (FBTCS; 7.9 min [13.6, 22.3]) compared to those without (27.4 min [21.2, 33.6], p = 0.013). Younger subjects had shorter MSL; MSL increased 3.2 min for every 10-year increase in age. CONCLUSION: We found a high prevalence of objective sleepiness/difficulty maintaining wakefulness on the MWT and subjective sleepiness using the ESS in AWE without a correlation between the two. More severe objective sleepiness was found in subjects with a history of FBTCS and younger age. Further research is needed to determine mechanistic underpinnings and optimal measurements of pathological sleepiness in people with epilepsy given the burden of it on quality of life.

Experimental GABA A Receptor Agonists and Allosteric Modulators for the Treatment of Focal Epilepsy.

GABA A receptors are ubiquitous in the central nervous system and there is a huge diversity of receptor subtypes in almost all regions of the brain. However, the expression of GABA A receptor subtypes is altered in both the gray and white matter of patients with focal epilepsy. Although there is a number of anticonvulsants with marketing authorization for the treatment of focal epilepsy which act through GABA A receptors, potentiating the inhibitory effects of GABA, it is necessary to develop more potent and more specific GABAergic anticonvulsants that are effective in drug-resistant patients with focal epilepsy. There are three orthosteric and at least seven allosteric agonist binding sites at the GABA A receptor. In experimental and clinical studies, full agonists of GABA A receptors showed a tendency to cause desensitization of the receptors, tolerance, and physical dependence; therefore, partial orthosteric agonists and positive allosteric modulators of GABA A receptors were further developed. Preclinical studies demonstrated the anticonvulsant efficacy of positive allosteric modulators with selective action on GABA A receptors with α2/α3 subunits, but only a handful of them were further tested in clinical trials. The best results were obtained for clobazam (already marketed), ganaxolone (in phase III trials), CVL-865 (in phase II trials), and padsevonil (in phase III trials). Several compounds with more selective action on GABA A receptors, perhaps only in certain brain regions, have the potential to become effective drugs against specific subtypes of focal-onset epilepsy. However, their development needs time, and in the near future we can expect only one or two new GABA A agonists to obtain marketing authorization for focal epilepsy, an advance that would be of use for just a fraction of patients with drug-resistant epilepsy.

Febrile seizures reduce hippocampal subfield volumes but not cortical thickness in children with focal onset seizures.

OBJECTIVES: Whether febrile seizures (FS) produce long-term injury to the hippocampus or other brain structures is a critical question concerning focal onset seizures in children. Our aims are to evaluate the effect of FS on subfields of the hippocampus, thalamic nuclei, amygdala, cortical thickness, and surface area quantitatively in children with FS who later developed focal seizures and to identify biomarkers based on MRI structures. METHODS: Children who had focal onset seizures with or without previous FS and normal 3-T MRI findings were included retrospectively. The MRI was performed within 2 years after the onset of focal seizures. Age-matched controls were also recruited. Hippocampal subfields and thalamic nuclei, amygdala volumes, cortical thickness, and cortical surface area in individual cortical regions were segmented by FreeSurfer version 7.1.1. Volumetric and morphometric data among children who had focal seizures with or without previous FS, as well as controls, were compared and correlated with clinical parameters. RESULTS: Children with a history of FS who had focal seizures exhibited smaller right cornu ammonis (CA) 1 and right molecular cell layer of the hippocampus, compared to those without FS. A larger left hippocampal fissure was also found in FS with focal seizures compared to age-matched controls. There were no statistically significant differences in each nucleus of the thalamus, amygdala, cortical thickness, and surface area of each cortical region among the three groups. A smaller whole hippocampal volume was found for the right hippocampus in children with FS and focal seizures compared to those without FS. A trend of negative correlation was found between the frequency of FS and the left and right CA1 subfield volume ratios of the hippocampus. CONCLUSIONS: We concluded that multiple episodes of FS may be associated with a trivial difference in volume reduction in the CA1 and molecular layer of the right hippocampus and an enlarged hippocampal fissure of the left hippocampus, but not with individual cortical thicknesses, surface area, thalamic nuclei, or amygdala in children with focal onset seizures.The hippocampal subfield CA1 and molecular layer of the right hippocampus may be more vulnerable than the cortices in children with focal seizures who experienced multiple FS episodes. This study highlights the minimal differences in brain volumes among children with recent onset focal seizures with or without FS history and controls, suggesting that the brain injurious aspects of the FS and recent onset focal seizures may have been previously overstated. This suggests that physicians can be reassuring about brain injury associated with these seizure types when discussing outcomes with parents and patients.

Responsive Neurostimulation as a Novel Palliative Option in Epilepsy Surgery.

Patients with drug-resistant focal onset epilepsy are not always suitable candidates for resective surgery, a definitive intervention to control their seizures. The alternative surgical treatment for these patients in Japan has been vagus nerve stimulation (VNS). Besides VNS, epileptologists in the United States can choose a novel palliative option called responsive neurostimulation (RNS), a closed-loop neuromodulation system approved by the US Food and Drug Administration in 2013. The RNS System continuously monitors neural electroencephalography (EEG) activity at the possible seizure onset zone (SOZ) where electrodes are placed and responds with electrical stimulation when a pre-defined epileptic activity is detected. The controlled clinical trials in the United States have demonstrated long-term utility and safety of the RNS System. Seizure reduction rates have continued to improve over time, reaching 75% over 9 years of treatment. The incidence of implant-site infection, the most frequent device-related adverse event, is similar to those of other neuromodulation devices. The RNS System has shown favorable efficacy for both mesial temporal lobe epilepsy (TLE) and neocortical epilepsy of the eloquent cortex. Another unique advantage of the RNS System is its ability to provide chronic monitoring of ambulatory electrocorticography (ECoG). Valuable information obtained from ECoG monitoring provides a better understanding of the state of epilepsy in each patient and improves clinical management. This article reviews the developmental history, structure, and clinical utility of the RNS System, and discusses its indications as a novel palliative option for drug-resistant epilepsy.

Electro-clinical analysis of epilepsy patients with generalized seizures on adjunctive perampanel treatment.

Quantifying epileptiform discharges before and after the initiation of treatment can be useful for evaluating the efficacy of antiepileptic drugs in generalized epilepsy. The aim of this study was to determine if the selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist perampanel alters the electroencephalographic signals in patients with drug resistant generalized seizures (primary or secondary). We also assessed the clinical efficacy, safety and tolerability of perampanel as an adjunctive treatment for patients with refractory generalized seizures after 3, 6 and 12 months of treatment to determine if there is an electro-clinical correlation. We carried out a 1-year retrospective, unicentric, observational, descriptive and non-interventional study to analyze changes in epileptiform discharges, seizure frequency and adverse effects in patients with generalized seizures taking perampanel as an add-on treatment. Perampanel significantly reduced the total number, total duration, maximal duration and average duration of epileptiform discharges in patients with primary generalized epilepsy (n = 44). In patients with focal onset epilepsy and secondary generalized seizures (n = 8) significant decreases in the maximal duration and average duration of epileptiform discharges were found. These findings correlate with the significant decrease in seizure frequency and clinical improvement observed after taking perampanel as an adjunctive therapy for 3, 6 and 12 months. To our knowledge, this is the first study to show that perampanel reduces epileptiform activity, and that this effect correlates with patients' clinical improvement. Analysing patients' electroencephalographic activity in response to perampanel could be useful for assessing the drug's efficacy and optimising adjunctive treatments.

Alice in wonderland syndrome in an elderly patient with focal onset epilepsy.

Alice in wonderland syndrome (AIWS) is a rare perceptual disorder characterized by subjective distortions of visual and somatosensory perception. Symptoms of AIWS are attributable to functional and structural changes of the visual and somatosensory perceptual system; however, few reports have investigated the pathophysiology of AIWS with regard to epilepsy, especially ictal electroencephalogram (EEG) changes. Herein, we describe the case of an 82-year-old woman with focal onset epilepsy presenting with AIWS, whose seizures were documented by video-EEG monitoring. Video-EEG revealed multiple focal impaired awareness seizures, and ictal EEG changes arose from the right occipital region with small periodic positive discharges with evolution towards the right centro-parietal regions. Our case highlights not only a relationship between epileptic seizures and AIWS but also provides pathological insight into AIWS.

A neuropsychological model for the pre-surgical evaluation of children with focal-onset epilepsy: An integrated approach.

This review explores the complexities of pre-surgical neuropsychological assessment for children with focal-onset epilepsy. A model is proposed outlining a range of factors that potentially influence the neuropsychological formulation. These factors include a developmental, epilepsy, psychological and cognitive dimension, together with family and social context and intrinsic factors. This model is child-centered and recognizes that these factors will be weighted differently for each individual. In some instances the neuropsychological profile might suggest localized and lateralized function, but there are significant limitations to this approach in the context of the contemporary view of epilepsy as a network disorder. This review recognizes that a range of issues impact on neuropsychological function in children with focal-onset epilepsy, including the connectivity between neural systems and the dynamic nature of development. The aim of this review is to provide a neuropsychological framework to enhance and support clinical decision-making in the pre-surgical evaluation of children with focal-onset epilepsy.

Adjunctive lacosamide treatment for adult focal-onset epilepsy: focus on comorbid intellectual/developmental disorders and differing responses.

BACKGROUND: Data regarding lacosamide treatment as an adjunctive therapy in patients representative of a focal-onset epilepsy population including those with and without intellectual/developmental disorders (IDDs) are limited. PURPOSE: To evaluate the retention rates of lacosamide in focal-onset epilepsy patients with and without IDD. PATIENTS AND METHODS: We retrospectively reviewed all consecutive electronic and paper medical records of patients diagnosed with focal-onset epilepsy who were treated with lacosamide in two tertiary epilepsy centers. RESULTS: One hundred and thirty-six patients who met the inclusion criteria were studied. Number of patients with IDD was 46 (33.8%). Median lacosamide dose was 300 mg/day. A total of 39 patients (28.7%) experienced side effects, and 22 of them (16.2%) discontinued lacosamide. The 1-, 2-, and 3-year retention rates of lacosamide in patients with IDD were 68%, 62%, and 53%, respectively. Kaplan-Meier survival analysis showed that the retention rates were significantly lower in patients with IDD when compared to patients without IDD (P=0.04). Cox regression analysis showed that concomitant use of sodium channel blocker antiepileptic drugs (AEDs) was the only independent predictor of retention rate of lacosamide treatment (P=0.03). In the subgroup of patients with IDD, the analysis was performed again and the number of background AEDs was the only predictor for the retention rate of lacosamide (P=0.04). CONCLUSION: When compared to patients without IDD, retention rates of lacosamide adjunctive therapy were lower in patients with IDD. However, these rates were higher than the rates suggested with previously registered AEDs including lamotrigine, levetiracetam, and topiramate. Therefore, irrespective of having comorbid IDD, we might suggest that lacosamide is a well-retained drug with a high efficacy profile in patients with focal-onset epilepsy.

LACONORTE study: Efficacy and security of lacosamide as first add-on therapy for focal-onset epilepsy in real-life setting.

RATIONALE: Many patients with epilepsy need a second antiepileptic drug (AED), due either to inefficacy or side effects of the first tried one. We evaluated the efficacy and safety of lacosamide (LCM) as first add-on therapy in the real-life setting. METHODS: LACONORTE is a multicenter, retrospective, one-year study. Patients with focal epilepsy on monotherapy with another AED who were started on lacosamide as first add-on therapy were included. Clinical data was obtained at 3, 6 and 12 months and then analyzed. RESULTS: Seventy-three patients (48.6% men) with a mean age of 50.3 and a median duration of the epilepsy of 3.0 years (range 0-65) were included. At 1 year, 91.8% were responders (with at least 50% reduction in the number of seizures) and 64.4% of all patients and 75.8% of those with secondary generalization were seizure-free. Fifteen patients (20.5%) had adverse events (AE), most of them were transient and no severe AEs were reported. LCM was withdrawn in 2 patients due to intolerance and in 1 patient because of inefficacy. Neither side effects nor withdrawal seemed to be related to total dose or to escalating regimes. Seventy patients (95.9%) continued on LCM after the last visit (median dose 200 mg/day, ranging 100-400). Eighteen (24.7%) converted to monotherapy during the 12-month period, 83.3% of them remaining seizure-free. CONCLUSIONS: These results of real-life setting show LCM to be efficacious and safe when used as first add-on therapy for focal-onset epilepsy. Most adverse events were mild and/or transient.

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

OBJECTIVE: The 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 METHODS: Chart reviews of patients aged 60years and older with focal-onset epilepsy treated with ZNS in two tertiary epilepsy centers were analyzed retrospectively. RESULTS: Eighty-five patients (41 males, 44 females) aged over 60years (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 200mg/day (range: 100-400) and 212.9±84.2mg/day, respectively. With ZNS treatment, 67.1% of the patients (n=57) were seizure-free for a median of 28months (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 8kg (range: 2-16). There was no significant correlation between weight loss and the administered doses of ZNS (r=0.34; p=0.12). CONCLUSION: Despite 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.