Hippocampal sclerosis is associated with celiac disease type immunity in patients with drug-resistant temporal lobe epilepsy.

BACKGROUND: A prior small-scale single center study suggested an association between celiac disease (CD)-type immunity and refractory temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). The present study addresses this putative association in a large, well-characterized group of drug-resistant epilepsy (DRE) patients. These patients were grouped based on the spectrum of CD and gluten sensitivity-associated antibodies. METHODS: In this cross-sectional study, 253 consecutive adult epilepsy patients (135 females, 118 males; age 16-76 years) were categorized into three groups: (i) CD-positive group with either prior diagnosis of CD or CD-specific TG2/EmA antibodies, (ii) AGA-positive group with antigliadin antibodies (AGA) but without CD, and (iii) CD/AGA-negative group without any gluten sensitivity-associated antibodies or CD. Clinical and immunological findings were then compared among the groups. RESULTS: TLE with HS was more common in the CD-positive group compared to CD/AGA-negative group (31.8% versus 11.9%, P = 0.019). Autoimmune disorders were more common in the AGA-positive group than in the CD/AGA-negative group (P = 0.025). Considering HS lateralization; left lateralization was more common in CD-positive group compared to CD/AGA-negative group (71.4% versus 25%, P = 0.030). TG6 seropositivity did not differ among the groups (P > 0.05). CONCLUSIONS: This study provides further evidence linking TLE with HS and CD-type autoimmunity suggesting that CD-type immune response to gluten can be one potential mechanism as a disease modifier leading to DRE and HS. Understanding these immunological factors is imperative for developing immunomodulatory or dietary treatments for DRE potentially preventing HS progression.

Indications for the use of intravenous second-line antiseizure medications in an emergency room setting.

BACKGROUND: Second-line iv antiseizure medications (ASMs) are used to treat status epilepticus (SE), but in the emergency room setting, there might be other intended and unintended indications for administration. We wanted to explore these different indications and assess the actual usage of first- and second-line ASMs for SE with reference to other uses, such as for SE mimics. METHODS: In this retrospective study, we searched the electronic patient registry with the following terms: "epilepsy", "SE", and "seizure", during 2015. Patients at least 16 years old and treated with iv second-line ASMs were further analysed. We reassessed the indications for the use of iv ASMs based on clinical features and examinations performed. RESULTS: A total of 166 episodes from 136 patients with a median age of 66 years were evaluated, constituting the following indication categories: ongoing SE (48.2%), recurrent seizures (19.3%), postictal (12.1%), seizure mimics (10.2%) and prophylactic use of ASMs (10.2%). Ongoing SE included the following subgroups: convulsive SE, focal aware SE, nonconvulsive SE (NCSE) and NCSE with coma. The seizure mimics group had a preexisting epilepsy diagnosis more often than the ongoing SE group (73% vs. 44%, p = 0.039). Ischaemic stroke was the most frequent seizure mimic. EEG was performed during hospital admission in 78% of patients with ongoing SE, 50% of patients with recurrent seizures, 75% of patients with postictal state, 53% of seizure mimic episodes and 12% of the prophylactic group. In NCSE and comatose NCSE, the diagnosis was made, and treatment was initiated only after an EEG in 52% and 30% of cases, respectively. The use of newer second-line ASMs (levetiracetam and lacosamide) was frequent in our study population. Immediate side effects of ASMs were infrequent. CONCLUSIONS: Even though most of the use of ASMs was justified and administered for SE, it is a diagnostic challenge where a prior diagnosis of epilepsy can be a misleading factor, and EEG is an essential tool when clinical features are often overlapping with other acute seizure disorders. Side effects of the newer second-line ASMs after a single dose are infrequent.

Elevated IL-6 plasma levels are associated with GAD antibodies-associated autoimmune epilepsy.

Background: Antibodies against glutamic acid decarboxylase (GADA) are present in multiple neurological manifestations, such as stiff-person syndrome, cerebellar ataxia, limbic encephalitis, and epilepsy. Increasing data support the clinical significance of GADA as an autoimmune etiology of epilepsy, however, there is not yet definitive evidence to confirm the pathogenic link between GADA and epilepsy. Objective: Interleukin-6 (IL-6), a pro-convulsive and neurotoxic cytokine, and interleukin-10 (IL-10), an anti-inflammatory and neuroprotective cytokine, are crucial inflammatory mediators in the brain. Increased production of IL-6 and its association with epileptic disease profiles are well established, suggesting the presence of chronic systemic inflammation in epilepsy. Therefore, in this study, we investigated the association of plasma cytokine concentrations of IL-6 and IL-10 and their ratio with GADA in patients with drug-resistant epilepsy. Methods: Interleukin-6 and IL-10 concentrations were measured by ELISA in plasma, and the IL-6/IL-10 ratio was calculated in a cross-sectional cohort of 247 patients with epilepsy who had their GADA titers measured previously for their clinical significance in epilepsy. Based on GADA titers, patients were grouped as GADA negative (n = 238), GADA low positive (antibody titers < 1,000 RU/mL, n = 5), and GADA high positive (antibody titers ≥ 1,000 RU/mL, n = 4). Results: Median IL-6 concentrations were significantly higher in patients with high GADA positivity [2.86 pg/mL, interquartile range (IQR) = 1.90-5.34 pg/mL] than in GADA-negative patients [1.18 pg/mL, interquartile range (IQR) = 0.54-2.32 pg/mL; p = 0.039]. Similarly, IL-10 concentrations were also higher in GADA high-positive patients [1.45 pg/mL, interquartile range (IQR) = 0.53-14.32 pg/mL] than in GADA-negative patients [0.50 pg/mL, interquartile range (IQR) = 0.24-1.00 pg/mL], however, the difference was not statistically significant (p = 0.110). Neither IL-6 nor IL-10 concentrations were different between GADA-negative and GADA low-positive patients (p > 0.05) or between GADA low-positive or GADA high-positive patients (p > 0.05). The IL-6/IL-10 ratio was also similar among all the study groups. Conclusion: Increased circulatory concentrations of IL-6 are associated with high GADA titers in patients with epilepsy. These data provide additional pathophysiological significance of IL-6 and help to further describe the immune mechanisms involved in the pathogenesis of GADA-associated autoimmune epilepsy.

Treatment outcomes in women with idiopathic generalized epilepsy.

OBJECTIVES: To evaluate the changes in prescription patterns in the treatment of idiopathic generalized epilepsy (IGE) due to updated treatment recommendations and to assess seizure outcomes of valproate compared to other antiseizure medications (ASMs), with emphasis on women with epilepsy (WWE). MATERIALS AND METHODS: Records of IGE patients treated at Tampere University Hospital between 1 January 2009 and 31 December 2018 were retrospectively inspected. Data were analysed for two subgroups based on age and sex. Seizure control with reference to the efficacy of different ASMs and their combinations was examined for each subgroup. RESULTS: The study compiled 263 subjects (166 females and 97 males). Of all patients, 72.6% remained seizure free. There was no difference in seizure control between sexes (OR 1.25, p = .48). Males used valproate more often than females while females used lamotrigine and levetiracetam more often than males. Lamotrigine and levetiracetam were used especially as monotherapy in WWE, and mostly as part of combination therapy in males. Valproate alternatives were found as effective as valproate when used in monotherapy in adults. Valproate remained the most used ASM in the paediatric subgroup. CONCLUSIONS: The use of valproate has decreased in daily clinical use with the simultaneous increased use of alternative ASMs compared to our previous study. Decreasing use of valproate in WWE did not increase the risk of seizure recurrence; therefore, valproate alternatives could be considered as first-line ASMs for WWE. Overall, IGE patients demonstrated good clinical outcomes with valproate or other broad-spectrum ASMs as monotherapy.

EpiTrack is a feasible tool for assessing attention and executive functions in patients with refractory epilepsy.

OBJECTIVE: The purpose of this cross-sectional retrospective study was to utilize EpiTrack to assess cognitive performance within the domain of attention and executive functions in patients with refractory epilepsy in consideration for treatment interventions either with antiepileptic drug (AED) changes and/or neuromodulation therapies. We also aimed to identify the relevant clinical and treatment factors possibly affecting EpiTrack performance. METHODS: The patient group consisted of 95 consecutive refractory epilepsy patients who were evaluated with EpiTrack. Based on their EpiTrack performance, the patients could be categorized as cognitively unimpaired, mildly, or severely impaired. The patients were also divided into three groups based on the planned treatment modification: AED group (n = 38) with only AED treatment, vagal nerve stimulation (VNS) group (n = 40) and deep-brain stimulation (DBS) group (n = 17). However, the effect of planned interventions was not the subject of this study. We retrospectively reviewed the medical records for detailed clinical characterization. RESULTS: EpiTrack performance was severely impaired in 48 (50.5%), mildly impaired in 22 (23.2%) and unimpaired in 25 (26.3%) of the patients. The DBS group had significantly lower EpiTrack scores (mean (SD) and median, 25.5 (4.81) and 27.0, respectively) compared to the AED group (28.6 (6.2) and 30.0, respectively, p = 0.049). Sixty-three (66.3%) of the whole study population had more than 2 AEDs. When comparing EpiTrack scores between patient groups based on the number of AEDs administered, there was a trend toward better performance in EpiTrack with 2 AEDs as compared to 3-4 AEDs. CONCLUSIONS: Deficits in attention and executive functions were frequent among patients with refractory epilepsy. Deficits were evident in all three treatment groups being most severe in the DBS group reflecting the patient selection. Furthermore, the effect of AED burden on executive functions was remarkable since two thirds of the patients had more than two AEDs and the deficits were more prominent among those with a higher AED burden. These results highlight the benefits of a feasible screening tool such as EpiTrack for assessing attention and executive functions when optimizing the treatment effects of neurostimulation therapies on cognition, and when evaluating the impacts of the AED burden.

Improving the effectiveness of ANT DBS therapy for epilepsy with optimal current targeting.

OBJECTIVE: Deep brain stimulation of the ANT is a novel treatment option in refractory epilepsy with an established efficacy at the group level. However, data on the effect of individualized programming are currently lacking. We report the effect of programming changes on outcome in deep brain stimulation of anterior nucleus of thalamus (ANT DBS). Secondly, we investigated whether the effect differs between seizure types. Thirdly, we compared the response status between patients with stimulation contacts verified inside the ANT with patients with contacts located outside of ANT. METHODS: The participants were 27 consecutive patients with ANT DBS implantation with at least two-year follow-up. Seizures were subdivided into focal aware (FAS), focal impaired awareness (FIAS), and focal to bilateral tonic-clonic seizures (FBTCS). The patients' seizure diaries were analyzed retrospectively to assess changes in different seizure types. Active contact locations for each patient were verified from preoperative MRI and postoperative CT fusion images using SureTune III (Medtronic Inc, Minneapolis, MN) software. RESULTS: A significant reduction in monthly mean seizure frequency occurred in FIAS: 56% at two-year and 65% at five-year follow-up. The effects on FAS and FBTCS were less pronounced. Patients with contacts inside the ANT or on the anterolateral border of ANT experienced a greater reduction in seizure frequency than patients with outside-ANT contacts. Ultimately, seven patients became responders due to changes in DBS programming or repositioning of contacts, increasing our responder rate from 44% to 70% as measured by a seizure reduction of at least 50%. SIGNIFICANCE: ANT DBS appears to be especially effective in reducing FIAS, when the appropriately chosen contacts are activated.

Frequency of Automatic Stimulations in Responsive Vagal Nerve Stimulation in Patients With Refractory Epilepsy.

BACKGROUND: In vagal nerve stimulation (VNS) therapy, the release of VNS model 106 (AspireSR) allowed for responsive VNS (rVNS). rVNS utilizes a cardiac-based seizure detection algorithm to detect seizure-induced tachycardia to trigger additional stimulation. There are some studies suggesting clinical benefits of rVNS over traditional VNS, but the performance and significance of autostimulation mode in clinical practice are poorly understood. OBJECTIVES: To assess the effect of initiation of rVNS therapy and altered stimulation settings on the number of daily stimulations and energy consumption in VNS therapy and to compare autostimulation performance in different epilepsy types. MATERIALS AND METHODS: Retrospective follow-up of 30 patients with drug-resistant epilepsy treated with rVNS including 17 new implantations and 13 battery replaces at a single center in Finland. Our data consist of 208 different stimulation periods, that is, episodes with defined stimulation settings and both autostimulation and total stimulation performance-related data along with clinical follow-up. RESULTS: The variation in autostimulation frequency was highly dependent on the duration of the OFF-time and autostimulation threshold (p < 0.05). There was a large additional effect of autostimulation mode on therapy time and energy consumption with longer OFF-times, but a minor effect with shorter OFF-times. Significantly more autostimulations were triggered in the temporal lobe and multifocal epilepsies than in extratemporal lobe epilepsies. CONCLUSIONS: The initiation of autostimulation mode in VNS therapy increased the total number of stimulations. Shortening the OFF-time leads to a decreased number and share of automatic activations. Epilepsy type may affect autostimulation activity.

Circadian distribution of autostimulations in rVNS therapy in patients with refractory focal epilepsy.

BACKGROUND: Responsive vagus nerve stimulation (rVNS) utilizes an electrocardiograph (ECG)-based algorithm to detect rapid sympathetic activations associated with the onset of a seizure. Abrupt sympathetic activation may also be associated with nocturnal arousals between sleep cycles or transitioning from sleep to wakefulness, a period in which many patients with epilepsy experience seizures. Because of circadian changes in autonomic function, we hypothesized that the autostimulation feature might also behave in a circadian fashion. OBJECTIVE: The aim of this study was to assess the circadian rhythmicity of autostimulations in rVNS treatment in patients with drug-resistant epilepsy (DRE). MATERIALS AND METHODS: We performed a retrospective follow-up study of 30 patients with DRE treated with rVNS including 17 new implantations and 13 battery replacements at a single center in Finland. After initiation of autostimulation mode, the exact rVNS stimulation parameters and the timestamps of all individual autostimulations delivered were registered. A clustered autostimulation was defined as any autostimulation that occurred within the duration of the therapeutic cycle during the therapy "OFF" time compared with both the previous autostimulation and the following autostimulation. RESULTS: Autostimulations and especially autostimulation clusters show a higher probability of occurring in the morning and less at night. This trend appeared to follow the circadian rhythm of cortisol concentration. CONCLUSIONS: Early morning peaks of autostimulations at low thresholds may reflect awakening-induced activation of the cardiovascular system, which is associated with a shift towards the dominance of the sympathetic branch of the autonomic nervous system. Cortisol release occurs in parallel driven by wakening-induced activation of the hypothalamic-pituitary-adrenal axis, which is fine-tuned by direct sympathetic input to the adrenal gland. This is of interest considering the known sympathetic hyperactivity in patients with epilepsy.

Autostimulation in Vagus Nerve Stimulator Treatment: Modulating Neuromodulation.

OBJECTIVES: Until now, the vagus nerve stimulation (VNS) treatment in epilepsy has consisted of two different modes: normal and magnet stimulation. A new vagus nerve stimulator model (106 AspireSR®, LivaNova, Houston, TX, USA) also allows automatic stimulation (AutoStim). The purpose of this study is to examine the effect of autostimulation on seizure frequencies together with energy consumption. MATERIALS AND METHODS: The study material consisted of 14 patients whose former stimulator model (102/103) was replaced with model 106. We calculated the theoretical charge (Q) in Coulombs for one day in both of those groups. We evaluated the follow-up data of the patients' seizure counts, with a mean follow-up time of 18.1 months (SD 8.1). RESULTS: The total charge, "VNS dose," was reduced with model 106 in comparison with models 102 or 103 (p = 0.001, Mann-Whitney test). The average charge (Qtotal ) for one day with AutoStim was 142.56 mC; without AutoStim, it was 321.09 mC. We were able to assess seizure diaries in 11 out of 14 patients. Four patients (36%) had >50% seizure reduction and two patients (18%) experienced a reduction in seizure severity with VNS with autostimulation. Five patients (46%) remained unchanged. In three out of four patients with improved seizure control, the duty cycle was maintained at the original level. The patients whose duty cycle was modified for a more prolonged OFF-time had unchanged seizure frequencies. CONCLUSION: VNS with AutoStim achieves maintenance of prior-established seizure control with markedly less energy consumption and can also improve seizure control as compared to former stimulator model.

Under-reporting of nocturnal seizures using video-based home monitoring: a case study on the evaluation of the effect of vagal nerve stimulation.

A challenge in treating epilepsy is the accurate documentation of seizure frequency, which is needed in order to assess the benefits of ongoing treatment. We present a 17-year-old girl who underwent video-based monitoring in order to establish an accurate seizure count before and after the implantation of a vagus nerve stimulator to treat refractory epilepsy. The results show a reduction in disabling seizure types after vagus nerve stimulator implantation and highlight the inconsistencies between the reported and actual seizure count in this patient. Our case adds to the recognised issue of inaccurate seizure documentation. [Published with video sequence on www.epilepticdisorders.com].

Reversible psychiatric adverse effects related to deep brain stimulation of the anterior thalamus in patients with refractory epilepsy.

OBJECTIVE: Anterior nucleus of thalamus (ANT) deep brain stimulation (DBS) is becoming a more common treatment for drug-resistant epilepsy. Epilepsy and depression display a bidirectional association. Anterior nucleus of thalamus has connections to anterior cingulate cortex and orbitomedial prefrontal cortex, hence, a possible role in emotional and executive functions, and thus, ANT DBS might exert psychiatric adverse effects. Our aim was to evaluate previous and current psychiatric symptoms in patients with epilepsy undergoing ANT DBS surgery and assess the predictability of psychiatric adverse effects. Programming-related psychiatric adverse effects are also reported. METHOD: Twenty-two patients with ANT DBS for retractable epilepsy were examined, and a psychiatric evaluation of depressive and other psychiatric symptoms was performed with Montgomery and Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Symptom Checklist prior to surgery, concentrating on former and current psychiatric symptoms and medications. The follow-up visit was one year after surgery. RESULTS: At the group level, no changes on mood were observed during ANT DBS treatment. Two patients with former histories of depression experienced sudden depressive symptoms related to DBS programming settings; these were quickly alleviated after changing the stimulation parameters. In addition, two patients with no previous histories of psychosis gradually developed clear paranoid and anxiety symptoms that also relieved slowly after changing the programming settings. CONCLUSION: The majority of our ANT DBS patients did not experience psychiatric adverse effects. Certain DBS parameters might predispose to sudden depressive or slowly manifesting paranoid symptoms that are reversible via programming changes.

Discontinuation of carbamazepine due to concerns of long-term consequences of enzyme induction.

OBJECTIVE: Treatment with carbamazepine (CBZ), a potent enzyme inducer, is known to affect the lipid profile, steroid, and vitamin D metabolism. Consequently, it has been postulated that patients on CBZ should be switched to noninducing antiepileptic drugs (AEDs). However, little is known about the seizure outcome following a CBZ switch in seizure-free patients. We aimed to address this issue using a controlled observational study design. METHODS: Fifty-eight patients taking CBZ for focal epilepsy were assessed for discontinuing CBZ treatment due to concerns of long-term adverse-effects; 34 discontinued its therapy and 24 continued with CBZ. Six-month seizure freedom was the primary end point. Furthermore, serum samples (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, sex hormone-binding globulin (SHBG), free testosterone, and 25-hydroxyvitamin D levels from before and at least 3 months after discontinuation or continuation were obtained from all patients. RESULTS: Seizure-free patients had a 5-fold elevated odds of seizure recurrence if CBZ was discontinued (95% confidence interval [CI 0.51-49.3; p = 0.17). A significant decrease in serum levels of TC, LDL, HDL, and SHBG as well as a significant increase in that of free testosterone were found in the discontinuation group compared with those who continued CBZ. Nonsignificant changes in triglycerides and vitamin D levels were detected. SIGNIFICANCE: Discontinuation of CBZ in seizure-free patients seems to carry a moderate, but legitimate, risk of relapse. Conversely, our results indicate that CBZ might have unfavorable effects on serum levels of TC, LDL, HDL, SHBG, and free testosterone.

Executive Functions May Predict Outcome in Deep Brain Stimulation of Anterior Nucleus of Thalamus for Treatment of Refractory Epilepsy.

BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) is an emerging treatment option for patients suffering from refractory epilepsy. ANT has extensive connections with hippocampus and retrosplenial cingulum, areas associated mainly with spatial memory and with anterior cingulum which is important in executive functions. As refractory epilepsy is often associated with cognitive decline and neuronal damage, the decreased connectivity between ANT and remote structures might impact on the effects of DBS. OBJECTIVE: We hypothesized that the neuropsychological profile could reflect the connectivity of ANT and further predict the efficacy of ANT DBS. We evaluated the cognitive performance of patients with refractory epilepsy with DBS to evaluate whether neuropsychological profiles could reflect the connectivity of ANT and further predict the efficacy of ANT DBS. METHOD: Sixteen patients with refractory epilepsy treated with ANT DBS with at least 2 years of follow-up were included in the study. Patients underwent a neuropsychological evaluation as a part of the protocol and their clinical outcome was determined by seizure frequency in the last 6 months compared to baseline. The patients were classified as responders if there was a ≥50% reduction in the frequency of the predominant seizure type, otherwise as nonresponders. RESULTS: There were 12 responders and 4 nonresponders for ANT DBS treatment in the study population. Nonresponders performed worse than responders in neuropsychological tasks measuring executive functions and attention, such as the Trail-Making Test. CONCLUSION: Better executive functions and attention seemed to predict improved clinical outcome after the ANT DBS surgery. Based on our preliminary descriptive findings and the anatomical connectivity hypothesis, we suggest that deficits in executive functions may relate to an inferior outcome. This finding might offer new tools for refining the selection of patients with refractory epilepsy scheduled to undergo ANT DBS surgery. Moreover, it highlights the need for further investigations of neural connectivity in epilepsy.

Similarities between the responses to ANT-DBS and prior VNS in refractory epilepsy.

OBJECTIVES: Neurostimulation has offered new treatment options in refractory epilepsy, first with vagus nerve stimulation (VNS) and more recently with deep brain stimulation (DBS). There is a lack of previous detailed data assessing the relationship between VNS and ANT-DBS. The aim of this study was to investigate the potential correlation between therapeutic responses to VNS and ANT-DBS. MATERIALS AND METHODS: A total of 11 patients with previous VNS therapy underwent ANT-DBS implantation. Monthly seizure counts starting from baseline before VNS extending to long-term DBS treatment were analyzed. The reasons for VNS discontinuation were assessed. RESULTS: Altogether in 10 of 11 patients, the response to VNS seemed to be similar to the response to DBS therapy. Progressive response to VNS was likely to correlate with a progressive response to DBS in three of three patients. Partial response to VNS was associated with a fluctuating response pattern to DBS in two patients. Five of six nonresponders to VNS were also nonresponders to DBS. One of the VNS nonresponders obtained progressive response to DBS. CONCLUSIONS: This is the first study to evaluate in detail the effect of both VNS and ANT-DBS in refractory epilepsy patients. There is a putative association between VNS and DBS responses suggesting the need for further studies.

Stimulation Induced Electrographic Seizures in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Do Not Preclude a Subsequent Favorable Treatment Response.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient's seizures in long-term follow-up. We therefore hypothesize that the occurrence of stimulation induced seizures at the onset of DBS therapy should not be considered as a failure in the DBS therapy, and the possibility of a subsequent favorable response to the treatment still exists.

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

INTRODUCTION: Lacosamide (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 60years 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 2weeks. RESULTS: Lacosamide 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 14months. The mean daily dose of LCM at the end of follow-up was 368mg (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. CONCLUSIONS: Lacosamide was well tolerated even at relatively high doses and in combination therapy.

Comparative effectiveness of eight antiepileptic drugs in adults with focal refractory epilepsy: the influence of age, gender, and the sequence in which drugs were introduced onto the market.

The first objective was to determine the long-term retention rate of eight antiepileptic drugs (AEDs) commonly used as adjunctive therapy in adults with focal refractory epilepsy. Second, we assessed the effects of age and gender on retention rates. Third, we examined if the retention rate could be influenced by the sequence in which the AEDs had entered the market. Patients with focal refractory epilepsy treated with any of the eight AEDs in Tampere University Hospital were identified retrospectively (N = 507). Retention rates were evaluated with the Kaplan-Meier method. Follow-up started at the first date of treatment and each individual was followed a maximum of 36 months. We calculated the following 3-year retention rates: lacosamide 77.1% (N = 137), lamotrigine 68.3% (N = 177), levetiracetam 66.7% (N = 319), clobazam 65.6% (N = 130), topiramate 61.6% (N = 178), zonisamide 60.4% (N = 103), pregabalin 54.6% (N = 127), and gabapentin 40.2% (N = 66). Lacosamide, levetiracetam, and clobazam were the most effective AEDs in the elderly. The retention rate for pregabalin was higher in males (65%) than females (51%) whereas females had higher retention rates for both topiramate (72 vs. 58%) and zonisamide (67 vs. 57%). The retention rate was influenced by the sequence in which these AEDs entered the market. We provide important information about practical aspects of these eight AEDs, revealing that there are differences in their effectiveness as adjunctive treatment for focal refractory epilepsy. Most importantly, the retention rate appears to be influenced by the sequence in which these AEDs were introduced onto the market.

The effect of newer antiepileptic drugs in combination therapy.

PURPOSE: To assess the impact of the new AEDs on overall outcome for patients with epilepsy. METHODS: In 2004, the effect of combination therapy on seizure frequency in adult patients with focal epilepsy was evaluated in a cross-sectional study in our center. We repeated this analysis ten years and eight new antiepileptic drugs (AED) later. RESULTS: In 2014, a higher percentage of patients with polytherapy (117 out of 396; 30%) were seizure-free compared with the original analysis (22%) (p=0.042). Eighty three out of 218 (38%) subjects on duo-therapy were seizure-free (27% in 2004) (p=0.040); in the 151 receiving triple therapy there were 30 (20%) seizure-free subjects (10% in 2004). Four out of 27 subjects (15%) with four AEDs were seizure-free (0% in 2004). The most common pairing of 52 different combinations for duo-therapy was levetiracetam-oxcarbazepine. Eighty different AEDs regimens were being used in the patients administered three AEDs. CONCLUSION: Our combined data from these two studies indicate that some patients with focal epilepsy might benefit from newer AEDs as an adjunctive therapy in the hope they could acquire seizure freedom.

Transition from oxcarbazepine to eslicarbazepine acetate: A single center study.

OBJECTIVES: There is limited clinical evidence for comparison between oxcarbazepine (OXC) and eslicarbazepine acetate (ESL) in terms of tolerability, or how to execute the change from OXC to ESL. We report the process of transitioning patients with focal epilepsy from previous OXC treatment to ESL due to tolerability problems. The rationale for change from OXC is reported, and the outcome with respective to this rationale is analyzed in terms of tolerability and efficacy. MATERIALS AND METHODS: The subjects were transitioned overnight from OXC to ESL in a hospital inpatient setting. An evaluation of the effects of the transition was made after 1 and 3 months. All adverse events (AEs) were recorded following the transition period. Subjects were classified by outcome in terms of AEs. RESULTS: Twenty-three subjects were transitioned from OXC to ESL. Fifteen patients OXC-related AEs reduced significantly after transition. Particularly, most of (93%) the AEs presented in the morning resolved after transition to ESL. No patient had an increase in seizure frequency following the transition. The incidence of ESL-related AEs was 39% at 1 month and 13% at 3 month follow-up; however, all patients continued ESL throughout the study period. CONCLUSIONS: This study demonstrates that patients suffering from OXC-related AEs improve in terms of tolerability after a switch to ESL with maintaining seizure control. This improvement is more pronounced if the OXC-related AEs are most evident following morning dosing of OXC. Transition can be safely executed in an outpatient setting.

Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and safety of i.v. haloperidol in treatment of acute migraine headache in a double-blind, randomized, placebo-controlled study design. BACKGROUND: Neuroleptics are mainly used as antiemetics in acute migraine. In a previous open trial haloperidol was effective in relieving migraine pain. DESIGN: Patients were randomized into 2 groups receiving intravenously either 5 mg haloperidol in 500 mL of normal saline or 500 mL of normal saline alone. Pain was assessed by visual analogue scale (VAS) before and 1 to 3 hours after the infusion. If the patient felt no relief in pain intensity 1 to 3 hours after the infusion and had received placebo, he/she then received haloperidol infusion as an open trial. The open trial also included 7 patients who refused from the placebo-controlled trial. About 1 month after the infusion the patients were contacted by telephone and interviewed about the side effects of the treatment. RESULTS: Forty patients were enrolled into the double-blind, placebo-controlled study. Before the infusion the VAS values were 7.7 in the haloperidol and 7.2 in the placebo group. After the infusion the VAS values were 2.2 in the haloperidol and 6.3 in the placebo group (P < .0001). Significant pain relief was achieved in 80% of the patients treated with haloperidol, whereas only 3 patients (15%) responded to placebo (P < .0001). Seventeen patients treated with placebo without response together with 7 patients who refused from the placebo-controlled study participated in the open trial. In this group VAS declined from 6.7 to 2.4 and 79% of these patients felt significant pain relief. The most common side effects caused by haloperidol were sedation and akathisia, the latter being more troublesome. These effects were very common in patients participating in the double-blind (80%) and open (88%) trials. Sixteen percent of the patients considered the side effects intolerable and would not like the migraine attacks to be treated with haloperidol in the future. Three patients (7%) returned to the emergency ward because of a relapse. CONCLUSIONS: This study shows that i.v. haloperidol is very effective in relieving migraine-associated pain. Because the majority of the patients had taken other medication without response, haloperidol appears to be an effective rescue medication even when other types of treatment have failed. Relapses are rare, but side effects are common, limiting the use of haloperidol in some patients.