Do all patients in the epilepsy monitoring unit experience the same level of comfort? A quantitative exploratory secondary analysis.

AIMS: To find out which variables may be associated with comfort of patients in an epilepsy monitoring unit. DESIGN: Exploratory, quantitative study design. METHODS: Data were collected from October 2018 to November 2019 in Austria and Southern Germany. A total of 267 patients of 10 epilepsy centres completed the Epilepsy Monitoring Unit Comfort Questionnaire which is based on Kolcaba's General Comfort Questionnaire. Secondary data analysis were conducted by using descriptive statistics and an exploratory model building approach, including different linear regression models and several sensitivity analyses. RESULTS: Total comfort scores ranged from 83 to 235 points. Gender, occupation and centre turned out to be possible influential variables. On average, women had a total comfort score 4.69 points higher than men, and retired persons 28.2 points higher than high school students ≥18 years. Comfort scores of younger patients were lower than those of older patients. However, age did not show a statistically significant effect. The same could be observed in marital status and educational levels. CONCLUSION: When implementing comfort measures, nurses must be aware of variables which could influence the intervention negatively. Especially, high school students ≥18 years should be supported by epilepsy specialist nurses, in order to reduce uncertainty, anxiety and discomfort. But, since the identified variables account only for a small proportion of the inter-individual variability in comfort scores, further studies are needed to find out additional relevant aspects and to examine centre-specific effects more closely. IMPACT: Nurses ensure patient comfort during a hospital stay. However, there are variables that may impair the effectiveness of the nursing measures. Our study showed that the experience of comfort was highly individual and could be explained by sociodemographic variables only to a limited extent. Nurses must be aware that additional factors, such as the situation in the individual setting, may be relevant.

Effects of an epilepsy-specific Internet intervention (Emyna) on depression: Results of the ENCODE randomized controlled trial.

OBJECTIVE: Depression and anxiety are highly prevalent among people with epilepsy (PwE) but often remain unrecognized and treated inadequately. Effective psychosocial treatments such as cognitive behavioral therapy (CBT) are rarely available to most PwE, which is one reason electronically delivered CBT (eCBT) is regarded as promising. This study examined an eCBT intervention, termed Emyna, that was tailored to suit the needs of PwE. It includes CBT-related content on depression, stress and anxiety, seizure triggers and auras, and lifestyle habits. The trial examined the efficacy of Emyna in reducing symptoms of depression (primary outcome) and anxiety as well as improving quality of life. METHODS: Participants (N = 200) with epilepsy, a diagnosis of a depressive disorder, and at least moderate depressive symptoms were randomized to Emyna or care as usual. At baseline and after 3, 6, and 9 months, participants were invited to complete online questionnaires. The primary outcome was improvement of depressive symptoms at 3 months. RESULTS: Relative to the control group, intervention group participants experienced significantly greater improvements in depression, anxiety, stress, social-occupational impairment, and epilepsy-related quality of life, in both intention-to-treat (ITT) and per-protocol analyses. In ITT analyses, effects of medium magnitude were observed, as measured by the Patient Health Questionnaire-9 items (Cohen d = 0.54, 95% confidence interval [CI] = 0.25-0.82, P < 0.001) and the Neurological Disorders Depression Inventory for Epilepsy (d = 0.51, 95% CI = 0.23-0.79, P < 0.01). At 3 months, intervention group participants also reported fewer illness-related days off work and fewer days hospitalized over the preceding months, compared to control group participants (P ≤ 0.05), whereas no such differences were present at baseline (P > 0.30). SIGNIFICANCE: These findings showed that Emyna, used adjunctively to usual care, could help improve mental health, social-occupational functioning, and quality of life among PwE. The program provides an additional treatment option that could produce clinically relevant symptom reductions and reduce key cost drivers (ie, hospitalization rates and illness-related inability to work).

Protocol for the ENCODE trial: evaluating a novel online depression intervention for persons with epilepsy.

BACKGROUND: Depression is common among persons with epilepsy (PwE), affecting roughly one in three individuals, and its presence is associated with personal suffering, impaired quality of life, and worse prognosis. Despite the availability of effective treatments, depression is often overlooked and treated inadequately in PwE, in part because of assumed concerns over drug interactions or proconvulsant effects of antidepressants. Internet-administered psychological interventions might complement antidepressant medication or psychotherapy, and preliminary evidence suggests that they can be effective. However, no trial has yet examined whether an Internet intervention designed to meet the needs of PwE can achieve sustained reductions in depression and related symptoms, such as anxiety, when offered as adjunct to treatment as usual. METHODS/DESIGN: This randomized controlled trial will include 200 participants with epilepsy and a current depressive disorder, along with currently at least moderately elevated depression (Patient Health Questionnaire (PHQ-9) sum score of at least 10). Patients will be recruited via epilepsy treatment centers and other sources, including Internet forums, newspaper articles, flyers, posters, and media articles or advertisements, in German-speaking countries. Main inclusion criteria are: self-reported diagnosis of epilepsy and a depressive disorder, as assessed with a phone-administered structured diagnostic interview, none or stable antidepressant medication, no current psychotherapy, no other major psychiatric disorder, no acute suicidality. Participants will be randomly assigned to either (1) a care-as-usual/waitlist (CAU/WL) control group, in which they receive CAU and are given access to the Internet intervention after 3 months (that is, a CAU/WL control group), or (2) a treatment group that may also use CAU and in addition immediately receives six-month access to the novel, Internet-administered intervention. The primary outcome measure is the PHQ-9, collected at three months post-baseline; secondary measures include self-reported anxiety, work and social adjustment, epilepsy symptoms (including seizure frequency and severity), medication adherence, potential negative treatment effects and health-related quality of life. Measurements are collected online at pre-treatment (T0), three months (T1), six months (T2), and nine months (T3). DISCUSSION: Results of this trial are expected to extend the body of knowledge with regard to effective and efficient treatment options for PwE who experience elevated depression and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02791724 . Registered 01 June 2016.

A noninterventional study evaluating the effectiveness and safety of lacosamide added to monotherapy in patients with epilepsy with partial-onset seizures in daily clinical practice: The VITOBA study.

OBJECTIVE: Evidence for the efficacy and safety of adjunctive lacosamide in the treatment of partial-onset seizures (POS) was gained during placebo-controlled clinical trials in patients with treatment-resistant seizures who were taking one to three concomitant antiepileptic drugs (AEDs). The VITOBA study (NCT01098162) evaluated the effectiveness and tolerability of adjunctive lacosamide added to one baseline AED in real-world clinical practice. METHODS: We conducted a 6-month observational study at 112 sites across Germany. Adult patients (≥ 16 years) with POS received lacosamide adjunctive to only one baseline AED. Seizure frequency reduction at the end of the observation period was compared with a 3-month retrospective baseline period. RESULTS: Five hundred seventy-one patients received lacosamide at least once (Safety Set [SS]); 520 provided evaluable seizure records (Full Analysis Set [FAS]); and 499 took in-label dosages of lacosamide (up to 400 mg) and were evaluated for effectiveness (modified FAS). Median baseline seizure frequency was 2.0 per 28 days: 47.1% of patients (235/499, mFAS) took a concomitant sodium channel-blocking (SCB) AED; 38.1% (190/499) had only one lifetime AED; and 18.4% (92/499) were aged ≥ 65 years (mFAS). At the final visit, 72.5% (358/494) of patients showed a ≥ 50% reduction in seizure frequency from baseline, 63.8% (315/494) showed a ≥ 75% reduction, and 45.5% (225/494) were seizure-free. Seizure freedom rates were higher in patients aged ≥ 65 years (56.7%) compared with patients aged <65 years (43.1%), in patients with ≤ 5 years epilepsy duration (52.5%) versus >5 years duration (41.0%), and when added to first monotherapy (60.5%) rather than as a later therapy option. Treatment-emergent adverse events (TEAEs) were reported by 48.5% (277/571) of patients (SS), with a profile similar to that observed in pivotal trials; 466 of patients (81.6%, SS) continued lacosamide therapy after the trial. SIGNIFICANCE: These results suggest that lacosamide use, added to one concomitant AED, was effective at improving seizure control and was well tolerated in patients treated in routine clinical practice.

Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized phase III study.

OBJECTIVE: To evaluate the efficacy and safety of USL255, Qudexy(™) XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. METHODS: In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥ 50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. RESULTS: Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. SIGNIFICANCE: The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects.

The LaLiMo Trial: lamotrigine compared with levetiracetam in the initial 26 weeks of monotherapy for focal and generalised epilepsy--an open-label, prospective, randomised controlled multicenter study.

BACKGROUND: Of the newer antiepileptic drugs, lamotrigine (LTG) and levetiracetam (LEV) are popular first choice drugs for epilepsy. The authors compared these drugs with regard to their efficacy and tolerability in the initial monotherapy for epilepsy. METHODS: A randomised, open-label, controlled, parallel group, multicenter trial was conducted to test the superiority of the LEV arm over the LTG arm. The primary endpoint was the rate of seizure-free patients in the first 6 weeks (two-sided Fisher's exact test, α=0.05, intent-to-treat set). Furthermore, efficacy, tolerability and quality of life were evaluated. The authors included 409 patients aged ≥12 years with newly diagnosed focal or generalised epilepsy defined by either two or more unprovoked seizures or one first seizure with high risk for recurrence. Patients were titrated to 2000 mg/day of LEV or 200 mg/day of LTG reached on day 22 or 71, respectively. Two dose adjustments by 500/50 mg were allowed. RESULTS: The proportions of seizure-free patients were 67.5% (LEV) versus 64.0% (LTG) 6 weeks after randomisation (p=0.47), and 45.2% (LEV) versus 47.8% (LTG) during the whole treatment period of 26 weeks. The HR (LEV vs. LTG) for seizure-free time was 0.86 (95% CI, 0.61 to 1.22). Adverse events occurred in 74.5% (LEV) versus 70.6% (LTG) of the patients (p=0.38). Adverse events associated with study discontinuation occurred in 17/204 (LEV) versus 8/201 (LTG) patients (p=0.07). CONCLUSIONS: There were no significant differences with regard to efficacy and tolerability of LEV and LTG in newly diagnosed focal and generalised epilepsy despite more rapid titration in the LEV arm. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT00242606.

Long-term safety and efficacy of brivaracetam in adults with focal seizures: Results from an open-label, multinational, follow-up trial.

BACKGROUND: This long-term follow-up (LTFU) trial was conducted to evaluate the long-term safety and tolerability of brivaracetam (BRV) at individualized doses (maximum of 200 mg/day) in patients with focal seizures. The secondary objective was to evaluate the efficacy of BRV over time. METHODS: Two Phase III, randomized, double-blind, historical-controlled conversion-to-monotherapy trials (N01276: NCT00698581; N01306: NCT00699283) were conducted in patients aged ≥16 years with uncontrolled focal seizures. Patients who completed either of these core trials or who met a protocol-defined exit criterion could enter this LTFU trial (N01315; NCT00761774). Patients entered LTFU at a recommended BRV dose of 100 mg/day, with flexible dosing of 50-200 mg/day, as monotherapy or adjunctive therapy; additional AEDs could be prescribed and adapted in dose if clinically indicated. Safety variables included treatment-emergent adverse events (TEAEs). Efficacy variables included duration of continuous monotherapy, reduction in focal seizure frequency and seizure freedom. Safety and efficacy variables were assessed for all patients in the safety set or efficacy set, respectively, regardless of BRV treatment regimen. In addition, a post hoc subgroup analysis was conducted for patients who completed the BRV monotherapy period in either core trial, and entered the LTFU on BRV monotherapy. For this subgroup, TEAEs were summarized by 3-month time intervals over the first 12 months of LTFU. RESULTS: 108 patients were enrolled in the LTFU trial between November 2008 and February 2010. 79 (73.1 %) patients discontinued the LTFU trial, most commonly due to lack of efficacy [37 (34.3 %)] and adverse events [16 (14.8 %)]. At core trial baseline, patients had a median of 6.3 focal seizures/28 days and 53 (49.1 %) had failed ≥5 previous lifetime AEDs. During LTFU, 70 (64.8 %) patients had ≥12 months and 56 (51.9 %) patients had ≥24 months of BRV treatment. TEAEs were reported by 98 (90.7 %) patients; most commonly (≥15 % of patients) convulsion (17.6 %), nasopharyngitis (17.6 %), depression (16.7 %) and fatigue (15.7 %). Median percent reduction from baseline in focal seizure frequency/28 days was 56.8 %. Among 86 patients who completed at least 6 months of treatment, 29 (33.7 %) patients were seizure-free for ≥6 months and 22 (25.6 %) were seizure-free for ≥12 months. 50/108 patients were included in the BRV monotherapy subgroup; 33/50 (66.0 %) patients reported a TEAE in the core trials, while 26/50 (52.0 %), 15/37 (40.5 %), 14/33 (42.4 %) and 9/27 (33.3 %) patients reported any TEAE during LTFU months 1-3, 4-6, 7-9 and 10-12, respectively. In the BRV monotherapy subgroup, the most common TEAEs (≥5% of patients) during LTFU months 1-3 were fatigue [3/50 (6.0 %)] and dizziness [3/50 (6.0 %)]. INTERPRETATION: Results from the LTFU trial support the long-term safety of BRV at individualized doses of up to 200 mg/day as a well-tolerated, and effective treatment for patients with focal seizures. Efficacy analyses indicate that seizure reductions with brivaracetam were generally maintained over time.

Changes in drug load during lacosamide combination therapy: A noninterventional, observational study in German and Austrian clinical practice.

INTRODUCTION: Effects of antiepileptic drug (AED) load changes in patients with focal seizures have not been well evaluated. METHODS: SP1065 (NCT01673282) was a noninterventional, prospective, observational study conducted in a clinical practice setting. Patients (aged ≥18 years) with focal seizures were enrolled within 7 days of being prescribed adjunctive lacosamide. Observation period was ~6 months. Drug load was assessed using percentage change in ratio of actual prescribed dose and World Health Organization defined daily dose (DDD) for concomitant AEDs and all AEDs (including lacosamide). Subgroups were defined for patients with at least one concomitant sodium channel-blocking AED (SCB [+]) and those without (SCB [-]). RESULTS: A total of 311 patients were assessed for safety, 302 for measurement of drug load, and 240 for effectiveness. Ratio of AED dose to DDD decreased for concomitant AEDs (-9.6%) and increased for all AEDs (including lacosamide; 15.5%). Median reduction in focal seizure frequency per 28 days was 100% (range: -100, 2275.8). 70.4% and 61.7% of patients had a ≥50% or ≥75% reduction in seizure frequency, respectively; 50.8% became seizure-free. In the SCB (+) subgroup (n = 149), ratio of AED dose to DDD decreased for concomitant AEDs (-15.0%) and increased for all AEDs (10.7%). In the SCB (-) subgroup (n = 153), ratio of AED dose to DDD decreased for concomitant AEDs (-4.4%) and increased for all AEDs (20.2%). Fifty-seven patients (18.3%) reported ADRs, most commonly dose >400 mg/d (7.1%). Seventeen patients (5.5%) had ADRs leading to discontinuation. SIGNIFICANCE: Addition of lacosamide resulted in reduction of concomitant AED drug load regardless of whether concomitant AEDs were SCB (+) or SCB (-). These results indicate that addition of lacosamide in patients with focal seizures could allow clinicians to withdraw or reduce the dose of less well-tolerated or less effective AEDs.

Conversion to brivaracetam monotherapy for the treatment of patients with focal seizures: Two double-blind, randomized, multicenter, historical control, Phase III studies.

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) approved for monotherapy (in the USA) and adjunctive treatment of focal (partial-onset) seizures in adults, at a dose range of 50-200 mg/day taken in two equal doses, with a recommended starting dose of 100 mg/day. Two Phase III, randomized, double-blind, multicenter, historical-controlled, conversion-to-monotherapy studies (N01276, NCT00698581; N01306, NCT00699283) were conducted to evaluate the efficacy, safety, and tolerability of conversion to BRV 50 mg/day monotherapy in adults with uncontrolled focal seizures. Patients aged 16-75 years, with 2-40 focal seizures per 4 weeks during an 8-week baseline, and on stable doses of 1-2 AEDs were enrolled. Patients were randomized to BRV 50 or 100 mg/day (3:1) in two equal doses without titration. The treatment period comprised 1-week BRV add-on, 8-week baseline AED tapering, and 8-week BRV monotherapy periods. Primary efficacy endpoint was Kaplan-Meier estimate of the cumulative exit rate due to pre-defined exit criteria at Day 112 (50 mg/day, efficacy population). The upper 95% confidence interval (CI) was compared with the historical control threshold (0.722). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs; intent-to-treat population). After randomization of 150 patients (N01276: 88; N01306: 62), both studies were terminated due to the confounding effects of a higher-than-expected discontinuation rate. For BRV 50 mg/day, ≥1 exit criterion was met by 26/67 (38.8%) patients (study N01276) and 18/45 (40.0%) patients (study N01306). In both studies, the cumulative exit rate was lower than the historical control threshold (N01276: 0.487, 95% CI 0.347, 0.626; N01306: 0.474, 95% CI 0.310, 0.638). However, with maximum 10% censoring due to early withdrawal (sensitivity analysis), cumulative exit rates were above historical control (N01276: 0.652, 95% CI 0.532, 0.772; N01306: 0.704, 95% CI 0.563, 0.844). Overall incidence of TEAEs was 110/150, 73.3% (treatment period); 78/147, 53.1% (baseline AED tapering period); 41/84, 48.8% (BRV monotherapy period). In conclusion, BRV 50 mg/day monotherapy demonstrated an exit rate lower than historical control. Results should be interpreted with caution as, following termination of both studies, patient numbers were too low to evaluate the efficacy of BRV monotherapy. These are the first published safety and tolerability data for BRV monotherapy. Monotherapy was well tolerated, with a relatively low incidence of TEAEs, though this should be interpreted with the caveat that the majority of common TEAEs were likely to have occurred earlier in the course of treatment with BRV. No new safety concerns were identified, supporting the favorable safety profile of BRV observed in adjunctive studies.

Frontal lobe epilepsy manifesting with seizures consisting of isolated vocalization.

Vocalizations may occur in focal epileptic seizures, which typically arise from frontal and temporal regions. They are commonly associated with other motor phenomena such as automatisms, tonic posturing, or head version. We report on a patient whose seizures were documented by video-EEG monitoring, but in whom the observable ictal semiology consisted solely of a brief, monotonous vocalization. Ictal EEGs showed left frontal seizure patterns. Isolated vocalizations can constitute an ictal epileptic event and may be the only observable clinical manifestation of a left frontal lobe epilepsy. [Published with video sequences].

Heart rate increase in otherwise subclinical seizures is different in temporal versus extratemporal seizure onset: support for temporal lobe autonomic influence.

Ictal heart rate was investigated in otherwise subclinical epileptic seizures to test the hypothesis as to whether ictal tachycardia is physiological and not a physical or psychological stress response. In addition, we aimed to evaluate the localizing significance of pure ictal tachycardia. We included 21 epilepsy patients, who showed an ictal EEG seizure pattern during 22, otherwise subclinical seizures. All patients underwent ictal video-EEG recordings to evaluate the possibility of resective epilepsy surgery. The changes in heart rate in these patients were investigated in order to determine their relationship to localization and duration of EEG seizure patterns. Ictal tachycardia was observed in 41% of the otherwise subclinical seizures (nine out of 22), and significantly more often in seizures arising from the temporal lobe than from extratemporal regions (62% versus 11%, p < 0.0018). The seizure duration as defined by EEG was significantly positively correlated with an increase of heart rate (p = 0.043). Ictal heart rate can increase as a result of epileptic activation of autonomic cortex, reflecting a temporal lobe autonomic influence. Thus, measurement of heart rate should be included in the evaluation of otherwise subclinical epileptic seizures, because of its localizing value.

A semiological classification of status epilepticus.

The classification of status epilepticus (SE) has been a subject of discussion for many years, yet no satisfactory agreement has been reached. Due to their complexity, status episodes often defy classification according to the current international classification scheme. The semiological seizure classification (SSC) has been in use in several epilepsy centers for more than a decade, and has proven to be a valid approach to the classification of epileptic seizures. Based on the detailed analysis of more than 100 episodes of SE documented with video-EEG recordings, the authors now present a proposal for a semiological classification of status epilepticus (SCSE). The SCSE reflects the assumption implied by all modern definitions of SE that "there are as many types of status as there are types of seizures" and relies on the same principles as the SSC, focusing on the main clinical manifestations and the evolution of the status episode. The clinical manifestations of SE are subdivided into semiological components and classified along three axes: the type of brain function predominantly compromised by the seizure activity, the body part involved, and the evolution over time. Each axis contains several subcategories, so that many different levels of accuracy are possible. The SCSE, just like the SSC, is meant to be part of a comprehensive epilepsy classification which classifies as independent variables (epileptogenic zone, ictal semiology, etiology, related medical conditions) the main features of the patient's epilepsy, allowing for each variable maximum flexibility.

Naming tools and animals: asymmetries observed during direct electrical cortical stimulation.

Semantically bounded disorders of verbal processing that result in selective dysnomias for items belonging to specific semantic categories have been well documented in lesion studies. Most commonly dissociations between the categories of living versus non-living things have been reported. Processing of living things such as animals seems to be impaired after bilateral lesions, whereas lesions resulting in impairment of processing of non-living things such as tools seem to be restricted to the left hemisphere. In this study, we tested the naming capabilities of epilepsy patients with subdural electrodes implanted for localization of the epileptogenic zone and preoperative mapping of cognitive functions. Tool and animal items were used, and the results show that during stimulation of the left hemisphere dysnomias for tool items were more pronounced than for animal items. This asymmetry is discussed within a model of more widely bilaterally distributed processing of living category members as compared to more restricted left-sided representation of non-living category members.

Clinical features and EEG findings differentiating mesial from neocortical temporal lobe epilepsy.

We evaluated whether mesial temporal lobe epilepsy (MTE) and neocortical temporal lobe epilepsy (NTE) can be distinguished on electroclinical grounds. One hundred and twenty-two consecutive MTE (n = 86) and NTE (n = 36) patients were included in this prospective study. All patients underwent prolonged EEG-video monitoring and high resolution magnetic-resonance imaging (MRI). MTE was defined as epilepsy with purely mesial temporal lesion in the absence of extramesial temporal pathology, based on pre-operative MRI or post-operative histology. NTE was defined as neocortical temporal MRI lesions, depth recorded neocortical temporal seizure onset and lack of mesial temporal lesions on MRI or histology. One thousand two hundred and fourty-nine epileptic seizures were analyzed. Congenital malformation (NTE 19% versus MTE 3%, P < 0.01), nonspecific auras (NTE 25% versus MTE 8%, P < 0.001) and early clonic activity following automatisms (NTE 22% versus MTE 8%, P < 0.03) were more frequent in NTE. In contrast, a history of febrile seizures (MTE 29% versus NTE 3%, P < 0,001), abdominal auras (MTE 62% versus NTE 33%, P < 0.005) and contralateral hand dystonia (MTE 43% versus NTE 22%, P < 0.03) were more often documented in MTE. Interictal epileptiform discharges in MTE occurred predominantly (> 67%) over the ipsilateral mesial temporal regions (MTE 65% versus NTE 33%, P < 0.001). No MTE patient had lateral neocortical temporal spike predominance (NTE 22%, P < 0.001). Multiple logistic regression revealed that a history of febrile seizures, abdominal auras, contralateral dystonic posturing and predominance of ipsilateral mesial temporal spikes point to MTE, with an accuracy of 73% (PPV 81%, NPV 70%). Analyzing clinical and EEG features, particularly the distribution of interictal epileptiform discharges, helps to differentiate between MTE and NTE.

Longterm-habituation of the startle response in mice is stimulus modality, but not context specific.

In mice, the specificity of longterm-habituation (LTH) of startle was tested in two experiments. In two strains of mice (C57Bl/6 and C3H) there was pronounced LTH over 10 days of acoustic stimulation in two different contexts of startle measurement. (We found LTH to be greater after stimulation with 14 kHz sine stimuli compared to noise or tactile stimuli). A change of context showed LTH to be independent of context, i.e., startle LTH in mice is a non-associative learning process. In the second experiment, 9 days of acoustic or tactile stimulation were given to C57B/6 mice. Both stimulus modalities produced LTH. When on the 10th day stimuli of the other modality were given, in both cases the long term habituated group showed no lower startle amplitude than a non-stimulated control group. This indicates LTH is stimulus-modality specific. Altogether, our results show that in mice-very similar to rats-LTH of startle is stimulus modality, but not context specific. In addition we found two indications that the LTH action site is on the sensory branch of the startle circuit.

Quality of life, anxiety and depression in adult patients after add-on of levetiracetam and conversion to levetiracetam monotherapy.

The aim of this study was to investigate the change of health related quality of life (HRQoL), anxiety and depression in adult patients in whom an adjunctive treatment with levetiracetam (LEV) was converted to a LEV monotherapy. A prospective, open, investigator initiated multicenter study enrolled 140 patients in whom LEV was added to the existing antiepileptic medication. A total of 65 patients who benefited from the 16-week add-on treatment with LEV (≥50% seizure reduction) were converted to LEV monotherapy (16-week follow-up). In LEV responders, HRQoL, anxiety and depression improved after add-on of LEV. The subsequent conversion to LEV monotherapy did not lead to a significant change in HRQoL, anxiety and depression. However, comparing baseline with LEV monotherapy, the improvements remained significant for most dimensions of HRQoL and for anxiety and depression. Patients' ratings of efficacy of LEV were related with their HRQoL after the conversion to monotherapy. Add-on therapy of LEV improved HRQoL, anxiety and depression in LEV responders. Conversion to a LEV monotherapy did not inevitably improve HRQoL in LEV responders, but the positive effect was maintained in the majority of the patients. The effects were highly related to seizure reduction.

Long term survival in anti-Hu associated adult neuroblastoma.

We report on a young lady suffering from adult neuroblastoma and anti-Hu associated paraneoplastic encephalomyelitis (PEM) with a tumour free survival of nine years up to now. Treatment included tumour surgery, radiation, high dose chemotherapy, and stem cell transplantation. Serological testing demonstrated a marked decline in anti-Hu antibody titres under therapy, and subsequent disappearance of the antibody 31 months after second tumour resection.