Implications for driving based on the risk of seizures after ischaemic stroke.

BACKGROUND: In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. METHODS: We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs. RESULTS: Seizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0-6 points) had low COSY (0.7%-11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3-13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7-13 points) had the highest risk (14%-92%). CONCLUSIONS: Personalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy.

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Infants, Children, and Adolescents with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy. Consensus methods identified 20 core outcomes. In addition to the outcomes identified for the ICHOM Epilepsy adult standard set, behavioral, motor, and cognitive/language development outcomes were voted as essential for all infants and children with epilepsy. The proposed set of outcomes and measurement methods will facilitate the implementation of the use of patient-centered outcomes in daily practice.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes. Measurement tools were recommended based on their evidence of strong clinical measurement properties, feasibility, and cross-cultural applicability. The essential outcomes included many non-seizure outcomes: anxiety, depression, suicidality, memory and attention, sleep quality, functional status, and the social impact of epilepsy. The proposed set will facilitate the implementation of the use of patient-centered outcomes in daily practice, ensuring holistic care. They also encourage harmonization of outcome measurement, and if widely implemented should reduce the heterogeneity of outcome measurement, accelerate comparative research, and facilitate quality improvement efforts.

The European Academy of Neurology NeuroCOVID-19 Task Force: A lesson for the future.

BACKGROUND: The COVID-19 pandemic has made its mark on world history forever causing millions of deaths, and straining health systems, economies, and societies worldwide. The European Academy of Neurology (EAN) reacted promptly. A special NeuroCOVID-19 Task Force was set up at the beginning of the pandemic to promote knowledge, research, international collaborations, and raise awareness about the prevention and treatment of COVID-19-related neurological issues. METHODS: Activities carried out during and after the pandemic by the EAN NeuroCOVID-19 Task Force are described. The main aim was to review all these initiatives in detail as an overarching lesson from the past to improve the present and be better prepared in case of future pandemics. RESULTS: During the pandemic, the Task Force was engaged in several initiatives: the creation of the EAN NEuro-covid ReGistrY (ENERGY); the launch of several surveys (neurological manifestations of COVID-19 infection; the pandemic's impact on patients with chronic neurological diseases; the pandemic's impact of restrictions for clinical practice, curricular training, and health economics); the publication of position papers regarding the management of patients with neurological diseases during the pandemic, and vaccination hesitancy among people with chronic neurological disorders; and the creation of a dedicated "COVID-19 Breaking News" section in EANpages. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force was immediately engaged in various activities to participate in the fight against COVID-19. The Task Force's concerted strategy may serve as a foundation for upcoming global neurological emergencies.

Temporal lobe epilepsy with GAD antibodies: neurons killed by T cells not by complement membrane attack complex.

Temporal lobe epilepsy (TLE) is one of the syndromes linked to antibodies against glutamic acid decarboxylase (GAD). It has been questioned whether 'limbic encephalitis with GAD antibodies' is a meaningful diagnostic entity. The immunopathogenesis of GAD-TLE has remained enigmatic. Improvement of immunological treatability is an urgent clinical concern. We retrospectively assessed the clinical, MRI and CSF course as well as brain tissue of 15 adult patients with GAD-TLE who underwent temporal lobe surgery. Brain tissue was studied by means of immunohistochemistry, multiplex fluorescent microscopy and transcriptomic analysis for inflammatory mediators and neuronal degeneration. In 10 patients, there was a period of mediotemporal swelling and T2 signal increase; in nine cases this occurred within the first 6 years after symptom onset. This resulted in unilateral or bilateral hippocampal sclerosis; three cases developed hippocampal sclerosis within the first 2 years. All CSF studies done within the first year (n = 6) revealed intrathecal synthesis of immunoglobulin G. Temporal lobe surgeries were done after a median disease duration of 9 years (range 3 weeks to 60 years). Only two patients became seizure-free. Brain parenchyma collected during surgery in the first 6 years revealed high numbers of plasma cells but no signs of antibody-mediated tissue damage. Even more dense was the infiltration by CD8+ cytotoxic T lymphocytes (CTLs) that were seen to locally proliferate. Further, a portion of these cells revealed an antigen-specific resident memory T cell phenotype. Finally, CTLs with cytotoxic granzyme B+ granules were also seen in microglial nodules and attached to neurons, suggesting a CTL-mediated destruction of these cells. With longer disease duration, the density of all lymphocytes decreased. Whole transcriptome analysis in early/active cases (but not in late/inactive stages) revealed 'T cell immunity' and 'Regulation of immune processes' as the largest overrepresented clusters. To a lesser extent, pathways associated with B cells and neuronal degeneration also showed increased representation. Surgically treated patients with GAD-TLE go through an early active inflammatory, 'encephalitic' stage (≤6 years) with CTL-mediated, antigen-driven neuronal loss and antibody-producing plasma cells but without signs of complement-mediated cell death. Subsequently, patients enter an apparently immunologically inactive or low-active stage with ongoing seizures, probably caused by the structural damage to the temporal lobe. 'Limbic encephalitis' with GAD antibodies should be subsumed under GAD-TLE. The early tissue damage explains why immunotherapy does not usually lead to freedom from seizures.

Evaluation of the clinical assessment scale for autoimmune encephalitis (CASE) in a retrospective cohort and a systematic review.

BACKGROUND: Autoimmune encephalitis (AE) poses significant challenges in clinical management, requiring effective monitoring tools for therapeutic success and relapse detection. This study aims to assess the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) as compared to the modified Rankin scale (mRS) in evaluating AE patients and to determine the real-world adoption of the CASE score. METHODS: A retrospective cohort study was conducted on 20 AE patients, assessing clinical data including symptomatology, diagnostic findings, and therapeutic regimens. Furthermore, we performed a systematic review on the test performance criteria and the real-world use of the CASE score. RESULTS: The CASE score showed a higher sensitivity in detecting clinical changes compared to the mRS, with a significant correlation between the two scales throughout the disease course (r = 0.85, p < 0.01). A systematic review of 150 articles revealed widespread adoption of the CASE score, especially in Asian populations, demonstrating high reliability and internal consistency. DISCUSSION: Despite limitations such as retrospective design and small sample size, our findings underscore the CASE score's utility in both clinical practice and research settings. The CASE score emerges as a valuable tool for monitoring AE patients, offering improved sensitivity over existing scales like the mRS. Further validation studies in diverse populations are warranted to establish its broader applicability and inform future therapeutic interventions.

Seizures after Ischemic Stroke: A Matched Multicenter Study.

OBJECTIVE: The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. METHODS: We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. RESULTS: In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. INTERPRETATION: Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy. ANN NEUROL 2021;90:808-820.

Detection of interictal epileptiform discharges in an extended scalp EEG array and high-density EEG-A prospective multicenter study.

OBJECTIVES: High counts of averaged interictal epileptiform discharges (IEDs) are key components of accurate interictal electric source imaging (ESI) in patients with focal epilepsy. Automated detections may be time-efficient, but they need to identify the correct IED types. Thus we compared semiautomated and automated detection of IED types in long-term video-EEG (electroencephalography) monitoring (LTM) using an extended scalp EEG array and short-term high-density EEG (hdEEG) with visual detection of IED types and the seizure-onset zone (SOZ). METHODS: We prospectively recruited consecutive patients from four epilepsy centers who underwent both LTM with 40-electrode scalp EEG and short-term hdEEG with 256 electrodes. Only patients with a single circumscribed SOZ in LTM were included. In LTM and hdEEG, IED types were identified visually, semiautomatically and automatically. Concordances of semiautomated and automated detections in LTM and hdEEG, as well as visual detections in hdEEG, were compared against visually detected IED types and the SOZ in LTM. RESULTS: Fifty-two of 62 patients with LTM and hdEEG were included. The most frequent IED types per patient, detected semiautomatically and automatically in LTM and visually in hdEEG, were significantly concordant with the most frequently visually identified IED type in LTM and the SOZ. Semiautomated and automated detections of IED types in hdEEG were significantly concordant with visually identified IED types in LTM, only when IED types with more than 50 detected single IEDs were selected. The threshold of 50 detected IED in hdEEG was reached in half of the patients. For all IED types per patient, agreement between visual and semiautomated detections in LTM was high. SIGNIFICANCE: Semiautomated and automated detections of IED types in LTM show significant agreement with visually detected IED types and the SOZ. In short-term hdEEG, semiautomated detections of IED types are concordant with visually detected IED types and the SOZ in LTM if high IED counts were detected.

COVID-19 vaccination hesitancy among people with chronic neurological disorders: A position paper.

BACKGROUND AND PURPOSE: Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course. METHODS: In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation. RESULTS: The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals.

A plea for equitable global access to COVID-19 diagnostics, vaccination and therapy: The NeuroCOVID-19 Task Force of the European Academy of Neurology.

Coronavirus disease 2019 (COVID-19), a multi-organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID-19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID-19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long-term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID-19 Task Force intends to raise awareness of the potential impact of COVID-19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.

Déjà vu and the entorhinal cortex: dissociating recollective from familiarity disruptions in a single case patient.

Past research has demonstrated a relationship between déjà vu and the entorhinal cortex in patients with wider medial temporal lobe damage. The aim of the present research was to investigate this crucial link in a patient (MR) with a selective lesion to the left lateral entorhinal cortex to provide a more direct exploration of this relationship. Two experiments investigated the experiences of déjà vécu (using the IDEA questionnaire) and déjà vu (using an adapted DRM paradigm) in MR and a set of matched controls. The results demonstrated that MR had quantitatively more and qualitatively richer recollective experiences of déjà vécu. In addition, under laboratory-based déjà vu conditions designed to elicit both false recollection (critical lures) and false familiarity (weakly-associated lures), MR only revealed greater memory impairments for the latter. The present results are therefore the first to demonstrate a direct relationship between the entorhinal cortex and the experience of both déjà vu and déjà vécu. They furthermore suggest that the entorhinal cortex is involved in both weakly-associative false memory as well as strongly-associative memory under conditions that promote familiarity-based processing.

PET and ictal SPECT can be helpful for localizing epileptic foci.

PURPOSE OF REVIEW: Functional neuroimaging with PET and SPECT is a commonly used tool in presurgical evaluation. The following article reviews the literature of PET and SPECT in presurgical assessment of epilepsies published in the last year. RECENT FINDINGS: FDG-PET adds concomitant information in temporal and extratemporal lobe epilepsy in adults and children. The pattern of hypometabolism in FDG-PET is a good additional predictor or seizure outcome in TLE with mesial temporal sclerosis or negative MRI. There is growing evidence that diagnostic value of FDG-PET increases with postprocessing. Although several methods were applied in the reviewed literature, all of them seem to outperform the visual analysis. Imaging of the epileptic focus with ictal SPECT is depending on short injection latencies. It is particularly useful in patients with nonlesional MRI and mostly of extratemporal localization. Areas of hyperperfusion remote of SOZ are reflecting the epileptic network. Combining more concordant investigations including PET and SPECT in MRI-negative evaluation adds to better presurgical stratification and therefore, better postsurgical outcome. FET-PET shows increased uptake in status epilepticus. SUMMARY: PET and SPECT are important investigations to localize the epileptic focus in temporal lobe and nonlesional extratemporal epilepsies. Postprocessing for both modalities is important to increase diagnostic value.

Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?

PURPOSE: To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy. METHODS: Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed. RESULTS: Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009). CONCLUSIONS: One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.

Depression correlates with quality of life in people with epilepsy independent of the measures used.

PURPOSE: A number of studies have suggested that depressed mood is one of the most important predictors of quality of life (QoL) in patients with epilepsy. However, the QoL measure used in previous studies was limited to the Quality of Life in Epilepsy (QOLIE) scales. It could be questioned whether correlation of QOLIE with measures of depression is influenced by the properties of the instruments used rather than being a valid effect. By using visual analogue scales, the current study aimed to clarify whether depression and QoL are truly correlated in patients with epilepsy. METHODS: Data from a sample of 261 outpatients with epilepsy attending the Epilepsy Clinics of the Atkinson Morley Outpatient Department, St George's Hospital in London, were analyzed. Patients were screened using the European Quality-of-Life scale (EQ-5D-3L) which includes an overall visual analogue score (EQ-VAS), the Emotional Thermometer (ET7), the Beck Depression inventory-II (BDI-II), the Hospital Anxiety and Depression scale (HADS), and the Major Depression inventory (MDI). RESULTS: Depression was found to significantly correlate with EQ-VAS score with r coefficient ranging from 0.42 to 0.51 and r(2) coefficients ranging between 0.18 and 0.26. In addition, we identified patients who were depressed according to DSM-IV criteria (MD) and those with atypical forms of depression (AD). The EQ-5D-3L scores in these subjects compared with those without depression (ND) showed a different impact of AD and MD on QoL. CONCLUSIONS: The relationship between depression and QoL in people with epilepsy has been demonstrated to be a robust and valid effect, not a result of potential bias of the specific measures used. However, the strength of the association is influenced by the individual instrument. Atypical or subsyndromic forms of depression are as relevant as DSM-based depression in terms of impact on QoL.

Selective lesion to the entorhinal cortex leads to an impairment in familiarity but not recollection.

The present research explored the effects of selective impairment to the entorhinal cortex on the processes of familiarity and recollection. To achieve this objective, the performance of patient MR, who has a selective impairment of the left entorhinal cortex, was compared to that of age and IQ-matched controls. Four experiments tested participants' recognition memory for familiar and unfamiliar faces and words. In all experiments, participants studied lists of items and then completed an old/new recognition test in which they also made remember/know/guess judgements. A fifth experiment tested participants' priming associated with the familiarity process. MR had intact performance in both face recognition experiments as well as having intact performance in pseudoword recognition. Crucially, however, in the familiar word experiment, whilst MR performed similarly to control participants in terms of recollection, she showed a marked impairment in familiarity. Furthermore, she also demonstrated a reversed conceptual priming effect. MR's impairment is both material-specific and selective for previously encountered but not new verbal items (pseudowords). These findings provide the first clear evidence that selective impairment of the entorhinal cortex impairs the familiarity process for familiar verbal material whilst leaving recollection intact. These results suggest the entorhinal cortex does not have attributes reflective of both recollection and familiarity as previously assumed, but rather supports context-free long-term familiarity-based recognition memory.

Bringing memory fMRI to the clinic: comparison of seven memory fMRI protocols in temporal lobe epilepsy.

fMRI is increasingly implemented in the clinic to assess memory function. There are multiple approaches to memory fMRI, but limited data on advantages and reliability of different methods. Here, we compared effect size, activation lateralisation, and between-sessions reliability of seven memory fMRI protocols: Hometown Walking (block design), Scene encoding (block design and event-related design), Picture encoding (block and event-related), and Word encoding (block and event-related). All protocols were performed on three occasions in 16 patients with temporal lobe epilepsy (TLE). Group T-maps showed activity bilaterally in medial temporal lobe for all protocols. Using ANOVA, there was an interaction between hemisphere and seizure-onset lateralisation (P = 0.009) and between hemisphere, protocol and seizure-onset lateralisation (P = 0.002), showing that the distribution of memory-related activity between left and right temporal lobes differed between protocols and between patients with left-onset and right-onset seizures. Using voxelwise intraclass Correlation Coefficient, between-sessions reliability was best for Hometown and Scenes (block and event). The between-sessions spatial overlap of activated voxels was also greatest for Hometown and Scenes. Lateralisation of activity between hemispheres was most reliable for Scenes (block and event) and Words (event). Using receiver operating characteristic analysis to explore the ability of each fMRI protocol to classify patients as left-onset or right-onset TLE, only the Words (event) protocol achieved a significantly above-chance classification of patients at all three sessions. We conclude that Words (event) protocol shows the best combination of between-sessions reliability of the distribution of activity between hemispheres and reliable ability to distinguish between left-onset and right-onset patients.

Self-reported aggressiveness during treatment with levetiracetam correlates with depression.

PURPOSE: The purpose of this study was to identify clinical correlates of self-reported aggressiveness (SRA) in patients with epilepsy treated with levetiracetam (LEV) with special reference to the role of depression. METHODS: A consecutive sample of adult outpatients with epilepsy was assessed with the Neurological Disorder Depression Inventory for Epilepsy, the Adverse Event Profile (AEP), and the Emotional Thermometer. RESULTS: From a total sample of 163 consecutive patients treated with LEV, SRA at any level (from rarely a problem to always) was associated with a 7-fold increased risk of being depressed (95% CI: 3.0-17.5; p<0.001). Self-reported aggressiveness was reported as "always" a problem by 9.8% of the patients. In these patients, apart from depression, SRA was associated with high AEP total scores (55.1 vs. 39.3; p<0.001) and polytherapy (43.8% vs. 19.8%; p=0.034). Anxiety scores were not elevated (4.9 vs. 3.6; p=0.183). CONCLUSIONS: Self-reported aggressiveness during treatment with LEV is not an isolated symptom but is associated with depressed mood. Anxiety-mediated mechanisms do not seem to be involved.