Irene García-Morales

Psychiatric comorbidities in epilepsy: identification and treatment.

Introduction:The relationship between epilepsy and psychiatric disorders, as well as their reciprocal influence, has been confirmed in several studies. The diagnosis of these psychiatric comorbidities becomes particularly complex, for clinical manifestations vary and patients may not fulfil the criteria of traditional diagnostic classifications. Results:Mood disorders are the more frequent conditions associated with epilepsy, followed by anxiety, attention-deficit, psychotic and personality disorders. Patients with focal epilepsies, and mainly those with temporal and frontal lobe epilepsy, have a greater incidence of depression, anxiety or psychosis, compared with the general population. For a long time, patients and physicians tended to focus solely on the control of epileptic seizures, while disregarding the presence of comorbid psychiatric symptoms and disorders. Recognition of their negative impact in the life of patients with epilepsy in recent years has highlighted the need for their early identification with a careful psychiatric history or, at the least, to screen for the presence of psychiatric symptoms with objective scales. Furthermore, the identification of psychiatric symptoms plays an important role in the choice of antiepileptic drugs as some are known to have positive or negative psychotropic effects. Conclusion:An early diagnosis of comorbid psychiatric disorders and a multidisciplinary approach in the evaluation and management of these patients result in the selection of an optimal comprehensive treatment.

Validation of the Italian version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)

The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was developed for the rapid detection of a major depressive episode in people with epilepsy. It has been proven to be a user-friendly screening instrument. This study describes the development, validation, and psychometric properties of the Italian version of the NDDI-E. A consecutive sample of 120 outpatients with epilepsy has been assessed using the M.I.N.I. Plus version 5.0.0 and the NDDI-E. All patients had no major difficulties in understanding or answering the questions of the Italian version. Cronbachs alpha coefficient was 0.851. Receiver operating characteristic analysis showed an area under the curve of 0.943 (CI95%=0.902-0.985; SE 0.021; p<0.001), a cut off score of 13, a sensitivity of 86.2%, a specificity of 89%, a positive predictive value of 71.4%, and a negative predictive value of 95.3%.

Remote Effects of Hippocampal Sclerosis on Effective Connectivity during Working Memory Encoding: A Case of Connectional Diaschisis?

Accumulating evidence suggests a role for the medial temporal lobe (MTL) in working memory (WM). However, little is known concerning its functional interactions with other cortical regions in the distributed neural network subserving WM. To reveal these, we availed of subjects with MTL damage and characterized changes in effective connectivity while subjects engaged in WM task. Specifically, we compared dynamic causal models, extracted from magnetoencephalographic recordings during verbal WM encoding, in temporal lobe epilepsy patients (with left hippocampal sclerosis) and controls. Bayesian model comparison indicated that the best model (across subjects) evidenced bilateral, forward, and backward connections, coupling inferior temporal cortex (ITC), inferior frontal cortex (IFC), and MTL. MTL damage weakened backward connections from left MTL to left ITC, a decrease accompanied by strengthening of (bidirectional) connections between IFC and MTL in the contralesional hemisphere. These findings provide novel evidence concerning functional interactions between nodes of this fundamental cognitive network and sheds light on how these interactions are modified as a result of focal damage to MTL. The findings highlight that a reduced (top-down) influence of the MTL on ipsilateral language regions is accompanied by enhanced reciprocal coupling in the undamaged hemisphere providing a first demonstration of “connectional diaschisis.”

Efficacy of intravenous levetiracetam as an add-on treatment in status epilepticus: A multicentric observational study

INTRODUCTION Treatment of status epilepticus (SE) has not changed in the last few decades, benzodiazepines plus phenytoin being the most common first line treatment. Intravenous levetiracetam (ivLEV) is a new antiepileptic drug with interesting properties for SE. MATERIAL AND METHODS Efficacy and effectiveness of ivLEV in SE were assessed in an observational, multicentric and retrospective study. Efficacy was defined as cessation of seizures in the 24h subsequent to starting ivLEV, with no need of any further antiepileptic drug. All patients were treated following the standard protocol (benzodiazepines plus phenytoin or valproate). ivLEV was used as add-on therapy, except in those cases with contraindication for the standard protocol, when it was administered earlier. RESULTS 40 patients were included, 57% men, with a mean age of 63 years. The most common type of SE was partial convulsive (90%). ivLEV was effective in approximately half of the patients (57.5%), in a mean time of 14.4h. ivLEV was used as add-on treatment in 26 patients (after benzodiazepines plus phenytoin, valproate or both) with an efficacy of 46.1%, and as early treatment (pretreatment with benzodiazepines or nothing) in 14 patients with an efficacy of 78.5% (p 0.048). Adverse events were observed in 15% of patients. CONCLUSIONS ivLEV was an effective antiepileptic drug for SE, but its efficacy depends on the timing of its administration, being more effective when used as early treatment, and less effective as add-on treatment.

Network reconfiguration and working memory impairment in mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (mTLE) is the most prevalent form of focal epilepsy, and hippocampal sclerosis (HS) is considered the most frequent associated pathological finding. Recent connectivity studies have shown that abnormalities, either structural or functional, are not confined to the affected hippocampus, but can be found in other connected structures within the same hemisphere, or even in the contralesional hemisphere. Despite the role of hippocampus in memory functions, most of these studies have explored network properties at resting state, and in some cases compared connectivity values with neuropsychological memory scores. Here, we measured magnetoencephalographic responses during verbal working memory (WM) encoding in left mTLE patients and controls, and compared their effective connectivity within a frontotemporal network using dynamic causal modelling. Bayesian model comparison indicated that the best model included bilateral, forward and backward connections, linking inferior temporal cortex (ITC), inferior frontal cortex (IFC), and the medial temporal lobe (MTL). Test for differences in effective connectivity revealed that patients exhibited decreased ipsilesional MTL-ITC backward connectivity, and increased bidirectional IFC-MTL connectivity in the contralesional hemisphere. Critically, a negative correlation was observed between these changes in patients, with decreases in ipsilesional coupling among temporal sources associated with increases contralesional frontotemporal interactions. Furthermore, contralesional frontotemporal interactions were inversely related to task performance and level of education. The results demonstrate that unilateral sclerosis induced local and remote changes in the dynamic organization of a distributed network supporting verbal WM. Crucially, pre-(peri) morbid factors (educational level) were reflected in both cognitive performance and (putative) compensatory changes in physiological coupling.

Anterobasal Temporal Lobe Lesions Alter Recurrent Functional Connectivity within the Ventral Pathway during Naming

An increasing amount of evidence supports a crucial role for the anterior temporal lobe (ATL) in semantic processing. Critically, a selective disruption of the functional connectivity between left and right ATLs in patients with chronic aphasic stroke has been illustrated. The aim of the current study was to evaluate the consequences that lesions on the ATL have on the neurocognitive network supporting semantic cognition. Unlike previous work, in this magnetoencephalography study we selected a group of patients with small lesions centered on the left anteroventral temporal lobe before surgery. We then used an effective connectivity method (i.e., dynamic causal modeling) to investigate the consequences that these lesions have on the functional interactions within the network. This approach allowed us to evaluate the directionality of the causal interactions among brain regions and their associated connectivity strengths. Behaviorally, we found that semantic processing was altered when patients were compared with a strictly matched group of controls. Dynamic causal modeling for event related responses revealed that picture naming was associated with a bilateral frontotemporal network, encompassing feedforward and feedback connections. Comparison of specific network parameters between groups revealed that patients displayed selective network adjustments. Specifically, backward connectivity from anterior to posterior temporal lobe was decreased in the ipsilesional hemisphere, whereas it was enhanced in the contralesional hemisphere. These results reinforce the relevance of ATL in semantic memory, as well as its amodal organization, and highlight the role of feedback connections in enabling the integration of the semantic information.

Early clinical experience with lacosamide as adjunctive therapy in patients with refractory focal epilepsy and nocturnal seizures

This retrospective study reports the early experience with lacosamide (LCM) as adjunctive therapy in Spanish patients with refractory focal epilepsy. Sixty patients (mean age 38.3 years, 54% women, mean epilepsy duration 27.2 years, mean seizure rate 9.7/month, and 28% with mainly nocturnal seizures) taking ≥2 antiepileptic drugs (mean 2.2) were included. LCM maintenance doses were 200, 300, 400, and 500mg/day in 31, 16, 10, and 3 patients, respectively. Patients were followed up for 13-24 months. Twenty-eight patients (47%) reported a ≥50% reduction in seizure frequency. A ≥50% reduction in seizure frequency was reported by 65% and 40% of patients in the nocturnal seizure and diurnal seizure subgroups, respectively (p>0.05). Of the 28 responders, 2 achieved stable periods of seizure freedom of 6 and 11 months after starting LCM. Twenty patients (33%) reported drug-related adverse events (AEs); the most common was dizziness (16 patients). LCM was withdrawn in 8 patients (13%). There were no serious AEs. These results support the efficacy and safety of adjunctive LCM in patients with partial-onset seizures.

A clinical and magnetoencephalography study of MRI-negative startle epilepsy

OBJECTIVE The goal of this study was to investigate clinical findings, ictal semiology, and results of video/electroencephalography (video/EEG), and magnetoencephalography (MEG) in patients with startle epilepsy and normal brain MRI. METHODS Four patients (mean age 12.5 years) with startle epilepsy were investigated with MRI, video/EEG, and MEG. RESULTS Epilepsy diagnosis was established in childhood, and all had spontaneous and reflex seizures. Reflex seizures were triggered by sudden, unexpected sounds and tactile stimuli. The neurological examinations and MRIs were normal. MEG recordings showed focal epileptiform activity. An ictal MEG was obtained in one patient. Source modeling yielded dipole sources in right central frontal region. CONCLUSION The present study demonstrates that the origin of epileptiform activity in startle epilepsy can be localized in brain areas associated with supplementary motor seizures, even in patients with normal brain MRI. MEG adds complementary information to the localization of epileptiform activity and can be useful in planning invasive studies in cases evaluated for epilepsy surgery.

Antiepileptic drugs: from scientific evidence to clinical practice.

Introduction:Evidence-based medicine establishes guidelines for clinical decision-making in which priority is given to processes that have the highest level of evidence. Although these guidelines provide valuable general guidance, the information is partial, because oftentimes obtaining evidence on antiepileptic drugs is promoted by commercial expectations and not by clinical priorities. Furthermore, the guidelines tend to classify different types of epilepsy into large groups, often without contemplating the different syndromes. Expert opinions are subject to criticism on the basis of methodology and their authoritarian aspect, although they can supplement medical literature and advice on specific clinical situations quickly and efficiently. Objectives:This review seeks to incorporate scientific evidence and expert opinion into drug treatment for epilepsy. Methods:To analyze this issue, a review of the literature was conducted by means of PubMed searches. Conclusion:We have found that in all types of epilepsy [except in focal epilepsy in children where a new drug (oxcarbamazepine) is considered to be the first choice for initial treatment], classic drugs (valproic acid in idiopathic generalized epilepsy and carbamazepine in focal epilepsy) are recommended as long as there are no contraindications due to adverse effects or concomitant use of other drugs that interact with the antiepileptics. However, despite the general recommendations, it can be deduced from the studies and reflections on the subject that the decision as to whether to start treatment or not, as well as the drug of choice, must be made on a case-by-case basis, taking into account the patients personal and social circumstances.

Modulation of medial temporal lobe activity in epilepsy patients with hippocampal sclerosis during verbal working memory.

It has been traditionally assumed that medial temporal lobe (MTL) is not required for working memory (WM). However, animal lesion and electrophysiological studies and human neuropsychological and neuroimaging studies have provided increasing evidences of a critical involvement of MTL in WM. Based on previous findings, the central aim of this study was to investigate the contribution of the MTL to verbal WM encoding. Here, we used magnetoencephalography (MEG) to compare the patterns of MTL activation of 9 epilepsy patients suffering from left hippocampal sclerosis with those of 10 healthy matched controls while they performed a verbal WM task. MEG recordings allow detailed tracking of the time course of MTL activation. We observed impaired WM performance associated with changes in the dynamics of MTL activity in epilepsy patients. Specifically, whereas patients showed decreased activity in damaged MTL, activity in the contralateral MTL was enhanced, an effect that became significant in the 600- to 700-ms interval after stimulus presentation. These findings strongly support the crucial contribution of MTL to verbal WM encoding and provide compelling evidence for the proposal that MTL contributes to both episodic memory and WM. Whether this pattern is signaling reorganization or a normal use of a damaged structure is discussed.