Olfactory function in focal epilepsies: Understanding mesial temporal lobe epilepsy beyond the hippocampus

Several lines of research have linked olfactory regions with the pathophysiology of focal epilepsies. Among those regions, the piriform cortex represents the major part of the primary olfactory cortex. According to these data, we raised the hypothesis that in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis exists an interictal dysfunction of olfactory processing that could be more significant compared to patients with extra‐hippocampal focal epilepsy and healthy controls. This could be the consequence of a dysfunctional epileptogenic network that extends beyond the hippocampus and affects other structures, including the piriform cortex. To test this hypothesis, we evaluated the olfactory function with the Sniffin' Sticks test in 32 patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis, 30 patients with extra‐hippocampal focal epilepsy, and 22 healthy controls. Compared to the other study groups, patients with temporal lobe epilepsy due to hippocampal sclerosis showed a basal olfactory dysfunction characterized by an impairment in odor discrimination and odor identification. We also found that high seizure frequency had a strong correlation with the evaluated olfactory tasks. Our results are consistent with neuroimaging and neuropathological data that establish a link between olfactory regions and the pathophysiology of temporal lobe epileps

Bilateral akinetic seizures: A clinical and electroencephalographic description

Purpose: The main feature of akinetic seizures is the inhibition of voluntary movements without impairment of awareness. Most clinical information about akinetic seizures has been obtained from cortical electrical stimulation studies, whereas clinical and video–electroencephalography (EEG) features have not been described thoroughly. Weaimed to analyze clinical and EEG characteristics of bilateral akinetic seizures (BAS).Methods: Patients with BAS were retrospectively identified from 1,858 consecutive video-EEG studies. All patients had ictal video-EEG, comprehensive clinical evaluation, neuropsychological testing, and brain magnetic resonance imaging (MRI).Results: Ten patients (nine men) were identified; mean age was 22.5 years (range 0.3–71 years) at the time of epilepsy onset and 34.9 years (range 5–73 years) at the time of evaluation. BAS was the only seizure type in four patients. BAS consisted of sudden speech and motor arrest in eight patients, whereas in two patients seizures were characterized by abrupt freezing precipitated by gait initiation. Startle precipitated BAS in four patients. Magnetic resonance imaging (MRI) showed mesial frontal lobe lesions in six patients. Epileptiform activity was restricted to the frontal midline electrodes in all patients, with variable extension to frontal regions. In five patients, BAS were initially misdiagnosed as generalized seizures or nonepileptic events. Discussion: BAS should be considered in the differential diagnosis of patients reporting paroxysmal inability to move with preservation of awareness, bearing in mind that these seizures can occur spontaneously or be precipitated by startle. The diagnosis can be achieved with video-EEG monitoring, showing stereotyped semiology and distinctive EEG abnormalities, and is often supported by the presence of lesions involving the frontal lobes

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.This work was supported by a research grant from the Spanish Ministry of Science and Innovation (Grant SAF2011-27920) to I.G.-M. P.C. was supported by a Ramo´n y Cajal Fellowship from the Spanish Ministry of Science and Innovation (RYC-2010-05748). C.P. was supported by Spanish Ministry of Science and Education (AP2009-4131)

A retrospective, multicentre study of perampanel given as monotherapy in routine clinical care in people with epilepsy

PURPOSE: Perampanel is approved for adjunctive treatment of focal seizures, with or without secondarily generalised seizures, and for primary generalised tonic-clonic seizures in people with epilepsy aged ≥12 years. Perampanel was recently approved for monotherapy use for partial seizures in the United States. This study provides insight into the feasibility of perampanel monotherapy in real-world settings. METHODS: This retrospective, non-interventional, multicentre study (NCT02736162) was conducted between January 2013 and March 2016 in specialist epilepsy centres in Europe and Russia. Eligible individuals had a diagnosis of epilepsy and received perampanel primary or secondary monotherapy as routine clinical care. The primary endpoint was proportion of individuals remaining on perampanel monotherapy, after conversion from perampanel adjunctive treatment, at 3, 6, 12, 18 and 24 months (retention rate). RESULTS: Sixty individuals were in the safety set (female, 63%; white, 97%; aged 18 to <65 years, 73%). Most (85%) received secondary monotherapy with perampanel. At study cut-off, 68% of individuals were continuing on perampanel monotherapy (secondary monotherapy: 55%). The median duration of retention was not calculable due to the high number of individuals ongoing on monotherapy. Twelve individuals had treatment-emergent adverse events that started during perampanel monotherapy, the most frequent was dizziness (5%). One serious treatment-emergent adverse event was reported (pneumonia during adjunctive perampanel treatment). CONCLUSIONS: In this small retrospective study of individuals who received perampanel monotherapy, the majority maintained monotherapy. Perampanel monotherapy may be an achievable option in some people with epilepsy

The burden of epilepsy and unmet need in people with focal seizures

BACKGROUND: Epilepsy is one of the most common neurological conditions worldwide. As a chronic condition, epilepsy imposes a significant burden on people with epilepsy and society. We aimed to assess the burden and unmet need of individuals with epilepsy and their caregivers, focusing on focal seizures, the main type of seizure in adults and children. METHODS: A targeted evidence review of the burden of epilepsy, focusing on focal seizures, was conducted to identify articles reporting: epidemiology, mortality, morbidity, quality of life (QoL), and costs. RESULTS: Focal seizures affect up to ∼61% of people with epilepsy. They are associated with an increased risk of injury and premature death than the general population. People with epilepsy also have high comorbidity, particularly depression, anxiety, and cognitive impairments. Higher seizure frequency, adverse treatment events, and employment concerns reduce QoL. A reduction in caregivers' QoL is also often reported. Epilepsy requires long-term treatment accounting for high individual costs. Hospitalizations and antiseizure medications (ASMs) are the leading cost drivers of inpatient management and indirect costs with high unemployment rates, particularly in drug-resistant populations. Despite the advent of new treatments, a high unmet need remains unaddressed; approximately 40% of people with epilepsy are drug-resistant, further increasing the risks associated with epilepsy. CONCLUSIONS: Our findings highlight a substantial burden of illness and unmet needs in individuals with focal seizures, especially those with drug-resistant epilepsy. Suboptimal treatment options negatively impact QoL and, consequently, a sizeable economic burden indicating the need for new treatments and prioritizing this condition

Morphometric and microstructural characteristics of hippocampal subfields in mesial temporal lobe epilepsy and their correlates with mnemonic discrimination.

Pattern separation (PS) is a fundamental aspect of memory creation that defines the ability to transform similar memory representations into distinct ones, so they do not overlap when storing and retrieving them. Experimental evidence in animal models and the study of other human pathologies have demonstrated the role of the hippocampus in PS, in particular of the dentate gyrus (DG) and CA3. Patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HE) commonly report mnemonic deficits that have been associated with failures in PS. However, the link between these impairments and the integrity of the hippocampal subfields in these patients has not yet been determined. The aim of this work is to explore the association between the ability to perform mnemonic functions and the integrity of hippocampal CA1, CA3, and DG in patients with unilateral MTLE-HE. To reach this goal we evaluated the memory of patients with an improved object mnemonic similarity test. We then analyzed the hippocampal complex structural and microstructural integrity using diffusion weighted imaging. Our results indicate that patients with unilateral MTLE-HE present alterations in both volume and microstructural properties at the level of the hippocampal subfields DG, CA1, CA3, and the subiculum, that sometimes depend on the lateralization of their epileptic focus. However, none of the specific changes was found to be directly related to the performance of the patients in a pattern separation task, which might indicate a contribution of various alterations to the mnemonic deficits or the key contribution of other structures to the function. we established for the first time the alterations in both the volume and the microstructure at the level of the hippocampal subfields in a group of unilateral MTLE patients. We observed that these changes are greater in the DG and CA1 at the macrostructural level, and in CA3 and CA1 in the microstructural level. None of these changes had a direct relation to the performance of the patients in a pattern separation task, which suggests a contribution of various alterations to the loss of function

A model for cyclotron resonance scattering features

(abbreviated version of the abstract) We study the physics of cyclotron line formation in the high-energy spectra of accreting X-ray pulsars using Monte Carlo methods, assuming that the line-forming region is a low-density electron plasma in a sub-critical magnetic field. We investigate the dependence of the shape of the fundamental line on angle, geometry, optical depth and temperature. We also discuss variations of the line ratios for non-uniform magnetic fields. These numerical predictions for the line profiles are linked to results from observational data analysis using an XSPEC model based on the Monte Carlo simulations. We apply this model to observational data from RXTE and INTEGRAL. The predicted strong emission wings of the fundamental cyclotron feature are not found in observational data, hinting at a bottom illuminated slab geometry for line formation.Comment: 16 pages, 15 figures, Astron. Astrophys. (in press

The contribution of fenfluramine to the treatment of Dravet syndrome in Spain through Multi-Criteria Decision Analysis

Introduction: Dravet Syndrome (DS) is a severe, developmental epileptic encephalopathy (DEE) that begins in infancy and is characterized by pharmaco-resistant epilepsy and neurodevelopmental delay. Despite available antiseizure medications (ASMs), there is a need for new therapeutic options with greater efficacy in reducing seizure frequency and with adequate safety and tolerability profiles.Fenfluramine is a new ASM for the treatment of seizures associated with DS as add-on therapy to other ASMs for patients aged 2 years and older. Fenfluramine decreases seizure frequency, prolongs periods of seizure freedom potentially helping to reduce risk of Sudden Unexpected Death in Epilepsy (SUDEP) and improves patient cognitive abilities positively impacting on patients' Quality of Life (QoL).Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. The aim of this study was to determine the relative value contribution of fenfluramine for the treatment of DS in Spain using MCDA.Method: A literature review was performed to populate an adapted a MCDA framework for orphan-drug evaluation in Spain. A panel of ten Spanish experts, including neurologists, hospital pharmacists, patient representatives and decision-makers, scored four comparative evidence matrices.Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. Results: Dravet syndrome is considered a severe, rare disease with significant unmet needs. Fenfluramine is perceived to have a higher efficacy profile than all available alternatives, with a better safety profile than stiripentol and topiramate and to provide improved QoL versus studied alternatives. Fenfluramine results in lower other medical costs in comparison with stiripentol and clobazam. Participants perceived that fenfluramine could lead to indirect costs savings compared to available alternatives due to its efficacy in controlling seizures. Overall, fenfluramine's therapeutic impact on patients with DS is considered high and supported by high-quality evidence.Conclusions: Based on reflective MCDA, fenfluramine is considered to add greater benefit in terms of effi-cacy, safety and QoL when compared with available ASMs.(c) 2022 The Authors. Published by Elsevier Inc

Epilepsy and cannabidiol:a guide to treatment

The growing interest in cannabidiol (CBD), specifically a pure form of CBD, as a treatment for epilepsy, among other conditions, is reflected in recent changes in legislation in some countries. Although there has been much speculation about the therapeutic value of cannabis-based products as an anti-seizure treatment for some time, it is only within the last two years that Class I evidence has been available for a pure form of CBD, based on placebo-controlled RCTs for patients with Lennox-Gastaut syndrome and Dravet syndrome. However, just as we are beginning to understand the significance of CBD as a treatment for epilepsy, in recent years, a broad spectrum of products advertised to contain CBD has emerged on the market. The effects of these products are fundamentally dependent on the purity, preparation, and concentration of CBD and other components, and consensus and standardisation are severely lacking regarding their preparation, composition, usage and effectiveness. This review aims to provide information to neurologists and epileptologists on the therapeutic value of CBD products, principally a purified form, in routine practice for patients with intractable epilepsy