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)

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

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

Aversive memory formation in humans involves an amygdala-hippocampus phase code

Memory for aversive events is central to survival but can become maladaptive in psychiatric disorders. Memory enhancement for emotional events is thought to depend on amygdala modulation of hippocampal activity. However, the neural dynamics of amygdala-hippocampal communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, here we show that successful emotional memory encoding depends on the amygdala theta phase to which hippocampal gamma activity and neuronal firing couple. The phase difference between subsequently remembered vs. not-remembered emotional stimuli translates to a time period that enables lagged coherence between amygdala and downstream hippocampal gamma. These results reveal a mechanism whereby amygdala theta phase coordinates transient amygdala -hippocampal gamma coherence to facilitate aversive memory encoding. Pacing of lagged gamma coherence via amygdala theta phase may represent a general mechanism through which the amygdala relays emotional content to distant brain regions to modulate other aspects of cognition, such as attention and decision-making

Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome A Randomized Clinical Trial

Question Is adjunctive cannabidiol at doses of 10 and 20 mg/kg/d superior to placebo in reducing convulsive seizure frequency in patients with Dravet syndrome? Findings This double-blind clinical trial randomized 199 children with Dravet syndrome to cannabidiol (10 or 20 mg/kg/d) or matched placebo for 14 weeks. Convulsive seizure frequency compared with baseline was reduced by 48.7% in the 10-mg/kg/d cannabidiol group and 45.7% in the 20-mg/kg/d cannabidiol group vs 26.9% in the placebo group. Meaning Both doses of adjunctive cannabidiol were similarly efficacious in reducing convulsive seizures associated with Dravet syndrome

Aphasic seizures in patients with temporopolar and anterior temporobasal lesions: a video-EEG study

Studies of patients with temporal lobe epilepsy provide few descriptions of seizures that arise in the temporopolar and the anterior temporobasal brain region. Based on connectivity, it might be assumed that the semiology of these seizures is similar to that of medial temporal lobe epilepsy. However, accumulating evidence suggests that the anterior temporobasal cortex may play an important role in the language system, which could account for particular features of seizures arising here. We studied the electroclinical features of seizures in patients with circumscribed temporopolar and temporobasal lesions in order to identify specific features that might differentiate them from seizures that originate in other temporal areas. Among 172 patients with temporal lobe seizures registered in our epilepsy unit in the last 15 years, 15 (8.7%) patients had seizures caused by temporopolar or anterior temporobasal lesions (11 left-sided lesions). The main finding in our study is that patients with left-sided lesions had aphasia during their seizures as the most prominent feature. In addition, while all patients showed normal to high intellectual functioning in standard neuropsychological testing, semantic impairment was found in a subset of 9 patients with left-sided lesions. This case series demonstrates that aphasic seizures without impairment of consciousness can result from small, circumscribed left anterior temporobasal and temporopolar lesions. Thus, the presence of speech manifestation during seizures should prompt detailed assessment of the structural integrity of the basal surface of the temporal lobe in addition to the evaluation of primary language areas