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The function of the claustrum and its role in neurological disorders remains a subject of interest in the field of neurology. Given the claustrum’s susceptibility to seizure-induced damage, there is speculation that it could serve as a node in a dysfunctional epileptic network. This perspective article aims to address a pivotal question: Does the claustrum play a role in epilepsy? Building upon existing literature, we propose the following hypotheses for the involvement of the claustrum in epilepsy: (1) Bilateral T2/FLAIR magnetic resonance imaging (MRI) hyperintensity of the claustrum after status epilepticus represents a radiological phenomenon that signifies inflammation-related epileptogenesis; (2) The ventral claustrum is synonymous with a brain area known as ‘area tempestas,’ an established epileptogenic center; (3) The ventral subsector of the claustrum facilitates seizure generalization/propagation through its connections with limbic and motor-related brain structures; (4) Disruption of claustrum connections during seizures might contribute to the loss of consciousness observed in impaired awareness seizures; (5) Targeting the claustrum therapeutically could be advantageous in seizures that arise from limbic foci. Together, evidence from both clinical case reports and animal studies identify a significant role for the ventral claustrum in the generation, propagation, and intractable nature of seizures in a subset of epilepsy syndromes.

Glutamate is the brain’s main excitatory neurotransmitter. Glutamatergic neurons primarily compose basic neuronal networks, especially in the cortex. An imbalance of excitatory and inhibitory activities may result in epilepsy or other neurological and psychiatric conditions. Among glutamate receptors, AMPA receptors are the predominant mediator of glutamate-induced excitatory neurotransmission and dictate synaptic efficiency and plasticity by their numbers and/or properties. Therefore, they appear to be a major drug target for modulating several brain functions. Perampanel (PER) is a highly selective, noncompetitive AMPA antagonist approved in several countries worldwide for treating different types of seizures in various epileptic conditions. However, recent data show that PER can potentially address many other conditions within epilepsy and beyond. From this perspective, this review aims to examine the new preclinical and clinical studies—especially those produced from 2017 onwards—on AMPA antagonism and PER in conditions such as mesial temporal lobe epilepsy, idiopathic and genetic generalized epilepsy, brain tumor-related epilepsy, status epilepticus, rare epileptic syndromes, stroke, sleep, epilepsy-related migraine, cognitive impairment, autism, dementia, and other neurodegenerative diseases, as well as provide suggestions on future research agenda aimed at probing the possibility of treating these conditions with PER and/or other AMPA receptor antagonists.

Introduction:The COVID-19 pandemic and its countermeasures have created changes in both life and healthcare. With the prioritization of COVID-19-related management, the risks and experiences of patients suffering from rare conditions, such as dystonia, during the pandemic remain understudied.Materials and MethodsUsing a framework analysis of a nationwide qualitative online survey, we sought to explore the perspectives of patients with dystonia on their clinical assistance and possible unmet needs during the first pandemic wave. An online survey consisting of 37 items (such as demographic characteristics, dystonia-related features, neurological service provision, therapeutic relationship with the neurologist, perceptions related to virus infection, perceptions about healthcare-related needs, work-related questions, requesting information, and seeking support during the pandemic) was carried out using both close and open-ended questions.ResultsResponses from 62 participants were collected, with most of them from the red zones in Italy, where they were confined indoors. Social isolation was a relevant stressor. Motor and non-motor symptoms increased with detrimental consequences for patients' job and daily functionality. Outpatient clinics and rehabilitation sessions were temporarily shut down, and even telephone/mail support was sparse. Despite efforts, patients felt alone in dealing with dystonia.ConclusionThe first wave of the pandemic and its related restrictions had detrimental consequences for people living with dystonia, and their relevant needs remained unmet. These findings may contribute to implementing remedial healthcare provisions in this pandemic or in future pandemics.

Objective: To evaluate local and distant blood oxygen level dependent (BOLD) signal changes related to interictal epileptiform discharges (IED) in drug-resistant temporal lobe epilepsy (TLE).Methods: Thirty-three TLE patients undergoing EEG–functional Magnetic Resonance Imaging (fMRI) as part of the presurgical workup were consecutively enrolled. First, a single-subject spike-related analysis was performed: (a) to verify the BOLD concordance with the presumed Epileptogenic Zone (EZ); and (b) to investigate the Intrinsic Connectivity Networks (ICN) involvement. Then, a group analysis was performed to search for common BOLD changes in TLE.Results: Interictal epileptiform discharges were recorded in 25 patients and in 19 (58%), a BOLD response was obtained at the single-subject level. In 42% of the cases, BOLD changes were observed in the temporal lobe, although only one patient had a pure concordant finding, with a single fMRI cluster overlapping (and limited to) the EZ identified by anatomo-electro-clinical correlations. In the remaining 58% of the cases, BOLD responses were localized outside the temporal lobe and the presumed EZ. In every patient, with a spike-related fMRI map, at least one ICN appeared to be involved. Four main ICNs were preferentially involved, namely, motor, visual, auditory/motor speech, and the default mode network. At the single-subject level, EEG–fMRI proved to have high specificity (above 65%) in detecting engagement of an ICN and the corresponding ictal/postictal symptom, and good positive predictive value (above 67%) in all networks except the visual one. Finally, in the group analysis of BOLD changes related to IED revealed common activations at the right precentral gyrus, supplementary motor area, and middle cingulate gyrus.Significance: Interictal temporal spikes affect several distant extra-temporal areas, and specifically the motor/premotor cortex. EEG–fMRI in patients with TLE eligible for surgery is recommended not for strictly localizing purposes rather it might be useful to investigate ICNs alterations at the single-subject level.

Ictal respiratory changes have been mainly described following generalized tonic-clonic seizures and recently considered to be a biomarker to assess the risk of sudden unexplained death in epilepsy (SUDEP). Nonetheless, modification of respiratory pattern can be related also to focal seizures, especially arising from the temporal lobe. Changes in cardiac function such as tachycardia or bradycardia could be often associated. We report a short case series of four patients with temporal lobe epilepsy admitted to our Epilepsy Monitoring Unit (EMU) presenting with an ictal central apnea as the first clinical manifestation of their seizures. None of these patients was aware of the occurrence of respiratory arrest. Age at onset ranged from 15 to 29 years. One patient had seizures with prolonged central apnea accompanied by a significant decrease in oxygen saturation. Neuroimaging in two patients showed alterations of mesial temporal lobe structures, including the amygdala. Recent neurophysiological studies supported the existence of a cortical network involving the limbic system that modulates downstream brainstem respiratory centers. Monitoring for respiratory changes and oxygen saturation in focal seizures is warranted for their potential value in identifying the epileptogenic zone and for a better understanding of ictal respiratory changes that could potentially define a subgroup of patients with high risk of seizure-related autonomic changes.

The developmental and epileptic encephalopathies (DEE) are the most severe group of epilepsies. Recently, NEXMIF mutations have been shown to cause a DEE in females, characterized by myoclonic–atonic epilepsy and recurrent nonconvulsive status. Here we used advanced neuroimaging techniques in a patient with a novel NEXMIF de novo mutation presenting with recurrent absence status with eyelid myoclonia, to reveal brain structural and functional changes that can bring the clinical phenotype to alteration within specific brain networks. Indeed, the alterations found in the patient involved the visual pericalcarine cortex and the middle frontal gyrus, regions that have been demonstrated to be a core feature in epilepsy phenotypes with visual sensitivity and eyelid myoclonia with absences.

Background: Platelet function testing is a valid tool to investigate the clinical response to antiplatelet therapy in different clinical settings; in particular, it might supply helpful information in patients with cerebrovascular disease. Oral antiplatelet treatment, such as Aspirin (ASA) and Clopidogrel, is the gold standard in secondary stroke prevention of non-cardiogenic ischemic stroke; conversely, its application as a primary prevention therapy is not routinely recommended in patients with vascular risk factors. Multiple electrode platelet aggregometry (MEA) impedance aggregometer is a validated device to test platelet inhibition induced by ASA or Clopidogrel.Case Report: We report the case of a 78-year-old patient without relevant clinical history, taking ASA as primary prevention strategy, who was admitted for sudden onset of dysarthria and left facial hyposthenia during physical effort. Brain CT revealed two small subcortical bilateral spontaneous intracranial hemorrhages. Platelet aggregometry with MEA performed upon admission revealed a very strong platelet inhibition induced by ASA (result of the ASPI Test was 5 U, consistent with an ultra-responsiveness to ASA, and the cutoff value of correct responsiveness is

Valproate is a drug widely used to treat epilepsy, bipolar disorder, and occasionally to prevent migraine headache. Despite its clinical efficacy, prenatal exposure to valproate is associated with neurodevelopmental impairments and its use in children and adults was associated with rare cases of reversible brain atrophy and ventricular enlargement. To determine whether valproate use is related with structural brain changes we examined through a cross-sectional study cortical and subcortical structures in a group of 152 people with epilepsy and a normal clinical brain MRI. Patients were grouped into those currently using valproate (n = 54), those taking drugs other than valproate (n = 47), and drug-naïve patients (n = 51) at the time of MRI, irrespectively of their epilepsy syndrome. Cortical thickness and subcortical volumes were analyzed using Freesurfer, version 5.0. Subjects exposed to valproate (either in mono- or polytherapy) showed reduced cortical thickness in the occipital lobe, more precisely in the cuneus bilaterally, in the left lingual gyrus, and in left and right pericalcarine gyri when compared to patients who used other antiepileptic drugs, to drug-naïve epilepsy patients, and to healthy controls. Considering the subgroup of patients using valproate monotherapy (n = 25), both comparisons with healthy controls and drug-naïve groups confirmed occipital lobe cortical thickness reduction. Moreover, patients using valproate showed increased left and right lateral ventricle volume compared to all other groups. Notably, subjects who were non-valproate users at the time of MRI, but who had valproate exposure in the past (n = 27) did not show these cortical or subcortical brain changes. Cortical changes in the posterior cortex, particularly in the visual cortex, and ventricular enlargement, are present in people with epilepsy using valproate, independently from clinical and demographical variables. These findings are relevant both for the efficacy and adverse events profile of valproate use in people with epilepsy.

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common type of “self-limited focal epilepsies.” In its typical presentation, CECTS is a condition reflecting non-lesional cortical hyperexcitability of rolandic regions. The benign evolution of this disorder is challenged by the frequent observation of associated neuropsychological deficits and behavioral impairment. The abundance (or frequency) of interictal centrotemporal spikes (CTS) in CECTS is considered a risk factor for deficits in cognition. Herein, we captured the hemodynamic changes triggered by the CTS density measure (i.e., the number of CTS for time bin) obtained in a cohort of CECTS, studied by means of video electroencephalophy/functional MRI during quite wakefulness. We aim to demonstrate a direct influence of the diurnal CTS frequency on epileptogenic and cognitive networks of children with CECTS. A total number of 8,950 CTS (range between 27 and 801) were recorded in 23 CECTS (21 male), with a mean number of 255 CTS/patient and a mean density of CTS/30 s equal to 10,866 ± 11.46. Two independent general linear model models were created for each patient based on the effect of interest: “individual CTS” in model 1 and “CTS density” in model 2. Hemodynamic correlates of CTS density revealed the involvement of a widespread cortical–subcortical network encompassing the sensory-motor cortex, the Broca's area, the premotor cortex, the thalamus, the putamen, and red nucleus, while in the CTS event-related model, changes were limited to blood–oxygen-level-dependent (BOLD) signal increases in the sensory-motor cortices. A linear relationship was observed between the CTS density hemodynamic changes and both disease duration (positive correlation) and age (negative correlation) within the language network and the bilateral insular cortices. Our results strongly support the critical role of the CTS frequency, even during wakefulness, to interfere with the normal functioning of language brain networks.