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Purpose: we characterized multifocal myoclonus in Dravet syndrome (DS) that was never systematically typified before., Methods: we studied EEG-EMG recordings of 19 consecutive patients, aged 2-29 years, with DS associated with SCN1A gene mutations to detect and evaluate myoclonus based on the spectrum of EMG activity on antagonist muscle pairs and cortico-muscular coherence (CMC)., Results: multifocal action myoclonus was detected in all patients corresponding to brief EMG bursts, which occurred synchronously on antagonist muscles at a frequency peaking in beta band. There was significant CMC in beta band, and a cortico-muscular transfer time consistent with a cortical origin of the jerks. The somatosensory evoked potentials (SSEPs) were giant in only one patient who also showed exaggerated long-loop reflexes (LLRs). The nine patients who had experienced myoclonic seizures showed greater CMC., Conclusions: The cortical myoclonus consistently observed in patients with DS shows features that are similar to those characterizing progressive myoclonus epilepsy, but differs because it does not have a severely worsening course and is not commonly associated with increased SSEPs or enhanced LLRs. This kind of myoclonus is an intrinsic feature of DS associated with SCN1A mutations, and may be a cause of disability., Significance: We hypothesize that myoclonus is generated in cortical motor areas by hyper-synchronous oscillations, which are possibly due to sodium channel dysfunction., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The prevailing understanding of generalized epilepsy is shaped by the traditional definition that "the responsible neuronal discharge takes place, if not throughout the entire grey matter, then at least in the greater part of it and simultaneously on both sides". This view is no longer tenable since concurrent findings using multiple methods have accumulated to reveal the role of bilateral networks of distributed and selective cortical and subcortical structures in so-called generalized ictogenesis. Most of this research has been focused on juvenile myoclonic epilepsy (JME), which today is commonly considered the archetypical syndrome of the idiopathic generalized epilepsies. Based upon recent research in the fields of clinical epileptology, neuropsychology and psychiatry, clinical neurophysiology, neuroimaging and epilepsy genetics this article, for the first time, unites these new findings into a comprehensive nosological view. Genetically determined dysfunctions of important cognitive systems like visuomotor coordination and linguistic communication appear now as key mechanisms of seizure generation in JME. This review suggests a new paradigm to consider JME as a system disorder of the brain analogous to other neurological system disorders., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aim of the Study: To compare the effects of perceived and assessed cognitive functions on quality of life (QoL) in patients with epilepsy (PWE)., Methods: The study analyzed the data from a series of PWE who compiled the Quality of Life in Epilepsy-89 Inventory (QOLIE-89) and the Multiple Ability Self-Report Questionnaire (MASQ) for QoL and perceived cognitive abilities, respectively. The State-Trait Anxiety and Beck Depression inventories were used to assess mood. Neuropsychological tests evaluated abstract reasoning, attention, conceptual-motor tracking, constructional praxis, language, verbal and non-verbal memory, abstraction, category shifting, verbal fluency, and visual-spatial abilities., Results: The QOLIE-89 overall score was predicted by the Mood and Attention and Executive Functions factors and MASQ scores, explaining 38, 6, and 4% of its variance, while disease duration, seizure frequency, and schooling determined 16%. The QOLIE-89 Psychosocial, Cognitive, and Physical Performance sub-domains related to mood. The Cognitive and Physical Performance factors also related to the MASQ and Attention and Executive Functions factor scores, respectively., Conclusions: In PWE, self-rated and assessed cognitive deficits may influence QoL, explaining 10% of its variance irrespective from mood and clinical variables. Treating cognitive deficits and their perception may help improve QoL., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Mutations of genes coding for ion channels cause several genetically determined human epileptic syndromes. The identification of a gene variant linked to a particular disease gives important information, but it is usually necessary to perform functional studies in order to completely disclose the pathogenic mechanisms. The functional consequences of epileptogenic mutations have been studied both in vitro and in vivo with several experimental systems, studies that have provided significant knowledge on the pathogenic mechanisms that leads to inherited human epilepsies, and possibly also on the pathogenic mechanisms of non-genetic human epilepsies due to "acquired channelopathies". However, several open issues remain and difficulties in the interpretation of the experimental data have arisen that limit translational applications. We will highlight the value and the limits of different approaches to the study of epileptogenic channelopathies, focussing on the importance of the experimental systems in the assessment of the functional effects of the mutations and on the possible applications of the obtained results to the clinical practice., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Seizures induced by musical stimulation are usually correlated to temporal epilepsy, although the precise localization of their epileptogenic networks are not well characterized. Brain imaging studies show that regional cerebral blood flow (rCBF) recorded during musicogenic seizures is increased in putative epileptogenic foci, as well as in other brain regions not directly related to seizure activity. These studies, however, afford only a virtual temporal relation between ictal discharges and rCBF changes, given that brain images are correlated with off-line EEG recordings. To obviate this problem, the simultaneous multimodal recording of the episode of musicogenic epilepsy is mandatory. The present study describes the EEG-fMRI co-recording of musicogenic elicited seizures in a case of simple partial epilepsy. Our results show that EEG features recorded in epileptogenic areas are largely coupled with rCBF increase. Furthermore, rCBF modifications in other regions suggest that additional aspects of musical processing are also elicited during musicogenic seizures.

Hypoxic-ischemic encephalopathy due to fetal or neonatal asphyxia is a major cause of acute mortality and chronic disability involving cerebral palsy, seizures, and mental retardation. The gestational age of the infant is one of the main variables determining the neuropathological picture of hypoxic-ischemic brain injury, and ulegyria (one of its neuropathological correlates) typically affects full-term infants. The damage usually involves the deeper sulcal portion of the convolutions while sparing the crowns, and includes subcortical white matter atrophy and gliosis. The aim of this study was to characterize the electroclinical features of hypoxic-ischemic encephalopathy when ulegyria is one of its main neuropathological features. To this end, nine patients with MRI-proven ulegyria and epilepsy underwent a complete neurological work-up. The ulegyric lesions were mainly distributed in the parasagittal watershed areas and frequently associated with other hypoxic-ischemic lesions. The neurological picture was characterized in most patients by mental retardation, motor deficits, and drug-refractory partial epilepsy. The ulegyria in our patients was associated with a complex clinical picture: epilepsy was a prominent component, and its severity directly correlated with the extent of the ulegyria and the associated hypoxic-ischemic lesions. Drug refractoriness was an almost constant correlate of this form of symptomatic epilepsy.

Despite the increasing number of patients affected by neuronal migration disorders (NMDs) recently diagnosed in vivo by means of magnetic resonance imaging (MRI), few detailed data on the correlation between the neuroradiological and the anatomical features in the single NMD case are available. The present paper reports a combined cytoarchitectural and immunocytochemical analysis, by means of antisera recognizing specific neuronal and glial markers, of three MRI diagnosed NMD patients surgically treated for the relief of intractable seizures. The first case was a giant subcortical nodular heterotopia of morphologically normal neurons lacking any type of cortical lamination. The second case was a layered polymicrogyria with an abnormal amount of ectopic neurons in the underlying white matter. The third case was a focal cortical dysplasia characterized by a dramatic disruption of the normal cortical layering associated with marked cytological abnormalities. The present data demonstrate that the macroscopical and microscopical brain abnormalities can be markedly different in different NMD subtypes, and suggest that different anatomical substrates can underlie the intrinsic hyperexcitability of these brain malformations. The relevance of further prospective clinico-morphological studies for a better understanding of the mechanisms determining the development of these brain malformations is underlined.

The neurophysiological properties of human dentate granule cells were studied in hippocampal slices prepared from patients undergoing surgical treatment for medically intractable temporal lobe epilepsy. In 24 neurons which were morphologically identified as dentate granule cells by intracellular staining with biocytin, there were 2 types of synaptic responses to perforant path stimulation: one showed an EPSP-IPSP sequence (n = 10) and the other showed prolonged EPSPs without accompanying hyperpolarizing IPSPs (n = 14). The prolonged EPSPs were markedly retarded by the application of an NMDA receptor antagonist, APV. Membrane properties of neurons showing the different classes of synaptic responses were similar in resting membrane potential (pooled average: -56.2 mV +/- 0.94 SEM) and spike amplitude (pooled average: 65.2 mV +/- 1.69 SEM). However, membrane resistance tended to be lower in neurons with prolonged EPSPs (31.8 M omega +/- 2.63 SEM) than in neurons that showed EPSP-IPSP responses (40.2 +/- 4.33) (P less than 0.05, Fisher). No spontaneous and/or evoked burst firing was observed. These data provide fuller information on the neurophysiological properties of human dentate granule cells in surgically resected epileptogenic hippocampus, implicating a role of NMDA receptor activation in human temporal lobe epilepsy.

Intracellular recordings in 'in vitro' hippocampal slices, prepared from intracisternally AlCl3-intoxicated rabbits, were obtained from 43 CA1 pyramidal neurons. The experiments were performed 12-20 days after aluminum administration. The electrotonic length was significantly shorter than that of 33 control neurons, in agreement with morphological evidence of an Al-induced dendritic impairment. Both postsynaptic and Ca2(+)-dependent K+ hyperpolarizing potentials were also found to be significantly decreased, with reciprocal enhancement of excitatory postsynaptic potentials and depolarizing after-potentials. The former finding is ascribed to a selective neurotoxic effect of aluminum on GABAergic interneurons; the latter can be accounted for by an Al-induced increase in cyclic AMP, which is known to block the Ca2(+)-activated K+ conductance responsible for after-hyperpolarizing potentials. It is concluded that aluminum can exert its epileptogenic effect through multiple neurotoxic mechanisms involving membrane electrotonic properties, K+ conductances, and synaptic influences, thus resulting in a neuronal hyperexcitable state. Such changes are detectable in the early stages of the Al-induced encephalopathy, when there is only slight evidence of cytoskeleton alterations (i.e., neurofibrillary degeneration).