Summary
The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms ...following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self‐limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.
Summary
The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of such a revision is to recognize that some seizure types can ...have either a focal or generalized onset, to allow classification when the onset is unobserved, to include some missing seizure types, and to adopt more transparent names. Because current knowledge is insufficient to form a scientifically based classification, the 2017 Classification is operational (practical) and based on the 1981 Classification, extended in 2010. Changes include the following: (1) “partial” becomes “focal”; (2) awareness is used as a classifier of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalized are eliminated; (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional; (5) atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalized onset; (6) focal to bilateral tonic–clonic seizure replaces secondarily generalized seizure; (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic–atonic, myoclonic–tonic–clonic; and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change, but allows greater flexibility and transparency in naming seizure types.
Summary
This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. ...Illustration of the classification is enacted by tables, a glossary of relevant terms, mapping of old to new terms, suggested abbreviations, and examples. Basic and extended versions of the classification are available, depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categories of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can further be optionally characterized by whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it a focal impaired awareness seizure. Focal seizures are further optionally characterized by motor onset signs and symptoms: atonic, automatisms, clonic, epileptic spasms, or hyperkinetic, myoclonic, or tonic activity. Nonmotor‐onset seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which might then progress to other signs and symptoms. Focal seizures can become bilateral tonic–clonic. Generalized seizures engage bilateral networks from onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic–atonic, myoclonic–tonic–clonic, tonic, or tonic–clonic. Nonmotor (absence) seizures are typical or atypical, or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown onset may have features that can still be classified as motor, nonmotor, tonic–clonic, epileptic spasms, or behavior arrest. This “users’ manual” for the ILAE 2017 seizure classification will assist the adoption of the new system.
The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with variable foci. A frameshift mutation in the ...DEPDC5 gene (encoding DEP domain-containing protein 5) was identified in a family with focal epilepsy with variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified 4 nonsense mutations and 1 missense mutation. Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway METHODS: We analyzed ...clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants.
The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign.
Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.
Summary
The discovery of intrinsic epileptogenicity of the hypothalamic hamartoma (HH) marked a new area in understanding the associated clinical syndrome, often manifesting as progressive epileptic ...encephalopathy. However, therapeutic procedures targeting the HH proved to be inefficient to cure seizures in up to 50% of cases, whereas in cases with partial improvement, the electroclinical patterns of persisting seizures suggest an involvement of distant cortical regions. The concept of kindling‐like secondary epileptogenesis has been suggested as a possible underlying mechanism. Yet the role of the hypothalamic lesion in the pathophysiology of the syndrome remains debatable. In the Strasbourg‐Kork series, the best outcomes were obtained when the duration of epilepsy before endoscopic HH surgery did not exceed 10 years. In two patients with HH ablation followed at a later time by a temporal lobectomy, only this second surgical step allowed complete seizure freedom. These findings suggest the existence of an independent, third stage of secondary epileptogenesis in human. In the Grenoble series, stereotactic intracerebral recordings (stereo electroencephalography SEEG) of five HH cases demonstrated that gelastic/dacrystic seizures were correlated with discharges within the HH, whereas other seizure types were related to discharges affecting cortical regions, which sometimes seemed to be triggered by HH. In the Marseille series, two cases explored by SEEG provided evidence of extended epileptogenicity outside the limits of the HH, forming complex epileptogenic networks, with HH still triggering clusters of neocortical seizures in the first, but not obligatory involved in spontaneous seizures in the second case. Taken together, our data argue for the existence of dynamic ictal network organization, with possible “kindling‐like” relationships between the HH and the neocortex or widespread epileptogenesis. Despite the existence of secondary epileptogenesis, the epileptogenic zone could still be limited to the hamartoma, for which early surgical treatment should be pragmatically considered as a first surgical step.
Summary
Objective
Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared ...heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings.
Methods
Clinically relevant biomarkers of epileptogenicity during ictal (epileptogenicity index; EI) and interictal recordings (high‐frequency oscillation and spike) were evaluated in 19 patients undergoing SEEG. These biomarkers were then compared between heterotopic cortex and neocortical regions. Seizures were classified as normotopic, heterotopic, or normoheterotopic according to respective values of quantitative analysis (EI ≥0.3).
Results
A total of 1,246 contacts were analyzed: 259 in heterotopic tissue (heterotopic cortex), 873 in neocortex in the same lobe of the lesion (local neocortex), and 114 in neocortex distant from the lesion (distant neocortex). No significant difference in EI values, high‐frequency oscillations, and spike rate was found comparing local neocortex and heterotopic cortex at a patient level, but local neocortex appears more epileptogenic (p < 0.001) than heterotopic cortex analyzing EI values at a seizure level. According to EI values, seizures were mostly normotopic (48.5%) or normoheterotopic (45.5%); only 6% were purely heterotopic. A good long‐term treatment response was obtained in only two patients after thermocoagulation and surgical disconnection.
Significance
This is the first quantitative SEEG study providing insight into the mechanisms generating seizures in nodular heterotopia. We demonstrate that both the heterotopic lesion and particularly the normotopic cortex are involved in the epileptogenic network. This could open new perspectives on multitarget treatments, other than resective surgery, aimed at modifying the epileptic network.
Formerly idiopathic, focal epilepsies (IFE) are self‐limiting, “age‐related” diseases that mainly occur during critical developmental periods. Childhood epilepsy with centrotemporal spikes, or ...Rolandic epilepsy (RE), is the most frequent form of IFE. Together with the Landau‐Kleffner syndrome and the epileptic Encephalopathy related to Status Epilepticus during slow Sleep syndrome (ESES), RE is part of a single and continuous spectrum of childhood epilepsies and epileptic encephalopathies with acquired cognitive, behavioral and speech and/or language impairment, known as the epilepsy‐aphasia spectrum (EAS). The pathophysiology has long been attributed to an elusive and complex interplay between brain development and maturation processes on the one hand, and susceptibility genes on the other hand. Studies based on the variable combination of molecular cytogenetics, Sanger and next‐generation sequencing tools, and functional assays have led to the identification and validation of genetic mutations in the GRIN2A gene that can directly cause various types of EAS disorders. The recent identification of GRIN2A defects in EAS represents a first and major break‐through in our understanding of the underlying pathophysiological mechanisms. In this review, we describe the current knowledge on the genetic architecture of IFE.
Purpose: To report three patients with drug‐resistant nocturnal hypermotor seizures (NHSs), no detectable brain lesion, and clinically defined nocturnal frontal lobe epilepsy (NFLE) or autosomal ...dominant NLFE (ADNFLE), whose intracerebral EEG ictal onset primarily involved the insula, rather than the mesial or orbital frontal cortex.
Methods: Fourteen to 15 intracerebral electrodes were implanted in each patient, primarily sampling the frontal lobes with 80 to 91 recording leads covering the most likely side of seizure onset, and two to six leads placed within the ipsilateral insula. Electrical stimulation was used to test the epileptic threshold of frontal and insular brain regions at the various recording sites.
Results: In all three patients, a low‐voltage fast activity was recorded within the anterosuperior aspect of the insula at ictal onset, either in isolation, or extending to the nearby frontal operculum in the ADNFLE patient. The role of the insula was further supported in all three patients either by the presence of high‐amplitude spikes that clearly predominated over that region (n = 2) or by triggering the patient's typical aura or seizure when applying an electrical stimulation at that site, selectively (n = 2).
Conclusions: The anterosuperior portion of the insula might play a pivotal role in generating nocturnal hypermotor seizures in some patients with nonlesional drug‐resistant epilepsy suggesting NFLE or ADNFLE. Whether these patients are amenable to successful surgery remain an open issue.
•Thermocoagulations induce the running-down of HFO and spikes in normo-heterotopic epileptogenic network.•Decreased epileptogenicity correlates well with significantly improved seizure ...control.•Combination of ictal and interictal biomarkers is crucial to define the epileptogenic zone.
Epilepsy associated with periventricular nodular heterotopia (PNH) is characterized by complex relationships between the heterotopic and the normotopic cortex during the interictal state and at seizure onset. High-frequency oscillations (HFO) have been proposed as a marker of epileptogenicity that might reflect disease activity. The effects of thermocoagulations on epileptogenicity in this context remain unknown. We aimed to investigate the interictal HFO- and spike profiles of different cortical structures before and after two consecutive SEEG-guided thermocoagulations, in correlation with seizure outcome, in a patient with PNH-related drug-resistant epilepsy.
The epileptogenic zone (EZ) was defined by SEEG analysis based on the Epileptogenicity Index. Interictal spikes, ripples (80–250 Hz) and fast ripples (FR, 250-330 Hz) were analyzed within the heterotopia, the temporal neocortex and the hippocampus.
The SEEG recordings revealed a distributed EZ involving the heterotopia and the posterior temporal neocortex. Both structures were targeted by thermocoagulations. Background spikes, ripples and FR-rates were significantly higher in PNH compared to the normotopic cortex. A drastic reduction of spikes (by over 80%) and absence of FR were demonstrated both in the PNH and in the neocortex during the second SEEG exploration 6 months after the first thermocoagulation, whereas no significant difference was observed in the posterior hippocampus. Ripples were significantly reduced by the first and suppressed by the second thermocoagulation within the three structures. Seizures relapsed after two months but decreased in frequency after the first thermocoagulation. Sustained seizure-freedom was achieved only after the second procedure.
Our data demonstrate the running down of interictal HFO and spikes within the epileptogenic network following thermocoagulations of heterotopic and normotopic sites involved at seizure onset. This dynamics was in good correlation with significantly improved seizure control.
Combination of ictal and different interictal markers of epileptogenicity, including HFO and spike analysis, is important to get the full picture of the epileptogenic zone and could help to evaluate the disease activity.
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