bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilepsy and ionic channels
Authors: Roll Patrice , Szepetowski Pierre
Published: March 2024

Ion channels play critical roles in a broad range of physiological processes. In particular, they represent a common basis for the excitable properties of different tissues. Consequently, ion channels of many different types have been implicated in several human genetic disorders of the heart, brain and skelctal muscle. An increasing number of genes encoding neurotransmitter‐ or voltage‐gated ion channel subunits have proved to be mutated in various idiopathic human epilepsies as well as in different animal models. The epilepsies could thus be considered as one of many paroxysmal disorders that are due to mutations in ion channel genes, the so‐called channelopathies. However, recent data supported the hypothesis that other genes with different properties could also be responsible for human idiopathic epilepsies, thus opening new and exciting areas of research. Effort is still needed to identify the genes responsible for the large variety of other epileptic disorders inherited as Mendelian traits and evaluate the role of these genes in the more common and polygenic forms. Defining the genetic bases of the latter will also require that exhaustive association studies are performed. These studies may help understand the pathophysiology of human epilepsies and represent the first step towards the discovery of new therapeutic targets, as exemplified in the case of the KCNQ potassium channels.
Long‐term neuropsychological follow‐up and nosological considerations in five patients with Continuous Spikes and Waves during Slow Sleep
Authors: Veggiotti Pierangelo , Termine* Cristiano , Granocchio Elisa , Bova Stefania , Papalia Grazia , Lanzi Giovanni
Published: March 2024

Continuous spikes and waves during slow sleep (CSWSS) is a well‐known EEG pattern that can be associated with cognitive and behavioural deterioration. We present the long‐term neuropsychological follow‐up and nosological considerations of five patients who developed CSWSS during childhood. All five of our patients presented CSWSS, although the duration and severity of this pattern varied. The outcome was of three basic types: acquired frontal dementia, language deficits and normal. Four of our patients were initially diagnosed with Landau‐Kleffner syndrome but have had markedly diverse outcomes in terms of the severity and type of compromise. Our data suggest that the initial diagnosis, according to current nosological categories, has almost no prognostic significance, while the length and the age of onset of CSWSS, the site of epileptiform activity and the individual neuropsychological profile are more useful for identifying the long‐term outcome of patients with CSWSS.
The role of the temporal pole in auditory processing
Authors: Bougeard Renaud , Fischer Catherine
Published: March 2024

Experiments in animals have shown that the temporal pole and the amygdala are involved in auditory processing. Comparable data are scarce in humans. It is only known that after temporal lobectomy, hearing may be impaired and dichotic listening scores reduced on the ear contralateral to the operated temporal lobe. Middle‐latency auditory evoked potentials (MLAEPs) and late auditory evoked potentials (LAEPs) have been recorded in 14 patients before and after temporal lobectomy for the treatment of drug‐resistant temporal lobe epilepsy. The Na and Pa components of MLAEPs were significantly delayed and the Pa component amplitude reduced before and after surgery as compared to a group of 21 healthy subjects. Data in pre‐ and postoperative period were not statistically different. N100 and P200 component of LAEPs were similarly altered. It is concluded that in humans the amygdala and probably the temporal pole may be involved in the process of auditory activation‐inhibition. The possible role of auditory processing impairment in cognitive deficits in TLE patients can also be questioned.
Children with Rolandic spikes and ictal vomiting: Rolandic epilepsy or Panayiotopoulos syndrome?
Authors: Covanis Athanasios , Lada Christina , Skiadas Konstantinos
Published: March 2024

Centrotemporal spikes are the EEG marker of Rolandic epilepsy, while ictus emeticus is one of the main seizure manifestations of Panayiotopoulos syndrome. Ictus emeticus has not been reported in Rolandic epilepsy. Out of a population of 1340 children with focal afebrile seizures we studied 24 children who had emetic manifestations in at least one seizure and centrotemporal spikes in at least one EEG. They were of normal neurological status and had a follow‐up of at least two years after the last seizure. All children had sleep EEG following sleep deprivation. Two groups of patients were identified. Group A (12 patients) with EEG centrotemporal spikes only and group B (12 patients) with centrotemporal spikes and spikes in other locations. In 21 patients, ictal emetic manifestations culminated in vomiting and in three only nausea or retching occurred. The commonest presentation was ictus emeticus at onset followed by deviation of the eyes or staring, loss of contact and floppiness. In 79%, seizures occurred during sleep. Autonomic status epilepticus occurred in 37.5%. The mean age at onset was 5.3 years. Overall analysis of the clinical and EEG data points out that the vast majority of these patients primarily suffer from Panayiotopoulos syndrome. Twenty patients (83%) had ictal semiology typical of Panayiotopoulos syndrome, but five also had concurrent Rolandic symptoms and four later developed pure Rolandic seizures. The other four patients (17%) had typical Rolandic seizures with concurrent ictus emeticus. These findings suggest a link between Rolandic epilepsy and Panayiotopoulos syndrome, the two most important phenotypes of the benign childhood seizure susceptibility syndrome.
Video‐EEG evidence of lateralized clinical features in primary generalized epilepsy with tonic‐clonic seizures
Authors: Casaubon Leanne , Pohlmann‐Eden Bernd , Khosravani Houman , Carlen Peter L. , Wennberg Richard
Published: March 2024

Background

Whether cortical or subcortical structures, specifically the thalamus, play the dominant role in generating primary generalized seizures has been the subject of long debate. Most experimental data implicate a hyperexcitable cortical generator of spike‐and‐wave activity, with the thalamus quickly recruited to sustain the generalized oscillations through a reverberating thalamocortical network. However, there is little clinical evidence to support the cortical generator hypothesis. We present video‐EEG recordings of generalized tonic‐clonic seizures in three patients with proven primary generalized epilepsy (PGE), all of whom showed a consistent pattern of lateralized seizure onset compatible with a focal frontal lobe generator.

Methods

Among 300 patients referred for video‐EEG monitoring for intractable epilepsy, three were found to have PGE with tonic‐clonic convulsions. All had a positive family history for epilepsy and no other epilepsy risk factors. Epilepsy onset was during adolescence (2/3) or childhood (1/3). Patients were taking 1‐4 antiepileptic drugs (AEDs) at admission, none of which was valproic acid.

Results

Interictal EEG showed very active, bilaterally synchronous generalized spike‐and‐wave or polyspike‐and‐wave discharges between 2.5‐4.5 Hz, maximal over the midfrontal structures symetrically in all patients. Ictal EEG showed generalized rhythmic activity without lateralization at seizure onset. Surprisingly, in all 6 recorded tonic‐clonic seizures there was a sustained (10‐15 seconds), stereotyped, clinical lateralization at onset, which took the form of a tonic “fencing posture” in one patient (two seizures) and forced head/eye/torso version in two patients (four seizures). Two patients became seizure‐free shortly after switching to valproate monotherapy. One patient refused valproate but has improved more than 90 % with a change in AEDs to lamotrigine and phenobarbital (follow‐up in all patients > 18 months).

Conclusions

Tonic‐clonic seizures are presumed to be generalized from onset in patients with PGE. However, video‐EEG monitoring in these patients is rarely performed and the actual clinical features of the seizures may be underappreciated. The demonstration of sustained lateralization at onset in our patients, with features clinically indistinguishable from focal onset frontal lobe seizures, is compatible with the hypothesis of a focal region of cortical hyperexcitability situated in the frontal lobes of some patients with PGE. Whether this cortical generator is autonomous or “triggered” by ascending, possibly normal, thalamocortical volleys is unresolved. [Published with video sequences].
Adding topiramate to valproate therapy may cause reversible hepatic failure
Authors: Bumb Anja , Diederich Nico , Beyenburg Stefan
Published: March 2024

The authors report a 51‐year‐old women with pharmacoresistant partial epilepsy who tolerated well valproate monotherapy and in combination with several other antiepileptic drugs, but developed symptoms and signs of reversible hepatic failure under a combination of valproate and topiramate. Symptoms resolved after discontinuation of VPA. This case provides further anecdotal evidence that topiramate may increase the risk of liver failure when given in combination with other potentially hepatotoxic antiepileptic drugs.
Positron emission tomography in epileptogenic hypothalamic hamartomas
Authors: Ryvlin Philippe , Ravier C. , Bouvard S. , Mauguière François , Le Bars D. , Arzimanoglou Alexis , Petit Jérôme , Kahane Philippe
Published: March 2024

Whether the intrinsic epileptogenicity of hypothalamic hamartomas (HH) is responsible for the entire clinical spectrum of epileptic, neuropsychological and behavioural disorders associated with HH, remains an open issue, in as much as morphologically similar HH can be associated with dramatically different seizure types and cognitive outcomes.

The aim of this study was to investigate brain glucose metabolism in patients with epileptogenic HH, in an attempt to identify signs of focal cortical and subcortical dysfunction which might correlate with other clinical data.

We have studied five patients with epileptogenic HH using [
18
F]‐fluorodesoxyglucose and positron emission tomography (FDG‐PET). All our patients also underwent an optimal MRI and a video‐EEG monitoring, as well as an intra‐cranial EEG recording in one of them. The anatomical distribution of FDG‐PET abnormalities was compared to that of interictal and ictal electroclinical findings.

All five patients demonstrated focal hypometabolism, ipsilateral to the predominant EEG abnormalities and side of HH. Hypometabolic areas greatly varied between patients, but were grossly concordant with the cortical regions suspected to participate in the ictal discharges in each individual.

Epileptogenic hypothalamic hamartomas are usually associated with focal cortical hypometabolism in regions which might participate in the overall HH‐driven epileptic network. Whether these cortical abnormalities only reflect the propagation of ictal discharges, or a potentially independent seizure onset zone remains unknown.
The ideal pharmacokinetic properties of an antiepileptic drug: how close does levetiracetam come?
Authors: Perucca Emilio , Johannessen Svein I.
Published: March 2024

The pharmacokinetic properties of a drug are the primary determinant of the extent and duration of drug action, and influence susceptibility to clinically important drug interactions. Most of the older‐generation antiepileptic drugs (AEDs) are far from ideal in terms of pharmacokinetics and interaction potential. For example, phenytoin, carbamazepine, and valproic acid exhibit non‐linear kinetics; carbamazepine and valproic acid have relatively short half‐lives; and most of these drugs cause either enzyme induction (phenytoin, phenobarbital, primidone, carbamazepine) or enzyme inhibition (valproic acid). Compared with older agents, certain new‐generation AEDs offer a number of pharmacokinetic advantages, particularly in terms of reduced inter‐patient variability in drug clearance and a lower interaction potential. One of the most recently developed of these drugs, levetiracetam, comes especially close to fulfilling the desirable pharmacokinetic characteristics for an AED: (1) it has a high oral bioavailability, which is unaffected by food; (2) it is not significantly bound to plasma proteins; (3) it is eliminated partly in unchanged form by the kidneys and partly by hydrolysis to an inactive metabolite, without involvement of oxidative and conjugative enzymes; (4) it has linear kinetics; and (5) it is not vulnerable to important drug interactions, nor does it cause clinically significant alterations in the kinetics of concomitantly administered drugs. Although its half‐life is relatively short (6 to 8 hours), its duration of action is longer than anticipated from its pharmacokinetics in plasma, and a twice‐daily dosing regimen is adequate to produce the desired response.
Safety profile of levetiracetam
Authors: Arroyo Santiago , Crawford Pamela
Published: March 2024

A good balance between safety and tolerability is necessary for an antiepileptic drug (AED) to be successful in the management of patients with epilepsy. Levetiracetam is one of the new generation of AEDs licensed as an add‐on therapy for the treatment of patients with partial‐onset seizures. Levetiracetam's mechanisms of action are not fully understood. Controlled clinical trials, open‐label studies, and postmarketing surveillance indicate that levetiracetam has a favorable safety profile characterized by little effect on vital signs or clinical laboratory values, reported adverse events that are mild to moderate, and no known drug‐drug interactions. The tolerability of levetiracetam may extend to both pediatric and elderly patients based on analyses of small numbers of patients. Tolerability is maintained over the long term. Levetiracetam does not appear to have a different safety profile in learning‐disabled patients. Levetiracetam appears to have a good balance between tolerability and efficacy in the treatment of a wide variety of patients with partial epilepsy.
Advanced MRI analysis methods for detection of focal cortical dysplasia
Authors: Bernasconi Andrea
Published: March 2024

In many patients, lesions of focal cortical dysplasia (FCD) may go unrecognized by standard radiological analysis. This is due to the fact that identification of many of these malformations on visual inspection of conventional MRI is difficult due to their subtlety and the complexity of the brain's convolutions. Quantitative MR image processing methods have the potential to help identify lesions that may be overlooked by conventional radiological evaluation. To increase the sensitivity of MRI for the detection of subtle lesions of FCD, we recently developed voxel‐based image post‐processing methods, including first‐order texture analysis and morphological processing modeled on known MRI features of FCD. Using these methods we were able to increase the sensitivity over conventional MRI analysis by more than 30%, while maintaining a high degree of reliability. The image processing methods we developed improve visual detection of FCD, even in cases where no lesion is obvious on MRI. Therefore, these techniques could allow a more precise evaluation of patients with partial epilepsy who could benefit from surgery.
Intra‐lesional stereo‐EEG activity in Taylor's focal cortical dysplasia
Authors: Francione Stefano , Nobili Lino , Cardinale Francesco , Citterio Alberto , Galli Carlo , Tassi Laura
Published: March 2024

Focal cortical dysplasia are a frequent histological finding in epilepsy surgery series. Among the different types of focal cortical dysplasia, distinctive anatomical, electrical and clinical details have been identified for Taylor's focal cortical dysplasia, and in a recent article we reported a better post‐surgical outcome in Taylor's focal cortical dysplasia than in other histological subtypes of cortical dysplasias. In the present study, we analysed the intra‐lesional electrical activity directly recorded inside Taylor's focal cortical dysplasia during a stereo‐EEG diagnostic procedure in 21 patients selected from among the 27 cases in which post‐operative neuropathological examination demonstrated this kind of lesion.

Our data show the existence of a peculiar interictal pattern characterised by the presence of repetitive and rhythmic spike and poly‐spike and wave, frequently associated with short bursts of fusiform micro poly‐spikes. Moreover, an almost pathognomonic ictal pattern (mid‐amplitude 14‐18 Hz rhythmic activity followed by a low voltage recruiting fast activity) is present in 12 of these 21 patients. These electrical peculiarities suggest a high level of epileptogenicity of Taylor's focal cortical dysplasia and could possibly explain the high percentage of post‐surgical success among patients with this kind of lesion.
Focal cortical resection in malformations of cortical development
Authors: Russo Giorgio Lo , Tassi Laura , Cossu Massimo , Cardinale Francesco , Mai Roberto , Castana Laura , Colombo Nadia , Bramerio Manuela
Published: March 2024

Malformations of cortical development may be associated with drug‐resistant partial epilepsy suitable for surgical therapy. From the anatomopathological point of view, this categorisation has been used in reference to a wide range of alterations of the cortical mantle. Focal cortical dysplasias represent the main group of malformations of cortical development, but there are also other types of alterations, such as heterotopias, double cortex or polymicrogyria. Defining candidacy for surgical therapy and tailored resection requires thorough pre‐surgical evaluation so that the approach will be individualised for each patient. We present our series of 126 patients with malformation of cortical development selected from 321 consecutively operated patients. Within this group encompassing different types of malformation of cortical development, including periventricular heterotopia (nine patients), polymicrogyria (three patients), hemimegalencephaly (one patient) and subcortical band heterotopia (one patient), the largest group was 81 individuals with focal cortical dysplasia. For this last group, we propose a simplified classification defining 42 architectural dysplasias, 12 cytoarchitectural dysplasias and 27 Taylor's focal cortical dysplasias. In addition, at routine neuropathological investigation, the only morphological alteration shown by 31 patients was diffuse neuronal heterotopia. All patients underwent scalp EEG and video‐EEG, and 75 patients (59.5%) also underwent stereo‐EEG. Magnetic resonance imaging and stereotactic stereoscopic angiography represented the indispensable premises for further studies, in particular stereo‐EEG, and for planning surgery and tailoring resection. Magnetic resonance imaging was unhelpful in 17 out of 81 patients with focal cortical dysplasia and in seven out of 31 with neuronal heterotopia, while signal alterations were present in all other cases. Common characteristics corresponding to clinical‐histopathological homogeneous subgroups were found within the focal cortical dysplasia group. In patients with architectural dysplasia, the epileptogenic zone was mainly in the temporal lobe and there was a lower seizure frequency than in patients with Taylor's focal cortical dysplasia. Patients with Taylor's type had an epileptogenic zone that was mainly extra‐temporal, and a distinctive interictal stereo‐EEG. The best outcome was observed in patients with Taylor's type dysplasia: 69% seizure‐free (Engel class Ia) after at least 1 year of follow‐up, compared with 45% of cytoarchitectural dysplasia and 49% of architectural dysplasia patients.
Alternating hemiplegia of childhood: presentation of two cases regarding the extent of variability
Authors: Saltik Sema , Çokar Ozlem , Uslu Turkan , Uludüz Derya , Dervent Aysin
Published: March 2024

Alternating hemiplegia of childhood is an episodic neurological disorder, the diagnosis of which is solely clinical. In this report, two patients with alternating hemiplegia, one as a representative of the classical picture and the other with unusual features, are presented by video display. Some clinical manifestations and the variability of symptoms are discussed with regard to their place in the diagnosis of the disease. (Published with videosequences)
Panayiotopoulos syndrome: video‐EEG illustration of a typical seizure
Authors: Demirbilek Veysi , Dervent Aysin
Published: March 2024

Panayiotopoulos syndrome (PS) is a form of idiopathic, partial epilepsy of childhood with a high prevalence rate, but with poor clinical recognition, possibly due to the characteristics of the seizure, which not infrequently lack common epileptic motor and/or sensory phenomena. Instead, autonomic symptoms such as retching and vomiting, predominate. Semiological knowledge of the seizures in PS depends mainly on parental observations, but not enough ictal‐EEG data are available, possibly due to the rarity of seizures. In addition to previous knowledge regarding the occipital onset of seizures in PS, it has been recognized that other areas, mainly the frontal regions, may be involved. The present report demonstrates the video‐EEG findings of a seizure in a patient with PS. Subclinical ictal EEG discharges with occipital onset precede the clinical autonomic symptoms; eye deviation which is typical of occipital involvement, appears in later sequences. These findings suggest that at least for certain seizures an occipital origin may be considered, even in seizures without the early manifestations typical of this region. (Published with videosequences).
Dissociation and childhood abuse history in epileptic and pseudoseizure patients
Authors: Akyuz Gamze , Kugu Nesim , Akyuz Aytekin , Dogan Orhan
Published: March 2024

The aim of this study was to examine dissociative experiences, childhood abuse and anxiety in epileptic and pseudoseizure female patients. Thirty‐three patients with pseudoseizures and thirty patients with epilepsy were recruited from Cumhuriyet University Hospital Psychiatry and Neurology Units. We assessed each participant using the Dissociative Experiences Scale, the Clinician‐Administered Dissociative States Scale and the Childhood Abuse and Neglect Questionnaire. The female patients with pseudoseizures showed significantly higher levels of dissociative experiences and childhood trauma. Epileptic female patients showed higher levels of anxiety. The significantly higher incidence of dissociative experiences and childhood trauma in the patients with pseudoseizures makes a case for dissociation in the pathogenesis of these seizures.
Induction of epileptic negative myoclonus by oxcarbazepine in symptomatic epilepsy
Authors: Hahn Andreas , Fischenbeck Anke , Stephani Ulrich
Published: March 2024

Provocation of various seizure types including epileptic negative myoclonus and generalised atonic seizures is rarely observed in children treated with carbamazepine (CBZ). Provocation of the latter seizure types by oxcarbazepine (OXC) is not described in the literature. We report a four year‐old boy with symptomatic epilepsy caused by left‐sided cerebral atrophy of unknown origin who developed numerous daily drop attacks when exposed to OXC. Polygraphic analysis revealed secondary generalised precentral sharp‐slow waves frequently associated with a silent period lasting for 100‐150 ms in the electromyogram recorded from the deltoid and neck muscles. These seizures stopped promptly within 36 hours after discontinuation of OXC. This case demonstrates that OXC, similar to CBZ, can provoke epileptic negative myoclonus in some children with focal epilepsies. [Published with videosequences]
Analysis of the characteristics of epilepsy in 37 patients with the molecular diagnosis of Angelman syndrome
Authors: Galván‐Manso Marta , Campistol Jaume , Conill Joan , Sanmartí Francesc‐Xavier
Published: March 2024

Angelman syndrome is a genetic disorder caused by defects in the maternally inherited imprinted domain located on chromosome 15q11‐q13. Most patients with Angelman syndrome present with severe mental retardation, characteristic physical appearance, behavioral traits, and severe, early‐onset epilepsy. We retrospectively reviewed the medical histories of 37 patients, all with the molecular diagnosis of Angelman syndrome and at least three years of follow‐up in our neurology department, for further information about their epilepsy: age of onset, type of seizures initially and during follow‐up, EEG recordings, treatments and response. The molecular studies showed 87% deletions
de novo
, 8% uniparental, paternal disomy, and 5% imprinting defects. The median age at diagnosis was 6.5 years, with 20% having begun to manifest febrile seizures at an average age of 1.9 years. Nearly all (95%) presented with epilepsy, the majority under the age of three (76%). The most frequent seizure types were myoclonic, atonic, generalized tonic‐clonic and atypical absences. At onset, two patients exhibited West syndrome. EEG recordings typical of Angelman syndrome were found in 68%. Normalization of EEG appeared in 12 patients after nine years. Control of epileptic seizures improved after the age of 8.5 years. The most effective treatments were valproic acid and clonazepam. We conclude that epilepsy was present in nearly all of our cases with Angelman syndrome, and that the EEG can be a useful diagnostic tool. On comparing the severity of epilepsy with the type of genetic alteration, we did not find any statistically significant correlations.
Periodic lateralized epileptiform discharges (PLEDs) as the sole electrographic correlate of a complex partial seizure
Authors: Singh Gagandeep , Wright Mary‐Anne , Sander Josemir W. , Walker Matthew C.
Published: March 2024

We describe a patient in whom the only electrographic manifestation of a complex partial seizure recorded by video‐EEG telemetry was periodic lateralized epileptiform discharges (PLEDs) with a left anterior temporal emphasis. The abnormality, which persisted throughout the whole recorded seizure, lends support to the claim that PLEDs can be an ictal phenomenon.
Ictal movement disorders and hypothalamic hamartoma
Authors: Szurhaj William , Daems‐Monpeurt Christine , Sediri Haouaria , Destée Alain , Derambure Philippe
Published: March 2024

We report the case of a woman presenting with unusual, symptomatic epilepsy related to a hypothalamic hamartoma, in the absence of mental retardation or precocious puberty. The seizures manifested themselves clinically as characteristic, paroxysmal movement disorders, such as choreic/ballistic movement. This type of phenomenon is rarely of epileptic origin: we thus suggest that the movement disorder observed here could be due to functional disorganization of the basal ganglia network by the epileptic discharge, causing loss of the inhibition of thalamic activity and thus allowing the occurrence of abnormal movements. [Published with videosequences]
Epilepsy in inborn errors of metabolism
Authors: Wolf Nicole I. , Bast Thomas , Surtees Robert
Published: March 2024

Although inborn errors of metabolism are rarely found to be the cause of epilepsy, seizures are a frequent symptom in metabolic disorders. In a few of these, epilepsy responds to specific treatment by diet or supplementation. However, in most, no such treatment is available and conventional antiepileptic drugs must be used, often with no great success. However, because uncontrolled epilepsy will hamper development and may even lead to further cerebral damage, treatment is necessary. Seizure types are rarely specific for a particular metabolic disorder, nor are EEG findings. Other symptoms and findings must be taken into account in order to achieve a diagnosis and, in some cases, specific management. We review the main characteristics of epilepsy due to inborn errors of energy metabolism, to disturbed neuronal function due to accumulation of storage products, to toxic effects and to disturbed neurotransmitter systems. We also discuss vitamin‐responsive epilepsies and a number of other metabolic disorders focusing on possible pathogenetic mechanisms and their implication for diagnosis and treatment.
Ipsilateral head deviation related to orbito‐frontal and fronto‐polar seizures
Authors: Rheims Sylvain , Demarquay Geneviève , Guénot Marc , Sindou Marc , Mauguière François , Ryvlin Philippe
Published: March 2024

The localizing and lateralizing values of eye and head ictal deviations during frontal lobe seizures are still matters of debate. In particular, no specific data regarding the origin of ipsilateral head turning in frontal lobe seizures are available. We report a patient with frontal lobe seizures associated with reproducible, early, ipsilateral head deviation, where imaging and videostereo‐electroencephalography data, as well as surgical outcome, demonstrated the fronto‐polar and orbito‐frontal origin of the epileptic discharge. We conclude that early ipsilateral head deviation, in the context of frontal lobe epilepsy, raises the possibility of fronto‐polar or orbito‐frontal seizure onset.
[Published with video sequences]
Heart rate increase in otherwise subclinical seizures is different in temporal
versus
extratemporal seizure onset: support for temporal lobe autonomic influence
Authors: Weil Sabine , Arnold Stephan , Eisensehr Ilonka , Noachtar Soheyl
Published: March 2024

Ictal heart rate was investigated in otherwise subclinical epileptic seizures to test the hypothesis as to whether ictal tachycardia is physiological and not a physical or psychological stress response. In addition, we aimed to evaluate the localizing significance of pure ictal tachycardia. We included 21 epilepsy patients, who showed an ictal EEG seizure pattern during 22, otherwise subclinical seizures. All patients underwent ictal video‐EEG recordings to evaluate the possibility of resective epilepsy surgery. The changes in heart rate in these patients were investigated in order to determine their relationship to localization and duration of EEG seizure patterns. Ictal tachycardia was observed in 41% of the otherwise subclinical seizures (nine out of 22), and significantly more often in seizures arising from the temporal lobe than from extratemporal regions (62%
versus
11%, p < 0.0018). The seizure duration as defined by EEG was significantly positively correlated with an increase of heart rate (p = 0.043). Ictal heart rate can increase as a result of epileptic activation of autonomic cortex, reflecting a temporal lobe autonomic influence. Thus, measurement of heart rate should be included in the evaluation of otherwise subclinical epileptic seizures, because of its localizing value.
A proposal for a five‐dimensional patient‐oriented epilepsy classification
Authors: Loddenkemper Tobias , Kellinghaus Christoph , Wyllie Elaine , Najm Imad M. , Gupta Ajay , Rosenow Felix , Lüders Hans O.
Published: March 2024

The recent proposal by the ILAE Task Force for Epilepsy Classification consists of a multi‐axial syndrome‐oriented approach. Epilepsy syndromes, as defined by the ILAE, group patients according to various, poorly defined parameters. The resulting syndromes have frequently no biological significance, with overlap among different syndromes and syndromes changing with age. Additionally, only a minority of patients can be classified syndromatically, and the axes of this classification system convey redundant information. We propose a five‐dimensional, patient‐oriented approach to classifying epilepsies. This approach shifts from the syndrome‐oriented approach to a standard, neurological, methodological, patient‐oriented approach, using independent criteria in each of the five dimensions. Similar to general neurology, the first step in each patient‐physician encounter in epileptology is to take a history of the presenting symptoms and generate a hypothesis regarding the localization and etiology of the symptom within the nervous system. Therefore, the main dimensions of this classification consist of: 1) localization of the epileptogenic zone, 2) seizure semiology classified according to the semiological seizure classification, 3) etiology, 4) seizure frequency, and 5) related medical conditions. These dimensions characterize all of the information necessary for patient management, are independent parameters, and include more pertinent information with regards to patient management than the ILAE axes. All patients can be classified according to this five‐dimensional system even at the initial patient encounter when no detailed test results are available. Information from clinical tests, such as MRI and EEG, are translated into the best possible working hypothesis at the time of classification, allowing for increasing precision of the classification as additional information becomes available. This patient‐oriented classification envisions an epileptic seizure as an independent symptom of a central nervous system dysfunction due to different causes, with various cortical localizations, occurring at various frequencies, and in conjunction with other diseases and clinical symptoms.
Developmental outcome of epilepsy surgery in tuberous sclerosis complex
Authors: Zaroff Charles M. , Morrison Chris , Ferraris Nina , Weiner Howard L. , Miles Daniel K. , Devinsky Orrin
Published: March 2024

In Tuberous sclerosis complex (TSC), neurological dysfunction, usually in association with epilepsy, is responsible for the greatest degree of disease‐related disability. Epilepsy surgery is increasingly recognized as a therapeutic option given the often medication‐resistant nature of the disease. Seven subjects with medically refractory epilepsy associated with TSC, who underwent surgery at a tertiary care epilepsy center and in whom both preoperative and postoperative neuropsychological data were available, were examined. The Vineland Adaptive Behavior Scales, and in one case, the WISC‐III were utilized. Postoperatively, the composite standard scores declined in six of the seven subjects, although for the most part this decline was quite modest (8 points or less in 5/6 subjects). The mean overall developmental/intellectual quotients were comparable across assessments (preoperative M = 55, SD = 20.3; postoperative M = 49 SD = 16.6). Good outcomes appeared to be related to seizure relief. Age estimates of developmental level indicated developmental progress in the majority of subjects in the current sample, and may yield greater clinical information for individuals with developmental delay than do standard scores.
Familial rectal pain: a familial autonomic disorder as a cause of paroxysmal attacks in the newborn baby
Authors: Bednarek Nathalie , Arbuès Anne‐Sophie , Motte Jacques , Sabouraud Pascal , Plouin Perrine , Morville Patrice
Published: March 2024

A 2‐day‐old baby exhibited impressive paroxysmal attacks consisting of bradycardia, bronchospasm and vasomotor fits (Harlequin type) related to a rare, dominantly inherited form of dysautonomy called “familial rectal pain”. These events were recurrently triggered by emotion, diaper changes or wiping of the perineal areas or eating. Sometimes they occurred spontaneously. Carbamazepine had an excellent effect on the fainting. At four years of age, the child had normal psychomotor development with only minimal symptoms, and very rare paroxysmal attacks. The father of the child has minimal symptoms of this entity, with essentially ocular manifestations. Familial rectal pain is a very rare entity that must always be considered as a possible aetiology of any life‐threatening event in an infant because of the availability of a very effective treatment. The existence of minimal forms of familial rectal pain is possible, and it is likely that this entity is underdiagnosed.
[Published with video sequences].
Typical childhood absence seizures are associated with thalamic activation
Authors: Labate A. , Briellmann R.S. , Abbott D.F. , Waites A.B. , Jackson Graeme D.
Published: March 2024

Functional MRI with simultaneously acquired EEG (fMRI/EEG) can identify areas of signal change associated with interictal discharges. We report the fMRI/EEG study of a child with newly‐diagnosed IGE, performed prior to the start of antiepileptic medication. The 7‐years‐old girl had very frequent absences, associated with eyelid myoclonia. Her EEG showed frequent, typical 3/sec discharges. Functional MRI was performed with a 3T scanner using whole brain gradient echo‐planar imaging, and the EEG was recorded with 18, non‐metallic, scalp electrodes. Ten bursts of generalized discharges were captured during 30 minutes fMRI/EEG acquisition. The bursts lasted 3.4 (SD ± 0.6) seconds. Event‐related analysis was performed with SPM2 and iBrain
TM
software. Functional MRI showed prominent, bilateral thalamic activation, and less pronounced areas of cortical activation and deactivation. This study demonstrates thalamic activation in typical, untreated childhood absence epilepsy. The cortical signal change may be related to a thalamo‐cortical circuit.
Mechanisms of drug resistance
Authors: Löscher Wolfgang
Published: March 2024

Despite the use of new antiepileptic drugs, approximately one third of patients with epilepsy have seizures that cannot be controlled satisfactorily by medical treatment. Drug resistance may exist at the time of the first seizure or may develop later as result of the disease process. The mechanisms of these different scenarios are likely to be multifactorial, and may include alterations in brain uptake or brain targets of antiepileptic drugs. Such alterations may be constitutive (intrinsic), thus underlying
de novo
drug resistance in epilepsy, or induced,
e.g
., as a consequence of recurrent seizures or disease progression. Alterations in drug efflux (“multidrug”) transporters and drug targets, such as voltage‐gated sodium channels, have been found in epileptogenic brain tissue from both patients with epilepsy, and rodent models of epilepsy. However, although the multidrug transporter and target hypotheses are biologically plausible, proof‐of‐principle is lacking for these hypotheses. An advantage of the multidrug transporter hypothesis is that it can be validated both experimentally and clinically by combining antiepileptic drugs with inhibitors of such transporters. Selective inhibitors of the major efflux transporter P‐glycoprotein are currently in clinical trials for reversing chemotherapy resistance in oncology and may soon be used to determine whether such inhibitors can prevent or reverse drug resistance in epilepsy.
The effect of valproate on silent period and corticomotor excitability
Authors: Kazis Dimitrios A. , Kimiskidis Vasilios K. , Papagiannopoulos Sotirios , Sotirakoglou Kyriaki , Divanoglou Daniel , Vlaikidis Nikolaos , Mills Kerry R. , Kazis Aristeidis
Published: March 2024

Objective

To investigate, by transcranial magnetic stimulation, the effects of valproate on silent period and corticomotor excitability. Methods: thirty patients with generalized epilepsy were studied at baseline, and re‐examined 4 (S1) and 25 (S2) weeks after the administration of valproate (mean dose: 1040 ± 284 mg). Transcranial magnetic stimulation was performed with a figure of eight coil (recording, first dorsal interosseous). Threshold was measured at 1% steps. Silent period was measured using a recently described protocol. Briefly, silent periods were elicited at 5% increments from 0 to 100% maximum stimulus intensity. At each stimulus intensity, 4 silent periods were obtained and the average value of silent period duration was used to construct a stimulus/response curve of stimulus intensity versus silent period. The resulting curves were then fitted to a Boltzman function and were statistically compared. The motor‐evoked potential recruitment curve was constructed under active conditions and analyzed in a similar way.

Results

Valproate increased threshold from 36.5 ± 5.99% at baseline to 41.02 ± 7.84% at S1 (p < 0.0001, paired t‐test). The maximum value of the silent period curve decreased from 257.5 ± 3.9 ms at baseline to 230.3 ± 3.9 ms at S1 (p < 0.0001, F‐test and AIC) while the other best‐fit values (V
50
, slope, threshold) were not significantly affected. Regarding the motor‐evoked potential recruitment curve, the maximum value decreased significantly post‐drug (from 0.449 ± 0.007 to 0.392 ± 0.009, p < 0.01, F‐test and AIC test), whereas the rest of the best‐fit values remained unaffected.

Conclusion

In patients with idiopathic generalized epilepsy, valproate increases threshold and reduces the maximum values of the silent period curve and the motor‐evoked potential recruitment curve. These findings probably reflect valproate's effects on voltage‐dependent Na
+
channels, as well as an activation of GABA
A
receptors.
Stimulus‐sensitive burst‐spiking in burst‐suppression in children: implications for management of refractory status epilepticus
Authors: Dan Bernard , Boyd Stewart G.
Published: March 2024

Status epilepticus refractory to sequential trials of multiple medication is a rare but significant problem in children. We describe stimulus sensitivity arising during the treatment of convulsive status epilepticus in children (stimulus‐sensitive burst‐spiking in burst‐suppression). We reviewed retrospectively clinical and EEG features in six children (three months to ten years), with status epilepticus requiring intensive care, in whom tactile, auditory and visual stimulation induced myoclonic jerks and bursts of EEG spikes. Sensitivity was not present at onset, but appeared after 24 hours as myoclonic jerks of the eyes, face and limbs, irrespective of the modality and site of stimulation. These were associated with burst‐suppression in the EEG, the induced spiking forming the burst component. Various antiepileptic drugs, including GABAergic and NMDA blockers had no effect, but halogenated agents (used in two patients) abolished the sensitivity. Two children died, but the remainder returned to their previous clinical state. We conclude that stimulus sensitivity may appear in the context of refractory status epilepticus treated with high‐dose barbiturates. Outcome may be more favorable than previously reported in adults, mostly in the context of post‐anoxic or toxic coma. Evaluation of ventilated children in status epilepticus should include electroclinical assessment using sensory stimulation. If present, the drug regime should be reviewed and halogenated agents considered.
Ketogenic diet in patients with myoclonic‐astatic epilepsy
Authors: Caraballo Roberto Horacio , Cersósimo Ricardo Oscar , Sakr Diego , Cresta Araceli , Escobal Nidia , Fejerman Natalio
Published: March 2024

For more than 80 years, the ketogenic diet has been used as an alternative to antiepileptic drugs for patients with refractory epilepsy. Myoclonic‐astatic epilepsy in early childhood is one of the malignant epilepsy syndromes that often proves refractory to antiepileptic drugs treatment.

Objective

In this prospective study we assess the efficacy and tolerability of the ketogenic diet in patients with myoclonic‐astatic epilepsy.

Material and methods

Between March 1, 1990 and August 31, 2004, 30 patients who met diagnostic criteria of myoclonic‐astatic epilepsy were seen at our department. Eleven of them were placed on the ketogenic diet using the Hopkins protocol and were followed for a minimum of 18 months.

Results

The children had previously received a mean of 5.2 different antiepileptic drugs and were on a mean of 2.2 antiepileptic drugs when the diet was started. Eighteen months after initiating the diet, six of the patients (54.5%) remained on the diet. Two patients (18%) were seizure‐free, two (18%) had a 75‐99% decrease in seizures, and the remaining two children (18%) had a 50% to 74% decrease in seizures. The first two patients were tapered off the diet after remaining seizure‐free, without antiepileptic drugs for several years. In the two patients who had sporadic seizures, antiepileptic drugs were reduced to one, and in the last two the seizure frequency was significantly reduced. No differences in seizure control were found when compared for age, sex, or seizure type. Five of our patients discontinued the ketogenic diet in less than 3 months (four because of lack of effectiveness and one because of persistent vomiting).

Conclusion

The ketogenic diet is a promising therapy for patients with myoclonic‐astatic epilepsy, with over half the children showing a > 50% reduction in seizures, and seizure‐freedom in 18%. In drug resistant cases of myoclonic‐astatic epilepsy, the diet should be considered early in the course of this syndrome and not as a last resort.
NARP syndrome and adult‐onset generalised seizures
Authors: Keränen Tapani , Kuusisto Hanna
Published: March 2024

The neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) syndrome is a maternally inherited disorder attributable to a heteroplasmic mtDNA point mutation. Catastrophic epilepsy may accompany severe, early onset forms of NARP, but seizures seem to be rare in cases with adolescent and adult onset. We describe a patient who developed clumsiness and visual problems in her teens. She had no clinical seizures but an EEG showed generalized spike and wave discharges. At this time the patient remained without a specific diagnosis. At the age of 21, the patient developed progressive ataxia and she also experienced a tonic‐clonic status epilepticus. Further examinations revealed NARP syndrome. EEG abnormalities may precede adult onset seizures in the NARP syndrome.
Ion channels and epilepsy
Authors: Mazzuca Michel , Lesage Florian , Lazdunski Michel
Published: March 2024

Ion channels play a central role in the generation and control of neuronal excitability. Genetic defects in ion channels are associated with several forms of human idiopathic epilepsies. These defects range from nonsense and missense point mutations to insertion, truncation and splice site mutations producing altered, non‐functional or negative‐dominant channel subunits. To date, 12 mutated genes have been identified. They code for Na
+
(
SNC1A, SNC2A, SNC1B
), K
+
(
KCNA1, KCNQ2, KCNQ3
) and Cl
‐
(
CLCN2
) channel subunits, as well as neurotransmitter receptor subunits including Cl
‐
channel GABAA receptor (
GABRA1, GABRG2
) and cationic channel acetylcholine receptor (
CHRNA4, CHRNB2
). One ion transporter Na
+
/K
+
ATPase gene (
ATP1A2
) has also been identified. The epilepsy syndromes related to these genes are as diverse as benign familial neonatal (BFNC ‐
KCNQ2
and
3
) and infantile (BFNIC ‐
SNC2A
and
ATP1A2
) convulsions, episodic ataxia with seizures (AE2 ‐
KCNA1
), generalized epilepsy with febrile seizure plus (GEFS+ ‐
SCN2A, 1A, 1B
and
GABRG2
), autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE ‐
CHRNA4
and
B2
), severe myoclonic epilepsy of infancy (SMEI ‐
SNC1A
), juvenile myoclonic epilepsy (JME ‐
GABRA1
and
CLCN2
), and childhood and juvenile absence epilepsy (CAE, JAE ‐
SNC1B, GABRG2
and
CLCN2
). Despite the difficulty to correlate genotypes and phenotypes, these studies have increased our understanding of causal mechanisms of epilepsy and open a wide range of possibilities for developing better antiepileptic drugs and treatments.
Cryptogenic epilepsies in children: when and how to look for a neurological disorder?
Authors: Echenne Bernard , Roubertie Agathe , Humbertclaude Véronique , Rivier François
Published: March 2024

We present a diagnostic procedure and the corresponding aetiological investigations for a comprehensive approach of a cryptogenic epilepsy in children aged 12 months or more. According to the characteristics of the epilepsy (generalized, partial or poorly defined), the successive steps of the clinical and biological investigations are described, taking into account the patient's age and the type of seizure; the importance of some metabolic diseases and of some chromosomal abnormalities is underlined.