bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of cannabinoids in epilepsy treatment: a critical review of efficacy results from clinical trials
Authors: Nabbout Rima , Thiele Elizabeth A.
Published: March 2024

CBD was shown to have anti‐seizure activity based on
in vitro
and
in vivo
models. However, several reports of small series or case reports of the use of cannabis extracts in epilepsy yielded contradictory results and the efficacy of cannabis use in patients with epilepsy have also been inconclusive. In 2013, the first Phase 1 trial for a purified form of CBD (Epidiolex/Epidyolex; >99% CBD), developed by GW Pharma, showed some efficacy signals and subsequently, a comprehensive program on the efficacy and tolerability of this compound for the treatment of drug‐resistant epilepsies was initiated. Results of these trials led to the FDA and EMA approval respectively in 2018 and 2019 for the treatment of seizures associated with two rare epilepsies: Lennox‐Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients two years of age and older. Thus, CBD became the first FDA‐approved purified drug substance derived from cannabis and also the first FDA‐approved drug for the treatment of seizures in DS. We detail the clinical studies using purified CBD (Epidiolex/Epidyolex), including the first open interventional exploratory study and Randomized Control Ttrials for DS and LGS.
A Chinese patient with epilepsy and
WWOX
compound heterozygous mutations
Authors: He Jing , Zhou Wenjing , Shi Jie , Zhang Bingqing , Wang Haixiang
Published: March 2024

Early infantile epileptic encephalopathy type 28 is a refractory epilepsy with early onset, poor prognosis, and hereditary causes. WW domain‐containing oxidoreductase (
WWOX
) gene mutation can result in epileptic encephalopathy, but the mechanism remains unclear. We present the case of a patient with epilepsy and
WWOX
compound heterozygous mutations. The seizures manifested as tonic‐clonic, convulsive and were refractory to drugs. Magnetic resonance imaging showed a widened subarachnoid space and thin corpus callosum. The patient died from asphyxia at the age of one year and 23 days. Peripheral blood was taken from the patient and his parents, and whole‐exome sequencing was investigated to determine possible gene mutation. Two compound heterozygous mutations were identified: c.172+1G>C (with no amino acid change) and c.984C>G (amino acid change: p.Tyr328Ter). The pathophysiology of epileptic encephalopathy related to the
WWOX
gene remains to be determined, and further studies are required to elucidate possible mechanisms.
The importance of semiological information based on epileptic seizure history
Authors: Wolf Peter , Benbadis Selim , Dimova Petia S. , Vinayan Kollencheri Puthenveettil , Michaelis Rosa , Reuber Markus , Yacubian Elza Márcia
Published: March 2024

Semiology is the backbone of any correct categorization of seizures, as epileptic or not, focal or bilateral, and is fundamental to elucidating how they are anatomically generated in the brain. An anatomical hypothesis derived from seizure history is the precondition for optimally designed ancillary studies. Without understanding seizure semiology, no rational therapy is possible. This article describes the semiological approach using patient history based on full use of patients’ self‐reports as well as descriptions by witnesses. Auras represent the subjective aspects of seizures and provide important semiological clues as observable signs, sometimes including rather precise direct anatomical information. Methods of extracting, facilitating and analysing self‐reports including linguistic conversation analysis are presented in detail. It is highlighted that prodromes, seizure triggers and reflex epileptic mechanisms can provide crucial information for diagnostics and therapy. Special issues considering seizure semiology in children are discussed in a separate section. Other sections are dedicated to the two most important issues of differential diagnosis: how to distinguish (1) focal from “generalized” epilepsies, particularly when focal seizure phenomena appear in a bilateral epilepsy; and (2) epileptic from a series of non‐epileptic events.
Clonic convulsion caused by epileptic discharges arising from the human supplementary motor area as studied by subdural recording
Authors: Ikeda Akio , Nagamine Takashi , Kunieda Takeharu , Yazawa Shogo , Ohara Shinji , Taki Waro , Kimura Jun , Shibasaki Hiroshi
Published: March 2024

In order to help clarify the mechanism of tonic convulsion, which is commonly seen in supplementary motor area (SMA) seizures, we investigated the temporal relationship between ictal discharges arising from the SMA and the associated EMG discharges in the foot, in a patient with SMA seizures, prior to surgical treatment. The patient's intractable seizures consisted of tonic followed by clonic convulsion of the left foot also involving at times, the left hand. Ictal EEGs were investigated by subdural electrodes placed on the SMA‐proper and pre‐SMA, which were defined by cortical stimulation and by recording cortical‐evoked potentials. Interictally, repetitive spike discharges were seen at the pre‐SMA. Each seizure initially had a tonic phase associated with an electrodecremental EEG pattern. It was followed by clonic convulsion as shown by clonic EMG discharges of the left tibialis anterior (TA) muscle. It had a duration of 300 to 500 msec, and on each occasion a positive cortical activity at the pre‐SMA preceded the EMG onset by 110 msec, and a negative spike at the SMA‐proper preceded the EMG onset by 50 to 60 msec. Epileptic discharges originating from the pre‐SMA spread to the SMA‐proper and possibly also to the primary motor cortex (MI) in this patient. Since both SMA‐proper and MI could elicit EMG discharges through the independent corticospinal tracts having different conduction velocities, even a single spike arising from the SMA could give rise to a long EMG burst, which may play some role in the tonic convulsion which characterizes SMA seizures.
Idiopathic partial epilepsy: electroclinical demonstration of a prolonged seizure with sequential rolandic and occipital involvement. Seizure spread due to regional susceptibility?
Authors: Parmeggiani Lucio , Guerrini Renzo
Published: March 2024

Benign rolandic epilepsy (BRE) and childhood epilepsy with occipital paroxysms (CEOP) are overlapping in age range of presentation. Some children have been reported to manifest occipital and rolandic seizures, as distinct events. However, the presence during the same seizure of rolandic and occipital symptoms is exceptional. We present a 7‐year‐old boy with BRE in whom we video‐EEG recorded two seizures at 4years of age. The first episode was a classic rolandic seizure during sleep, while the second was prolonged with initial rolandic and late occipital involvement. It is possible that a rolandic seizure, in a child within the age range of both BRE and early onset CEOP, could spread to selectively involve the occipital lobe, because there is susceptibility of cortical neurons of both areas to develop seizures at this age in idiopathic partial epilepsies.
Epilepsy and paroxysmal movement disorders in families: evidence for shared mechanisms
Authors: Singh Rita , Macdonell Richard A.L. , Scheffer Ingrid E. , Grassland Kathryn M. , Berkovic Samuel F.
Published: March 2024

The epilepsies have been regarded as clinically distinct from the paroxysmal movement disorders. Recently, a variety of ion channel defects have been identified as the biological basis of certain familial epilepsies and paroxysmal movement disorders. We studied two families with the cooccurrence of epilepsy, movement disorders and migraine.

Information was obtained on 147 individuals in the two families. In family WF, there was a co‐occurrence of epilepsy (benign infantile convulsions, idiopathic generalized epilepsy), episodic ataxia (with cerebellar atrophy and without myokymia) and common migraine. In family CL, epilepsy (febrile seizures, febrile seizures plus), kinesigenic paroxysmal dyskinesia and migraine (including hemiplegic migraine) were observed in various combinations over 3 generations.

The observations in these two families, together with review of the literature, suggest that the co‐occurrence of epilepsy (particularly benign infantile convulsions), paroxysmal movement disorders and migraine is not due to chance. Thus, these distinct clinical phenomena could have a shared biological basis and ion channel defects are an attractive possibility.
Video‐EEG telemetry: apparent manifestation of both epileptic and non‐epileptic attacks causing potential diagnostic pitfalls
Authors: Raymond A.A. , Gilmore W.V. , Scott C.A. , Fish D.R. , Smith S.J.M.
Published: March 2024

Video‐EEG telemetry is often used to support the diagnosis of non‐epileptic seizures (NES). Although rare, some patients may have both epileptic seizures (ES) and NES. It is crucially important to identify such patients to avoid the hazards of inappropriate anticonvulsant withdrawal. To delineate the electroclinical characteristics and diagnostic problems in this group of patients, we studied the clinical, EEG and MRI features of 14 consecutive patients in whom separate attacks, considered to be both NES and ES were recorded using video‐EEG telemetry. Only two patients were drug‐reduced during the telemetry. Most patients had their first seizure (ES or NES) in childhood (median age 7 years; range: 6 months‐24 years); 8/14 patients were female. Brain MRI was abnormal in 10/14 patients. Interictal EEG abnormalities were present in all patients; 13/14 had epileptiform and 1/14 only background abnormalities. Over 70 seizures were recorded in these 14 patients: in 12/14 patients, the first recorded seizure was a NES (p < 0.001), and 7 of these patients had at least one more NES before an ES was recorded. Only 3/14 patients had more than 5 NES before an ES was recorded. Recording a small number of apparently NES in an individual by no means precludes the possibility of additional epilepsy. Particular care should be taken, and multiple (>5) seizure recording may be advisable, in patients with a young age of seizure onset, interictal EEG abnormalities, or a clear, potential aetiology for epilepsy.
SPECT findings in reflex seizures induced by movement in non‐ketotic hyperglycemia
Authors: Suárez‐Moro R. , Salas‐Puig J. , Amorín M. , Róiz C. , Lahoz CH.
Published: March 2024

Content available: Video
Research perspectives in cortical dysplasia and associated epilepsies
Authors: Munari Claudio , Tassi Laura , Russo Giorgio Lo , Francione Stefano , Mai Roberto , Cardinale Francesco , Spreafico Roberto
Published: March 2024

Our understanding of cortical alterations and related epilepsies has grown enormously in the last decade thanks to the explosion of basic information from laboratory neuroscience combined with advances in diagnostic tools, therapeutic approaches and surgical techniques.

In the present paper, we briefly review the most important advances in these fields from the point of view of the clinician concerned with cortical malformation‐related epilepsies. We propose that a highly effective way forward, expected not only to widen knowledge of the basic mechanisms of seizure generation, but also to improved the management of patients, would be to promote interdisciplinary research programmes on resected human cortex that involve neurosurgeons, neurologists and laboratory neuroscientists.
Catastrophic epilepsy in infants and children: Identification of surgical candidates
Authors: Wyllie Elaine
Published: March 2024

Some pediatric candidates for epilepsy surgery have epilepsy which is considered catastrophic because of a high seizure frequency, often many per day, in association with developmental stagnation or regression. Increasing numbers of infants with catastrophic epilepsy are being considered for surgical treatment, if they have the key elements of surgical candidacy including medically intractable epilepsy, a localized epileptogenic zone, and a low risk of new, unacceptable, postoperative neurologic deficits. Most of these infants have had low grade tumor, cortical development malformations, or other epileptogenic lesions visualized on preoperative MRI. The assessment of potential risks and benefits for surgery in these patients involves complex, age‐related issues including the possible impact of uncontrolled seizures or surgery, on cognitive development. This review will address some of these issues in the context of two clinical cases.
“Dual pathology” and the significance of surgical outcome in “Dostoewsky's epilepsy”
Authors: Vera C.L. , Patel S.J. , Naso W.
Published: March 2024

A patient with a right occipital arteriovenous malformation (AVM) and seizures heralded by “lights”, and experiencing “ecstasy” underwent a right occipital lobectomy after the AVM was embolized. Thereafter, seizures began with motor arrest and lip smacking, but never again with “light and ecstasy”.

A right temporal lobectomy and electrocorticogram (E.Co.G) were performed under local anesthesia four years after occipital lobectomy. Abundant spiking activity was recorded from the right hippocampus which showed gliosis and neuronal loss in the pathology studies. Electrical stimulation of the lateral and basal temporal cortices failed to elicit the vision of “lights” or the experience of “ecstasy”.

The patient has had two seizures in the last two years as a result of a lapse in taking his anti‐convulsant medication. He now lives alone, seizure‐free.

The possible abnormally induced functional network organization and structures involved in the production of the “ecstasy” phenomenon are discussed.
Long‐term outcome of epilepsy
Authors: Sillanpää Matti
Published: March 2024

Few prospective, population‐based, long‐term follow‐up studies exist on people with epilepsy. Still fewer reports cover social outcome. Overall mortality is two to three times higher than expected. The contribution of epilepsy is variable. Importantly, the type of epilepsy syndrome and gender must be considered in the estimation of mortality rates in epilepsy. Sudden unexpected death and its mechanisms also need further consideration. Approximately, two thirds of surviving patients will be in terminal remission twenty years after onset of epilepsy and half of them are seizure‐free without medication. The best independent predictors of remission are absence of organic brain damage, low intensity seizure propensity and good early effect of drug therapy. The long‐term outcome is often predictable by observation of the early outcome of seizures. One third of children with epilepsy are mentally retarded. Poor social outcome is related to associated neurological disabilities, drug resistant seizures and polytherapy. However, even patients with uncomplicated epilepsy, idiopathic etiology and terminal remission without medication do less favourably than their matched controls in basic and vocational education, and reproductive activity. The employability of this subgroup, however, does not differ significantly from that of controls, compared with approximately 60% of all people with epilepsy. Further research is needed particularly to enable a better determination of predictors of long‐term outcome, recurrence of seizures after drug withdrawal and the role of drug therapy in long‐term prognosis.
Continuous spikes and waves during slow sleep (CSWS): outcome in adulthood
Authors: Hommet Caroline , Billard Catherine , Barthez Marie Anne , Gillet Patrice , Perrier Daniele , Lucas Brigitte , de Toffol Bertrand , Autret Alain
Published: March 2024

We report a longitudinal, electroencephalographic and neuropsychological analysis of epilepsy with continuous spikes and waves during slow sleep (CSWS) in a 19 year‐old boy. The clinical course fluctuated, with temporary worsening or improvement of the paroxysmal abnormalities, epilepsy and cognitive functions. At the end of the follow‐up period, seizures persisted. Evaluation of the boy's behaviour, language and cognitive function suggested a dysexecutive syndrome. We discuss the relationship between paroxysmal abnormalities and neuropsychological disorders.
Reflex epilepsy and reflex seizures of the visual system: a clinical review
Authors: Zifkin Benjamin G. , Trenité Dorothée Kasteleijn‐Nolst
Published: March 2024

Reflex epilepsy of the visual system is charecterised by seizures precipitated by visual stimuli. EEG responses to intermittent photic stimulation depend on the age and sex of the subject and on how stimulation is performed: abnormalities are commonest in children and adolescents, especially girls. Only generalised paroxysmal epileptiform discharges are clearly linked to epilepsy. Abnormal responses may occur in asymptomatic subjects, especially children. Photosensitivity has an important genetic component. Some patients are sensitive to patterns, suggesting an occipital trigger for these events. Myoclonus and generalised convulsive and nonconvulsive seizures may be triggered by visual stimuli. Partial seizures occur less often and can be confused with migraine. Although usually idiopathic, photosensitive epilepsy may occur in degenerative diseases and some patients with photosensitive partial seizures have brain lesions. Sunlight and video screens, including television, video games, and computer displays, are the commonest environmental triggers of photosensitive seizures. Outbreaks of triggered seizures have occurred when certain flashing or patterned images have been broadcast. There are regulations to prevent this in some countries only. Pure photosensitive epilepsy has a good prognosis. There is a role for treatment with and without antiepileptic drugs, but photosensitivity usually does not disappear spontaneously, and then typically in the third decade.
Ictal spitting during a left temporal lobe‐originated complex partial seizure: a case report
Authors: Özkara Çiğdem , Hanoğlu Lütfü , Eskazan Esat , Kulaksyzoğlu Işyl Baral , Özyurt Emin
Published: March 2024

We present a 35‐year‐old male patient with intractable temporal lobe epilepsy in whom spitting automatism was documented by ictal recordings during seizures. Spitting is an uncommon automatism and occurs mainly with right‐sided, nondominant, temporal focus. However, our patient had left mesial temporal sclerosis with nonverbal memory impairment, but intracarotid amobarbital test demonstrated language and memory dominance on the right hemisphere. The authors feel that this case supports the hypothesis of a nondominant, temporal lobe origin for the spitting automatism.
Drop episodes in Coffin‐Lowry syndrome: an unusual type of startle response
Authors: Caraballo R. , Rocha A. Tesi , Medina C. , Fejerman N.
Published: March 2024

We present a patient with a complete Coffin‐Lowry syndrome, associated with drop episodes precipitated by sudden auditory stimuli, which provoked in turn, a definite loss of muscle tone in both legs. Electrophysiological studies showed that these episodes are an unusual type of startle response and that they may be associated with Coffin‐Lowry syndrome.
Outcome of corpus callosotomy and other pediatric epilepsy surgery: parental perceptions
Authors: Sassower Kenneth C. , Rollinson Denise C. , Duchowny Michael
Published: March 2024

Purpose

Parental perceptions regarding the outcome of epilepsy surgery in their children were assessed preoperatively via telephone survey.

Methods

Twenty‐seven parents – sixteen mothers (MO), eleven fathers (FA) – of sixteen children (nine boys, seven girls; ages 6 months‐18 years) with intractable epilepsy (refractory to ≥ 3 anticonvulsants) were interviewed. Twenty‐four questions were posed during single, 20‐minute sessions to both parents.

Results

A majority of parents (63% MO, 82% FA) would consider epilepsy surgery successful if it achieved ≥ 75% seizure reduction. Incomplete seizure control would even be acceptable if the overall number of seizures were reduced (69% MO, 18% FA). In order to gain seizure remissions, behavioral deterioration would be accepted (57% MO, 50% FA). Less than total seizure control would be accepted if surgery produced behavioral improvement (57% MO, 51 % FA, Kappa > 0.6). For seizure reduction, parents would accept: visual field deficits (82% MO, 67% FA), short‐term memory deficits (33% MO, 75% FA), and speech problems (56% MO, 17% FA).

Conclusion

Parents of children with medically‐resistant seizures perceive adverse physical and behavioral consequences of epilepsy surgery to be acceptable if there is adequate seizure control. Their acceptance of postoperative deficits underscores the magnitude of the handicap produced by chronic childhood epilepsy.
Reversible aphasic disorder induced by lamotrigine in atypical benign childhood epilepsy
Authors: Battaglia Domenica , Luvone Laura , Stefanini Maria‐Chiara , Acquafondata Celeste , Lettori Donatella , Chiricozzi Francesca , Pane Marika , Mittica Antonio , Guzzetta Francesco
Published: March 2024

Purpose

We studied an eleven year‐old girl with atypical, benign partial epilepsy who acutely presented a severe aphasia associated with marked EEG deterioration after lamotrigine administration. A parallel monitoring of language disorders and EEG changes during the gradual withdrawal of lamotrigine was performed in order to evaluate their possible correlation with lamotrigine administration.

Methods

Detailed neuropsychological and linguistic examinations in association with awake and sleep EEG were periodically performed.

Results

The evolution of the aphasic disorder was closely related to the EEG abnormalities, and disappeared after the withdrawal of lamotrigine.

Conclusions

We considered the hypothesis that our case could be an expression of a paradoxical reaction to lamotrigine, in which the transitory aphasic disorder was sustained by an epileptiform electric activation.
Localisation de sources distribuées et comparaison avec PIRM fonctionnelle
Authors: Lantz Göran , Spinelli Laurent , Menendez Rolando Grave de Peralta , Seeck Margitta , Michel Christoph M.
Published: March 2024

Cet article détaille l'utilisation des algorithmes de localisation des sources électriques distribuées dans le cadre d'un bilan pré‐chirurgical pour des patients épileptiques pharmaco‐résistants. Contrairement au modèle de type dipôle équivalent, les méthodes de localisation de sources distribuées permettent de déterminer une zone d'activation comme on en trouve souvent en épilepsie. Les techniques utilisées ici reposent sur des algorithmes linéaires de résolution du problème inverse. De ce fait elles sont moins enclines à produire des erreurs de localisation lorsque l'espace de solution est contraint sur la matière grise de chacun des patients. Nous proposons trois solutions pour augmenter la résolution spatiale de ces reconstructions de sources à fin de pouvoir distinguer plusieurs sources distinctes au sein d'un même lobe. La première est l'augmentation du nombre d'électrodes au‐delà de 100, la seconde est l'utilisation des méthodes linéaires de haute exactitude pour détecter des sources focales (EPIFOCUS) et la troisième est la combinaison des reconstructions de sources électriques avec les activations relevées par l'IRMf déclenchée par l'EEG. Cette dernière approche est très importante car elle permet d'ajouter aux activations hémodynamiques relevées par l'IRMf une information temporelle et donc de différencier le foyer primaire des sites de propagation. Les techniques de localisations de sources peuvent s'appliquer aux données ictales et inter‐ictales. Dans le cas de l'EEG ictal, nous recherchons, dans un premier temps, à déterminer la ou les fréquences qui apparaissent au début des crises puis nous reconstruisons les générateurs responsables de ces fréquences caractéristiques.
Variations de l'activité des rythmes EEG en relation à un événement. Application à la physiologie et à la pathologie du mouvement
Authors: Szurhaj William , Labyt Etienne , Bourriez Jean‐Louis , Cassini François , Defebvre Luc , Hauser Jean‐Jacques , Guieu Jean‐Daniel , Derambure Philippe
Published: March 2024

La traduction la plus classique d'un événement répété sur l'électroencéphalogramme (EEG) est le potentiel évoqué dont la mise en évidence repose sur le moyennage de l'EEG. La condition nécessaire à cette technique est qu'il existe une relation de phase entre le stimulus et le potentiel évoqué par ce stimulus. La réactivité des rythmes EEG induite par un événement ne peut donc pas être mise en évidence par une simple technique de moyennage, cette réactivité ne survenant pas toujours à la même phase du signal. L'étude de cette réactivité est possible par la méthode des Désynchronisations et Synchronisations Liées à l'Événement (DLE/SLE) proposée par Pfurtscheller et Aranibar en 1977. Cette méthode consiste à mesurer l'évolution temporelle de la puissance du signal EEG dans une bande de fréquence donnée, avant, pendant, et après un événement. La DLE correspond à l'atténuation d'amplitude d'un rythme EEG en rapport avec un événement. Inversement, une augmentation d'amplitude en relation avec l'événement correspond à une SLE. Les DLE traduisent l'activation des aires corticales sous‐jacentes. Les SLE traduiraient en partie la mise au repos du cortex, et probablement également des phénomènes de réafférentation somesthésique. Cette méthode peut être appliquée à l'étude de nombreux processus: mnésiques, auditifs, attentionnels, anticipatoires et moteurs. Ainsi un mouvement volontaire auto‐commandé de la main dominante s'accompagne d'une DLE précoce des rythmes mu et bêta précédant le mouvement de respectivement 2 000 et 1 500 ms, enregistrée en regard de la région centrale contralatéral. Cette DLE devient bilatérale au début du mouvement et est maximale à la fin de celui‐ci. Elle est alors suivie d'une SLE des rythmes bêta. Nous montrons que ces phénomènes de DLE/SLE varient en fonction du type de mouvement, et permettent d'explorer les modifications de l'excitabilité corticale rencontrées au cours de la maladie de Parkinson et de l'épilepsie avec crises motrices.
Prospective study on concentration‐efficacy and concentration‐toxicity: Correlations with lamotrigine serum levels
Authors: Fröscher Walter , Keller Ferdinand , Vogt Heinrich , Krämer Günter
Published: March 2024

Rationale:

The relationship between lamotrigine (LTG) serum concentration and clinical response in patients with epilepsy is still controversial. We therefore performed a prospective study in which LTG was added to the existing therapeutic regimen in patients with poorly controlled epilepsy. The goal of the study was to determine the serum levels of patients with seizure reduction of at least 50% after addition of LTG, and to assess a possible relationship between the occurrence of adverse effects due to LTG and its serum concentration.

Methods:

Fifteen adult patients were evaluated with respect to seizure reduction. Nine patients had focal seizures with or without generalization, six patients had generalized seizures (Group I). The correlation between the occurrence of adverse effects and LTG serum concentration was calculated in a second group of 63 young adult, and adult patients with epilepsy (Group II).

Results:

The range of the LTG serum concentration in the 15 patients with a 50% or greater reduction of seizure frequency was 1.3‐7.1 μg/ml (median = 3.6 μg/ml). In group II patients the serum concentration associated with an adverse effect was not significantly different from the serum concentration in patients without adverse effects. There was, however, a tendency for higher serum concentrations in patients with adverse effects. In the serum concentration range of 5 to 13 μg/ml, the frequency of LTG levels which were accompanied by an adverse effect increased only slowly, whereas above 13‐14 μg/ml, there was a steep increase in adverse effects. The serum concentration of four patients with tremor (mean = 14 ± 2.8 μg/ml) was significantly higher than the LTG level which were in 42 patients who did not have adverse effects at any time (mean = 4.8 ± 4.1 μg/ml),
P
= 0.003.

Conclusion:

Our results suggest a target range for LTG serum concentrations of 1‐13 μg/ml, especially, if LTG is used as an add on‐drug.
Seizure‐induced hippocampal damage in the mature and immature brain
Authors: Lado Fred A. , Laureta E.C. , Moshé Solomon L.
Published: March 2024

Neurologists caring for patients who have experienced a first seizure or who are at increased risk of seizures are concerned with two questions. First, at what point do seizures lesion the brain and create the conditions for unprovoked, recurrent seizures,
i.e.
epilepsy. And second, seizure‐induced changes can be prevented pharmacologically following an initial prolonged seizure, or prophylactically in individuals deemed at high risk of epilepsy? The number, duration and severity of seizures each influence the likelihood that an individual will experience chronic seizure‐induced brain damage. However, the thresholds for deleterious seizure‐induced sequelae are not well understood. Will repeated brief seizures produce similar changes as a single prolonged seizure? Do permanent alterations of neuronal function result from a single brief seizure? How long can neurons resist damage caused by prolonged seizures? These are all questions of immediate clinical significance. The anatomical, synaptic and functional consequences of seizures have been most extensively studied in the hippocampus, an epileptogenic structure that plays a central role in the generation of temporal lobe seizures. In this review, we will discuss the spectrum of known hippocampal alterations in epilepsy and highlight mechanisms through which neuronal and synaptic changes accrue. In addition to discussing the effects of prolonged seizures on the hippocampus, we will also review current data regarding the effects of repeated brief seizures as well as the effect of a single brief seizure. We will also discuss the relevance of development and gender on the manifestations of seizure‐induced damage, in order to begin to stratify the risk of seizure sequelae to different human populations depending on age, and – to a lesser extent – on gender.

The decision whether to treat, and how to treat seizures, results from an understanding of the immediate and long‐term risks to the patient of either recurrent seizures, or of seizure‐induced brain damage. Paradigmatic to this type of decision is the assessment of febrile seizures, a common occurrence in childhood. Current clinical and laboratory data indicate that simple febrile seizures do not result in long‐term brain injury. However, novel laboratory findings indicate that even “benign” febrile seizures may produce subtle long‐term changes in neuronal behavior‐such as altered synaptic function. The improved understanding of the mechanism producing these long term effects is a necessary first step in the development of neuroprotective treatments that can be applied either in the acute setting at the time of an initial prolonged seizure, or prophylactically in individuals most likely to high risk of developing epilepsy.
Surgical pathology of drug‐resistant partial epilepsy: A 10‐year‐experience with a series of 327 consecutive resections
Authors: Pasquier Basile , Péoc'h Michel , Fabre‐Bocquentin Blandine , Bensaadi Lamia , Pasquier Dominique , Hoffmann Dominique , Kahane Philippe , Tassi Laura , Le Bas Jean‐François , Benabid Alim Louis
Published: March 2024

Herein we reviewed the histopathological findings in 327 consecutive surgical specimens from patients with pharmaco‐resistant epilepsy (PRE). Three major pathological groups (78.3% of all cases) were identified: Ammon's horn sclerosis (85 cases as an isolated lesion plus 18 as one part of a dual pathology), tumors (94 cases), and malformations (77 cases). Tumors, often associated with cortical dysplasias (CDs), were all of low histological grade and included 61 dysembryoplastic neuroepithelial tumors (DNTs), 29 gangliogliomas, and 4 pleomorphic xanthoastrocytomas (PXAs). Among the malformations were observed 52 CDs, 13 cavernomas, 8 cortical tubers, and 4 cysts. The remaining findings consisted of 16 scars (mostly posttraumatic) and 4 Rasmussen's encephalitis. Fifty‐one (15.6%) specimens contained non‐specific changes, and histological samples from 215 patients with presurgical implantation of electrodes revealed iatrogenic changes. All these figures are in agreement with the most recent and comparable series, and confirm the high incidence of DNTs that appear clearly as the most common tumoral entity in PRE. Our data also support the hypothesis of a close histogenetic relationship between DNT, ganglioglioma, and PXA, with a putative common origin from pluripotential progenitor CD34 positive cells of the subpial granular layer. As for CDs, our study confirms the clinical relevance of two main subtypes: severe CD (or Taylor's type CD) with neuronal cytomegaly and balloon cells, and non‐Taylor's type CDs with a better outcome. Eventually, this series demonstrates that most patients have significant histopathological lesions, among which, aspects that are relevant to the diagnostic surgical pathologist are highlighted [published with a complete image database on CD‐Rom].
Clinical features and EEG findings differentiating mesial from neocortical temporal lobe epilepsy
Authors: Pfänder Mona , Arnold Stephan , Henkel Anja , Weil S. , Werhahn Konrad J. , Eisensehr Ilonka , Winkler Peter A. , Noachtar Soheyl
Published: March 2024

We evaluated whether mesial temporal lobe epilepsy (MTE) and neocortical temporal lobe epilepsy (NTE) can be distinguished on electroclinical grounds. One hundred and twenty‐two consecutive MTE (
n
= 86) and NTE (
n
= 36) patients were included in this prospective study. All patients underwent prolonged EEG‐video monitoring and high resolution magnetic‐resonance imaging (MRI). MTE was defined as epilepsy with purely mesial temporal lesion in the absence of extramesial temporal pathology, based on pre‐operative MRI or post‐operative histology. NTE was defined as neocortical temporal MRI lesions, depth recorded neocortical temporal seizure onset and lack of mesial temporal lesions on MRI or histology. One thousand two hundred and fourty‐nine epileptic seizures were analyzed. Congenital malformation (NTE 19%
versus
MTE 3%,
P
< 0.01), nonspecific auras (NTE 25%
versus
MTE 8%,
P
< 0.001) and early clonic activity following automatisms (NTE 22%
versus
MTE 8%,
P
< 0.03) were more frequent in NTE. In contrast, a history of febrile seizures (MTE 29%
versus
NTE 3%,
P
< 0,001), abdominal auras (MTE 62%
versus
NTE 33%,
P
< 0.005) and contralateral hand dystonia (MTE 43%
versus
NTE 22%,
P
< 0.03) were more often documented in MTE. Interictal epileptiform discharges in MTE occurred predominantly (> 67%) over the ipsilateral mesial temporal regions (MTE 65%
versus
NTE 33%,
P
< 0.001). No MTE patient had lateral neocortical temporal spike predominance (NTE 22%,
P
< 0.001). Multiple logistic regression revealed that a history of febrile seizures, abdominal auras, contralateral dystonic posturing and predominance of ipsilateral mesial temporal spikes point to MTE, with an accuracy of 73% (PPV 81%, NPV 70%). Analyzing clinical and EEG features, particularly the distribution of interictal epileptiform discharges, helps to differentiate between MTE and NTE.
Idiopathic generalised epilepsies with 3 Hz and faster spike wave discharges: A population‐based study with evaluation and long‐term follow‐up in 71 patients
Authors: Siren Auli , Eriksson Kai , Jalava Heli , Kilpinen‐Loisa Päivi , Koivikko Matti
Published: March 2024

For several years we have been following patients with intractable, childhood‐onset idiopathic generalised epilepsies with ≥ 3 Hz spike‐wave discharges. Our need to find explanations for their intractability was the starting point for this study. We were interested in identifying characteristics, which would predict intractability; evaluating how these patients were treated and whether polytherapy was useful. We identified patients with ≥ 3 Hz spike‐wave discharges by reviewing EEG reports recorded between 1983 and 1992. Data were collected from medical records and through personal interviews. We identified 82 patients with tentative idiopathic generalised epilepsy. Eleven were excluded. Thirty‐eight patients had childhood absence epilepsy, 18 had juvenile absence epilepsy, 13 had juvenile myoclonic epilepsy and two had eyelid myoclonia with absences: 89.5, 78, 38 and 0% of the patients in each group, respectively, had been seizure free for more than 2 years. Twenty percent of the patients had intractable seizures. All intractable patients with juvenile absence epilepsy had rhythmic, random eyelid blinking and generalised tonic‐clonic seizures. A history of more than ten generalised tonic‐clonic seizures was associated with intractability in juvenile myoclonic patients. Monotherapy with ethosuximide or valproate resulted in seizure control in 65% of patients. Seventeen patients (24%) were treated with polytherapy, six achieved remission. These six patients had childhood absence epilepsy and juvenile absence epilepsy. Positive outcome was found in childhood absence epilepsy and juvenile absence epilepsy. Intractable seizures were more frequent among patients with juvenile myoclonic epilepsy. None of them benefited from polytherapy with conventional anti‐epileptic drugs.
Treatment options in pediatric epilepsy syndromes
Authors: Arzimanoglou Alexis
Published: March 2024

Recent evidence suggests that various epilepsy syndromes respond differently to antiepileptic drugs. It follows that a more precise diagnosis, together with a better understanding of AED mechanisms of action, enables them to be used more specifically, and therefore more effectively. Patient characteristics including age of onset, seizure frequency, EEG data and the findings of imaging studies, provide diagnostic pointers which enable the physician to reach a syndrome diagnosis and to choose the most appropriate AED for the individual patient. Home videotapes of paroxysmal events are becoming increasingly available and are often of great assistance. Parents should be encouraged to record their children's attacks. Careful history‐taking and correct interpretation of clinical data remain the cornerstones of accurate diagnosis and successful treatment.

However, the specificity of antiepileptic drugs is relatively limited and often pharmacotherapy should start using an agent with a broad spectrum of activity appropriate for the primary seizure type. It is in fact common that several antiepileptic agents have similar or identical effectiveness for one particular form of epilepsy. Therefore, the eventual side effects and the greater or lesser difficulties in handling the drug play an essential role in the choice of a therapeutic agent. Polypharmacy should be avoided and surgery should be considered early for selected patients, particularly children, who fail to respond to an appropriate drug trial. Correct diagnosis and the first drug(s) used may have a crucial impact on the evolution of given epilepsy. One major emphasis in the management of epilepsy is on information that should be complete, adapted to the level of understanding, and objective, although given in a positive manner. The understanding and cooperation of children and their families is clearly decisive for the success of therapy, and this requires a confident relationship between the physician and the patient.

Current knowledge, on antiepileptic drugs options in paediatric epilepsy syndromes, is discussed.
Fear, anger and compulsive behavior during seizure: involvement of large scale fronto‐temporal neural networks
Authors: Bartolomei Fabrice , Guye Maxime , Wendling Fabrice , Gavaret Martine , Régis Jean , Chauvel Patrick
Published: March 2024

Seizure‐related, abnormal affective and gestural behavior may involve some of the same processes as those underlying non‐pathological behavior, but their mechanisms remain largely unknown. In this report, we studied a patient in whom seizures initially involved the medial temporal region before involving the frontal cortex. Seizure semiology of the second part of the seizure included marked emotional disturbances (dominated by intense fear and anger) and compulsive behavior to bite into something. This patient underwent pre‐surgical evaluation including intracerebral electroencephalographic recordings (SEEG, stereoelectroencephalography).

Methods

In addition to SEEG examination, we used coherence analysis of signals as a means of studying functional coupling between different regions of the brain. Two seizures were studied. Coherence values from different periods of interest were compared to identify the neural structures involved at the onset of seizure activity as well as during the emotional behavioral changes.

Results

A first network of neural structures was identified within the right anterior temporal regions (amygdala, temporal pole, hippocampus, temporal neocortex). At the time of intense affective and compulsive changes, and by comparison with the first ictal period, a second network was identified characterized by significant functional coupling between the amygdala, the orbito‐frontal structures and the frontal opercular region, while a decrease in functional coupling between these regions and the dorsolateral region and the cingulate gyrus was apparent.

Conclusion

This study show that the emergence of an intense affective and behavioral state during a temporal lobe seizure could be related to the involvement of a network of structures including the anterior temporal lobe and the orbito‐frontal cortex. The decrease of coupling between these regions and the lateral prefrontal and cingulate regions could also participate in these phenomena.
Epilepsy and women's issues: An update
Authors: Tettenborn Barbara , Genton Pierre , Poison David
Published: March 2024

Although the fundamentals of epilepsy are similar for both males and females, the clinical management of epilepsy in women should take into consideration a variety of factors including: social and cultural issues, age, relationships, diagnosis and characterization, female specific syndromes, the influence of female hormones, hormonal contraceptives and hormonal replacement therapy, the cosmetic side effects of epilepsy treatment, fertility, pregnancy and child care. Regarding the issue of reproduction, there are several misconceptions in relation to fertility in women with epilepsy. In general, women with epilepsy do not have a markedly reduced fertility compared with those without. Standard AEDs in common use have been associated with an increased risk of foetal malformations and with newer AEDs there is very little information regarding teratogenicity. The incidence of congenital malformations is also known to increase with the number of AEDs. Before planning a pregnancy it is imperative that the best possible seizure control is achieved at the lowest possible AED dose, preferably in monotherapy. With this in mind, the importance of effective pre‐pregnancy counselling should be stressed and along with appropriate patient management and folic acid supplementation, effective patient education, most women with epilepsy can lead normal lives and deliver healthy children. This report will provide an update on these important considerations for women with epilepsy from both a social and medical perspective.
Seizures and the basal ganglia: a review of the clinical data
Authors: Vercueil Laurent , Hirsch Edouard
Published: March 2024

This article attempts an overview of the clinical and electrophysiological evidence supporting the involvement of the basal ganglia in epileptic seizures. In contrast to animal data, evidence for a role of these structures in human epilepsies is lacking. However, from the theoretical point of view, it remains conceivable that, given their strong interconnectivity, basal ganglia could be functionally linked to the cerebral cortex during an epileptic seizure. Several clinical ictal aspects have been suggested to be compatible with the involvement of basal ganglia, namely, ictal dystonic posturing during temporal lobe seizures, rotatory seizures and paroxysmal dyskinesia‐like seizures. On the other hand, basal ganglia dysfunction may also influence some aspects of epilepsy, as suggested by pure basal ganglia pathology such as Parkinson's disease, or the described effect of an acute basal ganglia lesion in epileptic patients. The data discussed in this review may stimulate further research to link basic scientific data to human epilepsies, and lead to the development of novel therapeutical solutions.
The control of seizures by the basal ganglia? A review of experimental data
Authors: Deransart Colin , Depaulis Antoine
Published: March 2024

Over the past few years, the role of the basal ganglia in epilepsy has been widely debated, the debate being mainly based on experimental data obtained from several animal models. In the present review, the possibility that basal ganglia circuits can generate some forms of seizure or participate to their initiation will first be addressed. In the second part of this chapter, recent data suggesting the involvement of the basal ganglia in the control of seizures will be discussed. Although it is clear that basal ganglia circuits cannot generate seizures and are unlikely to be involved in their initiation, numerous experimental data have revealed that seizures modify the activity of this system. More recently, the collection of pharmacological and electrophysiological data in animal models of epilepsy has led to the emergence of the basal ganglia as a possible control circuit for the seizures. These experimental data have already led to initial clinical trials in epileptic patients. The preliminary clinical data encourage the further development of experimental research in chronic models of epilepsy to better determine the exact output circuits involved in seizure interruption, the mechanisms participating in seizure control and whether the same circuits are involved in the control of different types of seizures. These studies may allow the identification of crucial structures and the types of epilepsy likely to benefit from this new therapeutic approach.
Rational conversion from antiepileptic polytherapy to monotherapy
Authors: Baulac Michel
Published: March 2024

For patients with epilepsy, the goal of treatment is to achieve seizure freedom with minimal or no adverse events. Around 60%‐70% of newly diagnosed patients will achieve this goal with single antiepileptic drug (AED) therapy, and there is universal agreement that prescription of a single agent constitutes best practice for such patients. For the 30%‐40% of patients with poorly controlled epilepsy, treatment options are less clear and many receive add‐on therapy with one or more AEDs in an attempt to improve seizure control. Because the therapeutic gain from adjunctive therapy is often marginal and may be complicated by increased drug toxicity, converting individual patients from polytherapy to monotherapy is a common clinical problem facing physicians managing patients with epilepsy today. Evidence from studies with both standard and new AEDs shows that selected patients, including those with previously resistant epilepsy, can be converted successfully from polytherapy to monotherapy without loss of seizure control and in some cases with improved seizure control. Adverse effects can be minimised during the conversion process by slow withdrawal of the first prescribed drug, while increasing the daily dose of the add‐on AED to achieve optimal therapeutic doses/levels for continued monotherapy. Deciding which drug(s) to withdraw and which to continue as monotherapy requires adequate consideration of individual patient needs with reference to clinical profiles (seizure type and severity), previous response to individual AEDs and the pharmacokinetic and pharmacodynamic implications of withdrawal.