C. Dravet

Multilobar polymicrogyria, intractable drop attack seizures, and sleep-related electrical status epilepticus.

Background and Objective: Patients with cortical malformations often have intractable seizures and are candidates for epilepsy surgery. Within an unselected series of patients with various forms of cortical malformation, nine patients with multilobar polymicrogyria had electrical status epilepticus during sleep (ESES) accompanied by infrequent focal motor seizures. Eight patients also had intractable atonic drop attack seizures. Because ESES usually is accompanied by a good long-term seizure prognosis, the objective of this study was to examine ESES outcome among patients with a structural lesion that is usually highly epileptogenic and has a low seizure remission trend. Methods: The nine patients had follow-up periods lasting 4 to 19 years. All underwent brain MRI, serial sleep EEG recordings, and cognitive testing during and after ESES. Results: ESES and drop attack seizures appeared between the ages of 2 and 5 years(mean, 4 years) and ceased between the ages of 5 and 12 years (mean, 8 years). At the last visit patients were 8 to 23 years of age (mean, 14.5 years) and were either seizure free or had very infrequent focal motor seizures during sleep. Three patients were free from antiepileptic drugs. In no patient was definite cognitive deterioration apparent after ESES in comparison with earlier evaluations. Conclusions: Age-related secondary bilateral synchrony underlying ESES may be facilitated in multilobar polymicrogyria. The good seizure outcome contrasts with that usually found in the presence of cortical malformations. For children with polymicrogyria and drop attack seizures, surgical treatment of the epilepsy should be considered cautiously, and sleep EEG recordings should be performed systematically.

Epileptic negative myoclonus

Five patients with partial epilepsy of diverse etiology insidiously developed action-activated jerks. The disorder was limited to one arm in two patients and to the legs in another, and was multifocal in the remaining two. Each jerk was related to an EMG silent period lasting 100 to 400 msec, causing a lapse followed by resumption of posture. Simultaneous EEG-EMG recording showed each postural lapse to be time-locked with a sharp or spike and slow-wave transient over the contralateral sensorimotor cortex, where almost continuous paroxysmal activity occurred. The three patients who were able to cooperate during neurologic evaluation also exhibited motor neglect in the most affected body segment and decreased awareness of the disorder. In three patients, the phenomenon was medically resistant, and in two of them it was continuous and could be defined as epilepsia partialis continua. In the other two, medical treatment induced remission of EEG, motor, and neuropsychological abnormalities. This disabling movement disorder can be classified as “epileptic negative myoclonus” and may result from focal-discharge-related transient disruption of cortical function in the sensorimotor cortex.

Early myoclonic epileptic encephalopathy (E.M.E.E.)

The authors describe the electroclinical aspects and evolution of nine cases of myoclonic epileptic encephalopathy which began between two days and ten weeks of life. at onset it is associated with: myoclonic jerks, partial fits and periodic paroxysmal EEG abnormalities. Repeated spasms coexisting with partial fits and ‘suppression-bursts’ (both appearing later) complete the electroclinical picture. The neurological status (initially normal) progressively deteriorates leading within a few months to a decerebrate posture with opisthotonos. In spite of thorough neuroradiological, biochemical, cytological, metabolic, and ultrastructural investigations, the etiology remained unknown. However, the electroclinical and evolutive patterns are similar to those of some metabolic diseases (Polyodystrophy, Non-Ketotic Hyperglycinemia, etc.). All these observations display a homogeneous electroclinical pattern for which the authors propose the name of Early Myoclonic Epileptic Encephalopathy. This type deserves to be classified as a particular electroclinical entity among the epileptic encephalopathies of the first year of life; since its course is regularly downhill in all cases there may be a familial recurence due to the possibility of a metabolic etiology.

A Study of the Rhythm of Petit Mai Absences in Children in Relation to Prevailing Situations: The Use of EEG Telemetry during Psychological Examinations, School Exercises and Periods of Inactivity

A telemetric EEG study was made of 30 patients with petit mal in the course of various activities (intelligence tests, projective tests and interviews, drawing and school exercises) and in periods of inactivity. The frequency of epileptic paroxysms was found to vary significantly with the various situations in which the subject was placed.

Partial Epilepsies in Infancy: A Study of 40 Cases

Summary: Forty patients with partial epilepsy that began before they were aged 3 years were recorded at the Centre Saint‐Paul between 1981 and 1986 with a follow‐up ranging from 1 year 9 months to 20 years. We analyzed the following data: age at onset, clinical features of seizures at onset and during the follow‐up period, ictal and interictal EEG features, etiologic circumstances, evolution of the epilepsy, and psychomotor development. The age of onset was mostly between 2 months and 2 years (more than two thirds of cases). Most had partial symptomatic epilepsy. In nine cases, epilepsy was preceded by febrile convulsions. Seizures at onset were of the following type (in order of decreasing occurrence): unilateral seizures, complex partial seizures, elementary partial seizures, and other seizures, often difficult to classify. A few patients with infantile spasms associated with focal or multifocal EEG abnormalities, differing from Wests syndrome, were included in this study. We discuss the problem arising from the classification of infantile seizures and epilepsies.

Electrical and autonomic cardiac function in patients with Dravet syndrome

Dravet syndrome (DS) is an epileptic encephalopathy related mainly to mutations in the SCN1A gene, encoding for neuronal sodium channels. Patients with DS have a high risk of sudden unexpected death in epilepsy (SUDEP). In this study we investigated whether patients with DS present abnormalities in electrical and autonomic cardiac function. To this aim we assessed ventricular repolarization and heart rate variability (HRV) on standard electrocardiography (ECG) and on 24‐h ECG Holter monitoring, respectively, in 20 patients affected by DS (6.8 ± 4 years, 11 female). As age‐ and sex‐matched control groups, we also studied 20 patients with other epileptic syndromes receiving antiepileptic drugs (ES/AED, 6.0 ± 5 years, 12 female), 20 patients with other epileptic syndromes without treatment (ES/no‐AED, 6.7 ± 4 years, 10 female), and 20 healthy children (HC, 7.2 ± 5 years, 11 females). Data analysis showed that patients with DS had depressed HRV variables compared to both ES patients (ES/AED and ES/no‐AED) and HC control group, whereas no significant differences in HRV variables were found between ES patients (with and without treatment) and HC. There was no significant difference between patients with DS and all the other control groups in RR intervals, QT, and QTc interval analysis. In conclusion, DS patients display an imbalance of cardiac autonomic function toward a relative predominance of adrenergic tone compared to both healthy children and patients with other forms of epilepsy, independent of antiepileptic therapy. Follow‐up studies should clarify the clinical significance of this autonomic impairment and whether HRV analysis can be helpful in predicting the risk of sudden death in patients with DS.

Severe myoclonic epilepsy in infancy (Dravet syndrome) 30 years later

Severe myoclonic epilepsy in infancy (SMEI) was first described in 1978 by Charlotte Dravet at Marseille, and it was briefly reported in a French medical journal (Dravet, 1978). Soon afterward it was recognized in Italy by Bernardo Dalla Bernardina and they together presented the first 42 cases diagnosed in Marseille at the International Epilepsy Congress in Kyoto in 1981 (Dravet et al., 1982). It became subsequently obvious that some patients exhibited overlapping characteristics, with the exception of myoclonic seizures, which led to the subdivision of typical and atypical, or borderline, forms (SMEIB), without obvious difference in the prognosis. For this reason, and because this form of epilepsy was not limited to infancy, the name was changed to the eponym Dravet syndrome (Commission on Classification and Terminology of the ILAE, 1989). In subsequent years, mutations of the SCN1A gene were identified in some families with the generalized epilepsy with the febrile seizures plus (GEFS+) spectrum. Because some patients with Dravet syndrome belonged to similar families, Claes et al. (2001) tested seven children with the syndrome and found all of them to be mutation positive (Claes et al., 2001). This finding was the starting point for a long series of studies that confirmed the genetic origin of both SMEI and SMEIB. A large number of mutations (>500) of the SCN1A gene have been described, and copy number variations causing deletions or duplication of SCN1A have also been detected (Marini et al., 2009), bringing the number of patients in whom an involvement of this gene can be demonstrated to about 80% of all the patients who are tested. Recently Depienne et al. (2009b) reported PCDH19 familial and ‘‘de novo’’ point mutations in 13 female patients with early onset epileptic encephalopathy mimicking Dravet syndrome. A male patient with a similar phenotype carried a mosaic PCDH19 mutation. The authors estimated that PCDH19 mutations might account for 5% overall of Dravet syndrome (Depienne et al., 2009b). However, approximately 15% of affected patients do not harbor an SCN1A or a PCDH19 gene mutation, even when the clinical picture is typical. It is unknown whether alterations of these two genes that are not demonstrable by current techniques may still be at play or if additional, unknown, causative genes are involved. As the number of reported patients has increased markedly, some variability of the clinical picture has become apparent regarding seizure type and frequency, triggering factors, neuropsychological impairment, response to drugs, and comorbidities. Genotype–phenotype correlations have not been clearly defined, however, and it is now obvious that mutations of SCN1A or PCDH19 are not the single determinants of phenotype, and that modifier genes, the genetic background, or epigenetic and environmental factors can also play a role. In the scheme proposed by the International League Against Epilepsy (ILAE) (Engel, 2001), Dravet syndrome is considered as an ‘‘epileptic encephalopathy,’’ defined as a condition in which the epileptiform abnormalities themselves are believed to contribute to the progressive disturbance in cerebral function. However, it is not proven that the cognitive decline observed in the first stages of the disease is simply the direct consequence of epilepsy. Studies focusing on neuropsychological outcomes are now being conducted prospectively by several groups in order to disentangle the causative factors underlying cognitive impairment. These studies are showing that there are different degrees of cognitive decline and that the patients most recently diagnosed seem to be less affected than patients in older studies. The animal models of the syndrome that have been developed are convincing and have already provided important insights on the mechanisms of Address correspondence to Charlotte Dravet, 4a Avenue Toussaint Samat 13009, Marseille, France. E-mail: charlotte.dravet@free.fr

Les états de mal dans le syndrome de Lennox-Gastaut

Summary Thirty patients with the Lennox-Gastaut syndrome presenting one or more status epilepticus (the first before age 15) were studied. Triggering factors, semiology, duration, severity and EEG features were considered. A comparison was made between this group of patients and another group having the Lennox-Gastaut syndrome but without status. No significant difference appears in the long-term prognosis, even when status were prolonged. Only three patients died during a status. For this reason the authors recommend prudence and avoidance of very strong treatment. In their experience, intravenous diazepines, intravenous phenytoin and intramuscular ACTH were the most effective drugs.

La Maladie De Lafora

Summary On the basis of 21 personal observations as well as those (82) from the litterature, it is concluded that the progressive myoclonic epilepsy with Lafora bodies (P.M.E.) constitutes a disease on its own. The clinical features are those described in the litterature observations and completed by some characteristics; the high frequency of visual symptoms ( 47 p. 100 personal cases); the relatively less bad evolution of epilepsy, perhaps in relation with use of modern drugs; the relatively moderate intensity of myoclonus which becomes complete only at the end of the evolution. From E.E.G. point of view, we can distinguish three periods: an initial one at the very onset of disease, who will show the same features as observated in primary generalized epilepsy, i. e. a well preserved background activity with superimposed generalized fast spikes and waves facilitated by the I.L.S. Then follows a period of evolutive E.E.G. (1–2 years after the onset of the disease) characterized by progressive slowing of the posterior background, enlargement of posterior slow activity and appearance of diffuse theta and delta activity. Simultaneously spikes and waves are taking less typical and bisynchronous aspect. Finally after 3 to 5 years from the onset there is a diffusely slow E.E.G. with superimposed fast multiple spikes. The E.E.G. findings in litterature usually refer only to this last period (stationary or terminal period) . Occipital independent multiple spikes are frequently observed and could correlate with the visual symptoms observated in the Lafora disease. Some elements of differential diagnosis are given with respect to primary generalized epilepsy at the onset of the disease and later on with respect to dyssynergia cerebellaris myoclonica and to the progressive myoclonic epilepsy without Lafora bodies.

Épilepsie partielle bénigne et état de mal électroencéphalographique pendant le sommeil

Summary The authors describe the electro-clinical state of four children having a type of epilepsy clinically characterized by rare partial motor seizures and frequent absences. From E.E.G. point of view they had focal (mainly frontal) and diffuse abnormalities. Such diffuse abnormalities became continuous during slow sleep, thus realizing an electrical status epilepticus. During such status partial subclinical seizures were recorded. At the onset such cases have electroclinical features resembling those observed in the form of epilepsy so-called « benign partial epilepsy of children with rolandic or mid-temporal foci . All cases, however, have behavioural problems (instability, desorientation) and decreased school performances. The epilepsy evolution, however, is favourable and such form should consequently be distinguished from the Lennox-Gastaut Syndrome.