Rolando-Epilepsie

Rolandic epilepsy (RE) belongs to the most frequent epilepsy syndromes in childhood. Short sensorimotor perioral seizures, frequently occurring during sleep are characteristic. The epilepsy is self-limiting and usually developmental outcome is good. However, in some patients, mostly transient, learning disorders occur. Centrotemporal spikes in the EEG are the neurobiological genetic marker. Atypical benign partial epilepsy of childhood (ABPE) is much rarer than RE. In addition to perioral sensorimotor seizures, atypical absences, astatic seizures, and focal motor seizures are observed. The EEG shows centrotemporal spikes, however, with a much more pronounced sleep activation, sometimes reaching a bioelectrical status epilepticus. Amazingly, genetic factors seem to play an even greater role in ABPE than in RE. Prognosis of the epilepsy is good in ABPE; however, it is guarded concerning developmental outcome. Epilepsy risk for siblings of children with RE is small. However, the EEG trait is present in about 15% of siblings. In siblings of children with ABPE, this rate is elevated to about 40%. Additionally, in a small number of siblings with RE/APRE, sequence variations in KCNQ2, KCNQ3, and ACHRNA7 were detected. A conclusive understanding and extension of these findings will only be possible using new comprehensive molecular genetic tools, e.g., whole exome sequencing.     

Delayed diagnosis of juvenile myoclonic epilepsy.

Fifteen cases of juvenile myoclonic epilepsy (JME) were identified from one hundred and eighty consecutive patients referred to a new epilepsy clinic at St Thomas' Hospital between April 1989 and December 1990, a prevalence of 8.3%. Of these, only one was referred with a putative diagnosis of JME. Diagnosis of the other patients on referral included "epilepsy", "grand mal", "temporal lobe epilepsy", "photoconvulsive epilepsy" and "alcohol-induced epilepsy". At least 11 of the 15 patients had been seen by a neurologist in the United Kingdom before referral. Definitive diagnosis was delayed by a mean of 14.5 years. In seven patients inappropriate anticonvulsants had been prescribed. Control of seizures was improved in most patients after diagnosis. Factors responsible for the delay in diagnosis include lack of familiarity with the syndrome, failure to elicit a history of myoclonic jerking and high prevalence of focal abnormalities on the EEG. Precipitation of fits by alcohol and sleep deprivation may not be recognised by the physician as part of the syndrome of JME. Diagnosis may also be delayed in patients whose absence and generalised tonic-clonic seizures pre-date myoclonic jerks.     

Magnetoencephalography localizing spike sources of atypical benign partial epilepsy

Rationale: Atypical benign partial epilepsy (ABPE) is characterized by centro-temporal electroencephalography (EEG) spikes, continuous spike and waves during sleep (CSWS), and multiple seizure types including epileptic negative myoclonus (ENM), but not tonic seizures. This study evaluated the localization of magnetoencephalography (MEG) spike sources (MEGSSs) to investigate the clinical features and mechanism underlying ABPE. Methods: We retrospectively analyzed seizure profiles, scalp video EEG (VEEG) and MEG in ABPE patients. Results: Eighteen ABPE patients were identified (nine girls and nine boys). Seizure onset ranged from 1.3 to 8.8 years (median, 2.9 years). Initial seizures consisted of focal motor seizures (15 patients) and absences/atypical absences (3). Seventeen patients had multiple seizure types including drop attacks (16), focal motor seizures (16), ENM (14), absences/atypical absences (11) and focal myoclonic seizures (10). VEEG showed centro-temporal spikes and CSWS in all patients. Magnetic resonance imaging (MRI) was reported as normal in all patients. MEGSSs were localized over the following regions: both Rolandic and sylvian (8), peri-sylvian (5), peri-Rolandic (4), parieto-occipital (1), bilateral (10) and unilateral (8). All patients were on more than two antiepileptic medications. ENM and absences/atypical absences were controlled in 14 patients treated with adjunctive ethosuximide. Conclusion: MEG localized the source of centro-temporal spikes and CSWS in the Rolandic-sylvian regions. Centro-temporal spikes, Rolandic-sylvian spike sources and focal motor seizures are evidence that ABPE presents with Rolandic-sylvian onset seizures. ABPE is therefore a unique, age-related and localization-related epilepsy with a Rolandic-sylvian epileptic focus plus possible thalamo-cortical epileptic networks in the developing brain of children.     

The Natural History of Myoclonic Astatic Epilepsy (Doose Syndrome) and Lennox-Gastaut Syndrome

Summary:  The purpose of this article is to present a short review of the natural history of myoclonic astatic epilepsy (MAE; Doose syndrome) and the Lennox-Gastaut syndrome (LGS). In the 1989 classification of the International League Against Epilepsy (ILAE, 1989), MAE and LGS were initially included in group 2.2: "Cryptogenic or symptomatic generalized epilepsies and syndromes." The subsequent classification of the Proposed Diagnostic Scheme for People with Epileptic Seizures and with Epilepsy (see Ref. 8 ) placed MAE in axis 3 in the "generalized epilepsy" group and LGS, severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and atypical benign partial epilepsy/pseudo-Lennox syndrome (ABPE/PLS) in the "epileptic encephalopathy" group. The semiology of MAE and LGS and their differential diagnosis from SMEI and ABPE/PLS are described. Before the onset of SMEI, MAE, and ABPE/PLS, the development of the child is usually normal. In contrast, in LGS, development is frequently retarded at the onset, depending on the etiopathogenesis of the underlying brain disease. The course of MAE is highly variable with regard to seizure outcome (complete remission in some cases, persistent epilepsy in others) and cognitive development (normal or delayed). The course of LGS and SMEI is generally poor, both with regard to the epilepsy and to the cognitive development whereas the course and seizure outcome of ABPE/PLS is favorable; the patients will be seizure-free at puberty. However, the neuropsychological outcome is less favorable; most patients remain mentally retarded.     

Carbamazepine-exacerbated epilepsy in children and adolescents

Forty-nine children and adolescents whose seizures reportedly worsened while receiving carbamazepine (CBZ) were studied retrospectively. Twenty-six patients met criteria for excellent documentation of carbamazepine-exacerbated seizures. Four epileptic syndromes were particularly affected: childhood absence epilepsy; focal symptomatic, frontal lobe epilepsy; Lennox-Gastaut syndrome; and severe myoclonic epilepsy of infancy. Eight of the 26 patients developed new-onset absence seizures and three patients with established absence epilepsy experienced absence status. Other seizure types, including atonic, tonic-clonic, and myoclonic, developed in eight patients treated with CBZ, and new generalized spike-and-wave discharges were observed in electroencephalograms of nine patients. CBZ is a widely used, effective antiepileptic drug, particularly for partial or partial complex seizures; however, if uncontrolled, generalized seizures occur after CBZ is prescribed for children or adolescents with absence or mixed seizures, a trial of CBZ discontinuation is warranted. The data reported here do not permit calculation of the incidence of this phenomenon.     

Levetiracetam monotherapy for primary generalised epilepsy.

PURPOSE: To evaluate the efficacy of levetiracetam in cases of refractory primary generalised epilepsy. METHODS: Three patients with refractory primary generalised epilepsy were treated with levetiracetam monotherapy; one with absence seizures, myoclonic jerks and generalised tonic-clonic (GTC) seizures one with myoclonic jerks and GTC seizures, and one with only GTC seizures. All three patients had generalised spike wave on the EEG and had failed at least three antiepileptic drugs (AEDs) before trying levetiracetam. RESULTS: All three patients tolerated levetiracetam well and became seizure free for at least 6 months. Therapeutic doses of levetiracetam ranged from 1250 to 3000 mg/day. CONCLUSION: Levetiracetam, a new AED with a novel mechanism(s) of action, should be considered for patients with refractory primary generalised epilepsy.     

Spectrum of epilepsy in terminal 1p36 deletion syndrome

PURPOSE: Previous reports have summarized the seizures types occurring in 1p36 deletion syndrome. To better define the spectrum of epilepsy, we studied 91 patients (median age 7.8 years) with confirmed 1p36 deletion. METHODS: Based on clinical charts, we retrospectively analyzed the evolution of both the EEG findings and seizures. RESULTS: Epilepsy occurred in 53 patients (58.2%), with onset at a median 2.75 months. First seizures were generalized tonic (8 cases), tonic and clonic (6) or myoclonic (12), simple partial (6), or complex partial (14). Thereafter, 20 patients (21.9%) developed infantile spasms with hypsarrhythmia, at a median age of 5 months. High doses of oral steroids were tried in nine cases, with a prompt remission of seizures in six. Among them, five were seizure-free at the time of evaluation. Conversely, two of three nonresponders to steroids developed severe and refractory epilepsy. At the time of evaluation, 32 patients were seizure-free, from a median age of 1.8 years. Nineteen patients (20.9%) had developed refractory epilepsy with polymorphic seizures, including generalized tonic and tonic-clonic seizures (13) combined with myoclonic seizures (11) and atypical absences (3), atonic seizures (2), or complex partial seizures (3). The EEG showed focal, multifocal or generalized spikes, polyspike, and waves, with poverty of the usual background rhythmic activities. CONCLUSIONS: Early epilepsy is a frequent finding in 1p36 deletion syndrome with infantile spasms as of the most common features that can contribute to a poor clinical outcome. Early diagnosis and management of infantile spasm in this condition is mandatory.     

Relation of photosensitivity to epileptic syndromes.

Photosensitivity is the most common mode of seizure precipitation. It is age-related, more frequent in females, and most often found in generalised epilepsies. Little is known about its relation to individual epileptic syndromes. This study on 1062 epileptic patients who had 4007 split screen video EEG investigations revealed that the relation to generalised epilepsy is even more close than generally believed. Versive seizures with visual hallucinations was the only focal seizure type related to photosensitivity. Of the syndromes of generalised epilepsy, only childhood absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with grand mal on awakening were related to photosensitivity. The closest correlation was with juvenile myoclonic epilepsy. This is confirmed by a relation to the poly-spike wave pattern, and by an increase of myoclonic seizures by intermittent light stimuli. No relation was found with early childhood syndromes of generalised epilepsy, or generalised tonic-clonic seizures in the evening, or, most remarkably, with juvenile absence epilepsy. In generalised epilepsies with onset around puberty, photosensitivity could thus act as a pathoplastic factor. The female preponderance in both childhood absences and photosensitivity could be due to the same unknown factor.     

Familial adult onset myoclonic epilepsy associated with migraine.

We report a new type of migraine associated epileptic syndrome in a family: adult onset myoclonic epilepsy with benign course and migraine. Affected members of the family had myoclonic and rare generalised tonic-clonic seizures. Most of the patients, but not all, had a history of migraine. Also, some cases of the family had only migraine. This family will be discussed because of two distinct features. Firstly, in this family a different type of epilepsy, adult onset myoclonic epilepsy was diagnosed that has not been classified in the ILAE 1989, classification(s), but was similar to that previously reported in Japanese families. Secondly, in most of the cases migraine was associated with the epilepsy.     

"Benign" form of myoclonic epilepsy in children

Among 62 children with myoclonic epilepsy who had first seizures between 1 and 10 years, without clinical or radiological evidence of brain lesion, we selected the 16 patients who had exhibited several types of fits and had stopped having seizures for over two years. First seizures occurred between 18 months and 4 years, and they were generalized clonic, tonic-clonic or tonic. After a mean 3 months' period, patients started also to have absence and myoclonic fits. During the period with various types of seizures, that lasted a mean 10 months, patients were ataxic and hyperkinetic, and 11 of them suffered myoclonic absence status for several hours or days. The EEG showed a high voltage rhythmic slow-wave activity with spikes, differing from the slow spike wave tracing of the Lennox-Gastaut syndrome, and there was no photosensitivity. The mean duration of the epilepsy was 1 year and 4 months and the last seizures were convulsive, occurring mainly during sleep. The clinical and EEG pattern, the high familial incidence are shared by the Doose syndrome, of which the present series seems to be a subgroup, as are other well-defined syndromes: benign and severe myoclonic epilepsies of infancy.     

When antiepileptic drugs aggravate epilepsy

Paradoxically, an antiepileptic drug (AED) may aggravate epilepsy. The number of AEDs is steadily increasing, and the occurrence of paradoxical aggravation will probably become a frequent problem. The overall status of the patient treated for epilepsy can be altered due to maladjustment to the diagnosis of epilepsy, to unwanted side-effects, to overdosage and to the occurrence of tolerance. However, the main mechanism of aggravation is the occurrence of an inverse pharmacodynamic effect. The specific effect of the AED is such that it controls epilepsy in most cases and increases seizures in other cases. Idiopathic generalised epilepsies (IGE) are particularly prone to pharmacodynamic aggravation: typical absences are constantly increased by carbamazepine (CBZ), vigabatrin, tiagabine, gabapentin, while phenytoin (PHT) is less aggravating. Juvenile myoclonic epilepsy is often aggravated by CBZ, less constantly by PHT and other AEDs. Generalised tonic-clonic seizures found in IGEs may respond to AEDs that aggravate the other seizure types. In symptomatic generalised epilepsies, patients have often several seizure types that respond differently to AEDs: myoclonias are generally aggravated by the same drugs that aggravated IGEs; tonic seizures in the Lennox-Gastaut syndrome respond to CBZ, which may however aggravate atypical absences. In severe myoclonic epilepsy of infancy, there is a nearly constant aggravating effect of lamotrigine. In some patients with benign rolandic epilepsy, a clear aggravation may be produced by CBZ, with occurrence of negative myoclonias, atypical absences, drop attacks, and at the maximum evolution into a state of electrical status epilepticus during sleep. It is much more difficult to pinpoint specific pharmacological sensitivity in other focal epilepsies, but aggravation clearly occurs. When treating epilepsy, the clinician should act according to seizure type, or, better, to epilepsy type. Patients are usually aware of aggravation before their doctors: we should listen carefully whenever they express a 'dislike' for an AED.     

Zonisamide in the management of epilepsy--Japanese experience

Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved in Europe for the adjunctive treatment of refractory partial seizures in adults, has undergone extensive evaluation in pre- and post-marketing double-blind and open-label studies in Japan (where zonisamide is used widely to treat partial and generalised seizures in adults and children). These data indicate that the clinical benefit of zonisamide extends across a range of seizure types and patient ages. In an analysis based on a mixture of controlled and open studies in adults and children with partial seizures, 51-57% responded to zonisamide treatment (achieving >or=50% reduction in baseline seizure frequency). Efficacy extends across a range of generalised seizures and 22-66% of adults and children experiencing tonic-clonic, tonic, clonic, myoclonic or absence seizures responded to treatment. Even greater responder rates have been reported when zonisamide was used as monotherapy for partial seizures and generalised seizures in patients refractory to other AEDs or with newly diagnosed epilepsy. Zonisamide is also efficacious in paediatric epilepsy syndromes, including Lennox-Gastaut Syndrome, West Syndrome and Ohtahara Syndrome. Across the spectrum of epilepsy syndromes studied, zonisamide is well-tolerated with a low incidence of adverse events, which are generally mild and CNS-related. These data indicate that zonisamide represents a valuable broad-spectrum option for the treatment of epilepsy.     

Double-Blind, Placebo-Controlled, Lamotrigine in Treatment-Resistant Generalised Epilepsy

Summary: Purpose : Lamotrigine (LTG) is recognised as effective add-on therapy for focal epilepsies, but this is the first double-blind, placebo-controlled, crossover study in treatmentresistant generalised epilepsy.
Methods: The study consisted of 2 × 8-week treatment periods followed by a 4-week washout period. Patients received doses of either 75 or 150 mg daily, depending on their concomitant antiepileptic drugs (AEDs). Long-term continuation was offered at the end of the study with open-label LTG.
Results: Five centres in Australia recruited 26 patients who were having absence, myoclonic, or generalized tonic-clonic seizures or a combination of these. Twenty-two patients completed the study. There was a significant reduction in frequency of both tonic-clonic and absence seizure types with LTG. A 250% decrease in seizures was observed for tonic-clonic seizures in 50% of cases and for absence seizures in 33% of evaluable cases. Rash was the only adverse effect causing discontinuation. Twenty-three of 26 opted for open-label LTG, with 20 still receiving LTG for a mean of 26 months. In these 20, 80% had 250% seizure reduction and five (25%) were seizure free.
Conclusions: This study shows that LTG is effective add-on therapy in patients with refractory generalised epilepsies. Statistically significant reduction in seizures in both absence and tonic-clonic seizure types was seen even with low doses of LTG.     

A survey of adolescents with epilepsy

Thirty-four adolescents with epilepsy, controls matched for age and sex (A) and controls matched for age, sex and general ability (B), were studied. The adolescents with epilepsy were more likely to arrive at school by car or taxi and to have more difficult behaviour in class. Competitive sports were less popular with them and significantly fewer anticipated ever driving a car. Illness and parental marital problems were not a feature of their families. Their comprehension of reading material was significantly poorer than that of control group A. Within the group, the lowest over-all reading scores were found in children with myoclonic seizures, partial seizures with secondary generalisation, or generalised tonic-clonic seizures; and in those whose EEG findings included two-per-second spike and wave, photosensitivity, generalised slow waves, or generalised spike and wave of non-specific frequency. Right focal slow waves, sharp waves and spikes on EEG were associated with problems of comprehension, even when the over-all reading score was acceptable.     

Juvenile Myoclonic Epilepsy: Characteristics of a Primary Generalized Epilepsy

Summary: Juvenile myoclonic epilepsy (JME) is a primary generalized epilepsy that affects approximately 7% of adolescent and adult epilepsy patients. JME is characterized by myoclonic seizures alone or combined with generalized tonic-clonic seizures or absence seizures. Seizures are precipitated by sudden awakening, sleep deprivation, photic stimulation, and alcohol consumption. The ictal electroencephalogram (EEG) shows a typical 4- to 6-Hz polyspike and wave pattern; the interictal EEG may be normal. Valproate controls seizures in approximately 80% of JME patients and is recommended for successful management of this disorder.     

Juvenile Myoclonic Epilepsy: Characteristics of a Primary Generalized Epilepsy

Summary: Juvenile myoclonic epilepsy (JME) is a primary generalized epilepsy that affects approximately 7% of adolescent and adult epilepsy patients. JME is characterized by myoclonic seizures alone or combined with generalized tonic-clonic seizures or absence seizures. Seizures are precipitated by sudden awakening, sleep deprivation, photic stimulation, and alcohol consumption. The ictal electroencephalogram (EEG) shows a typical 4- to 6-Hz polyspike and wave pattern; the interictal EEG may be normal. Valproate controls seizures in approximately 80% of JME patients and is recommended for successful management of this disorder.     

18FDG-PET in epilepsies of infantile onset with pharmacoresistant generalised tonic-clonic seizures

AIMS: To investigate the pathophysiology of pharmacoresistant epilepsies with cryptogenic generalised tonic-clonic seizures (GTCS) from infancy. METHODS: 18F-Deoxy-Glucose-Positron Emission Tomography 18FDG-PET) with statistical parametric mapping (SPM). Inclusion criteria were: pharmacoresistant chronic epilepsy with GTCS commencing in infancy, no focal seizures except alternating hemiconvulsions and no focal epileptic discharges in the EEG during the first year of the disease, no focal changes upon routine neuroradiological investigations, no indication of brain damage according to history and clinical examination. RESULTS: 15 boys and 15 girls with a mean age of 6.4 years (range l-14 years) were included. All still suffered from seizures despite past treatment with a mean of five drugs. Nearly all were mentally retarded, 19 to a severe and 10 to a minor degree. Fifteen were ataxic and 11 hypotonic. The EEG in 23 showed irregular generalised spike-wave discharges. PET SPM analysis revealed bioccipital hypometabolism related to sedation. Pathological monofocal hypometabolic areas were found in three, multifocal hypometabolic areas in 22 and diffuse bilateral hypometabolism in three patients. Frontal hypometabolism correlated to the degree of mental retardation, hypotonia, and ataxia. Temporomesial hypometabolism correlated to the occurrence of obtunded states and prominent delta rhythms in the EEG. Central and parietal changes were associated with the occurrence of myoclonic seizures and spike-wave discharges. CONCLUSIONS: 18FDG-PET in many of these children with cryptogenic generalised epilepsies showed multifocal hypometabolic areas of unknown aetiology. Primary cortical microdysgenesis and secondary changes due to the severe and long-standing epilepsy must be considered. Only a minority of patients showed restricted focal hypometabolism as a possible indication for surgical treatment.     

Delineation of cryptogenic Lennox-Gastaut syndrome and myoclonic astatic epilepsy using multiple correspondence analysis.

PURPOSE: To distinguish various types of childhood severe cryptogenic/idiopathic generalised epilepsy on the basis of reproducible diagnostic criteria, using multiple correspondence analysis (MCA). METHODS: We applied MCA to a series of 72 children with no evidence of brain damage, starting epilepsy between 1 and 10 years, with two or more types of generalised seizures. We excluded patients with infantile spasms or typical absences. MCA was performed on all clinical and EEG parameters, first throughout follow-up, then restricted to the first year of the disease. RESULTS: When including all follow-up variables, there were three groups: (1) Thirty-seven children with male predominance, familial history of epilepsy, simple febrile convulsions, massive myoclonus, tonic-clonic fits. Outcome was favourable, with no seizures and mildly affected cognitive functions. Interictal EEG showed short sequences of irregular 3-Hz spike-waves. (2) In 18 children, clinical characteristics were similar to those of the first group at the early stage, but 95% exhibited myoclonic status and vibratory tonic seizures, with persisting seizures on follow-up. EEG showed long sequences of generalised irregular spike and slow waves. Those two groups meet the characteristics of childhood onset myoclonic-astatic epilepsy (MAE) with respectively, favourable and unfavourable outcome. (3) Eleven children had later onset, atypical absences, tonic and partial seizures, and no myoclonus, or vibratory tonic seizures. All had mental retardation and persisting seizures. EEG showed long sequences of slow spike-wave activity and half the patients had spike and slow wave foci. These patients met the major characteristics of Lennox-Gastaut syndrome. Initial parameters failed to distinguish the first two groups, but Lennox-Gastaut syndrome (the third group) was distinct from both groups of myoclonic astatic epilepsy from the onset. Within MAE groups combined, clinical and EEG risk factors for mental retardation could be identified. CONCLUSION: It is possible to validate statistically the distinction between discrete epileptic syndromes. Myoclonic astatic epilepsy is therefore distinct from Lennox-Gastaut syndrome, and the distinction appears from the first year of the disorder.     

Long-Term Course of Childhood Epilepsy with Intractable Grand Mal Seizures

Abstract: Twenty-nine children with childhood epilepsy characterized by frequent grand mal (generalized tonic-clonic) seizures in spite of maximal doses of antiepileptic drugs and by an early onset of seizures (before 1 :year of age) were followed up for more than 5 :years. The children were divided into 3 :groups: severe myoclonic epilepsy in infancy (SME), no SME, and intractable childhood epilepsy with generalized tonic-clonic seizures (GTC). In all the 3 :groups, the grand mal seizures persisted, whereas the other types of seizures tended to disappear as the patients aged, and the prognosis for mental development was poor. In the majority of cases in all the 3 :groups, the waking grand mal seizures altered to sleep grand mal seizures with aging. Two pairs of monozygotic twins with SME suggested that genetic factors play a role in this epileptic syndrome. Intractable childhood epilepsy with GTC is distinguished by the absence of other types of generalized seizures. It cannot be regarded as an epileptic syndrome, but its pathogenesis and treatment require further studies.     

Focal epilepsy recruiting a generalised network of juvenile myoclonic epilepsy: a case report

We report a patient with juvenile myoclonic epilepsy who subsequently developed temporal lobe epilepsy, which gradually became clinically dominant. Video telemetry revealed both myoclonic seizures and temporal lobe seizures. The temporal lobe seizures were accompanied by a focal recruiting rhythm with rapid generalisation on EEG, in which the ictal EEG pattern during the secondary generalised phase was morphologically similar to the ictal pattern during myoclonic seizures. The secondary generalised seizures of the focal epilepsy responded to sodium valproate, similar to the myoclonic epilepsy. In this rare case of coexistent Juvenile Myoclonic Epilepsy and Temporal lobe epilepsy, the possibility of focal epilepsy recruiting a generalised epileptic network was proposed and discussed.