How to diagnose and classify idiopathic (genetic) generalized epilepsies.

Idiopathic or genetic generalized epilepsies (IGE) constitute an electroclinically well-defined group that accounts for almost one third of all people with epilepsy. They consist of four well-established syndromes and some other rarer phenotypes. The main four IGEs are juvenile myoclonic epilepsy, childhood absence epilepsy, juvenile absence epilepsy and IGE with generalized tonic-clonic seizures alone. There are three main seizure types in IGE, namely generalized tonic-clonic seizures, typical absences and myoclonic seizures, occurring either alone or in any combination. Diagnosing IGEs requires a multidimensional approach. The diagnostic process begins with a thorough medical history with a specific focus on seizure types, age at onset, timing and triggers. Comorbidities and family history should be questioned comprehensively. The EEG can provide valuable information for the diagnosis, including specific IGE syndromes, and therefore contribute to their optimal pharmacological treatment and management.

Clinical aspects of juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a recognizable, frequent epileptic syndrome. The most typical ictal phenomenon is bilateral myoclonia without loss of consciousness (M), with most patients also presenting with generalized tonic-clonic seizures (GTCSs) and some with absence seizures (ASs). The most striking features of JME are its onset around the time of puberty and the fact that seizure episodes occur after awakening from a sleep period or in the evening relaxation period and are facilitated by sleep deprivation and sudden arousal. Photic sensitivity is common in the EEG laboratory but uncommon or unrecognized in daily life. The clinical features of JME make it easy to diagnose. In recent years, awareness of JME has increased, and patients are often accurately diagnosed clinically before confirmation by EEG. The typical circumstance at diagnosis is a first GTCS episode, and one learns during the interview that the patient has had M in the morning for some time before the GTCS episode. There are only few differential diagnoses: the adolescent-onset progressive myoclonus epilepsies, or other forms of idiopathic generalized epilepsies of adolescence. With JME being so common, we propose that a first GTCS episode in a teenager should be considered as revealing JME until proven otherwise.

Classification of juvenile myoclonic epilepsy data acquired through scanning electromyography with machine learning algorithms.

In this paper, classification of Juvenile Myoclonic Epilepsy (JME) patients and healthy volunteers included into Normal Control (NC) groups was established using Feed-Forward Neural Networks (NN), Support Vector Machines (SVM), Decision Trees (DT), and Naïve Bayes (NB) methods by utilizing the data obtained through the scanning EMG method used in a clinical study. An experimental setup was built for this purpose. 105 motor units were measured. 44 of them belonged to JME group consisting of 9 patients and 61 of them belonged to NC group comprising ten healthy volunteers. k-fold cross validation was applied to train and test the models. ROC curves were drawn for k values of 4, 6, 8 and 10. 100% of detection sensitivity was obtained for DT, NN, and NB classification methods. The lowest FP number, which was obtained by NN, was 5.

Idiopathic generalized epilepsies of adolescence.

The prevalence of idiopathic generalized epilepsies (IGEs) has been assessed as being 15-20% of all epilepsies. The seizure types in IGEs are typical absences, myoclonic jerks, and generalized tonic-clonic seizures (TCS), alone or in varying combinations and with variable severity. The seizures tend to be more frequent on awakening and with sleep deprivation. This group of clinical conditions includes among others, age-related epilepsy syndromes of adolescence such as juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and IGE with generalized TCS or epilepsy with grand mal on awakening (EGMA). The classification of IGEs follows two schools of thought; one maintains that IGEs are a group of different and separate syndromes while the other suggests that IGEs are one biological continuum. Patients with IGEs may have mild impairment of cognitive functions, especially verbal memory and other frontal lobe functions, despite a normal IQ, and some seem to have characteristic personality traits, although further studies are needed to support this theory. They appear to lack a degree of self-control, to neglect their physical needs, and are poorly compliant with therapy. Some patients become obstinate and are impressionable. The cognitive and behavioral aspects of these patients suggest an involvement of frontal lobes.

Juvenile myoclonic epilepsy subsyndromes: family studies and long-term follow-up.

The 2001 classification subcommittee of the International League Against Epilepsy (ILAE) proposed to 'group JME, juvenile absence epilepsy, and epilepsy with tonic clonic seizures only under the sole heading of idiopathic generalized epilepsies (IGE) with variable phenotype'. The implication is that juvenile myoclonic epilepsy (JME) does not exist as the sole phenotype of family members and that it should no longer be classified by itself or considered a distinct disease entity. Although recognized as a common form of epilepsy and presumed to be a lifelong trait, a long-term follow-up of JME has not been performed. To address these two issues, we studied 257 prospectively ascertained JME patients and encountered four groups: (i) classic JME (72%), (ii) CAE (childhood absence epilepsy) evolving to JME (18%), (iii) JME with adolescent absence (7%), and (iv) JME with astatic seizures (3%). We examined clinical and EEG phenotypes of family members and assessed clinical course over a mean of 11 +/- 6 years and as long as 52 years. Forty per cent of JME families had JME as their sole clinical phenotype. Amongst relatives of classic JME families, JME was most common (40%) followed by grand mal (GM) only (35%). In contrast, 66% of families with CAE evolving to JME expressed the various phenotypes of IGE in family members. Absence seizures were more common in family members of CAE evolving to JME than in those of classic JME families (P < 0.001). Female preponderance, maternal transmission and poor response to treatment further characterized CAE evolving to JME. Only 7% of those with CAE evolving to JME were seizure-free compared with 58% of those with classic JME (P < 0.001), 56% with JME plus adolescent pyknoleptic absence and 62% with JME plus astatic seizures. Long-term follow-up (1-40 years for classic JME; 5-52 years for CAE evolving to JME, 5-26 years for JME with adolescent absence and 3-18 years for JME with astatic seizures) indicates that all subsyndromes are chronic and perhaps lifelong. Seven chromosome loci, three epilepsy-causing mutations and two genes with single nucleotide polymorphisms (SNPs) associating with JME reported in literature provide further evidence for JME as a distinct group of diseases.

Overview: idiopathic generalized epilepsies.

The idiopathic generalized epilepsies (IGEs) are an underemphasized topic. Two reasons for this relative lack of attention are that these epilepsies tend to be more easily controlled than the symptomatic partial and generalized epilepsies, and they are not as common. Because IGE usually arises in childhood or adolescence, these epilepsies may be thought of as a pediatric problem. However, a large number of patients continue to have seizures in adult life. Many exciting developments in understanding the pathophysiology, genetic etiology, and expanded treatment options warrant a reexamination of this important group of the epilepsies. This article reviews the more common IGE syndromes and associated seizure types as the first step in identifying the recent advances in our knowledge of these syndromes.

The new patient with a first seizure.

BACKGROUND: First seizures are common, with one in 20 people suffering a seizure at some time in their life. OBJECTIVE: This article aims to outline the assessment of patients with a first seizure, including making an accurate diagnosis of both seizure type and an epilepsy syndrome, if present. DISCUSSION: Seizures are classified into generalised and partial (arising from a focal region in the brain) based on clinical and electroencephalogram findings. However, as a partial seizure may proceed to a tonic clonic phase, differentiation may be difficult. Inquiring directly about 'minor' epileptic symptoms before the episode such as absences, myoclonic jerks, visual or auditory hallucinations or feelings of déjà vu, is needed to attempt to make a epilepsy syndrome diagnosis, as this has practical implications for treatment, prognosis and genetic counselling. Generalised epilepsies should be treated initially with valproate, while partial epilepsies should be treated with carbamazepine and switched to newer agents if intolerance occurs.

Nonconvulsion status epilepticus in patients with juvenile myoclonic epilepsy: types and frequencies.

Juvenile myoclonic epilepsy (JME) is an idiopathic, age-related generalized epileptic syndrome, featuring generalizedtonic-clonic and absence seizures as well as myoclonic jerks. Except for some case reports, little is known about type and frequency of nonconvulsive status epilepticus (NCSE) in adult patients with JME. In a retrospective study we therefore reviewed all patients with JME, who had been referred to our hospital between 1994 and 1999 for the occurrence of NCSE. Of the 69 patients with JME seen within these 6 years three women had typical absence status-one of them two times-and one woman had impulsive-petit-mal status. All four patients had a history of myoclonic, absence and generalized tonic-clonic seizures. Because of the extreme rarity of impulsive-petit-mal status the corresponding case history is presented in detail. According to our findings the prevalence of NCSE in JME can be estimated at 5.8%, the incidence at 1.2% per year with a clear preponderance of female gender.

Diagnosing idiopathic/cryptogenic epilepsy syndromes in infancy.

PURPOSE: To determine the characteristics that permit diagnosis of the type of epilepsy beginning in the 1st year of life, and to determine from what age such characteristics are recognisable. PATIENTS: From 430 non-selected patients who began having seizures in the 1st year of life and were referred to the neuropaediatric department of Saint Vincent de Paul Hospital, those with epileptic spasms as the first seizure type, those with recognisable aetiology, and those for whom early history was not reliable were excluded. METHODS: For the remaining 140 patients, the age at which clinical and electroencephalogram (EEG) characteristics met those of recognisable epilepsy syndromes according to the ILAE classification was studied. RESULTS: In most epilepsy syndromes, the diagnosis could be made within three months of onset of the disorder. The most difficult was to distinguish cryptogenic localisation related epilepsy from severe myoclonic epilepsy in infancy. Repeat focal seizures and persisting spike focus were the earliest and most reliable signs of localisation related epilepsy, whereas alternating focal seizures, generalised myoclonus, and/or spike waves appeared before the end of the 1st year in most infants with severe myoclonic epilepsy. However, for 39 patients it was not possible to reach the diagnosis of a precise syndrome. CONCLUSION: For over three quarters of infants with cryptogenic/idiopathic epilepsy, it is possible to reach a syndromic diagnosis within the first months of the disease, based on clinical and EEG characteristics. However, for one quarter, no diagnosis is possible based on the currently available classification.