Longterm follow-up of childhood epilepsy with absences. I. Epilepsy with absences at onset

The purpose of the follow-up study was to determine whether modern therapy with ethosuximide and/or valproate with/without phenobarbitone and its derivatives improves the longterm prognosis of absence epilepsy as compared to formerly used treatments. The patient population consisted of 194 cases (88 boys, 106 girls) with spike wave epilepsy starting with absences. In each case the diagnosis was confirmed by clinical observation and the typical EEG pattern. Only those patients were included who could be followed beyond the eighteenth year of life (up to age 45). The sample includes also older patients diagnosed during the fifties, before the present standard therapy was available. Because of the heterogeneity of the material and its selection, the data obtained are not suited to make a general statement about the ultimate prognosis of absences. The results demonstrate the effectiveness of regularly applied modern treatment. 72 out of 194 patients (37%) manifested generalized tonic clonic seizures (gtcs) during the course: 20 of these patients showed only incidental generalized tonic clonic seizures, which were not dependent on therapy. In 52 cases gtcs appeared without relation to precipitating factors. None of these patients received regular standard therapy before onset of gtcs. In 31 cases absence statuses were observed. These patients did not have an unfavourable outcome provided the standard therapy was instituted early and consequently. A change from absence epilepsy into an epilepsy with complex partial seizures sensu strictiori could not be observed. At final investigation 42 of 194 patients still had seizures: 7 with absences, 35 with grand mal with or without absences.(ABSTRACT TRUNCATED AT 250 WORDS)     

Partial Epilepsy with Seizures Appearing in the First Three Years of Life

We reviewed records of 5,000 epileptic patients and identified 154 cases of partial epilepsy with seizure onset in the first 3 years of life. Of these, 35 patients had initial partial seizures. In 57 patients, partial seizures were preceded by a hemiclonic seizure, which manifested as status epilepticus in 70%. Generalized seizures were the initial manifestation in 62 patients: 17 grand mal, 14 clonic or myoclonic, and 31 tonic or atonic seizures. Of the 119 patients, 31 showed a seizure free-interval of several years between the initial seizure and the occurrence of partial epilepsy. The atypical initial clinical presentation and the seizure-free interval before occurrence of more characteristic partial seizures raise the possibility that the diagnosis of partial epilepsies in the first years of life may be missed.     

Prognostic and electroclinical features of grand mal epilepsies

We studied the electroclinical features and prognosis of 103 patients with tonic-clonic seizures alone. Patients were classified into three groups according to seizure semiology and interictal EEG: primary grand mal, focal grand mal and indeterminate grand mal. Discriminant analysis showed that a number of other electroclinical features had no significant classificatory power. Patients have been followed for 2-10 years. At the last observation 40% of patients were free from tonic-clonic seizures and 23% had fewer than 1 seizure a year, without differences among the three groups. The appearance of 'minor' (absence or partial) seizures during follow-up occurred in 12 patients and did not change the prognosis of tonic-clonic seizures. At the end of follow-up, 96% of patients had a normal social adjustment. Grand mal epilepsies therefore appear to have a good prognosis.     

Dramatic Effect of Lamotrigine in Young Adults Suffering from Intractable Absences and Generalized Tonic–Clonic Seizures Since Childhood

The purpose of this study was to evaluate the efficacy of adding lamotrigine to valproic acid in patients with refractory absence seizures starting in childhood and persisting into adulthood. Lamotrigine was added to previous anticonvulsants (always including valproic acid) in 10 patients aged 23–44 years, with intractable absence and generalized tonic–clonic seizures. Seven patients became seizure free, three patients had > 75% reduction in seizure frequency. The patients have remained on comedication with valproic acid and lamotrigine, after gradually discontinuing most other anticonvulsants, for a follow-up period ranging from 1–4 years. There has been no increase in seizure frequency during this period. None of the patients reported any side effects. This study supports the growing evidence of therapeutic synergy between lamotrigine and valproic acid. This combination may be the therapy of choice for refractory absence and generalized tonic–clonic seizures both in children and adults.     

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.     

Video game induced seizures.

Fifteen patients who experienced epileptic seizures while playing video games are described together with a review of 20 cases in the English literature. Nine of the 15 cases and all but two of the reported cases experienced their first seizure while playing video games. Two thirds of patients had idiopathic generalised epilepsy and mainly reported generalised tonic clonic seizures, but some had typical absence seizures and myoclonic jerks while playing video games. In this series, 30% with idiopathic generalised epilepsy had juvenile myoclonic epilepsy. Overall, 70% of patients with idiopathic generalised epilepsy were photosensitive to intermittent photic stimulation and the mechanism of seizure provocation was probably similar to that of television induced seizures, although sensitivity to specific patterns was sometimes important. Two children had self induced video game seizures. Non-photic factors such as excitement, fatigue, sleep deprivation, cognitive processing, and diurnal variation in susceptibility seemed to be important seizure precipitants, particularly in non-photo-sensitive patients. Twenty nine per cent of patients had partial (mainly occipital) video game associated seizures. Occipital spikes were common in the EEG of these patients. Photosensitivity to intermittent photic stimulation may have been important in two patients but in the others, who all played arcade video games, other mechanisms need to be considered. Video game associated seizures are a feature of several epileptic syndromes and differ in precipitants and appropriate management.     

EEG in childhood absence epilepsy.

We performed a longitudinal clinico-electroencephalographic study of 23 children who were diagnosed as having absence epilepsy on their initial visits to our facility and we analysed those factors which lead to an unfavourable prognosis. SUBJECTS AND METHODS: We divided the 23 patients into three groups according to their clinical courses: Group A: eight patients who responded well to the therapy and became seizure free without relapse of epileptic discharges on EEGs; Group B: thirteen patients who suffered from relapse of epileptic discharges on EEGs despite clinical seizure cessation; Group C: two patients who continued to suffer from seizures. RESULTS: (1) Fifty-six percent of all patients had focal epileptic discharges, including a surprising 63% of patients in Group A. (2) "Lead in" in the ictal EEGs and automatisms during seizures were most commonly observed in patients in Group B, although there were no significant differences between the three groups. (3) The epilepsy of one patient in Group C evolved into complex partial seizures or absence status during her clinical course. She seemed to suffer from so-called "frontal absence", despite the fact that her initial EEG did not show any focal abnormalities. (4) Patients in Group B were treated with lower AED dosages than those in Group A. In addition, one patient in Group C was treated irregularly. CONCLUSION: We conclude that it is not uncommon for patients with absence epilepsy to show focal abnormalities on EEGs and clinical ictal automatisms. Thus, the existence of clinical ictal automatisms and focal signs in electroencephalographic features are not sufficient indicators of the final outcome. Furthermore, it appears that regular and adequate drug therapy is important for a favourable prognosis.     

Idiopathic generalized epilepsy presenting with hemiconvulsive seizures

PURPOSE: Unilateral seizures, or hemiconvulsive attacks, are motor seizures with tonic and/or clonic phenomena that involve only one side of the body. METHODS: We describe three adolescents who presented with hemiconvulsive seizures and were found to have 3-cps generalized spike-and-wave discharges on ictal and/or interictal EEG. All had normal neuroimaging studies. Two patients had been previously treated with carbamazepine, which led to a partial response in one patient. RESULTS: All three patients, however, are now seizure free on either sodium valproate or a combination of sodium valproate and lamotrigine. We believe the electroclinical diagnosis is that of idiopathic generalized epilepsy. CONCLUSIONS: Idiopathic generalized epilepsy presenting with hemiconvulsive seizures has not, to our knowledge, been previously described. However, the correct diagnosis of an idiopathic generalized seizure disorder, as opposed to a partial seizure disorder, has important treatment implications. The possible mechanism of hemiconvulsive seizures in idiopathic generalized epilepsy is discussed.     

Epilepsies with astatic seizures of late onset.

In 17 patients with a long course of epilepsy astatic seizures became apparent after the age of 14 years. In the patients' childhood astatic seizures had not been observed. The patients suffered from epilepsies with absences and awakening grand mal or psychomotor fits and sleeping grand mal. The EEG revealed spike-wave variant and spike-and-wave complexes as in the Lennox-Gastaut syndrome. Age dependency of Lennox-Gastaut syndrome is discussed. The described type of epilepsy can be understood as a "Lennox-Gastaut syndrome of late onset".     

TEMPORAL LOBE EPILEPSY

Types of seizures, age, at onset of epilepsy, preoperative duration of epilepsy, and age at operation were studied in the literature and in 74 patients who underwent unilateral temporal lobe resection in 1960–1969 in Denmark. the medical and surgical series were compared. the age at onset was significantly lower in the surgical series. Prognostically favourable factors were: i) preoperative presence of a single type of seizure; ii) duration of epilepsy of less than 4 years, and in grand mal epilepsy of less than 1 year; iii) operation for epilepsy in or before early adulthood. Prognostically unfavourable factors were: i) preoperative presence of grand mal; ii) age at onset of epilepsy or of the first grand mal seizure between 5 and 20 years; iii) preoperative duration of psychomotor epilepsy over 10 years.     

Petit mal epilepsy: a review and integration of recent information

Petit mal (absence) epilepsy remains one of the most enigmatic of neurological disorders, and there is no widely accepted theory of its etiology. This review covers some of the current issues concerned with the disorder, including treatment and prognosis, neurochemical research, behavioral and psychophysiological effects of wave-spiked discharges, and EEG studies of seizure control. With respect to treatment, although effective drug therapy (valproic acid, ethosuximide) exists for the "pure" form of absence epilepsy, other forms, in which there is an admixture of grand mal seizures, are less amenable to pharmacotherapy. Moreover, the frequency of fatal hepatic toxicity following valproic acid therapy has been estimated at 1 in 20,000. With respect to prognosis, follow-up studies indicate that many patients do not outgrow the disorder but continue to suffer absence seizures well into adulthood. In recent years, there has been considerable research on the neurochemical basis of absence epilepsy. Current theories, including those that implicate gamma-aminobutyric acid, catecholamines, and "endogenous" epileptogens, are summarized; and requirements for an experimentally induced animal model of absence epilepsy are discussed. The majority of behavioral studies of the disorder have concerned the effects of petit mal-type discharges on sensory and cognitive processes. Some of these studies are reviewed; and recent work bearing on these issues, involving event-related brain potentials, is presented. Our review concludes with a discussion of research aimed at the development of electrophysiologically based approaches to the reduction of seizure frequency in patients with absence epilepsy.     

Partial seizures during the course in patients with absence epilepsy]

We studied the incidence and clinicoelectrographic features of partial seizures in 46 patients with absence epilepsy. Ten patients (21.7%) showed obvious partial seizure symptoms during the course. Five patients had absence attacks with partial seizure symptoms, the ictal EEGs being a generalized 3 Hz spike-wave burst complex preceded by focal discharges. These absence attacks may be partial seizures with secondary bilateral synchronization, which originated from the frontal lobe. Three patients initially had partial seizures related to the frontal lobe, followed by absence attacks 8 months to 2.6 years after the start of CBZ therapy. The appearance of absence attacks may have been triggered by CBZ administration. Two patients had partial seizures at the relapse of epilepsy after the discontinuation of AED therapy for childhood absence epilepsy. This change of seizure types may be associated with the CNS maturation, or with localized cortical hyperexcitability subsequent to the foregoing generalized seizures. The prognosis of absence attacks in the all patients were excellent, and comparable to that of typical absence attacks. Our results suggest that localized cortical areas, especially the frontal lobe, are commonly involved in absence epilepsy. More detailed clinical observation is necessary to understand the pathogenesis of absence epilepsy.     

Long-Term Follow-Up of Childhood Epilepsy Associated with Tuberous Sclerosis

Summary: Purpose: To study the clinical and electroencephalographic (EEG) characteristics of patients whose epilepsy is associated with tuberous sclerosis, with special reference to their clinical course.
Methods: We investigated the electroclinical and radiologic features of 38 patients with epilepsy associated with tuberous sclerosis.
Results: Eleven patients showed only generalized epilepsy, and 10 showed only localization-related epilepsy throughout their clinical course. Among the other 17 cases, the nature of the epilepsy changed between generalized and localization-related epilepsies during the clinical course. A shift from generalized to localization-related epilepsies was more common than the reverse. Seventeen had West syndrome (WS), three had Lennox-Gastaut syndrome (LGS), and eight had epilepsies that evolved from WS to LGS. Tonic spasms, mostly in series, were seen in all 28 patients with generalized epilepsy. Eleven of the 28 patients had partial seizures and tonic spasms in the same period. Six of them showed "simultaneous seizures," consisting of tonic spasms in series and a partial seizure. Partial seizures were the main seizure type in 27 patients with localization-related epilepsy, but three of them also showed tonic spasms that included "simultaneous seizures." Ictal EEGs revealed multiple active foci in the same period that could shift during the clinical course. Neither the location nor number of tubers was related to the clinical course. As for seizure outcome, 12 (32%) of 38 patients were free from seizures at follow-up.
Conclusions: In epilepsies associated with tuberous sclerosis, there may be an interrelation between generalized and localization-related epilepsies, as well as one between generalized and partial seizures.     

Carbamazepine treatment of generalized tonic–clonic seizures in idiopathic generalized epilepsy

PurposeEvaluate the efficacy of carbamazepine in the treatment of idiopathic generalized epilepsy (IGE).MethodThe response of five patients with IGE, who experienced primarily generalized tonic–clonic seizures which were refractory to multiple antiepileptic drugs, is reported.ResultsCarbamazepine controlled multiple seizure types and did not induce or increase the frequency of myoclonic or absence seizures in these patients. Many family members also responded favorably to carbamazepine.ConclusionCarbamazepine can be used with caution as an alternative treatment option for refractory IGE, especially in cases in which the main seizure type is generalized tonic–clonic.     

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.     

Neonatal seizures with tonic clonic sequences and poor developmental outcome

Seizures consisting of a tonic followed by a clonic phase have rarely been described in neonates and are not included in the current classifications of neonatal seizures. Our video archive of 105 neonates with seizures or suspected seizures revealed six neonates with such tonic clonic or tonic myoclonic sequences. Two of those neonates had pyridoxine dependent seizures. The other four neonates had drug refractory seizures and demonstrated similarities in electro-clinical pattern, clinical course and outcome. Their seizures started with tonic posturing and after 10-20s tonic posturing was superimposed by focal or multifocal cloni or myocloni. Ictal EEG started with voltage attenuation followed by bilateral or alternating focal epileptic discharges. The interictal EEG was abnormal. One child died, while the other three children became seizure free but had severe motor delay and mental retardation. In one of those three children, a de novo missense mutation was detected in the voltage gated potassium channel gene KCNQ2, indicating a genetic relationship between drug refractory neonatal seizures of unknown etiology with tonic clonic or myoclonic sequences and the well-known syndrome of benign familial neonatal convulsions (BFNC).     

Effect of vagus nerve stimulation on adults with pharmacoresistant generalized epilepsy syndromes.

INTRODUCTION: Although vagus nerve stimulation (VNS) therapy is approved for the treatment of partial onset seizures, its efficacy for generalized seizures has not been fully evaluated. This Investigational Device Exemption assessed the outcome of VNS therapy among patients with generalized epilepsy syndromes. METHODS: Sixteen patients with pharmacoresistant generalized epilepsy syndromes and stable antiepileptic drug (AED) regimens were implanted with the VNS therapy device and were evaluated for changes in seizure frequency and type between baseline and follow-up of 12-21 months. RESULTS: The patients experienced a statistically significant overall median seizure frequency reduction of 43.3% (P = 0.002, Wilcoxon signed rank test) after 12-21 months of VNS therapy. Types of seizures that may involve a fall or collapse decreased with reductions in the frequency of myoclonic (60% reduction, n = 9; P = 0.016, Wilcoxon signed rank test), tonic (75% reduction, n = 8, NS), atonic (98.6%, n = 3, NS), and clonic seizures (86.7%, n = 1, NS). Conclusion: The benefits of reduced seizure frequency and reduced risk of injury merit consideration of VNS therapy for patients with pharmacoresistant generalized seizure syndromes.     

A study of idiopathic generalised epilepsy in an Irish population.

Idiopathic generalised epilepsy (IGE) is subdivided into syndromes based on clinical and EEG features. PURPOSE: The aim of this study was to characterise all cases of IGE with supportive EEG abnormalities in terms of gender differences, seizure types reported, IGE syndromes, family history of epilepsy and EEG findings. We also calculated the limited duration prevalence of IGE in our cohort. METHODS: Data on abnormal EEGs were collected retrospectively from two EEG databases at two tertiary referral centres for neurology. Clinical information was obtained from EEG request forms, standardised EEG questionnaires and medical notes of patients. RESULTS: two hundred twenty-three patients met our inclusion criteria, 89 (39.9%) male and 134 (60.1%) females. Tonic clonic seizures were the most common seizure type reported, 162 (72.65%) having a generalised tonic clonic seizure (GTCS) at some time. IGE with GTCS only (EGTCSA) was the most common syndrome in our cohort being present in 94 patients (34 male, 60 female), with 42 (15 male, 27 female) patients diagnosed with Juvenile myoclonic epilepsy (JME), 23 (9 male, 14 female) with Juvenile absence epilepsy (JAE) and 20 (9 male, 11 female) with childhood absence epilepsy (CAE). EEG studies in all patients showed generalised epileptiform activity. CONCLUSIONS: More women than men were diagnosed with generalised epilepsy. Tonic clonic seizures were the most common seizure type reported. EGTCSA was the most frequent syndrome seen. Gender differences were evident for JAE and JME as previously reported and for EGTCSA, which was not reported to date, and reached statistical significance for EGTCA and JME.     

Epileptic seizure semiology in different age groups

Aims. Seizure semiology provides information about the eloquent cortex involved during a seizure and helps to generate a hypothesis regarding the localization of the epileptogenic zone (EZ), a prerequisite for surgical management of epilepsy. We aimed to study the seizure semiology among all different age groups to better characterize semiological changes that occur with age. Methods. We performed a retrospective review of video‐EEG data in paediatric and adult patients admitted to the Epilepsy Monitoring Unit over a three‐year period. Authors independently reviewed and classified the seizure semiology while blinded to clinical, EEG, and neuroimaging data. A total of 270 patients were included in the study. Results. The most frequent EZ in patients who were one month to three years old was undetermined. Focal epilepsy became more frequent in patients older than 10 years. Among patients with focal epilepsy, a posterior quadrant EZ was most frequent in children younger than three years old, a temporal EZ between three and six years old, and a frontal EZ between six and 10 years old. The temporal lobe was the most frequent location for focal EZ in patients older than 18 years. Auras, automotor seizures, and generalized tonic‐clonic seizures were extremely infrequent in patients younger than 10 years old. The youngest patient with auras was 5.7 years old. The youngest patient with automotor seizures was 3.7 years old. We identified only three patients with generalized tonic‐clonic seizures who were younger than 10 years (aged six months, 6.6 years, and nine years, respectively). Patients younger than three years exhibited mostly generalized simple motor seizures and hypomotor seizures. Generalized epileptic spasms, generalized tonic seizures, and generalized clonic seizures were infrequent in patients older than 10 years. Conclusion. Seizure semiology and electroencephalographic changes most likely reflect the maturation of cortical functions.     

Seizure semiology in the elderly: a video analysis

PURPOSE: To describe the seizure semiology of patients older than 60 years and to compare it with that of a control group of younger adults matched according to the epilepsy diagnosis. METHODS: Available videotapes of all patients aged 60 years and older who underwent long-term video-EEG evaluation at the Cleveland Clinic Foundation (CCF) between January 1994 and March 2002 were analyzed by two observers blinded to the clinical data. A younger adult control group was matched according to the epilepsy diagnosis, and their seizures also were analyzed. RESULTS: Fifty-four (3.3%) of the 1,633 patients were 60 years or older at the time of admission. For 21 of them, at least one epileptic seizure was recorded. Nineteen patients had focal epilepsy (nine temporal lobe, two frontal lobe, two parietal lobe, eight nonlocalized), and two patients had generalized epilepsy. Seventy-three seizures of the elderly patients and 85 seizures of the 21 control patients were analyzed. In nine elderly patients and 14 control patients, at least one of their seizures started with an aura. Eleven elderly patients and 19 control patients lost responsiveness during their seizures. Approximately two thirds of the patients in both groups had automatisms during the seizures. Both focal and generalized motor seizures (e.g., clonic or tonic seizures) were seen less frequently in the elderly. CONCLUSIONS: Only a small percentage of the patients admitted to a tertiary epilepsy referral center for long-term video-EEG monitoring are older than 60 years. All seizure types observed in the elderly also were seen in the younger control group, and vice versa. Simple motor seizures were seen less frequently in the elderly.