Use of topiramate in childhood generalized seizure disorders

Topiramate is a sulfamate derivative of the naturally occurring monosaccharide D-fructose. It was initially approved in the United States as adjunctive therapy for partial seizures in 1997. However, there is increasing evidence that it is effective in the treatment of generalized seizures and epilepsy syndromes. Initially, open-label studies using topiramate as add-on therapy in children with refractory generalized seizure types were performed. These showed improvement in patients with the following generalized seizure types: typical and atypical absence, atonic, myoclonic, generalized tonic-clonic, and juvenile myoclonic epilepsy. Double-blind, placebo-controlled multicentered studies in patients with refractory primary generalized tonic-clonic seizures and epilepsy syndromes were performed. The median reduction in seizure frequency for primary generalized tonic-clonic seizures was 56.7% for topiramate and 9% for placebo. Additionally, 13.6% of topiramate-treated patients were primary generalized tonic-clonic seizure free for the study period. In the topiramate-treated juvenile myoclonic epilepsy patients, primary generalized tonic-clonic seizures were reduced > 50% in 73% of patients. Open-label extension showed that primary generalized tonic-clonic seizures were reduced >50% in 63% of topiramate-treated patients for > or = 6 months, and 16% were primary generalized tonic-clonic seizure free > or = 6 months. Accumulating evidence suggests that topiramate has a broad spectrum of antiepileptic effect. Moreover, life-threatening organ toxicity has not been attributed to topiramate. Topiramate is an effective treatment for refractory generalized seizure types and epilepsy syndromes encountered in children.     

Efficacy and Adverse Effects of Established and New Antiepileptic Drugs*

Summary: Antiepileptic drug (AED) selection is based primarily on efficacy for specific seizure types and epileptic syndromes. However, efficacy is often similar for the different AEDs, and other properties such as adverse effects, pharmacokinetic properties, and cost may also be of importance. For idiopathic generalized epilepsies with absence, tonic-clonic, and myoclonic seizures, the AED of choice is valproate (VPA). Secondarily generalized epilepsies with tonic, atonic, and other seizure types are difficult to treat with any single AED or combination of AEds. The AEDs of choice for absence seizures are ethosuximide (ESM) and VPA. For control of primary generalized tonic-clonic seizures, any of the other major AEDs can be effective. If VPA cannot be prescribed, carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), or primidone (PRM) may be effective, but ESM or a benzodiazepine (BZD) must be added to control associated absence or myoclonic seizures. The AEDs of first choice for partial epilepsies with partial and secondarily generalized tonic-clonic seizures are CBZ and PHT. Increasing evidence suggests that VPA is a good alternative when CBZ and PHT fail. PB and PRM are second-choice selections because of adverse effects. A combination of two of the five standard AEDs may be necessary to treat intractable seizures, but no studies have been done to indicate an optimal combination. Other epilepsy syndromes such as neonatal and infantile epilepsies, febrile epilepsy, alcoholic epilepsy, and status epilepticus require specific AED treatment. Ultimately, AED selection must be individualized. No “drug of choice” can be named for all patients. The expected efficacy for the seizure type, the importance of the expected adverse effects, the pharmacokinetics, and the cost of the AEDs all must be weighed and discussed with the patient before a choice is made. A number of new AEDs with unique mechanisms of action, pharmacokinetic properties, and fewer adverse effects hold important promise of improved epilepsy treatment.     

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.     

Potential role of brivaracetam in pediatric epilepsy

Brivaracetam (BRV) is a new antiseizure medication (ASM) that is currently approved for adjunctive treatment in patients with focal onset seizures. Similarly to levetiracetam (LEV), BRV works by binding SV2A vesicles with a high affinity and a linear pharmacokinetic profile. Retrospective studies and randomized clinical trials have already proven the efficacy of BRV, even in patients who failed treatment with LEV. Most studies about the efficacy and tolerability conducted so far were performed in adult cohorts, whereas few studies have been performed in children; however, BRV was proven to be a useful ASM for pediatric focal epilepsies, with fewer studies and conflicting results among patients with generalized epilepsies and epileptic syndromes. Retention rates were high in the cohorts analyzed, and no serious treatment‐emergent adverse events were reported in the majority of patients, with somnolence, drowsiness, irritability, aggression, and decreased appetite being the most frequently reported side effects. Although there are few original papers published on the subject so far, the analysis of the literature data demonstrated the efficacy and safety of BRV in pediatric patients, with more evidence for children aged 4‐16 years with an onset of focal seizures. However, a positive response was also achieved in patients affected by encephalopathic epilepsies (eg, Jeavons' epilepsy, Dravet syndrome, Lennox‐Gastaut syndrome, and juvenile myoclonic epilepsy), and ongoing studies are now testing BRV in order to widen its application to other forms of epilepsy and to test its effectiveness when used in monotherapy. This review aims to provide a comprehensive analysis of the literature surrounding the efficacy and tolerability of BRV for pediatric patients.     

Monotherapy for partial epilepsy: focus on levetiracetam

Levetiracetam (LEV), the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is a recently licensed antiepileptic drug (AED) for adjunctive therapy of partial seizures. Its mechanism of action is uncertain but it exhibits a unique profile of anticonvulsant activity in models of chronic epilepsy. Five randomized, double-blind, placebo-controlled trials enrolling adult or pediatric patients with refractory partial epilepsy have demonstrated the efficacy of LEV as adjunctive therapy, with a responder rate (>/=50% reduction in seizure frequency) of 28%-45%. Long-term efficacy studies suggest retention rates of 60% after one year, with 13% of patients seizure-free for 6 months of the study and 8% seizure-free for 1 year. More recent studies illustrated successful conversion to monotherapy in patients with refractory epilepsy, and its effectiveness as a single agent in partial epilepsy. LEV has also efficacy in generalized epilepsies. Adverse effects of LEV, including somnolence, lethargy, and dizziness, are generally mild and their occurrence rate seems to be not significantly different from that observed in placebo groups. LEV also has no clinically significant pharmacokinetic interactions with other AEDs, or with commonly prescribed medications. The combination of effective antiepileptic properties with a relatively mild adverse effect profile makes LEV an attractive therapy for partial seizures.     

Outcome of children with juvenile absence epilepsy

The incidence and natural history of childhood absence epilepsy are well documented, but those of juvenile absence epilepsy are poorly delineated. We conducted a retrospective chart study to evaluate the incidence and outcome of patients with juvenile absence epilepsy by retrieving the medical records of consecutive patients with juvenile absence epilepsy who were evaluated in three pediatric neurology outpatient clinics in Israel. Inclusion criteria included the onset of epilepsy after the age of 10 years and follow-up until at least 15 years of age. The patients with an electroencephalogram (EEG) suggestive of myoclonic epilepsy (polyspike and wave) were excluded from the study. Seventeen patients (10 female and 7 male) fulfilled the inclusion criteria for juvenile absence epilepsy. They presented with epilepsy at a mean age of 11.94 years (range 10-16.5 years). The mean duration of follow-up was 6.05 years (range 2-12 years). Five patients (29.4%) had a family history of epilepsy. All 17 patients had a normal neurodevelopmental status. Eight patients (47%) experienced generalized tonic-clonic seizures. At follow-up, eight patients (43.7%) were seizure free. Only three (37.5%) of the patients who experienced generalized tonic-clonic seizures were seizure free during follow-up compared with five (55.5%) patients without generalized tonic-clonic seizures. Our results indicate that the outcome of patients with juvenile absence epilepsy is less favorable than children with childhood absence epilepsy and that the presence of generalized tonic-clonic seizures is a predictor for poorer outcome.     

Prognostic Significance of Failure of the Initial Antiepileptic Drug in Children with Absence Epilepsy

PURPOSE: In children with childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE), to determine the impact of failure of initial antiepileptic drug (AED) for lack of efficacy in eventual seizure control and long-term remission of epilepsy. METHODS: Centralized EEG records for the province of Nova Scotia allowed identification of all children seen with CAE or JAE between 1977 and 1985. Information regarding success or failure of initial AED in fully controlling seizures and long-term seizure control and remission of epilepsy was collected by patient questionnaire and chart review. RESULTS: Eighty-six of 92 eligible patients were followed up (75 CAE, 11 JAE). Initial AED treatment was successful in 52 (60%) of 86. Success tended to be greater for valproate (VPA) than for other AEDs (p = 0.07), and lower if generalized tonic-clonic or myoclonic seizures coexisted (p < 0.004 and p < 0.03). Terminal remission was more likely if the initial AED was successful than if it had failed (69% vs. 41%; p < 0.02). Compared with those in whom the initial AED was successful, subjects whose initial AED had failed were more likely to progress to juvenile myoclonic epilepsy (JME) at last follow-up (32% vs. 10%; p < 0.02) and to develop intractable epilepsy (17% vs. 2%; p < 0.04). CONCLUSIONS: Initial AED was successful in 60% of children with AE. If the first AED failed, the outcome was less favorable, with a lower rate of terminal remission and a higher rate of progression to JME and intractable epilepsy.     

Incidence of Epilepsy in Childhood and Adolescence: A Population-Based Study in Nova Scotia from 1977 to 1985

Summary: Data from a regional EEG laboratory allowed us to identify almost all children in Nova Scotia (population 850,000) with one or more unprovoked, afebrile seizures from 1977 through 1985. We then reviewed hospital and pediatric neurology physician charts to limit cases to those with two or more definite afebrile seizures between the ages of 1 month and 16 years. In all, 693 children developed epilepsy: typical childhood absence seizures (AS) (97), either generalized tonic-clonic (GTCs) or partial seizures either secondarily generalized or not (511), and other generalized seizure types, including infantile spasms (IS) as well as myoclonic, akinetic, tonic, and atypical AS (85). The incidence of epilepsy was 118 in 100,000 for children aged < 1 year, 48 in 100,000 for those aged 1–5 years, 43 in 100,000 for those aged 6–10 years, and 21 in 100,000 for those aged 11–15 years. The incidence for each year of age between 1 and 10 years was remarkably constant (mean 46 in 100,000 ± 7 SD). Comparison of the incidence rates showed significant differences for those aged <1 year as compared with all others, and for those aged >10 years as compared with those aged 1–10 years. We conclude that the incidence of epilepsy is highest in the first year of life, plateaus in early childhood, and decreases markedly after age 10 years. The overall incidence of epilepsy in childhood is lower than that reported in previous studies.     

Two-year efficacy of lacosamide as adjunctive therapy for generalized tonic-clonic seizures in patients with juvenile myoclonic epilepsy

ObjectiveTo report the long-term efficacy of adjunctive lacosamide therapy in patients with juvenile myoclonic epilepsy whose generalized tonic-clonic seizures were significantly reduced by treatment.MethodsA retrospective study was conducted in patients who visited the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital and the Department of Pediatrics, National Hospital Organization Nagasaki Medical Center. Among patients who had been diagnosed with juvenile myoclonic epilepsy, those who received lacosamide as adjunctive therapy for refractory generalized tonic-clonic seizures for at least 2 years from January 2017 to December 2022, and who achieved seizure freedom or >50% seizure reduction in tonic-clonic seizures were included. The medical records and neurophysiological data of the patients were reviewed retrospectively.ResultsFour patients met the inclusion criteria. The mean age at the onset of epilepsy was 11.3 years (range 10–12), and the mean age of starting lacosamide was 17.5 years (range 16–21). All patients received two or more antiseizure medications prior to lacosamide. Three of four patients had seizure freedom for more than 2 years, and the one remaining patient had >50% seizure reduction for more than one year. Only one patient had recurrent myoclonic seizures after starting lacosamide. The mean lacosamide dose at the last visit was 425 mg/day (range 300–600).ConclusionAdjunctive lacosamide therapy might be a treatment option for juvenile myoclonic epilepsy with generalized tonic-clonic seizures, which are not responsive to standard antiseizure medications.     

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.     

Characteristics of patients initiated on the new antiepileptic drugs: a PADS study

Whereas randomized controlled trials remain a standard for evaluating and comparing efficacy and safety of the new antiepileptic drugs (AEDs), postmarketing drug research offers a useful means of comparing efficacy and safety of new AEDs. However, differences in baseline characteristics of patients in different drug groups create the potential for bias in drug comparison studies. In this study, baseline demographic characteristics of 1,386 patients initiating lamotrigine (LTG), tiagabine (TGB), or topiramate (TPM) were compared to identify patient characteristics that may influence AED use in epilepsy patients. Data were collected at 14 epilepsy centers and included medications, seizure types and syndromes, and prior adverse events. There were 402 patients in the LTG group, 725 TPM, and 259 TGB. The groups differed both in their number of concurrent AEDs (p<0.001) and in their number of prior AEDs (p<0.01). There was no difference in proportion with partial versus generalized epilepsy syndromes. The groups differed in the proportions of patients with complex partial seizures (p=0.049), primary generalized tonic-clonic seizures (p=0.01), and myoclonic seizures (p=0.03). Baseline behavioral adverse event rate was lowest in patients initiating TPM (p<0.01); LTG patients had the lowest rate of prior AED-related rash (p=0.02). There was no relationship between AED assignment and patient age, age of epilepsy onset, epilepsy duration, institutionalization status, gender, or psychiatric history. Numerous epidemiological differences were identified among patients placed on the new AEDs, including current and prior AED profiles, seizure types, and prior adverse event history. Accounting for these differences is of crucial importance because they may bias conclusions of nonrandomized post-marketing trials comparing the drugs.     

Evidence-based Treatment of Idiopathic Generalized Epilepsies with New Antiepileptic Drugs

Summary:  With the introduction of over ten new antiepileptic drugs (AEDs) since 1993, the hope has been that at least some of these agents would be useful for not just partial seizures, but also for the primary generalized seizures of the idiopathic generalized epilepsies (IGE). The development of evidence-based treatment guidelines in the IGE, however, faces a number of challenges, particularly after an antiepileptic drug (AED) receives approval for one indication. The majority of patients with IGE are controlled with first-line therapy if appropriately selected. Case reports or series typically appear with use in refractory patients, but these studies lack the rigor to allow formulation of guidelines. Still we are beginning to see some good class I and II data to support use of selected second-generation AEDs. It is postulated that lamotrigine (LTG), levetiracetam (LEV), topiramate (TPM), and zonisamide (ZSM) may have efficacy for a broad spectrum of seizure types including those of IGE. At the present time good class I and II evidence exists to support the use of LTG for typical absence, LEV for idiopathic myoclonic seizures, and TPM for primary generalized tonic–clonic seizures, even though only TPM has FDA approval for primary generalized seizures. This article examines the available rigorous evidence that can support these uses and also discusses some selected other reports that suggest a spectrum of efficacy for these new agents.     

Generalized spike-and-wave patterns in children: clinical correlates

All electroencephalograms performed in our institution between 1980 and 1990 were reviewed. The clinical characteristics of children with epilepsy and generalized spike-and-wave (SW) patterns were analyzed. The SW patterns were classified according to their frequency. Electroencephalograms of 154 children with epilepsy revealed SW patterns. Absence seizures were the most common first seizure, but partial seizures were frequent. More than 40% had several types of seizures. Sixty percent of the epileptic syndromes were generalized, but almost 25% were partial. The typical SW pattern was associated with absence seizures, a normal examination and computed tomographic scan, idiopathic generalized epilepsies, monotherapy, freedom from seizures, and lack of recurrence. The slow SW pattern was associated with West syndrome; a younger age at seizure onset; atonic, myoclonic, tonic, and partial simple seizures; an abnormal examination and computed tomographic scan; cryptogenic or symptomatic generalized epilepsy or symptomatic partial epilepsy; polytherapy; and poor seizure control. The fast SW pattern was associated with secondary generalized, partial, tonic-clonic, and complex partial seizures; a normal computed tomographic scan; cryptogenic partial epilepsy; isolated seizures; and seizure recurrence. Epilepsy with a typical SW pattern should be considered benign, epilepsy with a slow SW pattern malignant, and epilepsy with a fast SW pattern treacherous.     

Is vagus nerve stimulation a treatment option for patients with drug-resistant idiopathic generalized epilepsy?

Background –   The value of vagus nerve stimulation (VNS) for treating patients with drug-resistant idiopathic generalized epilepsy (IGE) is not well documented.
Patients and methods –   Twelve patients (2 males, 10 females) with a mean age of 31 years (11–48 years) and with drug-resistant IGE had VNS implanted in the period 1995–2006. All had generalized seizures documented by video-electroencephalogram. Mean follow-up period was 23 months (9–54 months).
Results –   There was a total seizure reduction of 61% (P = 0.0002). There was 62% reduction of generalized tonic-clonic seizures (P = 0.0020), 58% of absences (P = 0.0003) and 40% of myoclonic seizures (P = 0.0156). Eight patients were considered responders (>50% seizure reduction); two of these patients became seizure-free. Five out of seven patients with juvenile myoclonic epilepsy were responders. At the last follow-up visit, the patients had reduced the anti-epileptic drug (AED) usage from an average of 2.3 to 1.7 AED per patient (P = 0.0625). Two patients are currently being treated with VNS therapy only. Nine patients reported side effects, which were mostly mild and tended to diminish over time.
Conclusion –   Our results indicate that adjunctive VNS therapy is a favourable treatment option for patients with drug-resistant IGE. Rapid cycling seems worth trying in some of the non-responders.     

Clinical experience with zonisamide monotherapy and adjunctive therapy in children with epilepsy at a tertiary care referral center

We evaluated our clinical experience with zonisamide, a broad-spectrum antiepileptic drug, in a group of children with predominantly medically refractory epilepsy. A retrospective chart review was conducted on patients at our tertiary referral center following Institutional Review Board approval. Observers documented reports of seizure frequency, and seizure types were identified either clinically or by prior video-electroencephalography monitoring. We identified 68 patients (age range 1.9-18.1 years [median 6.9 years]; male to female ratio 1.3:1) treated with zonisamide for 0.7 to 28.9 months; at the last visit, 22% and 78% were on monotherapy and adjunctive therapy, respectively. The median duration of treatment and maintenance dose at the end of the follow-up were 11.2 months and 8.0 mg/kg/day, respectively. Seizure types included generalized (primary generalized tonic-clonic, myoclonic, tonic, atonic, absence) and partial (simple, complex, and secondarily generalized tonic-clonic seizures); 10 (15%) patients had both partial and generalized seizures. Sixteen (25.8%) patients were seizure free, although five of them were already in remission prior to starting zonisamide. Thirteen (21.0%) patients had a > 50% seizure reduction, 10 (16.1%) patients had a < 50% seizure reduction, 14 (22.6%) had no improvement in baseline seizures, and 9 (14.5%) reported having increased seizures. The latter were mostly associated with dosage alterations in concomitant antiepileptic drugs. Common side effects were central nervous system related, including behavioral or psychiatric (23.5%), cognitive dysfunction (12.0%), and sedation (10.3%). Eleven (16.2%) patients ultimately discontinued zonisamide, but only five were strictly due to side effects. Zonisamide is clinically effective against multiple seizure types in a significant proportion of children with epilepsy across a broad age range. Drug discontinuation as a result of side effects is uncommon.     

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.     

Clinical and neuropsychological considerations in a case of unrecognized myoclonic epileptic jerks dramatically controlled by levetiracetam

The International League Against Epilepsy (ILAE) classification recognizes 2 forms of myoclonic epilepsy with a good prognosis: benign myoclonic epilepsy of infancy (BMEI) and juvenile myoclonic epilepsy (JME); recent studies confirm the efficacy of levetiracetam (LEV) in treating idiopathic generalized epilepsies (IGE) in patients with myoclonic seizures. We report a girl referred to our Child Neuropsychiatry Unit at age 9 years because of massive myoclonic jerks, previously diagnosed as tics. Neuropsychological examination evidenced mild cognitive impairment. The clinical and electroencephalogram (EEG) data led to diagnosis of BMEI with late presentation. A dramatic suppression of interictal and ictal epileptiform activity was achieved after only one intake of LEV. Another neuropsychological examination after 6 months of treatment showed performance improvement probably related to EEG modifications. LEV may be suitable for the first-line treatment of myoclonic idiopathic seizures.     

Adult myoclonic epilepsy: a distinct syndrome of idiopathic generalized epilepsy

The authors present 11 cases of idiopathic generalized epilepsy that began in adulthood at a mean age of 39 years. All patients had myoclonic jerks, five had absence seizures, and nine had infrequent generalized tonic-clonic seizures. A majority had a family history of seizures. EEG in all patients showed generalized epileptiform abnormalities, whereas neuroimaging and neurologic examination results were normal. This series appears to represent a previously undescribed idiopathic generalized epilepsy syndrome of adult myoclonic epilepsy.     

Epilepsy With Myoclonic Atonic Seizures: An Electroclinical Study of 69 Patients

Epilepsy with myoclonic-atonic seizures is characterized by myoclonic-atonic, absence, tonic-clonic, and eventually tonic seizures, appearing in previously normal children at ages 18-60 months. We analyzed the electroclinical features, treatment, and outcome of 69 patients with myoclonic-atonic seizures; these patients were followed between 1990 and 2012 at the Juan P. Garrahan Pediatric Hospital, Buenos Aires, Argentina. No structural or metabolic etiology was identified. Based on the electroclinical features and evolution, two groups could be distinguished. The first group of 39 patients with myoclonic and myoclonic-atonic seizures with or without generalized tonic-clonic seizures and absences associated with generalized spike- and polyspike-and-wave paroxysms had excellent prognoses. The second group of 30 patients had myoclonic jerks and myoclonic-atonic seizures associated with other seizure types including tonic seizures; some had myoclonic status epilepticus and cognitive deterioration. The interictal EEG showed frequent generalized spike- and polyspike-and-wave paroxysms. In 16 patients, the seizures remitted within 3.6 years. The two groups were distinguished in retrospect, when enough time had elapsed to evaluate cognitive deterioration and different seizure types. In conclusion, epilepsy with myoclonic atonic seizures is an epileptic syndrome with a broad clinical spectrum and variable prognosis.