Generalized Tonic-Clonic Seizures in Patients with Complex-Partial Seizures: Natural History and Prognostic Relevance

Clinical course and long-term seizure prognosis were studied in 155 patients with complex-partial seizures during a follow-up of 10.1 +/- 1 (SD) years. In 79% of the patients generalized tonic-clonic seizures were recorded, mostly within the first 3 years of epilepsy but occurring as late as 20 years after the onset of epilepsy. Seizure control was defined as complete absence of all seizures, including auras, for a minimum of 2 years. Seizure control occurred in 20 of 32 patients (63%) with complex-partial seizures only and in 76 of 123 patients (62%) with complex-partial seizures and generalized tonic-clonic seizures. The onset of the epilepsy with generalized tonic-clonic seizures or complex-partial seizures did not influence the therapeutic outcome despite differences in their natural history. A family history of epilepsy and other generalized seizures (e.g., absence) were more frequent in patients with generalized tonic-clonic seizures at the onset of epilepsy. Seizure control was significantly lower (44%) in patients with a history of a maximum frequency of one or more generalized tonic-clonic seizures per month when compared to patients (79%) with a total of less than six generalized tonic-clonic seizures (p less than 0.05). The frequency of generalized tonic-clonic seizures is of predictive value for the seizure prognosis of patients with complex-partial seizures.     

Vagus nerve stimulation is associated with mood improvements in epilepsy patients

Vagus nerve stimulation (VNS) has gained increasing acceptance for treatment of drug-resistant seizures. The aim of this study was to evaluate effects of VNS on depressed mood in epilepsy patients during the first 6 months after implantation of the stimulation device. This study was conducted as an addition to the international multisite randomized and double-blind controlled trial on anti-seizure effects of VNS (EO3). Only adult patients with >4/month medication-resistant complex-partial seizures were included (N=11). During the acute phase of the study (3 months after implantation), patients were randomly assigned to low (stimulation detection) versus high stimulation (maximal tolerability, maximum 1.75 mA). Mood and mood changes were recorded based on standardized psychiatric rating scales and self-report questionnaires. Patients were assessed 4 weeks before (baseline) as well as 3 and 6 months after implantation. Significant positive mood effects were observed in most scales and subscales at the 3-month follow-up (P<0.05). Mood improvements were sustained at the 6-month follow-up and were independent of effects on seizure activity (9/11 mood responders versus 2/11 seizure responders). Mood effects appeared more pronounced in the high stimulation group after the acute study phase, but findings were not significant (P<0.10). VNS is associated with mood improvements in patients with epilepsy, but to confirm VNS dose effects, studies with more statistical power are needed.     

Psychiatric events in epilepsy.

Psychiatric events are thought to be more frequent in people with epileptic seizures than in the general population. However, inter-ictal psychiatric events attributable to epilepsy remain controversial. The aim of the present study was to evaluate the occurrence of psychiatric events in a population of fairly unselected patients with epilepsy and in the general population, and the correlation between psychiatric complaints and selected demographic and disease characteristics. The survey was part of a multicentre prospective cohort study of everyday life risks conducted in eight European countries and comparing referral children and adults with epilepsy referred to secondary/tertiary centers to age- and sex-matched non-epileptic controls. Nine hundred and fifty-one patients with epilepsy and 909 controls were studied. Each patient and his/her control received a diary to record any accident or illness, with severity, circumstances, causes, consequences, and (for the cases) the possible relation to a seizure. The follow-up period ranged between 1 and 2 years. Fifty-eight psychiatric events occurred in 25 patients (2.6%) and 88 in 19 controls (2.1%). Housewives (9.3%) and unemployed persons (4.1%) were mostly affected. No correlation was found between psychiatric events, demographic and disease characteristics. Our results suggest that people with epilepsy if unselected are not at higher risk for psychiatric disorders than the general population.     

A 15‐year follow‐up of first unprovoked seizures: a prospective study of 200 children

Epilepsy is associated with an extended spectrum of behaviour, psychiatric problems, and learning difficulties. The aim of this study was to establish the natural history of children with first unprovoked seizures. We studied prospectively 200 children under the age of 11 years who attended hospital emergency with a first unprovoked seizure. Demographic variables, personal and family history, neurological examination, EEG, psychiatric, and cognitive and educational profiles were analysed. Patients who developed epilepsy were characterised with respect to: time to relapse, remission rate, duration of epilepsy, neuroimaging, aetiology, epileptic syndrome, and therapeutic regimen. These results were compared to data of patients who had a single seizure over a follow‐up period of 15 years. Thirty percent of children who had a first unprovoked seizure developed epilepsy. Partial seizure type was a statistically significant variable for the development of epilepsy. An EEG with epileptic abnormalities proved to be the main risk factor for recurrence. Fifteen years later, the group with epilepsy exhibited a 2.6 greater risk of psychiatric and academic comorbidities, compared to the group without epilepsy.     

Predictive factors for controlling seizures using a behavioural approach.

A behavioural approach using EEG biofeedback for controlling complex-partial seizures has been successful at the Andrews/Reiter Epilepsy Research Program. Records for a random sample of 83 patients with uncontrolled seizures, one third of those receiving care between 1980 and 1985, document that 69 (83%) achieved control by completion of the programme. Additional data about initial age of seizure onset, number of years seizures had been uncontrolled and seizure frequency when treatment started were collected to determine whether these factors predicted seizure control. Only frequency was significantly related to whether seizures were controlled when treatment ended. Further study using discriminant analysis showed that earlier onset age and higher seizure frequency were associated with a significantly greater number of treatment sessions required. Thus, these two factors predicted difficulty in controlling seizures, as measured by number of sessions, although onset age did not predict whether control was eventually achieved. Since even the subgroup achieving the lowest rate of control (i.e., patients having daily seizures when treatment started) had 67% success, these results suggest that a behavioural approach can be useful for many people with currently uncontrolled complex-partial seizures regardless of their characteristics on factors examined in this study.     

Vagus nerve stimulation for drug-resistant epilepsy in children and young adults

We present our experience with the use of intermittent vagal nerve stimulation in 13 patients with medically intractable epilepsy. A surgical approach, with the exception of callosotomy, was impossible. The age range was 6-28 years (median 17 years). In all patients the epilepsy was severe and in six of them was symptomatic. Seven patients had Lennox-Gastaut syndrome, one epilepsy with myoclonic-astatic seizures, four localization-related and one symptomatic generalized epilepsy. The length of the follow-up averaged 22 months (range 8 months-3 years). Of the 13 patients, five (38.4%) had a 50% or more reduction in the number of seizures compared with preimplantation. Of these patients, one with a localization-related epilepsy had a 90% reduction as well as a significant improvement in alertness. Three patients showed no improvement with regard to the number of seizures but there was an improvement in alertness and, in one case in hyperactivity. Some seizure types responded better than others did: complex partial seizures with secondary generalization and atonic seizures. All our responsive patients improved in the first 2 months of VNS activation and only one case with further improvement was observed after this period. Considering the severity of the epilepsy the results can be considered satisfactory. We think that this treatment appears to be a safe adjunctive therapy for children and adults with medically and surgically intractable epilepsy.     

Long-Term Course of West Syndrome Associated with Tuberous Sclerosis

Summary: We retrospectively analyzed the long-term clinical profiles of 47 patients with West syndrome (WS) associated with tuberous sclerosis (TS) the follow-up study for >10 years showed that WS developed into epilepsies of various types in all patients. Their final diagnoses were symptomatic generalized epilepsy (SGE: 29 patients, 62%), symptomatic partial epilepsy (PE: 14 patients, 30%), and undetermined epilepsy (UE: 4 patients, 8%). Eighty-five percent of all patients continued to show the same types of epilepsy that they had at their first examination; but in 15% the diagnosis had to be revised at the end of the follow-up period. The outcome of seizures was unfavorable for the SGE group. In the PE group, however, seizures were controlled in 9 (64%) of the 14 patients, and disturbances of daily activity were mild. In patients with WS associated with TS, the seizure outcome and social activity varied depending on the type of epilepsy or epileptic syndrome that developed from WS. The complicated clinical developments from WS with TS multiple cortical tubers related to epileptogenesis in addition to impairment of brain development.     

Natural history and outcome of psychogenic seizures: a clinical study in 50 patients

Summary The natural history and the outcome of psychogenic seizures was studied in 50 patients by retrospective analysis and follow-up after a mean of 2 years. Concomitant epilepsy was definite in only 8% and possible in 14%, while 50% took anticonvulsants. Overall, 66% of patients showed heterogeneous psychiatric abnormalities, most commonly a depressive syndrome (24%), whereas hysterical personality features were rare (8%). Forty-two percent of patients were unemployed. Follow-up of 41 patients (82%) showed that 34% had become seizure free. Outcome was poor in those with a long history of psychogenic seizures and pathological psychiatric findings. In contrast, almost all patients with recent onset of psychogenic seizures and normal psychological status had become seizure free. At follow-up, 56% of patients were found to be in a poor or very poor state, which resulted from a combination of physical, psychic and social problems in most cases.     

Prevalence and Prognosis of Epilepsy in Patients with Multiple Sclerosis

An analysis of 599 clinically definite multiple sclerosis (MS) patients including all known cases of the southern province of Finland in January 1, 1979 revealed epileptic seizures in 21 (3.5%) patients. On that date, 12 patients needed treatment (2.0%). The age-adjusted prevalence of active epilepsy was significantly higher than that in the general population. The percentage of partial seizures (67%) was significantly increased in proportion to a series of 100 adult epilepsy patients, with a comparable age distribution. In 10 patients (including three patients with symptomatic epilepsy), the attacks appeared before the MS symptoms. The mean follow-up after the first seizures was 19.3 years. In 10 patients, the seizures disappeared totally during the surveillance until September 1985. Our results show an increased comorbidity between MS and epilepsy. In most cases, however, the prognosis of epilepsy was good and there seemed not to be any clear correlation between the severity of MS and epilepsy.     

Early-onset occipital idiopathic epilepsy: a syndrome to be treated?

The purpose of this study was to evaluate prognostic factors in early-onset childhood epilepsy with occipital paroxysms. We studied retrospectively a population of 46 patients, which was divided into three groups according to seizure frequency group 1, patients experiencing a single seizure (3396); group 2, patients experiencing two to six seizures (48%); and group 3, patients experiencing more than six seizures (20%). The mean follow-up period was about 5 years in the three groups. At the end of the first 6 months of this retrospective follow-up, the average number of seizures was higher in group 3 (2.9 seizures) than in groups 2 and 1 (1.8 and 1 seizure, respectively). We suggest that low seizure frequency in the first 6 months of follow-up could have prognostic value. We propose that the introduction of anti-epilepsy drugs be delayed for 6 months following epilepsy onset and be subsequently limited to patients with frequent seizure recurrence.     

Analysis of the characteristics of epilepsy in 37 patients with the molecular diagnosis of Angelman syndrome.

Angelman syndrome is a genetic disorder caused by defects in the maternally inherited imprinted domain located on chromosome 15q11-q13. Most patients with Angelman syndrome present with severe mental retardation, characteristic physical appearance, behavioral traits, and severe, early-onset epilepsy. We retrospectively reviewed the medical histories of 37 patients, all with the molecular diagnosis of Angelman syndrome and at least three years of follow-up in our neurology department, for further information about their epilepsy: age of onset, type of seizures initially and during follow-up, EEG recordings, treatments and response. The molecular studies showed 87% deletions de novo, 8% uniparental, paternal disomy, and 5% imprinting defects. The median age at diagnosis was 6.5 years, with 20% having begun to manifest febrile seizures at an average age of 1.9 years. Nearly all (95%) presented with epilepsy, the majority under the age of three (76%). The most frequent seizure types were myoclonic, atonic, generalized tonic-clonic and atypical absences. At onset, two patients exhibited West syndrome. EEG recordings typical of Angelman syndrome were found in 68%. Normalization of EEG appeared in 12 patients after nine years. Control of epileptic seizures improved after the age of 8.5 years. The most effective treatments were valproic acid and clonazepam. We conclude that epilepsy was present in nearly all of our cases with Angelman syndrome, and that the EEG can be a useful diagnostic tool. On comparing the severity of epilepsy with the type of genetic alteration, we did not find any statistically significant correlations.     

Atypical "benign" partial epilepsy or pseudo-Lennox syndrome. Part I: symptomatology and long-term prognosis

PURPOSE: Atypical benign partial epilepsy (ABPE) or pseudo-Lennox syndrome (PLS) is characterised by generalised minor seizures and focal sharp slow waves and spikes (SHW) as observed in Rolandic epilepsy (RE), but with exceptional pronounced activation during sleep. The aim of this study was to describe the full spectrum of ABPE in the hitherto largest group of patients. METHODS: We retrospectively analysed the clinical and EEG data of 43 children who fulfilled the following criteria: occurrence of generalised minor seizures as described for ABPE (i.e., atonicastatic seizures, myoclonic seizures, atypical absences) and focal SHW identical to those observed in RE, but with generalisation during sleep. RESULTS: Language development prior to onset of epilepsy was retarded in 26% of patients. In 74%, age at onset of epilepsy ranged from 2 to 6 years. Manifestation occurred earlier in boys than in girls. Generalised minor seizures constituted the predominating seizure type in 67% of patients. Twenty-eight percent of patients suffered from simple partial seizures of the oro-facial region or generalised tonic-clonic seizures originating from the oro-facial region. Additionally, generalised tonic-clonic (44%), unilateral (21%), partial motor (44%), versive (12%), focal atonic (9%), and complex-partial seizures (2%) were observed. A bioelectrical status was recorded in 56% of patients during sleep. No tonic seizures and no fast spike series (bursts of 10-20 Hz rhythms) were observed. At last follow-up, 84% of patients were in clinical remission. All subjects older than age 15 were seizure-free. However, 56% of patients attended a school for mentally handicapped children. CONCLUSIONS: ABPE or PLS broadly overlaps with RE, electrical status epilepticus during sleep, and Landau-Kleffner syndrome. Regarding the epilepsy, the prognosis is excellent, mental deficit, however, seems to be frequent. The differentiation from Lennox-Gastaut syndrome and myoclonic astatic epilepsy is essential. Instead of ABPE, the term pseudo-Lennox syndrome is proposed.     

Epilepsy in middle-aged and elderly people: a three-year observation.

An analysis of the medical documentation and investigation of 130 cases of epilepsy diagnosed in a group of people over 50 years of age (average: 65.4 years) revealed that the most common type of seizure in the group studied was partial (66.2%), followed by seizures with secondary generalization (33.8%). Epilepsy was caused by cerebrovascular disease (50.8%) considerably more often in patients over 74 years of age, craniocerebral trauma in patients addicted to alcohol (13.1%), especially those under 65 years of age, primary or metastatic neoplastic disease (10.7%), and others. The authors wish to draw attention to the leukoaraiosis factor, which might be the proepileptogenic cause of epilepsy recognized in the group of patients over 74 years of age (56.5%) and is much more frequent in this group than in the group of patients under 65 years of age (1.6%). Moreover, some drugs, such as L-dopa and Baclofen, might have been related to the epileptic seizures. In 29 patients (22.3%) the definite cause of late-onset epilepsy was unknown. The authors suggest in such cases, both follow-up tomographic examination and careful clinical examinations. In the study group of patients with initially unknown seizure etiology, some diseases, such as cerebral tumor or colon and pancreatic neoplasm, were diagnosed during follow-up examination. These processes were revealed several months after the first epileptic seizure.     

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.     

The clinical characterizations of benign partial epilepsy in infancy

The aim of this study is to clarify the detailed clinical features of benign partial epilepsy in infancy. The subject of the study was 33 patients with benign partial epilepsy in infancy confirmed by a long-term follow-up beyond 8 years of age. The data were obtained from medical records of the patients in combination with the data obtained from telephone interview. The median age at the first and last seizure was 5 and 8 months, respectively. In 26 patients, seizures disappeared within 3 months after the onset. Family history of benign partial epilepsy in infancy was seen in 17 patients. The median number of seizures was 7. A cluster of seizures was observed in 26 patients. The type of seizures was complex partial seizures alone in 6 patients, secondarily generalized seizures alone in 9, and both types in 18. Decreased responsiveness, lateral eye deviation, and cyanosis were commonly observed. Initial interictal electroencephalograms were normal in all patients. However, paroxysmal discharges were recognized in 2 patients in the second EEG during the first year of life. The main features of benign partial epilepsy in infancy were a high incidence of a cluster of seizures, short persistence of seizures, and normal initial interictal EEGs.     

De novo psychogenic nonepileptic attacks after adult epilepsy surgery: An underestimated entity

We retrospectively assessed all patients in a large cohort of patients with epilepsy surgery at the National Hospital for Neurology and Neurosurgery (NHNN) over 12 years, to identify patients with postoperative psychogenic nonepileptic attacks (PNEA). Twenty‐nine patients (23 women) were identified of a total of 790 patients, a frequency of 3.7%. Female gender and presurgical psychiatric diagnosis, other than psychosis, were significant risk factors for PNEA development. In female patients with a preoperative psychiatric diagnosis the chance of developing PNEA after epilepsy surgery was 8.5%. PNEA developed between 2 weeks and 10 years after epilepsy surgery, independently of outcome of epileptic seizures. In most cases, PNEA differed from the present or past epileptic seizures, and motor symptoms were the most common manifestations. Seizures after epilepsy surgery should be carefully evaluated. Physicians should consider the possibility of PNEA, especially in female patients with preoperative psychiatric comorbidity developing “atypical” seizures with motor manifestations postoperatively, even many years after epilepsy surgery.     

Provocation of pseudoseizures by psychiatric interview during EEG and video monitoring.

OBJECTIVE: This paper discusses a new technique for diagnosing pseudoseizures. The technique consists of an intensive psychiatric interview designed to provoke a pseudoseizure during EEG and video monitoring. We wished to determine the overall efficacy of the technique and learn how our patients felt about having undergone the procedure. We were also interested in whether their seizures persisted approximately three years later. METHOD: We reviewed medical records and conducted telephone interviews with thirty of thirty-two patients who had previously undergone the procedure as part of an evaluation for unusual or intractable seizures. All evaluations had been performed on a university hospital neurology service. The patients were consecutive referrals to the consultative psychiatry service for suspicion of pseudoseizures. RESULTS: Nineteen of the thirty-two patients interviewed had a pseudoseizure under EEG and video monitoring. Of the thirty reached by telephone for follow-up, twenty-two recalled the procedure as helpful or benign. None regarded the overall psychiatric consultation negatively. Among the patients who had exhibited pseudoseizures there was a variety of psychiatric diagnoses with a preponderance of personality disorders. Two thirds of those patients without coexisting epilepsy stopped having seizures or rarely had seizures following their evaluations. CONCLUSIONS: The diagnostic technique described here is useful in patients with possible pseudoseizures. It does not appear to be harmful when employed as part of a comprehensive psychiatric consultation. How it may compare with other methods of pseudoseizure diagnosis will have to be determined by further study.     

Prognosis of ischemic stroke in childhood: a long-term follow-up study

Little is known about long-term physical sequelae, cognitive functioning, and quality of life in children who have experienced ischemic stroke. Thirty-seven patients under 16 years of age were studied; the median interval after stroke was 7 years. CT-scans were reassessed to determine the type of infarction at baseline. Occurrences of death, of new cardiovascular events, and of seizures during follow-up were recorded. Surviving patients were invited for a follow-up examination, including physical check-up, global screening of cognition, and an inventory of subjective health perception. Only two patients were lost to follow-up. During follow-up four died, nine developed seizures, eight had transient ischemic attacks, and two experienced a recurrent ischemic stroke. None of the patients had cardiac complications during follow-up. In 11 of 27, no functional impairment was found, in 15 there was a hemiparesis of varying severity, and in one a paraplegia. There was a significant shift in cognitive functioning towards lower levels, especially in children with epilepsy. Remedial teaching was frequently needed. Many of the parents' perceived their child's behavior to be very changeable. Three-quarters of the children considered themselves as healthy as other children, and almost all of them as happy. The physical and functional prognosis after ischemic stroke in childhood is relatively good, particularly in children with no serious causative illness, but special education is often needed and social changes occur.     

The contributing factors to medical cost of epilepsy: an estimation based on a French prospective cohort study of patients with newly diagnosed epileptic seizures (the CAROLE study). Active Coordination of the Longitudinal Observational Network in Epilepsy.

Epilepsy is a common neurological condition with significant resource implications. An estimation was performed in France of the direct medical cost of patients presented with newly diagnosed seizures and followed during the first two years after diagnosis. This estimation was based on the service utilization data collected from French prospective cohort study (CAROLE: 1942 patients enrolled). Costs were estimated in a societal perspective in 1998 value. The impact on the costs of different factors like age, aetiologic categorization and severity of seizures (type and number of seizures), and treatment by anti-epileptic drugs (AEDs) was analysed. The mean annual direct epilepsy-related costs per patient were estimated to be 14 305 F and 3766 F for the first and the second year of follow-up respectively, 68% and 40% of the costs were devoted to inpatient care. Costs during the first year were highly sensitive to aetiologic categorization of seizures at inclusion and to other clinical parameters. Second-year costs had a much lower variance and were sensitive to frequency of seizures and the fact of being treated or not by AEDs. Our data emphasize the importance of seizure control as means of reducing the costs of epilepsy especially during the first year of follow-up.