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PubMedDate not supplied

Prognosis of epilepsy in newly referred patients: a multicenter prospective study. Collaborative Group for the Study of Epilepsy.

A multicenter prospective study was initiated at the time of first antiepileptic treatment for afebrile seizures with 283 unselected patients in Italy. Each patient started with monotherapy at standard daily doses. Data were collected at admission, at scheduled 6-month exams, and at unscheduled exams and included age, sex, general profile of the disease, and treatment. Prognosis of epilepsy was evaluated by actuarial methods using first seizure relapse after onset of treatment to indicate unfavorable prognosis. In addition, a maximum interval of complete seizure control was calculated and related to length of follow-up in order to grade the severity of the disease (defined as mild, moderate, or severe). The average length of follow-up was 21.6 months (range 2-40). Seizure relapse occurred in 52% of cases during follow-up (36% by 3 months, 43% by 6 months, and 49% by 12 months). A larger number of seizures before therapy and the presence of combined seizure patterns were the variables most commonly associated with relapse. In general, epilepsy was mild in 65% of the cases, moderate in 28%, and severe in 7%. The earlier the first relapse the higher the risk of developing more severe disease. A larger number of seizures before treatment, combined seizure types, earlier age at onset, and prolonged disease duration (1 month to 1 year) seemed to be more frequently associated with the development of moderate-to-severe epilepsy.

Actuarial Analysis↗
PubMed1989

Juvenile myoclonic epilepsy: characteristics of a primary generalized epilepsy.

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

Anticonvulsants↗
PubMed1997

Cause-specific mortality in epilepsy: a cohort study of more than 9,000 patients once hospitalized for epilepsy.

PURPOSE: We studied overall and cause-specific mortality rates in a large cohort of patients with epilepsy compared with mortality rates of the general population in the same geographic area. METHODS: The cohort consisted of all patients (N = 9,061) aged > 15 years admitted with a diagnosis of epilepsy for inpatient care in Stockholm during the years 1980-1989. All patients were followed in the National Cause-of-Death Register, from which the causes of death were obtained, until December 31, 1992. Thus, 53,520 person-years were observed. Mortality rates were compared with those of the general population of Stockholm. RESULTS: We observed 4,001 deaths in the cohort, compared with an expected number of 1,109 deaths in the general population. This yielded a standardized mortality ratio (SMR) of 3.6 [95% confidence interval (CI) 3.5-3.7]. Although highest in the younger patients, the SMR was significantly increased in all age groups. The excess mortality rate in the cohort was due to a wide range of causes of death, including malignant neoplasms [SMR 2.6 (2.4-2.8)], diseases of the circulatory system, [SMR 3.1 (3.0-3.3)], diseases of the respiratory system [SMR 4.0 (3.6-4.5)], diseases of the digestive system [SMR 5.1 (4.4-5.8)], and injuries and poisoning [SMR 5.6 (5.0-6.3)]. CONCLUSIONS: Our results demonstrate that this large subgroup of patients with a diagnosis of epilepsy, once hospitalized and discharged, is a population at risk, with an excess mortality rate due to several different causes.

Accidents↗
PubMed1999

The early prognosis of epilepsy in childhood: the prediction of a poor outcome. The Dutch study of epilepsy in childhood.

PURPOSE: To examine which variables available early in the course of childhood epilepsy are associated with a poor short-term outcome and to develop models to predict such an outcome. METHODS: We prospectively followed up 466 children with newly diagnosed epilepsy for 2 years. Variables were collected at intake and after 6 months. Outcome was defined as the duration of the terminal remission (TR): poor (<6 months) and not poor (> or =6 months). RESULTS: Of the subjects, 31% had a poor outcome. Multivariate analysis based on the intake variables identified number of seizures, seizure type, and etiology as risk factors for a poor outcome. With the intake and 6-month variables combined, seizure type, etiology, the number of seizures, and not attaining a 3-month remission during these 6 months, and the EEG at 6 months were predictive variables. A predictive model based on the multivariate logistic-regression analysis with the intake variables was correct in 56% of the children in whom it predicted a poor outcome and in 73% of the children in whom it predicted a not-poor outcome. With the intake and 6-month variables together, these percentages were 66 and 79%, respectively. The sensitivity of these models was low (29 and 47%, respectively); the specificity was good (90 and 89%). CONCLUSIONS: The 2-year outcome of childhood epilepsy is closely related to its early course. The prognosis is poor in approximately 30% of patients. By using our data, the prediction of a poor outcome is correct in almost two thirds of the patients; however, the models produce many false-negative predictions.

Age Factors↗
PubMed2004

Absence of cortical gray matter abnormalities in psychosis of epilepsy: a voxel-based MRI study in patients with temporal lobe epilepsy.

The authors retrospectively explored cortical differences between 26 patients with temporal lobe epilepsy and psychosis of epilepsy (POE), 24 patients with temporal lobe epilepsy (TLE) alone, and 20 healthy comparison subjects. Using voxel-based morphometry based on statistical parametric mapping (SPM99), which is an unbiased and fully automated technique to test for morphometric differences, magnetic resonance imaging (MRI) 3D-datasets were acquired and analyzed. There were no significant cortical gray matter differences between the POE and the TLE group. Since cortical pathology is prominent in schizophrenia, POE may be a clinical entity separate from schizophrenia.

Adult↗
PubMed2004

Mortality in epilepsy: driving fatalities vs other causes of death in patients with epilepsy.

OBJECTIVES: To estimate the risk to public safety posed by drivers with epilepsy, the authors compared annual totals and disease-specific risk for fatal crashes associated with seizures and other medical conditions. They compared individual risks for fatal crashes due to seizures and other causes of mortality in patients with epilepsy. METHODS: The authors analyzed Multiple-Cause of Mortality data files from death certificates provided by the National Center for Health Statistics (NCHS) for the years 1995-97. They analyzed International Classification of Diseases-9 codes for underlying causes of death and other major conditions and determined disease-specific rates of fatal crashes associated with seizures and other medical conditions. RESULTS: An average of 44,027 US drivers died annually as a result of motor vehicle crashes during 1995-97; however, only 86 (0.2%, range 82 to 97) of these deaths were associated with seizures in mortality reports. The incidence rate of fatal crashes for patients with seizures was 2.3 times the rate for patients with cardiovascular and hypertensive diseases and 4.6 times the rate for patients with diabetes. The proportionate mortality ratio for motor vehicle crashes in patients with seizures was low (0.2); most patients with epilepsy died of common cardiovascular and systemic disorders. CONCLUSION: Fatal driver crashes due to seizures are uncommon. This finding supports the current public policy of permitting patients whose seizures are controlled to drive.

Accidents, Traffic↗
PubMed2006

Enhancing GABA(A) receptor alpha 1 subunit levels in hippocampal dentate gyrus inhibits epilepsy development in an animal model of temporal lobe epilepsy.

Differential expression of GABA(A) receptor (GABR) subunits has been demonstrated in hippocampus from patients and animals with temporal lobe epilepsy (TLE), but whether these changes are important for epileptogenesis remains unknown. Previous studies in the adult rat pilocarpine model of TLE found reduced expression of GABR alpha1 subunits and increased expression of alpha4 subunits in dentate gyrus (DG) of epileptic rats compared with controls. To investigate whether this altered subunit expression is a critical determinant of spontaneous seizure development, we used adeno-associated virus type 2 containing the alpha4 subunit gene (GABRA4) promoter to drive transgene expression in DG after status epilepticus (SE). This novel use of a condition-dependent promoter upregulated after SE successfully increased expression of GABR alpha1 subunit mRNA and protein in DG at 1-2 weeks after SE. Enhanced alpha1 expression in DG resulted in a threefold increase in mean seizure-free time after SE and a 60% decrease in the number of rats developing epilepsy (recurrent spontaneous seizures) in the first 4 weeks after SE. These findings provide the first direct evidence that altering GABR subunit expression can affect the development of epilepsy and suggest that alpha1 subunit levels are important determinants of inhibitory function in hippocampus.

Animals↗
PubMed1998

Insular epilepsy. Similarities to temporal lobe epilepsy. Case report.

Insular epilepsy has been rarely reported and its clinical and electrographic features are poorly understood. The electrographic study of the insula is difficult since it is hidden from the brain surface by the frontal and temporal lobe. A 48 years-old woman started having simple partial autonomic and complex partial seizures with automatisms and ictal left arm paresis 8 years prior to admission. Seizure's frequency was 1 per week. Pre-operative EEG showed a right temporal lobe focus. Neuropsychological testing disclosed right fronto-temporal dysfunction. MRI showed a right anterior insular cavernous angioma. Intraoperative ECoG obtained after splitting of the sylvian fissure showed independent spiking from the insula and temporal lobe and insular spikes that spread to the temporal lobe. The cavernous angioma and the surrounding gliotic tissue were removed and the temporal lobe was left in place. Post-resection ECoG still disclosed independent temporal and insular spiking with a lower frequency. The patient has been seizure-free since surgery. Insular epilepsy may share many clinical and electroencephalographic features with temporal lobe epilepsy.

Brain Neoplasms↗
PubMed2000

Magnetic resonance imaging in temporal lobe epilepsy: usefulness for the etiological diagnosis of temporal lobe epilepsy.

With improvement in magnetic resonance (MR) imaging techniques, the ability to identify lesions responsible for temporal lobe epilepsy has increased. MR imaging has also enabled the in vivo diagnosis of hippocampal sclerosis. Brain tumors are responsible for 2-4% of epilepsies in adult population and 10-20% of medically intractable epilepsy. The sensitivity of MR imaging in the diagnosis of tumors and other lesions of the temporal lobe (vascular malformations, etc.) is around 90%. Both hippocampal sclerosis and other temporal lobe lesions are amenable to surgical therapy with excellent postsurgical seizure outcome. In this article, we characterize and underline distinguishing features of the different pathological entities. We also suggest an approach to reviewing the MR images of an epileptic patient.

Brain↗
PubMed2005

Normal magnetic resonance imaging and medial temporal lobe epilepsy: the clinical syndrome of paradoxical temporal lobe epilepsy.

OBJECT: The syndrome of medial temporal lobe epilepsy (MTLE) may occur in patients in whom magnetic resonance (MR) images demonstrate normal findings. In these patients, there is no evidence of hippocampal sclerosis on neuroimaging, and histopathological examination of the resected hippocampus does not reveal significant neuron loss. In this paper the authors describe the distinct clinical features of this MTLE subtype, referred to as paradoxical temporal lobe epilepsy (PTLE). METHODS: The authors selected 12 consecutive patients with preoperative findings consistent with MTLE in whom MR imaging did not demonstrate any hippocampal abnormality. Onset of hippocampal seizure was confirmed by long-term intracranial monitoring. There were six female and six male patients with a mean age of 32 +/- 11 years, (mean +/- standard deviation [SD]) at presentation. These patients' seizure histories, available hippocampal volumetric measurements, and hippocampal cell densities in different subfields were reviewed. Sharp electrode recordings from dentate granule cells that had been maintained in hippocampal slices provided a measure of excitation and inhibition in the tissue. We compared these data with those of a cohort of 50 randomly selected patients who underwent anteromedial temporal resection for medial temporal sclerosis (MTS) during the same time period (1987-1999). The durations of follow up (means +/- SDs) for the PTLE and MTS groups were 51 +/- 59 months and 88 +/- 44 months, respectively. A history of febrile seizure was present less frequently in the PTLE group (8%) than in the MTS group (34%). Other risk factors for epilepsy such as trauma, meningoencephalitis, or perinatal injuries were present more frequently in the PTLE group (50%) than in the MTS cohort (36%). In patients in the PTLE group the first seizure occurred later in life (mean age at seizure onset 14 years in the PTLE group compared with 9 years in the MTS group, p = 0.09). Ten patients (83%) in the PTLE cohort and 23 patients (46%) in the MTLE cohort had secondary generalization of their seizures. Among patients with PTLE, volumetric measurements (five patients) and randomized blinded visual inspection (seven patients) of the bilateral hippocampi revealed no atrophy and no increased T2 signal change on preoperative MR images. All patients with PTLE underwent anteromedial temporal resection (amygdalohippocampectomy, in five patients on the left side and in seven on the right side). Electrophysiological studies of hippocampal slices demonstrated that dentate granule cells from patients with PTLE were significantly less excitable than those from patients with MTS. The mean pyramidal cell loss in the CAI subfield in patients in the PTLE group was 20% (range 0-59%) and that in patients in the MTS group was 75% (range 41-90%) (p < 0.001). Maximal neuron loss (mean loss 38%) occurred in the CA4 region in six patients with PTLE (end folium sclerosis). At the last follow-up examination, six patients (50%) in the PTLE group were seizure free compared with 38 patients (76%) in the MTS group. CONCLUSIONS: Clinical PTLE is a distinct syndrome with clinical features and surgical outcomes different from-those of MTS.

Adolescent↗
PubMed1999

Pathology of temporal lobe epilepsy: An analysis of 100 consecutive surgical specimens from patients with medically refractory epilepsy.

The neuropathological features of temporal lobe epilepsy were studied utilising 100 consecutive surgical specimens from patients with medically refractory complex partial seizures. A wide spectrum of neuropathological changes was recorded in 98 specimens. Fifty-eight specimens showed features of Ammon's horn sclerosis. Diffuse accumulation of corpora amylacea were demonstrated in the resected temporal lobes from 54 patients. Six patients had neoplastic lesions of temporal lobe. One unique case of dysembryoplastic neuroepithelial tumour showed a melanotic component within the tumour. The neuropathological features were regarded as nonspecific in 31% of cases. Our results indicate that a majority of patients with medically intractable epilepsy of temporal lobe origin reveal significant neuropathological features. Careful documentation of the neuropathological features and its correlation with radiological, electrophysiological and pre- and post-surgical clinical features will help in predicting the seizure outcome after temporal lobectomy for medically refractory epilepsy.

Brain Neoplasms↗
PubMed2004

"Severe myoclonic epilepsy in infancy". Relevance for the clinician of severe epilepsy starting in infancy.

'Severe myoclonic epilepsy in infancy' or Dravet syndrome is a clear example of the impact of severe epilepsy on the developing child. Presenting with febrile seizures in infancy, children later on develop a severe epileptic syndrome with mental retardation. Nearly all children have life-threatening status epilepticus during the first two years of life. The clinical diagnosis can now be confirmed by DNA-analysis in a majority of patients. Most patients have a de novo mutation in the alfa subunit of the neuronal sodium channel SCN1A. In the past few years' treatment of severe myoclonic epilepsy in infancy has changed. Prevention of seizures, avoiding anti-epileptic drugs which only block sodium channels, a simple combination of two major anti-epileptic drugs (sodium valproate and topiramate) and a strict acute seizure treatment significantly improve the quality of life for these patients. Long-term follow up is necessary to evaluate if we can also improve the development possibilities for these children.

Child, Preschool↗
PubMed1992

Epilepsy, antiepileptic drugs, and malformations in children of women with epilepsy: a French prospective cohort study.

We conducted a prospective study of teratogenic effects of antiepileptic drugs (AEDs) in pregnant women with epilepsy in southeast France, comparing malformation rates with those collected by a birth defects registry. We evaluated isolated microcephalies separately. Malformations were seen in 7% of infants of mothers with epilepsy (IME) and in 1.36% of the general population. No significant relationship was found between type and severity of epilepsy and occurrence of malformations or isolated microcephaly. Valproate and phenytoin were the most teratogenic (all malformations). None of the malformations observed in IME whose mothers received valproate, phenytoin, or phenobarbital was seen in IME not exposed to the respective AEDs. Phenytoin plus phenobarbital was more teratogenic than phenobarbital alone. Benzodiazepines, prescribed only in combinations, had a borderline, nonspecific effect on microcephaly.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

[The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: I. Criteria for starting and discontinuing and the pharmacological bases of antiepileptic treatment].

AIMS: The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology's Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care.

Anticonvulsants↗
PubMedDate not supplied

[The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: III. Antiepileptic therapy in special situations].

AIMS: The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology's Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care.

Abnormalities, Drug-Induced↗
PubMed1991

Awakening epilepsy ('Aufwach-Epilepsie') revisited.

The concept of 'awakening epilepsy' (introduced by Janz, 1953) occupies a crucial position for the comprehension of primary generalized epilepsy. The associated electroencephalographic manifestations are discussed and the role of abnormal (paroxysmal) arousal responses ('dyshormia') is stressed. The origin of these bilateral-synchronous discharges appears to be located below the frontal midline scalp region in mesial portions of the supplementary motor region. 'Awakening epilepsy' is also interesting from the viewpoint of sleep research. There is also an important age factor; these seizures (mostly grand mal and classical petit mal absences) are most common in older children, adolescents and young adults. The general management of these patients has to take into account the patient's special vulnerability after a night of poor sleep.

Arousal↗
PubMedDate not supplied

[Usefulness of a strain of mice with genetically determined audiogenic epilepsy as a model of experimental epilepsy].

Behavioural and bioelectric characteristics of epileptic seizures caused by acoustic stimulus in mice from the Swiss Albino Rb strain with genetically determined audiogenic epilepsy are presented. The value of this epilepsy model is emphasized stressing that the epileptogenic stimulus acts from a distance, causing no damage to the nervous system and no artifacts. Besides that, seizures can be provoked at a definite frequency and at arbitrarily chosen time. A disadvantage of the model is the necessity of provoking each seizure separately which causes that this model cannot meet one of the conditions of Jasper's definition concerning spontaneity of seizure development. With regard to the course of seizure it is emphasized that it is somewhat similar to human grand mal epilepsy representing the basic phases of seizure. Electrophysiological investigations carried out under conditions of long-term fully reproducible experiment demonstrated presence of very evident and rich electrocorticographic symptomatology of audiogenic epileptic seizure whose behavioural phases show a high correlation with phasic changes in bioelectric brain activity. The investigations carried out in sleep failed to demonstrate differences in the susceptibility to seizure development when the stimulus was applied in waking state or in any of both phases of sleep. This strain is useful to morphological ultrastructural, biochemical and possibly electrophysiological investigations.

Animals↗
PubMedDate not supplied

Intractable epilepsy in children who develop epilepsy in the first decade of life--a prospective study.

Prospective studies on 347 children under treatment due to seizures which appeared in the first 10 years of life helped to evaluate and define the incidence of epilepsy resistant to treatment. With regard to each patient the following aspects were analysed: the kind of seizures, their etiology, accompanying neurological disorders and a type of epileptic syndrome, kind of treatment applied before admission to the clinical department as well as socioeconomic conditions of the families. Patients under study were divided into four age groups to evaluate the results. Epilepsy, which was completely resistant to treatment, was observed in 10% of the patients, partially resistant in 20%. Resistance is the outcome of the following factors: onset of epilepsy in early childhood, symptomatic etiology coexisting symptoms of CNS damage, occurrence of unfavourable epileptic syndromes such as Lennox-Gastaut, wrong selection and low dosage of drugs, inappropriate polytherapy and adverse social conditions. On the basis of the results obtained, the authors suggested point evaluation as a kind of screening in prediction of failures in treatment.

Age of Onset↗