Nationwide survey (incidence,clinical course,prognosis) of Rasmussen’s encephalitis

Purpose: Rasmussen’s encephalitis (RE) is a progressive and catastrophic epileptic disorder caused by chronic localized encephalitis. We performed a nationwide survey of RE to assess the clinical picture, treatment effect, and prognosis of Japanese RE patients. Subjects & methods: The subjects were 27 patients (male:12; female:15) from 13 medical facilities. All of them satisfied the clinical and neuroimaging criteria for RE, including 14 pathologically proven cases. Results: They were divided into the childhood-onset rapidly progressive type (CORP, n = 19), and late-onset slowly progressive type (LOSP, n = 8). The mean age at epilepsy onset was 4 years and 4 months in CORP, and 16 years in LOSP. The mean period between the onset age of epilepsy and development of frequent seizures was 1 year and 4 months in the former, and 3 years and 4 months in the latter. The immunomodulatory treatment including high-dose steroid (n = 14) and high-dose intravenous immunoglobulin therapies (IVIgG, n = 12) achieved more than a 50% reduction in the seizure frequency in 5 (36%) and 4 (33%) patients, respectively. Eight and seven patients underwent focal cortical resection and functional hemispherectomy, leading to significant improvement in 5 of the 8 patients and excellent seizure control in all 7 patients, respectively. Conclusion: Although the high-dose steroid and IVIG therapies may have alleviated the exacerbation of seizures in those with RE, they could not halt the disease progression. Functional hemispherectomy is still the only curative therapy for RE, despite the fact that the early introduction of this procedure remains controversial.     

Vagus nerve stimulator treatment in adult-onset Rasmussen's encephalitis

We describe a patient with adult-onset Rasmussen's encephalitis (RE) responsive to vagus nerve stimulation. This previously healthy woman developed RE in the right hemisphere at the age of 27. Despite antiepileptic drug polytherapy, she continued to experience subcontinuous, simple-partial left-sided motor seizures and slowly progressive cognitive impairment. Resective surgery was not considered owing to the preservation of left motor skills. She was implanted with a vagus nerve stimulator at the age of 41; after 6 months she experienced a greater than 50% reduction in seizure frequency, which persisted over 2 years together with improvement of her neurological and cognitive status.     

Absence of seizures in Rasmussen encephalitis with active inflammation

Severe focal motor epilepsy is considered a clinical hallmark of Rasmussen encephalitis (RE). The authors report a 6-year-old girl with progressive right sided hemiparesis, loss of language skills, left sided hemispheric atrophy, and brain pathologic features characteristic for RE. The patient did not experience seizures over a 2 year period after symptom onset and for several months during follow-up. This report expands the clinical spectrum of RE and suggests that seizures are not a universal symptom of RE. Our patient’s quite remarkable neurologic deficits along with active inflammation in the absence of epilepsy supports that, at least in some individuals, unilateral hemispheric progressive inflammation can occur without active seizure activity.     

Rasmussen encephalitis: long-term outcome after surgery

Background and purpose

Rasmussen encephalitis (RE) is characterized by intractable epilepsy, progressive hemiparesis, and unilateral hemispheric atrophy. The progression of the symptoms to significant neurological impairment usually occurs within months to a few years. RE causes are unknown, although evidence of an autoimmune process has been extensively described in the literature. Antiepileptic drugs are usually not effective to control seizures or cerebral atrophy; despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, for intractable seizures in RE patients with advanced disease, epilepsy surgery in the form of hemispheric disconnection has been considered the treatment of choice. This work describes the clinical and electrographic analyses, as well as the post-operative evolution of patients with RE.

Materials and methods

This work includes all the patients with RE evaluated from January 1995 to January 2008 by the Ribeirão Preto Epilepsy Surgery Program (CIREP), taking variables such as gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery, when done; duration of epilepsy; surgery complications; follow-up duration; anatomo-pathological findings; post-surgery seizure; language and cognitive outcome; and anti-epileptic drug treatment after surgery into account.

Results

Twenty-five patients were evaluated; thirteen were female. Mean age of epilepsy onset was 4.4?±?2.0 years. There were no differences between patients with slow and fast evolution with respect to age of epilepsy onset (p?=?0.79), age at surgery (p?=?0.24), duration of epilepsy (0.06), and follow-up (p?=?0.40). There were no correlations between the presence of bilateral EEG abnormalities or the absence of spikes and post-operative seizure outcome (p?=?0.06). Immunomodulatory therapy was tried in 12 patients (48%). Twenty-three patients underwent surgery. The mean follow-up was 63.3 months. Eleven patients had total seizure control. Twelve individuals persisted with seizures consisting of mild facial jerks (six patients), occasional hemigeneralized tonic–clonic seizures (three patients), and frequent tonic–clonic seizures (three patients). Mental and language impairment was observed in 15 and 12 patients, after surgery, respectively. Eight patients presented post-operative cognitive decline, while only two patients had cognitive improvement. Comparing pre- and post-operative language deficits, 66.7% of the 12 patients with language disturbance did not improve after surgery.

Conclusions

This retrospective study reported the clinical and electrographic analysis, as well as the evolution of 23 patients with RE. Patients were divided into two groups: fast evolution and slow evolution to hemiparesis and epilepsia partialis continua. These groups may represent different RE substrates. Fourteen patients achieved satisfactory seizure control, three patients had partial response to surgery, and five patients had maintenance of the pre-operative condition. All patients with left-side involvement presented with some language disturbance, which did not improve after surgery in 66.6% of patients. Cognitive evaluation showed that the majority of the patients did not have any significant improvement, and 38.1% had cognitive deterioration after surgery.     

Atypical presentation in Rasmussen encephalitis: delayed late-onset periodic epileptic spasms

A five-and-a-half-year-old girl started experiencing progressive left hemiparesis at age two and a half years. At age five years and four months she started presenting clusters of asymmetric periodic epileptic spasms with no hypsarrhythmia. The ictal EEG showed periodic, constant and stereotyped complexes. Serial brain imaging revealed progressive atrophy of the right hemisphere with increased T2 signal on MRI. She underwent a right hemispherotomy, and histological examination showed signs of inflammation and features of focal cortical dysplasia (FCD). She has been seizure-free for 16 months. This case is unique in the following aspects: the presence of typical Rasmussen encephalitis features of progressive unilateral brain involvement without seizures, a delay of almost three years prior to seizure onset; an atypical seizure type presentation with periodic epileptic spasms and the presence of FCD associated with inflammatory changes. [Published with video sequences].     

Epilepsy in hemiplegic cerebral palsy due to perinatal arterial ischaemic stroke

Aim The aim of this study was to describe the frequency, risk factors, manifestations, and outcome of epilepsy in children with hemiplegic cerebral palsy (CP) due to perinatal arterial ischaemic stroke (AIS). Method The study group comprised 63 participants (41 males, 22 females) from a population‐based CP register whose brain imaging showed perinatal AIS. Information collected included occurrence of neonatal seizures, family history of epilepsy, motor function and epilepsy onset, treatment, and outcome. Electroclinical findings were classified according to seizure semiology, seizure type, and epilepsy syndrome. Results Mean age of participants at the time of study was 10 years 6 months (SD 4y 7mo, range 4–20y). Gross Motor Function Classification System levels I and II were reported in 96% of participants, and Manual Ability Classification System levels I and II were reported in 79% of children. Thirty‐four children (54%) developed epilepsy. Term delivery and more severe motor impairment were associated with epilepsy, but neonatal seizures and family history of epilepsy were not. Initial seizures were epileptic spasms, focal seizures, or myoclonic seizures. Focal seizure semiology suggested Rolandic or occipital seizure origin in the majority of children. Focal epileptic discharges in children with focal seizures had features of idiopathic partial epilepsy. Only 15% of children had active epilepsy 10 years after onset. Interpretation Despite a high incidence of epilepsy in children with hemiplegic CP due to AIS, the prognosis for seizure remission is good. Many children have clinical features, electroencephalography findings, and remission typical of idiopathic partial epilepsy.     

Kainic acid induced hippocampal seizures in rats: comparisons of acute and chronic seizures using intrahippocampal versus systemic injections

Hyppocampal epilepsy is a recently defined syndrome occurring in 65% of all temporal lobe epilepsies as defined by: 1) electrographic (EEG) onset in the hippocampus (HC) prior to EEG seizures elsewhere, 2) post-resection hippocampal sclerosis and mossy fiber synaptic reorganizations and 3) relief of typical complex partial seizures after surgical resection of the hyppocampus. We used intrahippocampal kainic acid injections V² in rats at different developmental ages (postnatal 7 through adult) to develop long term spontaneous HC EEG spikes, EEG seizures, and behavioral seizures. Split-screen video/EEG monitoring demonstrated that this intrahippocampal kainic acid model produced progressive development of: 1) ipsilateral interictal spikes, 2) later polyspike complexes, 3) bilaterally-asynchronous EEG spiking, 4) unilateral HC EEG seizure onsets with occasional secondarily generalized spread to apposite HC and motor cortex to elicit complex partial seizures, and 5) in all seizing rats there was mossy fiber synaptic reorganization, even when injected at age 7 days. These results indicate that the intrahippocampal kainic acid injection model is similar to human hippocampal epilepsy.Supported by NIH Grants NS 02808, NS 31655 (T.L.B.); K08 NS 1603 (G.W.M.); and Fogarty Fellowship TWO 4959 (J.P.L.).     

Atonic variant of benign childhood epilepsy with centrotemporal spikes (atonic-BECTS): a distinct electro-clinical syndrome

Purpose

To describe the clinical and electroencephalographic features, treatment strategies and outcome in a series of children with the atonic variant of benign childhood epilepsy with centrotemporal spikes (atonic-BECTS).

Material and methods

Out of the 148 patients with BECTS reviewed from January 2005 to June 2010 in our Institute, there were seven (5%) with atonic-BECTS. All underwent video EEG, high-resolution magnetic resonance imaging (MRI), neuropsychological evaluation and language assessment. Their progress was followed. In addition to sodium valproate, three were treated with steroids, followed by intravenous immunoglobulin (IVIG) when the seizures relapsed while tapering or after stopping the steroids.

Results

All of the children had earlier onset (mean = 2.4 years), increased frequency and increased duration of focal seizures compared to typical BECTS. Head drop and truncal sway due to axial or axiorhizomelic atonia occurring several times per day or week was the key manifestation. The atonic seizures worsened with carbamazepine in three, clonazepam in two and clobazam in one. When the atypical seizures commenced, some children developed one or more of the following problems: hyperactivity, attention deficit, clumsy gait, and mild cognitive or language dysfunction. Three children became seizure free, one on steroids and the other two on IVIG.

Conclusions

BECTS in children with an early age of onset and frequent and prolonged seizures is more likely to evolve into atonic-BECTS. Carbamazepine and some benzodiazepines may worsen these seizures. Three children became seizure free with immunomodulatory therapy, one on steroids and the other two on IVIG, and had complete resolution of the transient motor and cognitive impairment. Atonic-BECTS needs to be differentiated from Lennox–Gastaut syndrome since it is potentially treatable and children recover with no sequel. Although all the children in this series continued to be on treatment with sodium valproate it is currently undetermined whether they would have required to do so if followed up for an extended period of time.     

Epilepsy surgery for hemispheric syndromes in infants: Hemimegalencepahly and hemispheric cortical dysplasia

Objective: Hemimegalencepahly (HME) and Hemispheric Cortical Dysplasia (HCD) are rare congenital diseases that occur with intractable epilepsy. They manifest by early epilepsy, mental retardation, hemianopsia and contralateral hemiplegia. Hemispheric disconnection (mainly anatomical hemispherectomy, peri-insular hemispherotomy, modified lateral hemispherotomy and vertical parasagittal hemispherotomy) have been reported to be efficient on seizures and also to prevent additional cognitive injury and developmental delay. Method: We reviewed literature about clinical presentation, predictors of outcome and expectation about epileptic seizures and cognitive outcome. Results: Clinical presentation and seizures outcome have been described in almost 600 children for the last thirty years. Epilepsy improved in most cases depending on the series and the follow-up duration. Percentage of seizure-free patients with HME or HCD was lower than in other groups (Rasmussen Encephalitis, Vascular Sequellae). Post-operative complications decreased with the hemispherotomy surgical procedures. EEG abnormalities on the “save” hemisphere did not negatively influence postsurgical outcome. Seizure free outcome did not seem to depend on the surgical procedure but the presence of residual insular cortex seemed to be associated with persistent postoperative seizures. Contralateral MRI abnormalities seemed to be associated with poorer prognosis for seizure free outcome and lack of cognitive improvement. Conclusion: Hemispheric disconnection remains the best treatment in order to control epileptic seizures. Hemispheric surgical procedures are safe and can be performed from the first month of life. Prospective studies of cognition are needed to emphasize benefits on long term outcome.     

Slowly progressive hemiparesis in childhood as a consequence of Rasmussen encephalitis without or with delayed-onset seizures

Five young children developed slowly progressive hemiparesis as the initial manifestation of Rasmussen encephalitis (RE). Three have remained seizure free over an observational period of 1.3–1.9 years. In the remaining two patients, seizures occurred after 0.5 and 0.6 years respectively. We suggest that RE might be presently underdiagnosed and should be suspected in cases of new onset hemiparesis. In this series, three out of five patients showed oligoclonal bands on examination of cerebrospinal fluid (CSF) which represented additional diagnostic hints towards an immune-mediated condition. According to recently published formal diagnostic criteria, evidence of progressive cerebral hemiatrophy or bioptic identification of RE-typical inflammation confirms the diagnosis in such cases. Long-term immunotherapy is recommended in order to prevent further tissue loss and functional decline.     

Callosotomy and subsequent surgery for children with refractory epilepsy

Callosotomy has been considered as a palliative therapy for refractory epilepsy patients with non-focal onset seizures. Residual partial seizures and unilateral epileptiform discharges on electroencephalography (EEG) are sometimes observed after callosotomy. These findings suggest that some patients may be candidates for subsequent resective surgery. Of 149 children who received a callosotomy, resective/disconnective surgery was subsequently performed in 19 patients. Most patients had generalized seizures and epileptiform discharges on EEG before callosotomy. Two-third had normal neuroimaging studies at initial presurgical evaluation. After callosotomy, ictal symptoms evolved into asymmetric features suggesting partial onset seizures. Post-callosotomy EEG showed completely lateralized or localized epileptiform discharges responsible for residual partial seizures in 16 of 19 patients. Fifteen patients underwent resective surgery of the unilateral frontal lobe, and the remaining received hemispherotomy or posterior quadrantectomy. After subsequent surgery, favorable seizure outcomes were obtained in 11 patients (57.9%). Favorable seizure outcomes may be achieved with callosotomy and subsequent surgery in selected patients who are not candidates for a conventional resective surgery at initial presurgical evaluation.     

Seizure frequency and cortisol and dehydroepiandrosterone sulfate (DHEAS) levels in women with epilepsy receiving antiepileptic drug treatment

PURPOSE: Hormonal changes occur in epilepsy because of seizures themselves and of antiepileptic drug (AED) effects on steroid production, binding, and metabolism. Conversely, steroids may influence neuron activity and excitability by acting as neuroactive steroids. This cross-sectional observational study aimed to evaluating cortisol and dehydroepiandrosterone sulfate (DHEAS) levels in female epilepsy patients with different disease severity, as assessed by a seizure frequency score (SFS). METHODS: Morning serum levels of cortisol and DHEAS were assayed in 113 consecutive women, aged 16 to 47 years, with varied epilepsy syndromes, receiving mono- or polytherapy with enzyme-inducing and/or noninducing antiepileptic drugs (AEDs). Hormonal data were correlated with clinical parameters (age, body mass index, epilepsy syndrome, disease onset and duration, SFS, AED therapy, and AED serum levels) and compared with those of 30 age-matched healthy women. RESULTS: In epilepsy patients, cortisol levels and cortisol-to-DHEAS ratios (C/Dr) were significantly higher, whereas DHEAS levels were significantly lower than those in controls. Patients with more frequent seizures showed higher cortisol and C/Dr values and lower DHEAS levels than did those with rarer or absent seizures during the previous 6 months. SFS mainly explained the increase of cortisol levels and C/Dr in patients with more active disease. Changes in DHEAS levels correlated with SFS and epilepsy syndrome, as well as with AED treatments and ages. CONCLUSIONS: Women with more frequent seizures had alterations of their adrenal steroids characterized by an increase of cortisol and a decrease of DHEAS levels. Such hormonal changes might be relevant in seizure control and in patient health.     

Effect of early versus late onset of major motor epilepsy on cognitive-intellectual performance: further considerations.

Two groups of adult patients, one with early (0-5 years), the other with late (10-15 years) age of seizure onset, were compared on 14 variables derived from the Wechsler Adult Intelligence Scale (WAIS) and Halstead's neuropsychological measures. The groups were matched for duration of the disorder and seizure frequency, and all subjects (Ss) had unequivocal histories of major motor seizures. The group with early age of onset obtained significantly lower WAIS, Verbal IQ, Performance IQ, and Full Scale IQ values than the group with late age of onset. No significant intergroup differences were obtained on Halstead's measures, although the performances of both groups were impaired vis-a-vis non-neurological control expectancy. The results suggest that early onset age, as operationally defined in this study, has a specifc differential influence which is restricted to psychometric intellectual functions as measured by the WAIS in groups matched for seizure duration and seizure frequency.     

Effect of major motor seizure frequency upon cognitive-intellectual functions in adults.

Wechsler Aandult Intelligence Scale and Halstead neuropsychological performances were investigated in three groups of adult subjects with major motor epilepsy classified according to low, moderate, and high seizure frequency. The groups were equated on seizure duration and age at onset variables. On 7 of the 14 psychological measures employed, significant between-group differences were obtained, with poorest, intermediate, and best test scores associated with the high, moderate, and low seizure frequency groups, respectively. Similar performance comparisons were made on two additional groups: a "high risk" group characterized by early onset age, long seizure duration, and high seizure frequency, and a "low risk" group characterized by late onset age, short seizure duration, and low seizure frequency. Highly significant differences were obtained between the high risk and low risk groups on 12 of 14 variables, with the high risk subjects demonstrating severe cognitive and adaptive impairment in comparison to the low risk subjects. The results support the conclusion that increased frequency of major motor seizures is associated with increasing levels of adaptive impairment, and that the probability of severe cognitive-adaptive dysfunction is further and substantially increased when high seizure frequency is accompanied by a history of early onset and long duration of the disorder.     

Periictal heart rate variability analysis suggests long‐term postictal autonomic disturbance in epilepsy

Background: One of the possible pathomechanisms of sudden death in epilepsy (SUDEP) is a postictal dysregulation of autonomic nervous system. We performed a heart rate variability (HRV) analysis of the periictal state to analyze whether a cardiac autonomic disturbance exists after an epileptic seizure. Methods: We included 31 periictal video–EEG–ECG recordings of 31 patients with epilepsy who had consecutively undergone pre‐surgical evaluation. Nine generalized tonic‐clonic (GTCS), 15 complex partial, and seven simple motor seizures were included. HRV was evaluated by analyzing 5‐min‐long ECG epochs, sampling from baseline, direct preictal, early‐postictal (<15 min after the seizure), and late‐postictal (5–6 h after the seizure) periods. Results: The heart rate was elevated immediately after the seizures, but 5–6 h postictally returned to the baseline level. Time‐domain components of HRV decreased after the seizure and this decrease lasted for 5–6 h. Low‐frequency power decreased in the early‐postictal phase and high‐frequency power of HRV dropped in the late‐postictal phase. GTCS had an impact on short‐term but not on long‐term postictal HRV decrease. Conclusions: We found decreased HRV immediately after the seizures, which lasted at least 5–6 h postictally, indicating a long‐term postictal disturbance of the autonomous nervous system. GTCS were accompanied by a more decreased HRV than other seizures. Our results may have relevance in explaining pathomechanism of SUDEP.     

Long term outcome of temporal lobe epilepsy surgery: analyses of 140 consecutive patients

OBJECTIVE: To analyse the long term results of temporal lobe epilepsy surgery in a national epilepsy surgery centre for adults, and to evaluate preoperative factors predicting a good postoperative outcome on long term follow up. METHODS: Longitudinal follow up of 140 consecutive adult patients operated on for drug resistant temporal lobe epilepsy. RESULTS: 46% of patients with unilateral temporal lobe epilepsy became seizure-free, 10% had only postoperative auras, and 15% had rare seizures on follow up for (mean (SD)) 5.4 (2.6) years, range 0.25 to 10.5 years. The best outcome was after introduction of a standardised magnetic resonance (MR) imaging protocol (1993-99): in unilateral temporal lobe epilepsy, 52% of patients became seizure-free, 7% had only postoperative auras, and 17% had rare seizures (median follow up 3.8 years, range 0.25 to 6.5 years); in palliative cases (incomplete removal of focus), a reduction in seizures of at least 80% was achieved in 71% of cases (median follow up 3.1 years, range 1.1 to 6.8 years). Most seizure relapses (86%) occurred within one year of the operation, and outcome at one year did not differ from the long term outcome. Unilateral hippocampal atrophy with or without temporal cortical atrophy on qualitative MR imaging (p < 0.001, odds ratio (OR) 5.2, 95% confidence interval (CI) 2.0 to 13.7), other unitemporal structural lesions on qualitative MR imaging (p < or = 0.001, OR 6.9, 95% CI 2.2 to 21.5), onset of epilepsy before the age of five years (p < 0.05, OR 2.9, 95% CI 1.2 to 7.2), and focal seizures with ictal impairment of consciousness and focal ictal EEG as a predominant seizure type (p < 0.05, OR 3.4, 95% CI 1.2 to 9.1) predicted Engel I-II outcome. Hippocampal volume reduction of at least 1 SD from the mean of controls on the side of the seizure onset (p < 0.05, OR 3.1, 95% CI 1.1 to 9.2) also predicted Engel I-II outcome. CONCLUSIONS: Outcome at one year postoperatively is highly predictive of long term outcome after temporal lobe epilepsy surgery. Unitemporal MR imaging abnormalities, early onset of epilepsy, and seizure type predominance are factors associated with good postoperative outcome.     

Neuropathological spectrum of Rasmussen encephalitis

BACKGROUND: Rasmussen encephalitis (RE) is a chronic epileptic disorder of unknown etiology, and is clinically characterized by progressive neurological deterioration, focal seizures often progressing to intractable epilepsy, cognitive decline and hemispheric atrophy. AIMS: We report the spectrum of neuropathological changes seen in RE, and discuss the evolutionary mechanisms of this disease. MATERIALS AND METHODS: Surgically obtained specimens from RE patients diagnosed during 2002-2004 at this institute were evaluated for the presence and extent of different histopathological features of RE. The H&E and immunohistochemistry stained slides were also evaluated for the type and distribution pattern of inflammatory infiltrates, along with a semiquantitative evaluation for the severity of inflammation. RESULTS: Four cases of RE were admitted during the study period, all of which presented with partial seizures with successive deterioration to intractable epilepsy. The age at onset varied between 5 and 10 years (mean 7.8 years), with three male and one female patients. Subsequently, all four patients underwent hemispherotomy. Histopathological features of perivascular lymphocytic infiltrate, neuronal loss, microglial nodules, and reactive astrocytosis, with or without evidence of neuronophagia confirmed a diagnosis of RE. These cases also had varying degrees of T-cell-rich (CD3-positive) inflammatory infiltrates and CD68-immunopositive microglial proliferation. It was observed that the severity of inflammation had a trend to inversely correlate with the duration of symptoms. CONCLUSION: It is proposed that an accurate evaluation and histopathological grading of these lesions may possibly have a role in patient prognostication.     

Changes in sex steroid levels in women with epilepsy on treatment: Relationship with antiepileptic therapies and seizure frequency

Purpose:   Reproductive dysfunction in epilepsy is attributed to the seizures themselves and also to antiepileptic drugs (AEDs), which affect steroid production, binding, and metabolism. In turn, neuroactive steroids may influence neuronal excitability. A previous study in this cohort of consecutive women with epilepsy showed that patients with more frequent seizures had higher cortisol and lower dehydroepiandrosterone sulfate levels than those with rare or absent seizures. The present study was aimed at evaluating, in these same women, the possible relationship between some clinical parameters, seizure frequency, AED therapies, and sex hormone levels.
Methods:   Estradiol (E2), progesterone (Pg), sex hormone-binding globulin (SHBG), and free estrogen index (FEI) were measured during the luteal phase in 113 consecutive females, 16–47 years old, with different epilepsy syndromes on enzyme-inducing AED (EIAED) and/or non–enzyme-inducing AED (NEIAED) treatments, and in 30 age-matched healthy women. Hormonal data were correlated with clinical parameters (age, epilepsy syndrome, disease onset, and duration), seizure frequency assessed on the basis of a seizure frequency score (SFS), and AED therapies.
Results:   E2, Pg, and FEI were lower, whereas SHBG levels were higher in the epilepsy patients than in the controls. However, sex steroid and SHBG levels were not different between groups of patients categorized according to SFS. Therapies with EIAEDs accounted for changes in E2 levels and FEI.
Conclusions:   Despite globally decreased sex steroid levels in serum, actual hormone titers were not significantly correlated with SFS in consecutive epilepsy women; rather, these hormonal changes were explained by AED treatments, mainly when EIAED polytherapies were given.     

Do partial seizures predict an increased risk of seizure recurrence after antiepilepsy drugs are withdrawn?

Most children who are seizure free on antiepilepsy drugs for 2 or more years remain seizure free when taken off antiepilepsy drugs. We studied 27 children with well-controlled epilepsy in whom seizures unexpectedly recurred after antiepilepsy drug withdrawal. Seizures were focal in 20 of 27 cases (74%). In 11 of the 20 cases (55%), there was also a late onset of seizures (after 2 years) and an abnormal electroencephalogram (EEG) at antiepilepsy drug withdrawal. Of the remaining 9 patients with focal seizures, 3 (15%) had only a late seizure onset, 3 (15%) had only an abnormal EEG, and 3 (15%) had neither a late onset of seizures nor an abnormal EEG. In the 7 patients without focal seizures, 6 of 7 (86%) had a late seizure onset and/or an abnormal EEG. Our study suggests that partial seizures can be the most important predictor of unanticipated seizure recurrence when antiepilepsy drugs are withdrawn, particularly with late onset of seizures and an abnormal EEG at antiepilepsy drug withdrawal. A large, multicenter, prospective study looking at these and other potential risk factors for seizure recurrence is needed.     

Characterization and health risk assessment of postmenopausal women with epilepsy

Postmenopausal women with epilepsy represent an understudied patient population. The objectives of this cross-sectional study were to characterize the impact of menopause on seizure activity and to conduct a health risk assessment. We conducted telephone interviews of 40 postmenopausal women with epilepsy concerning the effect of menopause on seizure frequency. We surveyed use of hormone replacement therapy, postmenopausal bone fractures, use of vitamins, and frequency of exercise. The average age and mean seizure duration were 55.8 and 27.6 years, respectively. Twenty-six women had onset of seizure activity before menopause. Of these 26, 3 reported fewer seizures after menopause, 7 reported more seizures, 11 reported no change, and 5 were unsure whether menopause affected their seizures. Only 30% of the 40 women were currently taking hormone replacement therapy. The impact of menopause on seizure activity was variable. Osteoporotic and cardiovascular preventive measures are underutilized. Patient education on these protective measures should be part of the comprehensive treatment approach in this "at-risk" patient population.