Showing papers in "Epilepsia in 2002"

Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology.

Abstract: INTRODUCTION PRINCIPLES FOR TERMS AND DEFINITIONS DATA SOURCES I GENERAL TERMS 1.0 SEMIOLOGY 2.0 EPILEPTIC SEIZURE 3.0 ICTUS 4.0 EPILEPSY 5.0 FOCAL 6.0 GENERALIZED 7.0 CONVULSION II TERMS DESCRIBING EPILEPTIC SEIZURE SEMIOLOGY 1.0 MOTOR 1.1 ELEMENTARY MOTOR 1.1.1 TONIC 1.1.1.1 EPILEPTIC SPASM 1.1.1.2 POSTURAL 1.1.1.2.1 VERSIVE 1.1.1.2.2 DYSTONIC 1.1.2 MYOCLONIC 1.1.2.1 NEGATIVE MYOCLONIC 1.1.2.2 CLONIC 1.1.2.2.1 JACKSONIAN MARCH 1.1.3 TONIC-CLONIC 1.1.3.1 GENERALIZED TONIC-CLONIC SEIZURE 1.1.4 ATONIC 1.1.5 ASTATIC 1.1.6 SYNCHRONOUS 1.2 AUTOMATISM 1.2.1 OROALIMENTARY 1.2.2 MIMETIC 1.2.3 MANUAL OR PEDAL 1.2.4 GESTURAL 1.2.5 HYPERKINETIC 1.2.6 HYPOKINETIC 1.2.7 DYSPHASIC 1.2.8 DYSPRAXIC 1.2.9 GELASTIC 1.2.10 DACRYSTIC 1.2.11 VOCAL 1.2.12 VERBAL 1.2.13 SPONTANEOUS 1.2.14 INTERACTIVE 2.0 NON-MOTOR 2.1 AURA 2.2 SENSORY 2.2.1 ELEMENTARY 2.2.1.1 SOMATOSENSORY 2.2.1.2 VISUAL 2.2.1.3 AUDITORY 2.2.1.4 OLFACTORY 2.2.1.5 GUSTATORY 2.2.1.6 EPIGASTRIC 2.2.1.7 CEPHALIC 2.2.1.8 AUTONOMIC 2.2.2 EXPERIENTIAL 2.2.2.1 AFFECTIVE 2.2.2.2 MNEMONIC 2.2.2.3 HALLUCINATORY 2.2.2.4 ILLUSORY 2.3 DYSCOGNITIVE 3.0 AUTONOMIC EVENTS 3.1 AUTONOMIC AURA 3.2 AUTONOMIC SEIZURE 4.0 SOMATOTOPIC MODIFIERS 4.1 LATERALITY 4.1.1 UNILATERAL 4.1.1.1 HEMI4.1.2 GENERALIZED (syn. “bilateral”) 4.1.2.1 ASYMMETRICAL 4.1.2.2 SYMMETRICAL 4.2 BODY PART 4.3 CENTRICITY 4.3.1 AXIAL Epilepsia, 42(9):1212–1218, 2001 Blackwell Science, Inc. © International League Against Epilepsy

Neural networks in human epilepsy: evidence of and implications for treatment

Abstract: A considerable amount of compelling evidence exists, predominantly from animal models and experimental paradigms, for the existence of specific cortical and subcortical networks in the genesis and expression of partialand generalized-onset seizures (1–13). My goal is to present the concept of human epilepsy as a disorder of large neural networks and to support through several lines of reasoning how applicable the observations from experimental models are to localization-related seizures in the human disorder. I do not attempt to define specifically every possible operational human network or even all the limits or components of those that I do address, but I hope to show in a compelling way that the evidence we already have is not consistent with any other explanation. This is a new way of understanding, diagnosing, and potentially treating the various forms of human epilepsy. In this context, I consider a network to be a functionally and anatomically connected, bilaterally represented, set of cortical and subcortical brain structures and regions in which activity in any one part affects activity in all the others. The essential operational component of this definition is the observation that vulnerability to seizure activity in any one part of the network is influenced by activity everywhere else in the network, and that the network as a whole is responsible for the clinical and electrographic phenomena that we associate with human seizures. Implicit in this idea is that the seizures may entrain this large neural network from any given part, such that it becomes irrelevant to discuss the “onset” of seizures in any specific part of the network. In other words, the electrical hyperexcitability associated with seizure activity reverberates within the neural structures of the network, which operate together and inextricably to culminate in the eventual expression of seizures. A singular concept is the distinction between the anatomic structures involved in seizure propagation, and those belonging to the neural network that underlies a specific patient’s epilepsy. The network structures are connected functionally and structurally; they are essential to the development of the seizure and thus the existence and maintenance of the epileptic disorder. Independently, seizures propagate in a variably extensive way that might involve any region or neural structure with anatomic connections to the primary seizure network; seizures can propagate to many more regions than those that are involved in the network. Important corollaries that derive from these ideas are that interruption of the network, in a structural sense, or modification of network activity by electrical, biochemical, or metabolic influences in any part of the network will alter seizure expression or its occurrence. The corollaries have the greatest implications for treatment, as we will see later. Based on extensive experience with a great number and diversity of human epilepsy patients with intractable seizures, I describe and support the evidence for three specific large human epilepsy networks. Many others are likely, but the data are not so extensive. The first is the network associated with the most common human intractable epilepsy, and the one about which we have the most information: the medial temporal/limbic network. The medial temporal/limbic network is bilateral, cortical, and subcortical, and includes the hippocampi, the amygdalae, the entorhinal cortices, lateral temporal neocortices, and extratemporal components of the medial thalamus and the inferior frontal lobes. The other two networks are less commonly identified, even in their component parts: the medial occipital/lateral temporal network and the superior parietal/medial frontal network. Two additional networks, for which evidence is highly suggestive, but which I do not discuss in detail, include the bifrontal/ pontine/subthalamic network and the parietal/medial temporal network. The lines of evidence that support the existence and importance of these networks in the genesis of human epilepsy are clinical observations, intracranial EEG, functional neuroimaging, anatomic observations, and the response of seizures to specific invasive treatments. Accepted December 7, 2001. Address correspondence and reprint requests to Dr. S.S. Spencer at Department of Neurology, Yale University School of Medicine, P.O. Box 208018, New Haven, CT 06520-8018, U.S.A. E-mail: susan.spencer@yale.edu Epilepsia, 43(3):219–227, 2002 Blackwell Publishing, Inc. © International League Against Epilepsy

Chronic anterior thalamus stimulation for intractable epilepsy.

Abstract: Summary: Purpose: A significant number of patients with epilepsy remain poorly controlled despite antiepileptic medication (AED) treatment and are not eligible for resective surgery. Novel therapeutic methods are required to decrease seizure burden in this population. Several observations have indicated that the anterior thalamic region plays an important role in the maintenance and propagation of seizures. We investigated neuromodulation of the anterior thalamus by using deep-brain stimulation (DBS) in patients with intractable seizures. Methods: Five patients with medically refractory epilepsy underwent stereotactic placement of and received stimulation through bilateral DBS electrodes in the anterior thalamus. Results: Treatment showed a statistically significant decrease in seizure frequency, with a mean reduction of 54% (mean follow-up, 15 months). Two of the patients had a seizure reduction of ≥75%. No adverse effects were observed after DBS electrode insertion or stimulation. Unexpectedly, the observed benefits did not differ between stimulation-on and stimulation-off periods. Conclusions: DBS of the anterior thalamus is a safe procedure and possibly effective in patients with medically resistant seizures.

Treatment of Refractory Status Epilepticus with Pentobarbital, Propofol, or Midazolam: A Systematic Review

Abstract: Summary: Background: New continuous infusion antiepileptic drugs (cIV-AEDs) offer alternatives to pentobarbital for the treatment of refractory status epilepticus (RSE). However, no prospective randomized studies have evaluated the treatment of RSE. This systematic review compares the efficacy of midazolam (MDL), propofol (PRO), and pentobarbital (PTB) for terminating seizures and improving outcome in RSE patients. Methods: We performed a literature search of studies describing the use of MDL, PRO, or PTB for the treatment of RSE published between January 1970 and September 2001, by using MEDLINE, OVID, and manually searched bibliographies. We included peer-reviewed studies of adult patients with SE refractory to at least two standard AEDs. Main outcome measures were the frequency of immediate treatment failure (clinical or electrographic seizures occurring 1 to 6 h after starting cIV-AED therapy) and mortality according to choice of agent and titration goal (cIV-AED titration to “seizure suppression” versus “EEG background suppression”). Results: Twenty-eight studies describing a total of 193 patients fulfilled our selection criteria: MDL (n = 54), PRO (n = 33), and PTB (n = 106). Forty-eight percent of patients died, and mortality was not significantly associated with the choice of agent or titration goal. PTB was usually titrated to EEG background suppression by using intermittent EEG monitoring, whereas MDL and PRO were more often titrated to seizure suppression with continuous EEG monitoring. Compared with treatment with MDL or PRO, PTB treatment was associated with a lower frequency of short-term treatment failure (8 vs. 23%; p < 0.01), breakthrough seizures (12 vs. 42%; p < 0.001), and changes to a different cIV-AED (3 vs. 21%; p < 0.001), and a higher frequency of hypotension (systolic blood pressure <100 mm Hg; 77 vs. 34%; p < 0.001). Compared with seizure suppression (n = 59), titration of treatment to EEG background suppression (n = 87) was associated with a lower frequency of breakthrough seizures (4 vs. 53%; p < 0.001) and a higher frequency of hypotension (76 vs. 29%; p < 0.001). Conclusions: Despite the inherent limitations of a systematic review, our results suggest that treatment with PTB, or any cIV-AED infusion to attain EEG background suppression, may be more effective than other strategies for treating RSE. However, these interventions also were associated with an increased frequency of hypotension, and no effect on mortality was seen. A prospective randomized trial comparing different agents and titration goals for RSE with obligatory continuous EEG monitoring is needed.

The Importance of Drug Interactions in Epilepsy Therapy

Abstract: Long-term antiepileptic drug (AED) therapy is the reality for the majority of patients diagnosed with epilepsy. One AED will usually be sufficient to control seizures effectively, but a significant proportion of patients will need to receive a multiple AED regimen. Furthermore, polytherapy may be necessary for the treatment of concomitant disease. The fact that over-the-counter drugs and nutritional supplements are increasingly being self-administered by patients also must be considered. Therefore the probability of patients with epilepsy experiencing drug interactions is high, particularly with the traditional AEDs, which are highly prone to drug interactions. Physicians prescribing AEDs to patients with epilepsy must, therefore, be aware of the potential for drug interactions and the effects (pharmacokinetic and pharmacodynamic) that can occur both during combination therapy and on drug discontinuation. Although pharmacokinetic interactions are numerous and well described, pharmacodynamic interactions are few and usually concluded by default. Perhaps the most clinically significant pharmacodynamic interaction is that of lamotrigine (LTG) and valproic acid (VPA); these drugs exhibit synergistic efficacy when coadministered in patients with refractory partial and generalised seizures. Hepatic metabolism is often the target for pharmacokinetic drug interactions, and enzyme-inducing drugs such as phenytoin (PHT), phenobarbitone (PB), and carbamazepine (CBZ) will readily enhance the metabolism of other AEDs [e.g., LTG, topiramate (TPM), and tiagabine (TGB)]. The enzyme-inducing AEDs also enhance the metabolism of many other drugs (e.g., oral contraceptives, antidepressants, and warfarin) so that therapeutic efficacy of coadministered drugs is lost unless the dosage is increased. VPA inhibits the metabolism of PB and LTG, resulting in an elevation in the plasma concentrations of the inhibited drugs and consequently an increased risk of toxicity. The inhibition of the metabolism of CBZ by VPA results in an elevation of the metabolite CBZ-epoxide, which also increases the risk of toxicity. Other examples include the inhibition of PHT and CBZ metabolism by cimetidine and CBZ metabolism by erythromycin. In recent years, a more rational approach has been taken with regard to metabolic drug interactions because of our enhanced understanding of the cytochrome P450 system that is responsible for the metabolism of many drugs, including AEDs. The review briefly discusses the mechanisms of drug interactions and then proceeds to highlight some of the more clinically relevant drug interactions between AEDs and between AEDs and non-AEDs. Understanding the fundamental principles that contribute to a drug interaction may help the physician to better anticipate a drug interaction and allow a graded and planned therapeutic response and, therefore, help to enhance the management of patients with epilepsy who may require treatment with polytherapy regimens.

Systematic review and meta-analysis of incidence studies of epilepsy and unprovoked seizures.

Abstract: Summary: Purpose: To evaluate the methodology of incidence studies of epilepsy and unprovoked seizures and to assess the value of their findings by summarizing their results. Methods: A Medline literature search from January 1966 to December 1999 was conducted. In each selected study, key methodologic items such as case definition and study design were evaluated. Furthermore, a quantitative meta-analysis of the incidence data was performed. Results: Forty incidence studies met the inclusion criteria. There was considerable heterogeneity in study methodology, and the methodologic quality score was generally low. The median incidence rate of epilepsy and unprovoked seizures was 47.4 and 56 per 100,000, respectively. The age-specific incidence of epilepsy was high in those aged 60 years or older, but was highest in childhood. Males had a slightly higher incidence of epilepsy (median, 50.7/100,000) than did females (median, 46.2/100,000), and partial seizures seemed to occur more often than generalized seizures. Developing countries had a higher incidence rate of epilepsy (median, 68.7/100,000) than did industrialized countries (median, 43.4/100,000). Similar results were found for unprovoked seizures. The incidence of epilepsy over time appears to decrease in children, whereas it increases in the elderly. Conclusions: The age-specific incidence of epilepsy showed a bimodal distribution with the highest peak in childhood. No definitive conclusions could be reached for the incidence of unprovoked seizures and other specific incidence rates of epilepsy. More incidence studies with an adequate study methodology are needed to explore geographic variations and time trends of the incidence of epilepsy and unprovoked seizures.

Functional role of inflammatory cytokines and antiinflammatory molecules in seizures and epileptogenesis

Abstract: Purpose: We investigated the changes in the expression of proinflammatory cytokines and related molecules in the rodent hippocampus after the induction of limbic seizures. We then studied the effects of pharmacologic intervention on the interleukin (IL)-1 system on limbic seizures and the susceptibility to seizures of transgenic mice overexpressing the naturally occurring antagonist of IL-1 (IL-1Ra) in astrocytes. Methods: Limbic seizures were induced in rodents by intrahippocampal injection of kainic acid or bicuculline methiodide or by electrical stimulation of the hippocampus causing status epilepticus (SE). Seizure activity was recorded by EEG analysis and behavioral observation according to Racine's scale. Cytokine expression in the hippocampus was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot quantification of the various messenger RNAs (mRNAs) and by immunocytochemistry. Results: We found that limbic seizures rapidly and transiently enhanced IL-1β, IL-6, and tumor necrosis factor (TNF)-α mRNA in the hippocampus with a peak effect at 6 h after SE. Immunoreactivity of the various cytokines was increased in glia. The increase of IL-1 Ra was delayed because the peak effect was observed at 24 h after SE. Moreover, IL-IRa was not produced in large excess, as during peripheral inflammation but in a molar ratio to IL-1β of 1:1. Intrahippocampal injection of IL-1β worsened seizure activity, whereas IL-1Ra was a powerful anticonvulsant in various models of limbic seizures. Transgenic mice overexpressing IL-1Ra in astrocytes were less sensitive to bicuculline-induced seizures. Conclusions: This study shows that limbic seizures in rodents rapidly and reversibly induce proinflammatory cytokines in glia and suggests that changes in the IL-IRa/IL-1β ratio in brain may represent an effective physiopathologic mechanism to control seizures.

Seizure reduction and quality of life improvements in people with epilepsy

Abstract: Summary: Purpose: Previous research suggests that seizure freedom may be necessary to improve health-related quality of life (HRQOL) for epilepsy surgery patients, but little is known regarding the seizure-frequency reduction needed to improve HRQOL among medically treated individuals. Methods: With data from 134 adults with refractory complex partial seizures participating in a randomized controlled antiepileptic drug (AED) trial, we compared the change in HRQOL across groups having different levels of change in seizure frequency: 100%, 75–99%, 50–74% reduction, and 0–50% increase or decrease. Changes over time within each seizure-reduction group also were assessed. HRQOL was measured by the QOLIE-31, QOLIE-89, and SF-36. Results: Subjects who became seizure free reported significantly more positive change than those who did not on the QOLIE-31 and QOLIE-89 overall scores, the QOLIE-89 mental health, physical health, and epilepsy-targeted composites, as well as the SF-36 mental health summary score. Changes over time in overall QOLIE-31 and QOLIE-89 scores were significantly more positive for subjects who achieved seizure freedom (i.e., 100% reduction in seizure frequency) than for those who did not. No significant change in QOLIE-31 and QOLIE-89 overall scores was observed for subjects who did not achieve seizure freedom. Conclusions: In this study, HRQOL improvement occurred primarily among patients who achieved complete seizure freedom. Many AED trials use a 50% seizure-frequency reduction criterion as a trial end point, but measurable impacts of this degree of reduction in seizure frequency on HRQOL in this sample were not observed. These results further support striving for seizure freedom as an epilepsy care goal.

Selective Blockade of N-Type Calcium Channels by Levetiracetam

Abstract: Purpose We investigated the effect of the new antiepileptic drug (AED) levetiracetam (LEV) on different types of high-voltage-activated (HVA) Ca2+ channels in freshly isolated CA1 hippocampal neurons of rats. Methods Patch-clamp recordings of HVA Ca2+ channel activity were obtained from isolated hippocampal CA1 neurons. LEV was applied by gravity flow from a pipette placed near the cell, and solution changes were made by electromicrovalves. Ca2+ channel blockers were used for separation of the channel subtypes. Results The currents were measured in controls and after application of 1-200 microM LEV. LEV irreversibly inhibited the HVA calcium current by approximately 18% on the average. With a prepulse stimulation protocol, which can eliminate direct inhibition of Ca2+ channels by G proteins, we found that G proteins were not involved in the pathways underlying the LEV inhibitory effect. This suggested that the inhibitory effect arises from a direct action of LEV on the channel molecule. The blocking mechanism of LEV was not related to changes in steady-state activation or inactivation of Ca2+ channels. LEV also did not influence the rundown of the HVA Ca2+ current during experimental protocols lasting approximately 10 min. Finally, LEV at the highest concentration used (200 microM) did not influence the activity of L-, P- or Q-type Ca2+ channels in CA1 neurons, while selectively influencing the activity of N-type calcium channels. The maximal effect on these channels separated from other channel types was approximately 37%. Conclusions Our results provide evidence that LEV selectively inhibits N-type Ca2+ channels of CA1 pyramidal hippocampal neurons. These data suggest the existence of a subtype of N-type channels sensitive to LEV, which might be involved in the molecular basis of its antiepileptic action.

Social functioning, psychological functioning, and quality of life in epilepsy.

Abstract: Summary: Purpose: Part of our research intended to explain “Quality of Life” (QoL) differences between people with epilepsy. To this end, a series of already existing generic and disease-specific health status measures were used. In this study, they were considered as determinants of people's QoL, whereas QoL itself was conceived as a general “value judgment” about one's life. Methods: From the records of four outpatient clinics, 210 persons with epilepsy were randomly selected. During their visit to the outpatient clinic, they completed a questionnaire assessing, among other things, health perceptions and social and psychological functioning. Additional information about their medical and psychosocial status was gathered from the patient files. Data were analysed by using a hierarchical regression analysis. Results: In decreasing order of importance, “psychological distress,”“loneliness,”“adjustment and coping,” and “stigma perception” appeared to contribute most significantly to the outcome QoL as judged by the patients themselves, regardless of their physical status. In the final model, none of the clinical variables (onset, seizure frequency, side effects of antiepileptic drugs) contributed significantly anymore to the patients' “quality-of-life judgement.” Apparently the effect of other variables such as seizure frequency and health perceptions, medication and side effects, life fulfilment, self-esteem, and mastery is mediated by these variables. Conclusions: Because all of the variance in QoL of the patients was explained by the psychosocial variables included in this study, health professionals should be aware of the significance of the psychosocial functioning of the patients and the role it plays in the achievement of a good QoL. Both informal and professional support may be an adjunct to conventional treatment. In future research, this issue should be given high priority.

Heart Rate Changes and ECG Abnormalities During Epileptic Seizures: Prevalence and Definition of an Objective Clinical Sign

Abstract: Summary: Purpose: To determine the prevalence of heart rate changes and ECG abnormalities during epileptic seizures and to determine the timing of heart rate changes compared to the first electrographic and clinical signs. To assess the risk factors for the occurrence of ECG abnormalities. Methods: We analyzed retrospectively 281 seizures in 81 patients with intractable epilepsy who had prolonged video-EEG and two-channel ECG. The nature and timing of heart rate changes compared to the electrographic and clinical seizure onset was determined. The ictal period (including one minute preictally and three minutes postictally) was analyzed for cardiac arrhythmias, conduction and repolarization abnormalities. Risk factors for cardiac abnormalities were investigated using parametric and non-parametric statistics. Results: There was an increase in heart rate of at least 10 beats/minute in 73% of seizures (93% of patients) and this occurred most often around seizure onset. In 23% of seizures (49% of patients) the rate increase preceded both the electrographic and the clinical onset. ECG abnormalities were found in 26% of seizures (44% of patients). One patient had an asystole for 30 seconds. Long seizure duration increased the occurrence of ECG abnormalities. No other risk factor was found. Conclusions: Heart rate changes occur frequently and occur around the time or even before the earliest electrographic or clinical change. The change can clarify the timing of seizure onset and the specific rate pattern may be useful for seizure diagnosis and for automatic seizure detection. ECG abnormalities occur often and repeatedly in several seizures of the same patient.

Memory Deficits after Resection from Left or Right Anterior Temporal Lobe in Humans: A Meta-Analytic Review

Abstract: Summary: Purpose: Memory deficits in epileptic patients have been found in some, but not all studies assessing the effects of side of seizures and resection from a temporal lobe on cognitive performance. The purpose of this study was to provide a quantitative review of previous studies on this issue. Methods: Based on conventional meta-analytic procedures, we identified 33 studies that assessed verbal and nonverbal memory performance before and after anterior temporal lobectomy. The Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale were used. These studies were then subjected to two levels of analyses: (a) vote-counting procedure, and (b) effect-size calculations and comparisons. Results: Overall, the data confirmed previous findings that verbal memory tasks are sensitive to left hemisphere dysfunction. The efficacy of a “nonverbal” task for tapping function in the nondominant (right) hemisphere was not confirmed, although a trend supporting this speculation was observed. With regard to the comparison of changes in verbal and nonverbal memory before and after resection from a temporal lobe, a clear trend was observed for decline in verbal memory function after resection from the left, especially significant for immediate verbal recall. A trend for contralateral improvement on nonverbal memory also was observed. The pattern of memory change after resection from the right temporal lobe was less clear. Conclusions: The findings of this study suggest that side of epileptic seizure and surgical resection from a temporal lobe affect verbal memory functions. The relations between the laterality of epileptic seizure, surgical resection from the temporal lobe, and nonverbal memory are to be verified by further research.

The neurodevelopmental impact of childhood-onset temporal lobe epilepsy on brain structure and function.

Abstract: Summary: Purpose: To characterize the neurodevelopmental correlates of childhood-onset temporal lobe epilepsy on brain structure and cognition compared with late-onset chronic temporal lobe epilepsy and healthy controls. Methods: Healthy controls (n 62) and patients with early (n 37) versus late (n 16) age at onset of temporal lobe epilepsy were compared with high-resolution quantitative magnetic resonance imaging (MRI) volumetrics and comprehensive neuropsychological assessment. Results: Patients with childhood-onset temporal lobe epilepsy (mean onset age, 7.8 years) exhibited widespread compromise in neuropsychological performance and substantial reduction in brain tissue volumes extending to extratemporal regions compared with healthy controls and late-onset temporal lobe epilepsy patients (mean onset age, 23.3 years). Most evident was reduced total white-matter volume among the childhood-onset patients. Reduction in brain tissue volume, especially total white-matter volume, was associated with significantly poorer cognitive status, attesting to the clinical significance of the volumetric abnormalities. Conclusions: Childhood-onset temporal lobe epilepsy appears to be associated with an adverse neurodevelopmental impact on brain structure and cognition that appears generalized in nature and especially evident in white-matter tissue volume. Key Words: Temporal lobe epilepsy—Cognition— MRI volumetrics—Neurodevelopment.

The global burden of epilepsy.

Abstract: Summary: We briefly describe the Global Burden of Diseases (GBD) study, its goals, and some of its outcomes as related to neurologic and psychiatric disorders. The summary measure of population health DALYs (Disability Adjusted Life Years) are described, as well as the implications for neuropsychiatric disorders of changing health indicators and the move from mortality toward disability indicators. The pressing need for new measures for health is answered by the new WHO Classification of Functioning Disability and Health, ICF, and a brief summary of its basic principles is provided. Although a better understanding of the physical, social, and economic burden of epilepsy has moved this disorder higher on the world's agenda, epilepsy still has problems to be recognized as a public health priority. The implications of a shift toward considering the disability of epilepsy, as outlined in the the WHO World Health Report 2001, are important. The burden of epilepsy is high and, for the year 2000, accounts for ∼0.5% of the whole burden of diseases in the world.

Modification of slow cortical potentials in patients with refractory epilepsy: a controlled outcome study.

Abstract: Summary: Purpose: To compare self-regulation of low-frequency EEG components (slow cortical potentials, SCPs) with other methods of seizure control for patients with drug-refractory partial epilepsy and to separate the real anticonvulsive effect from placebo effects. Methods: Results of a treatment program of SCP self-regulation (experimental group) are compared with two groups of patients, one of which learned self-control of respiratory parameters (end-tidal CO2 and respiration rate: RES group); the other received medication with new anticonvulsive drugs (AEDs) in combination with psychosocial counseling (MED group). Clinical, cognitive, behavioral, and personality measures were assessed before and after treatment. In addition, to control for placebo responses, patients repeatedly estimated their beliefs in the efficiency of the respective treatment, their satisfaction and expectations, and the quality of the relationship with their therapists. Results: SCP and MED groups showed a significant decrease of seizure frequency, but the RES group did not. Clear positive changes in the sociopsychological adjustment were obtained in all three groups, with the maximal improvement being attained in the RES group. Conclusions: All kinds of therapy result in considerable improvement of patients' emotional state, which may in part be due to potential placebo effects; however, this improvement is not related to the quality of the therapeutic effect proper (i.e., seizure reduction). Traditional double-blind control group designs are inappropriate for behavioral interventions or treatments with psychoactive pharmacologic drugs. Rather, specific tests can be developed to control the placebo effect and to separate it from the genuine therapeutic effects.

Does the Cause of Localisation‐Related Epilepsy Influence the Response to Antiepileptic Drug Treatment?

Abstract: Summary: Purpose: We investigated the response to antiepileptic drug (AED) therapy in patients with localisation-related epilepsy associated with different underlying causes. Methods: Five hundred and fifty adolescent and adult patients who had partial epilepsy treated with AEDs and who had undergone magnetic resonance imaging of brain were followed up prospectively from 1984 at a single centre. More than 70% were newly diagnosed. None had had epilepsy surgery. Results: Three hundred and twelve (57%) patients had been seizure free at their last clinic visit for at least a year. Patients with mesial temporal sclerosis (MTS; n = 73, 42% seizure free) were less likely to be controlled (p < 0.01) than were those with arteriovenous malformation (AVM; n = 14, 78%), cerebral infarction (n = 46, 67%), primary tumour (n = 35, 63%), cortical gliosis (n = 81, 57%), cerebral atrophy (n = 49, 55%), and cortical dysplasia (CD; n = 63, 54%). Among the seizure-free patients, those with MTS were more likely to require more than one AED compared with those with other aetiologies (48 vs. 35%; p < 0.05). There was no difference in outcome between patients with symptomatic and cryptogenic epilepsy (n = 361, 58% vs. n = 189, 56% seizure free, respectively). Patients with MTS, CD, and cryptogenic epilepsy were more likely (p = 0.02) to have a family history of epilepsy than were the other groups. MTS patients also had a higher incidence of febrile convulsions (p < 0.001). Conclusions: The majority of patients with focal-onset epilepsy became seizure free on AED treatment. MTS-related seizures had the worst prognosis. Although many patients with this pathology may benefit from epilepsy surgery, a considerable number will be controlled with AED therapy.

Seizures after Spontaneous Supratentorial Intracerebral Hemorrhage

Abstract: Summary: Purpose: To characterize seizures after intracerebral hemorrhage (ICH), evaluating the risk of occurrence and relapse, predisposing factors, and prognostic significance, and to assess the utility of antiepileptic drug (AED) therapy as used in clinical practice. Methods: The study sample consisted of 761 patients with spontaneous, nonaneurysmal, supratentorial ICH. Seizures were classified as immediate (within 24 h of ICH) and early (within 30 days of ICH). Baseline variables and clinical events were compared in the seizure and nonseizure group by using a multivariate regression model of failure time data. Results: Fifty-seven patients had one or more seizures. The 30-day actuarial risk of a post-ICH seizure was 8.1%. Lobar location and small volume of ICH were independent predictors of immediate seizures. Early seizures were associated with lobar location and neurologic complications, mainly rebleeding. In patients with lobar ICH, the risk of early seizures was reduced by prophylactic AED therapy. Among seizure patients, history of alcohol abuse increased the risk of status epilepticus. Immediate and early seizures were not independent predictors of in-hospital mortality. Conclusions: Patients with ICH are exposed to a substantial risk of seizures; however, short-term mortality was not affected, and the risk of epilepsy was lower than previously thought. The likelihood of immediate seizures is influenced by factors that are inherent characteristics of ICH, whereas the chance of developing early seizures is influenced not only by certain characteristics of ICH, but also by unpredictable events. A brief period of therapy soon after ICH onset may reduce the risk of early seizures in patients with lobar hemorrhage. Key Words: Intracerebral hemorrhage—Stroke—Seizures—Status epilepticus—Epilepsy. Seizures as a clinical feature of intracerebral hemorrhage (ICH) have not been fully investigated. Little is known about the frequency, temporal distribution, and characteristics of seizures, and even less about factors predisposing to seizures and their prognostic significance for short-term mortality and risk of epilepsy. Major aspects have often been ignored, including the fact that delayed post-ICH seizures may have different predisposing factors from onset seizures, that the number of patients at risk for seizure varies in time, and that many predisposing factors may act synergistically in time to cause seizures. In this study the occurrence of seizures in patients with computed tomography (CT)-proven supratentorial nontraumatic nonaneurysmal ICH was analyzed by using multivariate analyses to determine the risk of developing initial and recurrent seizures, to identify predisposing factors for onset and delayed seizures, to evaluate the impact of seizures on outcome, and to assess the value of prophylactic antiepileptic drug (AED) therapy as used in clinical practice.

Vagus Nerve Stimulation in Children with Refractory Seizures Associated with Lennox–Gastaut Syndrome

Abstract: Summary: Purpose: Vagus nerve stimulation (VNS) is approved for use for refractory partial seizures. Nevertheless, information regarding VNS therapy for special populations, including Lennox–Gastaut syndrome (LGS) is limited. We discuss the effectiveness, tolerability, and safety of VNS therapy in patients with LGS. Methods: A six-center, retrospective study evaluated the effectiveness of VNS therapy in patients with LGS at 3 and 6 months and compared preimplant and postimplant seizure frequency. Adverse effects and quality of life (QOL) were included as secondary measures. Results: Fifty patients, median age 13 years, with medically refractory epilepsy, were implanted. Median age at onset of seizures was 1.4 years, and a median of nine anticonvulsants (AEDs) had been tried before implantation. Data-collection forms were designed for retrospectively gathering data on each patient's preimplant history, seizures, implants, device settings, QOL, and adverse events. Median reductions in total seizures were 42% at 1 month, 58.2% at 3 months, and 57.9% at 6 months. The most common adverse events reported were voice alteration and coughing during stimulation. Other uncommon adverse events included increased drooling and behavioral changes. Investigators noted that QOL had improved for some patients in the study. Conclusions: VNS is an effective treatment for medically refractory epilepsy in LGS. This treatment is well tolerated, safe, and may improve QOL.

Focal cortical dysplasia of Taylor's balloon cell type: a clinicopathological entity with characteristic neuroimaging and histopathological features, and favorable postsurgical outcome.

Abstract: Summary:Background and Purpose: Focal cortical dysplasia of Taylor's balloon-cell type (FCD-BC) are a frequent cause of pharmacoresistant epilepsy in young patients. In order to characterize FCD-BC, we coupled MRI and histopathology, and analyzed the clinical outcome following epilepsy surgery. Methods: From an epilepsy data bank with 547 histological specimens, 17 FCD-BC were re-evaluated of which high resolution MRI was available. Five additional FCD-BC were prospectively identified by MRI. Histopathological and immunohistochemical features were related to MRI. Outcome following lesionectomy was analyzed as determined on routine examinations 3, 6 and 12 months following surgery. Results: All but one lesion were located outside the temporal lobe. A markedly hyperintense funnel-shaped subcortical zone tapering towards the lateral ventricle was the characteristic finding on FLAIR MRI. Histopathologically, the subcortical zone of the FCD-BC displayed hypomyelinated white matter with radially oriented balloon cells and gliosis. Dysplastic neurons were found in the adjacent, disorganized cortex. All patients with complete lesionectomy were seizure free one year following surgery. Conclusion: Focal cortical dysplasias of Taylor's balloon-cell type (FCD-BC) have characteristic MRI and histopathological findings. MRI recognition is important, since outcome following resective surgery is favorable.

Outcome of Severe Refractory Status Epilepticus in Children

Abstract: Summary: Purpose: Refractory status epilepticus (RSE) is the persistence of seizure activity despite appropriate therapy; it is treated with high-dose suppressive anesthetic agents. We report here the outcome of RSE in a large series of children. Methods: We retrospectively reviewed cases of RSE treated at Children's Hospital, Boston, between 1992 and 2000. Factors evaluated included age, history of seizures or neurologic impairment, etiology, outcome, including mortality or return to baseline, and initial EEG findings. Results: Twenty-two patients ages 4.5 months to 18 years were admitted to the intensive care unit for RSE. All were treated with high-dose suppressive therapy consisting of pentobarbital, midazolam, propofol infusion, or high-dose phenobarbital, either alone, or in combination, for ≤146 days. The overall mortality was seven of 22. Mortality was related to etiology, age, and EEG findings. No death occurred in the remote symptomatic group, and three of four younger than 3 years died, whereas only four of 18 older than 3 years died. The mortality rate among patients with focal abnormalities on the EEG was lower than that among those with multifocal or generalized abnormalities. None of the children with normal premorbid neurologic status returned to baseline. Conclusions: Our data demonstrate a high mortality and morbidity for childhood RSE. Mortality is related to etiology and is higher in younger children and with multifocal or generalized abnormalities on the initial EEG.

Memory lateralization in medial temporal lobe epilepsy assessed by functional MRI.

Abstract: Summary: Purpose: To determine the utility of functional magnetic resonance imaging (fMRI) in preoperative lateralization of memory function in patients with medial temporal lobe epilepsy (MTLE). Methods: Nine patients with MTLE underwent standard preoperative assessment including video-EEG and intracarotid amytal testing (IAT). fMRI was performed while subjects encoded four types of stimuli (patterns, faces, scenes, and words). Activation maps were created for each subject representing areas more active for novel than for repeated stimuli. Regions of interest were drawn around the MTL in individual subjects, suprathreshold voxels were counted, and an asymmetry index was calculated. Results: In eight of nine subjects, lateralization of memory encoding by fMRI was concordant with that obtained from the IAT. Group-level analysis demonstrated greater activation in the MTL contralateral to the seizure focus such that in the left MTLE group, verbal encoding engaged the right MTL, whereas in the right MTLE group, nonverbal encoding engaged the left MTL. Conclusions: fMRI is a valid tool for assessing of memory lateralization in patients with MTLE and may therefore allow noninvasive preoperative evaluation of memory lateralization. FMRI revealed that memory encoding may be reorganized to the contralateral MTL in patients with MTLE. Key Words: Epilepsy—Medial temporal lobe—fMRI—Memory. Epilepsy surgery is an important tool for the treatment of patients with medically refractory seizures and is particularly effective in patients with medial temporal lobe epilepsy (MTLE). These patients have frequent complex partial seizures originating from a sclerosed hippocampus. In well-selected patients, temporal lobectomy with resection of the mesial structures can significantly reduce or eliminate seizures in up to 90% of patients (1–3). The challenge in epilepsy surgery is to remove the seizure focus completely without causing significant postoperative neurologic deficits; this requires an understanding of the underlying functional anatomy. Patients with longstanding epilepsy may have variable anatomic localization of neurologic functions, such as memory, because of cerebral reorganization induced by the disease process. Understanding this functional anatomy is vital when planning surgical resections and relies on complex preoperative evaluations.

Epileptic syndromes in childhood: clinical features, outcomes, and treatment.

Abstract: We reviewed the clinical features, outcome, and treatment of many of the epileptic syndromes that begin in the childhood from 2 to 12 years of age, using a review of the literature and personal experience, with most references to authoritative texts. The developmental tasks of childhood are centered on refinement of motor skills and development of complex intellectual and social skills. The childhood onset epilepsies can be divided into benign, intermediate, and catastrophic based on their impact on childhood development. The clearest benign epilepsy is benign rolandic epilepsy, which often does not require medication treatment. The definition of benign occipital epilepsy is still often vague. In the intermediate category, childhood absence epilepsy often has associated learning disorders and a poor social outcome. About 50% of children with cryptogenic partial seizures have a very benign course, even though their epilepsy syndrome is not well defined. Generalized epilepsy with febrile seizures plus (GEFS+) has a dominant inheritance with a defined defect in cerebral sodium channels, but varies considerably in severity within affected members of the same kindred. The catastrophic epilepsies in childhood all have an inconsistent response to AED treatment and include continuous spike-wave in slow sleep (with variable severity), Landau-Kleffner syndrome (with a confusing overlap with autistic regression), the Lennox Gastaut syndrome (with broad defining features), and myoclonic-astatic epilepsy (with important overlaps with Lennox-Gastaut). Many of the epilepsies that begin in childhood are benign. Others interfere seriously with cognitive and social development.

Glutamate-glutamine Cycling in the Epileptic Human Hippocampus

Abstract: Summary: Purpose: Several findings suggest that energy metabolism and the glutamate–glutamine cycle may be impaired in epilepsy. Positron emission tomography often shows interictal hypometabolism of the epileptogenic hippocampus. In vivo microdialysis studies show that seizure-associated glutamate release is doubled, and clearance is slowed. We hypothesized that the glutamate–glutamine cycle between neurons and glia may be decreased in the epileptic human hippocampus. Methods: A 20% solution of 2-13C-glucose was infused before resection of the epileptogenic hippocampus. Blood glucose isotopic fractions were measured every 30 min. Blood and brain specimens were frozen quickly; perchloric acid extracts of the small metabolites were prepared and analyzed by proton and carbon magnetic resonance spectroscopy (MRS) at 11.75 Tesla. Results: Standard histology showed 12 with hippocampal sclerosis and five with minimal neuron loss. The relative rates of glutamate–glutamine cycling with respect to glutamate synthesis were decreased in biopsies affected by hippocampal sclerosis (mean, 0.08; 95% confidence interval, 0.04–0.12) compared with those with minimal neuron loss (0.52; 95% CI, 0.30–0.75). Mean cellular glutamate concentrations were higher in minimal neuron loss (8.9 mM; 95% CI, 7.4–10.4) than hippocampal sclerosis (7.3 mM; 95% CI, 5.9–8.7). Cellular glutamine concentrations (mean, 2.8 mM; 95% CI, 2.4–3.2; n = 17) were the same in all groups. Conclusions: The epileptogenic, gliotic human hippocampus appears to be characterized metabolically by slow rates of glutamate–glutamine cycling, decreased glutamine content, and a relative increase in glutamate content. We hypothesize that the low rate of glutamate–glutamine cycling that results from a failure of glial glutamate detoxification could account for slow glutamate clearance from synapses and continuing low-grade excitotoxicity.

The Efficacy of an Educational Treatment Program for Patients with Epilepsy (MOSES): Results of a Controlled, Randomized Study

Abstract: Summary: Purpose: To evaluate the efficacy of the educational program MOSES (Modular Service Package Epilepsy). It was developed to improve patients' knowledge and understanding about their epilepsy, its treatment, and psychosocial consequences. The program intends to improve patients' coping with the disease, to strengthen self-esteem, and to support patients to become experts in managing their epilepsy. Methods: A controlled, randomized study design was used to examine the efficacy of MOSES. Patients from 22 epilepsy centers in Germany, Austria, and Switzerland were randomly allocated to either MOSES group (treatment group) or waiting-list group (control group). The 242 patients were aged from 16 to 80 years. The MOSES group (n = 113) completed the questionnaires immediately before the educational course (T1) and 6 months later (T2), and the control group (n = 129), 6 months before (T1) and immediately before (T2) the course. The questionnaires included generic instruments (SF-36, Rosenberg self-esteem Scale, von Zerssen Depression Scale), and epilepsy-specific scales (Restrictions in Daily Life, Epilepsy-Related Fears, Coping with Epilepsy and Adaptation). Depression was used as a moderator variable. Seizure frequency and satisfaction with therapy also were assessed. Multivariate analysis of variance (MANOVA) with repeated measurements and univariate analyses of variance were performed. Results: The MANOVA showed that participants of the educational program improved significantly. Univariate analyses revealed improvements in knowledge (p < 0.001) and coping with epilepsy (p = 0.004), whereas important effects of MOSES on other epilepsy-specific measures and on generic questionnaires (SF-36, self-esteem) were not found. Participants of the MOSES program also improved in seizure outcome (p = 0.041) and became more satisfied with the therapy [better tolerability of antiepileptic drug (AED) therapy, fewer side effects; p = 0.014]. In addition, participants expressed being highly satisfied with the program. Conclusions: The study clearly indicates the need for patient education. Even patients with a long history of epilepsy and with additional handicaps or diseases benefitted from the MOSES program.

Propofol and Midazolam in the Treatment of Refractory Status Epilepticus

Abstract: Summary: Purpose: To explore outcome differences between propofol and midazolam (MDL) therapy for refractory status epilepticus (RSE). Methods: Retrospective chart review of consecutive patients treated for RSE between 1995 and 1999. Results: We found 14 patients treated primarily with propofol and six with MDL. Propofol and MDL therapy achieved 64 and 67% complete clinical seizure suppression, and 78 and 67% electrographic seizure suppression, respectively. Overall mortality, although not statistically significant, was higher with propofol (57%) than with MDL (17%) (p = 0.16). Subgroup mortality data in propofol and MDL patients based on APACHE II (Acute Physiology and Chronic Health Evaluation) score did not show statistically significant differences except for propofol-treated patients with APACHE II score ≥20, who had a higher mortality (p = 0.05). Reclassifying the one patient treated with both agents to the MDL group eliminated this statistically significant difference (p = 0.22). Conclusions: In our small sample of RSE patients, propofol and MDL did not differ in clinical and electrographic seizure control. Seizure control and overall survival rates, with the goal of electrographic seizure elimination or burst suppression rather than latter alone, were similar to previous reports. In RSE patients with APACHE II score ≥20, survival with MDL may be better than with propofol. A large multicenter, prospective, randomized comparison is needed to clarify these data. If comparable efficacy of these agents in seizure control is borne out, tolerance with regard to hemodynamic compromise, complications, and mortality may dictate the choice of RSE agents.

Caloric restriction inhibits seizure susceptibility in epileptic EL mice by reducing blood glucose.

Abstract: Summary: Purpose: Caloric restriction (CR) involves underfeeding and has long been recognized as a dietary therapy that improves health and increases longevity. In contrast to severe fasting or starvation, CR reduces total food intake without causing nutritional deficiencies. Although fasting has been recognized as an effective antiseizure therapy since the time of the ancient Greeks, the mechanism by which fasting inhibits seizures remains obscure. The influence of CR on seizure susceptibility was investigated at both juvenile (30 days) and adult (70 days) ages in the EL mouse, a genetic model of multifactorial idiopathic epilepsy. Methods: The juvenile EL mice were separated into two groups and fed standard lab chow either ad libitum (control, n = 18) or with a 15% CR diet (treated, n = 17). The adult EL mice were separated into three groups; control (n = 15), 15% CR (n = 6), and 30% CR (n = 3). Body weights, seizure susceptibility, and the levels of blood glucose and ketones (β-hydroxybutyrate) were measured over a 10-week treatment period. Simple linear regression and multiple logistic regression were used to analyze the relations among seizures, glucose, and ketones. Results: CR delayed the onset and reduced the incidence of seizures at both juvenile and adult ages and was devoid of adverse side effects. Furthermore, mild CR (15%) had a greater antiepileptogenic effect than the well-established high-fat ketogenic diet in the juvenile mice. The CR-induced changes in blood glucose levels were predictive of both blood ketone levels and seizure susceptibility. Conclusions: We propose that CR may reduce seizure susceptibility in EL mice by reducing brain glycolytic energy. Our preclinical findings suggest that CR may be an effective antiseizure dietary therapy for human seizure disorders.

Risk factors for suicide in epilepsy: a case control study.

Abstract: PURPOSE: Suicide is considered to be one of the most important causes of death contributing to the increased mortality of persons with epilepsy. We investigated the association between the risk of suicide in persons with epilepsy and clinical factors that might increase or have been suggested to increase the risk of suicide. METHODS: A case-control study was nested within a cohort of 6,880 patients registered in the Stockholm County In-Patient Register with a diagnosis of epilepsy. The study population was followed up through the National Cause of Death Register. Twenty-six cases of suicide, 23 cases of suspected but not proven suicide, and 171 controls, living epilepsy patients, were selected from the cohort. Clinical data were collected through medical record review. RESULTS: There was a ninefold increase in risk of suicide with mental illness and a 10-fold increase in relative risk (RR) with the use of antipsychotic drugs. The estimated RR of suicide was 16.0 [95% confidence interval (CI), 4.4-58.3] for onset of epilepsy at younger than 18 years, compared with onset after 29 years. The risk of suicide seemed to increase with high seizure frequency and antiepileptic drug (AED) polytherapy, although the estimates were imprecise and the associations not statistically significant. Insufficient data on seizure frequency and changes in AED dosage due to incomplete case records were associated with high RRs. We found no association between risk of suicide and any particular AED, with type of epilepsy, or localization or lateralization of epileptogenic focus on EEG [RR = 0.3 (95% CI, 0.1-1.7)]. CONCLUSIONS: The profile of the epilepsy patient who commits suicide that emerges from our study is a patient with early onset (particularly onset during adolescence) but not necessarily severe epilepsy, psychiatric illness, and perhaps inadequate neurologic follow-up. Previous reports of an association with temporal lobe epilepsy could not be confirmed. Language: en

The psychosocial burden of epilepsy.

Abstract: Epilepsy is a disorder associated with significant psychological and social consequences for everyday living (1). People with the condition report a significant impact of epilepsy and its management in terms of family dysfunction, reduced social and leisure opportunities, and increased levels of anxiety and depression and poor selfesteem compared with people without the condition (2). A central feature of the condition is its stigmatising nature (3). A number of studies have reported that the quality of life of people with epilepsy can be severely compromised by statutory conditions on driving and employment and by limitations in insurance provision, causing problems for well-being and independent living (4). Recent studies have, however, shown that people with wellcontrolled seizures are less likely to report psychosocial problems, and people in seizure remission (>2 years seizure free) report a quality of life not significantly different from those without the condition (5). Most of the evidence for the psychosocial problems associated with epilepsy has been drawn from studies in developed countries; in comparison, relatively little is known about the situation of people with epilepsy in developing countries. This is partly explained by the lack of resources available to conduct such research. A number of small studies have shown that attitudes toward and beliefs about epilepsy are largely pejorative, explained to some degree by the notion that the condition is infectious or the outcome of possession by evil spirits. Opportunities for marriage and employment are likely to be substantially worse for people with epilepsy in the developing world than for their developed world counterparts. The unpredictability of the nature and course of epilepsy is a key factor in the psychosocial handicaps it engenders for people in whom it develops. For centuries and across countries, epilepsy has been a condition with extremely negative connotations, and even now, the label of epilepsy is often rejected by those with the condition. I draw evidence from published research to highlight what is known about the psychosocial consequences of this condition and the contribution physical, social, and psychological variables make to its impact on the quality of life of those affected in both developed and developing countries.

Temporal lobe epilepsy surgery: outcome, complications, and late mortality rate in 215 patients.

Abstract: Summary: Purpose: We studied the surgical outcome, complications, and the late mortality rate in a large group of patients with medically refractory temporal lobe epilepsy (TLE). Methods: Two-hundred fifteen patients with TLE were treated surgically between 1984 and 1999 after a comprehensive presurgical evaluation. Patients were followed up at 6 weeks, 3–6 months, and yearly thereafter. In addition, questionnaires were sent on the anniversary of their surgery. Surgical outcome (Engel's classification), complication rate, and factors contributing to late mortality were analyzed. Standardized mortality ratios (SMRs) were calculated. Results: There was no surgical mortality. Two (0.9%) had mild hemiparesis, one (0.4%) had a hemianopia, seven (3.2%) had transient cranial nerve palsies, and eight (3.7%) had transient postoperative language difficulties. One hundred forty-eight (69%) became seizure free, 43 (20%) had rare seizures, 14 (6.5%) had worthwhile seizure reduction, and 10 (4.6%) had no improvement (follow-up, 1–15 years). Three (2%) of 148 seizure-free patients died during follow-up, compared with eight (11.9%) of 67 not seizure-free patients. The mean duration of epilepsy before surgery for the surviving patients was 17.8 years, and for those patients who died, 25.9 years (p < 0.05). Six (5.7%) of 104 patients with right-sided resections died during follow-up, compared with five (4.5%) of 111 with left-sided resections. Conclusions: Eighty-nine percent of patients became seizure free or had rare seizures, with low morbidity, and no surgical mortality. The late mortality occurred predominantly in patients with persistent seizures (SMR, 7.4). Those patients who died had a longer duration of epilepsy before surgery. In contrast, among those patients who became seizure free, the mortality rate was much lower, and similar to the general population of Indiana (SMR, 1.7).

Magnetic resonance imaging in the study of the lithium-pilocarpine model of temporal lobe epilepsy in adult rats

Abstract: Summary: Purpose: In temporal lobe epilepsy, it remains to be clarified whether hippocampal sclerosis is the cause or the consequence of epilepsy. We studied the temporal evolution of the lesions in the lithium–pilocarpine model of epilepsy in the rat with magnetic resonance imaging (MRI) to determine the progressive morphologic changes occurring before the appearance of chronic epilepsy. Methods: MRI was performed on an MR scanner operating at 4.7 T. We followed the evolution of lesions using T2- and T1-weighted sequences before and after the injection of gadolinium from 2 h to 9 weeks. Results: At 2 h after status epilepticus (SE), a blood–brain barrier breakdown could be observed only in the thalamus; it had disappeared by 6 h. At 24 h after SE, edema was present in the amygdala and the piriform and entorhinal cortices together with extensive neuronal loss; it disappeared progressively over a 5-day period. During the chronic phase, a cortical signal reappeared in all animals; this signal corresponded to gliosis, which appeared on glial fibrillary acidic protein (GFAP) immunohistochemically stained sections as hypertrophic astrocytes with thickened processes. In the hippocampus, the correlation between histopathology and T2-weighted signal underscored the progressive constitution of atrophy and sclerosis, starting 2 days after SE. Conclusions: These data show the reactivity of the cortex that characterizes the initial step leading to the development of epilepsy and the late gliosis that could result from the spontaneous seizures. Moreover, it appears that hippocampal sclerosis progressively worsened and could be both the cause and the consequence of epileptic activity.