Showing papers in "Epilepsia in 1995"
TL;DR: Reliability and validity of an instrument to measure health‐related quality of life (HRQOL) in epilepsy showed that the epilepsy‐targeted factor and three of its four component scales were more sensitive to categorization of patients by severity of seizure frequency and type than scales tapping physical health, mental health, or cognitive function.
Abstract: We developed an instrument to measure health-related quality of life (HRQOL) in epilepsy. A 99-item inventory was constructed from the RAND 36-Item Health Survey (generic core), with 9 additional generic items, 48 epilepsy-targeted items, and 6 other items concerning attitudes toward epilepsy and self-esteem. We administered the 99-item inventory to 304 adults with epilepsy at 25 epilepsy centers. Patients and patient-designated proxies completed the inventory and were retested 1-91 days later. A multitrait scaling analysis of these data led to retention of 86 items distributed in 17 multiitem scales (Cronbach's alpha ranged from 0.78 to 0.92). Factor analysis of the 17 multiitem scales yielded four underlying dimensions of health: an epilepsy-targeted dimension, a cognitive factor, mental health, and physical health. Construct validity was supported by significant patient-proxy correlations for all scales and correlations between neuropsychologic tests and self-reported emotional and cognitive function (all p values < 0.05). There were significant negative correlations between the four factor scores derived from the HRQOL scales and neurotoxicity, systemic toxicity, and health care utilization (except for the correlation between mental health factor and health care utilization; all p values < 0.05). Patients who were seizure-free in the preceding year reported better HRQOL for the overall score, three of the four factor scores, and 8 of the 17 scale scores than did patients with a high frequency of seizures. Relative validity analysis showed that the epilepsy-targeted factor and three of its four component scales were more sensitive to categorization of patients by severity of seizure frequency and type than scales tapping physical health, mental health, or cognitive function. These cross-sectional data support the reliability and validity of this measure of HRQOL in epilepsy. The addition of an epilepsy-targeted supplement to the generic core improved the sensitivity to severity of epilepsy. The 86 items included in the field testing were supplemented by three additional items to form the Quality of Life in Epilepsy (QOLIE-89) inventory.
584 citations
TL;DR: MDR1 expression is increased in brain of some patients with medically intractable epilepsy, suggesting that the patients’ lack of response to medication may be caused by inadequate accumulation of AED in brain.
Abstract: Why some patients with seizures are successfully treated with antiepileptic drugs (AEDs) and others prove medically intractable is not known. Inadequate intraparenchymal drug concentration is a possible mechanism of resistance to AEDs. The multiple drug resistance gene (MDR1) encodes P-glycoprotein, an energy-dependent efflux pump that exports planar hydrophobic molecules from the cell. If P-glycoprotein is expressed in brain of some patients with intractable epilepsy and AEDs are exported by P-glycoprotein, lower intraparenchymal drug concentrations could contribute to lack of drug response in such patients. Eleven of 19 brain specimens removed from patients during operation for intractable epilepsy had MDR1 mRNA levels > 10 times greater than those in normal brain, as determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Immunohistochemistry for P-glycoprotein from 14 of the patients showed increased staining in capillary endothelium in samples from epileptic patients as compared with staining in normal brain samples. In epileptic brain specimens with high MDR1 mRNA levels, expression of P-glycoprotein in astrocytes also was identified. Last, steady-state intracellular phenytoin (PHT) concentrations in MDR1 expressing neuroectodermal cells was one fourth that in MDR1-negative cells. MDR1 expression is increased in brain of some patients with medically intractable epilepsy, suggesting that the patients' lack of response to medication may be caused by inadequate accumulation of AED in brain.
523 citations
TL;DR: The incidence of seizures due to acute CNS insults for residents of Rochester, Minnesota, U.S.A., from 1935 though 1984 was 39.0/100,000 person‐years (United States 1970 population as standard).
Abstract: We determined the incidence of seizures due to acute CNS insults for residents of Rochester, Minnesota, U.S.A., from 1935 through 1984. The age-adjusted incidence rates for 1955-1984, the period of most complete case ascertainment, was 39.0/100,000 person-years (United States 1970 population as standard). The age-adjusted incidence was considerably higher in men: 52.0 as compared with 29.5 in women. The 3.6% risk of experiencing an acute symptomatic seizure in an 80-year lifespan approaches that of developing epilepsy. The major causes of acute symptomatic seizures were traumatic brain injury, cerebrovascular disease, drug withdrawal, and CNS infections. Each type of acute symptomatic seizure has age, gender, and time period patterns that reflect the occurrence of the underlying cause.
304 citations
TL;DR: All 14 sudden deaths occurred when the pupils were not under the close supervision of the school and most were unwitnessed, which has implications for prevention.
Abstract: Sudden death, often seizure related, may occur in patients with epilepsy. Population-based incidence is probably on the order of 1:1,000/year. The incidence is much higher in selected groups, however. We wished to establish the incidence of sudden unexpected death (SUD) in a young cohort with severe epilepsy and learning difficulties. The study cohort included 310 pupils with epilepsy enrolled at a special residential school between April 1970 and April 1993. The follow-up period totaling 4,135 person-years included a period of residence at the school as well as time after leaving. Age and sex standardized overall mortality ratio was 15.9 [95% confidence interval (CI) 10.6-23.0], with 20 of 28 deaths considered epilepsy related. An incidence of sudden death cases of 1:295/year was noted. All 14 sudden deaths occurred when the pupils were not under the close supervision of the school and most were unwitnessed, which has implications for prevention.
289 citations
TL;DR: The overall biochemical and anticonvulsant profile of TGB suggests potential utility in the treatment of chronic seizure disorders such as generalized clonic‐tonic epilepsy, photomyoclonic seizures, myoclonic petit mal epilepsy, and complex partial epilepsy.
Abstract: We review the neurochemical and behavioral profile of the selective gamma-aminobutyric acid (GABA) uptake inhibitor, (R)-N-(4,4-di-(3-methylthien-2-yl)but-3-enyl) nipecotic acid hydrochloride [tiagabine (TGB), previously termed NNC 05-0328, NO 05-0328, and NO-328], which is currently in phase III clinical trials for epilepsy. TGB is a potent, and specific GABA uptake inhibitor. TGB lacks significant affinity for other neurotransmitter receptor binding sites and/or uptake sites. In electrophysiological experiments in hippocampal slices in culture, TGB prolonged the inhibitory postsynaptic potentials (IPSP) and inhibitory postsynaptic currents (IPSC) in the CA1 and CA3 produced by the addition of exogenous GABA. In vivo microdialysis shows that TGB also increases extracellular GABA overflow in a dose-dependent manner. Together these biochemical data suggest that the in vitro and in vivo mechanism of action of TGB is to inhibit GABA uptake specifically, resulting in an increase in GABAergic mediated inhibition in the brain. TGB is a potent anticonvulsant agent against methyl-6,7-dimethyoxy-4-ethyl-B-carboline-3-carboxylate (DMCM)-induced clonic convulsions (mice), subcutaneous pentylenetetrazol (PTZ)-induced tonic convulsions (mice and rats), sound-induced convulsions in DBA/2 mice and genetically epilepsy-prone rats (GEPR), and electrically induced convulsions in kindled rats. TGB is partially efficacious, against subcutaneous PTZ-induced clonic convulsions, and photically induced myoclonus in Papio papio. TGB is weakly efficacious in the intravenous PTZ seizure threshold test and the maximal electroshock seizure (MES) test and produces only partial protection against bicuculline (BIC)-induced convulsions in rats. The overall biochemical and anticonvulsant profile of TGB suggests potential utility in the treatment of chronic seizure disorders such as generalized clonic-tonic epilepsy (GTCS), photomyoclonic seizures, myoclonic petit mal epilepsy, and complex partial epilepsy.
249 citations
TL;DR: Fourteen infants of both sexes had a previously unreported epileptic condition characterized by nearly continuous multifocal seizures, and extensive investigation failed to determine an etiology, and there was no familial recurrence.
Abstract: Fourteen infants of both sexes had a previously unreported epileptic condition characterized by nearly continuous multifocal seizures. The first seizures occurred at a mean age of 3 months, without antecedent risk factors. At 1 to 10 months, the seizures became very frequent. They were partial with variable clinical expression, and the EEG showed that the discharges randomly involved multiple independent sites, moving from one cortical area to another in consecutive seizures. Although their topography varied, the EEG ictal pattern of each seizure was very similar. It consisted of rhythmic alpha or theta activity which spread to involve an increasing area of the cortical surface. Patients regressed developmentally and became quadriplegic with severe axial hypotonia. Three patients died at age 7 months and at age 7 and 8 years, respectively. Seizures were controlled in only 2 patients, and only 3 children resumed psychomotor development. Extensive investigation failed to determine an etiology, and there was no familial recurrence. Neuropathological examination of the brain in two cases showed only severe hippocampal neuronal loss and accompanying gliosis.
244 citations
TL;DR: The data suggest that granule cell bursting activity is at least in part a function of compromised synaptic inhibition, since levels of γ‐aminobutyric acid (GABA) blockade that are generally subthreshold for burst induction were epileptogenic in some tissue samples from human epileptic hippocampus.
Abstract: Morphological and electrophysiological techniques were used to examine granule cells and their mossy fiber axons in nine surgically resected hippocampal specimens from temporal lobe epilepsy (TLE) patients. Timm histochemistry showed mossy fiber sprouting into the inner molecular layer (IML) of the dentate in a subset of tissue samples. In slices from five tissue samples, stimulus-induced bursting activity could be induced with a low concentration (2.5 microM) of bicuculline; bursts were sensitive to the N-methyl-D-aspartate (NMDA) blocker, APV. There was a general correlation between such sprouting and experimentally induced hyperexcitability. Fourteen granule cells from five tissue samples were intracellularly stained [with lucifer yellow (LY) or neurobiotin]. Axons from a subset of these neurons showed axon collaterals reaching into the IML, but this axon projection pattern for single cells was not directly correlated with degree of mossy fiber sprouting shown grossly by Timm staining. Electron microscopic examination of intracellularly stained elements showed mossy fiber axon terminals making asymmetric synaptic contacts (including autapses on the granule cell dendrite) with dendritic shafts and spines in both apical and basal domains. These data are consistent with the hypothesis that mossy fiber sprouting provides a structural basis for recurrent excitation of granule cells, but does not provide direct support of the hypothesis that mossy fiber sprouting causes hyperexcitability. The data suggest that granule cell bursting activity is at least in part a function of compromised synaptic inhibition, since levels of gamma-aminobutyric acid (GABA) blockade that are generally subthreshold for burst induction were epileptogenic in some tissue samples from human epileptic hippocampus.
236 citations
TL;DR: Ketamine is remarkably neuroprotective when administered after onset of SE, whether or not seizure discharges are eliminated.
Abstract: We investigated the neuroprotective effect of the noncompetitive N-methyl-D-asparatate (NMDA) antagonist ketamine when administered after onset of lithium-pilocarpine-induced status epilepticus (SE). Seizures were induced in Wistar rats with lithium chloride (3 mEq/kg) and pilocarpine (PC) (30-60 mg/kg intraperitoneally, i.p.). Fifteen minutes after SE onset, either ketamine 100 mg/kg or normal saline was injected i.p., and 3 h after SE onset atropine, diazepam (DZP), and phenobarbital (PB) were administered i.p. to terminate the seizures. Twenty-four hours later, rats underwent brain perfusion-fixation, with subsequent brain processing for light-microscopic examination. Rats adminstered saline (n = 5) had neuronal damage in 24 of 25 brain regions examined. Rats administered ketamine (n = 7) had significant neuroprotection in 22 of 24 damaged regions. Ketamine reduced the amplitude of seizure discharges, and in 3 rats EEG seizure activity ceased in 30 min; none of these rats had neuronal damage. In the other 4 rats, EEG seizure discharges persisted > 90 min; in these animals, 21 of 24 damaged regions were protected. In contrast, rats with 1-h high-dose PC-induced SE (400 mg/kg i.p. without lithium chloride preadministration) had 14 damaged regions, of which 7 were significantly different from the undamaged regions of the ketamine subgroup with persistent electrographic seizures. Thus, ketamine is remarkably neuroprotective when administered after onset of SE, whether or not seizure discharges are eliminated.
216 citations
TL;DR: A matched casecontrol study to identify risk factors for first febrile seizures, with special emphasis on characteristics of the acute illness episode, found that Gastroenteritis as the underlying illness had a significant inverse (i.e., protective) association with febRIle seizures.
Abstract: Summary We conducted a matched casecontrol study to identify risk factors for first febrile seizures, with special emphasis on characteristics of the acute illness episode. Cases were identified through hospital emergency departments; controls were identified through outpatient clinics and emergency departments. Sixtynine children with first febrile seizures and no history of previous unprovoked seizures were matched for age (±6 months), site of routine pediatric care, and date of visit (±weeks) with 1 or 2 febrile controls who had no history of previous febrile or unprovoked seizures. Medical records for the index visit were reviewed, and parents were interviewed by telephone. Illness characteristics examined included height of temperature, type of underlying illness, contact with a physician during the illness but before the index visit, and use of acetaminophen or decongestants. Family history of febrile and of unprovoked seizures, sociodemographic characteristics, daycare use, and selected preand perinatal variables were also studied. On multivariable analysis, significant independent risk factors were height of temperature, history of febrile seizures in a firstor in a higher degree relative. Gastroenteritis as the underlying illness had a significant inverse (i.e., protective) association with febrile seizures. Maternal smoking during pregnancy was a marginally significant predictor of febrile seizures.
212 citations
TL;DR: Most of the major AEDs, administered in therapeutic doses, cause little or no cognitive or behavioral impairment in group studies, however, individual variability is considerable, and some patients do not tolerate low serum levels, whereas others tolerate high levels without subjective or objective effects.
Abstract: All antiepileptic drugs (AEDs) have the potential for adverse effects on cognition and behavior Most of the major AEDs, administered in therapeutic doses, cause little or no cognitive or behavioral impairment in group studies However, individual variability is considerable, and some patients do not tolerate low serum levels, whereas others tolerate high levels without subjective or objective effects In the past, carbamazepine (CBZ) and valproate (VPA) have been reported to have the fewest adverse cognitive and behavioral effects in children and adults However, several recent, well-controlled studies have not found significant differences between the effects of phenytoin (PHT) and those of CBZ or VPA Greater adverse effects have been found for phenobarbital (PB) However, we must use environmentally relevant measures of cognitive and behavioral functioning to measure effects on daily functioning Future studies must define cognitive and behavioral toxicity in subpopulations (eg, post-traumatic epilepsy, mental retardation, depression) and with the new AEDs
212 citations
TL;DR: Generalized tonic‐clonic seizures decreased dramatically, almost disappearing in all cases, with a significant reduction in interictal paroxysmal discharges and a tendency toward an increase in EEG back‐ground frequency.
Abstract: Five patients with chronic incapacitating seizures averaging 15-5,000/month were selected for study. All patients had more than one seizure type and had received maximal doses of antiepileptic drugs (AEDs). The centromedian thalamic nucleus (CM) was stimulated electrically through bilateral multicontact platinum electrodes stereotaxically placed in CM and connected to internalized pulse generators. Electrophysiologic confirmation of electrode position included thalamically elicited recruiting responses and EEG desynchronization recorded at the scalp. Stimulation parameters were adjusted individually in the range of 450-800-microA intensity, 65 pps, 0.09 ms, in 1-min trains, alternating right and left side stimulation and with 4-min intervals delivered for 2 h/day. Quantitative evaluation included frequency of seizures/month, number of maximal interictal paroxysmal discharges, and frequency of background activities counted in selected scalp EEG samples, taken throughout the observation period (7-33 months). Significance of changes was evaluated by parametric Student's t test. Generalized tonic-clonic seizures (GTC) decreased dramatically, almost disappearing in all cases (p < 0.001), with a significant reduction in interictal paroxysmal discharges (p < 0.01) and a tendency toward an increase in EEG background frequency. Other generalized seizures (atypical absences) decreased significantly, but there was no change in the number of complex partial seizures (CPS). CM stimulation is useful in control of GTC, but its beneficial effect on other seizure types has not been established.
TL;DR: SUDEP incidence increased with male sex, number of AEDs ever prescribed, and prescription of psychotropic drugs and was highest in males with a history of treatment with three or more AEDS and four or more psychotropic drug prescriptions.
Abstract: Summary: To measure the incidence of sudden unexplained death in treated persons with epilepsy (SUDEP) and to identify risk factors for SUDEP, a cohort of 6,044 persons aged 15–49 years with more than four prescriptions for antiepileptic drugs (AEDs) was identified from the Saskatchewan Health prescription drug file. To exclude subjects whose sudden deaths (SUDs) might be misattributed to another chronic underlying disease, subjects with hospitalizations for cancer or heart problems were excluded. To exclude subjects without epilepsy, subjects with >2-year AED treatment followed by AED-free time and subjects receiving < 1 U/day were excluded. The final cohort consisted of 3,688 subjects. Follow-up was started at the first AED prescription listed in the prescription drug file and ended at the earliest of the following: age 50 years, death, or last registration in the Saskatchewan Health. For 153 of 163 deaths occurring in the cohort, copies of anonymized death certificates were obtained and copies of anonymized autopsy reports of potential SUDEP cases were examined. There were 18 definite/probable SUDs and 21 possible SUDEPs, yielding a minimum incidence of 0.54 SUDEP per 1,000 person-years and a maximum of 1.35 SUDEP per 1,000 person-years. SUDEP incidence increased with male sex, number of AEDs ever prescribed, and prescription of psychotropic drugs and was highest in males with a history of treatment with three or more AEDs and four or more psychotropic drug prescriptions. Poisson regression showed a 1.7-fold increase in risk of SUDEP for each increment in maximum number of AEDs administered, a likely surrogate for severity and persistence of seizures.
TL;DR: It is concluded that PNES cease or significantly decrease in most patients, but occupational status does not improve as often, and earlier diagnosis may improve outcome.
Abstract: Information regarding outcome in patients with psychogenic nonepileptic seizures (PNES) is limited. We attempted to contact 72 consecutive patients with PNES confirmed by video-EEG monitoring: 51 of 72 (71%) were reached a mean of 15 months (range 12-27 months) after diagnosis and agreed to answer a structured telephone questionnaire. The questionnaire assessed the number of PNES in the last 6 months, antiepileptic drug (AED) use, occupational status, global self-rating, and extent of psychotherapeutic treatments. PNES had ceased in 18 of 51 (35%), decreased > 80% in 21 of 51 (41%), and decreased < 80% in 12 of 51 (24%). Thirty-three of 51 (65%) were not taking AEDs. Occupational status improved in 20% and did not change in 75%. Overall, 29 of 51 (57%) rated themselves markedly improved and 15 of 51 (29%) rated themselves unchanged or worse. Persisting PNES were associated with longer duration of PNES before diagnosis (p < 0.02) and presence of additional psychiatric disease (p < 0.01). Persisting PNES were not associated with gender, presence of epileptic seizures, or extent of psychotherapeutic treatments after diagnosis. Placebo saline infusion had been administered in some patients to help precipitate PNES. This did not affect the number of psychotherapy visits or outcome. We conclude that PNES cease or significantly decrease in most patients, but occupational status does not improve as often. Earlier diagnosis may improve outcome.
TL;DR: Recent findings about individual isoforms of the cytochromes P450 involved in the metabolism of phe‐nytoin (PHT) and carbamazepine (CBZ) make prediction of inhibition‐based interactions possible.
Abstract: Recent findings about individual isoforms of the cytochromes P450 involved in the metabolism of phenytoin (PHT) and carbamazepine (CBZ) make prediction of inhibition-based interactions possible. PHT is eliminated principally by hydroxylation to p-HPPH, a reaction catalyzed primarily by CYP2C9 and secondarily by CYP2C19 (S-mephenytoin hydroxylase). The principle of isoform specificity (drugs metabolized by the same isoform should exhibit interactions with the same inhibitors) was applied to the interactions of PHT with 17 inhibitors using two probes for CYP2C9, S-warfarin and tolbutamide. Eleven of 17 interactions (sulfaphenazole, phenylbutazone, fluconazole, azapropazone, cotrimoxazole, propoxyphene, miconazole, amiodarone, disulfiram, metronidazole, and stiripentol) could be explained by inhibition of CYP2C9. The remaining interactions (felbamate, omeprazole, cimetidine, fluoxetine, imipramine, and diazepam) were attributed to inhibition of CYP2C19. For CBZ, studies utilizing chemical inhibitors, immunoinhibition, liver bank correlations, and expressed enzymes established that CYP3A4 is the main enzyme catalyzing formation of CBZ-10, 11-epoxide. This explains the pronounced interactions of CBZ with erythromycin, troleandomycin, and other macrolide antibiotics (clarithromycin, josamycin, flurythromycin, and ponsinomycin). Work is in progress to explain the interactions of CBZ with other inhibitors. The literature contains no other information on isoforms involved in the metabolism of other major antiepileptic drugs.
TL;DR: Stepwise regression analyses indicated that both later age at onset and older chronologic age were significant and selective predictors of episodic memory decrease for left ATL patients, and adequacy of preoperative memory performance was a nonspecific predictor, associated with decrease in post operative memory performance.
Abstract: Summary We examined the relationship of age of onset of epilepsy, chronological age at time of operation, and adequacy of preoperative memory performance to pre- to postoperative verbal memory decline. Patients who underwent left (n = 50) or right (n = 51) anterior temporal lobectomy (ATL) were administered tests of verbal episodic (list learning, paragraph recall) and semantic memory (visual naming, vocabulary), both preoperatively and 6 months postoperatively. As a group, left ATL patients showed the classic selective decrease on measures of episodic but not semantic memory. However, examination of episodic memory outcome showed considerable individual variability. Stepwise regression analyses indicated that both later age at onset and older chronologic age were significant and selective predictors of episodic memory decrease for left ATL patients. Adequacy of preoperative memory performance was a nonspecific predictor, associated with decrease in postoperative memory performance for both left and right ATL patients and for multiple types of memory indices. The clinical and theoretical implications are discussed.
TL;DR: Ten neurologically normal patients aged 8–30 years who had recurrent episodes of visually induced occipital seizures with age‐related onset and specific mode of precipitation are studied, finding that these patients have an idiopathic localization‐related epilepsy with age-related onset, and underrecognized type of epilepsy.
Abstract: We studied 10 neurologically normal patients (8 females, 2 males) aged 8-30 years (mean 17 years) who had recurrent episodes if visually induced occipital seizures. Television and computer screens were the main triggers. Seizure onset occurred between the ages of 5 and 17 years (mean 11 years). All seizures were stimulus related and began with elementary visual symptoms, followed in most patients by a slow clustering of cephalic pain, epigastric discomfort, and vomiting, with either normal of only mildly impaired responsiveness. EEG features included normal background activity, occipital spikes and waves, and a photoparoxysmal response which could be occipital, generalized, or both. Four patients also showed spontaneous generalized epileptiform abnormalities, and 3 had rolandic spikes. An Oz electrode was critical in identifying epileptiform activity in some patients. Complete seizure control was achieved in most patients with monotherapy, although occasional stimulus-related seizures occurred in 3 patients who showed a wider range of photosensitivity. These patients have an idiopathic localization-related epilepsy with age-related onset and specific mode of precipitation. Although this type of epilepsy has been reported previously, it has remained underrecognized, probably because it is difficult to differentiate clinically from migraine or from nonreflex childhood idiopathic occipital epilepsy.
TL;DR: The exposure to Western culture and socioeconomic system in Taiwan might have helped reduce the discrimination against epilepsy, and the attitudes toward epilepsy disclosed by this study were more favorable than those detected in a similar survey conducted in Henan Province, China.
Abstract: A survey of public awareness and understanding of and attitudes toward epilepsy was made in Taipei City and Chin-San Village, Taiwan in 1992. In a population sample of 2,610 adults, 87% had read or heard about epilepsy, 70% knew someone who had epilepsy, 56% had seen someone having a seizure, 18% would object to having their children associated with persons with epilepsy, 72% would object to having their children marry a person with epilepsy, 31% believed that epileptic persons should not be employed in jobs as other persons are, 7% believed that epilepsy was a form of insanity, 34% did not know the cause of epilepsy, 13% did not know what an epileptic attack was like, and 18% did not know what to recommend if their friends or relatives had epilepsy. Youth, higher education, and upper levels of employment were correlated with answers that were more favorable concerning epilepsy in all survey questions except for the question regarding marriage, for which the reverse was noted. The attitudes toward epilepsy disclosed by this study were more favorable than those detected in a similar survey conducted in Henan Province, China. The comparison suggests that the exposure to Western culture and socioeconomic system in Taiwan might have helped reduce the discrimination against epilepsy.
TL;DR: It is indicated that there is a specific risk to naming after dominant ATL for adult temporal lobe epilepsy (TLE) patients with a left hemisphere focus and the absence of an early risk factor for the development of seizures.
Abstract: We evaluated language functions in 154 patients with left hemisphere speech dominance undergoing anterior temporal lobectomy (ATL). Measures of phonemic and semantic fluency, confrontation naming, repetition, comprehension, and reading were administered before and 3 weeks postoperatively. Patients were grouped by focus (left, LT; right, RT) and presence of early risk factors for development of seizures (ER, early risk, < or = 5 years; NER, no early risk): (LT-ER, n = 45; RT-ER, n = 49; LT-NER, n = 27; RT-NER, n = 33). Preoperatively, the LT group showed a selective naming deficit as compared with the RT group. Postoperatively only the LT-NER group showed significant overall decline in language. For this group, the change was attributable to a selective decline in naming as compared with other functions. These data indicate that there is a specific risk to naming after dominant ATL for adult temporal lobe epilepsy (TLE) patients with a left hemisphere focus and the absence of an early risk factor for the development of seizures.
TL;DR: Visualization of BZD receptors with [11C]flumazenil PET appears to be a promising approach for noninvasive identification of frontal lobe epileptogenic regions.
Abstract: Presently available noninvasive methods correctly localize epileptogenic regions in only approximately 50% of patients with frontal lobe epilepsy (FLE). Earlier studies have shown that temporal lobe epileptogenic regions may be identified readily by positron emission tomography (PET) measurements of regional benzodiazepine (BZD) receptor binding. We tested the specific applicability of this method in patients with FLE. Six patients with frontal partial seizures and 7 healthy men were investigated with PET and the BZD receptor ligand [11C]flumazenil. All patients had magnetic resonance (MR) brain scans. The independent assessment of seizure-onset region was based on seizure semiology, intra- and extracranial EEG and, in 4 cases, also on [18F]fluorodeoxyglucose (FDG)-PET. The epileptic focus/seizure-generating region was correctly identified by [11C]flumazenil PET in all patients. This region was characterized by a significant reduction in BZD receptor density. The area with reduced BZD receptor density was better delimited than the corresponding hypometabolic region, which was observed in 50% of patients investigated with [18F]FDG-PET. MRI was normal in 5 patients. Visualization of BZD receptors with [11C]flumazenil PET appears to be a promising approach for noninvasive identification of frontal lobe epileptogenic regions.
TL;DR: The findings in these patients clearly overlapped presumably reflecting the interconnections between functionally related frontal zones; yet the manner in which the symptoms clustered and the sequence in which they occurred generally indicated the anatomic site of the epileptogenic zone.
Abstract: To define further the electroclinical manifestations of frontal lobe epilepsy (FLE), we studied 150 seizures manifested by 24 patients; 18 patients had subdural electrode arrays (SEA). The findings in these patients clearly overlapped presumably reflecting the interconnections between functionally related frontal zones; yet the manner in which the symptoms clustered and the sequence in which they occurred generally indicated the anatomic site of the epileptogenic zone. We divided the patients into three major groups: (a) those with supplementary motor seizures, (b) those with focal motor seizures, and (c) those with complex partial seizures (CPS, psychomotor seizures). Supplementary motor seizures began with tonic posturing of the extremities. Focal motor seizures generally began with conscious contralateral version or unilateral clonic focal motor activity; tonic posturing was noted only late in the seizure. CPS (psychomotor) began with unresponsiveness at onset, followed by staring or unconscious contraversion. We compared frontal lobe seizures with temporal lobe seizures reported previously; oral-alimentary automatisms, repetitive hand movements, or looking around, were more common in temporal lobe seizures, whereas tonic posturing and bicycling movements were more common in frontal lobe psychomotor seizures.
TL;DR: It is concluded that the incidence of seizures causing injury or death in the general population was 32.2 in 100,000 population and that 15% of seizures brought to medical attention resulted in injury and death.
Abstract: The literature contains little information regarding the incidence of injury or death in the general population caused by seizures. We prospectively surveyed all patient visits to the four emergency departments serving adults in the Halifax-Dartmouth metropolitan area (adult population 260,935) from September 1, 1990 to August 31, 1991 to identify patients treated as a result of a seizure. The medical examiner's records were also surveyed for deaths related to seizures. We identified 560 patient visits precipitated by seizures of all types and etiologies except those secondary to acute trauma. Injuries or deaths occurred during 84 of 560 seizures (15%). Sixty-three patients incurred 89 injuries during 77 seizures (some patients had more than one injury, and some patients had injuries on more than one occasion). The incidence of seizures resulting in injury was 29.5 in 100,000 population. The most common injuries were head contusions and head lacerations. Most injuries were minor and required little or no treatment. Deaths occurred during seven seizures (1.2%). The incidence of death as a complication of seizures was 2.68 in 100,000 population. Deaths were not restricted to patients with epilepsy. We conclude that the incidence of seizures causing injury or death in the general population was 32.2 in 100,000 population and that 15% of seizures brought to medical attention resulted in injury or death. Most injuries were minor but seven patients died during seizures, indicating that seizures remain a life-threatening event.
TL;DR: The results suggest a mechanism of infertility related to temporal lobe dysfunction that alters the release of hypothalamic trophic hormones that secondarily affect release of the pituitary gonadotropins, causing ovulatory failure.
Abstract: Women with epilepsy have lower fertility rates than women without epilepsy. We hypothesized that limbic dysfunction in temporal lobe epilepsy (TLE) alters the release of hypothalamic trophic hormones that secondarily affect release of the pituitary gonadotropins, causing ovulatory failure. We assessed ovulatory function over three consecutive menstrual cycles in 17 women with partial seizures arising from the temporal lobe (TLE), 7 women with primary generalized epilepsy (PGE), and 12 controls. We devised scores to reflect ovulatory function that were based on daily basal body temperature and monthly serum progesterone levels. Seizure frequency, antiepileptic drugs (AEDs), and depressive symptomatology were also evaluated. Anovulation was more frequent in subjects with TLE (35.3%) than in subjects with PGE (0%) or in controls (8.3%). Anovulatory cycles tended to occur more frequently in subjects with TLE who were treated with polytherapy than in those receiving monotherapy, but this result was not statistically significant. Seizure frequency and symptoms of depression did not affect ovulatory function. Although AED polytherapy may increase the likelihood of anovulation, our results suggest a mechanism of infertility related to temporal lobe dysfunction.
TL;DR: Medication monitoring showed differences in dose frequency compliance and dose interval compliance between investigational and concomitant medications, as well as study protocol noncompliance, by outpatients in a long‐term clinical trial.
Abstract: Compliance with medication regimens and clinical trial schedules was evaluated during a study of vigabatrin (VGB), an antiepileptic drug (AED). Medication Event Monitors (MEMS, Aprex Corp., Fremont, CA, U.S.A.) were provided to monitor use of VGB and other AEDs administered to 111 patients at 10 sites. MEMS reports showed the number of doses administered daily, times of doses, and intervals between doses. The 66 patients whose data were evaluable took VGB as prescribed (twice daily, b.i.d.) on 89 +/- 7% of days in the clinical trial (mean 189 +/- 63 days). However, only 66 +/- 24% of doses were taken within the 9-15-h dose interval window for twice-daily dosing, a lower rate than that for dose frequency compliance (p < 0.001). Concomitant medications prescribed b.i.d. (n = 66) (86 +/- 11% dose frequency compliance) were taken at lower rates than VGB (p < 0.02). Interval compliance also was lower for concomitant b.i.d. medications (59 +/- 26%) than for VGB (p < 0.01). Dose frequency compliance for thrice-daily (t.i.d.) medications (n = 36) was 80 +/- 18 and 40 +/- 19% for interval compliance (6-10 h) (both p < 0.0001 vs. VGB). Dose frequency compliance for four times daily (q.i.d.) medications (n = 23) was 80 +/- 23 and 33 +/- 18% for interval compliance (4-8 h) (both p < 0.0001 vs. VGB). Patients at eight sites did not use MEMS properly, often for practical reasons, voiding including of data for 93 medications (32%) because of noncompliance with the study design to monitor compliance.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: An accurate estimate of the public health burden of childhood epilepsy and determination of possible risk factors for idiopathic epilepsy both depend on conducting complete community‐based case ascertainment and obtaining detailed clinical data.
Abstract: Summary: With reported prevalence rates of 4–9 cases per 1,000 children, childhood epilepsy is a major public health concern. Reported prevalence rates vary, mainly because researchers often use different epilepsy definitions. In addition, total prevalence may be underestimated if incomplete case-ascertainment methods are used. We used a multiple-source case-ascertainment method that included obtaining information from electro-encephalogram laboratories to estimate the prevalence of epilepsy and to classify seizure types among 10–year-old children. In the metropolitan Atlanta (GA, U.S.A.) area, we found a lifetime prevalence of childhood epilepsy of 6 per 1,000 (95% confidence interval, 5. 5–6. 5) 10-year-old children. However, using capture-recapture analysis, this prevalence may be as high as 7. 7 per 1,000. Proportionately more boys than girls had epilepsy. The prevalence did not vary appreciably by race. Partial seizures, including secondarily generalized seizures, were the most common seizure type (58%). Of children with epilepsy, 35% had another developmental disability (mental retardation, cerebral palsy, visual impairment, or hearing impairment). An accurate estimate of the public health burden of childhood epilepsy and determination of possible risk factors for idiopathic epilepsy both depend on conducting complete community-based case ascertainment and obtaining detailed clinical data.
TL;DR: The data indicate that hypometabolism is a consequence of MTS in the temporolimbic region but not necessarily in the other parts of the temporal lobe, and suggest that the combination of PET and MRI may facilitate the noninvasive diagnosis of MTLE.
Abstract: Summary: The mechanism of interictal glucose hypometabolism remains unclear, but this abnormality occurs more frequently in temporal lobe epilepsy (TLE) than in other types of partial epilepsy. Therefore temporal hypometabolism has been suggested to reflect mesial temporal sclerosis (MTS). To investigate this, we selected 22 patients with refractory partial epilepsy of mesial temporal lobe origin (MTLE) who had hippocampal atrophy based on magnetic resonance imaging (MRI) volumetric analysis. We then analyzed the metabolic correlates of unilateral hippocampal atrophy. Thirteen temporal regions of interest (ROI) were defined on MRI scans for each individual and then applied to high-resolution FDG-positron emission tomography (PET) images obtained parallel to the long axis of the hippocampus. The most hypometabolic regions were the temporal pole and the hippocampal region. When we analyzed ensembles of temporal regions grouped into related networks, the temporolimbic network, which included the hippocampal region and the temporal pole, was abnormal in 95% of the patients at a 3-SD threshold. PET hypometabolism was highly correlated with the degree of hippocampal atrophy in this network, but not in other parts of the temporal lobe, which were less frequently hypometabolic. These data indicate that hypometabolism is a consequence of MTS in the temporolimbic region but not necessarily in the other parts of the temporal lobe. Our results also suggest that the combination of PET and MRI may facilitate the noninvasive diagnosis of MTLE.
TL;DR: Pediatric experience with gabapentin (GBP), a new antiepileptic drug (AED), is limited and the behavioral problems were sufficiently severe to require discontinuation of GBP despite moderately improved seizure control.
Abstract: Pediatric experience with gabapentin (GBP), a new antiepileptic drug (AED), is limited. We described 3 learning disabled children, 1 aged 7 and 2 aged 10 years, with intractable partial seizures who developed severe behavioral problems while receiving modest doses of GBP. The children became hyperactive and had explosive outburst consisting of aggressive and oppositional behavior. The behavioral problems were sufficiently severe to require discontinuation of GBP despite moderately improved seizure control.
TL;DR: It is believed it is possible, on the basis of the preoperative evaluation described, to identify a population of epileptic patients who will do very well postoperatively, and represent ∼20% of the patients treated surgically in the epilepsy unit in the past several years.
Abstract: Twenty-two patients with intractable complex partial seizures (CPS) were treated with temporal lobectomy. Eighteen of 22 (82%) are seizure-free while receiving medication, with a mean follow-up time of 4 years. In each case, the clinical seizure pattern, interictal and ictal scalp EEG, magnetic resonance imaging (MRI), neuropsychological testing, and results of the intracarotid amobarbital procedure (IAP) converged to indicate a localized abnormality. None of the patients in this series had mass lesions, vascular malformations, or cortical scars, but 18 of 22 had hippocampal atrophy on MRI and 20 had hippocampal sclerosis (HS) on pathologic examination. We believe it is possible, on the basis of the preoperative evaluation described, to identify a population of epileptic patients who will do very well postoperatively. Such patients do not require invasive EEG monitoring, and they represent approximately 20% of the patients treated surgically in our epilepsy unit in the past several years.
TL;DR: It is suggested that homocysteine cannot be considered a simple agonist of the kainate or NMDA type of excitatory amino acid receptors, as it elicited minimal, predominantly clonic, and major generalized tonic‐clonic seizures at six different developmental stages, from 7 days to adulthood.
Abstract: Summary: We studied the convulsant action of homocysteine in 211 immature and adult Wistar albino rats. Homocysteine elicited minimal, predominantly clonic, and major generalized tonic-clonic seizures at six different developmental stages, from 7 days to adulthood. Nevertheless, some age-dependent differences in the seizure pattern were apparent. Minimal seizures in immature rats lasted ≤20 min, thus representing an epileptic status, whereas in adult animals these seizures were much shorter, lasting only ≥40 s. In addition, flexion seizures were observed in 7-and 12-day-old rats, only rarely in 15-and 18-day-old animals, and never in the 25-day-old and adult rats. ECoG recordings demonstrated a nearly iso-electric pattern during homocysteine-induced seizures in 7-and 12-day-old rat pups. In older rats, spikes or sharp waves were recorded, but precise electroclinical correlations were poor. The greater sensitivity of younger animals to kainic acid (KA) and N-methyl-D-aspartate (NMDA), as reported previously, was not evident in the case of homocysteine-induced seizures. This observation, together with a different behavioral pattern, suggests that homocysteine cannot be considered a simple agonist of the kainate or NMDA type of excitatory amino acid receptors. The exact mechanism of the convulsant action of homocysteine, both during development and in adulthood, remains to be clarified.
TL;DR: A retrospective study of infantile spasms from the east‐central region of Sweden for the period 1987 1991, with a spread of 0.17–0.76 between the seven counties included, finds the value of modern neuroradiological techniques for etiological diagnosis is stressed.
Abstract: We performed a retrospective study of infantile spasms (IS) in 57 children (19 girls and 38 boys) from the east-central region of Sweden for the period 1987-1991. The incidence was 0.45/1,000 newborns a year, with a spread of 0.17-0.76 between the seven counties included. Forty-three cases (75%) were symptomatic and 14 (25%) were idiopathic. Cerebral malformations were diagnosed in 8 children, and chromosomal aberrations were diagnosed in 5. In addition, 2 children each were diagnosed as having tuberous sclerosis and neurofibromatosis. At follow-up, 57% in the idiopathic group had normal development, whereas 91% in the symptomatic group had died or developed a multihandicap. The value of modern neuroradiological techniques for etiological diagnosis is stressed.
TL;DR: It is concluded that the clinical features of TLS in younger children can be misleading and should be considered with caution in selecting patients for surgical procedures on the temporal lobe.
Abstract: Summary: The semiology of complex partial seizures(CPS) of temporal lobe origin in adults is well known and is important in establishing seizure localization in patients considered for epilepsy surgery. In contrast, the behavioral features of temporal lobe seizures (TLS) in children described in the literature have not been consistent. In the present study, we investigated children with TLS to compare their attacks to TLS occurring in adults. The study was based on video recordings of 29 children with TLS aged 18 months to 16 years. Children were included, if they became seizure-free after temporal lobectomy (except 4 children with a marked reduction in seizure frequency and 1 with isolated auras), and if clear unitemporal seizure onset in ictal EEG-recordings, unilateral radiological lesions, and corresponding histopathological findings were detected. Children aged >6 years had TLS with features similar to those of adults. In younger children, typical semiology included symmetric motor phenomena of the limbs, postures similar to frontal lobe seizures in adults, and head nodding as in infantile spasms. We concluded that the clinical features of TLS in younger children can be misleading and should therefore be considered with caution in selecting patients for surgical procedures on the temporal lobe.