An analysis of lifetime fractures in women with epilepsy.

OBJECTIVE: To clarify the relationship between fractures and antiepileptic drug (AED) use. METHODS: Menopausal women with epilepsy were interviewed at two clinics regarding site, year and circumstances of any fracture, duration of AED use and menopause. Fracture sites were analyzed according to AED use. RESULTS: Twenty-nine fractures occurred in 20 of the 50 interviewed subjects (mean age 54). Nine occurred prior to AEDs; seven attributed to accident and two to clumsiness. Twenty occurred on AEDs; 10 attributed to clumsiness (most in the leg and foot), eight to seizure (most in the arm or hand) and two to accident. Duration of AED exposure was similar in both groups and in osteoporotic vs non-osteoporotic sites. CONCLUSIONS: Epilepsy therapy may contribute more to the lifetime occurrence of fracture than seizures themselves. More screening for osteoporosis is required. While adjusting doses to prevent seizures, ongoing screening for neurotoxicity must be maintained in order to avoid fractures.

Status epilepticus arising de novo in hospitalized patients: an analysis of 41 patients.

Most of the information on predisposing factors and mortality in status epilepticus (SE) arises from data obtained from patients presenting to the casualty department. However, another population which is frequently seen by consultative neurologists are medically ill patients who develop SE while in hospital. These patients are often notoriously difficult to treat once SE arises. We sought to characterize patients at risk for SE arising when they are hospitalized for other reasons. By doing this, risk factors for developing SE and prognostic indicators might be determined. We retrospectively reviewed records from three urban hospitals in the United States to identify hospitalized patients developing SE over a 1 year period. SE was defined as a clinical seizure lasting 30 minutes or longer, or repeated seizures without recovery. Patients who were admitted in SE or for an epilepsy-related problem, or who were less than 1 year old were excluded from the study. Forty-one patients with in-hospital SE were identified. There were 28 males and 13 females with an age range from 1 to 91 years (mean: 60 years, median: 65 years). The mean interval from hospital admission to the onset of status epilepticus was 26 days. Nineteen (46%) patients had a prior history of either epilepsy or symptomatic seizures, and of these, 10 were inadequately treated as judged by serum anticonvulsant levels at the time SE developed. Focal brain abnormality was present in 26 (63%) patients, the most common of which was stroke (17 patients ). Major metabolic derangements including hypoxia, electrolyte imbalance, hepatic encephalopathy, and sepsis were present in 23 (56%) patients. Eleven (27%) patients were being treated with theophylline preparations at the time SE developed. Mortality in this group of patients with in-hospital SE was 61% (25 deaths), with about one-third dying while in status, and two-thirds dying subsequently in hospital. In this retrospective study, there was no clear relationship between mortality and the duration of SE in this group of patients. In-hospital development of SE is usually related to underlying focal brain abnormality, especially stroke, in combination with systemic metabolic derangement. Prognosis is poor, and appears to be more related to underlying conditions rather than to status duration. More accurate prospective studies are warranted.

Genome scan of idiopathic generalized epilepsy: evidence for major susceptibility gene and modifying genes influencing the seizure type.

Idiopathic generalized epilepsy (IGE) is a common, complex disease with an almost exclusively genetic etiology but with variable phenotypes. Clinically, IGE can be divided into different syndromes. Varying lines of evidence point to the involvement of several interacting genes in the etiology of IGE. We performed a genome scan in 91 families ascertained through a proband with adolescent-onset IGE. The IGEs included juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic clonic seizures (EGTCS). Our linkage results support an oligogenic model for IGE, with strong evidence for a locus common to most IGEs on chromosome 18 (lod score 4.4/5.2 multipoint/two-point) and other loci that may influence specific seizure phenotypes for different IGEs: a previously identified locus on chromosome 6 for JME (lod score 2.5/4.2), a locus on chromosome 8 influencing non-JME forms of IGE (lod score 3.8/2.5), and, more tentatively, two newly discovered loci for absence seizures on chromosome 5 (lod scores 3.8/2.8 and 3.4/1.9). Our data also suggest that the genetic classification of different forms of IGE is likely to cut across the clinical classification of these subforms of IGE. We hypothesize that interactions of different combinations of these loci produce the related heterogeneous phenotypes seen in IGE families.

An integrated functional magnetic resonance imaging procedure for preoperative mapping of cortical areas associated with tactile, motor, language, and visual functions.

OBJECTIVE: To evaluate an integrated battery of preoperative functional magnetic resonance imaging (fMRI) tasks developed to identify cortical areas associated with tactile, motor, language, and visual functions. METHODS: Sensitivity of each task was determined by the probability that a targeted region was activated for both healthy volunteers (n = 63) and surgical patients with lesions in these critical areas (n = 125). Accuracy of each task was determined by the correspondence between the fMRI maps and intraoperative electrophysiological measurements, including somatosensory evoked potentials (n = 16), direct cortical stimulation (n = 9), and language mapping (n = 5), and by preoperative Wada tests (n = 13) and visual field examinations (n = 6). RESULTS: For healthy volunteers, the overall sensitivity was 100% for identification of the central sulcus, visual cortex, and putative Wernicke's area, and 93% for the putative Broca's area (dominant hemisphere). For patients with tumors affecting these regions of interest, task sensitivity was 97% for identification of the central sulcus, 100% for the visual cortex, 91% for the putative Wernicke's area, and 77% for the putative Broca's area. These sensitivities were enhanced by the use of multiple tasks to target related functions. Concordance of the fMRI maps and intraoperative electrophysiological measurements was observed whenever both techniques yielded maps and Wada and visual field examinations were consistent with fMRI results. CONCLUSION: This integrated fMRI task battery offers standardized and noninvasive preoperative maps of multiple critical functions to facilitate assessment of surgical risk, planning of surgical routes, and direction of conventional, intraoperative electrophysiological procedures. Thus, a greater range of structural and functional relationships is brought to bear in the service of optimal outcomes for neurosurgery.

A beneficial effect on mood in partial epilepsy patients treated with gabapentin.

PURPOSE: Antiepileptic drugs (AEDs) are frequently used for their beneficial psychoactive effects on affective disorders. We sought to demonstrate a psychoactive effect of gabapentin (GBP) when used as add-on AED therapy. METHODS: Forty adult patients with partial epilepsy were studied in a prospective, non-randomized fashion with interviewer-rated and self-rated scales of mood and anxiety: the Cornell Dysthymia Rating Scale (CDRS), Beck Depression Inventory (BDI), and Hamilton Depression (Ham-D) and Anxiety (Ham-A) Scales. After completion of baseline mood and anxiety scales (time 1), 20 of the 40 patients were prescribed add-on GBP (treated group). The remaining 20 patients served as a control group. Both groups were similar in age and sex distribution. Follow-up mood and anxiety scales were performed in all patients approximately 3 months later (time 2). The average GBP dose at time 2 was 1,615 mg/day. All patients were taking stable doses of one to four AEDs at baseline and throughout the study. Seizure frequency was monitored throughout. Statistical significance was assessed by analysis of variance (ANOVA) by using a two-factor repeated-measures model. RESULTS: The GBP-treated group had a significant decrease in CDRS score over time compared with the control group (p = 0.04). No significant differences between the control and the treated groups were found for any of the remaining mood scales (BDI, p = 0.58; Ham-D, p = 0.59; Ham-A, p = 0.93). There was no significant difference or change in seizure frequency between groups. CONCLUSIONS: GBP treatment is associated with mood improvement as measured by the CDRS. This improvement was not accounted for by seizure improvement.

Asynchronous pentobarbital-induced burst suppression with corpus callosum hemorrhage.

OBJECTIVE: We describe the electroencephalographic (EEG) findings in a 9-year-old girl, who presented with generalized tonic-clonic status epilepticus requiring pentobarbital anesthesia, and correlate these findings with clinicoradiologic evidence of a ruptured AVM with hemorrhage into the body of the corpus callosum. METHODS: EEG analysis accompanied by clinical assessment, CT and MRI scans, and cerebral angiography were performed. RESULTS: With pentobarbital coma, the EEG showed burst suppression with prominent interhemispheric asynchrony. Suppression epochs >2 s in duration and with amplitude <20 microV in all channels were identified. In 12 min of the EEG analyzed, 6 unilateral and 20 bilateral epochs occurred. Of the 20 bilateral suppression epochs, interhemispheric asynchrony of >1 s was noted at onset for 5 epochs and at offset for one. Chi-square analysis revealed an equal tendency for unilateral suppressions to occur over either hemisphere, and for suppression in one hemisphere to begin before the other. CONCLUSIONS: We conclude that the corpus callosum plays a critical role in interhemispheric synchronization of cortical neuronal electrical activity and propose that: (1) normally, the corpus callosum modulates interhemispheric synchronization of cortical inhibition; and (2) with corpus callosal disruption, cortical areas are 'released' from such synchronization.

Common dynamics in temporal lobe seizures and absence seizures.

Similarities among the clinical features of complex partial temporal lobe seizures and absence (petit mal) seizures suggest shared underlying mechanisms, but dissimilar electrographic features of the two seizure types have cast doubt on common neuronal substrates. However, visual inspection and traditional approaches to quantitative analysis of the electroencephalogram and electrocorticogram, such as Fourier analysis, may not be appropriate to identify and characterize the highly non-linear mechanisms likely to underlie ictal events. We previously introduced a technique, non-linear autoregressive analysis, that is designed to identify non-linear dynamics in the electroencephalogram [Schiff N. D. et al. (1991) Society of Neuroscience 21st Annual Meeting, 638.6; Schiff N. D. et al. (1995) Biol. Cybern. 72, 519-526, 527-533]. The non-linear autoregressive analysis technique is aimed at describing seizure discharges as a disturbance of synchrony at the level of neuronal circuits. In absence seizures, we showed that non-linear autoregressive analysis revealed a consistent "fingerprint" of these non-linearities in 3/s discharges within and across patients. Here, we investigate the possibility that non-linear autoregressive modeling of seizure records from patients with temporal lobe epilepsy might reveal common circuit mechanisms when compared with the non-linear autoregressive analysis fingerprint of absence seizures. Electrocorticographic records of seizure activity were obtained in four patients who had received subdural grids or strips implanted in preparation for epilepsy surgery. Decomposition of the multichannel data recorded from these patients by principal component analysis revealed that at least three to five independent "generators" were required to model the data from each patient. Non-linear autoregressive analysis of these extracted generators revealed non-linear dynamics in two patients. In both patients, the temporal aspects of these non-linearities were similar to the characteristic non-linearities identified in the non-linear autoregressive analysis fingerprint of absence seizures. In particular, both patients showed a non-linear interaction of signals 90 ms in the past with signals 150 ms in the past. This was the most prominent interaction seen in all patients with absence seizures (typical and atypical). These results suggest that seizures from some patients with temporal lobe epilepsy may share common underlying circuit mechanisms with those of absence seizures. Physiological interpretations of these results are considered and proposed mechanisms are placed into the context of the alterations of consciousness seen in both epilepsies.

Ventricular asystole during vagus nerve stimulation for epilepsy in humans.

Electrical stimulation of the vagus nerve, a recently available option for patients with refractory epilepsy, has demonstrated safety and efficacy. We report four patients with refractory epilepsy who experienced ventricular asystole intraoperatively during initial testing for implantation of the vagus nerve stimulator. Acute intraoperative vagus nerve stimulation may create ventricular asystole in humans. Extracorporeal cervical vagus nerve stimulation testing with continuous EKG monitoring intraoperatively before generator implantation is warranted.

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

OBJECTIVE: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. BACKGROUND: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. METHODS: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. RESULTS: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. CONCLUSIONS: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 82/83.

This study evaluated gabapentin monotherapy in 275 patients with medically refractory complex partial or secondarily generalized seizures who were taking one or two antiepileptic drugs (AEDs). Following an 8-week baseline, patients received randomized dosages of gabapentin (600, 1,200, or 2,400 mg/d) during a 26-week double-blind phase comprising 2 weeks gabapentin add-on therapy, an 8-week AED taper, and a 16-week gabapentin monotherapy period. Patients exited the study if they experienced a protocol-defined exit event. Results of outcome measures, including time to exit, completion rate, and mean time on monotherapy, showed no significant differences among dosage groups. Possible reasons for this lack of a dose-response relationship include withdrawal seizures and the limited range of gabapentin dosages studied. Overall, 20% of patients completed the study. Completion rates were higher among patients who had discontinued one AED (23%) than two AEDs (14%), and higher among patients who were not withdrawn from carbamazepine (27%) than among those who were (16%).

Left hemispheric dominance of epileptiform discharges.

PURPOSE: We reviewed 1,360 EEG reports for all patients studied in two different neurophysiology laboratories during 1 calendar year to determine whether epileptiform discharges have a hemispheric dominance. METHODS: Both inpatients and outpatients, with or without epilepsy, were included. RESULTS: Ninety-four records (6.9%) demonstrated generalized epileptiform activity. Of 95 EEG reports indicating spikes solely from one hemisphere, spikes arose from the left in 61 and from the right in 34. Among 50 other records with bilateral independent spikes with lateralization, 40 were left hemisphere dominant and 10 were right hemisphere dominant. CONCLUSIONS: These findings raise the possibility that the left cerebral hemisphere may generate focal epilepsy more frequently than the right.

Contralateral temporal hypometabolism on positron emission tomography in temporal lobe epilepsy.

INTRODUCTION: No detailed case studies report lateralised hypometabolism on positron emission tomography (PET) contralateral to the epileptogenic focus in temporal lobe epilepsy (TLE). MATERIAL AND METHODS: We performed 18F fluorodeoxyglucose (FDG) PET in two intractable TLE patients. RESULTS: One had right temporal interictal spikes on electroencephalography (EEG) and a right medial temporal lobe lesion on magnetic resonance imaging (MRI). FDG-PET showed decreased uptake in the left temporal lobe. Right temporal ictal onset, with bilateral interictal epileptiform activity, occurred on intracranial EEG. He is seizure free after right temporal lobectomy and ganglioglioma resection. The second had right temporal lobe interictal and ictal EEG activity. MRI demonstrated right anteriomedial temporal increased T2 signal. Neuropsychology revealed bilateral cognitive dysfunction. FDG-PET showed left anterior temporal and lateral frontal hypometabolism. He is seizure free after right temporal lobectomy. CONCLUSION: These findings suggest that regional uptake asymmetry on FDG-PET may be give misleading lateralising information in TLE.

Electroencephalography in lacunar infarction.

To determine the occurrence and clinical implications of electroencephalographic (EEG) abnormalities in patients with acute lacunar infarction, we conducted a single-blinded EEG study in 55 patients. Twenty-nine (53%) had mild EEG abnormalities, which were focal and ipsilateral to the side of infarction in 7 patients (13%). Abnormalities were more common in patients with evidence of a prior stroke (10 of 12 patients, 83%). However, 43% (16 of 37 patients) of those without historical or radiologic evidence of a prior stroke also had mild EEG abnormalities. This represents a higher incidence of routine EEG abnormalities in lacunar infarction than is generally assumed. Indeed, these findings are more consistent with recent quantitative EEG studies that consistently have shown high rates of abnormalities in lacunar infarction. We did not find major EEG abnormalities, such as continuous or nearly continuous focal delta activity, in any patient with first lacunar infarction. We conclude that within the first 48 h after a first ischemic infarction, when computed tomography often fails to show abnormalities, an EEG that shows lateralized major abnormalities is useful in excluding the diagnosis of either lacunar infarction or infarction limited to the brain stem. Mild abnormalities occur more often than previously thought in lacunar infarction and do not exclude this diagnosis.

Cerebral metabolic topography in unilateral temporal lobe epilepsy.

OBJECTIVE: Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of temporal lobe epilepsy (TLE) generally report interictal hypometabolism in the vicinity of the seizure focus. Yet, other evidence suggests that interictal metabolic abnormalities might extend to remote brain areas. We used FDG-PET to evaluate metabolism in selected regions distant from the focus in TLE. SUBJECTS: Twenty adult patients with medically intractable TLE were selected by criteria favoring a unilateral mesiobasal temporal focus. Structural imaging in this sample were normal except for medial temporal sclerosis in 13 patients. Twenty normal volunteers were controls. DESIGN: PET imaging was performed interictally. Regional glucose metabolism normalized by global metabolism was analyzed using t tests and correlation analysis. RESULTS: Ipsilateral to the seizure focus, metabolism was depressed compared with normal in the temporal pole (p = 0.001), but relatively elevated in the mesiobasal region (p = 0.005). Contralateral to the focus, metabolism was elevated in lateral temporal cortex (p = 0.0003) and mesiobasal regions (p = 0.0001). Metabolic correlation between ipsilateral and contralateral mesiobasal regions was similar in normal subjects (r = 0.74) and patients (r = 0.68). In contrast, correlations were abnormal between temporal poles and other temporal lobe subregions, both ipsilateral and contralateral to the seizure focus. CONCLUSIONS: Relative to normal values, both elevations and depressions of metabolism exist interictally in TLE. Such abnormalities, and accompanying changes in interregional correlations, may have wide spatial distribution. These findings are atypical among PET studies but are consistent with other physiologic, anatomic, and neuropsychological investigations of TLE.

Permanent hemiparesis due to partial status epilepticus.

Partial status epilepticus (SE) produces permanent focal neurologic deficits if it lasts for months or is associated with systemic illness or CNS inflammation. We describe a patient in focal SE for just 5 days. Attacks were her habitual frontal lobe seizures. When SE stopped, permanent contralateral hemiparesis was present. There was no new cause for the weakness except the SE itself. We conclude that partial SE requires prompt and effective treatment, since it can lead to permanent neurologic dysfunction.

Characteristic nonlinearities of the 3/s ictal electroencephalogram identified by nonlinear autoregressive analysis.

We describe a method for the characterization of electroencephalographic (EEG) signals based on a model which features nonlinear feedback. The characteristic EEG 'fingerprints' obtained through this approach display the time-course of nonlinear interactions, rather than aspects susceptible to standard spectral analysis. Fingerprints of seizure discharges in six patients (five with typical absence seizures, one with complex partial seizures) revealed significant nonlinear interactions. The timing and pattern of these interactions correlated closely with the seizure type. Nonlinear autoregressive (NLAR) analysis is compared with other nonlinear dynamical measures that have been applied to the EEG.

High-dose intravenous lorazepam for the treatment of refractory status epilepticus.

We treated nine refractory status epilepticus cases with high-dose intravenous lorazepam. We monitored the EEGs continuously, and lorazepam dosing was titrated to stop clinical and electrographic seizures. Lorazepam doses needed to terminate status epilepticus ranged from 0.3 to 9 mg/hr. Lorazepam did not cause hypotension. All patients survived. Outcome was complete recovery in two cases, moderate disability in four, and severe disability in three. These findings suggest high-dose intravenous lorazepam may be an effective alternative to pentobarbital for the treatment of severe status epilepticus.

Central mid-temporal spikes triggered by blinking.

The closed-circuit TV-electroencephalogram (CCTV-EEG) of a 6-year-old boy revealed central mid-temporal spikes (CMTS) triggered by blinking. The spikes occurred spontaneously, as well as reflexly, following the blinks by 100-200 msec. Triggered spikes occurred in the light and dark and also while awake and drowsy. However, spontaneous spikes, not triggered by blinks, also occurred in drowsiness. These findings demonstrate activation of CMTS by an endogenous behavior (blinking).

Aphasia as the sole manifestation of simple partial status epilepticus.

Aphasia due to simple partial status epilepticus is rare, particularly in the absence of a seizure history. No previous report describes acute aphasia as the sole clinical manifestation of EEG-monitored status epilepticus, with prompt resolution with treatment. We report a 45-year-old man with a left temporal glioblastoma who acutely developed a global aphasia, during which an EEG revealed continual repetitive sharp waves emanating from the left hemisphere. After injection of i.v. diazepam, the EEG seizure activity ceased, and the patient's language output returned to preseizure levels.