Lithium-pilocarpine neurotoxicity: a potential model of status epilepticus

Convulsive status epilepticus (SE) is clinically defined as prolonged electrical and clinical seizure activity in which the patient does not regain consciousness to a normal alert state between repeated tonic-clonic attacks. The disorder is a neurological emergency associated with a mortality rate of 10-12% and an even greater morbidity. Seizures represent one of the most severe in vivo stimulatory stresses that the brain is exposed to and generalized status epilepticus represents a very severe form of seizures. The International Classification of Seizures has defined this condition as "a condition characterized by an epileptic seizure that is so frequent or so prolonged as to create a fixed and lasting condition". During SE, high-amplitude, high-frequency electrical activity lasting at least 5 min is seen in the EEG. Continuous seizure activity in itself will result in progressive brain injury. The longer the condition of SE, the more difficult it is to control and the more likely it is to result in permanent neuronal damage. Therefore, SE is an emergency situation requiring prompt medical attention if severe permanent brain damage or death is to be prevented. SE often occurs in individuals with a history of seizures, in whom there are neural substrates already predisposed towards supporting seizure activity.     

Patient self-assessment of tibial plateau fractures in 40 older adults

The prevalence of refractory partial seizure Thai patients at Prasat Neurological Institute was retrospectively from patient charts from January 1995-December 1996 and further prospectively analysed. All epileptic patients were screened by direct questions regarding the anti-epileptic drugs (AEDs) regimen, the frequency, nature of seizure attacks and risk factors of seizure. The criteria of clinical refractory partial seizure was defined as partial seizure which cannot be controlled by a combination of at least two AEDs for four weeks. The results were 3,018 cases of total epileptic patients out of 300,008 visits. These were classified as 2,802 cases of generalized seizures (92.8%), 184 cases of partial seizures (6.1%), and 32 cases of unclassified seizures (1.1%). In the partial seizures group, the number of clinical refractory partial seizures was found to be 48 cases (26.1% of partial seizure). We found that the major risk factor of refractory partial seizures was lack of therapeutic AEDs blood level monitoring (64.5% of cases) and the other risk factors were lack of compliance, loss of follow-up but continued medication, concomitant medication, and improper drug storage. AEDs dosage was adjusted until the blood levels were in the therapeutic range, and correction of other risk factors and patient counseling was given. The number of true refractory partial seizures was reduced to 10 cases (5.4% of partial seizure). This procedure revealed that AED blood level monitoring and correction of other risk factors were essential in controlling seizure frequency. Thus, the prevalence of true refractory partial seizure in our study was 3.3 cases of refractory partial seizure per 1,000 cases of the seizure population. We recommend that AEDs blood level monitoring and exclusion of other risk factors should be added to the criteria for the definition of refractory partial seizures. This criteria should be applied when considering the use of new AEDs as an add-on therapy in refractory Thai patients.     

Spatial and temporal characteristics of neonatal seizures

Thirty-two neonates (26 term and 6 premature) having seizures were prospectively recruited and studied. Using prolonged video/EEG monitoring, we quantified seizure variables (electrographic and clinical seizure durations, interictal periods and electrographic seizure spread) for all 1,420 seizures recorded. The effects of time and antiepileptic drug (AED) therapy were analyzed statistically. Seizures were generally frequent, with limited electrographic spread. However, some neonates had consistently longer interictal periods and 13% had mean interictal periods > 60 min. Seizure variables were relatively stable over time, but they changed with AED therapy. There was a trend to decreased seizure duration, increased length of interictal periods, and decreased electrographic spread. Furthermore, there was evidence of reduced clinical features after sequential AED infusions. Seizures ceased during the monitoring period in 22 neonates. Eighty-five percent of all seizures had no clinical manifestations. Among neonates with clear clinical correlates, clinical observations underestimated electrographic seizures in individual neonates by a mean of 54% (range 0-95%). Seizures generally had limited electrographic spread. Use of only four recording electrodes, characteristic of some portable EEG systems, underestimated seizures in 19 neonates, and missed all seizures in 2.     

Effect of chronic electrical stimulation of the centromedian thalamic nuclei on various intractable seizure patterns: I. Clinical seizures and paroxysmal EEG activity

Twenty-three patients with various intractable seizure patterns were divided into four groups based on their most frequent seizure type and their clinical and EEG response to chronic electrical stimulation of the centromedian thalamic nuclei (ESCM): group A, generalized tonic-clonic (GTC, n = 9); group B, partial motor (Rasmussen type) (n = 3); group C, complex partial seizures (CPS, n = 5); and group D, generalized tonic seizures (Lennox-Gastaut type) (n = 6). CM were radiologically and electrophysiologically localized by means of stereotaxic landmarks and by thalamically induced scalp recruiting-like responses and desynchronization. ESCM consisted of daily 2-h stimulation sessions for 3 months. Each stimulus consisted of a 1-min train of square pulses with a 4-min interstimulus interval, alternating right and left CM. Each pulse was 1.0 ms in duration at 60/s frequency and 8-15 V (400-1,250 microA) amplitude. Voltage (V), current flow (microA) and impedance (k omega) at the electrode tips were kept constant. A significant decrease in the number of seizures per month and paroxysmal EEG waves per 10-s spochs occurred in group A patients between the baseline period (BL) and the ESCM period. These changes persisted for > 3 months after discontinuation of ESCM (poststimulation period, Post). Post was accompanied by a significant decrease in the number of paroxysmal EEG discharges. A substantial decrease in seizures and paroxysmal discharges was also observed in patients of group B. In contrast, patients of groups C and D showed no significant changes from BL to ESCM and Post periods, except for a significant decrease in the number of seizures in group D patients from BL to Post periods.     

Effect of anticysticercal treatment on the prognosis of epilepsy in neurocysticercosis: a pilot trial

Epilepsy secondary to active or inactive neurocysticercosis (NCC) is a major public health problem in Latin American countries. In an open-label pilot trial, we evaluated and followed (mean = 13 months) 16 patients with epilepsy resulting from active NCC which was treated with anticisticercal (ACC) drugs. These patients were aged 12-68 years with confirmed active NCC and seizures not controlled by adequate antiepileptic drug (AED) therapy. Patients were treated with albendazole or praziquantel (ALB and PZQ, ACC drugs) and AED monotherapy. The number of NCC cysts was markedly reduced by ACC therapy. Thirteen patients remained seizure-free and 2 had only one seizure during follow-up. Our data suggest a positive effect of ACC treatment on the prognosis of epilepsy caused by active NCC, but a prospective, double-blind, controlled study with long-term follow-up must be performed to determine whether ACC therapy improves long-term seizure control.     

Echocardiographic findings, 24-hour electrocardiographic Holter monitoring in patients with rheumatoid arthritis according to Steinbrocker''s criteria, functional index, value of Waaler-Rose titre and duration of disease

This study aims to understand seizure control outcomes and the risk of developing new wake seizures (WS) related to the different types of pure sleep epilepsies (SE), which is important in making rational management plans. A retrospective review of the Yonsei Epilepsy Clinic Registry identified 63 patients with pure SE not belonging to any specific epileptic syndromes. They were divided into the group of generalized tonic-clonic seizures during sleep (S-GTCS : n = 21) and the group of partial epilepsies during sleep (S-PE: n = 42) on the basis of seizure phenomenology, EEG, and neuroimaging data. These patients were followed for 2 years and their clinical variables were analysed for seizure control outcomes and development of new WS. Of 21 patients with S-GTCS, 17 achieved a seizure-free outcome and only one patient developed a new WS, which was consistent with a partial-onset secondary GTCS in phenomenology. Of 42 patients with S-PE only 15 patients achieved a seizure-free outcome and 11 patients developed WS during the 2-year follow-up period. Higher baseline seizure frequency and longer duration of epilepsy were associated with a higher incidence of new WS. The results suggest that the patients with S-GTCS carry a favorable clinical course, thus driving privileges or freedom of daily activities can be conferred without delay once their seizures are well controlled. However, the seizure control outcome was poor and the development of WS was frequent in patients with recurrent S-PE.     

Vigabatrin and lamotrigin: experiences with 2 new anticonvulsants in the Swiss epilepsy clinic

Vigabatrin and lamotrigine are two new antiepileptic drugs which have recently become available. Vigabatrin is a specific and irreversible inhibitor of the enzyme gamma-amino-butyric-acid (GABA) transferase. Its administration leads to a long lasting increase in GABA, the most important inhibitory neurotransmitter. Vigabatrin is effective in both adults and children in the treatment of partial and especially complex-partial seizures. After add-on in vigabatrin to their therapeutic drug regime in 116 of our own patients, 39% of previously therapy resistant patients reported a reduced seizure frequency of at least 50% and 6% of them became seizure free. In secondarily generalized epilepsies the best results were observed in axial (infantile) spasms. In addition there was some improvement in tonic and convulsive seizures. Single patients showed increased myoclonic and clonic seizures. Initial efficacy was not always maintained during follow-up. In the experience of other authors, vigabatrin is also effective in the treatment of infantile spasms. It is not suitable for the treatment of generalized epilepsies with absences and myoclonic seizures. Most patients tolerate vigabatrin very well, although psychotic episodes are sometimes reported. So far there have been no relevant hepatic or hematological side effects. Lamotrigine is also effective in the treatment of partial seizures, for which it is approved. However, uncontrolled studies and our own experience have shown that it is even more effective in generalized seizures. As add-on therapy in absences and tonic or tonic-clonic seizures, a significant reduction in seizure frequency--in individual cases seizure freedom--can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictive factors of early seizures after acute cerebrovascular disease

BACKGROUND AND PURPOSE: Seizures within the first 48 hours of a first stroke or transient ischemic attack (TIA) are an independent prognostic factor for in-hospital mortality. The aim of this study was to determine predictive factors of early seizures in first-ever stroke patients. METHODS: Data of 1220 first-ever stroke patients admitted consecutively to an acute stroke unit of a 450-bed teaching hospital between January 1986 and December 1993 were collected from a stroke registry. Demographic, anamnestic, clinical, neurological, and neuroimaging variables in the seizure and nonseizure group were compared using the t test and the chi 2 test. The independent predictive value of each variable on the development of early seizures was assessed with a logistic regression analysis. RESULTS: Early epileptic seizures were diagnosed in 29 patients (2.4%). Seizures were significantly more frequent in patients with hemorrhagic stroke (4.3%) than in those with ischemic stroke (2%). Patients with seizures were significantly younger and significantly more likely to have acute confusional state, cortical involvement, large stroke, and involvement of the parietal, frontal, occipital, and temporal lobes than patients without seizures. The in-hospital mortality rate was 37.9% in the seizure group and 14.4% in the nonseizure group (P < .0005). After multivariate analysis, only cortical involvement (odds ratio of 6.01) and acute agitated confusional state (odds ratio of 4.44) were independent clinical factors for developing epileptic seizures. CONCLUSIONS: Cortical involvement in the neuroimaging studies and agitated acute confusional state at the onset of stroke were independent predictive factors of early seizures in first-ever stroke patients. The efficacy of anticonvulsant drugs in the prophylactic control of seizures should be assessed in prospective, randomized, double-blind clinical trials conducted in the subgroup of patients with the highest risk of developing epileptic seizures.     

Spectral EEG during short-term discontinuation of antiepileptic medication in partial epilepsy

The effect of short-term discontinuation of antiepileptic drugs (AEDs) on spectral analysis of EEG background activity (spectral EEG) was studied in patients undergoing preoperative evaluation for epilepsy surgery. We also wished to clarify whether AED discontinuation would provide lateralizing evidence in spectral EEGs of patients with temporal lobe epilepsy (TLE). Spectral EEGs were performed in 15 patients receiving their regular medication regimen and again after a 1-week period during AED withdrawal. A subgroup of 9 patients who had previously undergone temporal lobectomies (TLE group) was studied separately. In this group, we evaluated the effect of preceding seizures on spectral EEG derived from temporal neocortical areas. In all patients, spectral EEG changes were detected even after a short-term AED withdrawal. The total amount of absolute delta activity was reduced and occipital peak frequency and relative alpha activity were increased as compared with baseline values. In TLE patients with habitual seizures occurring < 20 h before the spectral EEG recording, lateralization was correctly identified by the greater amount of absolute delta activity ipsilateral to the epileptogenic focus. Epileptic seizures are accompanied by subtle focal slowing in spectral EEG for a much longer period than has been assumed. In addition, postictal spectral EEG over the temporal lobes may have lateralizing value. Further studies in larger numbers of patients are needed to evaluate the role of spectral EEG in the preoperative evaluation of patients for temporal lobe surgery.     

Surgical treatment for partial epilepsy among Norwegian children and adolescents

We conducted a retrospective longitudinal self-controlled study of 64 patients aged 4-19 years treated with resective surgery for partial epilepsy from 1952 to 1988. Approximately 60% of patients experienced > 95% reduction in seizure frequency, and 70% had worthwhile improvement of at least 75% reduction. Seizure relief was more frequent among patients who underwent operation after 1978, and significant differences by time period of operation were noted for those with temporal lobe excisions and patients with normal tissue histology. The region of resection and the age at treatment did not provide significant information with respect to seizure outcome. Postresection electrocorticography (ECoG) and EEG of the first postoperative year predicted later seizure outcome. Small neurologic deficits were more common among patients resected in the temporal lobe than in patients resected in the frontal lobe. Half of the patients with preoperative unilateral focal activity and a third of those with bilateral focal activity had normal EEG postoperatively. One fourth had discontinued antiepileptic drug (AED) therapy. As expected, long-term mortality was significantly higher than the mortality of the general population. Seven patients died during follow-up. Two male patients committed suicide.     

Release of nontransmembrane full-length Alzheimer''s amyloid precursor protein from the lumenar surface of chromaffin granule membranes

OBJECTIVE: To evaluate the effectiveness and safety of a single-dose treatment for acute repetitive seizure (ARS) episodes (e.g., clusters) administered in a nonmedical setting by caregivers. BACKGROUND: Patients with epilepsy may experience ARS episodes despite optimal anticonvulsant treatment. Such episodes require rapid treatment as medical emergencies. Typically, the patient is treated in an emergency medical setting with i.v. medication by trained medical personnel. METHODS: The authors undertook a multicenter, randomized, parallel, double-blind study of a single administration of Diastat (diazepam rectal gel) for treating episodes of ARS. ARS episodes and treatment criteria were defined for each patient at the start of the study. Caregivers were taught to determine ARS episode onset, administer a predetermined dose of study medication, monitor outcome, count respirations, and record seizures and adverse events. RESULTS: A total of 29 centers enrolled 158 patients, of whom 114 patients had a treated ARS episode (Diastat, n = 56; placebo, n = 58). Diastat treatment reduced median seizure frequency (p = 0.029). More Diastat patients were seizure free post-treatment (Diastat, 55%; placebo, 34%; p = 0.031). Kaplan-Meier analysis of the time to the next seizure favored Diastat treatment (p < 0.007). The most common adverse event was somnolence. CONCLUSION: Administration of a single rectal dose of Diastat was significantly more effective than placebo in reducing the number of seizures following an episode of ARS. Caregivers could administer treatment safely and effectively in a nonmedical setting.     

Preliminary evaluation of Rivotril in epilepsy

Treatment with Rivotril in doses of 2-10 mg daily was given to 26 patients with various forms of epilepsy, mostly refractory to previous treatment. In 2 cases the drug was withdrawn on account of intolerance, in 4 cases treatment was stopped after several days in view of greatly increased frequency of seizures. In the remaining cases the drug was administered during 2 to 27 months, (mean 7 months) in 3 cases as the only medication and in 17 with other anticonvulsants. The best therapeutic results were obtained in patients with partial seizures of complex symptomatology and in generalized non-convulsive seizures, the worst results in generalized seizures. Electroencephalographic findings included particularly disappearance of seizure activity, while focal changes persisted and even grew worse in some cases. Apart from 2 cases of acute intolerance in another 4 cases side effects were observed with somnolence, dizziness, equilibrium disturbances, and in one case granulocytopenia developed. Allergic changes and liver or renal damage were never observed. The authors suggest introduction of the drug in treatment of epilepsy in view of its favourable clinical effect even in cases refractory to previous treatment, especially since the drug is relatively well tolerated.     

Short-term mortality after a first episode of status epilepticus

PURPOSE: Studies evaluating short-term mortality among people who experience status epilepticus (SE) have produced conflicting results. Most studies are derived from clinical series with results affected by unspecified follow-up period and select referral of cases. This study was planned to evaluate short-term mortality after a first episode of SE. METHODS: We performed a population-based retrospective cohort study to determine the short-term mortality following a first episode of SE. Between January 1, 1965 and December 31, 1984, we studied all first episodes of afebrile SE who received medical attention in Rochester, Minnesota. Cases were followed until death or end of the study (February 1996). RESULTS: Mortality within the first 30 days was 19% (38 deaths out of 201 incident SE). Thirty-four deaths (89%) occurred among those with nonfebrile acute symptomatic SE, while 4 deaths (11%) occurred among those with unprovoked SE. Within the acute symptomatic group, after adjusting for age, there was a decreased risk of death in women (RR = 0.4; 95% CI: 0.2-0.9). No effect of duration or seizure type was shown after adjusting for other risk factors. CONCLUSIONS: One out of 5 subjects with SE died within the first 30 days. Short-term mortality is associated with the presence of an underlying acute etiology. Among acute symptomatic cases, women had a decreased risk of dying.     

Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies

The association of propofol with excitatory motor activity, such as myoclonic jerking and opisthotonus, in humans and in animals suggests that it may aggravate clinical seizure activity in some circumstances, although evidence suggests that under other circumstances, propofol inhibits seizure activity. In the current study, we assessed the effect of sedating doses of propofol on lidocaine-induced seizure activity in spontaneously breathing rats receiving no other anesthetics. Adult Sprague-Dawley male rats, 300-400 g, were divided into a control group and three experimental groups representing three graded levels of propofol sedation. The control rats then received a lidocaine infusion at the rate of 150 mg x kg(-1) x h(-1), resulting in a slow, progressive increase in systemic lidocaine concentrations. At the onset of electroencephalographic (EEG) seizure activity, arterial lidocaine concentrations were obtained. The treated rats received propofol according to three different dose schedules: Dose 1 = 10 mg x kg(-1) x h(-1) after a 2.5-mg/kg bolus; Dose 2 = 20 mg x kg(-1) x h(-1) after a 5-mg/kg bolus; Dose 3 = 40 mg x kg(-1) x h(-1) after a 10-mg/kg bolus. After 30 min, a steady level of sedation, dependent on the dose of propofol, was achieved. The lidocaine infusion was then started, and systemic lidocaine levels were obtained at the onset of EEG seizure activity. The lidocaine was continued until the onset of death by cardiac arrest. Plasma lidocaine was measured by gas chromatography. Analysis of variance and Dunnett's t-test were used for comparisons with the control values. Continuous propofol sedation increased the seizure dose of lidocaine from 37.7 +/- 3.5 mg/kg (mean +/- SEM) to 52.5 +/- 2.6 mg/kg (Dose 1, P < 0.05) and 67.9 +/- 8.6 mg/kg (Dose 2, P < 0.05), and completely abolished lidocaine seizures at Dose 3. The lethal dose of lidocaine, 89.4 +/- 10.5 mg/kg control versus 108.7 +/- 10.3 mg/kg (Dose 1), 98.3 +/- 10.1 mg/kg (Dose 2), and 93.5 +/- 10.4 mg/kg (Dose 3) did not differ among groups. The lidocaine levels at seizure threshold were increased in the propofol-treated rats: 16.9 +/- 0.5 microg/mL control versus 19.2 +/- 0.7 microg/mL (Dose 1, P = not significant) and 23.7 +/- 1.8 microg/mL (Dose 2, P < 0.05). Continuous propofol sedation in spontaneously breathing rats receiving no other anesthetics exerts a protective effect against lidocaine-induced seizures in a monotonic, dose-dependent fashion. The cardiac arrest dose of lidocaine is unaffected by propofol under these conditions. IMPLICATIONS: The i.v. anesthetic drug propofol, given to rats to produce sedation, was found to suppress seizure activity caused by overdosage of the local anesthetic lidocaine.     

Cold preservation of the porcine pancreas with histidine-tryptophan-ketoglutarate solution

OBJECTIVES: To describe the prescribing and use of antiepileptic drug (AED) therapy in nursing facility residents. DESIGN: A retrospective, multicenter drug use evaluation. SETTING: A total of 85 nursing facilities (average size, 119 beds) in five states. PARTICIPANTS: 1132 residents of the total 10,168 residents screened were prescribed at least one AED. MEASURES: Demographic information, primary indication for AED, comorbid conditions, prescribing physician's specialty, concomitant medications, and AED dosage regimen information were collected. Laboratory tests obtained in the most recent 6 months and seizure occurrence and seizure-related diagnostic assessments made in the most recent 3 months were also recorded. RESULTS: Of 1132 residents receiving AED therapy, 892 (78.8%) were prescribed AED therapy for a seizure-related diagnosis although 86% of seizure types were unspecified. Another 215 residents (19.0%) were prescribed AEDs for nonseizure diagnoses, and 25 (2.2%) had no indication for AED therapy. AEDs most frequently prescribed were phenytoin (56.8%), carbamazepine (23.0%), phenobarbital (15.6%), and valproic acid (13.1%). For residents with a seizure diagnosis, the most frequently prescribed monotherapy agents were phenytoin (52.0%), carbamazepine (12.2%), and phenobarbitol (7.1%). Almost 25% of residents with a seizure diagnosis took a combination of AEDs; more than 50% of all combinations included phenobarbital. About 9% of residents with a seizure diagnosis had one or more documented seizures during a 3-month review period. CONCLUSION: Among the substantial percentage of residents treated with AEDs, the lack of diagnosis of seizure type has serious implications for the choice of AED therapy. Opportunities exist for prescribing physicians, consultant pharmacists, and nursing staff to improve the medical management of nursing facility residents with seizures and of others receiving AEDs.     

Dizziness, epilepsy and the EEG

EEGs were done on 97 patients with the complaint of dizziness and were compared to a normal control group. In patients with dizziness of a syncopal-like type there was a small but significant increase in the incidence of bitemporal sharp wave discharges. Another group, consisting of 48 patients with seizures was evaluated; 71% had noted dizziness, significantly more than a control group. Most seizure patients experienced dizziness as a syncopal-like sensation with an abrupt onset just before their clinical seizures. The majority also experienced identical episodes of dizziness unassociated with their seizures, possibly as an abortive epileptic phenomenon. Dizziness described as rotational (vertigo) was uncommon in these epileptics.     

Imaging the induction and spread of seizure activity in the isolated brain of the guinea pig: the roles of GABA and glutamate receptors

1. The induction and spread of seizure activity was studied using imaging and electrophysiological techniques in the isolated whole brain of the guinea pig. We examined the role of GABA and glutamate receptor subtypes in controlling the spread of seizure activity across the olfactory cortex from a focus in the entorhinal cortex. Seizure spread was monitored by video imaging of intrinsic optical signals (reflectance changes) combined with multiple extracellular recordings. Both the unilateral and bilateral spread of seizure activity was monitored in different experiments. 2. Electrical stimulation of the lateral entorhinal cortex (10-15 V, 5 Hz, 5-10 s) evoked seizure activity that originated in the entorhinal cortex/hippocampus and later spread preferentially toward the posteromedial cortical amygdaloid nucleus ipsilaterally and bilaterally. The pattern of seizure spread in a given brain was highly reproducible. 3. The influence of gamma-aminobutyric acid (GABA) receptors on the spread of seizure activity was monitored at higher resolution on one side of the brain. Perfusion of a low concentration of the GABAA antagonist bicuculline methiodide (20 microM) resulted in spontaneous seizures that spread to the posteromedial cortical amygdaloid nucleus more rapidly than electrically evoked seizures [spread times: 5.5 +/- 3.7 s vs. 15.5 +/- 2.7 s, respectively (means +/- SE)]. Seizure spread was also more extensive in the presence of bicuculline involving the posterior perirhinal cortex and larger areas over the medial amygdala. Higher concentrations of bicuculline (100 microM) resulted in even more widespread propagation of spontaneous seizure activity throughout the olfactory cortex as well as to the perirhinal, insular, and occipital cortices. This concentration of bicuculline also further reduced the time required for seizure activity to spread from the entorhinal cortex to the posteromedial cortical amygdaloid nucleus (spread time = 2.3 +/- 1.7 s). The GABAB antagonist, CGP 35348 (200 microM), in contrast, had no significant effect of seizure induction or propagation. 4. The role of glutamate receptor subtypes in seizure propagation was studied by examining the bilateral spread of seizures. Perfusion of the kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (K/A) receptor antagonist (6-cyano-7-nitroquinoxaline-2,3-dione, CNQX, 20 microM) completely and reversibly suppressed stimulus-evoked seizure activity as detected electrophysiologically and optically. CNQX also reduced the magnitudes of field potentials recorded in the isolated brain in a reversible manner by an average of 70.8 +/- 2.21% of control. The N-methyl-D-aspartate (NMDA) receptor antagonist dibenzocyclohepteneimine (MK-801) did not significantly alter the magnitudes or shapes of field potentials recorded in the isolated brain nor did it significantly alter seizure activity measured optically or electrophysiologically. 5. Perfusion of the metabotropic glutamate receptor agonist [trans-1-amino-(IS,3R)-cyclopentanedicarboxylic acid (trans-ACPD), 150 microM] completely and reversibly suppressed stimulus-evoked seizure activity as detected electrophysiologically and optically. The magnitudes of field potentials recorded in the isolated brain also were reduced by trans-ACPD an average of 75.4 +/- 5.39% of control values. 6. These results demonstrate that GABAA-mediated transmission is functionally present and may play an important role in epileptic tissue in limiting the spread of seizure activity from the entorhinal cortex to the posteromedial cortical amygdaloid nucleus and in creating functional pathways or preferential routes of seizure spread. GABAB-mediated postsynaptic inhibition played no significant role in the induction or spread of seizure activity in this study. K/A receptors but not NMDA receptors are necessary for the induction and subsequent spread of seizure activity originating in the entorhinal cortex/hippocampus.     

Rapid arrest of seizures with an inhalation aerosol containing diazepam

Diazepam (DZP) and a mixture of Chinese herbs customarily used to treat epilepsy were prepared as an aerosol under the trade name Aerosolum Diaiepami Compositae or Flvalscop (FVS). FVS was studied in a single-blind trial in 101 patients with seizures preceded by an aura and in 19 without an aura to whom was administered by another person. FVS or a control preparation was administered. In 16-22 s, (average 18.5 s), the aura was interrupted and no seizure ensued in 90% of the cases treated with FVS and in 26% of cases treated with the control preparation. Of the 120 patients, 8 had elementary partial seizures with Jacksonian march, 18 had complex partial seizures (CPS), 7 had simple partial seizures with autonomic symptoms, and 87 had secondarily generalized tonic-clonic seizures. Eleven patients have now received FVS for 2 years (400 ml each). Forty patients for 1 year (150-200 ml each); none of these patients have shown any side effects or abnormal laboratory findings. An aerosol-administered drug may be a valuable adjunct to the antiepileptic drug (AED) arsenal and merits more extensive evaluation.     

EEG findings in frontal lobe epilepsies

As a group, epilepsies of frontal lobe origin are thought to be poorly localized using surface EEG recordings. This finding may depend on the specific areas of frontal lobe from which the seizures originate or the pathologic substrate. We reviewed the presurgical surface EEGs of patients with frontal lobe epilepsy who underwent epilepsy surgery. The specific area of the frontal lobe where seizures originated was determined by 1) intracranial ictal EEG recordings, or 2) the presence of a structural lesion, identified by imaging studies in patients who achieved complete seizure control following surgery. We differentiated patients whose seizures began in the dorsolateral frontal convexity from those whose seizures began in the medial frontal region, and we correlated EEG findings in the interictal, postictal, and ictal states with seizure semiology, pathologic substrate, and surgical outcome. Four of nine patients had seizures originating in the dorsolateral frontal convexity and five had medial frontal onset seizures. Patients whose seizures originated from the dorsolateral convexity had focal interictal epileptiform abnormalities that localized to the region of seizure onset. Patients whose seizures began in the medial frontal region had either no interictal epileptiform abnormality or had multifocal epileptiform discharges. Patients whose seizures began in the dorsolateral convexity showed focal electrographic seizure activity that was localizing. This rhythmic fast activity did not appear to be substrate-specific. Patients whose seizure onset localized to the medial frontal region did not show focal electrographic seizure at clinical onset. We conclude that the scalp EEG recordings of frontal lobe epilepsies contain features that enable differentiation of seizures originating from two different regions of the frontal lobe.     

Family studies and human leukocyte antigen class II typing in Indian probands with seizures in association with single small enhancing computed tomography lesions

PURPOSE: To define the clinical features of the syndrome of seizures associated with single, small, enhancing computed tomography (CT) lesions (SSELs) in 235 Indian probands and seizure types among their family members. Human leukocyte antigen (HLA) class II genomic typing in randomly selected 41 probands was done to identify the role of hereditary factors in this syndrome. METHODS: The seizure types among 235 probands, their clinical outcome, and seizures in their family members were studied. Family data were collected on relatives of 212 additional probands with neurologic diseases other than epilepsy. HLA class II antigens were studied by using polymerase chain reaction (PCR) amplified DNA and sequence-specific oligonucleotide probe (PCR-SSOP) hybridization. RESULTS: The seizures in 86% were partial with or without generalization; 77% had fewer than five seizures before the first CT scan. Evanescent focal neurologic deficits after seizures were noted in 40%. Most patients (97%) were treated with a single antiepileptic drug (AED). Significant resolution of the CT scan lesion was noted within 6 months in 125 (53%) of 235 cases. Two thirds of patients had no seizures while taking a single AED, and an additional 18% had no seizures even after their AEDs were discontinued. Epilepsy among relatives of Indian probands having seizures in association with SSELs was more common as compared with relatives of probands with other neurologic diseases. A family history of seizures was noted in 21% probands, the ratio of affected first- to second-degree relatives was 4.3:1, and 60% of affected sibs had syndromic concordance with probands. There was a positive association of HLA-DRB1*13 (Pc = 0.036) with this syndrome. CONCLUSIONS: The syndrome of seizures in association with SSELs seems to be a benign localization-related epileptic syndrome. Our results of HLA studies point to an inherited susceptibility to an infective agent, which in most cases is of cysticercal etiology.