bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of Felbamate with Several Other Antiepileptic Drugs Against Seizures Induced by Maximal Electroshock in Mice
Authors: Gordon Robert , Gels Margaret , Wichmann Joseph , Diamantis William , Sofia R. Duane
Published: October 2005

Summary: The anticonvulsant effects of felbamate (FBM) alone or in combination with phenytoin (PHT), carbamazepine (CBZ), valproate (VPA), or phenobarbital (PB) were investigated against maximal electroshock (MES) seizures in mice. Nonprotective doses of the prototype antiepileptic drugs (AEDs) enhanced the protective effects of FBM against electrically induced seizures, as shown by significant reduction of FBM ED50 values. Toxicity as determined by rotorod test was not significantly potentiated, however, and the protective index (PI = TD50/ED50) of FBM was increased by >100% for each AED interaction. The increase in anticonvulsant potency of FBM after its combination with nonprotective doses of AEDs could not be accounted for by a pharmacokinetic mechanism.
Anticonvulsant Properties of Calcium Channel Blockers in Mice: N‐Methyl‐D‐, L‐Aspartate‐ and Bay K 8644‐Induced Convulsions are Potently Blocked by the Dihydropyridines
Authors: Palmer Gene C. , Stagnitto Mary L. , Ray Ranjit K. , Knowles Marilyn A. , Harvey Rosemary , Garske George E.
Published: October 2005

Summary: Ten calcium channel blockers were evaluated in mice after intraperitoneal (i.p.) administration for prevention of seizures induced by various convulsants. The dihydropyridines (class II calcium antagonists, i.e., nisoldipine, nitrendipine, nicardipine, nifedipine, and nimodipine) selectively prevented seizures elicited by administration of pentylenetetrazol (PTZ), N‐methyl‐D, L‐ aspartate (NMDLA) and the dihydropyridine calcium channel agonist BAY K 8644. With regard to prevention of NMDLA‐induced seizures and the subsequent mortality, these compounds were similar in potency to the noncompetitive NMD A receptor antagonist MK801. Unlike MK801 (IC50= 0.014 μM), the dihydropyridines did not inhibit in vitro binding of MK801 to synaptic membrane fractions prepared from rat cerebrohippocampal tissue. The dihydropyridines did not influence seizures elicited by maximal electroshock (MES). Flunarizine (diphenyl‐alkylamine, class IV) was selectively active in the MES test, considerably less potent against NMDLA‐induced convulsions/mortality, exhibited weak noncompetitive NMD A antagonism in vitro (IC50= 28 μM), and was inactive in the PTZ and BAY K 8644 testing paradigms. Diltiazem, a class III benzothiazepine, possessed relatively weak broad spectra of activity against MES, PTZ, NMDLA, and BAY K 8644 test situations. It was inactive in vitro as a noncompetitive NMDA antagonist. The class I compound verapamil (phenylalkylamine) displayed only moderate inhibition of NMDLA‐evoked seizures/ mortality. Prenylamine (class V) was moderately active against convulsions produced by MES and NMDLA while retaining a degree (IC50=16 μM) of noncompetitive NMDA antagonism. Lidoflazine (class VI) was inactive in all tests. The Ca2+ channel blockers and MK801 were inconsistent in their ability to prevent bicuculline (BlC)‐elicited convulsions. Inhibition of these seizures by 40–50% was rare; usually higher doses were less effective or led to appearance of side effects. The reference agent, MK801, worsened the convulsions and subsequent catatonia after administration of BAY K 8644. The data show unexpected action(s) of dihydropyridines with NMDA receptor‐mediated mechanisms and suggest thrée possibilities: (a) prevention of presynaptic/Ca2+ regulated release of excitatory amino acid, (b) direct depolarization by NMDA of dihydropyridine‐regulated Ca2+ channels, and (c) coupled/indirect regulation of dihydropyridinesensitive channels after NMDA receptor activation.
Anticonvulsant Effect of Fluoxetine on Focally Evoked Limbic Motor Seizures in Rats
Authors: Prendiville S. , Gale K.
Published: October 2005

Summary: Fluoxetine was evaluated for anticonvulsant effects in a rat model of focally evoked complex partial seizures (CPS) secondarily generalized. Fluoxetine was administered intraperitoneally (i.p.) 1 h before seizures were induced by focal intracerebral application of the GABAA receptor antagonist, bicuculline methiodide (118 pmol) unilaterally into a discrete epileptogenic site in the deep prepiriform cortex (“area tempestas,” AT) of rats. Significant dose‐dependent protection from clonic motor seizures was obtained after 5‐, 10‐, and 20‐mg/kg doses of fluoxetine, with 50% protection occurring after the 5‐mg/kg dose. Suppression of electrographic seizure activity was concomitant with suppression of motor seizures. These observations support and extend previous findings of other investigators who showed that fluoxetine exerts anticonvulsant actions against maximal electroshock (MES) convulsions and audiogenic convulsions in genetically seizure‐prone rodents.
Role of Brainstem Structures in Seizures Initiated from the Deep Prepiriform Cortex of Rats
Authors: Browning Ronald , Maggio Roberto , Sahibzada Niaz , Gale Karen
Published: October 2005

Summary: Previous studies showed that brainstem sei zures can still be evoked after transections that separate forebrain from brainstem. We sought to determine wheth er forebrain‐evoked electrographic seizures require brain stem connections for initiation and generalization. Male Sprague‐Dawley rats weighing 295–320 g implanted with epidural electrodes had brain transections placed at the pre‐, mid‐, or postcollicular level. In experiment 1, the transections were limited to severing the brainstem, spar ing the telencephalon laterally; these are referred to as “core” transections. In experiment 2, the transections severed the brainstem and also cut through the lateral telencephalon. These “extended” transections were ei ther (a) bilateral, (b) unilateral (i.e., a hemitransection confined to one hemisphere), or (c) partial (sparing path ways ventral to the pretectal nuclei). All transections were performed under ether anesthesia, and seizures were initiated 3 h later by focal infusion of bicuculline (BIC) into the area tempestas (AT) through a previously implanted guide cannula. In experiment 1, bilateral fore brain electrographic seizures occurred in the complete absence of connections between forebrain and brainstem, showing that the brainstem is not required for forebrain evoked seizures. In experiment 2, forebrain seizures evoked by BIC in AT were suppressed by bilateral ex tended transections which interrupted connections be tween AT and the caudal lateral telencephalon. Under these circumstances, application of carbachol with BIC reinstated the forebrain seizure response. These results indicate that carbachol application served to compensate for loss of an excitatory influence on AT resulting from the severing of connections with the caudal telencepha lon. The demonstration of direct projections from ento rhinal cortex to AT using Fluoro‐Gold tracing together with the finding that extended brain transections caudal to the telencephalon do not suppress focally evoked fore brain seizures provided further support for the notion that AT afferents from the caudal telencephalon regulate the sensitivity of AT to BIC. The present findings provide further evidence that seizure substrates in the forebrain and brainstem are separable and independent.
Olfactory Bulb Kindling in Mice Susceptible and Resistant to Ethanol Withdrawal
Authors: Green Robert C. , Rees Howard D. , Feller Daniel J.
Published: October 2005

Summary: The relation between kindling and susceptibil ity to ethanol withdrawal seizures was investigated using withdrawal seizure‐prone (WSP) and withdrawal seizure resistant (WSR) mice. These lines were developed by se lective breeding to be prone and resistant, respectively, to handling‐induced convulsions after chronic exposure to ethanol. Development of kindled seizures in response to electrical stimulation of the olfactory bulb was inves tigated in mice aged 2 and 8 months with no exposure to ethanol. Older WSP mice kindled more slowly than older WSR mice, requiring significantly more stimulations to reach the first stage 3 and the first stage 5 seizures. In younger mice, there was no significant difference be tween the two lines in the rate of kindling. The lower kindling rate in mature WSP mice is in contrast to their higher sensitivity to handling‐induced convulsions on withdrawal from ethanol and other agents. This finding suggests that separate genetic factors underlie these two models of mouse seizures.
Manganese and Epilepsy: Brain Glutamine Synthetase and Liver Arginase Activities in Genetically Epilepsy Prone and Chronically Seizured Rats
Authors: Carl G. F. , Blackwell L. K. , Barnett F. C. , Thompson L. A. , Kissinger C. J. , Olin K. L. , Critchfield J. W. , Keen C. L. , Gallagher B. B.
Published: October 2005

Summary: Low blood manganese (Mn2+) concentration is associated with epilepsy in humans and rats. The low Mn2+ concentration is attributed by some investigators to the seizure activity associated with the epilepsy, whereas others propose that the low Mn2+ concentration may be secondary to genetic mechanisms underlying the epilepsy. To begin to differentiate between these possibilities, Mn2+‐binding enzymes of liver and brain (i.e., arginase and glutamine synthetase, respectively) were assayed in rats exposed to chronically induced seizures and in genetically epilepsy‐prone rats (GEPRs). Chronic seizures caused a decrease in whole blood Mn2+ levels but did not affect brain Mn2+ concentrations. Arginase activity was increased in livers of rats with chronic seizure as compared with controls, but this difference was eliminated when Mn2+ was added to the assay. Brain glutamine synthetase activity was unaffected by chronic seizures, but the activity of this enzyme was significantly lower in GEPR brain than in control brain. Liver arginase activity tended to be lower in GEPRs, although the difference was not statistically significant. These data indicate that seizures affect liver arginase activity through changes in liver Mn2+ concentration, but GEPRs show abnormalities in Mn2+ ‐dependent enzymes apparently independent of seizure activity.
Pathogenic Role of Glutamate in Hyperthermia‐Induced Seizures
Authors: Morimoto Takehiko , Nagao Hideo , Yoshimatsu Makoto , Yoshida Kazuhiro , Matsuda Hiroshi
Published: October 2005

Summary:Hyperthermia induces seizures in both humans and rodents, but the underlying mechanism remains unknown. The present study showed that hyperthermia, causing rapid increase in body temperature, increases the concentration of glutamate (Glu) released into a cortical perfusate before onset of seizures in rats and that this increase in Glu concentration correlated with a decrease in seizure threshold temperature. These results indicate that increased cortical extracellular Glu induced by hyperthermia contributes to onset of seizures. The same mechanism may be involved in clinical seizures induced by fever in patients with febrile convulsions or epilepsy.
Parietal and Occipital Lobe Epilepsy: A Review
Authors: Sveinbjornsdottir S. , Duncan J. S.
Published: October 2005

Summary: Parietal and occipital seizures have been investigated relatively little. Recent interest in seizures of frontal lobe origin has led to a definition of several well‐identifiable clinical patterns of frontal lobe seizures. A similar delineation of the clinical and EEG pattern of parietal and occipital epilepsy, using modern investigations, appears appropriate, not least because the few reported series of surgical treatment in parietal and occipital epilepsy have indicated that operation may be relevant in selected cases, not only for removal of space‐occupying lesions. Such a study is currently being undertaken at the National Hospital for Neurology and Neurosurgery and The Chalfont Centre for Epilepsy with the aim of developing and evaluating diagnostic criteria for these seizures. From the existing literature we can conclude that precise incidence and prevalence are largely unknown. A recent community‐based study of 252 subjects with partial epileptic seizures in an epileptic population of 594, showed that parietal seizures and seizures of posterior origin each comprised 6.3% and central or sensory‐motor seizures comprised 32.5% of focal seizures in the 160 cases in which seizures could be subclassified (Manford et al., 1992). This incidence seems low for occipital seizures as compared with the 1953 study by Gibbs and Gibbs, who observed occipital epileptiform activity in 8% of subjects with focal epilepsy. The most prominent clinical manifestations of parietal epilepsy are elementary sensory phenomena at the beginning of seizures and elementary visual hallucinations in occipital epilepsy. These symptoms are not associated solely with posterior hemisphere epilepsy, however, and more studies are obviously needed to define how close this relation is. Scalp EEG is frequently negative or maybe misleading; further‐more, spread of epileptic discharges from the parietal and occipital lobes to frontal and temporal regions may obscure seizure origin. Because of these controversial symptoms, diagnostic criteria may be difficult to define. The wide difference in clinical and EEG manifestations between reported series of parietal and occipital epilepsy also reflects a considerable problem with patient sampling. Classification of epilepsy according to the anatomic division of the brain may be arbitrary, and it may be appropriate to define epileptic syndromes such as sensorimotor seizures or occipitotemporal seizures that cross such artificial divides.
Parietal Lobe Lesional Epilepsy: Electroclinical Correlation and Operative Outcome
Authors: Cascino Gregory D. , Hulihan Joseph F. , Sharbrough Frank W. , Kelly Patrick J.
Published: October 2005

Summary: We retrospectively studied ictal behavior, extracranial EEG, and operative outcome in 10 consecutive patients with intractable partial epilepsy of presumed parietal lobe origin who received a lesionectomy, i.e., resection of the neuroimaging‐identified abnormality, at the Mayo Clinic. Nine patients had a pathologically verified foreign‐tissue lesion, e.g., tumor or vascular malformation, and 1 patient had gliosis. All patients with foreign‐tissue lesions were rendered seizure‐free. The patient with gliosis experienced a reduction in seizure tendency. There were no operative complications. The most common seizure type was a simple partial seizure with visual, motor, or sensory symptoms (n = 8). Complex partial seizures (n = 5) and secondarily generalized tonic‐clonic seizures (GTC, n = 2) were also observed. The ictal behavior was often nonspecific although useful in identifying lateralization of the epileptogenic zone. Extracranial interictal and ictal EEG changes were unreliable markers of the parietal lobe origin of seizure activity. Lesionectomy without chronic intracranial monitoring or functional mapping may be an effective and safe alternative surgical procedure in patients with partial epilepsy related to parietal lobe lesions.
Intracranial EEG Monitoring in Landau‐Kleffner Syndrome Associated with Left Temporal Lobe Astrocytoma
Authors: Solomon Gail E. , Carson Deborah , Pavlakis Steven , Fraser Richard , Labar Douglas
Published: October 2005

Summary: A 3½‐year‐old boy developed partial complex seizures with right‐sided motor activity, occasionally secondarily generalized at age 18 months. Initial EEG showed left‐sided focal epileptiform discharges. Seizures became refractory to antiepileptic drugs (AEDs). At age 3 years, there was severe language deterioration consistent with Landau‐Kleffner syndrome (LKS). At that time, an EEG showed almost continual generalized spikes and poly spikes, worse during sleep. Video‐EEG showed generalized tonic seizures associated with generalized EEG ictal activity. Magnetic resonance imaging (MRI) showed a cystic and solid lesion of the left hippocampal and parahippocampal gyri without surrounding edema. Subdural strip electrodes under the left temporal and overlying the left frontal lobes demonstrated interictal spikes simultaneously in all recording contacts. Ictal EEG activity occurred in the temporal electrodes 0.2–1 s before appearing in the frontal electrodes. After left temporal lobectomy with subtotal resection of a low‐grade astrocytoma, he had an immediate marked decrease in seizures. In 1 month he was seizure‐free, and in 6 months had no further seizures and markedly improved language. These findings provide further evidence that left temporal structural epileptogenic lesions may contribute significantly to the pathophysiology of LKS.
Kynurenine Pathway Metabolites in Cerebrospinal Fluid and Serum in Complex Partial Seizures
Authors: Heyes Melvyn P. , Saito Kuniaki , Devinsky Orrin , Nadi N. Suzan
Published: October 2005

Summary: The kynurenine pathway metabolites, quinolinic acid (QUIN) and L‐kynurenine are convulsants, whereas kynurenic acid (KYNA) is an antagonist of excitatory amino acid receptors. Imbalances in the concentrations of these metabolites have been implicated in the etiology of human seizure disorders. In the present study, L‐kynurenine and QUIN concentrations in both cerebrospinal fluid (CSF) and serum were reduced in patients with intractable complex partial seizures (CPS) in both the postictal period (15–75 min after a seizure) and the interictal period (absence of seizure for >24 h) as compared with neurologically normal control subjects. Linear regression analyses and analysis of covariance showed that the reductions in serum QUIN and L‐kynurenine were correlated to blood antiepileptic medication. L‐Tryptophan (L‐TRP) levels also tended to be lower in both CSF and serum of the seizure patients. CSF KYNA and serum 3‐hydroxykynurenine concentrations were not affected in seizure patients, whereas serum levels of KYNA were reduced. 3‐Hydroxykynurenine was not detected in the CSF of either control or seizure patients. The results do not support a role for a generalized reduction in KYNA concentrations or an increased ratio of QUIN:KYNA, or increases in CSF L‐kynurenine in initiation and maintenance of intractable CPS humans.
Magnetoencephalographic Evaluation of Children and Adolescents with Intractable Epilepsy
Authors: Paetau R. , Hämäläinen M. , Hari R. , Kajola M. , Karhu J. , Larsen T. A. , Lindahl E. , Salonen O.
Published: October 2005

Summary: Magnetoencephalographic (MEG) discharges were recorded with multichannel superconducting quantum interference device (SQUID) gradiometers in 13 young candidates for epilepsy surgery. The sources of epileptic activity were related to generators of somatosensory and auditory evoked cortical responses and projected on magnetic resonance imaging (MRI) scans. Seven subjects had restricted or regional MEG foci, located in the frontoopercular (1), sensorimotor (3), perisylvian (1), mesiotemporal (1), or temporooccipital cortex (1). The MEG foci in the 3 patients who underwent operation agreed with the intracranial findings. Findings in the other patients emphasize the need to collect further data to define the ultimate role of MEG in preoperative evaluation of epilepsy.
Video‐Polygraphic Analysis of Myoclonic Seizures in Juvenile Myoclonic Epilepsy
Authors: Oguni Hirokazu , Mukahira Kyoko , Oguni Miyako , Uehara Takashi , Su Yu‐Hsien , Izumi Tatsuro , Fukuyama Yukio
Published: October 2005

Summary: We studied myoclonic seizures (MS) in 5 patients with juvenile myoclonic epilepsy (JME) using video polygraphic recordings to investigate the clinical characteristics of MS in this epileptic syndrome. The total number of MS analyzed was 302 (range 27–125, mean 60) seizures per patient. MS occurred either singly or repetitively (37 vs. 63%) and corresponded to generalized bilaterally synchronous single or multispike‐and‐wave complexes at 3–5 Hz. Video analysis of the myoclonic jerks demonstrated that either distal or proximal muscle involvement predominated. In the former, there was mild bilateral flexion and some external rotation of the forearms. In the latter, flexion of both arms at the elbow, flexion and abduction of the thighs, and extension of the back was observed. Asymmetry of MS was noted in 4 of 5 patients. Facial involvement of MS occurred infrequently in 2 patients. When the patients kept both arms outstretched, the arms dropped or there was sudden interruption of ongoing electromyographic (EMG) potentials immediately after myoclonic jerks (postmyoclonic inhibition) in all patients. One should inquire about these clinical characteristics of MS in JME when taking a thorough history in patients with primary generalized tonic‐clonic seizures (GTC).
Circling Seizures in a Case of Juvenile Myoclonic Epilepsy
Authors: Lancman Marcelo E. , Asconapé Jorge J. , Golimstok Angel
Published: October 2005

Summary: Circling seizures (CS) have been described in association with focal lesions as well as with generalized EEG discharges. We report 1 patient with juvenile myoclonic epilepsy (JME) who developed CS. There were no focal findings on clinical examination, EEG, or imaging studies. We propose that CS in this patient may represent a profound asymmetry in expression of an idiopathic generalized epilepsy rather than a partial condition.
Is HLA‐DRW 13 (W6) Associated with Juvenile Myoclonic Epilepsy in Arab Patients?
Authors: Obeid Tahir , El Rab Mohamed Osman Gad , Daif Abdul Kader , Panayiotopoulos Chrysostomos P. , Halim Kamal , Bahakim Hassan , Bamgboye Elijah
Published: October 2005

Summary: In a study of 32 unrelated Arab patients with juvenile myoclonic epilepsy (JME), we compared the frequencies of human leukocyte antigen (HLA) class I and II alleles with those of unrelated healthy controls. A significant difference between the phenotypic frequencies in JME patients and controls was observed for DRW13, the split of DRW6 (37.5 vs 11% of controls). The strength of association as measured by the relative risk was 4.85 for this antigen (p = 0.002). The possible association of JME with HLA‐DRW6 recently reported in Caucasians was confirmed in this study. This finding speaks for the homogeneity of the disease among Arabic and Caucasian JME patients. The existence of this association is evidence of a locus in the HLA region that influences expression of JME.
Subclinical Anterior Horn Cell Involvement in Juvenile Myoclonic Epilepsy
Authors: Ertekin Cumhur , Araç Nilgün , Bilgin Safiye , Ediboǧlu Hakan , Ertaş Mustafa
Published: October 2005

Summary: Although clinical signs of muscle wasting and weakness were not present, electromyographic (EMG) evidence of subclinical anterior horn cell involvement of spinal cord was noted in 5 patients with juvenile myoclonic epilepsy (JME). Quantitative interference pattern analysis of EMG recorded from the anterior tibial muscle showed that the ratio (amplitude:turn/turn:second, A:T/T:S) was significantly increased in 10 patients with JME and 12 patients with lower motor neuron disorders (LMND) as compared with those of 22 normal subjects and 15 patients with frequent generalized tonic‐clonic seizures (GTC). Subclinical anterior horn cell involvement detected by EMG techniques can be related to a genetically determined component of JME.
Vertebral Arch Nonfusion and Juvenile Myoclonic Epilepsy
Authors: Sundqvist Anders , Gustafsson Johan , Tomson Torbjörn
Published: October 2005

Summary: Neural tube defects (NTD) are known to occur at a higher rate in pregnancies of women with epilepsy. Antiepileptic drugs (AEDs), notably valproate (VPA) and carbamazepine (CBZ), have been identified as risk factors, but a familial aggregation of this condition also occurs in the absence of pharmacologic teratogens. Spina bifida occulta, defined as a nonsymptoinatic non‐fusion of vertebral arches, has been suggested to be genetically determined, with an increased prevalence in patients with primary generalized epilepsy, and that the presence of this trait in fetal development can be enhanced pharmacologically to produce NTD such as meningomyelocele. In this study, plain abdominal radiographs were obtained from 56 patients with juvenile myoclonic epilepsy (JME) and 56 ageand sex‐matched controls. The radiographs were presented in a random order to an unbiased radiologist. No difference in prevalence of vertebral arch nonfusion (VAN) was noted between the two groups. Even if it has no increased frequency in patients with epilepsy, however, VAN is a common radiologic finding, and its relation to symptomatic neural tube defects should be clarified in future studies.
Arylsulfatase A Pseudodeficiency and Lafora Bodies in a Patient with Progressive Myoclonic Epilepsy
Authors: Tinuper P. , Plazzi G. , Monari L. , Sangiorgi S. , Pellissier J.‐F. , Cerullo A. , Provini F. , Capellari S. , Baruzzi A. , Lugaresi E. , Montagna P.
Published: October 2005

Summary: Since age 12 years, a 25‐year‐old woman had a syndrome with myoclonic epilepsy, cerebellar signs, and spontaneous myoclonus. Skin biopsy showed typical Lafora bodies (LB), but she lacked a progressive course and mental impairment, hallmarks of Lafora disease. Lysosomal enzyme assays showed low level arylsulfatase A (ASA) activity. DNA study disclosed a homozygous ASA Pd genotype. Both parents carried one Pd allele. The still‐unknown relationship between the pathologic level of ASA activity and myoclonic epilepsies suggests introduction of ASA assays in patients with PME.
Use of Alternative Medicine by Patients with Epilepsy: A Survey of 265 Epileptic Patients in a Developing Country
Authors: Danesi M. A. , Adetunji J. B.
Published: October 2005

Summary: We evaluated the use of alternative treatment methods, in various forms, by epileptic patients who had used these forms of treatment before seeking hospital treatment. Among the 265 epileptic patients, 47.6% used African traditional medicine alone: 24.1% combined traditional medicine with spiritual healing, 20.4% used spiritual healing alone, and 7.5% used other forms of alternative medicine. Patients used the alternative treatments for <1 year to >5years before seeking hospital treatment, presumably when alternative medicine failed to control seizures. Relatives, friends, and neighbors had marked influence on the health‐seeking behavior of these epileptic patients: 86% of them were influenced to use alternative medicine. After initiation of hospital treatment, only 14.6% of patients who had earlier used African traditional medicine continued with such treatment; more than two thirds of the patients who had earlier used spiritual healing continued using such treatment, suggesting that many of these patients perceived some continuing benefits from these alternative treatments. This observation suggests that alternative medicine, especially spiritual healing, cannot be considered irrelevant in management of epilepsy in Africa. Further investigations are required to determine the efficacy, supportive role, and limitation of alternative medicine in management of epilepsy in developing countries.
Partially Successful Treatment of Rasmussen's Encephalitis with Zidovudine: Symptomatic Improvement Followed by Involvement of the Contralateral Hemisphere
Authors: DeToledo John C. , Smith Dennis B.
Published: October 2005

Summary: An 18‐year‐old woman with a 4‐year history of Rasmussen's encephalitis (RE) manifested by progressive aphasia, right hemiparesis, and nearly continuous intractable simple partial seizures that frequently secondarily generalized was treated with zidovudine (AZT). Seizures had not responded to any of the major antiepileptic drugs (AEDs) administered to high and toxic levels, or to ACTH. AZT was given for 62 days and discontinued because of granulocytopenia. Within 6 weeks of AZT initiation, seizure stopped and neurologic deterioration was arrested for ∼21 months. Subsequently, partial somatomotor seizures developed, affecting the previously uninvolved left hemibody. A 2‐week repeat course of AZT was attempted, but unremitting fever and gastrointestinal (GI) side effects precluded continuation of AZT treatment. Spontaneous, sustained remission of seizures has not been reported in untreated RE. Seizure control and arrest of neurologic deterioration in this case outlasted use of AZT by 19 months. Because of the apparent response of this patient to AZT, clinical studies designed to assess long‐term palliative/curative properties of antiviral agents, particularly in patients with involvement of the hemisphere dominant for language, appear warranted.
Rapid Arrest of Seizures with an Inhalation Aerosol Containing Diazepam
Authors: Xi Liu Yu , Zheng Wang Ming , Zhen Sun Mei , Xian Niao Shu
Published: October 2005

Summary: 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.
Randomized, Double‐Blind, Placebo‐Controlled, Clinical Trial of D‐α‐Tocopherol (Vitamin E) as Add‐on Therapy in Uncontrolled Epilepsy
Authors: Raju G. B. , Behari M. , Prasad K. , Ahuja G. K.
Published: October 2005

Summary: In a double‐blind, cross‐over trial, vitamin E, and placebo were compared as add‐on therapy in 43 patients with uncontrolled epilepsy. The study consisted of a 3‐month baseline period followed by two treatment phases of vitamin E or placebo with cross‐over to the second phase after 3 months. No significant side effects were noted during the study. Mean seizure frequency in the baseline period was 15.9 ± 10.5 as compared with 11.8 ± 10.9 during the placebo phase and 13.7 ± 11.1 during the vitamin E phase. No significant change in seizure frequency was observed with vitamin E as compared with placebo (p > 0.1). Similar observation was noted in subgroups with generalized seizures (n = 25), partial with secondarily generalized seizures (n = 11), or complex partial seizures (CPS) (n = 7). This study did not corroborate the earlier claims of therapeutic efficacy of vitamin E as add‐on therapy in refractory epilepsy in adults.
Vigabatrin: Clinical Evidence Supporting Rational Polytherapy in Management of Uncontrolled Seizures
Authors: de Bittencourt P. R. M. , Mazer S. , Marcourakis T. , Bigarella M. M. , Ferreira Z. S. , Mumford J. P.
Published: October 2005

Summary: Monotherapy is the policy for management of patients with epilepsy. With increasing knowledge of the biology of epilepsy and of the modes of action of antiepileptic drugs (AEDs), this concept must be reevaluated. When monotherapy fails to control seizures, subsequent treatment should be based on “rational pharmacology,” taking into consideration the mode of action of the drugs, to provide improved efficacy with maintained tolerance and ease of administration. Introduction of vigabatrin (VGB) as a new AED calls for just such a reevaluation. VGB is an enzyme‐activated irreversible inhibitor of γ‐aminobutyric acid (GABA)‐transaminase that increases brain and cerebrospinal (CSF) GABA concentrations in animals and humans. It has limited efficacy in the classic animal seizure screening tests, but in many clinical studies has halved the incidence of seizures in ∼50%of patients, especially those with partial epilepsies. We evaluated the efficacy of VGB in “socially integrated and active outpatients” as a likely subset to demonstrate any advantage of rational polytherapy. The criteria for this evaluation included the effects on seizure frequency, patient tolerability, and cognitive performance in a battery of psychometric tests. Fourteen of the 19 patients (73%) completing the study had >50% réduction in seizure frequency, and 10 of 19 (52%)had >70% réduction in seizure frequency. Tolerability appeared good; somnolence was the most frequent adverse event. Three patients complained of a worsening of their seizures, 1 with an increase in frequency and 2 with development of myoclonic jerks not previously reported. No deleterious effect of VGB on cognitive function was noted, and performance in late recognition tests showed significant improvement by the end of the maintenance period, which may have been due to the réduction in seizure frequency. The efficacy of VGB in this study in controlling seizures as compared with results of earlier published studies of refractory epilepsy may be related to selection of patients with more benign partial epilepsy, but does support the need for further studies in such patients to evaluate the hypothesis of rational polytherapy.
Impact of Valproate and Phenytoin on Cognitive Function in Elderly Patients: Results of a Single‐Blind Randomized Comparative Study
Authors: Craig Ian , Tallis Raymond
Published: October 2005

Summary: Thirty‐eight patients (median age 77 years; range 62–88 years) with elderly‐onset seizures were entered into a single‐blind, randomized study designed to compare the impact of phenytoin (PHT) and valproate (VPA) on cognitive function. A stratified minimization program matched the two groups for age, sex, and seizure type. Attention, concentration, psychomotor speed, and memory were assessed twice before treatment (to minimize practice effects), at 6 weeks and (for patients remaining in the study) at 3 months, 6 months, and 1 year by an extensive battery of psychologic tests. Changes in cognitive function were minor, and some tended toward improvement. Contrary to expectation, there was little difference between PHT and VPA with regard to impact on cognitive function. Frequent noncognitive adverse effects were reported. Thus, we did not replicate the findings of previous literature. We conclude that antiepileptic drug (AED) monotherapy as used in our trial did not produce significant adverse cognitive effects. The choice of AED in the elderly may therefore be more influenced by consideration of other adverse effects.
Reversible Valproate‐Induced Extrapyramidal Disorders
Authors: Sasso Enrico , Delsoldato Simona , Negrotti Anna , Mancia Domenico
Published: October 2005

Summary: We observed transient parkinsonism in 2 young epileptic patients with valproate (VPA) therapy. Complete recovery from extrapyramidal disorder occurred spontaneously in a few weeks. The lack of apparent susceptibility related to age and to VPA dosage, the rapid recovery from the extrapyramidal reaction, and the prevalence of negative signs such as bradykinesia and bradyphrenia can be considered the main clinical findings of this disease process. Pathophysiologic mechanisms of this rare “toxic” reaction remain unknown, although a transient imbalance between functionally reciprocal subgroups of GABA pathways leading to remediable dopa‐mine inhibition might be hypothesized.
Reflex Sympathetic Dystrophy Associated with Antiepileptic Drugs
Authors: Falasca Gerald F. , Toly Travis M. , Reginato Antonio J. , Schraeder Paul L. , O'Connor Carolyn R.
Published: October 2005

Summary: Reflex sympathetic dystrophy syndrome (RSDS) complicating antiepileptic drug (AED) therapy is not well acknowledged in the neurologic literature. We report 4 patients with reflex sympathetic dystrophy that occurred while they were receiving AEds. All patients had shoulder and hand involvement, which in 2 was bilateral, and 1 had ipsilateral foot involvement. Two patients did not respond to a change in AEDs, but all improved with a course of prednisone. One patient with phenobarbital (PB)‐associated RSDS relapsed on inadvertent rechallenge with secobarbital. A review of the literature showed that several other fibrosing disorders are associated with AED administration, including Du‐puytren's contractures, frozen shoulder, plantar and hand nodules, and Peyronie's disease. RSD associated with AEDs is important to recognize because it may result in permanent disability if treatment is delayed.
Circadian Carbamazepine Toxicity
Authors: Haefeli Walter E. , Meyer Peter G. , Lüscher Thomas F.
Published: October 2005

Summary: Owing to marked fluctuations in plasma con‐centrations, circadian CNS toxicity (maximum in the early afternoon) occurred in a 69‐year‐old female patient being treated with an instant‐release formulation of carbamazepine (CBZ). The neurologic syndrome was reversible after administration of the same daily dose as sustained‐release formulation. This case illustrates the importance of correct timing of blood sampling to detect drug‐induced toxicity and of use of sustained‐release for‐mulations in antiepileptic therapy with CBZ.
Zonisamide‐Induced Behavior Disorder in Two Children
Authors: Kimura Seiji
Published: October 2005

Summary: Zonisamide (ZNS)‐induced behavior disorders are reported in a 1‐year‐old girl and a 3‐year‐old boy. Both patients, who had no previous developmental or mental problems, displayed secondarily generalized motor seizures. Serum concentrations of ZNS were not high, 8.8 and 12.3 μg/ml(effective range 10–30 μg/ml) respectively. Although many cases of ZNS‐related psychotic reactions and/or behavior disorders have been reported, all affected patients had complex partial seizures (CPS) and had received combination therapy with phenytoin (PHT). Thus, whether the disorders were induced only by ZNS, by an interaction between ZNS and PHT, or by CPS could not be determined. In the children reported, however, ZNS clearly induced behavior disorders at plasma ZNS levels within or even below the therapeutic range.
Determination of Valproate in the Presence of Felbamate in Human Plasma by Narrow Bore Capillary Gas Chromatography
Authors: Romanyshyn L. A. , Wagner M. C. , Wichmann J. K. , Kucharczyk N. , Sofia R. D.
Published: October 2005

Summary: A narrow bore capillary gas chromatographic method with one extraction step has been developed for quantitation of valproate (VPA) in the presence of felbamate (FBM) in human plasma. The method uses 0.250‐ml aliquots of human plasma and one internal standard (IS). Chromatographic conditions include a DBWAX, 0.25 mm ID × 15 m, 0.25‐μm film thickness column; splitless injection; and flame ionization detection. The linear quantitation range for VPA is 1.00‐256 μg/ml.
Quantum Pharmacologic Studies Applicable to the Design of Anticonvulsants: Theoretical Conformational Analysis and Structure‐Activity Studies of Barbiturates
Authors: Bikker Jack Andrew , Kubanek Julia , Weaver Donald F.
Published: October 2005

Summary: We report the first large‐scale systematic quantitative structure‐activity relationship (QSAR) study of barbiturates, correlating molecular structures with anticonvulsant activity. To achieve this QSAR study, we devised a four‐step strategy. In step 1, an optimal quantum mechanical technique for determining the geometry and shape (conformation) of barbiturates was ascertained; this is the AM1 semiempirical molecular orbital method. In step 2, the AM1 method was used to optimize the structures and molecular properties of 48 barbiturates with varying anticonvulsant activity. In step 3, discriminant analysis and regression analysis statistical calculations were used to correlate the molecular properties of the 48 analogues against maximal electroshock (MES) and subcutaneous metrazol (s.c.Met)‐induced seizures. In step 4, the contribution of molecular electostatic prop‐erties to barbiturate anticonvulsant activity was further refined by quantum mechanical derived molecular electrostatic potential (MEP) maps. Using this four‐step strat‐egy, we defined the pharmacophore, the portion of a molecule responsible for bioactivity, for anti‐MES and anti‐s.c.Met activity. For anti‐s.c.Met activity, barbiturate lipophilicity and geometry are important considerations; for anti‐MES activity, barbiturate topologic and electronic properties have increased relevance.
Effect of a γ‐Aminobutyric Acid Uptake Inhibitor, NNC‐711, on Spontaneous Postsynaptic Currents in Cultured Rat Hippocampal Neurons: Implications for Antiepileptic Drug Development
Authors: Oh Dong Jin , Dichter Marc A.
Published: October 2005

Summary: The effect of a novel γ‐aminobutyric acid (GABA) uptake inhibitor, NNC‐711, on spontaneous postsynaptic currents was studied in cultured rat hippocampal neurons by the whole cell patch clamp method. NNC‐711 decreased the amplitude of inhibitory postsynaptic currents (IPSCs) and did not prolong the decay. NNC‐711 also decreased the amplitude of excitatory PSCs (EPSCs). The GABAB receptor antagonist 2‐OH saclofen abolished the effect on both IPSCs and EPSCs. NNC‐711 itself induced no current and had no effect on currents induced by exogenously applied GABA. These findings suggest that duration of GABAA‐receptor mediated IPSCs is not determined by GABA uptake and that GABA uptake inhibitors may work by allowing GABA to remain in the synaptic area long enough to activate presynaptic GABAB receptors.
Nuclear Magnetic Resonance Detection of Increased Cortical GABA in Vigabatrin‐Treated Rats In Vivo
Authors: Preece N. E. , Jackson G. D. , Houseman J. A. , Duncan J. S. , Williams S. R.
Published: October 2005

Summary: 1H Nuclear magnetic resonance ([1H]NMR) spectroscopy was used to detect elevation of γ‐aminobutyric acid (GABA) in rat brain after administration of the antiepileptic drug vigabatrin (VGB). Rats were treated for 3 weeks with VGB added to their drinking water to deliver a dose of 250 mg/kg body weight per day. NMR spectroscopy was performed noninvasively in vivo, and a GABA concentration of 6.0 ± 2.3 mmol/kg wet weight (mean ± SD, n = 5) was measured. GABA could not be detected in control animals in vivo. Postmortem GABA levels of 1.3 ± 0.5 and 4.5 ±l 1.0 mmol/kg (mean ± SD, n = 5) were measured in perchloric acid extracts of frozen brain from control and treated animals, respectively. Noninvasive measurement of increased cerebral GABA should allow detailed studies of the pharmacology of GABA‐increasing drugs in vivo. With future developments, these measurements may be feasible in human subjects.
Dose‐Response Relationships with Nimodipine Against Electroshock Seizures in Mice
Authors: Sills G. J. , Carswell A. , Brodie M. J.
Published: October 2005

Summary: The anticonvulsant effect of the dihydropyridine calcium channel blocker, nimodipine (NMD) was evaluated against electroshock‐induced seizures in mice. At 1 h postdosing, NMD elicited a dose‐dependent reduction in the occurrence of tonic hindlimb extension (THE) after maximal electroshock (MES). The calculated ED50 for NMD was 87 mg/kg. A single dose of NMD (75 mg/kg) produced a significant (p < 0.05) reduction in occurrence of THE for 12 h postdosing. NMD was detectable for 6 h, and plasma and brain drug concentrations correlated well (r= 0.677, p < 0.01) for that period. At 1 h postdose, a single dose of NMD (75 mg/kg) produced a 40% increase (p < 0.001) in the threshold for tonic seizures as determined by minimal electroshock (Min‐ES). NMD is an effective anticonvulsant against experimental seizures induced by electroshock. The pharmacodynamic effect of NMD appears to extend beyond the time anticipated from the pharmacokinetic profile.
Calcium Channel Blockers Verapamil and Nimodipine Inhibit Kindling in Adult and Immature Rats
Authors: Wurpel John N. D. , Iyer Shridhar N.
Published: October 2005

Summary: The calcium channel blockers verapamil (VPM) and nimodipine (NMD) were administered to adult or immature (16‐day‐old) rats to determine their effects on amygdala‐kindled seizures. The afterdischarge thresh‐old (ADT) kindling rate and degree of postictal refractoriness were determined for two doses of VPM (0.5 and 5.0 mg/kg in rat pups and 2 and 10 mg/kg in adult rats) or 30 mglkg nimodipine (NMD). Neither VPM nor NMD affected the ADT of the amygdala in adult or immature rats. VPM retarded the rate of kindling in both adult and immature rats in a dose‐dependent manner; the number of stimulations required to progress through seizure stages were increased. NMD 30 mg/kg reduced the kindling rate and AD duration in both adult and immature rats. Neither drug was able to suppress recurrent seizures elicited by repetitive stimulation. These results suggest that verapamil, and possibly NMD may be of clinical utility in treatment of epilepsy, especially complex partial sezures.
Outpatient Video‐EEG Monitoring in Children
Authors: Connolly Mary B. , Wong Peter K. H. , Karim Yasmin , Smith Sherry , Farrell Kevin
Published: October 2005

Summary: Video‐EEG monitoring enables correlation of behavioral activity with EEG activity, which is useful in recognition of pseudoepileptic seizures and in investigation of patients for epilepsy surgery. Because most patients are monitored for a prolonged time as in‐patients, the cost of the procedure is high. We investigated the value of brief (2–3 h) outpatient video‐EEG monitoring in 43 children with frequent seizures, most of whom had symptomatic generalized epilepsy. Indications for monitoring included differentiation of epileptic from nonepileptic behavior, seizure classification, and determination of seizure frequency. Clinical episodes were recorded in 36 of 43 children (83%). A definite diagnosis was established in 9 of the 17 patients investigated to determine the nature of the clinical behavior. Seizures were classified in 1.5 of the 25 patients investigated to determine seizure type, and classification was different from the original in 9 of the 15 children. A change in epilepsy syndrome classification was made in 9 children. The video‐EEG allowed diagnosis in 25 of the 43 children (59.5%). Video‐EEG appears to be an effective method for outpatient investigation of children with frequent seizures, particularly those with symptomatic géneralizéd epilepsy.
Complex Partial Seizures in Young Children
Authors: Bye Ann M. E. , Foo Sharon
Published: October 2005

Summary: We retrospectively analyzed the clinical manifestations of complex partial seizures (CPS) in children aged 10 years using video and EEG telemetry and evaluated their course, investigations, management, and seizure status at follow‐up. Seventeen patients with CPS were studied at the Prince of Wales Children's Hospital (POWCH) and Prince Henry Hospital (PHH) between 1987 and 1992. Because 1.5 of the 17 patients had intractable seizures, the population was selective. Mean age was 6.5 years; 4 patients were aged 2 years. Clinical features were normal or mild intellectual handicap (1 3); hemiplegia (5); and infantile spasms preceding CPS (4); of these, 2 also had simple partial motor seizures. Structural abnormalities were noted on scanning in 9 patients. Eighty‐seven seizures were reviewed. Mean duration of each clinical seizure was 59.7 s (total population), 108 s (subgroup 1, aged 2 > years), and 48.5 s (subgroup 2, aged 2 years). Major ictal manifestations were auras (9), staring (9), autonomic changes (6), and automatisms (17). In subgroup 1, automatisms were simple and mainly oroalimentary and gestural. Two patients had no change in surface ictal recordings, and 2 had normal interictal EEGs. At follow‐up, 8 patients were seizure‐free for 6 months, 1 was partially controlled (more than two seizures a month), and 8 had intractable seizures (two or more seizures a month). Seven patients underwent operation for intractable epilepsy, and 4 achieved a class 1A outcome (Engel classification).