bluuebunny/crossref_metadata_2025 huggingface dataset:
Epileptic Syndromes in Infancy and Childhood: Recent Advances
Authors: Dulac Olivier
Published: August 2005

Summary: Epileptic syndromes are more reliable than etiology in determining prognosis and optimal treatment in infants and children. Benign neonatal and infantile convulsions are either idiopathic or dominantly inherited, the latter being genetically nonallelic. Forms of idiopathic generalized epilepsy (IGE) include absence epilepsy, benign myoclonic epilepsy of infancy, and epilepsy with generalized myoclonic atonic seizures. Forms of idiopathic partial epilepsy include benign partial epilepsy with centrotemporal spikes (BECT), benign partial epilepsy with occipital paroxysms, idiopathic partial epilepsy with affective seizures, and benign partial epilepsies with extreme somatosensory evoked potentials (SEPS). These idiopathic epilepsies appear to result from a multifactorial genetic predisposition. The diagnosis is based on strict clinical and EEG criteria. In epileptogenic encephalopathies, cognitive disorders are the main feature and are linked to so–called interictal abnormalities. Some epileptic syndromes, particularly myoclonic epilepsies, remain unclassifiable because of poor understanding of nosology or heterogeneous outcome.
Pediatric Community Care in Epilepsy
Authors: Ross Euan M.
Published: August 2005

Summary: In the United Kingdom, two simultaneous pressures are poised to have an influential role in improving services for young people with epilepsy (a) the advent of consultant community pediatricians who have a lead role in the care of handicapped young people and (b) the creation of regional centers for specialized epilepsy. Consultant‐led community pediatric services can make major contributions as part of a move toward better services for people with epilepsy.
Electrical Stimulation of the Centromedian Thalamic Nucleus in Control of Seizures: Long‐Term Studies
Authors: Velasco Francisco , Velasco Marcos , Velasco Ana Luisa , Jimenez Fiacro , Marquez Irma , Rise Mark
Published: August 2005

Summary: Five patients with chronic incapacitating seizures averaging 15–5,000/month were selected for study. All patients had more than one seizure type and had received maximal doses of antiepileptic drugs (AEDs). The centromedian thalamic nucleus (CM) was stimulated electrically through bilateral multicontact platinum electrodes stereotaxically placed in CM and connected to internalized pulse generators. Electrophysiologic confirmation of electrode position included thalamically elicited recruiting responses and EEG desynchronization recorded at the scalp. Stimulation parameters were adjusted individually in the range of 450–800‐μA intensity, 65 pps, 0.09 ms, in 1‐min trains, alternating right and left side stimulation and with 4‐min intervals delivered for 2 h/day. Quantitative evaluation included frequency of seizures/month, number of maximal interictal paroxysmal discharges, and frequency of background activities counted in selected scalp EEG samples, taken throughout the observation period (7–33 months). Significance of changes was evaluated by parametric Student's t test. Generalized tonic‐clonic seizures (GTC) decreased dramatically, almost disappearing in all cases (p < 0.001), with a significant reduction in interictal paroxysmal discharges (p < 0.01) and a tendency toward an increase in EEG back‐ground frequency. Other generalized seizures (atypical absences) decreased significantly, but there was no change in the number of complex partial seizures (CPS). CM stimulation is useful in control of GTC, but its beneficial effect on other seizure types has not been established.
Role of L‐Type Calcium Channel Modulation in Nonconvulsive Epilepsy in Rats
Authors: van Luijtelaar E. L. J. M. , Ates N. , Coenen A. M. L.
Published: August 2005

Summary:Old male Wistar rats spontaneously showing hundreds of spike‐wave discharges daily were used to investigate the role of calcium ions in nonconvulsive epilepsy. The effects of the L‐type calcium channel blocker nimodipine and the L‐type channel opener BAY K 8644 on number and duration of these spike‐wave discharges were investigated. In rats aged 84–94 weeks standard EEG electrodes were chronically implanted; animals were allowed to recover for 10 days. After a baseline registration, nimodipine 2.2, 8.8, and 35.2 mg/kg or BAY K 8644 in dosages of 0.12, 0.47, and 1.88 mg/kg was administered. A control group received the solvent. EEG recordings were made to evaluate drug effects. The highest dose of nimodipine increased the number of spike‐wave discharges, whereas BAY K 8644 reduced the number of spike‐wave discharges dose dependently. The highest dose of BAY K 8644 also induced fatal convulsions in 3 animals. Our results demonstrate that the L‐type calcium antagonist nimodipine facilitates spike‐wave discharges and that the L‐type calcium agonist BAY K 8644 protects against these discharges, in contrast to previous results suggesting that calcium channel blockers act as antiepileptic drugs (AEDs) and that calcium channel openers act as convulsants. Our results are a further example of the different pharmacologic profile of convulsive and nonconvulsive epilepsy and are also in contrast to what has been described for T‐type calcium channel modulation. We therefore propose that modulation of L‐type and T‐type calcium channels have opposite effects in nonconvulsive epilepsy.
Emanuel Swedenborg
Authors: Foote‐Smith Elizabeth , Smith Timothy J.
Published: August 2005

How is it that the name of a brilliant 18th century scientist and philosopher, many of whose exceptional achievements were often advanced for his time, is almost never mentioned in the annals of science? And how did it happen that a man very deeply dedicated to the advancement of science experienced a vision that completely altered the course of his life? We suggest, based on his extensive self‐analytical writings, that the source of his spiritual experiences was temporal lobe epilepsy (TLE) and that he is among the group of creative religious thinkers also suspected or known to have had epilepsy, from St. Paul and Mohammed to Dostoevsky, who have changed Western civilization.
Diet‐Induced Ketosis Does Not Cause Cerebral Acidosis
Authors: Al‐Mudallal Ali S. , LaManna Joseph C. , Lust W. David , Harik Sami I.
Published: August 2005

Ketosis is beneficial for seizure control, possibly through induction of cerebral acidosis. However, cerebral intracellular pH has not previously been measured in ketotic humans and the animal data are sparse. We describe a high‐fat diet, avidly consumed by rats, that induced consistent and moderate ketosis. Adult male rats were fed either the high‐fat ketogenic diet, a high‐carbohydrate diet with the same protein content as the ketogenic diet, or regular laboratory chow. Five to 6 weeks later, the rats were anesthetized, paralyzed, and injected with neutral red; their brains were frozen in situ. Intracellular pH of the cerebral cortex and cerebral glucose, lactate, ATP, phosphocreatine, and y‐aminobutyric acid (GABA) levels were measured. Rats fed the ketogenic diet had > 10–fold increase in their plasma ketones, but we noted no significant differences in cerebral pH or in cerebral metabolites and GABA levels among the three groups. Therefore, the antiepileptic effect of the ketogenic diet probably is not mediated by cerebral acidosis or changes in total cerebral GABA levels.
Pharyngeal Dysesthesia as an Aura in Temporal Lobe Epilepsy
Authors: Carmant L. , Carrazana E. , Kramer U. , Helmers S. L. , Holmes G. L. , Black P. McL. , Mikati M. A.
Published: August 2005

Summary: Purpose: Because oral, buccal, an d sometimes oral‐pharngeal manifestations in epilepsy are linked to the central‐temporal region, we studied 3 patients with childhood‐onset partial seizures that consistently began with pharynteal dysesthesias, described as either throat tingling or burning, to loicalize seizure onset.

Methods: Because of an intractable clinical course, each patient underwent invasive video‐EEG monitoring, which localized the epileptogenic zone to the mesial temporal lobe, The 3 patients underwent temporal lobe resections.

Results: All 3 patients achieved remission of the pharyngeal auras and a 90–100% reduction in the frequency of their seizures.

Conclusions: Pharyngeal dysesthesias can be the initial manifestation of complex partial seizures (CPS) of temporal lobe origin.
Self‐Reported Sexual Function and Sexual Arousability in Women with Epilepsy
Authors: Morrell Martha J. , Guldner Gregory T.
Published: August 2005

Summary: Purpose: Women with epilepsy are at risk for sexual dysfunction but the frequency and types of dysfunction have not been well characterized.

Methods: Self‐reported sexual function was evaluated in 116 women aged 18‐65 years with epilepsy and no concomitant medical or psychiatric illness, including 99 with localization‐related epilepsy (LRE) and 17 with primary generalized epilepsy (PGE). Variables evaluated included seizure frequency, age of seizure onset, and antiepileptic drug (AED) exposure. Standardized inventories assessed sexual functioning, sexual arousability and anxiety, sexual behavior, and depression.

Results: Although sexual experience was not reduced, women with PGE and LRE reported significantly less sexual arousability and women with LRE reported significantly more sexual anxiety. Women with LRE experienced significantly more dyspareunia, vaginismus, arousal insufficiency, and sexual dissatisfaction, whereas women with PGE experienced an‐orgasmia and sexual dissatisfaction. Sexual symptoms were not associated with seizure frequency, AED exposure, sexual experience, depression, or prepubertal seizure onset.

Conclusions: In contrast to subjects of previous research, the women in our study did not have a disorder of sexual desire, but more than one third experienced disorders of sexual arousal, implying a physiological deficit. Although the etiology for these arousal phase dysfunctions has not been defined, such conditions are treatable and warrant referral to a gynecologist versed in the treatment of sexual disorders.
Learning Impairment in 1–2‐Day‐Old Epileptic Chicks
Authors: Gervais‐Fagnou D. D. , Tuchek J. M.
Published: August 2005

Summary: The cause of learning impairment in children with seizure disorders is obscure, in part because of the lack of adequate animal models of learning deficiencies that can be used for study. The discriminating passive avoidance test has been used extensively to study learning behavior in chicks. In the present study, we applied the passive avoidance test to epileptic chicks to determine if learning deficiencies could be demonstrated in this epileptic model. Epileptic fowl have a hereditary form of primary generalized epilepsy characterized by tonic‐clonic seizures. The seizures occur spontaneously and can also be induced by photic stimulation. The epileptic phenotype is the result of an autosomal recessive mutation. Heterozygotes do not have seizures and were used as age‐matched controls. The discriminating passive avoidance test used in the present study was based on the observation that chicks readily peck at bright shiny beads. Once chicks taste a colored bead coated with a bitter chemical (methylanthranilate), they refuse to peck the bead on subsequent presentations. In addition, chicks can discriminate between colored beads and will continue to peck at a bead of different color than the methylanthranilate (MeA)‐coated bead. Compared to carriers, epileptic chicks demonstrated significantly less ability to discriminate between colored beads. Furthermore, this learning impairment was observed in epileptic chicks treated with phenobarbital (PB), indicating that the learning impairment in epileptic chicks is an inherent neurological problem and not a consequence of seizure activity.
Failure of Chronic Treatment with Abecarnil to Induce Contingent and Noncontingent Tolerance in Pentylenetetrazol‐Kindled Rats
Authors: Serra M. , Ghiani C. A. , Maciocco E. , Pisu M. G. , Tuligi G. , Porceddu M. L. , Biggio G.
Published: August 2005

Summary: We examined the effect of chronic treatment with abecarnil, a selective agonist at γ‐aminobutyric acidA (GABAA) receptors, on the development of tolerance to its anticonvulsant effect in pentylentetrazole (PTZ)‐kindled rats. We used two different experimental protocols to differentiate between pharmacological (non‐contingent) and contingent tolerance. In one group of animals, kindling was suspended and abecarnil (1 mg/kg intraperitoneally, i.p.) was administered three times daily for 15 days. In a second group of rats, PTZ‐kindling was continued during chronic treatment with abecarnil. Tolerance to the anticonvulsant effect of a subsequent challenge dose of abecarnil (0.5 mg/kg i.p.) did not develop in either experimental group.
Prevalence of Epilepsy in a Rural Community of Guatemala
Authors: Mendizabal Jorge E. , Salguero Luis F.
Published: August 2005

Summary: We conducted a cross‐sectional epidemiological study to assess the prevalence and patterns of epilepsy in a small rural village of Guatemala (population 2,111); 1,882 subjects (97.3%) were surveyed. By administering the World Health Organization (WHO) standard questionnaire and performing neurological examinations, we detected 16 cases of epilepsy. The crude prevalence rate for this community was 8.5 in 1,000 general population. Eleven cases were further classified as active epilepsy, giving a prevalence rate of 5.8 in 1,000 general population for this form. The most common type of seizure was generalized tonicclonic seizures (GTCS, 50%), followed by complex partial seizures (CPS, 37.5%), simple partial seizures (SPS, 6.2%) and generalized atonic seizures (6.2%). The age‐specific prevalence ratio was highest among the group aged 20–29 years, although the difference between that group and the other age groups was not statistically significant (z < 2, p > 0.05). Fourteen persons (87.5%) had sought medical care for their seizures at least once in their lifetime, 5 (31.25%) were receiving an antiepileptic drug (AED), and 9 (56.25%) had previously received treatment and 2 (12.5%) had never been treated for their illness. Phenobarbital was the most common AED prescribed; 7 persons had positive family history of epilepsy, 5 reported a history of significant head trauma, 4 had history of central nervous system disease, and 1 had a history of chronic alcohol intake.
Significance of Simple Partial Seizures in Temporal Lobe Epilepsy
Authors: Sirven Joseph I. , Sperling Michael R. , French Jacqueline A. , O'Connor Michael J.
Published: August 2005

Summary: We determined how localization of simple partial seizures (SPS) correlated with localization of complex partial seizure (CPS) in scalp/sphenoidal EEG and assessed prognosis after temporal lobe resective surgery in patients with an ictal correlate of SPS in scalp/sphenoidal EEG recordings. EEGs were recorded with the 10–20 system of electrode placement and supplemented with sphenoidal electrodes. Between 1985 and 1992, 183 patients with temporal lobe epilepsy (TLE) reported an aura (SPS) during inpatient monitoring; all were eligible for inclusion in our study. The EEGs during SPS showed ictal changes in 51 patients (28%, 117 SPS). Forty‐four patients had unilateral temporal interictal spikes (IIS), and SPS and CPS always arose from the same region. Seven patients had bitemporal interictal spikes; SPS colocalized with CPS in 4 patients (57%), SPS were contralateral to CPS in 2 patients, and 1 patient had bilateral independent CPS but unilateral SPS. SPS accompanied by EEG ictal changes conveyed a favorable prognosis in patients who underwent epilepsy surgery. Scalp/sphenoidal recorded IIS but were less reliable in identifying the location of CPS onset in patients with bitemporal spikes.
Photic‐Induced Epileptic Negative Myoclonus: A Case Report
Authors: Gambardella Antonio , Aguglia Umberto , Oliveri Rosario Luciano , Pucci Franco , Zappia Mario , Quattrone Aldo
Published: August 2005

We present the first documented case of photic‐induced epileptic negative myoclonus. A 17‐year‐old girl had experienced two generalized tonic‐clonic seizures (GTCS) while watching television. The only EEG abnormality was a photoparoxysmal response (PPR), which was sometimes accompanied by loss of postural tone in both arms. Valproate was effective in abolishing photosensitivity. Negative myoclonus should be included among the ictal phenomena accompanying PPR.
Parental Assessment of Functional Outcome After Corpus Callosotomy
Authors: Gilliam Frank , Wyllie Elaine , Kotagal Prakash , Geckler Cheri , Rusyniak George
Published: August 2005

Summary: Purpose: We wished to evaluate functional outcome and parental satisfaction after corpus callosotomy.

Methods: We studied a cohort of parents of 17 patients who had received an anterior corpus callosotomy > 7 months earlier (mean 26 months) for severe, intractable seizures. Parental satisfaction with the overall surgical results was the primary outcome measure. In addition, the parents assessed behavior changes that had been emphasized preoperatively as important aspects of their children's function, including alertness and responsiveness, falls and injuries, and special care needs. Degree of seizure reduction and extent of corpus callosum were also measured.

Results: The parents of 15 (88%) patients reported satisfaction with the surgical outcome. All parents who expressed satisfaction would recommend callosotomy to another family in a similar situation. The behavior change most closely associated with satisfaction was improved alertness and responsiveness (p < 0.03). Although 9 patients experienced > 80% reduction in targeted seizures, satisfaction was not reported at a greater rate as compared with the 6 patients with 50–80% reduction.

Conclusions: Most parents report satisfaction with the outcome of their child's corpus callosotomy, but are influenced by improvement in aspects of function and behavior in addition to seizure reduction.
Hippocampus and Epilepsy Surgery
Authors: Sano Keiji
Published: August 2005

Summary: Sclerosis of the cornu Ammonis, or Ammon's horn sclerosis (AHS), is an “often‐described, yet hitherto enigmatic phenomen,” as Spielmeyer described it in 1927. It has been detected in cases with ischemia, anoxia, or hypoglycemia and in more than half of the epileptic brains examined postmortem. Various theories about its pathogenesis have been propounded. Among them, the “Pathoklise” theory of the Vogts and the vascular theory of Spielmeyer et al. had prevailed until recently. In 1953, two articles were published to contribute to the pathogenesis of ictal automatism (a type of complex partial or temporal lobe seizure). One is the incisural sclerosis theory of Penfield et al., and the other is the AHS theory of Sano and Malamud. The former researchers described a diffuse sclerosis of the inferomesial temporal structures without, however, specifically relating it to AHS. They considered it to be the result of localized anoxia of that portion of the brain caused by incisural herniation occurring during parturition. Sano and Malamud maintained that AHS is a result of convulsions, a distinct scar adjacent to which epileptogenic foci may develop in the course of time to cause ictal automatism. The latter theory was corroborated by Sano, Falconer, and other investigators. Falconer expanded the theory to the assertion that not only ictal automatism but other types of intractable epilepsy may be due to “mesial temporal (Ammon's horn) sclerosis.” The most recent development in the pathogenesis of AHS is the excito‐toxicity theory, i.e., that AHS is caused by excessive excitation of neurons, probably by putative excitatory neurotransmitters, especially glutamate. For this theory, there is a significant body of evidence. Recent developments in glial physiology suggest that the existence of gliosis itself may actively exert a great influence on neurons so that neurons generate high‐frequency synchronous discharges as epileptogenic foci.
Ictal SPECT in Temporal and Extratemporal Epilepsy
Authors: Watanabe Eiju , Mayanagi Yoshiaki
Published: August 2005

Summary: Single photon emission computed tomography (SPECT) with HMPAO shows distinctive and rapidly changing blood flow patterns at the time of seizures. We analyzed the pattern of hyperperfusion in the early phase of epileptic seizures in 42 consecutive patients with medically intractable epilepsy. Seizures were induced by bemegride injection. Two ‘blinded’ observers identified the location of hyperperfusion. The perfusion changes in ictal SPECT provide consistent and reliable information about medial‐lateral differentiation as well as laterality of the seizure. Accordingly, SPECT with HMPAO injection during seizures is a selective method for identifying seizure foci noninvasively.
Surgical Treatment of Frontal Lobe Epilepsy
Authors: Shimizu Hiroyuki
Published: August 2005

Summary: The surgical treatment of frontal lobe epilepsy (FIE) yields far less satisfactory results than that of temporal lobe epilepsy (TLE). To cope with this problem, we have introduced several new techniques, including intraoperative electrocorticography (ECoG) with sevoflurane anesthesia, corpus callostomy for diagnosis and treatment, and multiple subpial transection (MST) for eloquent cortices and extensively disseminated epileptic areas. General anesthesia was maintained by sevoflurane during surgery, and intraoperative ECoG was repeated after each procedure. When preoperative semiology suggested involvement of the bilateral frontal lobes or ECoG detected bilaterally synchronized epileptic discharges, anterior corpus callosotomy was performed before the main surgical procedure. MST was applied to unresectable motor or speech zones. This technique was also useful for treatment of widely disseminated epileptic zones. We obtained satisfactory results in surgical treatment of FLE. At >1 year of follow‐up, >70% of the patients operated on have become seizure‐free or almost seizure‐free. Relevant combined use of ECoG, callosotomy, andor MST has proved to be very effective in achieving satisfactory surgical results for treatment of FLE, especially when preoperative magnetic resonance imaging (MRI) does not detect any structural lesions.
Cost‐Effectiveness of Anterotemporal Lobectomy in Medically Intractable Complex Partial Epilepsy
Authors: Langfitt John T.
Published: August 2005

Summary: Purpose: The value of high‐cost health technologies is being increasingly scrutinized by providers of health care. An understanding of the costs and outcomes of high‐technology epilepsy care is required to ensure efficient resource allocation.

Methods: Decision analysis was used to estimate the cost effectiveness of anterotemporal lobectomy (ATL) as compared with standard medical management in medically‐intractable epilepsy. Local (Rochester, NY, U.S.A.) cost data were applied to a model of lifetime discounted costs and outcomes of evaluation, ATL, and follow‐up in a hypothetical cohort of patients.

Results: Base case analysis yielded a marginal cost‐effectiveness ratio (MECR) of $15,58/quality‐adjusted life year (QALY). Extensive sensitivity analyses identified extreme conditions in which evaluation for ATL was dominant (more effective and less costly) or in which it might be considered not worth the cost (MCER >$50,00O/QALY).

Conclusions: Estimates of ATL cost effectiveness fall within a generally acceptable range, even when uncertainty about many model parameters is taken into account. Under assumptions based on available data in the literature, the cost effectiveness of ATL compares favorably with that of other health technologies. Prospective multicenter studies of regional cost and practice variations; long‐term probabilities of year‐to‐year transitions between seizure outcome states and their effects on quality of life (QOL), and the effect of nonsurgical treatments on seizure control and QOL are needed to provide the critical data to confirm and constrain these estimates.
Clinical and Electroencephalographic Correlates in Rasmussen's Encephalitis
Authors: Andrews P. Ian , McNamara James O. , Lewis Danell V.
Published: August 2005

Summary: Purpose: Rasmussen's encephalitis (RE) is a progressive childhood disease characterized by unilateral brain dysfunction, seizures, and inflammatory histopathology. Converging lines of evidence suggest that an autoimmune process is important in the pathogenesis of RE.

Methods: Two patients with pathologically confirmed RE and increased levels of circulating glutamate receptor subunit (GluR3) antibodies were studied prospectively before, during, and after trials of plasmapheresis (PEX) and other immunomodulation. Frequency, duration, and intensity of clinical seizures were directly correlated with the abundance of interictal epileptiform activity on serial EEGs.

Results: Serial EEGs in these patients suggest that early in the course of RE interictal epileptiform activity is localized to the affected hemisphere and that disease progression is associated with increasingly frequent bilaterally synchronous and contralateral epileptiform activity.

Conclusions: The clinical and EEG parameters of epileptogenesis were transiently diminished by PEX, which suggests that circulating factors induce dose‐dependent, reversible epileptogenic effects in some patients with RE.
Benign Focal Epileptiform Discharges in Children After Severe Head Trauma: Prognostic Value and Clinical Course
Authors: Wohlrab Gabriele , Schmitt B. , Boltshauser E.
Published: August 2005

Summary: Purpose: To assess the occurrence and prognosis of benign focal epileptiform discharges (BFED) in EEG after severe head trauma (SHT) in children.

Methods: Between January 1987 and December 1994, 47 of 828 children with anamnestic SHT showed a single or dominant epileptic focus in EEG. Spike wave localization and morphology were either suggestive for BFED (group I, 21 children) or were suspected to be symptomatic (group II, 26 children). We analyzed the course of epilepsy and epileptic discharges in EEG, neuroradiologic findings, neurologic outcome, and school adjustment.

Results: After SHT, spike waves appeared immediately (within 72 h) or delayed (maximum 7 years) and disappeared between ages 3 and 14 years in 14 children of group I and between ages 8 and 23 years in 10 of group II. Children with persistent spike waves in group I were all younger than 14 years; in group II, seven were older than 15 years. Computed tomographic (CT) lesions, ipsilateral to the epileptic focus, were seen in 10 children of group I and 15 of group II. Early seizures occurred in nine children of group I and eight of group II and late‐onset seizures in one of group I and nine of group II (p = 0.028). Epilepsy developed in three children of group I and 12 of group II and was drug refractory in six children of group II, all with persistent epileptic foci. Regular schools were attended by 14 (67%) children in group I and 12 (48%) of group II.

Conclusions: Benign focal epileptiform discharges in post‐traumatic EEGs have the same favorable prognosis as in benign focal epilepsy and should be handled as recommended for classic benign focal epilepsy.
Topiramate Monotherapy for Partial Onset Seizures
Authors: Sachdeo Rajesh C. , Reife Ross A. , Lim Pilar , Pledger Gordon
Published: August 2005

Summary: Purpose: Evaluation of topiramate (TPM) as monotherapy in patients with uncontrolled partial onset seizures.

Methods: A total of 48 patients were evaluated in a doubleblind, parallel‐group trial. During a 56‐day baseline period, patients had at least eight partial onset seizures while being treated with one or two standard antiepileptic drugs (AEDs). After 1–2 weeks of open‐label treatment with TPM 100 mg/day, patients were randomly assigned, in equal proportions, to receive double‐blind therapy with TPM 100 or 1,000 mg/day in a 5‐week conversion and an 11‐week monotherapy period. The study endpoint was completion of 112 study days (success) or fulfillment of one or more exit criteria: doubling of average 28‐ day or highest 2‐day baseline seizure rate, a generalized tonic‐clonic seizure (GTCS) if none had occurred at baseline, or significant prolongation of generalized seizure duration.

Results: Time until exit was longer (p = 0.002) and success frequency was higher (p = 0.005) with TPM 1,000 as compared with 100 mg/day. Seizure‐rate reductions of 50, 75, or 100% were achieved by 46, 25, and 13% of the 1,000‐mg/day group, respectively, as compared with 13, 8, and 0% of the 100‐mg/day group, respectively. Most adverse events (AE) were mild or moderate in severity.

Conclusions: Monotherapy with TPM 1,000 mg/day for partial onset seizures with or without secondarily generalized seizures was effective, with a favorable safety profile.
Involvement of Proprioceptive Feedback in Brainstem‐Triggered Convulsions
Authors: Maton Bruno , Vergnes Marguerites , Hirsch Edouard , Marescaux Christian
Published: August 2005

Summary: Purpose: In rodents, specific motor components of generalized convulsive seizures depend on two distinct anatomic substrates: (a) forebrain networks are responsible for facial and forelimb clonus with or without rearing and falling; and (b) brainstem networks are responsible for running‐bouncing fits and tonic convulsions. To investigate the requirement of proprioceptive inputs in the generation of these two different types of seizures, we compared the effects of neuromuscular blockade by D‐tubocurarine on the EEG expression of brainstem and forebrain‐triggered seizures.

Methods: Unilateral electrical stimulations were applied for 50 consecutive days in freely moving male adult rats through a bipolar electrode aimed at the dorsal hippocampus (n = S), the occipital cortex (n = 4), the inferior colliculus (n = 6), or the midbrain reticular formation (n = 6). Two days after the last stimulation, rats were paralyzed with d‐tubocurarine and stimulated in the same way.

Results: In brainstem structures, the first electrical stimulation induced tonic seizures concomitant with low‐voltage cortical activity; repetition of daily stimulations progressively induced tonic‐clonic seizures associated with high‐amplitude cortical spike‐wave discharges. After immobilization by d‐tubocurarine, brainstem stimulations failed to induce any EEG paroxysm. In forebrain structures, repeated electrical stimulations produced a classic kindling with progressive occurrence of clonic seizures associated with large cortical discharges; d‐tubocurarine left unchanged the EEG pattern of these latter seizures.

Conclusions: These data suggest that proprioceptive reafferentation resulting from movement is necessary for the generation of self‐sustained brainstem seizures but is not implicated in the elaboration of forebrain seizures.
Abnormal Cortical Activation During Planning of Voluntary Movement in Patients with Epilepsy with Focal Motor Seizures: Event‐Related Desynchronization Study of Electroencephalographic mu Rhythm
Authors: Derambure P. , Bourriez J. L. , Defebvre L. , Cassim F. , Josien E. , Duhamel A. , Destée A. , Guieu J. D.
Published: August 2005

Summary: Purpose: The spatiotemporal distribution of EEG mu rhythm desynchronization was analyzed in patients with partial epilepsy to determine whether frequent focal motor seizures could induce a change of cortical activation during the planning of a voluntary movement.

Methods: The event‐related desynchronization (ERD) of the mu rhythm was quantified during a self‐paced voluntary movement of the thumb. The results were compared betyeen two groups of patients with epilepsy: in one group (n = 12), the patients had frontal lobe epilepsy with frequent focal motor seizures (FMS); in the second group (n = 12), they had temporal lobe epilepsy (TLE) with complex partial seizures but no ictal movement disorder. The results were also compared with those of control subjects of same age (n = 10).

Results: In the control group, desynchronization of murhythm began over the contralateral central region 2,000 ms before the movement onset. In the FMS group, the desynchronization of mu rhythm was delayed, appearing only 500 ms before the movement onset, and the amplitude of ERD was increased over the frontocentral region. In the TLE group, the spatiotemporal pattern of ERD was the same as in normal subjects, but the amplitude of ERD was increased.

Conclusions: These results indicate that there is a change of reactivity of mu rhythm in patients with partial epilepsy. The change in spatiotemporal pattern of ERD in patients with frequent focal motor seizures suggests that there is an abnormal cortical activation during the planning of a voluntary movement.
Magnetic Source Imaging of Abnormal Low‐Frequency Magnetic Activity in Presurgical Evaluations of Epilepsy
Authors: Gallen C. C. , Tecoma E. , Iragui V. , Sobel D. F. , Schwartz B. J. , Bloom F. E.
Published: August 2005

Summary: Purpose: Regional cortical dysfunction associated with epileptogenic activity was predicted from interic‐tal localized abnormal low frequency neuromagnetic activity (ALFMA) using Magnetic Source Imaging (MSI). ALFMA can be detected in patients who show no interictal spikes.

Methods: A large array biomagnetometer was used in a blinded, rapid screening protocol. The MSI procedure required no alteration in epileptic medications. MSI results were compared with the presumed epileptogenic region as determined by a consensus of standard techniques, which included MR and electroclinical monitoring.

Results: One or more sites of localized abnormality were detected by MSI ALFMA in 29 of the 33 epileptic patients. ALFMA mapped with MSI showed a 48.5% specificity with respect to the presumed epileptogenic region. MSI ALFMA was in agreement with the final consensus as often as was ictal noninvasive video EEG monitoring, and was exceeded in specificity overall only by invasive ictal video EEG monitoring, which was required for conventional localization in 21 of the 33 patients tested with MSI.

Conclusions: ALFMA measurements with MSI may augment the array of noninvasive methods used for reaching a consensus for epilepsy surgery.
Is Partial Epilepsy Progressive? Ten‐Year Follow‐Up of EEG and Neuropsychological Changes in Adults with Partial Seizures
Authors: Holmes Mark D. , Dodrill Carl B. , Wilkus Robert J. , Ojemann Linda M. , Ojemann George A.
Published: August 2005

Summary: Purpose: This study was undertaken to determine what changes, if any, occur in the electroencephalogram (EEG) and in neuropsychological test findings of adults with medically intractable complex partial epilepsy over a 10‐year period.

Methods: We studied 35 adults, with a mean age of 32 years (range, 16–59 years) at time of initial testing. We compared the distribution of epileptiform patterns documented on the initial pair of waking and sleeping EEGs to those observed on another pair obtained 10 years later. During this same 10‐year period, we also examined changes in the Wechsler Adult Intelligence Scale (WAIS) and on the tests from the Neuropsychological Battery for Epilepsy.

Results: The EEGs of 28 (80%) of patients at the tenth year were identical to those seen initially. Five (14%) of patients demonstrated EEGs after 10 years with either no discharges or only unilateral discharges, where bilateral discharges were seen a decade earlier. Only two (6%) of patients had EEGs at the tenth year that showed bilateral discharges where only unilateral discharges were seen originally. We found no general change in intelligence or neuropsychological functioning after 10 years, although a few subtle losses were noted on several neuropsychological measures.

Conclusions: For most adults with medically intractable complex partial epilepsy, the EEG and neuropsychological test scores remain reasonably stable over a decade.
Conversion to High Dose Gabapentin Monotherapy in Patients with Medically Refractory Partial Epilepsy
Authors: Beydoun A. , Fakhoury T. , Nasreddine W. , Abou‐Khalil B.
Published: August 2005

Summary: Purpose: To evaluate the safety and efficacy of high dose gabapentin (GBP) monotherapy (3,0004,800 mg/ day) in patients with medically refractory partial epilepsy.

Methods: GBP monotherapy at daily doses up to 4,800 mg was attempted in patients participating in the open‐label phase of a double‐blind, dose‐controlled, GBP monotherapy trial. For those who achieved monotherapy, the types and severity of adverse events were assessed and the average seizure frequency per 28 days while maintained on the highest daily GBP dose was compared to the seizure frequency during the baseline phase of the double blind trial. Correlation analysis between GBP serum level, total daily dose, and percentage of seizure change from baseline was performed.

Results: A total of 45 patients participated in the open‐label phase of the trial and 23 (51%) were converted successfully to GBP monotherapy. In those patients, the average daily gabapentin dose was 3,900 mg and the mean length of follow‐up was 252 days. Compared to baseline, there was a mean reduction of 54%, 43%, and 14% for simple partial, complex partial and secondarily generalized seizures respectively, while maintained on high‐dose GBP monotherapy. A significant linear correlation between daily GBP dosage (2,4004,800 mg) and resultant mean serum levels was found (r = 0.51; p < 0.01). There was no significant correlation between seizure frequency and total daily GBP dose or with serum levels. High‐dose GBP monotherapy was well tolerated; only one patient exited the trial because of adverse events. The most common adverse event was tiredness/sleepiness and was not dose‐related.

Conclusions: GBP monotherapy is well tolerated in daily doses of up to 4,800 mg and is effective in a subgroup of patients with medically refractory partial epilepsy.
Rapid Switchover to Carbamazepine Using Pharmacokinetic Parameters
Authors: Kanner Andres M. , Bourgeois Blaise F. D. , Hasegawa Hisanori , Hutson Paul
Published: August 2005

Summary: Purpose: The standard practice of switching patients to carbamazepine (CBZ) involves initiating a low dose and raising it by small increments until the desired dose is reached, to avoid intolerable adverse effects (AE). In a pilot study, a protocol using single‐dose kinetic studies was developed to switch patients to CBZ through rapid‐dose increments and to manage concurrent rapid taper of the previous antiepileptic drugs (AEDs) without causing AE. The purpose of this prospective study was (a) to reassess whether a rapid switchover to CBZ could be done with minimal or no AE and without causing an increase in seizures; (b) to determine whether the maintenance dose of CBZ predicted at the time of the singledose kinetic study can yield the desired concentration at steady state (Css); and (c) to determine the degree to which the calculated maintenance dose of CBZ will need to be adjusted after the previous AED has been discontinued for a four‐week period.

Methods: Twenty‐five patients taking phenytoin (PHT) and/ or phenobarbital (PB) andor primidone (PRM) underwent a rapid switchover to CBZ following a 10 mg/kg single‐dose kinetic study (day 1) which allowed calculation of a maintenance dose necessary to yield a mean Css of 10.2 (±2.2) mgA. On day 2, patients received a CBZ dose equivalent to 10 mgkg + 200 mg; thereafter, they underwent daily dose increments of 200 mg until the calculated maintenance dose was reached. Dose increments were modified in the case of AE. Concurrent tapering of the previous AED was started as of day 1: PHT by 100 mg/day, while PB and PRM were stopped on day 1: PB was restarted before patients were to be discharged from the hospital if a PB serum concentration above 10 mgA was identified at that time. Pharmacokinetic data and occurrence of AE were compared between the two groups at the time of the single‐dose kinetic study, at the completion of the switchover to CBZ, and 4 weeks after discontinuation of the previous AED.

Results: All patients completed the switchover to CBZ within a mean time period of 6 days (±2), reaching a mean maintenance dose of 1, 639 mg/day (±370) which yielded a mean CSS of 11.3 (±3.2) mg/l. The maintenance dose had to be lowered by 20.4% (±8.3) in 59% of patients within the four‐week period following discontinuation of at least one of the previous AEDs. None of the patients experienced an increase in seizure frequency relative to baseline. Fifteen (60%) patients had no AE; five (20%) experienced AE of mild severity. AE rated as moderately severe (n = 4) or severe (n = 1) occurred in patients with a static encephalopathy (p = 0.02, Fisher's exact test) and among patients 2–55 years (p = 0.017, Fisher's exact test).

Conclusions: A rapid switch‐over to CBZ from PHT, PB, or PRM can be carried out safely with no, or minimal, AE in young adults, unless they suffer from static encephalopathy.
Intracranial EEG Seizure‐Offset Termination Patterns: Relation to Outcome of Epilepsy Surgery in Temporal Lobe Epilepsy
Authors: Brekelmans Geert J. F. , Velis Demetrios N. , van Veelen Cees W. M. , van Rijen Peter C. , Lopes da Silva Fernando H. , van Emde Boas Walter
Published: August 2005

Summary: Purpose: Studies using stereo‐EEG (SEEG) and electrocorticography (ECoG) should not only identify a patient's epileptogenic zone, but also should provide prognostic information for surgical outcome. In this respect, seizure‐offset patterns have so far been the subject of only one study, in which they were shown to be associated with poor outcome when recorded over cortical areas outside the temporal lobe of seizure onset. To clarify whether seizure‐offset patterns are reliable in predicting seizure outcome, we studied SEEG/ECoG in a similar group of patients with temporal lobe epilepsy (TLE).

Methods: SEEGECoG records of 44 patients with refractory TLE were analyzed. The areas of seizure termination were classified as ipsilateral or contralateral (mesial and/or lateral) temporal, (temporal and) frontal, and diffusehilateral. Patients were classified with respect to seizure outcome as either seizure‐free (UCLA class la) or not seizure free (UCLA class 2–4); both groups were correlated with specific seizure‐offset categories using Fisher's exact probability test and analysis of variance (ANOVA).

Results: Of the 44 patients, the majority (n = 36) had at least part of their seizure offsets in the ipsilateral temporal lobe, whereas 8 patients manifested no seizure offsets in this lobe. Only 9 patients (20%) showed exclusive offsets in the ipsilateral temporal lobe. No statistically significant difference was evident between patients with all seizure offsets in the ipsilateral temporal lobe and those with offsets elsewhere. Similarly, no statistically significant difference was evident between patients with a diffuse seizure offset and those with seizure offsets of a different category.

Conclusions: Seizure‐offset patterns in SEEGECoG are unreliable in predicting seizure outcome after resective activity surgery for TLE.
Brain Distortions in Patients with Primarily Generalized Tonic‐Clonic Seizures
Authors: Savic Ivanka , Seitz Rudiger J. , Pauli Stefan
Published: August 2005

Summary: Purpose: A precondition for the diagnosis of primarily generalized epilepsy with tonic‐clonic seizures (GTCS) is absence of brain pathology. This definition, based on normal findings on computed tomography (CT) and magnetic resonance imaging (MRI) is challenged however, by observation of microscopic migrational disturbances in patients with GTCS. In the present study, we examined whether hitherto undiscovered gross manifestations of the reported migrational disturbances may be detected by analysis of CT and MRI scans with a computerized anatomic brain atlas.

Methods: The atlas program permitted group comparisons of size, intrinsic proportion, and shape of the brain. Healthy men (n = 20), patients with partial seizures (n = 8), secondarily generalized partial seizures (n = 8), and patients with GTCS (n = 10) were studied. The contours of the brain of the computerized atlas were first transformed and adjusted to the contours, central structures, and ventricles of each subject's MRI scans. During this process, the specific parameters for the shape, size, and proportion of the brain were determined, resulting in a set of values for each subject. These values were then applied for comparisons between the four investigated groups.

Results: In relation to the controls, patients with GTCS had brains significantly flattened in the craniocaudal direction (p = 0.002), with a disproportionally small caudal part. The anterior portion of their brain was also, relatively elongated as compared with the posterior portion (p = 0.04). Similar systematic abnormalities were not observed in patients with partial epilepsy.

Conclusions: The observed deformations are compatible with previously reported findings of Purkinje cell degeneration and frontal lobe microdysgenesis in GTCS. The study suggests a new approach to identify effects of morphologic abnormalities in the brain when results of conventional structural neuroimaging are normal.
Regional Distribution of Interictal 31P Metabolic Changes in Patients with Temporal Lobe Epilepsy
Authors: van der Grond Jeroen , Gerson Jack R. , Laxer Kenneth D. , Hugg James W. , Matson Gerald B. , Weiner Michael W.
Published: August 2005

Summary: Purpose: We compared the 31P metabolites in different brain regions of patients with temporal lobe epilepsy (TLE) with those from controls.

Methods: Ten control subjects and 11 patients with TLE were investigated with magnetic resonance imaging (MRI) and [31P]MR spectroscopic imaging (MRSI). [31P]MR spectra were selected from a variety of brain regions inside and outside the temporal lobe.

Results: There were no asymmetries of inorganic phosphate (Pi), pH, or phosphomonoesters (PME) between regions in the left and right hemispheres of controls. In patients with TLE, Pi and pH were higher and PME was lower throughout the entire ipsilateral temporal lobe as compared with the contralateral side and there were no significant asymmetries outside the temporal lobe. The degree of ipsilateral/contralateral asymmetry for all three metabolites was substantially greater for the temporal lobe than for the frontal, occipital, and parietal lobes, and these asymmetries provided additional data for seizure localization. As compared with levels in controls, Pi and pH were increased and PME were decreased on the ipsilateral side in patients with TLE. There were changes in Pi, pH, and PME on the contralateral side in persons with epilepsy as compared with controls, contrary to changes on the ipsilateral side.

Conclusions: Our findings provide some insight into the metabolic changes that occur in TLE and may prove useful adjuncts for seizure focus lateralization or localization.