bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Intractable Epilepsy as the Only Symptom of Primary Brain Tumor
Authors: Morris Harold H. , Estes Melinda L. , Gilmore Robin , Van Ness Paul C. , Barnett Gene H. , Turnbull John
Published: August 2005

We identified 39 patients with chronic epilepsy (seizures ≥2 years) proven to have primary brain tumors. These cases represent ∼12% of the surgery cases for epilepsy in the same period. Mean age of seizure onset was 13.2 years: mean duration before operation was 10.5 years. Thirty‐eight of 39 had normal neurologic examination. Twenty‐six tumors were temporal, 7 were frontal, 4 were parietal, and 2 were occipital. Nine of 26 (34.6%) of the temporal group had contralateral interictal EEG spikes. Pathology was 15 ganglioglioma, 13 low‐grade astrocytoma, 4 oligodendroglioma, 2 low‐grade mixed glioma, 1 pleomorphic xanthoastrocytoma, 2 dysembryoplastic neuroepithelial tumor, and 1 ependymoma. Postoperative seizure frequency (minimum follow‐up 6 months) ranged from 15 to 16 seizure‐free or auras only in patients with temporal tumors and total gross tumor removal (mean follow‐up 28 months) to 0 of 6 seizure‐free in patients with extratemporal tumors who underwent subtotal resections or biopsy.
Psychogenic Seizures in Old Age: A Case Report
Authors: Fakhoury Toufic , Abou‐Khalil Bassel , Newman Karen
Published: August 2005

Psychogenic seizures are unusual after age 60 years, A 73‐year‐old woman had onset of psychogenic seizures at age 69 years. Five to six attacks occurred each month, usually at night, characterized by an initial subjective sensation and headache followed by generalized stiffening and shaking. Continuous EEG‐closed circuit television (EEG‐CCTV) monitoring clearly showed these episodes to be nonepileptic. Discontinuation of antiepileptic drugs (AEDs) did not increase the frequency or severity of attacks. Epileptiform discharges were not recorded during the awake, drowsy, or sleeping states. Psychiatric evaluation identified significant turmoil in the patient's life and a history of childhood sexual and physical abuse. Psychogenic seizures may begin in old age and should be considered in the differential diagnosis of intractable seizures in the elderly. Predominantly nocturnal occurrence should not exclude the diagnosis.
Effect of Chronic Electrical Stimulation of the Centromedian Thalamic Nuclei on Various Intractable Seizure Patterns: I. Clinical Seizures and Paroxysmal EEG Activity
Authors: Velasco Francisco , Velasco Marcos , Velasco Ana Luisa , Jimenez Fiacro
Published: August 2005

Twenty‐three patients with various intractable seizure patterns were divided into four groups based on their most frequent seizure type and their clinical and EEG response to chronic electrical stimulation of the centromedian thalamic nuclei (ESCM): group A, generalized tonic‐clonic (GTC, n = 9); group B, partial motor (Rasmussen type) (n = 3); group C, complex partial seizures (CPS, n = 5); and group D, generalized tonic seizures (Lennox‐Gastaut type) (n = 6). CM were radiologically and electrophysiologically localized by means of stereotaxic landmarks and by thalamically induced scalp recruitinglike responses and desynchronization. ESCM consisted of daily 2‐h stimulation sessions for 3 months. Each stimulus consisted of a 1‐min train of square pulses with a 4‐min interstimulus interval, alternating right and left CM. Each pulse was 1.0 ms in duration at 60/s frequency and 8–15 V (400–1,250 μ‐A) amplitude. Voltage (V), current flow (μA) and impedance (kΩ) at the electrode tips were kept constant. A significant decrease in the number of seizures per month and paroxysmal EEG waves per 10‐s epochs occurred in group A patients between the baseline period (BL) and the ESCM period. These changes persisted for >3 months after discontinuation of ESCM (poststimulation period, Post). Post was accompanied by a significant decrease in the number of paroxysmal EEG discharges. A substantial decrease in seizures and paroxysmal discharges was also observed in patients of group B. In contrast, patients of groups C and D showed no significant changes from BL to ESCM and Post periods, except for a significant decrease in the number of seizures in group D patients from BL to Post periods.
Effects of Monotherapy and Polytherapy on the Blink Reflex in Epileptic Patients
Authors: Lancman Marcelo Elias , Cristiano Edgardo , Golimstok Angel , Granillo Rubens Jorge
Published: August 2005

We performed the blink reflex (BR) in 20 normal volunteers, 13 epileptic patients receiving antiepileptic drug (AED) monotherapy, and 13 epileptic patients receiving AED polytherapy. Comparison of R1, ipsilateral and contralateral R2 and VIIth nerve latencies in the three groups showed no statistically significant differences in R1 and VIIth nerve latencies among the three groups. There were statistically significant differences between the polytherapy group and the monotherapy and control groups in comparisons of ipsilateral and contralateral R2. There were no significant differences between the monotherapy group and the control group for ipsilateral and contralateral R2. We hypothesized that AED polytherapy might interfere with synaptic transmission in the polysynaptic pathway of the blink reflex, prolonging the latency of R2. These results provide further evidence of the pathophysiologic effects associated with polytherapy in epileptic patients.
Seizures with Clonazepam: Discontinuation and Suggestions for Safe Discontinuation Rates in Children
Authors: Sugai Kenji
Published: August 2005

Clinical characteristics of clonazepam (CZP) discontinuation seizures were clarified from 17 patients who developed seizure exacerbation after rapid discontinuation, including abrupt discontinuation, reduction, or replacement with nitrazepam (NZP). Safe discontinuation rates of CZP were estimated by comparing these patients with 23 patients without CZP discontinuation seizures. The seizures consisted of status epilepticus or frequent attacks of generalized tonic‐clonic seizures (GTC) or non‐GTC, and the first attack of GTC. Incidence did not differ significantly between CZP‐effective cases and CZP‐ineffective cases at discontinuation. The reasons for abrupt discontinuation included adverse effects, insufficient efficacy, difficulty in taking CZP owing to pneumonia, or carelessness of the doctors or the families. Seizure exacerbation occurred 1–6 days after CZP discontinuation. Most of the problems improved with readministration of the original or smaller dosages of CZP or of NZP in an amount threefold or more greater than the original CZP dose. Safe discontinuation rates were estimated to be ≤0.04 mg/kg for abrupt discontinuation, ≤0.04 mg/kg/ week for reduction, and replacement with NZP of 2.5 or more times the original amount of CZP. These safe discontinuation rates were prospectively confirmed by 84 cases of CZP discontinuation in 54 other patients, and no seizure exacerbation occurred with these discontinuation rates.
Hematologic Manifestations of Long‐Term Valproate Therapy
Authors: May Ronald B. , Sunder Theodore R.
Published: August 2005

Sixty patients receiving long‐term valproate (VPA) monotherapy were studied for hematologic side effects. All were patients in a long‐term care facility and ranged in age from 2 to 29 years (mean 14.6 years). Twenty developed at least one prominent hematologic abnormality. Thrombocytopenia and macrocytosis were the most common findings. In patients with macrocytosis, platelet counts were inversely related to VPA levels. Serum B12 levels were increased in 51 of the patients. In 12 patients with macrocytosis who were extensively studied, no etiology for the increased MCV could be identified. An increased number of Pelger‐Huet‐like cells was noted in these 12 patients. None of the patients demonstrated hepatic dysfunction. Hematologic toxicity was never severe enough to discontinue therapy and always responded to small decrements in VPA therapy. VPA was discontinued in only 1 patient, owing to poor seizure control.
Comparative Study of the Anticonvulsant Effect of γ‐Aminobutyric Acid Agonists in the Feline Kindling Model of Epilepsy
Authors: Morimoto Kiyoshi , Sanei Toshifumi , Sato Keiko
Published: August 2005

We made a comparative study of the anticon‐vulsant effect of GABA agonists on feline amygdala or hippocampal kindled seizures. Progabide (PGB) [γ‐ami‐nobutyric acid (GABA) receptor agonist 25–100 mg/kg intraperitoneally, i.p.] significantly reduced both the kindled seizure stage and after discharge (AD) duration in a dose‐dependent manner. SKF89976A (GABA uptake inhibitor 0.5–2.0 mg/kg i.p.) also significantly reduced the kindled seizure stage. Toxic doses of SKF89976A caused generalized paroxysmal EEG discharges and myoclonus, but AD generation in the kindled focus was suppressed completely. Furthermore, γ‐vinyl GABA (GABA cata‐bolic enzyme inhibitor, GVG 50–200 mg/kg i.p.) significantly reduced the seizure stage, while causing prolongation of the AD duration. In contrast, baclofen (selective GABAB receptor agonist, 1 or 5 mg/kg) did not show anticonvulsant effects on any parameters of kindled seizures. Therefore, these GABA agonists, which potentiate the inhibitory function of the GABAA systems, have potent anticonvulsant effects on partial onset and secondarily generalized limbic seizures.
Anticonvulsant Effects of Bretazenil (Ro 16‐6028) During Ontogenesis
Authors: Kubová H. , Rathouská J. , Mare P.
Published: August 2005

Anticonvulsant action of a new benzodiaze‐pine, bretazenil (Ro 16–6028), was studied in 240 rats in five age groups: age 7, 12, 18, 25 and 90 days. Motor seizures induced by metrazol (pentamethylenetetrazol, PTZ, 100 mg/kg subcutaneously (s.c.) except for 18‐day‐old rats which received a dose of 90 mg/kg) served as a model. Animals were pretreated with Ro 16–6028 in doses of 0.001–0.1 mg/kg intraperitoneally (i.p.) 10 min before metrazol. Both types of metrazol‐induced seizures, minimal (mMS, predominantly clonic with preserved righting ability) and major (MMS, generalized tonic‐clonic), were suppressed by Ro 16–6028 in a dose‐dependent manner. Major seizures were always more sensitive to Ro 16–6028 than were minimal seizures. The youngest rats exhibited maximal effects of Ro 16–6028 against major seizures. On the other hand, this drug increased the incidence of minimal seizures in 7‐ and 12‐day‐old rats, i.e., in age groups in which this type of seizure is rare under control conditions.
Effects of a Benzodiazepine, Bretazenil (Ro 16‐6028), on Rhythmic Metrazol EEG Activity: Comparison with Standard Anticonvulsants
Authors: Brabcová R. , Kubová H. , Velíšek L. , Mareš P.
Published: August 2005

A novel anticonvulsant benzodiazepine breta‐zenil (Ro 16–6028) was studied electrophysiologically in a model of human absence seizures: rhythmic metrazol activity (RMA) in rats. The effects of Ro 16–6028 pretreatment (0.01, 0.05, or 0.1 mg/kg intraperitoneally, i.p.) were compared with those of clonazepam (CZP, 0.02 or 0.1 mg/kg i.p.), valproate (VPA, 200, 300, or 400 mg/kg) and ethosuximide (ESM, 31.25, 62.5, or 125 mg/kg i.p.) in 45 rats with implanted electrocorticographic electrodes. RMA was elicited by an injection of pentylenetetrazol (metrazol, PTZ) in a dose of 40 or 35 mg/kg i.p. The effects of Ro 16–6028 were similar to those of CZP and VPA, i.e., suppression of RMA episodes, an increase in latency and a decrease in number, and total as well as mean duration. On the other hand, ESM differed from these antiepileptic drugs (AEDs) in inability to shorten the duration of RMA episodes. Based on these results, Ro 16–6028 might be predicted to be efficient against human absence seizures.
Low‐Grade Glial Neoplasms and Intractable Partial Epilepsy: Efficacy of Surgical Treatment
Authors: Britton Jeffrey W. , Cascino Gregory D. , Sharbrough Frank W. , Kelly Patrick J.
Published: August 2005

Summary: We performed a retrospective study of 51 consecutive patients who underwent operation for intractable partial epilepsy related to low‐grade intracerebral neoplasms between 1984 and 1990. All patients had medically refractory partial seizures and a mass lesion identified on neuroimaging studies. Lesionectomy was performed on 17 patients, and 34 had lesion resection and corticectomy. Mean postoperative follow‐up was 4.4 years (range 2–8 years). Sixty‐six percent of patients were seizure‐free, and 88% experienced a significant reduction in seizure frequency. In 16 patients (31%), antiepileptic drugs (AEDs) were successfully discontinued. Twenty‐five of 31 (81%) eligible patients obtained a driver's license after successful operation. Patients with complete tumor resection and no interictal epileptiform activity on postoperative EEG studies had the best operative outcome. Epilepsy surgery can result in long‐term improvement in seizure control and quality of life (QOL) in selected patients with intractable tumor‐related epilepsy. Our results should be useful to clinicians considering treatment options for patients with intractable seizures related to low‐grade intracerebral neoplasms.
Treatment of Severe Myoclonic Epilepsy in Infants with Bromide and Its Borderline Variant
Authors: Oguni Hirokazu , Hayashi Kitami , Oguni Miyako , Mukahira Akiko , Uehara Takashi , Fukuyama Yukio , Umezu Ryoji , Izumi Tatsuro , Hara Michiko
Published: August 2005

Summary: We studied the efficacy of bromides (BR) as add‐on therapy in 11 patients with severe myoclonic epilepsy in infants (SME) and in another 11 with the borderline variant of SME (BVSME). Study subjects were aged 8.5–183 months (mean 64.4 months). Longest duration of BR treatment was 37 months (range 4–37 months; mean 19.7 months). Eight of 22 (36%) of patients with generalized tonic‐clonic seizures (GTCS) had an excellent effect (>75% reduction in total seizure frequency or duration) and 9 (41%) had a moderate effect (50–75% reduction) 3 months after introduction of BR. Twelve months after initiation of BR, 5 of the patients with significant improvement were no longer responsive; ultimately, therefore, 6 had an excellent effect and 2 had a moderate effect. Of those with partial seizures (n=5) and myoclonic/absence seizures (n = 5), only 1 patient in each group showed a moderate effect at the 12‐month time‐point. Dosages and serum concentrations of BR ranged from 30 to 100 mg/kg (mean 58 mg/kg) and from 64 to 159 mg/dl (mean 101 mg/dl), respectively. Of the 12 patients experiencing side effects, including drowsiness, appetite loss, and skin rash, 1 required a reduction in BR dosage because of an extensive acneiform rash on the face. The results show that BR treatment holds promise for patients with SME and BVSME and should therefore be investigated further.
Quantitative Analysis of Seizure Frequency 1 Week and 6, 12, and 24 Months After Surgery of Epilepsy
Authors: Lüders H. , Murphy D. , Awad I. , Wyllie E. , Dinner D. S. , Morris H. H. , Rothner A. D.
Published: August 2005

Summary: We made quantitative analysis of seizure frequency 1 week and 6, 12, and 24 months after seizure surgery. Seizure recurrence was significantly higher when seizures occurred in the first postoperative week. Seizure recurrence increased progressively with longer follow‐ups, but the 6 month postoperative follow‐up period was an excellent index of long‐term outcome. In operative follow‐up studies, seizure frequency should be reported at fixed follow‐up periods, e.g., at 6 months and 1, 2, 5, and 10 years. Meaningful comparison of outcomes between different studies is possible only when reports include outcome at fixed postoperative follow‐up periods (as opposed to ranges of follow‐up periods).
Altered Responsiveness During Hyperventilation‐Induced EEG Slowing: A Non‐Epileptic Phenomenon in Normal Children
Authors: Epstein M. A. , Duchowny M. , Jayakar P. , Resnick T. J. , Alvarez L. A.
Published: August 2005

Summary: The relation between hyperventilation (HV)‐induced high‐amplitude rhythmical slowing (HIHARS) and altered responsiveness without generalized spike and wave activity has not been clearly defined. To test whether altered responsiveness is a nonspecific physiologic response rather than a symptom of generalized epilepsy, we assessed verbal recall ability and motor response testing in 12 healthy nonepileptic children (mean age 9.6 years). Both tasks were administered as a baseline before HV, during HV but before onset of EEG slowing, and during HIHARS. Verbal recall and motor responsiveness remained unchanged during baseline and HV before onset of slowing. During HIHARS, all children exhibited impaired verbal recall (p<0·005) and 8 of 12 failed to respond to repeated auditory clicks (p < 0·005). Our findings indicate that in a normal setting, responsiveness may be impaired during HV in healthy nonepileptic children.
Chronic Localized Encephalitis (Rasmussen's Syndrome) Preceded by Ipsilateral Uveitis: A Case Report
Authors: Fukuda Tokiko , Oguni Hirokazu , Yanagaki Shigeru , Fukuyama Yukio , Kogure Mitsuko , Shimizu Hiroyuki , Oda Masaya
Published: August 2005

Summary: Chronic localized encephalitis (Rasmussen's syndrome) developed in an 11‐year‐old girl 1 month after operation for residual cataract due to chronic uveitis that had appeared at age 9 years ipsilateral to the affected cerebral hemisphere. Although the pathogenesis of Rasmussen's syndrome remains unknown, our case provides additional evidence indicating that a viral ocular infection is a possible cause or part of the disorder.
Agenesis of Internal Carotid Artery Associated with Symptomatic Partial Epilepsy
Authors: Wang Pen‐Jung , Liu Hon‐Man , Young Chainllie , Lin Ming‐Yi , Shen Yu‐Zen
Published: August 2005

Summary: An 8‐year‐old Chinese girl had a first episode of symptomatic partial epilepsy at age 2 years. Despite regular treatment with antiepileptic drugs (AEDs), the seizures remitted and exacerbated. Epileptiform EEG discharges were evident, arising from the left centroparietal region. Magnetic resonance imaging (MRI) and computed tomography (CT) scan of the temporal bone and cerebral angiography demonstrated absence of the left internal carotid artery and ipsilateral bony carotid canal. Perfusion brain single photon emission CT (SPECT) with [99mTc] HMPAO showed a perfusion defect at the left posterior temporoparietal lobe. Brain ischemia due to agenesis of the left internal carotid artery (ICA) was speculated as the cause of the partial epilepsy.
Allergy to Carbamazepine: Parallel In Vivo and In Vitro Detection
Authors: Troost Roger J. J. , Van Parys Johan A. P. , Hooijkaas Herbert , van Joost Theodoor , Benner Robbert , Prens Errol P.
Published: August 2005

Summary: Purpose: Five to 20% of patients discontinue antiepileptic drug (AED) therapy because of adverse reactions. Careful reintroduction, however, may be considered if true drug allergy can be ruled out. Definitive assessment of such immunologically mediated reactions requires demonstration of either specific antibodies or sensitized lymphocytes.

Methods: We investigated whether skin patch tests (PTs) and in vitro lymphocyte proliferation assays (LPAs) were suitable for detection of allergy to carbamazepine (CBZ) and the possibly cross‐reactive oxcarbazepine (OCBZ). Data of 65 patients displaying a wide range of possibly allergic side effects to CBZ were available for analysis. Data of CBZ users without any side effects and healthy volunteers served as controls. Both PTs and LPAs were done with CBZ, OCBZ and three metabolites [CBZ‐10,11‐epoxide (CBZ‐E), 10‐monohydroxy‐CBZ (MHD), and 10,11‐dihydroxy‐CBZ (DIOL)].

Results: Positive PTs with CBZ were seen in 20% and with OCBZ in 14% of the patients. Positive LPA results with CBZ and OCBZ, respectively, were found in 40 and 19%. Both tests were positive in 14 and 7% of the patients. Cross‐reactivity to OCBZ was seen in ‐40% of CBZ‐reactive patients in both PTs and LPAs.

Conclusion: These data illustrate the additional value of LPAs in the detection of CBZ allergy while showing that a major part of side effects to CBZ and OCBZ is not immunologically mediated, according to PTs and LPAs.
Long‐Term Prognosis of Lennox‐Gastaut Syndrome
Authors: Oguni Hirokazu , Hayashi Kitami , Osawa Makiko
Published: August 2005

Summary: We investigated the long‐term prognosis of Lennox‐Gastaut syndrome (LGS) in 72 patients followed up for >10 years. Long‐term seizure and intellectual outcomes were poor, as previously reported. The diagnosis of LGS was first made in the age range from 2 to 15 years with peak occurrence at 5 years. Progressive IQ score deterioration with age was apparent. At the last examination, 33% of patients with cryptogenic and 55% with symptomatic LGS had lost the characteristics of LGS, and their seizure disorders were classifiable as symptomatic generalized epilepsies, severe epilepsy with multiple independent spike foci, or localization‐related epilepsies. Disabling drop attacks appeared in 46% of patients and tended to occur at older than 10 years. Gait deterioration was recognized in 12 patients and seemed to be due largely to, progression of the epileptic encephalopathy. The gait disturbances, as well as increased frequency of violent drop attacks, were disabling in daily life and resulted in some patients being wheelchair bound.
Evolution of Lennox‐Gastaut Syndrome: A Long‐Term Longitudinal Study
Authors: Yagi Kazuichi
Published: August 2005

Summary: In 102 patients with Lennox‐Gastaut syndrome (LGS) observed for an average of 16 years (range, 10–20 years), 12 of the patients worked normally, 36 worked part‐time or at a sheltered workshop, and most of the remaining 54 were under home care or institutionalization. LGS evolved from West syndrome or from unspecified epilepsies, or as the primary form, mostly in childhood and rarely in adolescence or adulthood. At the worst stage, there were diverse types of generalized seizures, slow spike‐and‐wave EEG complexes, fast rhythms, and multiple spike‐and‐wave complexes. Mental subnormality progressively worsened. Characteristic symptoms of LGS continued in one third of patients, and various abortive forms of LGS were seen in the other two thirds, although LGS did not evolve into a localization‐related epilepsy during the survey period. The evolution of seizure and EEG epileptic discharges suggests that LGS has a characteristic clinical course as it progresses. The persistent generalized tonic seizures of various magnitude over a long time in the vast majority of patients indicate that the brainstem rather than the cortical mantle is involved as the seat of seizure‐generating mechanisms in LGS.
Mesial Temporal Lobe Epilepsy in Childhood
Authors: Murakami Nagako , Ohno Shigeru , Oka Eiji , Tanaka Akio
Published: August 2005

Summary: To clarify the clinical picture of mesial temporal lobe epilepsy (MTLE) in childhood, we carried out a clinical, electroencephalographic, and neuroradiologic study of 19 patients. MTLE was noted in 19 (0.82%) of 2,319 epileptic patients with childhood onset. Three types of initial seizure were recognized: febrile convulsion, afebrile generalized convulsion, and complex partial seizure (CPS). As presumed causes, various prolonged convulsions (persisting for >30 min) were found in 12 (63.2%) cases. Regardless of the presence of preceding convulsions (febrile or afebrile), the clinical course was not uniform, with CPS in the early period temporarily controlled in some cases and intractable from the early period in others. Unilateral hippocampal abnormalities were confirmed on magnetic resonance imaging (MRI) before the age of 5 years in two cases, suggesting that mesial temporal sclerosis (MTS) is formed within a relatively short period in some cases. Seizures were controlled for >6 months in only two (10.5%) cases and persisted in 17. In four (21.1%) cases, surgical treatment was considered to be available.
Epilepsy in the Developing Brain: Lessons from the Laboratory and Clinic
Authors: Holmes Gregory L.
Published: August 2005

Summary: Children with epilepsy present unique challenges to the clinician. In addition to having differences in clinical and EEG phenomena, children differ from adults in regard to etiological factors, response to antiepileptic drugs (AEDs), and outcome. It is now recognized that the immature brain also differs from the mature brain in the basic mechanisms of epileptogenesis and propagation of seizures. The immature brain is more prone to seizures due to an imbalance between excitation and inhibition. γ‐Aminobutyric acid (GABA), the major CNS inhibitory neurotransmitter in the mature brain, can lead to depolarization in the hippocampal CA3 region in very young rats. There are also age‐related differences in response to GABA agonists and antagonists in the substantia nigra, a structure important in the propagation of seizures. These age‐related differences in response to GABAergic agents provide further evidence that the pathophysiology of seizures in the immature brain differs from that in the mature brain. Although prolonged seizures can cause brain damage at any age, the extent of brain damage after prolonged seizures is highly age dependent. Far less histological damage and fewer disturbances in cognition result from prolonged seizures in the immature brain than from seizures of similar duration and intensity in mature animals. However, detrimental effects of AEDs may be greater in the immature brain, than in the mature brain. These lessons from the animal laboratory raise questions about the appropriateness of current therapeutic approaches to childhood seizure disorders.
Prognosis of Epilepsy: A Review and Further Analysis of the First Nine Years of the British National General Practice Study of Epilepsy, a Prospective Population‐Based Study
Authors: Cockerell Oliver C. , Johnson Anthony L. , Sander Josemir W. A. S. , Shorvon Simon D.
Published: August 2005

Summary: Purpose: To understand the prognosis of newly diagnosed epilepsy to provide rational therapy and advice for patients and their physicians.

Methods: The National General Practice Study of Epilepsy (NGPSE) is the first large population‐based study that has assessed the prognosis of patients with newly diagnosed epilepsy prospectively over a prolonged period. We review the previously published data on the prognosis of epilepsy after 9 years of follow‐up. One thousand ninety‐one patients with newly diagnosed or suspected epilepsy who were attending 1 of 275 general practices throughout the United Kingdom between 1984 and 1987 were ascertained. Cases in this study were defined as the occurrence of one or more seizures, including provoked seizures. Prognosis in terms of remission of seizures, and mortality, was analyzed in the patients who were classified 6 months after recruitment as having definite epilepsy (n = 564) or possible/probable epilepsy (n = 228).

Results: Only 33 patients were completely lost to follow‐up. After 9 years, 86% [95% confidence interval (CI) 81, 901 of patients with definite epilepsy had achieved a remission of 3 years, and 68% (CI 61, 73, had achieved a remission of 5 years. For the complete cohort, with possible/probable epilepsy included, the rates increased to 87% (CI 83, 91) for 3‐year remission and 71% (CI 65, 77) for 5–year remission. The proportion of patients with definite epilepsy who were still in remission at 9‐year follow‐up (terminal remission) was 68% (CI 62, 74) for 3‐year remission and 54% (CI 48, 60) for 5‐year remission. When stratified by etiology, the proportions achieving 5–year remission by 9 years was 69% (CI 60, 77) for idiopathic seizures, and 61% (CI 46, 75) for remote symptomatic epilepsy. Age and seizure type had small effects on the chances of achieving remission, with children experiencing slightly lower rates than older patients, and partial seizures having lower remission rates than generalized seizures. The overall standardized mortality ratio (SMR) for patients with definite or possible/probable epilepsy was 2.5 (CI 2.1, 2.9), and 3.0 (CI 2.5, 3.7) for patients who were classified as having definite epilepsy. The SMR for patients with idiopathic epilepsy was 1.6 (CI 1.0, 2.4), for those with remote symptomatic epilepsy it was 4.3 (CI 3.3, 5.3, and for those with acute symptomatic epilepsy it was 2.9 (CI 1.7, 4.5).

Conclusions: Overall, most patients with epilepsy wiil enter remission; however, there is a higher than expected risk of death, especially in those with symptomatic epilepsy.
Effects of Sleep and Sleep Stage on Epileptic and Nonepileptic Seizures
Authors: Bazil Carl W. , Walczak Thaddeus S.
Published: August 2005

Summary: Purpose: Previous studies of patients with epilepsy and animal models of epilepsy suggest that sleep increases the frequency, duration, and secondary generalization of seizures. This information is, however, incomplete.

Methods: We retrospectively examined video‐EEG monitoring reports from our comprehensive epilepsy center. We recorded seizure type, site of onset (for partial seizures), sleep state at onset, and whether partial seizures secondarily generalized. Seizures arising from sleep were then reviewed to determine sleep state.

Results: We analyzed 1,116 seizures in 188 patients. Thirty‐five percent of complex partial seizures (CPSs) starting during sleep underwent secondary generalization compared with 18% in wakefulness (p < 0.0001). Frontal lobe CPSs secondarily generalized at equal rates during sleep (22%) and wakefulness (20%), but temporal lobe CPSs generalized much more frequently during sleep (45%) than in wakefulness (19%; p < 0,0001). Frontal lobe seizures were more likely to occur during sleep (37%) than were temporal lobe seizures (26%; p = 0.0068). CPSs were more frequent in stages 1 and 2 and occurred rarely during REM. Seizures starting during slow‐wave sleep were significantly longer than seizures starting during wakefulness or stage 2 sleep. Psychogenic nonepileptic seizures (PNESs) were rare between midnight and 6 a.m. and never occurred during sleep.

Conclusions: Sleep has a pronounced effect on secondary generalization of partial seizures, especially those of temporal lobe origin. Frontal lobe seizures occur more often during sleep than do temporal lobe seizures, and occurrence during sleep helps to distinguish PNESs from CPSs.
Colonic Absorption of Antiepileptic Agents
Authors: Stevenson Cheryl Miles , Kim JaeSun , Fleisher David
Published: August 2005

Summary: Purpose: To evaluate a canine intestinal access‐port model to study colonic absorption of drugs. The antiepileptic drugs phenytoin and gabapentin were chosen to study absorption of a lipophilic and hydrophilic compound, respectively.

Methods: Drug plasma level—time plots were generated subsequent to small intestinal and colonic drug administration of both drugs. The poorly water‐soluble phenytoin was administered in two doses to evaluate the impact of dissolution rate limits on colonic absorption. Maximal plasma concentration (Cmax) and area under the plasma level‐time curve (AUC) were used to assess the relative contribution of colonic absorption to plasma levels.

Results: Whereas colonic gabapentin AUC and Cmax were only 0.25 and 0.15 of those seen after small intestinal administration, colonic phenytoin AUC and Cmax were one half and equivalent to, respectively, those observed for small intestinal administration. Furthermore, colonic administration of a higher phenytoin dose showed secondary maxima and continued increases in drug plasma levels with time.

Conclusions: Colonic gabapentin absorption is poor compared with upper intestinal absorption, consistent with membrane transport rate limits to the absorption of this hydrophilic AED. Peak phenytoin plasma levels from colonic and small intestinal administration are comparable, indicating membrane transport does not limit absorption of this lipophilic agent. Continued plasma‐level increases from higher phenytoin doses are consistent with dissolution‐rate control of drug absorption in the colon. We suggest that colonic absorption provides a greater potential for toxicity from phenytoin overdose as a function of continued drug dissolution than for gabapentin overdose.
False Lateralization of Seizure Perceived by a Patient with Infarction of the Right Parietal Lobe Who Showed the Neglect Syndrome
Authors: Heo Kyoung , Kim Sang‐Jin , Kim Jong‐Hwan , Kim Oeung‐Kyu , Cho Hyo‐Kun
Published: August 2005

Summary: A 66–year‐old right‐handed man developed seizures characterized by an electric sensation and convulsive movements involving the left arm, which sometimes secondarily generalized. The patient, however, reported that the seizures occurred in his right arm. Neurological examination showed many features of left hemineglect, including allesthesia, secondary to acute infarction of the right parietal lobe. Although allesthetic response was not documented during the seizure, it is likely that sensory symptoms of the seizures were localized inappropriately or that he had false memory for lateralization of seizures. In this case, the neglect syndrome caused by infarction of the right parietal lobe extended to symptoms of the seizure itself.
Characterization of Phenytoin‐Resistant Kindled Rats, a New Model of Drug‐Resistant Partial Epilepsy: Comparison of Inbred Strains
Authors: Cramer Sybille , Ebert Ulrich , Löscher Wolfgang
Published: August 2005

Summary: Purpose: Previous work from our laboratory showed that amygdala‐kindled Wistar outbred rats can be selected according to the increase of afterdischarge threshold (ADT) after phenytoin application. Animals that consistently do not respond to phenytoin (PHT) with an ADT increase (non‐responders) are the first animal model of pharmacoresistant complex partial seizures. In this study, we determined the ability to respond to PHT in male kindled rats of different inbred strains.

Methods: The experiments were performed in fully kindled rats of five different inbred strains, Wistar‐Kyoto, Lewis, Fischer 344, ACI, and Brown Norway. The response type of each rat was revealed by four consecutive PHT applications (75 mg/kg, i.p.) in fully kindled rats.

Results: PHT application resulted in plasma concentrations ranging from some 16 μg/ml in Lewis rats to 35 μg/ml in Fischer 344 rats, and in slight ataxia, most strongly in Fischer 344 rats. The rats of each strain did not show a homogeneous response to PHT. A significant increase of ADT was found after 86–97% of applications in Lewis, Wistar‐Kyoto, and Fischer 344 rats. In contrast, Brown Norway rats responded in only 34% of experiments. This led to a considerable number of responders (i.e., consistent ADT increase by >20%) in Fischer 344, Wistar‐Kyoto, and Lewis rats. The only strain revealing nonresponders (i.e., consistent lack of ADT increase by >20% with PHT treatment) was Brown Norway.

Conclusions: Inbred strains, although genetically more homogenous than outbred strains, differ in their response to PHT. Brown Norway rats can offer advantages for further detailed investigation of the resistance to PHT in the kindling model of complex partial seizures.
Individual Memory Change After Anterior Temporal Lobectomy: A Base Rate Analysis Using Regression‐Based Outcome Methodology
Authors: Martin Roy C. , Sawrie Stephen M. , Roth David L. , Gilliam Frank G. , Faught Edward , Morawetz Richard B. , Kuzniecky Ruben
Published: August 2005

Summary: Purpose: To characterize patterns of base rate change on measures of verbal and visual memory after anterior temporal lobectomy (ATL) using a newly developed regression‐based outcome methodology that accounts for effects of practice and regression towards the mean, and to comment on the predictive utility of baseline memory measures on postoperative memory outcome.

Methods: Memory change was operationalized using regression‐based change norms in a group of left (n = 53) and right (n = 48) ATL patients. All patients were administered tests of episodic verbal (prose recall, list learning) and visual (figure reproduction) memory, and semantic memory before and after ATL.

Results: ATL patients displayed a wide range of memory outcome across verbal and visual memory domains. Significant performance declines were noted for 25–50% of left ATL patients on verbal semantic and episodic memory tasks, while one‐third of right ATL patients displayed significant declines in immediate and delayed episodic prose recall. Significant performance improvement was noted in an additional one‐third of right ATL patients on delayed prose recall. Base rate change was similar between the two ATL groups across immediate and delayed visual memory. Approximately one‐fourth of all patients displayed clinically meaningful losses on the visual memory task following surgery. Robust relationships between preoperative memory measures and nonstandardized change scores were attenuated or reversed using standardized memory outcome techniques.

Conclusions: Our results demonstrated substantial group variability in memory outcome for ATL patients. These results extend previous research by incorporating known effects of practice and regression to the mean when addressing meaningful neuropscyhological change following epilepsy surgery. Our findings also suggest that future neuropsychological outcome studies should take steps towards controlling for regression‐to‐the‐mean before drawing predictive conclusions.
Clonidine‐ and Methohexital‐Induced Epileptiform Discharges Detected by Magnetoencephalography (MEG) in Patients with Localization‐Related Epilepsies
Authors: Kirchberger K. , Schmitt H. , Hummel C. , Peinemann A. , Pauli E. , Kettenmann B. , Stefan H.
Published: August 2005

Summary: Purpose: During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings to localize the epileptogenic focus. To increase the number of epileptiform discharges required for MEG analysis, methohexital a short‐acting barbiturate that is known to activate epileptiform activity, was used. Additionally, we investigated the spike‐provoking properties of clonidine in comparison to methohexital.

Methods: After oral premedication with clonidine, short‐lasting anesthesia was provided by intravenously administered methohexital. The number and location of epileptiform MEG discharges were assessed after clonidine premedication and during methohexital anesthesia. Results were compared with baseline MEG recordings.

Results: Methohexital increased the frequency of focal epileptiform discharges in eight of 13 patients (one of the 14 patients did not receive methohexital after premedication with clonidine). Additionally, premedication with clonidine was found to increase focal epileptiform discharges in nine of 14 patients. When compared with baseline MEG recordings, recordings after treatment with both clonidine premedication and methohexital anesthesia showed a significant increase in the total number of epileptiform signals and the number of spikes contributing to MEG source localizations.

Conclusions: This study confirms the selective proconvulsant effects of methohexital on the epileptogenic focus as suggested previously by EEG and electrocorticogram (ECoG) investigations. Additionally, our data establish for the first time that clonidine increases epileptiform activity in patients with seizure disorders. These results indicate that clonidine is suited as an activating agent for the localization of epileptogenic foci by means of MEG. This effect of clonidine on specific epileptic activity also indicates that clonidine should be used with caution as an antihypertensive drug in patients with seizure disorders.
Chronic Stimulation of the Left Vagal Nerve in Children: Effect on Swallowing
Authors: Schallert Gloria , Foster Jeffrey , Lindquist Nancy , Murphy Jerome V.
Published: August 2005

Summary: Purpose: To learn whether stimulation of the left vagal nerve would influence swallowing.

Methods: Eight children receiving intermittent left vagal nerve stimulation (VNS) for their pharmacoresistant epilepsy underwent barium swallow studies with their generators off, on, and at maximally tolerated settings.

Results: Laryngeal penetration of barium was present in three patients without stimulation, and was caused by VNS in one other patient. Aspiration never occurred.

Conclusions: Stimulation of the left vagal nerve under conditions used to treat epilepsy does not cause aspiration.
Evidence of Enhanced Kindliig and Hippocampal Neuronal Injury in Immature Rats with Neuronal Migration Disorders
Authors: Germano Isabelle M. , Sperber Ellen F. , Ahuja Shalini , Moshé Solomon L.
Published: August 2005

Summary: Purpose: Neuronal migration disorders (NMD) are often found in patients with epilepsy. However, the mechanisms linking these two pathologies are not yet fully understood. In this study, we evaluated whether NMD increased kindling seizure susceptibility and seizure‐induced acute neuronal damage in the immature brain.

Methods: Experimental NMD were produced by exposing pregnant rats (gestation day 15) to methylazoxymethanol acetate (MAM, 25 mg/kg, ip). Seizures were induced in rat pups (postnatal day 15) transplacentally exposed to MAM and controls by hippocampal kindling. Afterdischarge (AD) threshold and duration, seizure stage, and number of stimulations required to reach each seizure stage were recorded. Acute seizure‐induced damage was histologically assessed in Nissl‐stained and silver‐impregnated hippocampal tissue 24 h after kindling.

Results: Rat pups with NMD had a significantly lower AD threshold than controls (91 ± 18 vs. 163 ± 23 μA; p < 0.05). Furthermore, rats with NMD required fewer stimulations to reach seizure stage 3.5 and 4 than did controls. Additionally, rats with NMD had longer AD the second day of stimulation (2,094 ± 416 s vs. 1,755 ± 353 s; p < 0.05). Histologic examination revealed that in rats with NMD, acute seizure‐induced neuronal hippocampal damage occurred bilaterally in CA3 hippocampal neurons.

Conclusions: The lowered AD threshold and more rapid kindling to stages 3.5 and 4 indicate that in the presence of severe NMD, hippocampal kindling is facilitated. Furthermore, this study suggests that in the immature brain, seizure‐induced hippocampal neuronal damage occurs if there is an underlying pre‐existing pathology.
Chronic Intracranial EEG Monitoring for Localizing the Epileptogenic Zone: An Electroclinical Correlation
Authors: Schiller Yitzhak , Cascino Gregory D. , Sharbrough Frank W.
Published: August 2005

Summary: Purpose: To evaluate the diagnostic yield and identify predictive factors of the surgical outcome in patients with intractable partial epilepsy undergoing chronic intracranial EEG monitoring (CIEM).

Methods: The clinical, magnetic resonance imaging (MRI) and electrophysiologic data of 108 patients that underwent CIEM were retrospectively reviewed. The discharge pattern and spatial extent of the initial ictal discharge were determined by blinded visual inspection and computerized analysis.

Results: The main predictive indicator for epilepsy surgery outcome in patients that underwent CIEM was the presurgical MRI findings. Most patients with hippocampal atrophy or complete lesionectomy were rendered seizure free after epilepsy surgery (83 and 80%, respectively), whereas only a small minority of patients with partial lesipectomy or no detected MRI lesion had seizure–free operative outcomes (21 and 22%, respectively). Multifocal independent initiation of the initial ictal discharge was associated with a poor surgical outcome. In contrast, the pattern and local spatial extent of the initial ictal discharge observed with CIEM failed to predict the surgical outcome.

Conclusions: The main predictor of the surgical outcome in patients that underwent CIEM was the MRI findings, whereas CIEM had only limited use in localizing the epileptogenic zone in the absence of an MRI lesion. The reported findings indicate a low specificity of CIEM in defining the site of seizure onset, which in turn significantly impairs the reliability of CIEM in delineating the epileptogenic zone for epilepsy surgery. Further studies are required to define the indications and patient sub–populations who can benefit from CIEM before epilepsy surgery.
Double‐Blind, Placebo‐Controlled, Lamotrigine in Treatment‐Resistant Generalised Epilepsy
Authors: Beran R. G. , Berkovic S. F. , Dunagan F. M. , Vajda F. J. E. , Danta G. , Black A. B. , Mackenzie R.
Published: August 2005

Summary: Purpose: Lamotrigine (LTG) is recognised as effective add‐on therapy for focal epilepsies, but this is the first double‐blind, placebo‐controlled, crossover study in treatmentresistant generalised epilepsy.

Methods: The study consisted of 2 × 8‐week treatment periods followed by a 4‐week washout period. Patients received doses of either 75 or 150 mg daily, depending on their concomitant antiepileptic drugs (AEDs). Long‐term continuation was offered at the end of the study with open‐label LTG.

Results: Five centres in Australia recruited 26 patients who were having absence, myoclonic, or generalized tonic‐clonic seizures or a combination of these. Twenty‐two patients completed the study. There was a significant reduction in frequency of both tonic‐clonic and absence seizure types with LTG. A 250% decrease in seizures was observed for tonic‐clonic seizures in 50% of cases and for absence seizures in 33% of evaluable cases. Rash was the only adverse effect causing discontinuation. Twenty‐three of 26 opted for open‐label LTG, with 20 still receiving LTG for a mean of 26 months. In these 20, 80% had 250% seizure reduction and five (25%) were seizure free.

Conclusions: This study shows that LTG is effective add‐on therapy in patients with refractory generalised epilepsies. Statistically significant reduction in seizures in both absence and tonic‐clonic seizure types was seen even with low doses of LTG.
Training for a New Generation
Authors: Imber‐Black Evan
Published: August 2005

Teachers … can never tell where their influence stops.

Henry Brooks Adams (1907)
Now You See It, Now You Don't: Feminist Training in Family Therapy
Authors: Goodrich Thelma Jean , Silverstein Louise Bordeaux
Published: August 2005

This article describes the state of feminist training in family therapy. Methods of assessment include questionnaires to all programs accredited by COAMFTE in universities and institutes and to leading institutes not accredited; interviews with editors of the Journal of Feminist Family Therapy; interviews with many who pioneered the feminist critique in family therapy; inspection of two major national conferences; and a search of publications. Although most program directors describe their programs as feminist and judge their training to be sufficient, their report contrasts with the perspectives of many of the journal editors and pioneers, with the small amount of training in gender issues at national conferences, and with the small number of publications. The authors offer discussion of the findings and recommendations.
The State of the Art of Training in Systemic Family Therapy in Switzerland
Authors: Welter‐Enderlin Rosmarie
Published: August 2005

This article presents a training program in systemic therapy with families and couples. Our training institute was founded by an interdisciplinary group of psychologists, psychiatrists, sociologists, and social workers in 1987 in Meilen (Zürich), Switzerland, and has from the beginning been connected to the field of family therapy in Europe and the United States. The specific organization of our institute, our training program, and the theoretical base of the training concept are highlighted. Our multidimensional treatment and training model is grounded in a variety of conceptual frameworks and inspired by the tradition of Enlightenment in European philosophy. We pay special attention to the personal and professional development of the emerging family therapist.