bluuebunny/crossref_metadata_2025 huggingface dataset:
What is the Significance of Subjective Events Recorded During Long‐Term EEG Video Monitoring?
Authors: Holmes Mark D. , Dodrill Carl B.
Published: August 2005

Summary: Purpose: Purely subjective events, identified as “seizures” by patients but not accompanied by any clinical or EEG changes, commonly occur during evaluation of patients for intractable epilepsy. We wished to determine the significance of such events.

Methods: We analyzed the frequency of subjective episodes in 379 adults who underwent EEG video monitoring as part of their evaluation for intractable epilepsy and the relationship of these experiences to epileptic and psychogenic nonepileptic (NES) seizures. We examined the results of tests of mental ability and of emotional, psychosocial, and quality of life (QOL) adjustment to determine if individuals with subjective events alone could be distinguished from those with epileptic seizures only, NES only, or no events, by these measures.

Results: We noted subjective events in 39% (147 of 379) of the patients. Of patients with subjective episodes, 52% also had epileptic seizures, 7% had NES, 1% had both epileptic seizures and NES, and 40% had subjective events alone. As a group, patients with subjective events alone were slightly more intelligent and less impaired neuropsychologically than people in the other groups, hut they performed more poorly on several important measures of adjustment.

Conclusions: The identification of persons with purely subjective episodes apart from all other episodes is important both phenomenologically and from a practical viewpoint.
Adverse Effects of Vigabatrin in Angelman Syndrome
Authors: Kuenzle Ch. , Steinlin Maja , Wohlrab Gabriele , Boltshauser E. , Schmitt B.
Published: August 2005

Summary: New antiepileptic drugs designed for enhancing GABAergic inhibition, such as vigabatrin (VGB) may be effective in Angelman syndrome (AS), because associated convulsions could be related to a reduced GABA‐receptor density or receptor abnormality. From our preliminary experiences in four children with AS treated with VGB, we conclude that it may induce and increase seizures in patients with AS.
Ictal Behaviors During Nonepileptic Seizures Differ in Patients with Temporal Lobe Interictal Epileptiform EEG Activity and Patients Without Interictal Epileptiform EEG Abnormalities
Authors: Henry Thomas R. , Drury Ivo
Published: August 2005

Summary: Purpose: Ictal behaviors during psychogenic non‐epileptic seizures (NES) vary considerably among individuals, and can closely resemble common semiologies of epileptic seizures (ES). We tested the hypothesis that behaviors during NES in patients who have temporal spikes would more closely resemble behaviors during ES in patients with temporal lobe epilepsy than would behaviors during NES in patients who do not have EEG spikes.

Methods: We identified 20 patients who had interictal temporal EEG spikes and EEG‐video recorded NES (Study Group), 133 patients with temporal EEG spikes and recorded ES, without NES (Epileptic Group), and 24 patients with recorded NES and no epileptiform EEG abnormalities, without ES (Nonepileptic Group).

Results: The hypothesis was supported with regard to ictal motor behaviors. Motionless staring or complex automatisms occurred mainly during NES in the Study Group and during ES in the Epileptic Group. In contrast, convulsive movements or flaccid falls were most common during NES in the Nonepileptic Group. Duration of unresponsiveness was longer, and there were fewer postictal states in NES both in the Study and Non‐epileptic Groups. Unresponsiveness was briefer and postictal states were more consistent in ES in the Epileptic Group, however.

Conclusions: Stereotyped motor activities during NES presumably represent learned behaviors. Processes underlying acquisition of ictal behaviors of NES probably differ in patients with interictal epileptiform EEG abnormalities compared to those without. Prior experiences and temporal lobe dysfunctions that are associated with epilepsy, and psychological characteristics that are unrelated to interictal epileptic dysfunctions, may determine ictal behaviors during NES.
Ganglioglioma and Intractable Epilepsy: Clinical and Neurophysiologic Features and Predictors of Outcome After Surgery
Authors: Morris H. H. , Matkovic Z. , Estes M. L. , Prayson Y. A. , Comair Y. G. , Turnbull J. , Najm I. , Kotagal P. , Wyllie E.
Published: August 2005

Summary: Purpose: To review the clinical, neurophysiologic, and radiological data of patients with ganglioglioma who had undergone evaluation and surgery in our Epilepsy Program.

Methods: The medical and neurophysiologic records of 38 patients with intractable epilepsy and ganglioglioma were re‐ viewed. Data underwent statistical analysis.

Results: There were 28 temporal and 10 extratemporal resections, with a mean age at seizure onset of 10.5 years and mean age at surgery of 22 years. Five tumor resections performed earlier were recorded. Twenty‐nine patients had auras and 20 had secondarily generalized seizures. All 28 patients with temporal tumor had complex partial seizures. Preoperative MRI demonstrated the tumor in 36 of 36 patients: 17 of 29 demonstrated gadolinium enhancement, and 17 of 36 had mass effect. Scalp interictal sharp waves were present in 32 patients, and in 15 they were multiregional. In two patients, scalp EEG seizure onset was from the hemisphere contralateral to the tumor. Postoperatively, 79% of patients (30 of 38) were seizure‐free (Engel's class I) at 6 months, 72% at 1 year (26 of 36), and 63% at 2 years (20 of 32). Excellent outcome was associated with a lower age at operation (p = 0.008), shorter duration of epilepsy (p = <0.01), absence of generalized seizures (p = <0.01), and no epileptiform discharges on a postoperative EEG (p = 0.01).

Conclusions: Good surgical outcome is expected in patients with ganglioglioma despite years of medically resistant seizures. Good outcome may be achieved despite EEG findings that may conflict with tumor location, and is more likely when surgery is performed relatively soon after epilepsy onset.
Developmental Background and Outcome in Patients with Nonepileptic Versus Epileptic Seizures: A Controlled Study
Authors: Berkhoff Magdalena , Briellmann Regula S. , Radanov Bogdan P. , Donati Filippo , Hess Christian W.
Published: August 2005

Summary: Purpose: This study was designed to evaluate the relevance of developmental emotional stress factors, which are considered to influence emotional functioning, as contributing factors in the development of psychogenic symptoms.

Methods: Ten patients with nonepileptic seizures (non‐ESs)(frequently referred to as psychogenic seizures), in whom diagnosis had been confirmed by a placebo‐infusion test (PT), and 10 control patients with complex partial seizures (ESs) were evaluated with regard to developmental background by using structured in‐depth interviews performed by a single interviewer blinded to the diagnosis. In addition, outcome assessment in the non‐ES group after PT was done.

Results: There were no significant differences between groups in developmental psychosocial stress or in any single developmental stress factor. Six months after PT, the outcome was favorable in patients with non‐ES: six were seizure free, and two had a considerable reduction in frequency of seizures.

Conclusions: Our research indicates the following: (a) a high incidence of developmental stress factors and functional disturbances may be found in patients with non‐ESs and ESs; (b) assessment of developmental emotional stress and functional disturbances as a basis for validating the diagonsis of non‐ES should be treated with caution; (c) use of PT followed by supportive information about the nonepileptic origin of the attacks may have a positive therapeutic effect or help to introduce psychotherapeutic treatment.
Evaluating Health‐Related Quality of Life Outcomes in Clinical Trials of Antiepileptic Drug Therapy
Authors: Leidy Nancy Kline , Rentz Anne M. , Grace Eileen M.
Published: August 2005

Summary: Purpose: To provide an overview of condition‐specific health‐related quality of life (HRQL) assessment in clinical trials of antiepileptic drug (AED) therapy in adults. We describe the key measurement issues in HRQL evaluation, identify the instruments that have been used in this population, summarize the psychometric characteristics of these instruments, propose areas of HRQL most likely to change with treatment, and offer recommendations for further research.

Methods: We conducted a comprehensive review of the literature using repeated searches of the MEDLINE database together with a review of reference lists from published papers. Psychometric information on the instruments was gathered from published literature.

Results: Three epilepsy‐specific HRQL measures were identified: the Epilepsy‐Surgery Inventory (ESI‐55), the Liverpool Assessment Battery, and the Quality of Life in Epilepsy Inventory (QOLIE, the 89‐, 31‐, and 10‐item versions). One new measure, the Epilepsy Foundation of America (EFA) Concerns Index was also found. The psychometric characteristics of these instruments are discussed in relationship to performance or expected performance in a clinical trial setting. A review of descriptive studies and trials to date suggests that subscales reflecting the psychological and social domains of HRQL may be most sensitive to treatment designed to increase seizure‐free periods, reduce seizure severity, and minimize undesirable side effects.

Conclusions: Although evaluation of HRQL outcomes in clinical trials of epilepsy is still in its infancy, several reliable and valid condition‐specific measures are available for understanding the impact of disease and treatment on HRQL. Further research is needed to determine minimal clinically important change scores and to assess the psychometric stability of measures across cultures and mode of administration (self, interview, telephone). Studies of patient p for health outcomes in the form of utilities will provide needed data for evaluating the cost‐effectiveness of new treatments.
Aspiration: A Potential Complication to Vagus Nerve Stimulation
Authors: Lundgren Johan , Ekberg Olle , Olsson Rolf
Published: August 2005

Summary: Purpose: Vagus nerve stimulation (VNS) is reported to reduce the frequency of seizures in children and adults without causing serious side effects. However, clinical observation of swallowing difficulties in 2 children treated with VNS made further investigation necessary.

Methods: Seven patients aged 4–18 years and treated with VNS for 6–14 months were investigated with videoradiography during barium swallow. The children performed 5–30 barium swallow investigations with the VNS device turned off, running as programmed, or set at continuous stimulations. The degree of aspiration was scored from 0 to 3.

Results: In 5 of 7 children, of whom reported transient swallowing difficulties, no change in the degree of aspiration was noted. The 2 children with swallowing difficulties, however, showed increased aspiration score when the stimulator was set at continuous stimulations. In 1 the score also appeared to increase with the VNS running as programmed (p > O.05). Both children had severe mental and motor disabilities.

Conclusions: Before and during VNS treatment patients should be evaluated with regard to swallowing problems. There needs to be an easy way to turn the device on and off to avoid aspirations, a hazardous and potentially life‐threatening complication of VNS.
Ictal Patterns of Neocortical Seizures Monitored with Intracranial Electrodes: Correlation with Surgical Outcome
Authors: Kutsy Roman L. , Farrell Donald F. , Ojemann George A.
Published: August 2005

Summary: Purpose: Numerous factors have been analyzed in attempts to predict the outcome of surgical resections in patients with neocortical epilepsy. We examined the correlation between surgical outcome and electrocorticographic features of neocortical ictal patterns.

Methods: Twenty six patients with neocortical epilepsy underwent monitoring with subdural grid electrodes before surgery. Ictal patterns were analyzed retrospectively and correlated with three types of outcome: seizure free, worthwhile improvement (>75% reduction of seizure frequency), and no worthwhile improvement. The duration of follow‐up was 2–5 years.

Results: Ictal patterns were divided according to the size of epileptogenic zone (focal, regional, multifocal); velocity and type of seizure propagation (fast contiguous, slow contiguous, noncontiguous); pattern of the onset of ictal activity; part of the cortex involved in the origin of the seizure (frontal, frontocentroparietal, etc.). Spread to medial temporal structures (as assessed by subtemporal strips) also was evaluated in selected cases. Statistically significant correlation with surgical outcome (p = 0.026) was shown for only one variable: type of spread. Patients with slow spread (n = 8) demonstrated the best outcomes (five are seizure free), whereas patients with noncontiguous spread (n = 5) demonstrated the worst outcomes (four did not improve significantly). Patients with fast contiguous spread (n = 13) showed intermediate outcomes.

Conclusions: Types of propagation of ictal neocortical activity correlate with surgical outcome. Analysis of ictal pattern during intracranial recordings may help to predict surgical outcome for neocortical epilepsy.
Periictal SPECT Localization Verified by Simultaneous Intracranial EEG
Authors: Spanaki Marianna V. , Zubal I. George , MacMullan John , Spencer Susan S.
Published: August 2005

Summary: Purpose: We investigated whether blood‐flow changes measured by ictal or immediate postictal single photon emission computed tomography (SPECT) reflect with accuracy the actual location of ictal discharge as measured by simultaneous intracranial EEG. In addition, we evaluated the reliability of ictal SPECT obtained with implanted electrodes by comparing results with those of ictal SPECT performed during scalp EEG monitoring in selected patients.

Methods: Eleven patients with intractable partial epilepsy who had both ictal and interictal SPECT scans during invasive EEG monitoring were studied. We analyzed perfusion differences based on registration, normalization, and subtraction of perüctal and interictal SPECT images. SPECT results were interpreted in relation to location and evolution of ictal EEG change, as reflected by simultaneous intracranial EEG. In five patients, we also compared ictal SPECT results that were obtained during both scalp and intracranial EEG monitoring.

Results: In 10 of 11 patients, localized increases or decreases in blood flow or both were identified in regions of ongoing or prior seizure discharge, respectively, at the time of SPECT brain perfusion. In one patient, SPECT localization could not be verified by the available electrode array.

Conclusions: Localization of ictal discharge during or before SPECT injection accurately determines increase or decrease in perfusion, respectively, and both are of equal validity in reflecting the region of epileptic discharge. SPECT perfusion changes can be reliably obtained during intracranial monitoring.
Once‐Daily Versus Twice‐Daily Vigabatrin: Is There a Difference? The Results of a Double‐Blind Pilot Study
Authors: Zahner B. , Stefan H. , Blankenhorn V. , Krämer G. , Richens A. , Thümler R. , Mumford J. P.
Published: August 2005

Summary: Purpose: Vigabatrin (VGB) has been approved in Europe and is prescribed for either once or twice‐daily administration. This choice has been based on the pharmacodynamic activity of VGB. The purpose of this study was to compare the efficacy and tolerability of these two different medication regimens.

Methods: The study design was a double‐blind randomized two‐period cross‐over study in adults who had responded to add‐on VGB for previously uncontrolled seizures. Each study period consisted of three months. Patients were maintained on the same daily dose of VGB to which they had demonstrated a clinical response. In addition to the primary efficacy criteria of seizure frequency on the two treatment regimens, this study included blinded ratings of overall efficacy and “well being” by both physician and patient. The primary tolerability criterion was the reported incidence of adverse events by phase.

Results: Fifty patients were initially entered into the study, and 13 patients withdrew before completion, only one reported as due to an adverse event. There was no statistical difference in seizure frequency or the tolerability of the medication. Blinded physician and patient rating scales for seizure control, and patient well being showed a nonstatistical trend toward once‐daily administration as compared with twice‐daily administration.

Conclusions: This clinical study provides support for the pharmacological evidence that this preparation may be administered on a once or twice daily basis, depending on the individual patient's preference, total dosage and co‐medication.
Lamotrigine Associated with Insomnia
Authors: Sadler Mark
Published: August 2005

Summary: Purpose: To review the incidence of lamotrigine (LTG)‐associated insomnia in an adult tertiary care epilepsy outpatient clinic.

Methods: The records of all patients who had received LTG were reviewed to identify patients who had experienced insomnia after introduction of this drug. Patients were included if they had experienced a sleep disturbance of sufficient severity to require a discontinuation of LTG or a dose reduction.

Results: Among 109 patients exposed to LTG, seven (6.4%) had a sleep disturbance of a severity to required a change in therapy. The descriptions of the sleep disturbance were similar among the patients, and the LTG‐induced insomnia appeared to be dose dependent. Unlike the few previous descriptions of LTG‐induced insomnia in the literature, no factors predisposing to this adverse effect were identified.

Conclusions: The results of this retrospective review suggest an association between LTG and intolerable insomnia in a small proportion of patients. Physicians should inquire about sleep disturbances in patients treated with LTG.
Depression in Temporal Lobe Epilepsy Before Epilepsy Surgery
Authors: Kohler Christian , Norstrand Julie A. , Baltuch Gordon , O'Connor Michael J. , Gur Raquel E. , French Jacqueline A. , Sperling Michael R.
Published: August 2005

Summary: Purpose: This study examined the association of depression with laterality of epilepsy surgery in patients with temporal lobe epilepsy before standard lobectomy.

Methods: Forty‐nine patients presented for EEG telemetry for localization of epilepsy and eventual temporal lobectomy. Patients underwent routine neuropsychiatric evaluation blinded for epileptic focus, including ratings on depression. Patients were grouped according to right (n = 25, M = 10/F = 15) and left (n = 24, M = 13/F = 11) temporal lobectomy. Analysis of variance included side of surgery as grouping variable and sex, general depressive, cognitive depressive, and vegetative depressive symptoms as dependent variables. χ2 Analyses included categoric variables of sex, handedness, education, neuropathologic findings, and current affective disorders. t Tests were performed on variables of age, epilepsy duration, and cognitive function.

Results: Right and left temporal epilepsy groups did not differ with regard to sex, handedness, age, duration of epilepsy, education, cognitive function, and neuropathology. Patients with right temporal epilepsy rated higher on general, cognitive, and vegetative depression scores. Women scored higher on general, cognitive, and vegetative depression scores. Current affective disorders were more common in the right temporal epilepsy group.

Conclusions: Depression ratings and diagnoses were more prominent in patients with right temporal lobe epilepsy and in women in particular. The strength of this laterality finding lies in the selection of patients, as all underwent epilepsy surgery. The finding on gender difference partly reflects the higher incidence of depression in women and needs further exploration. The laterality finding contrasts with recent findings in epilepsy, stroke, and trauma that associate depression with left hemispheric lesions. However, our results are consistent with findings in electrically hyperactive lesions such as gelastic and dacrystic epilepsy.
An Angiographically Occult Arteriovenous Malformation in the Medial Parietal Lobe Presenting as Seizures of Medial Temporal Lobe Origin
Authors: Fujii Masami , Akimura Tatsuo , Ozaki Satoshi , Kato Shoichi , Ito Haruhide , Neshige Ryuji
Published: August 2005

Summary: We present an unusual case of a patient who was diagnosed with temporal lobe epilepsy and whose seizures were reduced markedly after excision of an angiographically occult arteriovenous malformation (AVM) located in the left medial parietal lobe. A 38‐year‐old man had complex partial seizures characterized by motionless staring with oroalimentary and behavioral automatisms since the age of 15 years. Magnetic resonance imaging (MRI) demonstrated a small lesion extending from the left posterior cingulate gyrus to the precuneus. There was no MRI evidence of mesial temporal sclerosis. Intracranial EEG recordings showed ictal onset from the left medial parietal lobe propagating to the medial temporal lobes. Clinical signs appeared when these discharges reached the temporal lobes. After excision of the lesion (which was histologically confirmed as an AVM), together with the marginal cortex, seizures were reduced significantly. Careful diagnostic evaluation of lesions such as the this one may reveal an epileptogenic lesion (zone) far from the region where scalp ictal discharges seem to arise. In our case, we hypothesize that false localization was due to propagation of ictal discharges from the parietal focus through the limbic system.
Hippocampal Cell Density and Subcortical Metabolism in Temporal Lobe Epilepsy
Authors: Dlugos Dennis J. , Jagg Jurg , O'Connor William M. , Ding Xin‐Sheng , Reivich Martin , O'Connor Michael J. , Sperling Michael R.
Published: August 2005

Summary: Purpose: Correlations between hippocampal cell density and subcortical metabolism in patients with temporal lobe epilepsy (TLE) were studied to explore possible links between subcortical function and the regulation of hippocampal excitability.

Methods: Resected hippocampal cell densities were correlated with cortical and subcortical regional cerebral metabolic rate for glucose (CMRglu), as measured by [18F]‐fluorodeoxyglucose positron emission tomography (18‐FDGPET), in 39 patients with intractable TLE who underwent anterior temporal lobectomy (ATL). CMRglu was measured ipsilateral and contralateral to the resected temporal lobe. Linear regression techniques were used for statistical analysis.

Results: Hilar cell densities correlated positively and significantly with CMRglu in the bilateral thalamus, putamen and globus pallidus, and the ipsilateral caudate. Dentate granule cell densities correlated positively and significantly with CMRglu in the bilateral thalamus and putamen. There was no significant correlation between cell densities and CMRglu in any cortical region, including the hippocampus.

Conclusions: We postulate that hippocampal cell loss results in decreased efferent synaptic activity to the thalamus and basal ganglia, causing decreased neuronal activity in these structures with consequent hypometabolism. This synaptic activity has a significant bilateral component. Subcortical hypometabolism in patients with TLE may reinforce the epileptogenic potential of mesial temporal lobe discharges.
Evaluation of Functional Changes in the Medial Temporal Region During Intracarotid Amobarbital Procedure by Use of SPECT
Authors: Kim Byung Gon , Lee Sang Kun , woo Nam Hyun , chun Song Ho , Lee Dong Soo
Published: August 2005

Summary: Purpose: Because the main blood supply to the medial temporal region is through the posterior cerebral artery, the validity of the intracarotid amobarbital procedure (IAP) is still debated. To verify clinical validity of the IAP, we investigated changes in neuronal function in the medial temporal region during IAP.

Methods: Brain single photon emission computed tomography (SPECT) was performed during IAP (IAP‐SPECT) in 22 patients with temporal lobe epilepsy (TLE), and regional cerebral blood flow (rCBF) in the medial and lateral temporal regions of interest (ROIs) was measured quantitatively. To determine the distribution of sodium amobarbital, in another 20 patients with TLE, SPECT images were obtained after intracarotid injection of 99mTc‐HMPAO mixed with sodium amobarbital.

Results: Mean rCBF was 89.2% in the medial temporal region and 81.6% in the lateral temporal region; in the former region, it was significantly lower than that shown by the results of interictal SPECT (99.1%; p < 0.001). In a few patients, however, rCBF did not decrease in the medial temporal region. In only 25% of patients, the medial temporal region was visualized in SPECT images obtained after intracarotid injection of 99mTc‐HMPAO.

Conclusions: The results in this study demonstrate that IAP is valid because the medial temporal region is inactivated in spite of infrequent delivery of sodium amobarbital. We assume that intratemporal diaschisis is operating for the inactivation of neuronal function. IAP‐SPECT with intratemporal ROIs may be useful for monitoring changes in neuronal function in the medial temporal region during IAP.
Criterion‐Based Validity of an Intracarotid Amobarbital Recognition‐Memory Protocol
Authors: McGlone J. , Black S. E. , Evans J. , Parkin A. , Sadler M. , Sita A. , Squires E. , Stuss D. , Wilson B. A.
Published: August 2005

Summary: Purpose: We tested whether the behavioral components of an Intracarotid Amobarbital Protocol (IAP) had criterion validity. It was hypothesized that a recognition‐memory test designed for intracarotid injections and used to predict the risk of global amnesia before an elective temporal lobectomy should also identify persons who are severely amnesic due to other neurologic causes. Divergent validity predicts that speech tasks would be unaffected by amnesia. Test‐retest reliability also was measured.

Methods: Fifteen persons with severe amnesia were administered four alternate forms of a yes/no recognition‐memory protocol and a speech protocol. No drug injection occurred. Standardized neuropsychological tests were used to divide the amnesic group into those with Global Amnesia (i.e., retain no ongoing memories), Severe Amnesia (i.e., memory impaired), and Amnesia Plus (severe amnesia plus other neuropsychologic deficits).

Results: Two persons with Global Amnesia obtained scores at or below chance (i.e., failed) on the memory protocol. Unexpectedly, 12 of 13 severely amnesic persons obtained near‐perfect memory scores. Amnesia had no impact on the speech protocol. Pass/Fail outcomes were highly correlated across all four sets.

Conclusions: A four‐item IAP memory protocol showed good reliability and criterion validity in identifying the rare condition of Global Amnesia, but it was insensitive to other disabling, severe amnesic disorders. This IAP memory protocol might have validity in predicting a postsurgical Global Amnesic disorder, but it did not identify and therefore could not predict other more common severe amnesic disorders.
A Comprehensive Profile of Clinical, Psychiatric, and Psychosocial Characteristics of Patients with Psychogenic Nonepileptic Seizures
Authors: Ettinger Alan B. , Devinsky Orrin , Weisbrot Deborah M. , Ramakrishna Ravindra K. , Goyal Amit
Published: August 2005

Summary: Purpose: To attain a comprehensive profile of clinical, psychiatric and psychosocial characteristics of patients with psychogenic nonepileptic seizures (NESs), and to assess the relation of these factors to NES outcome.

Methods: We administered a telephone‐based structured questionnaire to 56 patients with NESs (16 male and 40 female patients; mean age, 35 years) at a mean follow‐up time of 18 months after making the diagnosis of NES.

Results: Mean age of NES onset was 28 years with a mean duration of 8 years. Episodes resolved in 29 (51.8%) cases, decreased in 24 (42.9%), persisted unchanged in two (3.6%), and increased in frequency in one (1.8%). Thirty (53.6%) patients, including 13 (44.8%) of patients whose NESs resolved, were rehospitalized for NESs or for other symptoms. Twenty‐nine (51.8%) had significant depressive symptoms, 22 (39.3%) had suicidal ideation, and 11 (19.6%) attempted suicide [including 6 (21%) of the patients whose NESs resolved]. Believing the NES diagnosis was associated with resolution or improvement of NES frequency (p < 0.029), whereas anger in response to receiving the diagnosis did not predict a poorer outcome. Patients' perceptions of having good health (p < 0.02) and good occupational functioning (p < 0.04) were highly correlated with NES resolution. Only patients whose episodes resolved were employed at the time of follow‐up.

Conclusions: At a mean of 1.5 years, NES outcome was poor, with resolution in only half the group and with frequent rehospitalizations after NES diagnosis, even among patients whose NES resolved. Depressive symptoms, suicidal ideation, and suicide attempts were common. Believing the NES diagnosis and patient perceptions of having good health and good occupational functioning correlated well with NES resolution.
Vigabatrin
Authors: French Jacqueline A.
Published: August 2005

Vigabatrin (VGB) is a structural analogue of the inhibitory neurotransmitter γ‐amino butyric acid (GABA), which produces its antiepileptic effect by irreversibly inhibiting the degradative enzyme GABA‐transaminase. This produces an increase in central nervous system (CNS) GABA levels. VGB is among the few antiepileptic drugs (AEDs) that was synthesized with a specific targeted mechanism in mind and was subsequently demonstrated to function by that mechanism. Tiagabine, a GABA reuptake blocker, is the only other “designer drug” among the currently available AEDs. Therefore, VGB is among the few AEDs for which the mechanism of action is well understood. Recently, safety issues have been raised with regard to the use of vigabatrin. This article reviews the mechanism of action, pharmacokinetics, safety, and efficacy of VGB.
Evidence‐based Medicine and Antiepileptic Drugs
Authors: Privitera Michael D.
Published: August 2005

Evidence based health care uses systematic literature reviews with statistical strategies like meta‐analysis to aid decision‐making. This information can help clinicians by organizing data and providing up‐to‐date quantitative summaries of efficacy and adverse effects of treatments. Limitations of meta‐analysis include problems inherent in combining data from trials of somewhat different design, choice of appropriate dosages, and summarizing complex questions as a single odds ratios. I summarize the results of a meta‐analysis of the following antiepileptic treatments for partial seizures in adults: gabapentin, lamotrigine, topiramate, tiagabine, valproate and the vagal nerve stimulator. Each treatment was significantly more efficacious than placebo, and there were nonsignificant trends toward differences among the treatments in efficacy and tolerability. Quantitative analysis of adverse effects is presented. Absent the availability of a comprehensive randomized controlled trial for comparison, a rigorously conducted meta‐analysis provides some useful information.
Nonepileptic Uses of Gabapentin
Authors: Magnus Leslie
Published: August 2005

For decades, antiepileptic drugs (AEDs) have been used to treat a variety of nonepileptic conditions such as chronic pain, psychiatric disorders, and movement disorders. As indicated by recent published reports, gabapentin, a relatively new AED, is useful for treating a wide range of neurologic and psychiatric conditions. Although its exact mechanism of action has yet to be determined, gabapentin is likely to have multiple effects. Unlike conventional AEDs used to treat non‐epileptic disorders (e.g., carbamazepine, phenytoin, valproate) gabapentin offers the advantages of low toxicity and a favorable side‐effect profile. The largest area of nonepileptic use of gabapentin is neuropathic pain, in which it has demonstrated efficacy in treatment of postherpetic neuralgia, diabetic neuropathy, and trigeminal neuralgia. It has also been reported effective as therapy for several psychiatric disorders, most notably bipolar disorder. In addition, review of the published literature reveals the usefulness of gabapentin in movement disorders, migraine prophylaxis, and cocaine dependence. Future clinical studies will provide further insight into the range of conditions for which gabapentin is effective.
Characteristics of a Unique Visual Field Defect Attributed to Vigabatrin
Authors: Wild J. M. , Martinez C. , Reinshagen G. , Harding G. F. A.
Published: August 2005

Summary: Purpose: Vigabatrin (VGB) therapy is associated with a loss of peripheral vision. The characteristics and prevalence of VGB‐attributed visual field loss (V‐AVFL) and associated risk factors were evaluated in patients with epilepsy.

Methods: The material comprised the visual fields and case notes of 88 patients with suspected V‐AVFL (25 spontaneous reports and 63 cases from an open‐label extension trial) and of 42 patients receiving alternative antiepileptic drugs (AEDs) from a cross‐sectional study.

Results: Forty‐two reliable cases of visual field loss could not be assigned to an alternative known cause and were therefore attributed to VGB (13 spontaneous reports and 29 from the open‐label study). All cases except one were asymptomatic. Seven cases of field loss were present in the reference cohort of 42 patients; all cases could be attributed to a known aetiology. Thirty‐six of the 42 confirmed cases of V‐AVFL exhibited a bilateral defect that was most profound nasally, and three, a concentric constriction. The prevalence of V‐AVFL was 29% (95% confidence interval, 21–39%). Male gender was associated with a 2.1‐fold increased relative risk of V‐AVFL (95% confidence interval, 1.20–4.6%). Age, body weight, duration of epilepsy, and daily dose of VGB, and concomitant AEDs did not predict the occurrence of V‐AVFL.

Conclusions: The unique visual field defect attributed to VGB is profound in terms of the frequency of occurrence and the location and severity of loss. The asymptomatic nature of the field loss indicates that V‐AVFL can be elicited only by visual field examination.
Occurrence of Hippocampal Sclerosis: Is One Hemisphere or Gender More Vulnerable?
Authors: Briellmann Regula S. , Jackson Graeme D. , Mitchell L. Anne , Fitt Greg J. , Kim Sung E. , Berkovic Samuel F.
Published: August 2005

Summary: Purpose: We analyzed a large group of patients investigated for suspected seizures to test whether gender or side are important factors in the origins of hippocampal sclerosis (HS).

Methods: We studied 996 consecutive patients (48% men, 52% women) by using standard hippocampal T2‐relaxometry methods.

Results: HS was associated with a highly abnormal T2 time (113 ms). Categoric analysis showed that hippocampal T2 time was independent of gender and side. T2 time was bilaterally normal in 81% of men and in 79% of women; it was unilaterally abnormal in 15% of both men and women; and bilaterally abnormal in 4% of men and in 6% of women. Highly abnormal T2 relaxometry, suggesting HS, occurred with equal frequency in men and women and on the right and left sides. Quantitative analysis of hippocampal T2 times showed values not differing significantly between men and women or between the right and left hemispheres. There was no significant interaction between gender and side.

Conclusions: In patients with seizure disorders, hippocampal T2 relaxometry is not different in adult men and women and in the right and left hemispheres.
NMDA‐Receptor Activity Visualized with (S)‐[N‐Methyl‐11C]Ketamine and Positron Emission Tomography in Patients with Medial Temporal Lobe Epilepsy
Authors: Kumlien Eva , Hartvig Per , Valind Sven , Øye Ivar , Tedroff Joakim , Långström Bengt
Published: August 2005

Summary: Purpose: To determine whether neurochemical activation of the N‐methyl‐D‐aspartate (NMDA) receptor‐gated ion channel shows quantitative changes, measured as binding of 11C‐labeled (S)‐[N‐methyl]ketamine, in patients with medial temporal lobe epilepsy (MTLE).

Methods: Eight patients with MTLE who were evaluated regarding epilepsy surgery underwent positron emission tomography (PET) with (S)‐[N‐methyl‐11C]ketamine. The presurgical investigations included magnetic resonance imaging (MR1), PET with 18F‐fluoro‐deoxyglucose (18FDG), and seizure monitoring by using video‐EEG. The uptake of (S)‐[N‐methyl‐11C]ketamine in the temporal lobe of ictal onset was compared with the contralateral side and correlated to changes in regional glucose metabolism measured by PET with 18FDG.

Results: (S)‐[N‐methyl‐11C]ketamine rapidly reached the brain, and high radioactivities were measured in the striatum, thalamic nuclei, and cortical regions. Overall the brain uptake and regional binding potentials of (S)‐[N‐methyl‐11C]ketamine were similar to measurements observed previously in healthy controls. However, 20 min after administration, when blood flow influence was negligible, a side‐to‐side comparison revealed a 9–34% reduction of tracer radioactivity in the temporal lobes of ictal onset. At earlier times, the differences in binding potentials were less pronounced, 9–21%. The magnitude and distribution of the reduction were similar to the metabolic pattern seen on PET scans with 18FDG.

Conclusions: Radioactivity uptake of intravenously administered (S)‐[N‐methy]‐11C]ketamine was reduced in temporal lobes of ictal in patients with TLE. This may reflect reduced NMDA‐receptor density, reduced perfusion, focal atrophy, or other factors.
Age‐Specific N‐Methyl‐D‐Aspartate—Induced Seizures: Perspectives for the West Syndrome Model
Authors: Kábová Radka , Liptáková Soña , Šlamberová Romana , Pometlová Marie , Velíšek Libor
Published: August 2005

Summary: Purpose: With intraperitoneal N‐methyl‐D‐aspartate (NMDA; 15–200 mg/kg) administration, we attempted to develop an animal model of age‐specific West syndrome to serve for testing of putative anticonvulsant drugs and to determine the mechanisms of this disorder.

Methods: Experiments were performed in 12‐, 18‐, and 60‐day‐old (adult) rats. The effects of systemic pretreatment with hydrocortisone (5–25 mg/kg), pyridoxine (20–250 mg/kg), and sodium valproate (VPA; 200 and 400 mg/kg) against the NMDA‐induced automatisms, emprosthotonic (hyperflexion), and clonic‐tonic seizures were determined. NMDA‐induced EEG changes and alterations of the performance in horizontal bar, rotorod, open field, and elevated plus‐maze tests were recorded.

Results: In young rats, hydrocortisone had proconvulsant effects. High doses of pyridoxine induced epileptiform activity independent of and distinct from that induced by NMDA. Only VPA had moderate effects against the NMDA‐induced syndrome. EEG consisted of periods of suppression mixed with ictal activity of serrated waves and high‐voltage chaotic EEG activity. In adult rats, EEG alterations involved spike and spike‐and‐wave activity. NMDA also deteriorated performance of young rats in the open field, rotorod, and elevated plus maze tests.

Conclusions: NMDA syndrome in rats fulfills some, but not all, criteria of the West syndrome model, such as occurrence of flexion seizures, nonspecific diffuse EEG changes, refractoriness to antiepileptic therapy (but a response to VPA), as well as long‐term alteration of behavioral tasks. However, NMDA‐induced seizures represent an acute model without the occurrence of spontaneous seizures, whereas in the clinical situation, both the seizures and neurologic deterioration are chronic. Further, in the West syndrome and the NMDA seizure model, there is an incongruent response to therapy with antiepileptic drugs.
Lupus Anticoagulant Induced by the Combination of Valproate and Lamotrigine
Authors: Echaniz‐Laguna Andoni , Thiriaux Anne , Ruolt‐Olivesi Isabelle , Marescaux Christian , Hirsch Edouard
Published: August 2005

Summary: A 5‐year‐old boy with generalized absence seizures was treated with valproate (VPA), 30 mg/kg/day. One month after VPA introduction, routine examination showed moderate reduction in fibrinogen and prolonged partial throm‐boplastin time (PTT). The search for lupus anticoagulant (LAC) was negative. After 10 months of VPA treatment, seizures persisted, and lamotrigine (LTG), 2 mg/kg/day, was progressively given with VPA. Seizures disappeared, but PTT was more prolonged than before LTG introduction. The search for LAC was positive, and enzyme‐linked immunosorbent assays (ELISAs) for immunoglobulin G (IgG) anticardiolipid antibodies were positive. Serum autoantibody screen and rheumatoid factor were negative; serum complement was normal. LAC eventually disappeared with VPA discontinuation. We believe that LTG may have exacerbated an initially mild immune response induced by VPA without clinical evidence of systemic disease. We therefore suggest that careful surveillance for LAC and systemic disease should be instituted when VPA is used with LTG.
The Generalized Tonic‐Clonic Seizure in Partial Versus Generalized Epilepsy: Semiologic Differences
Authors: Niaz Faiz E. , Abou‐Khalil Bassel , Fakhoury Toufic
Published: August 2005

Summary: Purpose: To study differences in the clinical manifestations of generalized tonic‐clonic seizures (GTCS) of partial versus generalized onset.

Methods: We studied 10 GTCSs in nine patients with idio‐pathic generalized epilepsy (IGE) and 10 GTCSs in 10 patients with temporal lobe epilepsy (TLE). Videotaped seizures were reviewed for all clinical features, focusing on asymmetries during different phases of each seizure.

Results: In the IGE group, focal features were seen before generalized motor activity in seven seizures. The most common was adversive head turn (six seizures). One patient had opposite direction of head turning in two recorded seizures. The tonic phase was always symmetric. In the last generalized clonic phase, asymmetry or asynchrony of motor activity was seen transiently in three seizures. The TLE group showed focal features before generalization in all seizures. Adversive head turning occurred in nine patients and was always contralateral to the focus. Focal clonic activity occurred before generalization in three and was always contralateral to the focus. The generalized tonic phase was usually asymmetric, and in the last clonic phase, motor activity was asymmetric or asynchronous in eight seizures (p > 0.05, IGE vs. TLE).

Conclusions: Brief focal features or asymmetry at onset are common in the GTCSs of IGE. However, asymmetry or asynchrony during the last clonic phase are uncommon in IGE, in contrast to TLE.
A Ketogenic Diet Increases the Resistance to Pentylenetetrazole‐Induced Seizures in the Rat
Authors: Bough Kristopher J. , Eagles Douglas A.
Published: August 2005

Summary: Purpose: The purpose of this study was to test the hypothesis that a ketogenic diet would increase the resistance of rats to pentylenetetrazole (PTZ)‐induced seizures and to understand the relation of ketonemia to seizure resistance.

Methods: A freely consumed, high‐fat (ketogenic) diet was administered to male Sprague‐Dawley rats for 5–10 weeks, while control animals were fed either rodent chow or a high‐carbohydrate diet. Ketonemia was measured as plasma levels of β‐hydroxybutyric acid (β‐OHB). Seizures were induced by tail‐vein infusion of pentylenetetrazole.

Results: The ketogenic diet produced a highly significant (p <0.01) increase in β‐OHB levels within 5 days. Induction of seizures by PTZ 35 days after animals were placed on their respective diets showed that ketogenic animals had a significantly (p <0.01) increased threshold for seizure induction compared with those fed an isocaloric diet of either high‐carbohydrate or normal rodent chow. Ketogenic animals did not exhibit increased seizure severity relative to controls, despite receiving consistently higher doses of PTZ.

Conclusions: The ketogenic diet resulted in an increased seizure threshold, confirming the hypothesis, and seizure threshold was found to be a direct function of the level of ketonemia.
Interictal Spikes Increase Cerebral Glucose Metabolism and Blood Flow: A PET Study
Authors: Bittar R. G. , Andermann F. , Olivier A. , Dubeau F. , Dumoulin S. O. , Pike G. B. , Reutens D. C.
Published: August 2005

Summary: Purpose: In patients with reflex epilepsy, it is sometimes possible to evoke interictal spikes predictably, thus providing an uncommon but important experimental paradigm for examining the physiological changes produced by epileptiform discharges.

Methods: To examine the changes in regional cerebral blood flow (rCBF) and glucose consumption (rCMRglc) produced by interictal spikes, we performed positron emission tomography (PET) scans with the blood‐flow tracer [15O]H2O and with [18F]fluorodeoxyglucose in a patient with fixation‐off epilepsy. The scans were performed in states of high and low spike frequency produced by eye closure and opening, respectively.

Results: The rCBF study revealed a focal increase in blood flow associated with the state of increased interictal spiking. The focus was in the posterior portion of the left superior parietal lobule (Talairach coordinates: x: ‐36, y: ‐71, z: 39; t = 4.5; p <0.05) and corresponded to the site of maximal ictal EEG abnormality recorded with implanted electrodes. In a volume of interest of 10‐mm diameter centered on the t statistic peak in the rCBF study, the mean rCMRglc was 39.1 μmol/100 g/min with eyes open and 44.1 μmol/100 g/min (13% increase) with eyes closed. An identical activation paradigm was used in six normal subjects studied with functional magnetic resonance imaging. In the normal subjects, no significant activation was observed in the parieto‐occipital region, indicating that the changes observed in the patient were due to interictal spiking rather than to task performance alone.

Conclusions: Interictal spiking produces focal increases in cerebral blood flow and glucose metabolism.
Adjustment of Carbamazepine Dose to Offset the Effects of the Interaction with Remacemide Hydrochloride in a Double‐Blind, Multicentre, Add‐On Drug Trial (CR2237) in Refractory Epilepsy
Authors: Mawer George E. , Jamieson Virginia , Lucas Samuel B. , Wild Janet M.
Published: August 2005

Summary: Purpose: The efficacy of remacemide hydrochloride (REM) as an antiepileptic drug (AED) was tested in a double‐blind, add‐on trial in patients with refractory epilepsy. Concurrent drugs included carbamazepine (CBZ). The interfering effects of the pharmacokinetic interaction between REM and CBZ were offset by the monitoring of plasma CBZ concentration and the appropriate reduction of CBZ dose by an unblinded observer.

Methods: Patients taking CBZ entered a 4‐week run‐in period to stabilise their dosage regimen to Tegretol tablets and blinded capsules containing Tegretol tablets. They then entered an 8‐week baseline period during which variation of plasma CBZ concentration was used to derive an individual Shewart Control Chart for each patient. These charts were used to define the threshold for CBZ dose reduction after the addition of trial drug. Where necessary the unblinded observer adjusted that portion of the daily dose of CBZ concealed in the opaque capsules, thereby maintaining the blind for the investigator and the patient.

Results: CBZ dosage reductions ranging from 14 to 50% were required by 63% of patients who received REM. Substantial increases in plasma CBZ concentration, which would have confounded the results of the trial, were thus avoided. The small increases in CBZ concentration that occurred in spite of this procedure were of similar magnitude in responders (patients who experienced ≤50% reduction in seizure frequency during treatment) and nonresponders, and in both groups the mean increase was <1 mg/L.

Conclusions: The method is offered as a model solution for problems caused by pharmacokinetic interactions in add‐on trials.