Randomized dose-controlled study of topiramate as first-line therapy in epilepsy.

OBJECTIVES: To evaluate the efficacy and tolerability of topiramate as monotherapy, using a dose-controlled study design. MATERIALS AND METHODS: We conducted a multinational, randomized, double-blind trial in adults and children (> or =6 years old) with epilepsy that was not being treated when randomized to 400 or 50 mg/day topiramate as target maintenance dosages. In addition to > or =2 lifetime unprovoked seizures, patients had to have one or two partial-onset seizures or generalized-onset tonic-clonic seizures in the 3-month retrospective baseline. The primary efficacy end point was time to first seizure; a secondary efficacy measure was the seizure-free rate at 6 months and 1 year. Double-blind treatment continued until 6 months after the last patient was randomized. RESULTS: Kaplan-Meier survival analyses for time to first seizure (intent-to-treat, n = 470) favored 400 mg/day over 50 mg/day (P = 0.0002) as a target maintenance dosage. The first evaluation point with a significant difference (P = 0.046) favoring the higher dose was at day 14 when patients were receiving 100 or 25 mg/day. The probability of being seizure-free at 6 months was 83% in patients randomized to 400 mg/day and 71% in those randomized to 50 mg/day (P = 0.005). Seizure-free rates at 12 months were 76% and 59%, respectively (P = 0.001). Differences favoring the higher dose were significant in patients with partial-onset seizures (P = 0.009) and in those with generalized-onset tonic-clonic seizures (P = 0.005). The most common dose-related adverse events were paresthesia, weight loss, and decreased appetite. Discontinuations due to cognitive-related adverse events were 2% in the 50-mg group and 7% in the 400-mg group. Overall, 7% and 19%, respectively, discontinued with adverse events during the median treatment duration of 9 months. CONCLUSION: Topiramate is effective as monotherapy in adults and children. Because a therapeutic effect emerges during titration, clinicians should adjust dosages in step-wise fashion with intermediate stopping points, e.g., 100 mg/day, to evaluate patient response and achieve the optimal maintenance dosage.

Valproic acid blood genomic expression patterns in children with epilepsy - a pilot study.

OBJECTIVE: Valproic acid (VPA) is a commonly used anticonvulsant with multiple systemic effects. The purpose of this pilot study is to examine the blood genomic expression pattern associated with VPA therapy in general and secondly VPA efficacy in children with epilepsy. MATERIALS AND METHODS: Using oligonucleotide microarrays, gene expression in whole blood was assessed in pediatric epilepsy patients following treatment with VPA compared with children with epilepsy prior to initiation of anticonvulsant therapy (drug free patients). RESULTS: The expression of 461 genes was altered in VPA patients (n = 11) compared with drug free patients (n = 7), among which a significant number of serine threonine kinases were down-regulated. Expression patterns in children seizure free on VPA therapy (n = 8) demonstrated 434 up-regulated genes, many in mitochondria, compared with VPA children with continuing seizures (n = 3) and drug free seizure patients (n = 7). CONCLUSION: VPA therapy is associated with two significant and unique blood gene expression patterns: chronic VPA monotherapy in general and a separate blood genomic profile correlated with seizure freedom. These expression patterns provide new insight into previously undetected mechanisms of VPA anticonvulsant activity.

Topiramate, carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy.

OBJECTIVES: To compare topiramate (TPM) with investigator's choice of carbamazepine (CBZ) or valproate (VPA) for initial treatment in patients with newly diagnosed epilepsy. MATERIAL AND METHODS: In patients with epilepsy diagnosed within previous 3 months, investigators selected CBZ (600 mg/day) or VPA (1250 mg/day) as preferred therapy based on the patient's clinical presentation. Based on investigators' treatment choice, patients (n=613) were assigned to the CBZ or VPA treatment branch. Within each branch, patients were randomized to double-blind treatment with the traditional antiepileptic drugs (CBZ or VPA), TPM 100 mg/day, or TPM 200 mg/day. Patients continued double-blind treatment until exiting the study or until 6 months after last patient randomized. RESULTS: No statistically significant differences between fixed doses of TPM and CBZ or VPA were observed in efficacy measures: time to exit, time to first seizure, and the proportion of patients seizure-free during the last 6 months of treatment. TPM 100 mg/day was associated with the fewest discontinuations due to adverse events. CONCLUSION: In patients with newly diagnosed epilepsy, an initial target dose of TPM 100 mg/day is at least as effective as therapeutic doses of CBZ and VPA.

An open-label study of levetiracetam at individualised doses between 1000 and 3000 mg day(-1) in adult patients with refractory epilepsy.

BACKGROUND: The novel antiepileptic drug (AED) levetiracetam (LEV, Keppra) is indicated as adjunctive therapy for partial epilepsy. The primary aim of this study was to measure the safety and tolerability of LEV individualised dosing in a heterogeneous refractory epilepsy population. METHODS: LEV was evaluated in a 10- to 16-week open-label, multicentre study in adult patients with epilepsy refractory to previous treatment with at least two AEDs. Individualised LEV doses up to 3000 mg x day(-1) were determined in an initial up-titration phase, and optimal doses were administered as adjunctive treatment during an 8- to 10-week evaluation period. Concomitant AEDs and their doses could not be changed during the study. Safety and tolerability were monitored by expression of adverse events as well as by retention rate. The effect of LEV on concomitant AED concentration was also studied. Efficacy was assessed using global clinical evaluation (GCE) scores, seizure frequency, and >or=50% responder rate. RESULTS: LEV therapy was initiated in 219 patients; 183 had localisation-related epilepsy and 37 had generalised epilepsy. In one patient, epileptic syndrome was defined as both localisation-related and generalised. About 81.7% (179/219) continued and completed treatment throughout the study, and 79% (172/219) chose to continue LEV in a follow-up study. The most common adverse events were asthenia, dizziness, and somnolence. Most adverse events occurred during up-titration. LEV treatment did not alter the concentration of concomitant AEDs. LEV improved GCE scores in 79.5% (152/191) of patients. LEV reduced the median total seizure frequency of all patients from a median of 2.25 seizures per week at baseline (n=219) to 1.10 seizures per week during the evaluation period (n=191 patients with at least one seizure count during evaluation). The >or=50% responder rate was 48.2% for all seizure types, 49.4% for partial-onset, and 51.4% for generalised-onset seizures. Throughout the evaluation period (i.e. from the start of the evaluation period until completion or early discontinuation), 26/191 (13.6%) had a 100% reduction in total seizure frequency, while in a follow-up study, 10.5% (18/172) were seizure-free for at least 6 months and 6.4% (11/172) were seizure-free for at least 1 year. CONCLUSION: LEV was well tolerated, as evidenced by limited adverse event reporting and the high retention rate, and appeared effective in both generalised and partial epilepsy.

Vagus nerve stimulation for partial seizures.

BACKGROUND: Vagus nerve stimulation (VNS) has recently been introduced as an adjunct for treating patients with seizures. The aim of this systematic review was to overview the current evidence for the effects of vagus nerve stimulation, when used as an adjunctive treatment for patients with drug-resistant partial epilepsy. OBJECTIVES: To determine the effects of VNS high-level stimulation compared to low-level (presumed subtherapeutic dose) stimulation. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register, MEDLINE (January 1966 to October 2000) and The Cochrane Controlled Trials Register (Cochrane Library Issue 4, 2000). SELECTION CRITERIA: Randomized, double-blind controlled trials of VNS comparing high and low stimulation paradigms. Studies in adults or children with drug-resistant partial seizures. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios (ORs) were estimated for each outcome. MAIN RESULTS: Results of the overall efficacy analysis show that VNS stimulation using the high stimulation paradigm was significantly better than low stimulation. The overall OR (95% Confidence Interval (CI)) for 50% responders across all studies is 1.93 (1.1,3.3). This effect did not vary substantially and remained statistically significant for both the best and worst case scenarios. Results for the outcome "withdrawal of allocated treatment" suggest that VNS is well tolerated as no significant difference was found between the high and low stimulation groups, and withdrawals were rare. Statistically significant adverse effects associated with implantation (low versus baseline) were hoarseness, cough, pain and paresthesia. Statistically significant adverse effects associated with stimulation (high versus low) were hoarseness and dyspnea, suggesting the implantation is associated with hoarseness, but the stimulation produces additional hoarseness. REVIEWER'S CONCLUSIONS: VNS for partial seizures appears to be an effective and well tolerated treatment. Adverse effects of hoarseness, cough, pain, paresthesias and dyspnea are associated with the treatment but appear to be reasonably well tolerated as dropouts were rare. Typical central nervous system adverse effects of antiepileptic drugs such as ataxia, dizziness, fatigue, nausea and somnolence were not statistically significantly associated with VNS treatment.

Postictal language dysfunction in complex partial seizures: effect of contralateral ictal spread.

The authors report postictal language evaluation in patients monitored with bitemporal depth electrodes. Patients whose seizures began in the nondominant temporal lobe and propagated to the contralateral temporal lobe had a prolonged postictal language delay (PILD) with paraphasic errors compared with seizures that did not spread. Shorter propagation time was also associated with a longer PILD. Our study suggests that ictal involvement of the dominant temporal lobe is important in postictal language behavior.

Levetiracetam add-on for drug-resistant localization related (partial) epilepsy.

BACKGROUND: The majority of patients with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug. However, up to 30% develop refractory seizures, particularly those with partial seizures. In this review, we summarise the current evidence regarding a new antiepileptic drug, levetiracetam, when used as an add-on treatment for drug-resistant localization related (partial) epilepsy. OBJECTIVES: To evaluate the effects of levetiracetam on seizures, side effects, quality of life and cognition, when used as an add-on treatment for patients with a drug-resistant localization related (partial) epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2000). In addition, we contacted UCB SA (makers of levetiracetam) and experts in the field to seek any ongoing studies or unpublished studies. SELECTION CRITERIA: Randomized placebo controlled add-on trials of levetiracetam in patients with a drug-resistant localization related (partial) epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) side effects; (d) cognitive effects; (e) quality of life. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios (ORs) were estimated for each outcome. Dose response was evaluated in regression models. MAIN RESULTS: Four trials (1023 patients) were included. All four trials had data for treatment withdrawal and side effect outcomes. Three trials (904 patients) had data for 50% or greater reduction in seizure frequency. Three trials (595 patients) had data for quality of life and cognitive outcomes. The overall Odds Ratio (OR) (95% Confidence Interval (CI)) for 50% or greater reduction in total seizure frequency outcome was 3.81 (2.78,5.22). Dose regression analysis shows clear evidence that levetiracetam reduces seizure frequency with an increase in efficacy with increasing dose of levetiracetam. Approximately 15% of patients taking 1000 mg and 20-30% of patients taking 3000 mg levetiracetam per day have a 50% or greater reduction in seizure frequency. Patients were not significantly more likely to have levetiracetam withdrawn, OR (95% CI) 1.25 (0.87,1.80). The following side effects were significantly associated with levetiracetam: dizziness 2.36 (1.21, 4.61) and infection 1.82 (1.05, 3.14) whereas accidental injury was significantly associated with placebo 0.55 (0.32, 0.93). Quality of life and cognitive effect outcomes suggest that levetiracetam has a positive effect on cognition and some aspects of quality of life. REVIEWER'S CONCLUSIONS: Levetiracetam reduces seizure frequency when used as an add-on treatment for patients with a drug-resistant localization related (partial) epilepsy, and seems well tolerated. Minimum effective and maximum tolerated doses have not been identified. The trials reviewed were of 16-24 weeks duration and results cannot be used to confirm longer term effects. Our results cannot be extrapolated to monotherapy or to patients with other seizure types or epilepsy syndromes. Great care should also be taken with any attempt to apply these results to children.

Four-year incidence of psychogenic nonepileptic seizures in adults in hamilton county, OH.

In this retrospective study, the incidence of psychogenic nonepileptic seizures in Hamilton County, OH, between 1995 and 1998 was determined. The mean incidence of psychogenic nonepileptic seizures was 3.03/100,000, with the highest incidence in 1998 (4.6/100,000). Most patients with the diagnosis of psychogenic nonepileptic seizures were aged 25 to 45 years (4.38/100,000).

Efficacy of gabapentin as adjunctive therapy in a large, multicenter study. The Steps Study Group.

The objective of this study was to determine the efficacy of gabapentin as adjunctive therapy in doses required to achieve the most effective seizure control. There were 2016 patients with partial seizures requiring adjunctive therapy who received gabapentin at doses up to 3600 mg/day in this open-label, multicenter, 16-week study. Of the 1055 patients evaluable for efficacy, 573 received gabapentin < or =1800 mg/day and 482 received > 1800 mg/day as the highest dose received. For the overall efficacy evaluable population, the percentage of patients achieving at least a 50% reduction in seizure frequency was 76.0%; 46.4% of the patients were seizure free. Patients whose highest gabapentin dose did not require > 1800 mg/day had, at baseline, fewer seizures and were receiving fewer concomitant antiepileptic drugs (AEDs) at baseline than those patients requiring > 1800 mg/day. This suggests that patients requiring higher doses of gabapentin were more refractory to drug treatment at the start of the study. Gabapentin was well tolerated at all doses in this study. The results of the study demonstrate that gabapentin is effective as adjunctive therapy in patients with partial seizures whose seizures are inadequately controlled by traditional AEDs.

Detection of epileptogenic focal cortical dysplasia by depth, not subdural electrodes.

Centers that perform presurgical epilepsy evaluations disagree on whether depth or subdural electrodes represent the optimal technique for invasive recording, especially in seizures originating outside the temporal lobe. A 13-year-old girl with a normal magnetic resonance imaging scan had unlocalized partial onset seizures, despite scalp and subdural grid ictal video/EEG recordings. Repeat video/EEG with depth electrodes showed a discrete site of continuous interictal spiking and seizure onset that was located 2-2.5 cm beneath the surface of the sensory cortex. The resected region showed focal cortical dysplasia and the patient had greater than 95% seizure frequency reduction at 3-year follow-up. We conclude that although subdural electrodes have many advantages when recording seizures outside the temporal lobes, depth electrodes may provide superior recordings when the epileptogenic region is beneath the cortical surface.

Directed forgetting deficits in patients with temporal lobe epilepsy: an information processing perspective.

Although mesial temporal lobe brain damage is frequently associated with memory loss, it is unclear whether the deficit results entirely from a disruption in the processing of relevant information or whether it also reflects interference from irrelevant information. Directed forgetting is one procedure that can be used, along with standard tests of memory, to investigate this distinction. Seventeen patients with a diagnosis of complex-partial seizures of temporal lobe origin and 17 healthy volunteers were compared on lexical decision, free recall, and recognition tests in a directed-forgetting paradigm. These tests created a memory profile to measure the influence of task relevant and irrelevant information in implicit and explicit memory. Compared with healthy volunteers, the patients were significantly impaired on the memory tasks overall [F(5,25) = 5.01, p < .01]. Specifically, directed forgetting in lexical decision and recognition both discriminated between the groups [stepdown F(1,26) = 6.84, eta 2 = .26, p < .05 and stepdown F(1,25) = 5.36, eta 2 = .13, p < .05, respectively]. The results suggest that interictal memory performance in temporal lobe epilepsy may be disrupted in part because of a deficit in the differential processing of task relevant and task irrelevant information, particularly at retrieval.

Evidence-based medicine and antiepileptic drugs.

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.

Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study.

PURPOSE: To evaluate the tolerability and safety of gabapentin (GBP) as add-on therapy for seizure control. METHODS: Conducted in an outpatient setting and reflecting usual practice, this study compared tolerability of GBP dosages < or = 1,800 versus >1,800 mg/day, when these doses were required to achieve the most effective seizure control. Two analyses of adverse events are presented: tolerability and safety. In the tolerability analysis, each patient served as his or her own control to compare the occurrence of adverse events at GBP < or =1,800 versus >1,800 mg/day. The safety analysis required patients to receive at least one dose of GBP and have a follow-up contact. RESULTS: A total of 2,216 patients enrolled in this open-label, 16-week study and were evaluable for safety. Of these, 74.0% completed the 16-week study, and 281 met the tolerability criteria. Within these 281 patients, two mutually exclusive groups were compared (a) those reporting adverse events at only < or =1,800 mg/day (low dose); and (b) those reporting adverse events at only >1,800 mg/day (high dose). Three adverse events (asthenia, headache, and dizziness) were observed in a statistically significantly larger number of patients at only the low dose than in the group reporting these same adverse events at only the high dose, suggesting that patients who tolerated GBP at < or = 1,800 mg/day did not experience a significant increase in adverse events with dosages >1,800 mg/day. Overall, 10.6% of the 2,216 patients in the safety population prematurely withdrew because of adverse events, and 3.5% discontinued because of lack of efficacy. Safety and tolerability of GBP was rated as excellent or good for 78.5% of all patients. CONCLUSIONS: Gabapentin doses >1,800 mg/day were as well tolerated as doses < or =1,800 mg/day and were not associated with more adverse events.

Cerebral metabolism of the remote area after epilepsy surgery.

To clarify whether epilepsy surgery improves cerebral metabolism, pre- and postoperative positron emission tomography (PET) scans were performed, with special reference to hypometabolism outside the resected epileptogenic zones in nine patients (8 males, 1 female) with medically intractable complex partial seizures and multiple hypometabolic zones. Seven patients underwent unilateral anterior temporal lobectomy, one patient underwent selective amygdalohippocampectomy, and one patient underwent parieto-occipital cortical resection and anterior temporal lobectomy. PET scans were obtained at least 6 months after surgery. Eight patients became seizure-free, and one patient had fewer than three seizures per year. Four patients showed improved glucose metabolism in the formerly hypometabolic zones, which were remote to the surgical site and ipsilateral to the epileptogenic foci. Five patients, who showed bilateral temporal hypometabolism preoperatively, had contralateral temporal hypometabolism after surgery. The relative glucose uptake in four of these patients showed increased metabolism of the adjacent lobes ipsilateral to the surgical site. The lobes that showed increased glucose metabolism after surgery were mostly frontal. Hypometabolism is reversible in the ipsilateral remote area, and may be caused by inhibition via the intercortical pathway. Contralateral temporal hypometabolic zones that persist after surgery may be caused by a different mechanism, and neither indicate the presence of seizure foci nor affect the seizure outcome.

Vigabatrin: a novel therapy for seizure disorders.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of vigabatrin and its role in the management of seizure disorders. METHODS: A MEDLINE search of English-language literature from January 1993 through January 1999 was conducted using vigabatrin as a search term to identify pertinent studies and review articles. Additional studies were identified from the bibliographies of reviewed literature. The manufacturer provided postmarketing surveillance data. Priority was given to randomized, double-blind, placebo-controlled studies. FINDINGS: Vigabatrin is a selective and irreversible inhibitor of gamma-aminobutyric acid transaminase. In controlled clinical trials of vigabatrin add-on therapy in patients with uncontrolled partial seizures, 24-67% of patients achieved a < or =50% reduction in seizure frequency. Data from two comparative trials with carbamazepine monotherapy indicate that vigabatrin monotherapy reduces the frequency of partial seizures in patients with newly diagnosed epilepsy. Vigabatrin also controls infantile spasms, particularly those associated with tuberous sclerosis. Vigabatrin is more effective in patients with partial seizures than in those with generalized seizures. The drug is generally well tolerated. Headache and drowsiness were the most common adverse effects observed in controlled clinical trials; visual field defects, psychiatric reactions, and hyperactivity also have been reported. There are no known clinically significant drug interactions. CONCLUSIONS: Vigabatrin improves seizure control as add-on therapy for refractory partial seizures and may produce therapeutic benefits in the treatment of infantile spasms. Vigabatrin is generally well tolerated, with a convenient administration schedule, a lack of known significant drug interactions, and no need for routine monitoring of plasma concentrations.

Topiramate: a new antiepileptic drug.

OBJECTIVE: To review proposed mechanisms of action, clinical pharmacology, efficacy, safety, and tolerability of the antiepileptic drug (AED) topiramate. METHODS: All available data from the clinical development program--published and unpublished data (provided by investigators or the RW Johnson Pharmaceutical Research Institute)--were analyzed, with emphasis on the results of double-blind, placebo-controlled trials. Data from open-label studies provided information about long-term efficacy and tolerability. FINDINGS: Topiramate is highly effective in the control of previously therapy-resistant partial seizures, with or without secondary generalization. In the refractory adult patient population enrolled in controlled clinical trials, seizures were reduced by 50% or more in 27-47% of patients compared with 0-18% in placebo-treated patients and by 75% or more in 9-36% of the patients compared with 0-9% of those receiving placebo. The most common adverse effects involve the central nervous system and are mild to moderate in nature. Adverse effects include somnolence, fatigue, psychomotor slowing, and concentration problems. The currently recommended dosing is lower and titration slower than schedules used in the clinical trials; this may improve the tolerability of topiramate. Topiramate has few interactions with currently available AEDs, but phenytoin concentrations increased in some patients. Topiramate can be used initially as adjunctive therapy. Plasma topiramate concentrations are reduced substantially when used with enzyme-inducing AEDs. Open-label data and a single double-blind trial suggest that topiramate monotherapy may be effective. Open-label data also indicate that topiramate may be effective in generalized seizures of nonfocal origin, including those associated with Lennox-Gastaut syndrome. CONCLUSIONS: The robust clinical effects of topiramate expand the therapeutic options for patients with epilepsy. Controlled clinical trials are needed to verify initial observations that topiramate may be effective against a broad spectrum of seizure types and to directly compare efficacy and tolerability with other new and standard AEDs.

Current developments in neurology, Part II: Advances in the pharmacotherapy of Alzheimer disease, Parkinson's disease, and stroke.

Disorders of the central nervous system provide innumerable challenges to the clinician. Often the underlying pathophysiology is not completely understood, thus preventing the design of treatment strategies aimed at correcting the underlying process. In this decade of the brain, basic science research combined with difficult but necessary clinical trials may answer some of these seemingly over-whelming questions for these devastating illnesses.

Current developments in neurology, Part I: Advances in the pharmacotherapy of headache, epilepsy, and multiple sclerosis.

When caring for patients with disorders of the central nervous system such as migraine headaches, epilepsy, or MS, clinicians are faced with increasingly complex pharmacotherapeutic options. Pharmacotherapeutic strategies directed toward prevention, reversal, or cure of these diseases are hampered by an incomplete understanding of the underlying pathophysiology. In this decade of the brain, basic science research combined with difficult but necessary clinical trials may answer some seemingly overwhelming questions for these devastating illnesses.

Psychopathology and trauma in epileptic and psychogenic seizure patients.

Forty-one patients admitted to an inpatient epilepsy unit for intractable seizures were evaluated for the presence of Axis I and Axis II diagnoses and for a history of trauma by use of a structured clinical interview. Both the interviewer and the patient were blind to the seizure diagnosis. Following video and electroencephalographic evaluation, 27 patients were diagnosed with epileptic seizures, and 14 had psychogenic seizures. The history of Axis I and Axis II disorders did not distinguish the two groups of patients. A history of trauma was significantly more likely in the patients with psychogenic seizures. The experience of trauma appears to be an important factor in the development of psychogenic seizures. Sexual trauma alone, however, was not significantly associated with psychogenic seizures.

Repetition and the arcuate fasciculus.

According to the traditional model of language organization, repetition deficits arise following damage to the arcuate fasciculus of the dominant hemisphere (conduction aphasia). Conduction aphasia may result from lesions that spare the arcuate fasciculus. However, these patients have atypical language organization. We describe a man with normal language architecture who underwent a resection of the anterior portion of his arcuate fasciculus and retained his ability to repeat words and sentences. We propose that the arcuate fasciculus is not necessary for speech repetition by the lexical route.