bluuebunny/crossref_metadata_2025 huggingface dataset:
Triptans Versus Analgesics
Authors: Robbins Lawrence
Published: March 2003

Objective.—To retrospectively assess patient preferences between triptans and analgesics in treating migraine headache.

Methods.—The study assessed patient preferences for triptans versus commonly used migraine analgesic preparations. Over a 3‐month period, 663 patients with migraine between the ages of 17 and 62 years completed an office‐based survey.

Results.—Most patients preferred a treatment regimen that included either a triptan alone (52%) or a triptan with an analgesic medication within 1 hour (18%). Overall, 70% of patients who had been given triptans in the past chose to continue to use them, either alone or with an analgesic. Patients who preferred analgesics alone comprised 21% of the total. Nine percent preferred not to take either triptans or analgesic medications. Among the patients who preferred triptans, 62% stated that increased efficacy was the primary reason for their preference. Thirty percent cited both efficacy and decreased adverse events. The remaining 8% believed that decreased adverse events was the basis for their preference.

Conclusions.—Despite cost and other limitations of triptans, most patients prefer them over nontriptan medications. Enhanced efficacy was the main reason for choosing triptans over analgesics.
Analysis of the Patients Attending a Specialist UK Headache Clinic over a 3‐Year Period
Authors: Dowson Andrew J.
Published: March 2003

Objective.—This study analyzed the profile of patients who attended a specialist UK headache clinic over a 3‐year period.

Methods.—An audit was conducted of the clinical records of patients attending the specialist headache clinic at King's College, London, between January 1997 and January 2000. Data were collected for diagnoses given, current medications taken, medications prescribed and recommended, and investigations conducted. Results were calculated as numbers and proportions of patients for the 3‐year period and for the 3 separate 12‐month periods.

Results.—A total of 458 patients were included in the audit. Most patients were diagnosed as having chronic daily headache (CDH, 60%) or migraine (33%). Prior to the clinic visit, most patients with CDH and migraine treated their headaches with analgesics, and there was little use of prophylactic medication. In the clinic, 74% of patients with CDH and 85% of migraineurs were prescribed prophylactic medication, and 81% of migraineurs were given triptans for acute treatment. Diagnostic testing was performed in 12% of the patients, and all results were normal or negative.

Conclusions.—CDH and migraine were the most common headache types encountered in this UK secondary‐care clinic. Review of treatment patterns used prior to the initial clinic evaluation suggests that management of CDH and migraine in UK primary care is suboptimal, and educational initiatives are needed to improve headache management.
Coprescription of Triptans With Potentially Interacting Medications: A Cohort Study Involving 240 268 Patients
Authors: Tepper Stewart , Allen Christopher , Sanders David , Greene Alison , Boccuzzi Stephen
Published: March 2003

Background Little information exists about the actual prescription of triptans within large, geographically diverse populations, in terms of demographic characteristics and co‐prescriptions with other medications with potential interactions.

Objectives To investigate the demographic characteristics associated with triptan use, and examine the rate of co‐prescription of triptans with specified pharmacologic agents with the potential for drug interactions.

Methods This study examined the rate of co‐prescription of triptans available in the US up to May 2001 (sumatriptan, naratriptan, rizatriptan, and zolmitriptan) with specified agents with potential for drug interactions. A cohort of 240,268 patients receiving pharmacy benefits from Merck‐Medco (N  =  65  +  M) was followed over a one‐year period. This analysis included patients who received at least two triptan prescriptions during the study (6/00‐5/01). Ninety‐one percent of the cohort remained on the same triptan during the study period. ‘Co‐prescription’ was defined as any fill for a medication that was contraindicated or could potentially adversely interact with a triptan, obtained between and during the first and last triptan fills throughout the study period.

Results Mean patient age was 43 (SD  ±  11.6) and 82% were female. Twenty‐one percent were co‐prescribed selective serotonin reuptake inhibitors, reflecting the considerable co‐morbidity of migraine and depression. Patients taking triptans were almost never co‐prescribed monoamine oxidase inhibitors (0.02%), and co‐prescription of ergots was also low (1.45%). Less than one percent (0.45%) received cimetidine while taking zolmitriptan, while 2.7% of patients taking rizatriptan 10 mg also took propranolol. While agents unavailable in the U.S. were not evaluated in this cohort, six percent of patients were treated with potent CYP 3A4 inhibitors, which would not be expected to cause any problems with the triptans in the survey. However, such agents are specifically contraindicated for use with one triptan (eletriptan), recently launched in the EU, suggesting that continued vigilance will be necessary to avoid coprescription of medicines with the potential for producing adverse side effects.

Conclusions Triptan use mirrors migraine demographics. The frequency of co‐prescription of triptans with SSRIs is about 20%. Continued vigilance will be necessary to avoid co‐prescription of medicines with the potential for producing adverse drug events.
Material‐Specific Memory Changes after Anterior Temporal Lobectomy as Predicted by the Intracarotid Amobarbital Test
Authors: Chiaravalloti Nancy D. , Glosser Guila
Published: March 2003

Summary:  Purpose: The intracarotid amobarbital test (IAT) has been shown to predict verbal memory changes after anterior temporal lobectomy (ATL). Seeking to extend these findings, we examined two questions: (a) What is the relationship between material‐specific aspects of IAT memory and material‐specific memory changes after ATL? and (b) Which IAT memory score(s) optimally predict memory changes after surgery, the memory score after injection ipsilateral to the seizure focus, the memory score after injection contralateral to the seizure focus, or the IAT asymmetry score, comprising the ipsilateral minus contralateral injection scores?

Methods: Seventy left hemisphere language‐dominant patients undergoing ATL for treatment of medically refractory seizures were administered a verbal and visuospatial recognition memory test before surgery and 3 weeks after surgery. IAT memory recognition scores for words and designs were used to predict verbal and visuospatial memory changes after surgery.

Results: After surgery, left ATL patients declined in verbal memory, whereas right ATL patients declined in visuospatial memory. IAT total recognition memory scores (collapsed across all types of materials) and IAT word memory scores were associated with postoperative verbal memory decline. This relationship was significant for the IAT ipsilateral injection memory scores and the IAT hemispheric asymmetry scores. IAT memory performances were not related to visuospatial memory changes.

Conclusions: Results indicate IAT memory measures to be related to postoperative verbal, but not visuospatial, memory change. A specific relationship was found between postoperative verbal memory change and IAT verbal memory after injection ipsilateral to the seizure focus, when relying primarily on the contralateral hemisphere. This finding is consistent with the functional reserve model of memory change in ATL.
Idiopathic Generalized Epilepsies: Do Sporadic and Familial Cases Differ?
Authors: Briellmann Regula S. , Torn‐Broers Yvonne , Berkovic Samuel F.
Published: March 2003

Summary:  Purpose: Genetic factors are the only identified cause of idiopathic generalized epilepsies (IGEs), but the majority of cases do not have affected first‐degree relatives. Here we investigate whether subjects with sporadic and familial IGE differ in terms of antecedent events and clinical and EEG features. Differences would support the hypothesis of a different etiology for sporadic cases, which has implications for choice of subjects for genetic association studies.

Methods: We analyzed 98 patients with IGE, diagnosed on clinical and EEG criteria. All patients and, if possible, one relative were interviewed, with special emphasis on potential antecedent events and family history. Patients with first‐degree relatives affected with epileptic seizures were regarded as “familial,” and the other patients were regarded as “sporadic.”

Results: Of the 98 IGE patients, 32 (33%) patients were familial. The risk for seizures was 13.2% for siblings, and 7.7% for parents. The distribution of the IGE subsyndromes, the presence of antecedent events, and other electroclinical features did not differ between familial and sporadic IGE groups.

Conclusions: No differences were found between familial and sporadic IGE patients. This does not the support the hypothesis that sporadic and familial IGE cases have separate etiologies.
Unsuspected Atypical Hemispheric Dominance for Language as Determined by fMRI
Authors: Spreer J. , Quiske A. , Altenmüller D. M. , Arnold S. , Schulze‐Bonhage A. , Steinhoff B. J. , Schumacher M.
Published: March 2003

Summary:  Purpose: We sought to illustrate the value of functional magnetic resonance imaging (fMRI) in the presurgical assessment of hemispheric dominance for language by means of an illustrative case report.

Methods: fMRI with two language paradigms was performed in a right‐handed patient without familial sinistrality suffering from a left frontal focal epilepsy.

Results: Both fMRI paradigms revealed unequivocally lateralized right hemispheric activation. Atypical language representation was confirmed by Wada test. The further presurgical workup could be restricted to subdural strip recordings instead of the initially intended grid implantation. After resective surgery, no language deficits were apparent.

Conclusions: Hemispheric dominance for language should be assessed by fMRI in all patients before surgery in areas potentially relevant for language in either cerebral hemisphere. fMRI may influence the further diagnostic workup and should be performed before other invasive diagnostic procedures.
Manic Episode in Epilepsy and Bipolar I Disorder: A Comparative Analysis of 13 Patients
Authors: Kudo T. , Ishida S. , Kubota H. , Yagi K.
Published: March 2003

Summary: Purpose: To determine whether the manic episode of patients with epilepsy has different characteristics from manic episode of patients with bipolar disorder.

Methods: Interictal manic episodes in patients with epilepsy (epilepsy group) were compared with mood disorders in patients with bipolar I disorder (bipolar group), as defined by the DSM‐IV. There were 13 patients (five women and eight men) in each group.

Results: Five epilepsy patients had relatives with epilepsy and/or convulsions, and four bipolar patients had relatives with mood disorders. In the epilepsy group, two had substance‐related or organic factors associated with the episodes besides epilepsy, and two exhibited a postictal manic state that had the same symptoms as those of their interictal manic episodes. Ten patients of the epilepsy group had dependent–childish behavior. The epilepsy group had fewer severe mood episodes than the bipolar group. Ten epilepsy patients had fluctuating mood disturbances, and eight had rapid cycling of mood episodes. The epileptogenic zone was in the frontal and/or temporal lobes of eight patients and in multiple lobes of two others; it could not be localized in the three remaining patients.

Conclusions: The clinical features of the interictal manic episodes in the epilepsy group were different from those in the bipolar group. The manic episodes of the epilepsy group appeared heterogeneous in their causal factors. An epileptogenic zone in the frontal and temporal lobes seems to play an important role in the mood episodes of the majority of patients with epilepsy.
Ictal Automatisms with Preserved Responsiveness in a Patient with Left Mesial Temporal Lobe Epilepsy
Authors: Park S. A. , Heo K. , Koh R. , Chang J. W. , Lee B. I.
Published: March 2003

Summary:  Purpose: To describe the possible mechanism of ictal automatisms with preserved responsiveness (APRs) in a patient with left mesial temporal lobe epilepsy, which had not been reported previously.

Methods: Ictal EEGs recorded from bilateral foramen ovale electrodes with scalp–sphenoidal electrodes were analyzed in respect to the ictal semiology.

Results: The patient had a right hemispheric language dominance in the dextral. Electroclinical analysis revealed that the onset of oroalimentary automatisms coincided with the involvement of the left mesial and lateral temporal structures by spreading ictal discharges. The ictal discharge spreading was limited to the ipsilateral hemisphere throughout the seizure, which explained the intact consciousness and preserved responsiveness of the patient.

Conclusions: This case suggests that APRs take place in seizures originating from the nondominant temporal lobe, during which ipsilateral mesial and lateral temporal structures are diffusely involved without spreading to the contralateral side.
The Midline Thalamus: Alterations and a Potential Role in Limbic Epilepsy
Authors: Bertram Edward H. , Mangan Patrick S. , Zhang DeXing , Scott Carol A. , Williamson John M.
Published: March 2003

Summary:  Purpose: In limbic or mesial temporal lobe epilepsy, much attention has been given to specific regions or cell populations (e.g., the hippocampus or dentate granule cells). Epileptic seizures may involve broader changes in neural circuits, and evidence suggests that subcortical regions may play a role. In this study we examined the midline thalamic regions for involvement in limbic seizures, changes in anatomy and physiology, and the potential role for this region in limbic seizures and epilepsy

Methods: Using two rat models for limbic epilepsy (hippocampal kindled and chronic spontaneous limbic epilepsy) we examined the midline thalamus for evidence of involvement in seizure activity, alterations in structure, changes in the basic in vitro physiology of the thalamic neurons. We also explored how this region may influence limbic seizures.

Results: The midline thalamus was consistently involved with seizure activity from the onset, and there was significant neuronal loss in the medial dorsal and reuniens/rhomboid nuclei. In addition, thalamic neurons had changes in synaptically mediated and voltage‐gated responses. Infusion of lidocaine into the midline thalamus significantly shortened afterdischarge duration.

Conclusions: These observations suggest that this thalamic region is part of the neural circuitry of limbic epilepsy and may play a significant role in seizure modulation. Local neuronal changes can enhance the excitability of the thalamolimbic circuits.
Do Interictal Discharges Promote or Control Seizures? Experimental Evidence from an In Vitro Model of Epileptiform Discharge
Authors: Avoli Massimo
Published: March 2003

Summary: Interictal and ictal discharges are recorded from limbic structures in temporal lobe epilepsy patients. In clinical practice, interictal spikes are used to localize the epileptogenic area, but they also are assumed to promote ictal events. Here I review data obtained from combined slices of mouse hippocampus–entorhinal cortex that indicate an inverse relation between interictal and ictal events. In this preparation, application of 4‐aminopyridine or Mg2+‐free medium induce (a) interictal discharges that originated from CA3 and propagate (via the Schaffer collaterals) to CA1 and entorhinal cortex, to return to the hippocampus through the dentate area; and (b) ictal discharges that initiate in the entorhinal cortex and propagate to the hippocampus via the dentate gyrus. Interictal activity occurs throughout the experiment (up to 6 h), whereas ictal discharges disappear after 1–2 h. Schaffer collateral cut abolishes interictal discharges in CA1, entorhinal cortex, and dentate and reestablishes entorhinal ictal discharges. Moreover, ictal discharge generation in the entorhinal cortex after Schaffer collateral cut is prevented by mimicking CA3 activity with rhythmic electrical stimulation of CA1 outputs. Thus hippocampal interictal activity controls the ability of the entorhinal cortex to generate seizures. It also may be proposed that Schaffer collateral cut may model the epileptic condition in which CA3 damage results in loss of hippocampal control over the entorhinal cortex. In conclusion, these experiments demonstrate that interictal activity controls rather than promotes ictal events, and functional integrity of CA3 constitutes a critical control mechanism in temporal lobe epilepsy.
Assessment of Quality of Life in People with Epilepsy: Some Practical Implications
Authors: Baker Gus A.
Published: March 2003

Summary: Growing recognition of the need to assess the impact of epilepsy on psychosocial functioning has led to a number of initiatives to quantify quality of life (QOL) in patients with this condition. To understand the impact of epilepsy and its treatment, physical, social, neuropsychological, and psychological functioning aspects must be considered. It also is apparent from previous research work that measures of QOL should be comprehensive enough to address the question under consideration, but also simple and as brief as possible. A number of QOL measures for assessing the impact of epilepsy and its treatment exist, such as the Washington Psychosocial Seizure Inventory, the Social Effects Scale, the Epilepsy Surgery Inventory, the Quality of Life in Epilepsy (QOLIE) questionnaire, and the Liverpool QOL Battery. These measures have in most cases been shown to be reliable, valid, and sensitive to change, although at the current stage of development, some are better validated than others. It is generally agreed that the best approach is to use a standard generic instrument with disease‐specific additions. Selection of a measure already in existence is recommended, as the process of producing a new measure is costly in terms of both resources and time. Some consideration also needs to be given to factors such as the process of administration (e.g., self‐completion or administration at interview) or the timing of data collection. Then questions such as the cross‐cultural applicability of QOL measures and the real relevance of the changes remain to be answered. It is hoped that, over the next few years, significant progress will be made in addressing these issues.
Psychosocial Aspects of Epilepsy in Oman: Attitude of Health Personnel
Authors: Al‐Adawi Samir , Al‐Ismaily Salem , Martin Rodger , Al‐Naamani Aziz , Al‐Riyamy Kassim , Al‐Maskari Masoud , Al‐Hussaini Ala'Aldin
Published: March 2003

Summary:  Purpose: To assess with a questionnaire the awareness and attitudes of the doctors in Oman toward epilepsy. Attitudes of society toward epilepsy have a wide‐ranging influence, affecting issues as diverse as compliance with treatment and doctor–patient communication. Recent studies in both developing and developed countries suggest that within the medical profession, there is a lack of knowledge and negative attitudes toward people with epilepsy (PWE). There are no equivalent studies for Oman or the Arab world.

Methods: The questionnaire included queries on the backgrounds of the physicians, including their training and qualifications, the main sources of their knowledge of epilepsy, as well as their perceptions of the attributes and care requirements of PWE.

Results: Sixty‐two percent (n = 121) of those questioned, who were medical personnel working in different regions of Oman, responded. The results suggest that, despite coming from diverse cultural backgrounds and nationalities, the practicing doctors in Oman gained knowledge of epilepsy much earlier than did their counterparts in developed countries. The majority of the respondents thought that PWE have more propensities toward dysfunctional personality and behavioral characteristics than do “normal” people. On questions relating to public image, our respondents opined that, although the general public is negative toward PWE, the realities regarding PWE should be publicized because PWE are capable of having a normal family life and being an integral part of society.

Conclusions: In spite of having an earlier exposure to seizures and sympathetic acceptance of PWE, negative views still persist on matters related to cognitive and behavior domains. It is concluded that a developing country such as Oman must inculcate more realistic perceptions and attitudes among their doctors toward PWE.
High and Low Perceived Self‐Control of Epileptic Seizures
Authors: Spector Shiri , Cull Christine , Goldstein Laura H.
Published: March 2003

Summary:  Purpose: To define behaviours and to identify psychological, demographic, and epilepsy‐related variables associated with high as opposed to low perceived self‐control of seizures.

Method: In a semistructured interview, 100 adults with intractable seizures were asked about their seizure precipitants and attempts at self‐control of seizures. They also completed four psychological questionnaires. Latent Class Analysis was used to analyse the interview data to create two groups, High Controllers and Low Controllers, who were then compared on demographic, epilepsy, and psychological characteristics.

Results: Being able to identify and seeking out low‐risk‐for‐seizure situations, avoiding high‐risk‐for‐seizure situations, and making attempts at seizure inhibition were seizure behaviours that discriminated High from Low Controllers. The general probability of being a High Controller was greater than that of being a Low Controller. Perceived high self‐control of seizures was associated with low chance‐health locus of control. For Low Controllers, current age, age at onset of seizures, and duration of epilepsy history were related to psychological variables. A significantly higher proportion of the Low Controllers than High Controllers were women.

Conclusions: Many people with intractable seizures do not accept their epilepsy as a condition over which they have no control. Perceived self‐control of seizures, however, involves a complex interaction between epilepsy and psychological factors, with health locus of control an apparently important discriminator between High and Low Controllers.
Visual Field Loss Associated with Vigabatrin: Quantification and Relation to Dosage
Authors: Hardus P. , Verduin W. M. , Engelsman M. , Edelbroek P. M. , Segers J. P. , Berendschot T. T. J. M. , Stilma J. S.
Published: March 2003

Summary:  Purpose: To describe the correlation between visual field loss and the duration, dosage, and total amount of vigabatrin (VGB) medication in a group of patients with epilepsy. Co‐medication of antiepileptic drugs (AEDs) and compliance were also studied.

Methods: Ninety‐two patients (53 male and 39 female) taking VGB medication in the past or the present, attending the Outpatient Epilepsy Clinic in Utrecht, were examined with the Goldmann perimeter. The amount of visual field loss was calculated by the Esterman grid method and by a new method, with which the percentage surface loss of the visual field is measured. A complete drug history was compiled, specifying the amount and duration of VGB medication. Concomitant AED medication was noted. Serum levels of AEDs were determined.

Results: Linear regression showed the total amount of VGB as the most significant parameter to predict visual field loss (p < 0.001). Further, men were more affected than women (p = 0.026). Compliance was good, and other AEDs did not influence the results.

Conclusions: Because prolonged use of VGB medication is correlated with the amount of visual field loss, VGB should be prescribed only when there are no alternatives. In such cases, we recommend an examination of the peripheral visual field before starting therapy and a repeated examination every 6 months.
Antiepileptic Drug Therapy and Its Management in Sudden Unexpected Death in Epilepsy: A Case–Control Study
Authors: Nilsson L. , Bergman U. , Diwan V. , Farahmand B. Y. , Persson P‐G. , Tomson T.
Published: March 2003

Summary:  Purpose: Because frequent seizures constitute a major risk factor for sudden unexpected death in epilepsy (SUDEP), the treatment with antiepileptic drugs (AEDs) may play a role for the occurrence of SUDEP. We used data from routine therapeutic drug monitoring (TDM) to study the association between various aspects of AED treatment and the risk of SUDEP.

Methods: A nested case–control study was based on a cohort consisting of 6,880 patients registered in the Stockholm County In Ward Care Register with a diagnosis of epilepsy. Fifty‐seven SUDEP cases, and 171 controls, living epilepsy patients, were selected from the cohort. Clinical data including data on TDM were collected through medical record review.

Results: The relative risk (RR) of SUDEP was 3.7 (95% CI, 1.0–13.1) for outpatients who had no TDM compared with those who had one to three TDMs during the 2 years of observation. RR was 9.5 (1.4–66.0) if carbamazepine (CBZ) plasma levels at the last TDM were above and not within the common target range (20–40 μM). High CBZ levels were associated with a higher risk in patients receiving polytherapy and in those with frequent dose changes. Although the subgroup of patients with high CBZ levels was small (six cases of 33 with CBZ therapy), and the result should be interpreted with caution, no similar associations were demonstrated for phenytoin plasma levels and risk of SUDEP. No association was found between SUDEP risk and within‐patient variation in AED levels over time.

Conclusions: Polytherapy, frequent dose changes, and high CBZ levels as identified risk factors for SUDEP all point to the risks associated with an unstable severe epilepsy. It is unclear whether high CBZ levels per se represent a risk factor or just reflect other unidentified aspects of a severe epilepsy. Our results, however, prompt further detailed analyses of the possible role of AEDs in SUDEP in larger cohorts and suggest that reasonable monitoring of the drug therapy may be useful to reduce risks.
Contribution of the MHC Class II Antigens to the Etiology of Infantile Spasm in Mexican Mestizos
Authors: Suastegui Roberto A. , De La Rosa Gabriela , Carranza Juan M. , Gonzalez‐Astiazaran Adalberto , Gorodezky Clara
Published: March 2003

Summary: Purpose:Infantile spasms (ISs) are age‐dependant epileptic seizures, which may be flexor, extensor, lightning or nods, or mixed. The aim of this study was the analysis of genetic factors within the human leukocyte antigen (HLA) complex associated with ISs.

Methods:Sixty‐five patients diagnosed according to the established international criteria were compared with 229 healthy individuals; all of them were Mexican Mestizos. Five families were also analyzed (seven affected and five healthy sibs); HLA class I and class II antigens were typed using the standard microlymphocytotoxicity methods.

Results:The findings showed female gender preference (2:1). Two thirds were symptomatic, and prevalent seizures were of mixed type (67%). A strong association with HLA‐DR17 was detected in the IS group (pc < 0.01; OR = 3.6; EF = 0.20). DR17 was also found increased in the symptomatic patients (p = 0.009; OR = 3.16) and in those with other types of seizures (p = 0.001; OR = 2.0). Conversely, HLA‐DQ6 was significantly decreased (pc < 0.002; PF = 0.37) in the total and in the symptomatic groups (p < 0.01). Haplotype linkage was not confirmed in the families; however, those with more than one affected sib shared at least one haplotype.

Conclusions:These findings suggest the contribution of DR locus to the susceptibility and the participation of DQ region in the resistance to IS. Severity seems also to be influenced by HLA‐DR17, and therefore class II typing may be a helpful tool for disease prognosis.
AUStralian Study of Titration to Effect Profile of Safety (AUS‐STEPS): High‐Dose Gabapentin (Neurontin) in Partial Seizures
Authors: Beran Roy , Berkovic Samuel , Black Andrew , Danta Gytis , Dunne John , Frasca Joseph , Grainger Keith , Kilpatrick Christine , McKenzie Roderick , McLaughlin Daniel , Schapel Graham , Somerville Ernest
Published: March 2003

Summary:  Purpose: To evaluate the safety, tolerability, efficacy, and impact on quality of life of gabapentin (Neurontin; GBP) as adjunctive therapy in patients with refractory partial seizures.

Methods: AUS‐STEPS was an open‐label, multicenter, prospective study in patients experiencing partial seizures who were inadequately controlled with one to three concurrent antiepileptic drugs (AEDs). GBP treatment was titrated to a maximum of 4,800 mg/day, over a treatment period of 24 weeks, to achieve an efficacious and tolerable dosage. Efficacy was assessed by seizure‐frequency data. Quality of life was evaluated by using the QOLIE‐10 questionnaire, and safety was assessed by adverse‐event reports and clinical laboratory findings.

Results: A total of 176 patients received treatment with GBP, with 174 evaluable for intention‐to‐treat (ITT) efficacy analysis. A reduction of >50% in overall seizure frequency was observed in 93 patients (53%). There was a small (4.6%) overall improvement in QOLIE‐10 score. The most frequent adverse events were dizziness (31%), fatigue (29%), somnolence (27%), headache (21%), and ataxia (20%), with no major increase seen in adverse events necessitating discontinuation as the dose of GBP was titrated upward.

Conclusions. This study indicates that patients with partial epilepsy may be effectively treated with GBP at dosages of 4,800 mg/day, without altering the safety profile of the drug.
Correlation of Scalp EEG and 1H‐MRS Metabolic Abnormalities in Temporal Lobe Epilepsy
Authors: Maton B. , Gilliam F. , Sawrie S. , Faught E. , Hugg J. , Kuzniecky R.
Published: March 2003

Summary:  Purpose: To correlate the interictal spike field and region of seizure onset with the distribution of 1H‐MRS abnormalities in temporal lobe epilepsy (TLE) and improve our understanding of the clinical significance of 1H‐MRS abnormalities.

Methods: Scalp electroencephalogram (EEG) monitoring and proton magnetic resonance spectroscopy (1H‐MRS) results were correlated in 31 consecutive patients with TLE.

Results: Lateralized 1H‐MRS–based hippocampal abnormalities were recorded in 95% of the patients with unilateral interictal spikes, with a high degree of concordance for the lateralization side (90%). In 64% of the patients with normal or bilateral interictal EEG spikes, 1H‐MRS provided lateralizing information. Bilateral 1H‐MRS abnormalities, with or without lateralization, were 3 times more frequent than bitemporal EEG spikes. Anterior predominance of the 1H‐MRS abnormalities was more frequent in patients with anterior temporal EEG spiking (50%), than in patients without this EEG distribution (18%). Similar association was noted between distribution of 1H‐MRS abnormalities and region of EEG seizure onset.

Conclusions: Our results show a moderate level of concordance between the distribution of 1H‐MRS and EEG abnormalities. 1H‐MRS identifies abnormalities contralateral to the predominant seizure focus more often than does EEG and may provide lateralizing information in patients with nonlateralizing interictal EEG.
Verbal Retention Lateralizes Patients with Unilateral Temporal Lobe Epilepsy and Bilateral Hippocampal Atrophy
Authors: Sawrie Stephen M. , Martin Roy C. , Gilliam Frank , Knowlton Robert , Faught Ed , Kuzniecky Ruben
Published: March 2003

Summary:  Purpose: To examine the lateralization utility of preoperative verbal retention in patients with and without bilateral hippocampal atrophy.

Methods: The sample consisted of 74 patients with EEG‐defined unilateral temporal lobe epilepsy (TLE) who had also undergone volumetric magnetic resonance imaging (MRI). Verbal retention was operationalized by the Logical Memory percentage retention subtest (LM%) of the Wechsler Memory Scale. Patients were divided into groups with (a) bilaterally normal hippocampal volumes, (b) unilateral atrophy, or (c) bilateral atrophy. Two different thresholds (empirically derived vs. normative) were used to lateralize on the basis of LM%. LM% lateralization was then examined by group using χ2, sensitivity, positive predictive values, and odds ratios. Analyses were also conducted separately in the subset of patients who were seizure free after surgery.

Results: Mean LM% performance was significantly lower in patients with left versus right TLE in the subset with bilateral hippocampal atrophy (p = 0.018), but not in patients with a normal MRI (p = 0.918) or unilateral atrophy (p = 0.087). The odds of a correct lateralization by LM% increased from 1.67 in patients with normal MRI to 36.11 in patients with bilateral hippocampal atrophy. The power of a right and left lateralization prediction by LM% was 100% and 75%, respectively, in patients with bilateral hippocampal atrophy. Similar results were obtained when analysis was restricted to patients who were seizure free after surgery.

Conclusions: Preoperative verbal retention as measured by LM% may provide meaningful lateralization information in patients who are difficult to lateralize via MRI.
Comparison of Epilepsy and Asthma Perception Among Preschool Teachers in Taiwan
Authors: Hsieh Liang‐Po , Chiou Hua‐Huei
Published: March 2003

Summary:  Purpose: The purpose of this study was to investigate preschool teachers' perceptions to children with epilepsy and asthma in middle areas of Taiwan.

Methods: Two‐hundred sixteen preschool teachers were investigated with a questionnaire regarding their knowledge, attitude, and practice. There were 22 questions in the questionnaire (half of the questions were for epilepsy, and others for asthma). Differences between teachers' perceptions of children with epilepsy and asthma were analyzed.

Results: More teachers thought epilepsy was a hereditary disease and asthma was an acquired disease. Over 30% of participants thought epileptic seizures were associated with insanity but asthma attacks were not. Acceptance of children with epilepsy was significantly lower than that of children with asthma. Children with epilepsy were less encouraged by teachers to play with others. Teachers have more consideration for aggression of children with epilepsy than of those with asthma. More teachers were worried about the objection from the other parents if there were a child with epilepsy in the class.

Conclusions: Perceptions of epilepsy and asthma among preschool teachers were different significantly. The finding may explain why the children with epilepsy showed lower school performance among the children with chronic illness in past studies.
Regional Analyses of CNS Microdialysate Glucose and Lactate in Seizure Patients
Authors: Cornford Eain M. , Shamsa Kamran , Zeitzer Jamie M. , Enriquez Cathleen M. , Wilson Charles L. , Behnke Eric J. , Fried Itzhak , Engel Jerome
Published: March 2003

Summary:  Purpose: To correlate glucose (and lactate) results obtained from microdialysate to recent studies suggesting that glucose transporter activity may be significantly altered in seizures.

Methods: We used a fluorometric technique to quantify glucose and lactate levels in microdialysates collected from two to four depth electrodes implanted per patient in the temporal and frontal lobes of a series of four patients. Hour‐by‐hour and day‐to‐day changes in brain glucose and lactate levels at the same site were recorded. Additionally we compared regional variations in lactate/glucose ratios around the predicted epileptogenic region.

Results: Lactate/glucose ratios in the range of 1–2:1 were the most commonly seen. When the lactate/glucose ratio was <1:1, we typically observed a relative increase in local glucose concentration (rather than decreased lactate), suggesting increased transport, perhaps without increased glycolysis. In some sites, lactate/glucose ratios of 3:1–15:1 were seen, suggesting that a circumscribed zone of inhibition of tricarboxylic acid cycle activity may have been locally induced. In these dialysates, collected from probes closer to the epileptogenic region, the large increase in lactate/glucose ratios was a result of both increased lactate and reduced glucose levels.

Conclusions: We conclude that regional variations in brain extracellular glucose concentrations may be of greater magnitude than previously believed and become even more accentuated in partial seizure patients. Data from concomitant assays of microdialysate lactate and glucose may aid in understanding cerebral metabolism.
Magnetic Resonance Spectroscopy in Epilepsy: Clinical Issues
Authors: Cendes Fernando , Knowlton Robert C. , Novotny Edward , Min Li Li , Antel Samson , Sawrie Stephen , Laxer Kenneth D. , Arnold Douglas
Published: March 2003

Summary: Proton magnetic resonance spectroscopy (MRS) studies have shown focal reductions of N‐acetyl aspartate (NAA) signal in patients with different forms of temporal lobe epilepsy (TLE), including those with normal magnetic resonance imaging (MRI), as well as extratemporal partial epilepsies. Both single‐voxel and multivoxel 1H‐MRS have high sensitivity for detecting low NAA, indicative of neuronal dysfunction in focal epilepsies. Decreases in NAA correlate strongly with EEG abnormalities and severity of cell loss, and may be a more sensitive measure than structural MRI. However, the NAA decrease is often more widespread than the epileptogenic focus. The results of published MRS studies suggest that in patients with partial epilepsy, there is a metabolic abnormality throughout the brain, with patterns of asymmetry and focal accentuation that are useful for noninvasive localization of epileptogenic foci. A major limitation of current proton MRS studies in epilepsy is the inability to cover the entire brain in a single acquisition, thus leading to major sampling bias. The area of maximal abnormality may reside farther away, even when there is an abnormality inside of the volume of interest used for that particular examination. Decreased NAA ratios are present even in children at the onset of their epilepsy, and evidence points to a gradual and progressive course of further reduction in NAA values. Conversely, the relative NAA concentration can recover ipsilaterally and contralaterally after successful resection of a temporal lobe focus. These observations, together with the fact of the often widespread NAA abnormality, must be taken into account for the correct and adequate interpretation of proton MRS studies in the assessment of partial epilepsies.
Clinical Significance of Pharmacokinetic Interactions Between Antiepileptic and Psychotropic Drugs
Authors: Spina Edoardo , Perucca Emilio
Published: March 2003

Summary: As antiepileptic drugs (AEDs) and psychotropic agents are increasingly used in combination, the possibility of pharmacokinetic interactions between these compounds is relatively common. Most pharmacokinetic interactions between AEDs and psychoactive drugs occur at a metabolic level, and usually involve changes in the activity of the cytochrome P450 mixed‐function oxidases (CYP) involved in their biotransformation. As a consequence of CYP inhibition or induction, plasma concentrations of a given drug may reach toxic or subtherapeutic levels, and dosage adjustments may be required to avoid adverse effects or clinical failure. Enzyme‐inducing AEDs, such as carbamazepine (CBZ), phenytoin (PHT), and barbiturates, stimulate the oxidative biotransformation of many concurrently prescribed psychotropics. In particular, these AEDs may decrease the plasma concentrations of tricyclic antidepressants, many antipsychotics, including traditional compounds, i.e., haloperidol and chlorpromazine, and newer agents, i.e., clozapine, risperidone, olanzapine, quetiapine, and ziprasidone, and some benzodiazepines. Conversely, new AEDs appear to have a lower potential for interactions with all psychotropic drugs. While antipsychotics and anxiolytics do not significantly influence the pharmacokinetics of most AEDs, some newer antidepressants, such as viloxazine, fluoxetine, and fluvoxamine, may lead to higher serum levels of some AEDs, namely CBZ and PHT, through inhibition of CYP enzymes. No significant pharmacokinetic interactions have been documented between AEDs and lithium. Information about CYP enzymes responsible for the biotransformation of individual agents and about the effects of these compounds on the activity of specific CYP enzymes may help in predicting and avoiding clinically significant interactions. Apart from careful clinical observation, serum level monitoring of AEDs and psychotropic drugs can be useful in determining the need for dosage adjustments, especially if there is any change in seizure control, or possible toxicity.
Models for Epilepsy and Epileptogenesis: Report from the NIH Workshop, Bethesda, Maryland
Authors: Stables James P. , Bertram Edward H. , White H. Steve , Coulter Douglas A. , Dichter Marc A. , Jacobs Margaret P. , Loscher Wolfgang , Lowenstein Daniel H. , Moshe Solomon L. , Noebels Jeffrey L. , Davis Mirian
Published: March 2003

Summary:  Purpose: The workshop explored the current problems, needs, and potential usefulness of existing methods of discovery of new therapies to treat epilepsy patients. Resistance to medical therapy (pharmacoresistance) and the development of epilepsy (epileptogenesis) are recognized as two of the major problems in epilepsy treatment today. At the same time, there is growing awareness that the development of new therapies has slowed, a trend that has economic and scientific roots. To move toward new and more effective therapies, novel approaches to therapy discovery are needed.

Methods: A workshop was held in March 2001 with the charge to develop a plan to move the exploration and discovery process forward. Participants from academia, government, and industry reviewed the current status of epilepsy therapy and explored the identification of potential new therapies.

Results: At the end of the 2‐day meeting, the panel made a series of recommendations. The two major recommendations were (a) to establish a means for continuing the examination of new approaches to therapy discovery, and (b) to identify models and approaches to therapy discovery that may identify treatments that are more successful than those available. Further recommendations were made to support the development of technology (miniaturization, computerization, video monitoring, etc.) to facilitate the use of the new models and to identify the mechanisms of therapy success and failure.

Conclusions: Understanding the epidemiology of therapy resistance and providing support for new approaches to therapy development were identified as key issues for introduction of new and more effective treatments.
Survival of Patients with Epilepsy: An Estimate of the Mortality Risk
Authors: Shackleton Darian P. , Westendorp Rudi G. J. , Kasteleijn‐Nolst Trenité Dorotheé G. A. , De Craen Anton J. M. , Vandenbroucke Jan P.
Published: March 2003

Summary:  Purpose: To investigate the extent and causes of the differences in mortality found in studies on mortality in epilepsy based on a quantitative review of the literature.

Methods: We used MEDLINE database and Cumulative Index Medicus for 1960–2001, Excerpta Medica for 1948–1965, and relevant journals and bibliographies. We selected comparative studies investigating mortality in epilepsy patients conducted in the last 100 years. The Standardized Mortality Ratio (SMR) was selected as primary outcome. Nineteen studies were included. Pooled estimates were precision weighted and tested for homogeneity. Sources of variability between risk estimates were explored by using multivariate fixed‐effects models.

Results: SMRs ranged from 1.3 to 9.3. Risk estimates proved heterogeneous (χ2 test statistic: 1,177; df = 18; p < 0.001). The most important determinant was “source population,” explaining half of the variance of the estimates (R2, 0.47; p = 0.006). SMRs in community studies ranged from 1.3 to 3.1, and for institutionalized populations, from 1.9 to 5.1.

Conclusions: Our results show that the mortality risk in patients with epilepsy is dependent on source population of patients. Within the different source populations, considerable unexplained variance remains. Hence no uniform summary estimate for the elevated mortality could be determined.
Diet Enriched with Omega‐3 Fatty Acids Alleviates Convulsion Symptoms in Epilepsy Patients
Authors: Schlanger Simon , Shinitzky Meir , Yam Daniel
Published: March 2003

Summary:  Purpose: We examined whether a dietary supplement containing omega‐3 polyunsaturated fatty acids (n‐3 PUFAs) can alleviate and/or reduce the frequency of epileptic seizures in patients with central nervous system (CNS) diseases treated with anticonvulsive drugs (ACDs).

Methods: A special spread containing 65% n‐3 PUFAs was added to the daily diet. The patients consumed 5 g of this spread at every breakfast for 6 months.

Results: Five patients completed the study. In all of them, a marked reduction in both frequency and strength of the epileptic seizures was recorded.

Conclusions: Incorporation of the dietary supplement containing n‐3 PUFAs may be beneficial in suppression of some cases of epileptic seizures.
Regional Expression of Multidrug Resistance Genes in Genetically Epilepsy‐prone Rat Brain after a Single Audiogenic Seizure
Authors: Kwan Patrick , Sills Graeme J. , Butler Elaine , Gant Timothy W. , Meldrum Brian S. , Brodie Martin J.
Published: March 2003

Summary:  Purpose: The multidrug resistance (mdr) gene family encodes the drug transport macromolecule P‐glycoprotein (P‐gp), which contributes to the functionality of the blood–brain barrier. Recent evidence suggests that P‐gp–mediated drug extrusion may play a facilitatory role in refractory epilepsy. We investigated the regional expression of mdr genes in genetically epilepsy‐prone rat (GEPR) brain after a single audiogenic seizure.

Methods: Three groups of adult male GEPRs (n = 5/group) were exposed to a seizure‐inducing audiogenic stimulus and killed at 4 h, 24 h, and 7 days thereafter. A further group (n = 5) served as a stimulus‐naïve control. Expression of mdr1a and mdr1b in distinct anatomic brain regions (cortex, midbrain, pons/medulla, hippocampus) was determined by quantitative reverse transcriptase–polymerase chain reaction (RT‐PCR) in the presence of competitive internal standards.

Results: When compared with control, mdr1a expression in cortex and midbrain was significantly (p < 0.05) increased at 24 h after a single audiogenic seizure. Cortical mdr1a expression remained elevated at 7 days after stimulus. In contrast, mdr1a expression in pons/medulla and hippocampus was unchanged. The mdr1b isoform was quantifiable in hippocampus alone and not influenced by seizure activity.

Conclusions: These findings suggest that acute seizures in the GEPR can induce the expression of mdr genes. The pattern of increased expression appears to follow the anatomic pathway of audiogenic seizures in these animals, with initiation in the midbrain and propagation to the cortex. Further studies are required to investigate the effects of recurrent seizure activity and to characterise mdr expression in other experimental seizure models.