bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Migraine Headache Affect Cognitive Function in the Elderly? Report From the Maastricht Aging Study (MAAS)
Authors: Jelicic Marko , Van Boxtel Martin P.J. , Houx Peter J. , Jolles Jelle
Published: March 2003

The aim of this study was to examine two aspects of cognitive functioning—information processing speed and memory—in both young/middle‐aged and older subjects with and without migraine, using data from a large population‐based sample. We found that, although age had a large effect on processing speed and memory, migraine did not influence cognitive performance. In addition, there was no significant interaction between age and migraine on processing speed and memory. Our results suggest that, in the general population, migraine does not seriously affect cognitive functioning in young/middle‐aged or older adults.
Is Blood Homocysteine Elevated in Migraine?
Authors: Hering‐Hanit R. , Gadoth N. , Yavetz A. , Gavendo S. , Sela B.
Published: March 2003

Objective.—To determine total serum homocysteine levels in a large group of patients with migraine with and without aura.

Background.—Hypercoagulable state is a known risk factor for stroke in the young. The existence of a hypercoagulable state has been postulated in migraine and homocysteinemia with young‐onset stroke. To the best of our knowledge, blood homocysteine has not been studied in a significant number of patients with various forms of migraine.

Methods.—Total serum homocysteine was measured with high‐performance liquid chromatography in 78 patients with migraine and in 126 age‐ and sex‐matched healthy volunteers.

Results.—Seventy‐eight patients aged 18 to 65 years were studied: 22 with migraine with aura and 56 with migraine without aura. Only 1 man had significantly elevated blood homocysteine (38.6 μmol/L), while another had a borderline elevation (15.8 μmol/L) (reference value for both sexes in our laboratory is 4 to 14 μmol/L). Both patients suffered from migraine without aura.

Conclusions.—Blood homocysteine is not elevated in migraine.
Does Relaxation Treatment Have Differential Effects on Migraine and Tension‐type Headache in Adolescents?
Authors: Fichtel Åsa , Larsson Bo
Published: March 2003

The present study evaluated the effects of relaxation treatment in 36 adolescents aged 13 to 18 years (mean  ±  SD, 15.4 ± 1.55 years) suffering from migraine or migraine and tension‐type headache as compared with a waiting‐list condition group. The subjects rated various characteristics of migraine and tension‐type headache in a diary. Significant reductions were found for total headache sum (P < .05) and intensity scores of total headache activity (P < .05) as well as for migraine intensity (P < .05) for subjects treated with relaxation as compared with those in the waiting‐list condition group. However, no significant differences between the two groups were found for tension‐type headache. Fifty percent of the adolescents treated with relaxation training attained a clinically significant improvement, compared with 12% of those in the waiting‐list condition. It is suggested that treatment goals for migraine and migraine occurring with tension‐type headache might be different and that relaxation training also might benefit from focusing on specific aspects of the two headache types.
Comparative Study of a Combination of Isometheptene Mucate, Dichloralphenazone With Acetaminophen and Sumatriptan Succinate in the Treatment of Migraine
Authors: Freitag Frederick G. , Cady Roger , DiSerio Frank , Elkind Arthur , Gallagher R. Michael , Goldstein Jerome , Klapper Jack A. , Rapoport Alan M. , Sadowsky Carl , Saper Joel R. , Smith Timothy R.
Published: March 2003

Objective.—To compare the safety and efficacy of isometheptene mucate, dichloralphenazone with acetaminophen to sumatriptan succinate for the treatment of mild‐to‐moderate migraine, with or without aura, when taken at the first sign of an attack.

Background.—The Food and Drug Administration approved sumatriptan succinate and the combination of isometheptene mucate, dichloralphenazone with acetaminophen for the treatment of migraine. As part of the stratified treatment of migraine, those patients whose headaches are mild or moderate may benefit from nontriptan medications. Additionally, early treatment of acute migraine before the headache has become moderate or severe may improve response to treatment.

Methods.—This was a multicenter, double‐blind, randomized, parallel‐group study to assess the safety and efficacy of the combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the early stages of a single migraine attack. Patients diagnosed with migraine, with or without aura, as defined by the International Headache Society diagnostic criteria were enrolled.

Results —One hundred thirty‐seven patients were enrolled in the study. Data for efficacy were available for 126 patients; safety data were available for 128 patients. No statistically significant difference between the two active agents in the patient's response to treatment was demonstrated. Headache recurrence was not significantly different over the 24‐hour evaluation period for those patients responding in the first 4 hours. In those with headache recurrence, it was statistically significantly more severe in those patients treated with sumatriptan succinate. Improvement in functional disability was, in general, better among those treated with isometheptene mucate, dichloralphenazone with acetaminophen. Global analysis of efficacy was similar in the two active groups. Patients treated with sumatriptan succinate were somewhat more likely to have adverse effects than the isometheptene mucate, dichloralphenazone with acetaminophen group.

Conclusions.—Both isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate are safe and effective when used early in the treatment of an acute migraine. Several parameters suggest that isometheptene mucate, dichloralphenazone with acetaminophen may have a slight advantage compared with sumatriptan succinate in the early treatment of mild‐to‐moderate migraine.
Oral Magnesium Load Test in Patients With Migraine
Authors: Trauninger Anita , Pfund Zoltán , Koszegi Tamás , Czopf József
Published: March 2003

Objective.—To determine whether migraineurs may have a systemic deficiency of magnesium.

Background.—Magnesium deficiency has been shown to play a potential role in the pathogenesis of migraine, but there are no data on total body magnesium status in migraineurs.

Methods.—An oral magnesium load test was performed by giving 3000 mg of magnesium lactate during a 24‐hour interictal period to 20 patients with migraine (15 women and 5 men; mean age, 37.9 years) and 20 healthy volunteers (16 women and 4 men; mean age, 39.6 years). Baseline and postload magnesium concentrations were determined from serum and 24‐hour urine specimens.

Results.—There was no significant difference between the groups in the baseline serum and urine magnesium concentrations, although the latter tended to be lower (P = .064) in the migraine group. The postload magnesium concentrations were significantly higher within both the migraine (P  <  .0001 and P < .0001) and the control (P = .0009 and P < .0001) groups compared to the baseline values. After loading, the 24‐hour urinary magnesium excretions were significantly lower (P = .0007) in the patients with migraine than in the controls, but serum values did not differ.

Conclusions.—Magnesium retention occurs in patients with migraine after oral loading, suggesting a systemic magnesium deficiency.
Low‐Dose Tizanidine With Nonsteroidal Anti‐inflammatory Drugs for Detoxification From Analgesic Rebound Headache
Authors: Smith Timothy R.
Published: March 2003

Objective.—To describe an outpatient regimen for analgesic detoxification and resolution of analgesic rebound headache.

Background.—Frequent analgesic use is believed to promote the transformation of episodic migraine into a chronic, pervasive headache syndrome. Management of pain precipitated by analgesic withdrawal is crucial to treatment success. Outpatient treatment protocols designed to achieve successful withdrawal will reduce costs and potentially lead to more widespread implementation of therapy.

Methods.—Patients with appropriate histories were managed on an outpatient basis for detoxification by discontinuation of the offending analgesic and initiation of treatment with tizanidine and a long‐acting nonsteroidal anti‐inflammatory drug. Patients kept diaries of pain and medication use. Results were evaluated at 6 and 12 weeks. Patients able to tolerate no or trivial analgesic use (ie, 4 or fewer doses in each 2‐week period) were considered responders.

Results.—At 6 weeks, 36 patients (65%) were responders. At 12 weeks, 38 patients (69%) were responders. The chronic daily headache pattern had resolved at 12 weeks in 34 patients (62%).

Conclusions.—This treatment protocol was well tolerated and yielded a high degree of efficacy, demonstrating that outpatient management can be effective for achieving analgesic withdrawal and resolution of analgesic rebound headache.
Depression, Automatic Thoughts, Alexithymia, and Assertiveness in Patients With Tension‐type Headache
Authors: Yücel Basak , Kora Kaan , Özyalçín Süleyman , Alçalar Nilüfer , Özdemir Özay , Yücel Aysen
Published: March 2003

Objective.—The role of psychological factors related to headache has long been a focus of investigation. The aim of this study was to evaluate depression, automatic thoughts, alexithymia, and assertiveness in persons with tension‐type headache and to compare the results with those from healthy controls.

Methods.—One hundred five subjects with tension‐type headache (according to the criteria of the International Headache Society classification) and 70 controls were studied. The Beck Depression Inventory, Automatic Thoughts Scale, Toronto Alexithymia Scale, and Rathus Assertiveness Schedule were administered to both groups. Sociodemographic variables and headache features were evaluated via a semistructured scale.

Results.—Compared with healthy controls, the subjects with headache had significantly higher scores on measures of depression, automatic thoughts, and alexithymia and lower scores on assertiveness. Subjects with chronic tension‐type headache had higher depression and automatic thoughts scores than those with episodic tension‐type headache.

Conclusions.—These findings suggested that persons with tension‐type headache have high depression scores and also may have difficulty with expression of their emotions. Headache frequency appears to influence the likelihood of coexisting depression.
Tumor Necrosis Factor Gene Polymorphism in Migraine
Authors: Trabace Simonetta , Brioli Gloria , Lulli Patrizia , Morellini Marina , Giacovazzo Mario , Cicciarelli Germana , Martelletti Paolo
Published: March 2003

Objective.—To better define the involvement of human leukocyte antigen region (HLA) genes in migraine via an association study of the tumor necrosis factor (TNF) genes, located in the HLA class III region, with migraine with and without aura.

Background.—Migraine without aura and migraine with aura are disorders involving multiple factors—environmental and genetic. In a previous study, we hypothesized a protective role for the HLA‐DR2 antigen, providing additional basis for the proposed genetic heterogeneity between migraine without aura and migraine with aura. The cytokines produced by TNF genes are polypeptide effectors of inflammatory reaction and endothelial function.

Methods.—Tumor necrosis factor (TNF)‐308 (TNF−308A and TNF−308G alleles) and lymphotoxin α (TNFB*1 and TNFB*2 alleles) polymorphisms were analyzed by the NcoI‐cleaved polymerase chain reaction‐amplified fragments in 47 patients with migraine without aura, 32 patients with migraine with aura, and 101 migraine‐free controls.

Results.—The frequency of TNFB*2 allele was significantly increased in our patients with migraine without aura as compared with the control group (78.72% versus 61.4%, Pc = .004), but no significant differences were found between patients with migraine with aura and controls. Additionally, there was a significant decrease of TNFB*1 homozygotes in patients with migraine without aura compared with the control group (2.13% versus 16.8%, Pc = .0201). Carriage of the TNFB*2 allele confers a high risk for the development of migraine without aura. No significant association was found at TNF‐308 polymorphism.

Conclusion.—These data support the hypothesis that lymphotoxin α could be a susceptibility gene in migraine without aura and confirm previous data indicating that migraine with and without aura are distinct entities with different genetic backgrounds.
Auditory Hallucinations Associated With Migraine
Authors: Rubin David , McAbee Gary N. , Feldman‐Winter Lori B.
Published: March 2003

Objective.—Two children experienced auditory hallucinations during migraine (one with migraine without aura and one with migraine with aura). These hallucinations only occurred during headache.

Background.—Auditory hallucinations are rarely reported in patients with migraine. These patients often have other psychiatric or neurologic disorders such as affective disorder or epilepsy.

Methods.—Case report and a review of the literature.

Results.—No other neuropsychiatric disorder was identified in either patient at presentation or upon follow‐up.

Conclusions.—Auditory hallucinations can rarely occur in patients with migraine. Further study of this association might provide insight to any relationship between migraine, auditory hallucinations, and the temporal lobe.
Migraine and Coronary Heart Disease in Women and Men
Authors: Cook Nancy R. , Benseñor Isabela M. , Lotufo Paulo A. , Lee I‐Min , Skerrett Patrick J. , Chown Marilyn J. , Ajani Umed A. , Manson JoAnn E. , Buring Julie E.
Published: March 2003

Objective.—We evaluated migraine as an independent risk factor for subsequent coronary heart disease (CHD) events among women in the Women's Health Study (WHS) and men in the Physicians' Health Study (PHS).

Background.—Although several studies have suggested that migraine is associated with increased risk of stroke, there are few and conflicting data on whether migraine predicts risk of future CHD events.

Methods.—The WHS is an ongoing randomized, double‐blind, placebo‐controlled trial of low‐dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer in 39,876 women health professionals aged 45 years in 1993, and the PHS is a completed randomized, double‐blind, placebo‐controlled trial of aspirin and β‐carotene in the primary prevention of cardiovascular disease and cancer in 22,071 men physicians aged 40 to 84 years in 1982. Primary endpoints were defined as major CHD (nonfatal myocardial infarction [MI] or fatal CHD) and total CHD (major CHD plus angina and coronary revascularization).

Results.—After adjusting for other CHD risk factors, female health professionals and male physicians reporting migraine were not at increased risk for subsequent major CHD (women: relative risk [RR], 0.83; 95% confidence interval [CI], 0.53 to 1.29; men: RR, 1.02; 95% Cl, 0.79 to 1.31) or total CHD (women: RR, 1.01; 95% Cl, 0.76 to 1.34; men: RR, 0.98; 95% Cl, 0.82 to 1.18). When considered separately, there was also no increase in risk of MI or angina.

Conclusion.—These prospective data suggest that migraine is not associated with increased risk of subsequent CHD events in women or men.
Impact of Chest Pain on Cost of Migraine Treatment With Almotriptan and Sumatriptan
Authors: Wang Joseph T. , Barr Charles E. , Goldfarb Scott D.
Published: March 2003

Chest‐related symptoms occur with all triptans; up to 41% of patients with migraine who receive sumatriptan experience chest symptoms, and 10% of patients discontinue treatment. Thus, the cost of chest pain‐related care was estimated in migraineurs receiving almotriptan 12.5 mg versus sumatriptan 50 mg. A population‐based, retrospective cohort study used data to quantify the incidence and costs of chest pain‐related diagnoses and procedures. An economic model was constructed to estimate annual cost savings per 1000 patients receiving almotriptan versus sumatriptan based on the reported rates of chest pain. Annual direct medical cost avoided was calculated for a hypothetical health plan covering 1 million lives. Among a cohort of 1390 patients, the incidence of chest pain‐related diagnoses increased significantly by 43.6% with sumatriptan (P=.003). Aggregate costs for chest pain‐related diagnoses and procedures increased from $22  713 to $30  234. Payments for inpatient hospital services, costs for primary care visits, and costs for outpatient hospital visits increased by over 100%, 53.1%, and 14.4%, respectively. The model predicted $11  215 in direct medical cost savings annually per 1000 patients treated with almotriptan versus sumatriptan. Annual direct medical costs avoided totaled $194 358, and when applied to recent estimates of 86 million lives currently covered by almotriptan treatment, translates into an annual cost savings of just under $17 million for chest pain and associated care. Thus, using almotriptan in place of sumatriptan will likely reduce the cost of chest pain‐related care.
Prognostic Significance of Failure of the Initial Antiepileptic Drug in Children with Absence Epilepsy
Authors: Wirrell Elaine , Camfield Carol , Camfield Peter , Dooley Joseph
Published: March 2003

Summary:  Purpose: In children with childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE), to determine the impact of failure of initial antiepileptic drug (AED) for lack of efficacy in eventual seizure control and long‐term remission of epilepsy.

Methods: Centralized EEG records for the province of Nova Scotia allowed identification of all children seen with CAE or JAE between 1977 and 1985. Information regarding success or failure of initial AED in fully controlling seizures and long‐term seizure control and remission of epilepsy was collected by patient questionnaire and chart review.

Results: Eighty‐six of 92 eligible patients were followed up (75 CAE, 11 JAE). Initial AED treatment was successful in 52 (60%) of 86. Success tended to be greater for valproate (VPA) than for other AEDs (p = 0.07), and lower if generalized tonic–clonic or myoclonic seizures coexisted (p < 0.004 and p < 0.03). Terminal remission was more likely if the initial AED was successful than if it had failed (69% vs. 41%; p < 0.02). Compared with those in whom the initial AED was successful, subjects whose initial AED had failed were more likely to progress to juvenile myoclonic epilepsy (JME) at last follow‐up (32% vs. 10%; p < 0.02) and to develop intractable epilepsy (17% vs. 2%; p < 0.04).

Conclusions: Initial AED was successful in 60% of children with AE. If the first AED failed, the outcome was less favorable, with a lower rate of terminal remission and a higher rate of progression to JME and intractable epilepsy.
Interictal 99mTc‐HMPAO SPECT in Temporal Lobe Epilepsy: Relation to Clinical Variables
Authors: Avery Robert A. , Zubal I. George , Studholme Colin , Slawski Jessica , Corsi Maria , Spencer Dennis D. , Spencer Susan S.
Published: March 2003

Summary:  Purpose: Factors affecting blood flow observed by interictal single‐photon emission computed tomography (SPECT) images in temporal lobe epilepsy (TLE) have not been systematically studied or consistently demonstrated. We evaluated interictal SPECT results with respect to many clinical variables in a large population of TLE patients, all of whom underwent temporal lobectomy.

Methods: Interictal 99mTc‐HMPAO SPECT scans from 61 TLE patients were obtained before an anterior temporal lobectomy. SPECT was analyzed using a region of interest analysis (ROI) in the cerebellum, anterior temporal lobe, lateral temporal lobe, mesial temporal lobe, whole temporal lobe, and inferior frontal lobe. Asymmetry indices (AIs) were calculated. Correlative analysis of AIs and clinical variables was performed.

Results: The AIs from TLE patients differed significantly from those of controls in the anterior temporal (p < 0.01), lateral temporal (p < 0.001), and whole temporal (p < 0.01) regions. No consistent overall correlation between the AIs and clinical variables existed. In right TLE (RTLE) only, AIs in the lateral and whole temporal lobe were positively correlated with age of onset (r = 0.470, p < 0.05; r = 0.548, p < 0.01, respectively). Similarly, in RTLE only, duration of epilepsy was negatively correlated with the anterior (r = −0.395, p < 0.05) and mesial (r = −0.45, p < 0.05) temporal lobe AI. No correlations were found between clinical variables and AIs in left TLE (LTLE) patients.

Conclusions: Significant correlation of age at onset and duration of epilepsy with AIs in RTLE but not LTLE suggests physiologic processes may be determined in part by laterality of TLE. Clinical applications are problematic.
Medically Intractable, Localization‐related Epilepsy with Normal MRI: Presurgical Evaluation and Surgical Outcome in 43 Patients
Authors: Siegel Adrian M. , Jobst Barbara C. , Thadani Vijay M. , Rhodes C. Harker , Lewis Petra J. , Roberts David W. , Williamson Peter D.
Published: March 2003

Summary:  Purpose: High‐resolution magnetic resonance imaging (MRI) plays a crucial role in the presurgical evaluation of patients with medically refractory partial epilepsy. Although MRI detects a morphologic abnormality as the cause of the epilepsy in the majority of patients, some patients have a normal MRI. This study was undertaken to explore the hypothesis that in patients with normal MRI, invasive monitoring can lead to localization of the seizure‐onset zone and successful epilepsy surgery.

Methods: A series of 115 patients with partial epilepsy who had undergone intracranial electrode evaluation (subdural strip, subdural grid, and/or depth electrodes) between February 1992 and February 1999 was analyzed retrospectively. Of these, 43 patients (37%) had a normal MRI.

Results: Invasive monitoring detected a focal seizure onset in 25 (58%) patients, multifocal seizure origin in 12 (28%) patients, and in six patients, no focal seizure origin was found. Of the 25 patients with a focal seizure origin, cortical resection was performed in 24, of whom 20 (83%) had a good surgical outcome with respect to seizure control. Six of the 12 patients with multifocal seizure origin underwent other forms of epilepsy surgery (palliative cortical resection in two, anterior callosotomy in two, and vagal nerve stimulator placement in two).

Conclusions: Successful epilepsy surgery is possible in patients with normal MRIs, but appropriate presurgical evaluations are necessary. In patients with evidence of multifocal seizure origin during noninvasive evaluation, invasive monitoring should generally be avoided.
Bilateral Medial Prefrontal and Temporal Neocortical Hypometabolism in Children with Epilepsy and Aggression
Authors: Juhász Csaba , Behen Michael E. , Muzik Otto , Chugani Diane C. , Chugani Harry T.
Published: March 2003

Summary: Purpose:To identify brain regions with abnormal function in children with intractable partial epilepsy and aggressive behavior by using 2‐deoxy‐2‐[18F]fluoro‐d‐glucose (FDG) positron emission tomography (PET).

Methods:Six children (mean age, 9.9 years) with intractable partial epilepsy and aggressive behavior underwent detailed psychodevelopmental assessment and FDG‐PET scanning. The objective technique of statistical parametric mapping (SPM) was applied to define focal abnormalities of glucose metabolism, and compared those with those of a group of normal adult subjects (n = 17) as well as age‐matched children with epilepsy with similar seizure characteristics but without aggression (n = 7). The findings were analyzed further by using a region‐of‐interest (ROI) approach.

Results:The aggressive children all showed developmental delay, and four of them also manifested autistic symptoms. SPM analysis demonstrated extensive glucose hypometabolism in the aggressive group bilaterally in the temporal and prefrontal cortex compared with that in normal adult controls. A focal area of medial prefrontal glucose hypometabolism was defined in the aggressive children as compared with the nonaggressive pediatric group with SPM, whereas ROI comparison of these groups confirmed prefrontal hypometabolism and also showed glucose hypometabolism of the temporal neocortex in the aggressive children. Severity of aggression correlated inversely with glucose metabolism of the left temporal as well as bilateral medial prefrontal cortex.

Conclusions:Bilateral prefrontal and temporal neocortical brain glucose hypometabolism in children with epilepsy and aggressive behavior may indicate a widespread dysfunction of cortical regions, which normally exert an inhibitory effect on subcortical aggressive impulses. PET studies may be used to elucidate the neurobiologic basis of aggressive behavior in children.
Hypohidrosis Related to the Administration of Topiramate to Children
Authors: Arcas Joaquín , Ferrer Teresa , Roche María C. , Martínez‐Bermejo Antonio , López‐Martín Valentín
Published: March 2003

Summary:  Purpose: Topiramate (TPM) is an antiepileptic agent, first licensed in the United Kingdom in 1994, that is used in the treatment of patients with refractory seizure disorders. TPM is a monosaccharide d‐fructose derivate, with sulfamate function, and so far, few adverse side effects have been reported.

Methods: We describe three patients with epilepsy who were treated with TPM and developed hypohidrosis, heat and exercise intolerance, as well as fever. The sudomotor function was assessed after peripheral stimulation with pilocarpine iontophoresis.

Results: Sweat response was reduced in all three patients. Signs and symptoms ceased after drug suppression.

Conclusions: This side effect associated with TPM, which has not been described previously, can be clinically significant during heat stress and exercise challenge.
Overexpression of Multiple Drug Resistance Genes in Endothelial Cells from Patients with Refractory Epilepsy
Authors: Dombrowski Stephen M. , Desai Shailesh Y. , Marroni Matteo , Cucullo Luca , Goodrich Kris , Bingaman William , Mayberg Marc R. , Bengez Ljiljana , Janigro Damir
Published: March 2003

Summary: Purpose:It has been suggested that altered drug permeability across the blood–brain barrier (BBB) may be involved in pharmacoresistance to antiepileptic drugs (AEDs). To test this hypothesis further, we measured multiple drug resistance (MDR) gene expression in endothelial cells (ECs) isolated from temporal lobe blood vessels of patients with refractory epilepsy. ECs from umbilical cord or temporal lobe vessels obtained from aneurysm surgeries were used as comparison tissue.

Methods:cDNA arrays were used to determineMDRexpression. MDR protein (MRP1) immunocytochemistry and Western blot analysis were used to confirm cDNA array data.

Results:We found overexpression of selected MDR and significantly higher P‐glycoprotein levels in “epileptic” versus “control” ECs. Specifically,MDR1,cMRP/MRP2,andMRP5were upregulated in epileptic tissue, whereasPgp3/MDR3levels were comparable to those measured in comparison tissue. The gene encoding cisplatin resistance–associated protein (hCRA‐α) also was overexpressed in epileptic tissue. Immunocytochemical analysis revealed thatMDR1immunoreactivity was localized primarily in ECs; MRP1 protein levels also were significantly higher in epileptic tissue.

Conclusions:Complex MDR expression changes may play a role in AEDs pharmacoresistance by altering the permeability of AEDs across the BBB.
Fosphenytoin: Pharmacokinetics and Tolerance of Intramuscular Loading Doses
Authors: Pryor Flavia M. , Gidal Barry , Ramsay R. Eugene , DeToledo John , Morgan Robert O.
Published: March 2003

Summary:  Purpose: Fosphenytoin (FPHT; Cerebyx) is well absorbed when given intramuscularly (IM). All prior pharmacokinetic studies had the first plasma sample obtained 30 min after IM administration. The objectives of this study were to determine the rate and extent of FPHT absorption and to evaluate the tolerability of IM FPHT compared with IM saline.

Methods: This was an open‐label, double‐blinded study in which patients received 10 mg/kg dose of IM FPHT in one gluteus and IM saline in the other gluteus. Half the patients received saline injection of equal volume to FPHT (up to 19.5 mL); the other half received 2 mL of saline. Neurologic examination, vital signs, PHT blood samples, injection site examination, and subjective pain scores at injection site were obtained before and at timed intervals for 6 h.

Results: Total PHT serum concentrations 10 μg/mL were obtained in 5 min in 14.3% of patients and in 26.3% after 10 min. More than half the patients had therapeutic serum concentrations at 30 min; 45.8% of patients reported no pain at either the FPHT or saline injection site. No significant difference in pain was noted between FPHT and saline injection sites at 60 min and thereafter. Early decrease in blood pressure occurred but was not clinically significant. Classic PHT‐induced central nervous system (CNS) side effects were evident in one third of patients within 1 h after injection.

Conclusions: (a) IM FPHT is rapidly absorbed (therapeutic levels achieved as early as 5–20 min). (b) IM FPHT is well tolerated by most patients irrespective of injection volume.
Disparity of Perfusion and Glucose Metabolism of Epileptogenic Zones in Temporal Lobe Epilepsy Demonstrated by SPM/SPAM Analysis on 15O Water PET, [18F]FDG‐PET, and [99mTc]‐HMPAO SPECT
Authors: Lee Dong Soo , Lee Jae Sung , Kang Keon Wook , Jang Myoung Jin , Lee Sang Kun , Chung June‐Key , Lee Myung Chul
Published: March 2003

Summary:  Purpose: To elucidate uncoupling of perfusion and metabolism and its significance in epilepsy, 15O water and 18F fluorodeoxyglucose (FDG) positron emission tomography (PET) and Tc‐99m hexamethyl‐propyleneamine‐oxime (HMPAO) single‐photon emission computed tomography (SPECT) were examined by SPM (statistical parametric mapping) and quantitation by using SPAM (statistical probabilistic anatomic map).

Methods: [15O]water and [18F]FDG‐PET, and [99mTc]‐HMPAO SPECT were performed in 25 patients (SPECT in 17 of 25) with medial temporal lobe epilepsy. For volume of interest (VOI) count analysis, the normalized counts using VOI based on SPAM templates of PET and SPECT were compared with those of the normal controls. Perfusion or metabolism was found abnormal if the Z score was >2 for each VOI. For SPM analysis, the differences between each patient's image and a group of normal control images (t statistic for p < 0.01) on a voxel‐by‐voxel basis were examined to find significant decreases in perfusion or metabolism.

Results: With SPAM VOI count analysis, areas of hypoperfusion were found in 13 patients in the epileptogenic temporal lobes by [15O]water PET and areas of hypometabolism in 21 patients by [18F]FDG‐PET. With voxel‐based SPM analysis, the epileptogenic zones were localized in 15 by [15O]water PET and in 23 patients by [18F]FDG‐PET. The localization by [15O]water PET was concordant with that of [18F]FDG‐PET. The areas of hypoperfusion on [15O]water PET were absent or smaller than the areas of hypometabolism on [18F]FDG‐PET. Interictal [99mTc]‐HMPAO SPECT revealed the hypoperfused zones in seven of 17 patients on visual assessment.

Conclusions: SPAM VOI count and SPM analysis of [15O]water and [18F]FDG‐PET and [99mTc]‐HMPAO SPECT revealed that in the same patients, the areas of hypoperfusion were concordant with but smaller than the areas of hypometabolism. Discordance of perfusion and metabolic abnormalities represents an uncoupling of perfusion and metabolism in the epileptogenic zones, and this might explain the lower diagnostic accuracy of perfusion imaging in temporal lobe epilepsy.
Diagnostic Performance of [18F]FDG‐PET and Ictal [99mTc]‐HMPAO SPECT in Occipital Lobe Epilepsy
Authors: Kim Seok‐Ki , Lee Dong Soo , Lee Sang Kun , Kim Yu Kyeong , Kang Keon Wook , Chung Chun Kee , Chung June‐Key , Lee Myung Chul
Published: March 2003

Summary:  Purpose: We investigated whether interictal F‐18 fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) or ictal [99mTc]‐HMPAO single‐photon emission computed tomography (SPECT) was useful to find epileptogenic zones in occipital lobe epilepsy (OLE).

Methods: We reviewed visually and quantified patterns of hypometabolism in interictal [18F]FDG‐PET and those of hyperperfusion in ictal SPECT in 17 OLE patients (27 ± 6.8 years old; M/F, 10/7; injection time, 30 ± 17 s). OLE was diagnosed based on invasive electroencephalography, surgery, and postsurgical outcome (Engel class I in all at an average of 26 months after surgery).

Results: Epileptogenic zones were correctly localized in nine (60%) of 15 patients by interictal [18F]FDG‐PET, and asymmetric indices corroborated visual diagnosis. Epileptogenic hemispheres were correctly lateralized in 14 (93%) of 15 patients on [18F]FDG‐PET. Epileptogenic hemispheres were correctly lateralized in 13 (76%) of 17 patients using ictal SPECT, but localization was possible in only five (29%) patients. Interictal [18F]FDG‐PET was helpful in two of the patients who showed no abnormality on magnetic resonance imaging (MRI) and no possible localization with ictal SPECT.

Conclusions: In OLE, ictal SPECT was helpful in lateralization, but less helpful in localization. Interictal [18F]FDG‐PET was helpful in localization or lateralization of epileptogenic zones, even in patients with ambiguous MRI or ictal SPECT findings.
Tooth Brushing–Induced Seizures: A Case Report
Authors: Koutroumanidis Michael , Pearce Ronald , Sadoh Danesi R. , Panayiotopoulos Chrysostomos P.
Published: March 2003

Summary: We report a 28‐year‐old woman of normal intellect, who had three late‐onset seizures with unusual ictal features and secondary generalization during prolonged and vigorous tooth brushing. Neurologic examination and brain magnetic resonance imaging (MRI) were normal, but interictal EEG showed left frontal epileptiform activity. Reasonable precautions (regular but briefer and less vigorous brushing of her teeth) combined with a moderate dose of carbamazepine effectively prevented seizure recurrence. This case may be an example of cryptogenic form of reflex epilepsy with seizures induced exclusively by tooth brushing.
Seizure‐Associated Headache in Epilepsy
Authors: Leniger Tobias , Isbruch Katrin , Von Den Driesch Sandra , Diener Hans Christoph , Hufnagel Andreas
Published: March 2003

Summary:  Purpose: Headache is often ignored as a symptom of epileptic seizures. The purpose of this prospective study was to analyze frequency, classification, and characteristics of seizure‐associated headache (SH) according to the criteria of the International Headache Society.

Methods: Over a period of 15 months, 341 patients with epilepsy, consecutively evaluated at our outpatient clinic for SH, completed a standardized questionnaire.

Results: Of the 341 epilepsy patients, 115 (34%) experienced SH with a pain intensity of 6.1 ± 1.6 (SD) on the visual analogue scale and a duration of 12.8 ± 15.7 (SD) h. Seizures were always accompanied by headache in 69 (60%) of these 115 patients. SH occurred in four (3%) of 115 patients only preictally, in 31 (27%) of 115 patients periictally, and in 80 (70%) of 115 patients only postictally. In the majority of the 115 patients (55.7%), SH could be classified as migraine headache, whereas in 36.5%, as tension‐type headache. The type of SH was not correlated with sex, an epilepsy syndrome, or a seizure type. Migraine‐like SH was significantly associated with a history of migraine (p < 0.001). In 20 (77%) of the 26 patients experiencing migraine‐like SH with a history of migraine, the phenomenology of migraine‐like SH and migraine attacks was identical.

Conclusions: SH is a frequent, long‐lasting, and severe symptom of epileptic seizures, causing major impairment of daily living. A history of migraine significantly increases the risk for developing migraine‐like SH.
Electroencephalographic Characterization of an Adult Rat Model of Radiation‐Induced Cortical Dysplasia
Authors: Kondo Shinji , Najm Imad , Kunieda Takeharu , Perryman Scott , Yacubova Karina , Lüders Hans O.
Published: March 2003

Summary:  Purpose: Cortical dysplasia (CD) is a frequent cause of medically intractable focal epilepsy. The mechanisms of CD‐induced epileptogenicity remain unknown. The difficulty in obtaining and testing human tissue warrants the identification and characterization of animal model(s) of CD that share most of the clinical, electroencephalographic (EEG), and histopathologic characteristics of human CD. In this study, we report on the in vivo EEG characterization of the radiation‐induced model of CD.

Methods: Timed‐pregnant Sprague–Dawley rats were irradiated on E17 using a single dose of 145 cGy or left untreated. Their litters were identified and implanted with bifrontal epidural and hippocampal depth electrodes for prolonged continuous EEG recordings. After prolonged EEG monitoring, animals were killed and their brains sectioned and stained for histologic studies.

Results: In utero–irradiated rats showed frequent spontaneous interictal epileptiform spikes and spontaneous seizures arising independently from the hippocampal or the frontal neocortical structures. No epileptiform or seizure activities were recorded from age‐matched control rats. Histologic studies showed the presence of multiple cortical areas of neuronal clustering and disorganization. Moreover, pyramidal cell dispersion was seen in the CA1>CA3 areas of the hippocampal formations.

Conclusions: Our results further characterize the in vivo EEG characteristics of the in utero radiation model of CD using long‐term EEG monitoring. This model may be used to study the molecular and cellular changes in epileptogenic CD and to test the efficacy of newer antiepileptic medications.
Typical and Atypical Perfusion Patterns in Periictal SPECT of Patients with Unilateral Temporal Lobe Epilepsy
Authors: Wichert‐Ana Lauro , Velasco Tonicarlo Rodrigues , Terra‐Bustamante Vera Cristina , Araújo David , Júnior Veriano Alexandre , Kato Mery , Leite João Pereira , Assirati João Alberto , Machado Hélio Rubens , Bastos Alexandre Cunha , Sakamoto Américo Ceiki
Published: March 2003

Summary:  Purpose: To characterize perfusion patterns of periictal single‐photon emission tomography (SPECT) in patients with unilateral temporal lobe epilepsy (TLE) and to determine their relationship to the epileptogenic zone (EZ).

Methods: We studied periictal SPECT scans of 53 patients after anterior mesial temporal lobectomy who had good seizure outcome after surgery. Ictal SPECT scans were performed during video‐EEG monitoring. Typical SPECT patterns consisted of ipsilateral ictal hyperperfusion or ipsilateral postictal hypoperfusion. Atypical ictal patterns included normal scans, bilateral temporal hyperperfusion, or contralateral patterns. These perfusion patterns were retrospectively analyzed searching for concordance rate with the EZ.

Results: We obtained 51 ictal and two early postictal scans. In the typical group, 40 (75.4%) patients had ipsilateral ictal temporal lobe hyperperfusion, and one (1.9%) patient had ipsilateral postictal temporal lobe hypoperfusion. Twelve (22.7%) patients exhibited atypical perfusion patterns: seven (13.2%) patients had bitemporal ictal hyperperfusion (four cases showed asymmetric temporal lobe changes), four (7.6%) patients had contralateral hyperperfusion, and one (1.9%) patient had a normal SPECT scan. All four patients with bitemporal asymmetric hyperperfusions showed greater perfusion lateralized to the side of the EZ. Three of the four patients who had contralateral hyperperfusion also had a complex postictal‐like pattern in the ipsilateral temporal lobe consisting of anteromesial hyperperfusion with adjacent lateral hypoperfusion.

Conclusions: This study analyzed typical and atypical perfusion patterns in unilateral TLE, and suggested that not only typical, but also some atypical perfusion patterns may contribute to the lateralization of EZ.
Hemifacial Seizure of Cerebellar Ganglioglioma Origin: Seizure Control by Tumor Resection
Authors: Chae Jong Hee , Kim Seung‐Ki , Wang Kyu‐Chang , Kim Ki Joong , Hwang Yong‐Seung , Cho Byung‐Kyu
Published: March 2003

Summary: The cerebellum is known to have an inhibitory effect on seizures. Nevertheless, cerebellar dysplastic lesions can be epileptogenic. A 4‐month‐old infant had paroxysmal facial contractions; tachypnea and nystagmoid eyeball and tremulous movements were occasionally combined. These evolved to stereotypic clinical patterns and frequencies, which increased despite administration of antiepileptic drugs (AEDs). Magnetic resonance imaging (MRI) demonstrated a mass arising from the superior cerebellar peduncle, although video‐scalp EEG monitoring revealed no abnormal findings. Positron emission tomography with [18F]fluorodeoxyglucose revealed focal hypermetabolism in the same area identified by MRI. A depth electrode implanted in the mass revealed focal spike‐and‐wave discharges. The lesion was partly removed; pathologic diagnosis was ganglioglioma. Because of incomplete seizure control and residual tumor visible on MRI, a second operation was performed. After complete excision of the tumor, the patient became seizure free without AEDs. This case confirms the presence of seizure originating from the cerebellum and emphasizes the need for the complete removal of an epileptogenic lesion.
Usefulness of the Head‐Upright Tilt Test for Distinguishing Syncope and Epilepsy in Children
Authors: Eirís‐Puñal J. , Rodríguez‐Núñez A. , Fernández‐Martínez N. , Fuster M. , Castro‐Gago M. , Martinón J. M.
Published: March 2003

Summary:  Purpose: Episodic loss of consciousness in children, whether or not associated with hypertonia or short‐duration clonic movements, presents a diagnostic challenge to the pediatrician and child neurologist. We provide some evidence of the usefulness of the head‐upright tilt test for investigating the causes of transient loss of consciousness in children, and for distinguishing between syncope, convulsive syncope, and epilepsy.

Methods: We studied nine children previously diagnosed as epileptic on the basis of compatible clinical events and epileptiform findings in routine EEGs who were treated over the long term with antiepileptic drugs, but whose clinical records suggested syncope or convulsive syncope rather than epilepsy on reevaluation. All subjects underwent head‐upright tilt testing.

Results: The tilt‐test result was positive in all nine cases, with the patients reporting the same symptoms as in the previously considered epileptic attacks.

Conclusions: Inadequate histories and misuse/overinterpretation of EEG results often lead to misdiagnosis of epilepsy in children. The head‐upright tilt test is a useful and reliable diagnostic technique, allowing syncopal events to be induced and evaluated under controlled conditions. In a subset of patients, it may help to distinguish epilepsy from simple or convulsive syncope.
A Postmarketing Surveillance Study of Gabapentin as Add‐on Therapy for 3,100 Patients in England
Authors: Wilton Lynda V. , Shakir Saad
Published: March 2003

Summary:  Purpose: Our aim was to monitor the use of gabapentin (GBP) by patients prescribed this drug by primary care physicians in England soon after it was marketed in the United Kingdom.

Methods: A noninterventional observational cohort study was conducted by using the technique of prescription‐event monitoring. Patients were identified from dispensed National Health Service prescriptions. Outcome data were obtained from questionnaires sent to the doctor ∼6 months after the initial prescription. These data included demographic information, events reported since starting GBP, and reason for stopping the drug, if it was stopped. Incidence rates were calculated for given periods for all events reported. Additional information was requested for selected events of medical interest, including pregnancies. Standardised mortality ratio (SMR) was calculated.

Results: The cohort comprised 3,100 patients, of whom 136 (4%) were children. The median duration of treatment was 8.1 months. The most frequently reported adverse events reported during the first month of treatment, drowsiness/sedation, dizziness, and malaise/lassitude, also were the commonest reasons for discontinuing GBP and reported as suspected adverse drug reactions (ADRs). There were no congenital anomalies in the 11 babies born to women who used GBP during the first trimester of pregnancy. Crude mortality rate was 5 times that in general population but similar to that in other published studies.

Conclusions: Neurologic‐related events were the most frequently reported adverse events. They also were the commonest reasons for discontinuing treatment and reported as suspected ADRs. No previously unrecognised adverse events were detected in this large cohort of patients who were among the first treated with gabapentin in England.
Performance Reassessment of a Real‐time Seizure‐detection Algorithm on Long ECoG Series
Authors: Osorio Ivan , Frei Mark G. , Giftakis Jon , Peters Tom , Ingram Jeff , Turnbull Mary , Herzog Michele , Rise Mark T. , Schaffner Scott , Wennberg Richard A. , Walczak Thaddeus S. , Risinger Michael W. , Ajmone‐Marsan Cosimo
Published: March 2003

Summary:  Purpose: Automated seizure detection and blockage requires highly sensitive and specific algorithms. This study reassessed the performance of an algorithm by using a more extensive database than that of a previous study and its suitability for safety/efficacy closed‐loop studies to block seizures in humans.

Methods: Up to eight electrocorticography (EcoG) channels from 15 subjects were analyzed off‐line. Visual and computerized analyses of the data were performed by different (blinded) investigators. Independent visual analysis also was performed for clinical seizures and for detections identified only by the algorithm. The following were computed: FP rate, number of FNs, latency to automated detection, warning rate for clinical onset and warning times, seizure duration/intensity, and interrater agreement. Adaptations to improve performance were performed when indicated.

Results: Fourteen subjects met inclusion criteria. Generic algorithm “relative sensitivity” for clinical seizures was 100%; two undetected subclinical seizures and two unclassified seizures were captured after adaptation. FPs/day were zero in seven and fewer than one in an additional three subjects. Adaptations for four subjects with greater than 1 FP/day (7.7–66.6/day) reduced the rate to 0 in one subject and to fewer than five FP/day (1.7–4.2/day) in the remainder. Generic latency to automated detection was <5 s in eight of 13 subjects, and in 12 of 13 after adaptation. Detections provided warning of clinical onset in three of four subjects in whom it always followed electrographic onset, and in four of four after adaptation. Interrater agreement was low for FPs and EDs.

Conclusions: The generic algorithm demonstrated high sensitivity, specificity, and speed, characteristics further enhanced by adaptation. This algorithm is well suited for seizure detection/warning and use in safety/efficacy closed‐loop therapy studies.