bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of Combined Lysine Acetylsalicylate and Metoclopramide: Repeated Intakes in Migraine Attacks
Authors: Pradalier A. , Chabriat H. , Danchot J. , Baudesson G. , Joire J.E.
Published: March 2003

The efficacy of the combination of lysine acetylsalicylate and metoclopramide in the treatment of migraine attacks has been established previously. The value of repeated doses of such a combination has been reported in a recent study.

The purposes of this open‐label study performed by general practitioners on a very large sample of migraine sufferers were to confirm that repeated doses of the combined treatment are efficient and well‐tolerated, and to assess the efficacy of treatment according to the initial headache intensity.

Three thousand seven hundred twenty‐seven general practitioners entered 7259 migraine sufferers. Patients had to use a first dose, the efficacy of which was assessed 2 hours later. In the case of failure, they were then able to take a second dose and possibly a third dose, 2 hours after the second, in the case of persistent failure. Twelve thousand five hundred sixty‐two migraine attacks were analyzed. Tolerance, as assessed by the patients, was considered as good in more than 85% of attacks, whatever the number of doses utilized. Five hundred thirty‐five adverse effects were reported after the use of 22 697 sachets. Of 12 515 attacks documented for efficacy, patients considered the treatment as good or excellent in 80% of attacks treated with one dose, 55% of those treated with two doses, and 27% of those treated with three doses. Relief of headache (reduction of its severity from grade 3 or 2 to 1 or 0) was observed in 51% of episodes after the first sachet, 51% of episodes treated with a second sachet, and 56% of episodes treated with a third sachet. The first dose of treatment was found to be more effective when the initial severity of the headache was moderate (improvement in 66% of attacks) than when it was severe (improvement in 30% of attacks). Efficacy appeared to increase according to the number of doses when headache was initially severe.

This trial confirms that repeated doses of this combination is well‐tolerated and effective. Our results show that repeated doses are particularly useful for severe attacks.
Headache and Cardiovascular Risk Factors: Positive Association With Hypertension
Authors: Cirillo Massimo , Stellato Davide , Lombardi Cinzia , De Santo Natale G. , Covelli Vito
Published: March 2003

The study analyzes the prevalence of cardiovascular risk factors in 1343 patients with severe headache (399 men and 944 women), aged 15 to 64 years; analyses were controlled for sex, age, and type and frequency of headache. Prevalence of various forms of headache was different between men and women. Age and days per year with headache were significantly different among various forms of headache. For men and women with headache, age directly related to prevalence of hypertension, hypercholesterolemia, and obesity. Due to low prevalence, analyses by age were not done for diabetes mellitus. For cigarette smoking, prevalence was not related to age in men, but was inversely related to age in women. With control for age, prevalence of cardiovascular risk factors was not significantly different among patients with different forms of headache, except for cluster headache. Among men with cluster headache, prevalence was high for cigarette smoking, but low for hypercholesterolemia. With control for age, days per year with headache did not relate to prevalence of cardiovascular risk factors except for cigarette smoking in men. Compared to data for a population sample used as control, patients with headache had higher prevalence of hypertension in both sexes, independent of age (odds ratio 1.51, 95% confidence interval 1.28 to 1.80); the difference between patients with headache and the control population was lower with increasing age. The high prevalence of hypertension among patients with headache was not due to overweight. The data indicate that headache is significantly associated with hypertension, but not with other cardiovascular risk factors.
Prothrombotic Genetic Risk Factors in Patients With Coexisting Migraine and Ischemic Cerebrovascular Disease
Authors: Iniesta J.A. , Corral J. , González‐Conejero R. , Rivera J. , Vicente V
Published: March 2003

The role of hemostatic elements in stroke has been clearly defined but several prothrombotic polymorphisms of hemostatic factors, important for other thromboembolic disorders, seem not to be very significant in stroke. Recently, the high prevalence of factor V Leiden in patients with stroke and a history of migraine has suggested an association between migraine and prothrombotic genetic risk factors. Stroke being a multifactorial disease, the aim of this study was to test whether prothrombotic tendencies increase the risk of stroke in patients with migraine.

We determined the prevalence of four prothrombotic genetic risk factors (factor V R/Q 506, factor II 20210 G/A, decanucleotide insertion/deletion in the factor VII promoter, and the platelet HPA‐1 alloantigen system) in 17 patients with coexisting ischemic cerebrovascular disease and migraine, 107 patients with ischemic cerebrovascular disease, 106 patients with migraine, and 202 control subjects. Genotyping for all polymorphisms analyzed in our study were performed after specific genomic polymerase chain reaction, and confirmed by single‐strain conformation polymorphism analysis.

In the group of patients with coexisting ischemic cerebrovascular disease and migraine, the prevalence of prothrombotic genotypes (factor V Leiden, 5.8%; factor II 20210 A, 0%; factor VII A1, 70.6%; and HPA‐1b, 35.3%) was similar to that obtained in all other groups. We can conclude that the studied polymorphisms do not seem to be associated with the development of ischemic cerebrovascular disease in those patients with migraine.
Histamine as a Therapeutic Alternative in Migraine Prophylaxis: A Randomized, Placebo‐Controlled, Double‐Blind Study
Authors: Millán Guerrero Rebeca O. , Isais Cárdenas Mario A. , Antonio Ocampo Abdiel , Pacheco Mauro F.
Published: March 2003

This study was undertaken to test the efficacy of the subcutaneous administration (twice a week) of consecutively increasing doses of histamine (0.1 to 1 ng) in the prophylaxis of migraine, compared to placebo, under a controlled, double‐blind, clinical trial for 12 weeks. Sixty patients were selected, under criteria established by the International Headache Society (both sexes, 18 to 65 years of age, a migraine history of more than 1 year, one to six headache attacks per month), having no additional neurological or cardiovascular pathologies, and after a complete clinical and laboratory examination including computer‐assisted tomography. Comparison between the groups treated with placebo (n=30) and histamine (n=30), on data collected for the 4th, 8th, and 12th weeks of treatment, revealed that histamine exerted a significantly (P<.0001) greater reduction (compared to placebo) in the frequency, intensity, and duration of migraine attacks, as well as on the use of rescue medication. No significant (P>.05) adverse experiences or side effects in either group developed to impede the blinding of the study or the planned order of events. We conclude that the subcutaneous administration of histamine (at very low doses) constitutes a novel and effective therapeutic approach in migraine prophylaxis, aimed at limiting excessive inflammatory responses involved in the pathophysiology of migraine through the activation of H3 receptors.
Objective Behavior Associated With an “Ordinary” Mild Headache: A Surprising Failure of Pain Onset to Signal Self‐protective or Self‐regulatory Behavior
Authors: Hovanitz Christine A. , Reynolds David J. , Cote Max P. , Christianson Amy , Stokes‐Crowe Linda A. , Altum Shari , Chase‐Carmichael Cheryl Ann
Published: March 2003

Objective.—The goal of this study was to determine whether onset of an “ordinary” headache initiated self‐protective behavior or self‐regulation, as indexed by a reduction in effort expenditure.

Methods.—A nonclinical sample was employed. The ambition and performance accuracy of a headache‐developing group (n=23) and a sex‐matched, headache‐free group (n=23) was compared during a series of mental arithmetic problems. Embedded within the series of math problems was a task involving recall of a stressor previously found to induce headache in many subjects.

Results.—Onset of mild head pain did not lead to effort conservation; instead, heightened ambition appeared to characterize the headache‐developing participants before as well as after headache onset. Headache‐developing subjects also displayed a performance accuracy deficit.

Conclusions.—The data suggest unusually ambitious, effortful task engagement may contribute to the onset of mild “ordinary” headache. This possibility requires further examination under other controlled conditions as well as in the natural environment.
Frequency of Headache in the Medical Students of Santa Catarina's Federal University
Authors: Da Costa Marianges Zandrozny Gouvêa , Soares Cláudia Bernadet , Heinisch Liana Miriam Miranda , Heinisch Roberto Henrique
Published: March 2003

Studies in well‐defined populations are useful in identifying factors that influence frequency and severity of headache and in understanding its impact on people.

The aims of this study were to determine the frequency of headache in the medical students of Santa Catarina's Federal University, examine associated factors, verify the diagnostic impressions of the different types of headache, and describe the self‐medication level.

This study included 408 medical students who were interviewed by a questionnaire from October 1997 to August 1998.

The frequency of headache in this group was 33%, with women and students in the five last semesters of the medical course experiencing increased headache frequency. The diagnostic impressions of the different types of headache were migraine without aura (31.3%), migraine with aura (8.2%), episodic tension‐type headache (32.1%), chronic tension‐type headache (7.5%), and tension‐type headache combined with migraine without aura (3%). Self‐medication was reported by 51.8% of the medical students with headache; 34.4% used prescribed medications. The most common self‐help techniques used by students during a headache were to lie down or isolate themselves from their surroundings.
Hypnic Headache Associated With Stage 3 Slow Wave Sleep
Authors: Arjona José Antonio Molina , Jiménez‐Jiménez Félix Javier , Vela‐Bueno Antonio , Tallón‐Barranco Antonio
Published: March 2003

We describe the polysomnographic data of a 79‐year‐old woman with an 11‐year history of nocturnal headaches that were clinically consistent with hypnic headache. A polysomnographic study showed arousal at stage 3 slow wave sleep because of a headache episode. Although this finding could be nonspecific, it suggests the possible relationship between stage 3 slow wave sleep and hypnic headache.
A Pilot Study to Measure Cognitive Efficiency During Migraine
Authors: Farmer Kathleen , Cady Roger , Bleiberg Joseph , Reeves Dennis
Published: March 2003

Background and Objectives.—The measurement of cognitive efficiency during migraine has produced conflicting results primarily due to the types of tests used. The objectives of this pilot study were two‐fold: to measure cognitive efficiency during migraine, compared to a migraine‐free period, and to evaluate the effects of therapy with a 5‐HT1 agonist (sumatriptan injection, 6 mg) on the cognitive efficiency of migraineurs during a migraine.

Method.—The Headache Care Center‐Automated Neuropsychological Assessment Metrics was administered to 10 migraineurs, three times without a migraine, once during a migraine, and three times after administration of sumatriptan injection (6 mg).

Results.—The results demonstrated a significant drop in cognitive efficiency during migraine and recovery 15 minutes after therapeutic injection.

Conclusions.—This pilot study is the first to document a significant drop in cognitive functioning during migraine and recovery after administration of a migraine‐specific medication.
Indirect Costs of Migraine in a Public Brazilian Hospital
Authors: Bigal Marcelo E. , Moraes Fábio A. , Fernandes Luciana C. , Bordini Carlos A. , Speciali José G.
Published: March 2003

Objectives.—To evaluate the indirect costs of migraine affecting employees of a public Brazilian hospital.

Background.—Migraine is a common primary headache which has a negative influence on the well‐being and quality of life, as well as the professional life, of affected individuals.

Methods.—Our series consisted of 846 employees with migraine. The Lost Hours Equivalence Index, which considers both the hours lost due to the absence from work and reduction in productivity, was used to estimate the number of working hours lost due to migraine.

Results.—Of the employees with migraine studied, 91% presented a mean 56.9% loss of productivity. The mean number of total lost working hours per month due to migraine was 6.5. The estimated total indirect cost of migraine was R $986  903.77 (US $815  622.54), implicating costs of R $241.30 (US $199.42) per employee per year.

Conclusions.—Based on its impact on life and the resulting costs, migraine should be considered a public health problem and thus measures should be adopted to reduce its impact on the individual and on society.
Preference Comparison of Rizatriptan ODT 10‐mg and Sumatriptan 50‐mg Tablet in Migraine
Authors: Loder Elizabeth , Brandes Jan Lewis , Silberstein Stephen , Skobieranda Franck , Bohidar Norman , Wang Lixia , Boyle Denise , Kolodny Andrea , Guerra Filippa , Santanello Nancy , Johnson‐Pratt Lisa ,   the Rizatriptan Protocol 060 Study Group
Published: March 2003

Objective.—To compare the proportion of patients who prefer rizatriptan orally disintegrating tablet (ODT) 10‐mg to sumatriptan 50‐mg tablet.

Background.—Migraineurs express treatment preference based on a variety of attributes including the speed of pain relief and medication formulation. Rizatriptan ODT is an orally disintegrating formulation of rizatriptan, a selective 5‐HT1B/1D receptor agonist. This study was conducted to determine patient preference between rizatriptan ODT 10‐mg and sumatriptan 50‐mg tablet for the acute treatment of migraine.

Methods.—This was a multicenter, randomized, open‐label, two‐period crossover study conducted in the United States with 524 enrolled patients. Patients treated a single moderate or severe headache in each treatment period. Patients treated one migraine with either rizatriptan ODT 10‐mg or sumatriptan 50‐mg tablet, then treated a second migraine with the alternate therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90, and 120 minutes postdose and rated headache severity on a 4‐point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following treatment of their second migraine, patients expressed preference for one of the two study medications by completing an interviewer‐administered Global Preference Question and then responded to a self‐administered series of questions to capture their most important reason for preferring one study medication over the other. Safety measurements were recorded through standard adverse experience reporting.

Results.—Three hundred eighty‐six patients treated two migraine attacks. For those patients who expressed a preference for either rizatriptan ODT or sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT 10‐mg (57%, n = 213) was significantly greater than those who preferred sumatriptan 50‐mg tablet (43%, n = 161) (P<.01). For those patients who treated two migraine attacks and had drug severity measures for both attacks (n = 384), a significantly greater percentage of patients reported pain relief after taking rizatriptan ODT than sumatriptan at the 45‐ and 60‐minute time points (38% versus 29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly greater percentage of patients taking rizatriptan ODT reported a pain‐free status at the 60‐ and 120‐minute time points (23% versus 17%[P<.05] and 60% versus 52%[P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated.

Conclusions.—A significantly greater proportion of patients preferred rizatriptan ODT 10‐mg to sumatriptan 50‐mg tablet for the acute treatment of migraine. Efficacy and safety data are consistent with the preference findings.
Statuslike SUNCT in Two Young Women
Authors: Montes Enrique , Alberca Román , Lozano Pilar , Franco Emilio , Martínez‐Fernández Eva , Mir Pablo
Published: March 2003

Objective.—To describe the statuslike pattern of SUNCT (short‐lasting unilateral neuralgiform pain with conjunctival injection and tearing) in two young women.

Background.—SUNCT syndrome is a rare condition characterized by a short‐lasting periocular pain associated with marked autonomic symptoms. Twenty‐five cases have been reported in the literature with a high preponderance of males and a mean age of 51 years. The frequency of episodes shows a wide variability, not just among individuals but also in the same patient, and a statuslike pattern of almost continuous attacks has been described.

Methods.—We report the cases of two young women (aged 26 and 23 years) with typical SUNCT features who suffered bouts of up to 60 paroxysms of pain per hour. Paraclinical investigations showed no abnormalities.

Conclusions.—Although unusual, paroxysms in SUNCT may overlap into a clinical status. A strong relationship with hormonal changes was noted in one patient. In both cases, the pain was refractory to treatment with indomethacin, carbamazepine, and hypnotics, and only intravenous methylprednisolone with oral carbamazepine may have been partially effective in one case.
Effectiveness of Nasal Sumatriptan in 5‐ to 12‐Year‐Old Children
Authors: Hershey Andrew D. , Powers Scott W. , LeCates Susan , Bentti Anna‐Liisa
Published: March 2003

Objective.—To assess the tolerability and effectiveness of nasal sumatriptan in the treatment of migraine in 5‐ to 12‐year‐old children.

Background.—Although headaches are a common disorder and occur in up to 10.6% of children, many of the new migraine abortive agents have not been well evaluated in this population. It has recently been reported that nasal sumatriptan is effective in the treatment of migraine in adolescents. In younger children, it is yet to be characterized. In addition, many children have significant amounts of vomiting with their migraines, limiting their use of oral medications.

Design and Methods.—Children with headache were evaluated by a child neurologist, child psychologist, and pediatric nurse practitioner. Clinical and International Headache Society diagnoses were established for each child. Patients with headaches that were either unresponsive to oral medications or had significant vomiting were treated with nasal sumatriptan. Initial administration and tolerability were performed in the Headache Center at Cincinnati's Children's Hospital Medical Center. Patients or their parents were contacted to assess the overall effectiveness of nasal sumatriptan after home administration.

Results.—Ten patients aged between 5 and 12 years (mean, 9.9 years) received either a 5‐mg (n = 2) or 20‐mg (n = 8) dose of sumatriptan. All 10 patients had a clinical diagnosis of migraine; 7 met the International Headache Society criteria for migraine. The mean age of headache onset was 6.6 years. A total of 57 headaches were treated; 47 (82.5%) responded to sumatriptan. Of the patients who treated headaches, the mean number of headaches treated was 5.2, while the mean number of responsive headaches was 4.3. One patient had no response, 2 patients had a 50% response, and 6 patients had 100% response to the nasal sumatriptan. Three patients reported persistent “bad taste.”

Conclusions.—This report demonstrates that nasal sumatriptan may be effective in aborting migraine in young children (aged 5 to 12 years). It also suggests that there may be subgroups for which it works well. This information suggests that double‐blind, placebo‐controlled studies are necessary to determine the overall effectiveness of nasal sumatriptan in this age group.
Gender Differences in Treatment‐Seeking Chronic Headache Sufferers
Authors: Marcus Dawn A.
Published: March 2003

Objective.—To identify gender differences within a group of patients seeking treatment for chronic headache. Previous studies of the general population have reported differences in headache symptoms, frequency, disability, and psychological distress, with women affected with more severe and disabling symptoms than men. This study evaluated these features in a population seeking treatment.

Methods.—Two hundred fifty‐eight consecutive patients with headache attending a university headache clinic were evaluated with questionnaires about headache symptoms and psychological distress. Comparisons between men and women were made for headache symptoms, severity, frequency, trigger factors, comorbid depression and anxiety, and response to treatment.

Results.—There were no gender differences in headache symptoms, frequency, severity, and duration. Headache triggers were gender‐specific, with men more likely to endorse exercise and women more likely to endorse stress and exposure to odors. Psychological comorbidity was similar among men and women seeking treatment, with a mean Beck Depression Inventory score of 10 and a mean Spielberger trait anxiety score of 39 for both men and women. Disability was greater in men, with 46% reporting restrictions in activities more than 3 days per week because of headache compared with 29% of women. In addition, men were more likely to contribute headache control to external figures than women.

Conclusions.—Patients seeking treatment for chronic headache do not have the same gender‐specific differences that have been reported in general population surveys. Men who seek treatment for headache are more likely to have significant disability, and are equally likely to have symptoms of depression and anxiety as women who seek treatment. Clinical and research investigations of headache triggers need to be gender‐specific.
The Occurrence of Recall Bias in Pediatric Headache: A Comparison of Questionnaire and Diary Data
Authors: Van Den Brink M. , Bandell‐Hoekstra E.N.G. , Abu‐Saad H. Huijer
Published: March 2003

Objective.—To investigate whether children and adolescents can recall prior headache complaints accurately and to study whether age, gender, headache severity, preferred coping strategies, depression, somatization, and trait anxiety are related to recall errors, causing recall bias.

Methods.—A retrospective headache questionnaire and a prospective 4‐week headache diary were filled out by 181 children aged 9 to 16 years who experienced headache at least weekly. In addition, several other questionnaires were administered, measuring coping strategies, depression, somatization, and trait anxiety. Headache frequency, intensity, and duration, as scored on the questionnaire and the diary, were compared using Wilcoxon tests. Regression analyses were performed to study whether age, gender, headache severity, preferred coping strategies, depression, somatization, and trait anxiety can predict the size of differences between the diary and the questionnaire.

Results.—Compared with the diary, headache intensity and headache duration were overestimated on the questionnaire. At group level, median headache frequency as measured by the diary and the questionnaire was equal. Regarding headache frequency and headache intensity, age and headache severity were statistically related to errors in recall. For headache frequency, depression was also predictive of the size of recall error.

Conclusions.—Recall errors occur when children are asked to report their headaches on a retrospective questionnaire. As compared to a prospective diary, pain complaints are evaluated more negatively on a questionnaire. Other factors such as age, depression, and headache severity influence the way children and adolescents recall their headaches. To minimize bias, the use of a diary when studying recurrent headache complaints in children is recommended.
Direct Superoxide Scavenging Activity of Nonsteroidal Anti‐inflammatory Drugs: Determination by Electron Spin Resonance Using the Spin Trap Method
Authors: Ikeda Yukio , Matsumoto Kiyoshi , Dohi Kenji , Jimbo Hiroyuki , Sasaki Ken , Satoh Kazue
Published: March 2003

Nonsteroidal anti‐inflammatory drugs (NSAIDs), which are used widely to manage pain, are known to inhibit cyclooxygenase, but details of the mechanisms of NSAID action remain unclear. We investigated the ability of three NSAIDs (indomethacin, loxoprofen, and etodolac) to eliminate and inhibit free radicals. Superoxide scavenging activity of these NSAIDs was measured in vitro by electron spin resonance spectrometry using 5,5‐dimethyl‐1‐pyrroline‐1‐oxide (DMPO) as a spin trap. Electron spin resonance demonstrated that formation of superoxide‐DMPO spin adduct was completely inhibited by two nonselective cyclooxygenase inhibitors, indomethacin (3 mmol) and loxoprofen (3 mmol). The electron spin resonance study also demonstrated that the formation of superoxide‐DMPO spin adduct was strongly inhibited by a selective cyclooxygenase‐2 inhibitor, etodolac, in a concentration‐dependent manner. These results indicate that NSAIDs, including indomethacin, loxoprofen, and etodolac, have direct superoxide scavenging activity.
Ophthalmoplegic Migraine With Reversible Enhancement of Intraparenchymal Abducens Nerve on MRI
Authors: Te Gyu Lee  , Choi Woo‐Suk , Chung Kyung‐Cheon
Published: March 2003

We describe a patient with ophthalmoplegic migraine and right abducens nerve palsy, in whom serial magnetic resonance imaging showed a transient, gadolinium‐enhancing lesion in the right lower pons, during both headache and the headache‐free period. The enhancing linear lesion was felt to represent intraparenchymal fibers of the affected abducens nerve. The possible pathophysiology of this unique finding is discussed.
Red Ear Syndrome and Migraine: Report of Eight Cases
Authors: Raieli Vincenzo , Monastero Roberto , Santangelo Giuseppe , Eliseo Giovanni Luca , Eliseo Mario , Camarda Rosolino
Published: March 2003

We describe eight idiopathic cases of red ear syndrome in seven children and one adult. All were migraineurs with a history of paroxysmally painful and red ear, unilateral or alternating, in isolation or associated with migraine attacks. The reported duration of these episodes varied from 30 minutes to 1 hour. Neurologic examination, brain MRI and CT scans, and x‐rays of the cervical spine were normal. The close temporal relationship between the “red ear episodes” and migraine attacks suggests an association between the two conditions.
Sexual Headache and Stroke in a Heavy Cannabis Smoker
Authors: Álvaro Luis C. , Iriondo Imanol , Villaverde Francisco J.
Published: March 2003

Sexual headaches usually develop during orgasm. Stroke complicating is rare. We report the case of a young man and heavy cannabis smoker who suffered posterior cerebral artery infarction during his first episode of coital headache.
Cryptic Pituitary Hemorrhage Presenting With Headache
Authors: Krimsky William , Weiss Howard
Published: March 2003

We report a case of pituitary hemorrhage and review the literature on that condition. Our patient presented with a sudden bifrontal headache associated with vague transient visual blurring but without nausea or other associated symptoms. After a negative workup at another hospital, including an unremarkable brain computed tomography without contrast, and resolution of headache following treatment with injectable sumatriptan, he was diagnosed with “atypical migraine.” The patient's symptoms soon returned, and brain magnetic resonance imaging revealed an enlarged, cystic pituitary gland with a small intraparenchymal hemorrhage.
Labetalol for Prophylactic Treatment of Intractable Migraine During Pregnancy
Authors: Dey Ranjan , Khan Sajid , Akhouri Vimal , Wootton Joshua , Bajwa Zahid H.
Published: March 2003

Headaches tend to improve in the majority of migraineurs during pregnancy, but some patients report a worsening of migraine and present a management challenge because of the restrictions of pharmacotherapy during pregnancy. Treatment options become even more limited for pregnant migraineurs who develop preeclampsia. Labetalol was tried successfully in reducing the frequency, duration, and intensity of migraine attacks in a pregnant woman with preeclampsia. There were no significant side effects and the patient delivered a healthy baby without complications.
Cognitive Development in Children with Migraine and Their Healthy Unaffected Siblings
Authors: Haverkamp F. , Hönscheid A. , Müller‐Sinik K.
Published: March 2003

The discussion about neuropsychological sequalae from migraine occurring in adults is controversial. The purpose of our study was to examine whether children with migraine may be at risk for impaired intellectual development compared with their siblings free of migraine.
Sumatriptan Scavenges Superoxide, Hydroxyl, and Nitric Oxide Radicals: In Vitro Electron Spin Resonance Study
Authors: Ikeda Yukio , Jimbo Hiroyuki , Shimazu Motohiko , Satoh Kazue
Published: March 2003

Background.—The molecular mechanisms of migraine have not yet been clarified. Oxygen free radicals have been implicated in the genesis of many pathological processes, including migraine. Sumatriptan succinate is known to be a very effective drug for acute relief of migraine attack.

Objective.—To investigate the direct scavenging activities of sumatriptan for superoxide, hydroxyl, and nitric oxide (NO) radicals using electron spin resonance (ESR) spectroscopy.

Methods.—Measurement of superoxide and hydroxyl radical scavenging activities was performed by ESR using 5,5‐dimethyl‐1‐pyrroline‐N‐oxide as a spin trap. NO was generated from 1‐hydroxy‐2‐oxo‐3‐(N‐3‐methyl‐3‐aminopropyl)‐3‐methyl‐1‐triazene and analyzed by 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl produced from the reaction between 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide and NO.

Results.—The ESR study demonstrated that sumatriptan scavenged superoxide, hydroxyl, and NO in a dose‐dependent manner.

Conclusion.—Sumatriptan has direct scavenging activity on free radicals and NO. Acute migraine drugs with antioxidant properties may provide heretofore unheralded benefits via this mechanism.
What Do Patients With Migraine Want From Acute Migraine Treatment?
Authors: Lipton Richard B. , Hamelsky Sandra W. , Dayno Jeffrey M.
Published: March 2003

Migraine is a common chronic condition with an ever‐expanding therapeutic armamentarium. As therapeutic options multiply, it is increasingly important to understand patients' attitudes and preferences regarding various treatment characteristics. Several strategies have evolved to establish treatment priorities in migraine and rationalize and prioritize end points and outcomes to meet the needs of patients. A survey of a population‐based sample of migraineurs indicated that an overwhelming majority of patients consider complete relief of head pain, no recurrence, and rapid onset of action as important or very important attributes of acute migraine therapy. An analysis of the relationship between clinical end points and satisfaction found that more than 90% of patients who were pain‐free at 2 hours were at least somewhat satisfied with treatment, but satisfaction was dependent on relatively rapid relief. Using a “willingness‐to‐pay” approach, results indicated that while patients will pay more for migraine treatment that produces rapid, consistent relief without adverse effects or recurrence, speed of complete relief is the most valued attribute. By assessing physician preferences and practices, degree of pain relief and rapid onset were identified as the most important attributes of acute therapy. Based on results from preference studies of triptans, 50% of patients cited more rapid pain relief as the most important determinant of treatment preference. Based on these various approaches, the consensus view is that both clinicians and patients desire a broad range of positive migraine treatment attributes, but rapid onset of complete pain relief is a particularly important priority.
In Vivo Evidence for P‐Glycoprotein–Mediated Transport of Phenytoin at the Blood–Brain Barrier of Rats
Authors: Potschka Heidrun , Löscher Wolfgang
Published: March 2003

Summary:  Purpose: The multidrug transporter P‐glycoprotein (P‐gp) is expressed at high levels in a variety of tissues such as the endothelial cells of the blood–brain barrier (BBB) capillaries, where it is thought to be involved in the exclusion of various drugs from the capillary endothelial cells, blocking their entry into brain. It was previously shown that pharmacoresistant partial epilepsy is associated with an increased expression of P‐gp in brain capillary endothelium and astrocytes, leading to the hypothesis that increased P‐gp expression may be involved in medically intractable epilepsy. However, it is not known whether the distribution of antiepileptic drugs (AEDs) into the brain is limited by P‐gp. We used in vivo microdialysis in freely moving rats to study whether the concentration of the major AED phenytoin (PHT) in the extra‐cellular fluid (ECF) of the cerebral cortex can be enhanced by inhibition of P‐gp.

Methods: Three different P‐gp inhibitors, sodium cyanide, verapamil, and PSC 833, were used. These drugs were given via the microdialysis probe in the right frontal cortex, while a probe in the left cortex served as vehicle control side. Perfusion with the inhibitor started 15–60 min before systemic (i.p.) administration of PHT, 50 mg/kg.

Results: PHT rapidly entered the brain ECF compartment, but ECF plasma ratios at time of maximal ECF levels were only ∼0.04. All P‐gp inhibitors significantly increased the ECF concentrations of PHT after local administration, indicating that P‐gp in the BBB normally limits the distribution of PHT into the brain parenchyma. Cremorphor EL, the vehicle used to administer PSC, also was able to increase ECF PHT, which is explained by the previously reported inhibitory effect of cremophor on P‐gp.

Conclusions: Provided that multidrug transporters such as P‐gp also are involved in the BBB outward transport of other AEDs, increased expression of multidrug transporters, leading to inadequate accumulation of AEDs in the brain, would be a likely explanation for pharmacoresistant epilepsy.
Thyroid Function in Men Taking Carbamazepine, Oxcarbazepine, or Valproate for Epilepsy
Authors: Isojärvi Jouko I. T. , Turkka Jukka , Pakarinen Arto J. , Kotila Mervi , Rättyä Johanna , Myllylä Vilho V.
Published: March 2003

Summary:  Purpose: Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This study aimed to evaluate thyroid function in men taking carbamazepine (CBZ), oxcarbazepine (OCBZ), or valproate (VPA) for epilepsy.

Methods: Ninety men with epilepsy (40 taking CBZ, 29 taking OCBZ, and 21 taking VPA monotherapy) and 25 control subjects participated in the study. After clinical examination, a blood sample for hormone, γ‐glutamyl‐transferase (GGT) and antibody (ab) assays was obtained.

Results: Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in men taking CBZ or OCBZ. Forty‐five percent of men taking CBZ and 24% of men taking OCBZ had serum T4 and/or FT4 levels below the reference range. However, no correlations were found between T4 or FT4 and GGT concentrations in men taking CBZ or OCBZ. Thirteen percent of men taking CBZ, 17% of men taking OCBZ, and 6% of control men had increased levels of thyroid peroxidase (TPO)‐ab and/or thyroglobulin (TG)‐ab, but these were not associated with altered serum thyroid hormone concentrations. Serum triiodothyronine and thyrotropin levels in men taking CBZ or OCBZ were normal. In men taking VPA, the concentrations of thyroid hormones, thyrotropin, and antithyroid ab were normal.

Conclusions: Serum thyroid hormone concentrations are low in CBZ‐ or OCBZ‐treated men. However, these low levels do not seem to be due to liver enzyme induction or activation of immunologic mechanisms. Therefore, interference with hypothalamic regulation of thyroid function by CBZ and OCBZ seems possible. VPA does not have any significant effects on thyroid function.
Incidence of Epilepsies and Epileptic Syndromes in Children and Adolescents: A Population‐Based Prospective Study in Germany
Authors: Freitag Christine M. , May Theodor W. , Pfäfflin Margarete , König Stephan , Rating Dietz
Published: March 2003

Summary:  Purpose: To estimate the incidence rate of epilepsies and epileptic syndromes in German children and adolescents aged 1 month to <15 years, and to provide data on their classification.

Methods: A population‐based prospective study was performed between July 1, 1999, and June 30, 2000. All children aged 1 month to <15 years with a newly diagnosed epilepsy or epileptic syndrome were recorded by private pediatricians, EEG laboratories, and the two University Children's Hospitals in the neighboring cities of Heidelberg and Mannheim. The diagnoses were classified according to the International Classification of Epilepsies and Epileptic Syndromes of the International League Against Epilepsy (ILAE).

Results: The total age‐adjusted annual incidence rate was 60/100,000 (95% confidence interval, 42–84), with the highest incidence in the first year of life (146/100,000). Focal epilepsies or epileptic syndromes (58%; incidence rate, 35/100,000) were more common than were generalized ones (39%; incidence rate, 24/100,000), and 3% (incidence rate, 2/100,000) of the epilepsies or epileptic syndromes were undetermined. The rate of idiopathic (47%; incidence rate, 29/100,000) and symptomatic or cryptogenic epilepsies (50%; incidence rate, 30/100,000) was equal. No significant difference in incidence between boys and girls was found.

Conclusions: Incidence rates for epilepsy in German children aged 1 month to <15 years are about equal to those of other countries in Europe and North America. In accordance with studies from the United States and from many European countries, incidence was highest in the first year of life, and no difference in the incidence between girls and boys was found. In Germany as throughout Europe, idiopathic generalized epileptic syndromes are more often diagnosed than in the United States.
Epileptic Encephalopathy
Authors: Dulac Olivier
Published: March 2003

Summary:Epileptic encephalopathies are conditions in which neurologic deterioration results mainly from epileptic activity. It can be due to very frequent or severe seizures, or to subcontinuous paroxysmal interictal activity. The former consists mainly of severe myoclonic epilepsy in infancy (SMEN), in which patients exhibit seizures from the middle of the first year of life with repeated episodes of status epilepticus, and migrating partial epilepsy in infancy, in which, from the first trimester of life, partial seizures affect various areas of the cortex randomly and in a subcontinuous fashion. Cases with subcontinuous paroxysmal interictal activity affect newborns with suppression bursts, thus consisting of either Ohtahara syndrome or neonatal myoclonic encephalopathy, and infants with infantile spasms (IS), although rare cases do not start until age 4 years. In childhood, it consists of various types of generalized seizures combined with either slow spike–waves of the Lennox–Gastaut syndrome (LGS) or with myoclonus and 3‐Hz spike–waves of myoclonic–astatic epilepsy, and continuous spike–waves in slow sleep (CSWS) combined with various neuropsychological patterns including Landau–Kleffner syndrome, frontal lobe syndrome, orofacial dyspraxia, or negative myoclonus. Management differs for all these syndromes, with the combination of clobazam (CLB) and stiripentol (STP) being promising for SMEN, vigabatrin (VGB) for IS, lamotrigine (LTG) for LGS, and steroids for CSWS. It is important to avoid potential drug‐induced worsening by phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), tiagabine (TGB), and VGB; in children and especially in infants, treatment with valproate is preferred each time the proper diagnosis is not reached.
Comparison of the Anticonvulsant Efficacies and Neurotoxic Effects of Valproic Acid, Phenytoin, and the Ketogenic Diet
Authors: Bough Kristopher J. , Eagles Douglas A.
Published: March 2003

Summary: Purpose:The purpose of this study was to measure quantitatively the effectiveness of the ketogenic diet (KD) in comparison to two clinically important anticonvulsant drugs (AEDs), valproic acid (VPA) and phenytoin (PHT), and to evaluate possible associated neurotoxicity.

Methods:Rats were maintained on either a calorie‐restricted, KD or calorie‐restricted, rodent‐chow diet for 3–5 weeks, after which neurobehavioral and seizure testing was completed. AEDs (either VPA or PHT) were injected acutely at the time to peak effect before neurotoxic and seizure assessment. Seizures were induced by timed infusion of pentylenetetrazole (PTZ) and maximal electroshock (MES).

Results:VPA protected from both MES‐ and PTZ‐induced seizures, whereas the KD only elevated PTZ seizure threshold; PHT only attenuated MES‐induced seizures. The KD was as effective as a high dose of VPA (i.e., 300 mg/kg) and combined treatment (i.e., KD + VPA) showed an additive increase in PTZ seizure threshold. No observed neurobehavioral deficits were associated with either diet treatment; however, drug‐related side effects were noted with high doses of either VPA or PHT.

Conclusions:These data suggest that the KD ranks among VPA and PHT as an effective treatment for seizures, without observed drug‐associated neurobehavioral contraindications. In combination with AEDs, our results indicate that the KD plus VPA work synergistically to increase seizure threshold, whereas the KD plus PHT may be complementary, elevating seizure threshold (KD) and reducing seizure severity (PHT). These findings may provide insights into future directions for rational polytherapy; however, it is important to be aware that the KD has been shown to elevate VPA‐induced hepatotoxicity.
A Prospective Study of the Incidence of the Purple Glove Syndrome
Authors: Burneo Jorge G. , Anandan J. V. , Barkley Gregory L.
Published: March 2003

Summary:  Purpose: Phenytoin (PHT) has been widely used intravenously for the treatment of seizures since 1956, and for many years, it has been considered first‐line therapy for status epilepticus. It is routinely administered intravenously in emergency departments and hospitals for patients who have had isolated seizures and for many patients undergoing neurosurgical procedures who are unable to receive oral medication. Adverse reactions from PHT have been widely studied for years, but in the past decade, new adverse reactions have been identified. One of these adverse reactions is the purple glove syndrome (PGS), characterized by edema, discoloration, and pain distal to the site of i.v. administration of PHT. Because there have been no prospective reports of the incidence of PGS, the objective of the study was to report the incidence of this syndrome.

Methods: We enrolled 179 consecutive exposures to i.v. PHT at Henry Ford Hospital. Distal portions of the upper extremities were examined and digitally photographed by one of the authors (J.G.B.). The photos were blindly evaluated by the third author (G.L.B.) for PGS. Demographic and pertinent medical history was recorded for all patients, and outcome for those who experienced PGS was recorded. Associations between PGS, demographic, and medical history information were assessed.

Results: In only three of the 179 exposures did PGS develop. In both patients, the severity of the clinical picture was mild and did not required prolonged hospitalization or specialized treatment.

Conclusions: PGS is an infrequent and mild adverse effect of i.v. PHT administration.
Focal Functional Deficits in Temporal Lobe Epilepsy on PET Scans and the Intracarotid Amobarbital Procedure: Comparison of Patients with Unitemporal Epilepsy with Those Requiring Intracranial Recordings
Authors: Salanova V. , Markand O. , Worth R.
Published: March 2003

Summary:  Purpose: To analyze the relationship between the intracarotid amobarbital procedure (IAP) and positron emission tomography (PET) and study the lateralizing value of these tests in patients with unitemporal epilepsy and those requiring intracranial recordings.

Methods: We compared 51 patients with unitemporal epilepsy (group1) with 26 patients in whom surface recordings failed to reveal a distinct unitemporal focus, necessitating invasive recordings (group 2).

Results: The brain magnetic resonance imaging (MRI) scans for group 1 showed mesial temporal sclerosis in 70.5% of the patients. PET showed unilateral temporal hypometabolism in 88%. In addition, 74.5% of the patients in group 1 had impaired memory on the epileptogenic side on the IAP, and 89.4% of those patients also had ipsilateral temporal hypometabolism on PET scans. All the group 1 patients underwent temporal resections. The pathologic examination showed hippocampal sclerosis in 72% of the patients. Eighty percent of group 1 patients became seizure free, and 16% had rare seizures (follow‐up, 2–7 years). MRIs for group 2 showed mesial temporal sclerosis in 31% of the patients; PET scans showed temporal hypometabolism in 39%. The IAP was lateralized in 47.8%. Sixty‐nine percent had temporal lobe resections. The pathologic examination showed hippocampal sclerosis in 44% of the patients. Forty‐four percent of group 2 patients became seizure free, and 27.7% had rare seizures (follow‐up, 2–8 years).

Conclusions: Ninety‐six percent of the patients with unitemporal foci had focal functional deficits on the epileptogenic side on 18‐fluorodeoxyglucose‐(FDG) PET scans, the IAP, or both. The results of the FDG‐PET were predictive of impaired memory on the IAP. Memory impairment contralateral to the temporal hypometabolism found on the PET scans was never seen. These patients had an excellent outcome. In contrast, <50% of the patients requiring intracranial recordings had focal functional deficits, suggesting that more a diffuse pathology may account for their less favorable outcome.