bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoradiographic Distribution of [3H]sumatriptan-Binding Sites in Post-Mortem Human Brain
Authors: Pascual J , del Arco C , Romon T , del Olmo E , Castro E , Pazos A
Published: March 2003

The anatomical distribution of [3H]sumatriptan-binding sites was analysed in brain tissue sections from 11 subjects. Relevant concentrations of [3H]sumatriptan-binding sites were seen in areas such as visual cortex>locus niger>globus pallidus>layers IV-V of the frontal cortex>subiculum>entorhinal cortex>nucleus tractus solitarius>nucleus trigeminalis caudalis. This distribution of [3H]sumatriptan-binding sites in the human brain shows some differences when compared with that of 5HT1D receptors, confirming that, besides 5HT1D, sumatriptan also binds to 5HT1F receptor subtype. Some species differences are evident between the distribution of [3H]sumatriptan-binding sites in the human brain and that reported for guinea-pig and rat brains, emphasizing that caution is needed in extrapolating experimental data from animals to humans. Furthermore, these data help to explain some of the therapeutic actions of sumatriptan. The remarkable levels of binding found in areas such as nucleus tractus solitarius and nucleus trigeminalis caudalis suggest that in migraine attacks sumatriptan could exert its specific anti-emetic effects and, partly at least, induce analgesia by directly acting over these brain nuclei.
Serotonin Syndrome Complicating Migraine Pharmacotherapy
Authors: Mathew NT , Tietjen GE , Lucker C
Published: March 2003

Serotonin syndrome, a condition with numerous clinical neurological manifestations, is the result of central serotonergic hyperstimulation. Features of the syndrome include mental status and behavioral changes (agitation, excitement, hypomania, obtuniation), motor system involvement (myoclonus, hemiballismus, tremor, hyperreflexia, motor weakness, dysarthria, ataxia) and autonomic symptoms (fever, chills, diarrhea). Serotonin syndrome has been reported exclusively in patients on medications for psychiatric illness and Parkinsonism, despite the fact that the putative action of many antimigraine agents also involves the serotonin system. We herein report six patients with migraine who developed symptoms suggestive of the serotonin syndrome. Five were taking one or more serotomimetic agents for migraine prophylaxis (sertraline, paroxetine, lithium, imipramine, amitriptyline). In each case the symptoms and signs developed in close temporal proximity with use of a migraine abortive agent known to interact with serotonin receptors. In three instances the agent was subcutaneous sumatriptan and, in three, intravenous dihydroergotamine. In each instance the symptoms were transiers and there was full recovery. With the ever increasing use of migraine medications active at serotonin receptor sites, cases of serotonin syndrome will likely occur more frequently. It is important that physicians creating migraine are aware of the serotonin syndrome and are able to recognize its varying presentations.
The International Headache Society Classification of Chronic Daily and Near-Daily Headaches
Authors: Olesen J , Rasmussen BK
Published: March 2003

The classification of the International Headache Society (IHS) published in 1988 has been positively received throughout the world. However, the classification of headaches occurring daily or almost daily has been criticized repeatedly. This criticism is discussed in the present review. It is possible to classify virtually all chronic headache patients using the IHS Classification and there seems to be more need for emphasizing a correct application of the classification than for a revision in this regard. The entity of transformed migraine is disputed and so is the existence of hemicrania continua. Neither of these syndromes has been adequately defined nor studied. Chronic daily headache of sudden onset (new persistent daily headache) is not adequately classified at present and should be included as a separate entity in the next edition of the IHS Classification. In a future revision it should also be possible to classify drug-related headache simply on the basis of drug consumption and without mandatory demands for withdrawal. Better longitudinal studies of patients with chronic daily headache are necessary to evaluate finally whether a revision of the classification of these headache syndromes is necessary. Eventually the ongoing discovery of migraine genes is likely to change radically the classification of migraine.ÿ
Serotonin Receptor Adaptation in Patients with Analgesic-Induced Headache
Authors: Srikiatkhachorn A , Anthony M
Published: March 2003

Analgesic abuse has recently been recognized as a cause of deterioration in primary headache patients. Although the pathogenesis of this headache transformation is still obscure, alteration of serotonin receptor function is one possible mechanism. To assess the plasticity of 5HT2 serotonin receptors in this condition, we investigated receptor binding by the platelet membrane in patients with analgesic-induced headache (AIH), migraine and non-headache controls. The technique involved radioligand binding with (phenyl-4-3H)spiperone and ketanserin. A greater density of receptor numbers (Bmax) was found in patients with AIH and in non-headache controls (96.47±10.2 and 92.01±13.15 fmol/mg protein), as compared to migraine patients (49.52±5.14 fmol/mg protein). The value of dissociation equilibrium constant (KD) remained unchanged (3.07±0.49, 2.24±0.24 and 2.9±0.42 nM for patients with AIH, migraine and non-headache controls, respectively). Based on these findings, we suggest that up-regulation of 5HT2 serotonin receptors may be a possible mechanism of headache transformation in patients with AIH.
Platelet Serotonin in Patients with Analgesic-Induced Headache
Authors: Srikiatkhachorn A , Anthony M
Published: March 2003

The purpose of this study was to investigate the role of serotonin (5HT) in patients with analgesic-induced headache (AIH). We estimated platelet 5HT concentration in patients with AIH, migraine patients and non- headache controls, by using high performance liquid chromatography with electrochemical detection. Our results revealed a significant decrease ( p < 0.00) in platelet 5HT content in patients with AIH as compared to migraine patients and non-headache controls (221.8 ± 30.7, 445.3 ± 37.4 and 467.2 ± 38.5 ng/109 platelets, respectively). In contrast, a difference of lesser statistical significance ( p=0.022) was observed in platelet 5HT content after incubation with excess 5HT (1940.0 ± 195.1, 2610.0 ± 173.1 and 2560 + 165.2 ng/109 platelets for patients with AIH, migraine patients and non-headache controls, respectively). These data suggest that analgesic-induced suppression of 5HT uptake may interfere with the function of the pain modulatory system in the brainstem. Although the process by which analgesics interfere with this system is as vet unknown, it is possible that it may not be entirely due to defective 5HT uptake mechanisms.
Alniditan in the Acute Treatment of Migraine Attacks
Authors: Goldstein J , Dahlöf CGH , Diener H-C , Olesen J , Schellens R , Senard JM , Simard D , Steiner TJ
Published: March 2003

Alniditan is a new 5HT1D receptor agonist, belonging to a different chemical class from sumatriptan and other indole derivatives used or being developed for the treatment of acute migraine. In a multinational double-blind randomized parallel-groups dose-finding trial, alniditan was given subcutaneously in hospital to patients with migraine headache of moderate or severe intensity at doses of 0.8 mg ( n = 44), 1.0 mg ( n = 42), 1.2 mg ( n=46) and 1.4 mg ( n=39). Efficacy, tolerability and safety of each dose were compared with those of placebo ( n =41 ). At 2 h after injection, headache was absent or mild in 83% and 82% of patients receiving alniditan 1.2 and 1.4 mg respectively compared with 39% for placebo (p0.002). Complete relief from headache was achieved in 72% (1.4 mg) Time to onset of relief decreased with increasing alniditan dose, and there was a dose-dependent reduction in headache recurrence rate: 25% of patients receiving 1.4 mg had responded by 15 min and headache recurred within 24 h in only 16% of the patients who initially responded to alniditan 1.4 mg, significantly less than for placebo (p=0.018). Alniditan was superior to placebo in reducing the associated symptoms of nausea, phonophobia and photophobia, and in increasing patients' functional ability. The use of rescue medication was reduced when compared with placebo, and up to 87% of patients said that they would use the drug again if available. No clinically relevant cardiovascular effects were seen, nor consistent changes in clinical laboratory findings. Adverse effects, mainly head pressure, paraesthesia, and hot flushes, were reported by 34% of placebo-treated patients and up to 70% of patients receiving alniditan, but all doses were very well tolerated and no clear relationship with dose was established. Comparison with published findings suggests that alniditan 1.4 mg sc may have advantages over sumatriptan 6 mg sc in providing complete relief from acute migraine headache, and may be associated with fewer headache recurrences within 24h. Both of these suggestions warrant further and larger trials of alniditan in acute migraine.
SUNCT Syndrome Associated with Cavernous Angioma of the Brain Stem
Authors: De Benedittis G
Published: March 2003

A 62-year-old male patient with 2 years f SUNCT syndrome is described. The patient presented with long-lasting periods of frequent attacks of intense orbital pain with a duration of about 1 min, associated with ipsilateral conjunctival injection, lacrimation and rhinorrhea. Cranial MRI and cerebral angiography demonstrated an ipsilateral cavernous angioma of the pons, involving the trigeminal roots. As the pain was refractory to most treatments, including carbamazepine, the patient asked for, and eventually underwent, direct surgical excision of the malformation. Following the operation, his neurological conditions rapidly deteriorated and he died of postoperative complications (hemorrhage).
Visual System Dysfunction in Migraine
Authors: Chronicle EP , Mulleners WM
Published: March 2003

This paper reviews both clinical and experimental literature relating to visual dysfunction in migraine, starting with the eye and progressing via the retina and visual pathways to the visual cortex. Migraine is associated with (i) a pupillary sympathetic hypofunction, and (ii) a cortical hypersensitivity to visual stimuli (perhaps only in migraine with aura), the pathogenesis of which remains to be determined. Various hypotheses are discussed, and it is proposed that the methods of visual psychophysics may represent a useful approach in the future study of cortical hyperexcitability in migraine. Paradoxically, little research has been directed towards understanding (i) the photophobia of migraine attacks, and (ii) how migraine may be triggered by visual stimuli. Research aimed at elucidating the mechanisms of these phenomena may enhance understanding of the pathogenes is of migraine.

The clinical and psychophysical findings reviewed above reveal a broad agreement that migraine is associated with (i) a pupillary sympathetic hypofunction, and (ii) a cortical hypersensitivity to visual stimuli (perhaps only in migraine with aura). Evidence for other dysfunctionality in the eye, retina or visual pathways is, in our view, equivocal.

In spite of the research effort thus far, visual phenomena which are integral to migraine symptomatology are very poorly understood. We would contend that research aimed at understanding the neurological basis of the visual triggering of migraine and of photophobia would assist a more complete understanding of the disorder, and perhaps shed light on processes occurring at the very initiation of an attack. We suggest also that further investigations into the nature and cause of the dysfunction of the visual cortex in migraine with aura may assist the development of general pathophysiological theories.
Hyperprolactinaemia and Depression Induced by Oxetorone
Authors: Pradalier A
Published: March 2003

Two cases of hyperprolactinaemia and one case of depression caused by oxetorone are described. These rare side effects are probably related to the pharrnacological properties of the drug.
Prevalence of Migraine in Japan
Authors: Sakai F , Igarashi H
Published: March 2003

This study presents the first nationwide survey of migraine in Japan. A representative sample of 4029 subjects aged 15 years or older was selected from the Japanese population according to the quota method. A combination of telephone interview and mailed questionnaire methods was used. Diagnosis of migraine was based on the International Headache Society (IHS) Classification. The overall prevalence of migraine in the past year was 8.4%; 5.8% was migraine without aura and 2.6% was migraine with aura. Significant correlation was found between the prevalence of migraine and such variables as gender, age and district of residence. Doctor attendance rate was very low and 69.4% with migraine had never consulted a physician for headache. Yet, 74.2% complained that migraine headache impaired their daily activity significantly. Only 11.6% were aware that their headache was migraine and 56.9% were using only the over-the-counter drugs. The study revealed a comparably high prevalence of migraine in the general population of Japan compared with other countries. A genetic factor was speculated as the cause of regional difference in migraine prevalence.
Recurrence of Spontaneous Intracranial Hypotension with Subdural Hematomas
Authors: Sato Y , Honda Y , Maruoka H , Fujimatsu Y , Oizumi K
Published: March 2003

A 59-year-old man developed postural headache associated with a low CSF pressure. A CT scan revealed no abnormal findings and the orthostatic symptoms resolved without treatment 6 weeks after onset. He was diagnosed as having spontaneous intracranial hypotension (SIH) and remained symptom-free until he experienced recurrence of postural headache 9 months later. A lumbar puncture demonstrated low CSF pressure, and a CT scan revealed slit-like ventricles with narrowing of the sulci, Sylvian fissures, and infratentorial cisterns, in addition to bilateral subdural masses. After draining the hematomas, his symptoms resolved completely, and a follow-up CT scan was normal. We hypothesize that recurrent SIH in this case was due to small recurrent tears of a root sleeve. This case emphasizes the importance of follow-up of SIH for at least 9 months after resolution of symptoms.
Preventive Treatment of Migraine
Authors: Silberstein SD
Published: March 2003

The pharmacologic treatment of migraine may be acute (abortive, symptomatic) or preventive (prophylactic). Most migraine preventive medications were designed to treat other disorders (e.g., propranolol for hypertension, valproate for epilepsy, etc.). Preventive medication is usually given daily for months or years; however, treatment can be episodic, subacute, or chronic. The medications can be divided into two major categories: (i) Alternatives of high efficacy, which include β- blockers, tricyclic antidepressants, and divalproex, and of lower efficacy, which include selective serotonin reuptake inhibitors, calcium channel antagonists, and non-steroidal antiinflammatory drugs and (ii) second-line choices of high efficacy, which include methysergide and monoamine oxidase inhibitors. The choice of preventive treatment depends on the individual drug's efficacy and side effects, the patient's wants, needs, and response to prior treatment, and the presence of any comorbid or coexistent disease.

Most patients require acute headache treatment. Some require preventive treatment. Patients on preventive medication still require acute treatment for breakthrough attacks. Many patients find that their acute attacks are more manageable if they are on a preventive medication. The choice of preventive treatment depends on the individual drug's efficacy and side effects, the patient's wants, needs, and response to prior treatment, and the presence of any comorbid or coexistent disease.
Prophylactic Treatment of Migraine with Gamma-Linolenic and Alpha-Linolenic Acids
Authors: Wagner W , Nootbaar-Wagner U
Published: March 2003

Polyunsaturated fatty acids (PUFA) were administered to 168 patients over a period of 6 months in an open-label uncontrolled study. In 129 patient available for study, 86% experienced reduction in severity, frequency and duration of migraine attacks, 22% became free of migraine and more than 90% had reduced nausea and vomiting. Self-medication changed to simple analgesics in the majority except in 14% of patients without improvement.
Naratriptan
Authors: Connor HE , Feniuk W , Beattie DT , North PC , Oxford AW , Saynor DA , Humphrey PPA
Published: March 2003

The biological profile of naratriptan (N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethane-sulphona-mide), a novel 5HT1B/1D receptor agonist, was investigated in a variety of experimental models of relevance to migraine. Naratriptan has high affinity for human recombinant 5HT1B and 5HT1D receptors (pKi = 8.70.03 and 8.30.1, respectively) and causes contractions of dog isolated basilar and middle cerebral artery (EC50 values of 0.11 and 0.07 M, respectively). Naratriptan causes small contractions of human isolated coronary arteries (EC50 value of 0.17 M; maximum contraction equivalent to 33% of 5HT maximum). In anaesthetized dogs, naratriptan causes selective vasoconstriction of the carotid arterial bed (CD50 dose = 193 g kg-1) and, in anaesthetized rats, naratriptan selectively inhibits neurogenic plasma protein extravasation in the dura (ID50 = 4.1 g kg-1). In a variety of antinociceptive tests, naratriptan has no effect even at high doses. In conscious rats and dogs, naratriptan has high oral bioavailability (71% and 95%, respectively). The data show that naratriptan is a selective agonist at 5HT1B/1D receptors, with a pharmacological profile very similar to that of sumatriptan, albeit 2–3 fold more potent. These observations, coupled with high oral bioavailability in animals, suggest that naratriptan has the profile of an orally effective anti-migraine drug.
Direct Evidence for Central Sites of Action of Zolmitriptan (311C90)
Authors: Goadsby PJ , Knight YE
Published: March 2003

The trigeminovascular system consists of bipolar neurons which innervate pain-sensitive intracranial structures and projecting to neurons in the superficial laminae of the caudal trigeminal nucleus and of the dorsal horns of C1 and C2. The serotonin (5HT1B/D) agonist zolmitriptan (311C90) has been shown to be effective in the treatment of acute attacks of migraine and experimental data suggest that it may have both peripheral and central sites of action. This study sought to further investigate possible central effects of zolmitriptan (311C90) by examining its distribution in the central nervous system. Specific binding of [3H]-zolmitriptan was determined both ex vivo and in vitro in the cat brain. For the ex vivo studies, cats were anaesthetized with halothane and -chloralose (60 mg/kg intraperitoneal). A femoral vein catheter was inserted for injection of the [3H]-zolmitriptan and then 1 h after injection the brain removed. For the in vitro studies fresh frozen brain slices were incubated with labelled and masking concentrations of zolmitriptan. The distribution of [3H]-zolmitriptan was determined using quantitative autoradiographic methods. The in vitro work demonstrated specific binding of [3H]-zolmitriptan in the superficial laminae of the trigeminal nucleus caudalis and dorsal horns of the C and C2 cervical spinal cord. The density of binding was 53 9 fmol/mg for the trigeminal nucleus caudalis, 47 7 fmol/mg for C1 and 50 6 fmol/mg for C2. The ex vivo work demonstrated binding in anatomically identical areas which was less dense than that seen with the in vitro method. These data confirm the existence of a population of receptors that specifically bind zolmitriptan following systemic administration. These receptors may, in part, be responsible for its clinical efficacy and reinforce the importance of central trigeminal neurons as a possible site of action of anti-migraine drugs.
Migraine with and Without Aura in the Same Patient
Authors: Centonze V , Polito BM , Valerio A , Cassiano MA , Amato R , Ricchetti G , Bassi A , Valente A , Albano O
Published: March 2003

Migraine with aura and migraine without aura may be different clinical expressions of one disease. This theory is debated, however. In order to further address the issue, we administered a standardized questionnaire to 45 migraineurs. The results indicate a significant overlap between migraine with and without aura, most importantly with respect to response to therapy; 70% of patients had similar responses.
Light-Induced Discomfort and Pain in Migraine
Authors: Vanagaite J , Pareja JA , St⊘ren O , White LR , Sanc T , Stovner LJ
Published: March 2003

Quantitative thresholds for discomfort and pain with monocular and binocular light stimuli were measured in 67 controls and 67 migraine patients 37 migraine with aura and 30 migraine without aura). Patients were more photophobic during attack than outside attack ( p<0.03), and they were more sensitive to light than controls even between attacks ( p0001). We found no differences in light sensitivity between migraine with aura and migraine without aura ( p0.93). Unilateral pain affected light sensitivity on both sides. When asked with a questionnaire, 74% of patients answered that they were sensitive to light outside attack and 100% were sensitive during attack. Pain thresholds were generally lower among sensitive than non-sensitive patients ( p=0.004), indicating some agreement between subjective opinion and objective measurements of photophobia. Photophobia seems to be an intrinsic property of migraineurs. It is increased by migraine pain, but seems to be unrelated to migraine characteristics such as nausea, severity of attacks, pain character and pain laterality.
Headache During Pregnancy
Authors: Maggioni F , Alessi C , Maggino T , Zanchin G
Published: March 2003

A questionnaire was submitted to 430 women 3 days after delivery, asking mainly about features of headache before and during pregnancy and their possible modification or recurrence; moreover, delivery modalities and the condition of the newborn were evaluated. One-hundred-and-twenty-six (29.3%) were found to be primary headache sufferers (IHS criteria, 1988), 81 of whom had migraine without aura (MO), 12 migraine with aura (MA), and 33 tension-type headache (TH). In all three groups, about 80% showed complete remission or a higher than 50% decrease in the number of attacks. The improvement was more evident after the end of the first trimester; this trend was common to the three primary headaches considered. In our series of primary headaches, there was only one case (MO) which began during pregnancy. In a subgroup of pluripara, headache maintained the improvement presented in the first pregnancy also during the following gravidic periods in about 50% of cases, whereas in the remaining 50% a worsening in parallel with successive pregnancies was found. Primary headaches “per se” do not seem to increase the pregnancy or delivery risks, nor the vitality of the newborn. During pregnancy, drug use was very much reduced and was restricted to a limited number of compounds.
The Time Course of Post-Lumbar Puncture Headache
Authors: Vilming ST , Kloster R
Published: March 2003

According to the leakage theory, the time taken for pain to develop upon rising to the upright position will increase during the time course of post-lumbar puncture headache (PPH) as a consequence of the decreasing size of the healing dural rent, and the pain will decline. The aim of the present prospective study was to test this hypothesis, and to describe the temporal course of time and pain variables in PPH. The study showed that the course was fairly stable for all variables except on the first day, the second last day, and the last day. In the recumbent position, the headache was more severe on the first day ( p< 0.05) and milder on the last day ( p< 0.001) compared with the interim days; maximal headache in the upright position was milder on the second last ( p< 0.005) and last days ( p< 0.0001). Compared with the interim days, the time prior to increase of pain upon rising was shorter on the first day ( p< 0.05) and longer on the last day ( p< 0.001), and from start of increase until maximum was longer on the last day ( p< 0.01). The time to pain relief upon lying down did not vary significantly throughout the PPH period. The mobility of the patient as expressed by the PPH grade was fairly stable throughout the course of PPH until it increased in the last 2 days. The results are in good accord with the leakage theory.
Myogenic Cerebrovascular Autoregulation in Migraine Measured by Stress Transcranial Doppler Sonography
Authors: Heckmann JG , Hilz MJ , Katalinic A , Marthol H , Mück-Weymann M , Neundörfer B
Published: March 2003

Background and purpose: Transcranial Doppler sonography (TCD) studies may help to elucidate the nature and role of vascular abnormalities in migraine. Our aim in this study was to evaluate cerebrovascular autoregulative response in migraine patients with and without aura to blood pressure increase using stress TCD.

Patients and methods: Using transcranial Doppler ultrasound at rest and during ergometer stress (stress TCD), we studied the changes in mean flow velocities and resistance index (RI) in relation to physical stress in the middle cerebral artery. Fifteen migraine patients without aura, 15 migraine patients with aura, and 15 healthy control subjects were examined. Patients suffered from predominantly unilateral headache and were studied during an attack-free period. The Pourcelof's RI as a measure of cerebrovascular reactivity was calculated by dividing the difference between systolic and diastolic velocity by the systolic velocity.

Results: None of the subgroups showed any difference during ergometer exercise with regard to blood pressure, endtidal CO2, heart rate, or mean flow velocity. In all subgroups, sufficient physical stress was achieved. With respect to RI change, migraine patients without aura and healthy controls did not differ ( p>0.05). However, the RI change of migraine patients with aura was significantly lower than the RI change of migraine patients without aura or healthy subjects ( p>0.05). The discrimination analysis showed in addition that RI change (absolute and as a percentage) and mean flow velocity change (as a percentage) could be used as diagnostic variables to detect patients with aura symptoms.

Conclusion: Differences exist in cerebrovascular reactivity in migraine patients with aura that may contribute to the neurologic disturbances in these patients during attack. We propose that there is disorder of myogenic cerebrovascular autoregulation in migraine patients with aura during headache-free intervals.
Gender Ratio of Cluster Headache Over the Years: A Possible Role of Changes in Lifestyle
Authors: Manzoni GC
Published: March 2003

Changes in the male-to-female (M/F) ratio of cluster headache (CH) over the years were investigated through a comparative analysis of the distribution of the disease by sex and decade of onset in 482 patients (374M and 108F). Variations over the last few decades were also investigated in the employment rate, level of school education, smoking habit, and coffee and alcohol intake of the population living in the same area as the CH patients. The M/F ratio has fallen from 6.2:1 for patients with CH onset before 1960, to 5.6:1, 4.3:1, 3.0:1, and 2.1:1 for patients with CH onset in the 1960s, 1970s, 1980s, and 1990s, respectively. Correspondingly, in those same decades, the M/F ratio has fallen from 2.6:1 to 2.4:1, 2.2:1, 2.0:1, and 1.7:1, respectively, for the employment rate, and from 8.6:1 to 7.8:1,3.3:1,2.5:1, and 1.9:1 for the smoking habit. Such a close correlation suggests that the significant changes that have occurred over the last few decades in the lifestyle of both sexes—and particularly that of women—may have played a major role in altering the gender ratio of CH.
The Hypnic Headache Syndrome: Report of Three New Cases
Authors: Morales-Asín F , Mauri JA , Iñiguez C , Espada F , Mostacero E
Published: March 2003

Three new cases compatible with hypnic headache syndrome (HHS) are presented. The patients were 70, 77, and 79 years of age (2F, 1M). They described a history of nocturnal headache ranging from 5 months to 7 years. One patient was afflicted with diffuse pain but the other two had unilateral pain. In one patient headache was clearly related with dreams, but in the other two this point could not be confirmed. Except for headache being unilateral in two cases, the remaining HHS criteria were present. It is noteworthy that pain responded to flunarizine in two patients.
Structural and Neurochemical Markers of Brain Injury in the Migraine Diathesis of Systemic Lupus Erythematosus
Authors: Rozell CL , Sibbitt WL , Brooks WM
Published: March 2003

Objective: To determine whether migraine in systemic lupus erythematosus (SLE) is associated with accentuated brain injury and disease activity.

Methods: Forty SLE patients (11 without headache, 11 with non-migraine headache, and 18 with migraine) underwent clinical evaluation, magnetic resonance imaging (MRI), and spectroscopy (MRS).

Results: Recurrent headache occurred in 75% of SLE patients. MRI abnormalities and reduced N-acetylaspartate were common. However, migraine in SLE was not associated with increased disease activity or severity, neuropsychiatrie manifestations, or end-organ involvement compared to patients without migraine ( p>0.05). There were no differences in the prevalence or severity of MRI or MRS abnormalities between SLE patients with migraine, with non-migraine headache, or without headache ( p>0.05).

Conclusions: Headache does not identify SLE patients at risk for brain injury, increased disease activity, or increased end-organ involvement. Aggressive immunosuppressive therapy for headache alone is not indicated in SLE.
Pattern Reversal Visual Evoked Potentials in Migraine with Aura and Migraine Aura Without Headache
Authors: Shibata K , Osawa M , Iwata M
Published: March 2003

Pattern reversal visual evoked potentials (PVEPs) were recorded in 20 patients with migraine with aura (MA), 19 patients with migraine without headache (migraine equivalent; ME) during interictal periods, and 34 normal subjects. All migraine patients had hemianopsia or fortification spectra during attacks. In both MA and ME patients of less than 49 years of age, there were significant ( p<0.01) differences in amplitude of PVEPs at the mid-occipital and contralateral to visual aura electrode sites compared to normal subjects. Amplitude of PVEPs in MA and ME showed significant ( p<0.001) increases when recorded soon after attacks, especially within 10 days. There was a significant ( p<0.01) correlation between percentage asymmetries and the duration of illness in both MA and ME. We conclude from our PVEP findings that cortical spreading depression remains the most likely explanation for the migraine visual aura.
Screening for Migraine in the General Population: Validation of A Simple Questionnaire
Authors: Gervil M , Ulrich V , Olesen J , Russell MB
Published: March 2003

We present validation of a simple questionnaire designed to screen the general population for migraine. It comprises four questions: (1) “Have you ever had migraine?” (2) “Have you ever had severe headache accompanied by nausea?” (3) “Have you ever had severe headache accompanied by hypersensitivity to sound and light?” (4) “Have you ever had visual disturbances lasting 5–60 min followed by headache?” A telephone interview carried out by a physician was used as an index of validity. The study population was 5,360 twins from the population-based Danish Twin Registry. All twin pairs where at least one twin had answered “yes” to at least one of our questions were eligible for the telephone interview ( n=2,272 twins). The response rate to the questionnaire was 87%; the participation rate in the telephone interview was 90%. The questionnaire ascertained 85% of all migraineurs (sensitivity). A combination of two questions (questions 1 and 4) extracted 93% of the twins with migraine with aura and 74% of the twins with migraine without aura, yet only 26% of the sample needed to be interviewed. We conclude that in the Danish population two simple questions are sufficient to screen for migraine in selecting participants for a diagnostic clinical interview. Our questionnaire clearly merits further study to document its universal applicability.
Safety Trial with the 5Ht1B/1D Agonist Avitriptan (BMS-180048) in Patients with Migraine who have Experienced Pressure, Tightness, and/or pain in the Chest, Neck, and/or throat following Sumatriptan
Authors: Dahlöf CGH , Falk L , Risenfors M , Lewis CP
Published: March 2003

We investigate whether symptoms of pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of the 5HT1B/1D agonist avitriptan were associated with objective impairment of the myocardial function on 12-lead electrocardiogram (ECG), continuous ECG (Holter) monitoring, and echocardiography. Migraine sufferers who in two-thirds of all attacks treated with sumatriptan had experienced chest/throat/neck symptoms were chosen for study. Baseline measures included vital signs, a 12-lead ECG and an echocardiogram. Patients ( n=51) who had no clinically significant abnormality at baseline received a high dose (150 mg) of avitriptan orally outside of a migraine attack. If pressure, tightness, and/or pain in the chest, neck, and/or throat occurred, an ECG was obtained, and a repeat echocardiogram was done while the symptoms were present in order to monitor for impairment of myocardial function. If symptoms of these types did not occur within 60 min after administration of the study drug, a second echocardiogram was obtained. Forty-five patients (88%) reported at least one adverse event and 23 (45%) experienced pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of avitriptan. No clinically significant myocardial abnormalities were observed in any patient, even in those who had experienced the targeted symptoms. No other serious adverse event occurred. We concluded that the typical 5HT1B/1D agonist-induced chest/throat/neck symptoms are most unlikely to be of cardiovascular origin.
Migraine, Female Hormones, and Stroke
Authors: Bousser M-G
Published: March 2003

“Migraine, female hormones, and stroke” The title of this work suggests three different topics (migraine and female hormones, migraine and stroke, female hormones and stroke), each of which would merit a study on its own. Taking female hormones as the connecting thread, however, I decided to review their relationships with migraine and stroke, using as examples a few selected points, such as the sex ratio of these two conditions and the influence that oral contraceptives, pregnancy, menopause and hormone replacement therapy has upon them. I will deal briefly with migraine and expand on stroke.
Reliability of the Migraine Disability Assessment Score in A Population-Based Sample of Headache Sufferers
Authors: Stewart WF , Lipton RB , Kolodner K , Liberman J , Sawyer J
Published: March 2003

Background. The Migraine Disability Assessment (MIDAS) score is used to quantify headache-related disability. In a previous study, we showed that the MIDAS score was highly reliable in population-based samples of migraine headache sufferers in two countries.

Objectives. To examine the test–retest reliability and internal consistency of the five items comprising the MIDAS score and the overall MIDAS score in a population-based sample of both migraine and nonmigraine headache sufferers.

Methods. Using a clinically validated telephone interview, a population-based sample of migraine and nonmigraine headache sufferers was identified in Baltimore, Maryland, USA. A total of 97 migraine cases and 80 nonmigraine subjects completed the MIDAS questionnaire on two occasions an average of 3 weeks apart. The MIDAS score is derived from five questions about missed time from work (or school) and household work (one question each about missed days and days with at least 50% reduced productivity) and missed days of nonwork activities.

Results. Among all headache sufferers die test–retest Spearman's correlations of individual MIDAS questions ranged from 0.67 to 0.73. The Spearman's correlation for the MIDAS score (i.e., sum of lost days and reduced effectiveness days in each domain) was 0.84. Cronbach's alpha, a measure of internal consistency, was 0.83. Mean and median item values and the overall MIDAS scores differed between migraine and nonmigraine cases. Even after adjusting for differences in headache frequency, the mean MIDAS scores differed substantially (i.e., 10.3 points) between migraine cases and nonmigraine cases.

Conclusions. The reliability and internal consistency of the MIDAS score are high, as tested in a population-based sample of headache sufferers. MIDAS scores are substantially higher in migraine cases than in nonmigraine cases, supporting the validity of the measure.
Prolonged Migraine Aura Without Headache Arrested by Sumatriptan. A Case Report with Further Considerations
Authors: Kowacs PA , Piovesan EJ , Tatsui CE , Lange MC , Ribas LC , Werneck LC
Published: March 2003

The case of a 42-year-old woman with prolonged migraine visual aura without headache, whose long-lasting episodes of visual aura were successfully controlled by oral sumatriptan, is reported. Effectiveness of sumatriptan was unequivocal, since, after taking sumatriptan, duration of aura would drop from 1.5 h to approximately 20 min. This case suggests that sumatriptan may cross the blood-brain barrier and block spreading depression.
Time-To-Event Analysis, Or Who Gets Better Sooner? an Emerging Concept in Headache Study Methodology
Authors: Allen C , Jiang K , Malbecq W , Goadsby PJ
Published: March 2003

Survival analysis, or, more generally, time-to-event analysis, is of interest when the data represent the time to a defined event. While well established in oncology, it has not been widely applied to migraine research, possibly because the data are usually collected intermittently, rather than continuously, and because of the awkwardness of interpreting treatment effect in survival terms. However, it represents an interesting approach for the analysis of time-to-headache relief, which addresses the clinically relevant question of who gets better sooner. The analysis uses data from all time-points to define the likelihood of headache relief following treatment throughout the entire assessment period. These data can then be used to quantify and test the difference between two therapies.
Vasodilator Agents and Supracollicular Transection Fail To Inhibit Cortical Spreading Depression in the Cat
Authors: Kaube H , Knight YE , Storer RJ , Hoskin KL , May A , Goadsby PJ
Published: March 2003

It remains an open question as to whether cortical spreading depression (CSD) is the pathophysiological correlate of the neurological symptoms in migraine with aura. In the experimental animal, CSD is an electrophysiological phenomenon mainly mediated via NMDA receptors. However, according to case reports in humans, visual aura in migraine can be alleviated by vasodilator substances, such as amyl nitrite and isoprenaline. There is also circumstantial evidence that brainstem nuclei (dorsal raphe nucleus and locus coeruleus) may play a pivotal role in the initiation of aura. In this study, CSD was elicited in α-chloralose anesthetized cats by cortical needle stab injury and monitored by means of laser Doppler flowmetry. Topical application of isoprenaline (0.1-1%) and amyl nitrite (0.05%) onto the exposed cortex had no effect on the elicitation or propagation of CSD. Also, after supracollicular transection, subsequent CSDs showed no differences in the speed of propagation and associated flow changes. We conclude from these data that—given CSD probably exists in humans during migraine—spreading neurological deficits during migraine aura are independent of brainstem influence and have a primarily neuronal rather than vascular mechanism of generation.
Open-Labeled Long-Term Study of the Efficacy, Safety, and Tolerability of Subcutaneous Sumatriptan in Acute Migraine Treatment
Authors: Göbel H , Heinze A , Stolze H , Heinze-Kuhn K , Lindner V
Published: March 2003

In a multicenter study, a long-term analysis was made of the efficacy, safety, and tolerability of subcutaneous (s.c.) sumatriptan in the acute treatment of migraine attacks over a period of up to 18 months. A total of 2263 patients took part in the study, all able to perform their own acute treatment of migraine attacks at home by s.c. administration of 6 mg of sumatriptan. A headache diary was used by each patient to record the various migraine parameters before the injection and 1 h and 2 h after it. A total of 43,691 attacks were treated and analyzed during the study period from October 1991 to June 1993. Therapy was successful in 89.5% of attacks. Freedom from headache was achieved in 71.0% of cases. In 22.7% of the attacks a second injection was administered on recurrence of the headache; 82.9% of the patients achieved an intraindividual therapy success rate ranging from over 80% to 100%. In the course of treatment there was no change in either the therapy success rate or in the frequency of attacks. Some 4.9% of the patients withdrew from the study because of insufficient efficacy or adverse events. A total of 44.5% of patients reported adverse events, and these were rated serious in the case of 1.7%. S.c. administration of sumatriptan for acute migraine therapy is an effective treatment method, with reliable action, that can be used with good tolerability provided the contraindications are taken into account.
The Cortical Silent Period is Shortened in Migraine with Aura
Authors: Aurora SK , Al-Sayeed F , Welch KMA
Published: March 2003

Objectives: Central neuronal hyperexcitability may be the physiological disturbance that predisposes subjects to migraine attacks. To test this hypothesis, we studied the cortical stimulation silent period (CSSP) elicited by transcranial magnetic stimulation (TMS), which is in part a measure of central inhibition of motor pathways in migraine with aura (MwA) patients and normal controls.

Methods: In nine MwA patients (mean age 35.9 ± 7) and 9 controls (mean age 37.6 ± 7), we carried out transcranial stimulation using a 95 mm circular coil and Caldwell MES 10 stimulator to determine resting motor threshold (MT) for bilateral FDI muscles. All subjects performed isometric voluntary contraction of bilateral FDI maintained at 20% of maximal effort, during which we measured bilateral CSSP at (i) the stimulus intensity (SI) determined for the MT and (ii) an SI of 1.5 x MT.

Results: Although the mean MT was higher in MwA compared with controls (63.1 ± 14.4 vs 58.1 ± 8.9), the difference was not significant. At an SI of 1.5 x MT the mean CSSP did not differ between the groups (MwA 141.7 ± 31.9 vs controls 162.4 ± 36.6). At the SI of the MT, however, the CSSP was shorter in MwA patients than in controls (62.9 ± 27.3 vs 106.3 ± 19.6, p=0.001). There was an inverse correlation between the duration of CSSP and an increased frequency of headache ( p=0.02).

Conclusions: The shortened CSSP that we measured in MWA patients compared to normal with low intensity magnetic stimulation suggests reduced central inhibition resulting in increased excitability of cortical neurons in migraine subjects. The association of CSSP reduction with increased frequency of migraine is further suggestive that brain excitability is the basis of susceptibility to migraine attacks.
T-Cell Subsets and Expression of Integrins in Peripheral Blood of Patients with Migraine
Authors: Empl M , Sostak P , Breckner M , Riedel M , Müller N , Gruber R , Förderreuther S , Straube A
Published: March 2003

Neurogenic inflammation is considered as an animal model of human migraine attacks. Using flow cytometry, we examined T-cell subsets and their integrin expression in the peripheral blood of 32 migraine patients in order to evaluate a possible inflammatory process in humans, as postulated in the migraine animal model. Our results show that migraine patients have a significant increased proportion of T-helper (47.4 ± 6.3% vs 43.2 ± 5.8%; p< 0.01) and T-helper memory cells (23.6 ± 5.9 vs 20.3 ± 6.5%; p< 0.01). Moreover, the 22 migraine patients without aura also exhibited an increase of LFA-1 expression of T-helper cells (34.7 ± 11.5%) compared to the 35 controls (27.5 ± 12.0%; p< 0.01). These preliminary results support the hypothesis that immunological mechanisms (such as an enhanced lymphocyte endothelium interaction) could be part of the migraine pathophysiology in humans.
Personality and Response To Repeated Visual Stimulation in Migraine and Tension-Type Headaches
Authors: Wang W , Wang G-P , Ding X-L , Wang Y-H
Published: March 2003

Migraine sufferers potentiate their visual evoked potentials (VEPs) from a short period of 2 min to a longer period of 15 min. As a lack of habituation is linked to higher level arousal, we thus hypothesized that short-term VEP potentiation might be correlated with an arousal-related personality trait. We therefore carried out short-term VEPs, Plutchik-van Praag's Depression Inventory, Zuckerman's Sensation-Seeking Scales (Form V), and Zuckerman-Kuhlman's Personality Questionnaire in 26 healthy subjects, 22 patients suffering from migraine without aura between attacks, 13 episodic and 20 chronic tension-type headaches. The chronic tension-type headache sufferers showed increased depression compared with other groups, which might be a consequence of the headache itself. Migraines, however, showed steeper habituation slopes of N1-P1 and P1-N2, decreased thrill and adventure-seeking, and general sensation-seeking man healthy controls; in addition, the habituation slope of P1-N2 was positively correlated with experience-seeking in migraine. The short-term VEP potentiation and the decreased thrill and adventure-seeking and general sensation-seeking in migraine might be related to a high level of cortical arousal and a low 5HT neurotransmission. In compliance with the long-term VEP study, the positive correlation between the P1-N2 habituation slope and experience-seeking in migraine suggests a continuous metabolic overload for the brain interictally, which can trigger the activation of a migraine attack.