Headache The Journal of Head and Face Pain

Published by Wiley
Online ISSN: 1526-4610
Print ISSN: 0017-8748
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Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.
 
Rizatriptan is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This double-blind, placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients were allocated to one of five groups for treatment of two attacks: rizatriptan 5 mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10 mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For each attack, patients rated headache severity, presence of associated symptoms, and functional disability prior to dosing and at intervals through 4 hours thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively. The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication. All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing. All active treatments were well-tolerated and showed comparable safety profiles.
 
SYNOPSIS Seventeen patients have taken part in a double-blind, controlled, randomized, cross-over trial, completing four months, two months on each arm of the trial, in which pizotifen 0.5 mg t.d.s. has been compared with 1.5 pizotifen at night. Sixteen patients improved significantly. No significant difference was noted between patients on 0.5 mg t.d.s. compared with 1.5 mg nocte but there was a trend to suggest that initially patients may respond better to the t.d.s. dosage but then maintenance would be more easily carried out on a once nightly regime of pizotifen 1.5 mg nocte. Weight gain appeared to be related to the t.d.s. dosage regime and if this finding is confirmed in subsequent studies then the single dosage at night would certainly be preferable to a t.d.s. dosage regime. We confirm previous studies which show that pizotifen is extremely useful in the prophylaxis of migraine.
 
SYNOPSIS Descriptions of migraine and muscle tension headaches have been based primarily on retrospective medical histories. To obtain a more accurate picture of symptoms patients use to classify these headaches, a sample of 10,000 headaches was gathered from daily diaries. Patients experiencing both migraine and tension headaches are able to differentiate these disorders consistently, using moderate ratings of intensity, low ratings of disability, and short length for tension headaches, and ratings of relatively high intensity and disability, moderately long duration, and occasional gastrointestinal upset for migraine headaches. These configurations confirm the general view obtained from medical histories.
 
To analyze the incidence and characteristics of the first 1000 headaches in an outpatient clinic. Headache is a common cause of medical consultation, both in primary care and in specialist neurology outpatient clinics. The International Classification of Headache Disorders, 2nd Edition (ICHD-II), enables headaches to be classified in a precise and reproducible manner. In January 2008, an outpatient headache clinic was set up in Hospital Clínico Universitario, a tertiary hospital in Valladolid, Spain. Headaches were classified prospectively in accordance with ICHD-II criteria. In each case we recorded age and sex, duration of headache, ancillary tests required, and previous symptomatic or prophylactic therapies. In January 2010, the registry included 1000 headaches in 682 patients. The women/men ratio was 2.46/1 and the mean age of the patients was 43.19 ± 17.1 years (range: 14-94 years). Patients were referred from primary care (53.4%), general neurology clinics (36.6%), and other specialist clinics (9%). The headaches were grouped (ICHD-II classification) as follows: group 1 (Migraine), 51.4%; group 2 (Tension-type headache), 16%; group 3 (Trigeminal autonomic cephalalgias), 2.6%; group 4 (Other primary headaches) and group 13 (Cranial neuralgias), 3.4%. The diagnostic criteria of chronic migraine were satisfied in 8.5% of migraines. Regarding secondary headaches, 1.1% of all cases were included in group 5 (Headaches attributed to trauma) and 8.3% in group 8 (Headaches attributed to a substance or its withdrawal). Only 3.4% of headaches were classified in group 14 (Unspecified or not elsewhere classified), and 5.2% were included in the groups listed in the ICHD-II research appendix. This registry outlines the characteristics of patients seen in an outpatient headache clinic in a tertiary hospital; our results are similar to those previously reported for this type of outpatient clinic. Migraine was the most common diagnosis. Most headaches can be classified using ICHD-II criteria.
 
The introduction of oral sumatriptan in the United States at doses of 25 and 50 mg, compared with 100-mg tablets worldwide, has created the need to develop a protocol for appropriate dosing. We evaluated the first 104 patients in our practice to treat two migraine attacks with oral sumatriptan. For their first treatment with oral sumatriptan, patients were evaluated on their response to 25-mg tablets and the total number of tablets taken. For their second treatment, patients were evaluated on their response to sumatriptan, number of 25-mg tablets taken, and dosage prescribed for future migraines. [table see text] After the second treatment, 41 patients (40%) continued therapy with 25-mg tablets, 54 (53%) were prescribed 50-mg tablets, 2 patients (2%) were prescribed two 50-mg tablets, and 5 patients (5%) were prescribed injectable sumatriptan. Seventy patients had previously used injectable sumatriptan, while 34 had not previously used sumatriptan. There were no significant differences in their response to oral sumatriptan. Oral sumatriptan was effective in clinical practice at doses of 25 and 50 mg. The majority of patients required more than one 25-mg tablet for a migraine attack, reflecting both inadequacy of dosing for some migraines and recurrence of headache, yet 40% of patients continued on treatment with 25-mg tablets. There were no significant differences in response to therapy in patients being switched from injectable to oral sumatriptan compared with those initiating therapy with oral sumatriptan. Both tablet strengths of oral sumatriptan are useful in clinical practice.
 
SYNOPSIS This study initiated by a self-help migraine group investigated disability caused by visual environmental stimuli, e.g. glare, flicker, pattern and color. One thousand forty-four women with migraine completed the self-report questionnaire on visual environmental stimuli reported in earlier studies to precipitate or aggravate migraine. One hundred twenty-one female controls were obtained from general practice and hospital out-patients. The responses of the classical, common and non-migraine groups were compared. Women with classical migraine expressed greater disability than those with common migraine or controls both in respect of number of visual sensitivities reported (P < 0.0001 ) and severity of consequences of such stimuli (P < 0.0001). This study indicated differences between classical and common migraine outside of the attack phase apart from aura. Reported range of sensitivities for the migraineurs peaked between the ages of 46–60 years. A high level of unrealized disability caused by visual environmental stimuli was thus identified in hitherto unexplored self-help groups.
 
BC-105 is an effective prophylactic medication against vascular headache with effectiveness range similar to, or only slightly less than, methysergide, that is about 2/3 of the patients received significant benefit. Despite its supposed antidepressive effects, the author did not find it to be of benefit in patients suffering from tension headaches. Drowsiness and weight gain may limit its dosage but no dangerous side effects have been recorded. Research into the action of these drugs may give new insight into the mysterious mechanisms of migraine.
 
SYNOPSIS Several disturbances in platelet function have been reported in migraine and tension-type headache (TH). The plasma 11-dehydrothromboxane B 2 (11-dTXB 2 ) is free from artifactual increase during blood sampling, and it can be a reliable indicator of thromboxane A 2 (TXA 2 ) production in vivo. TXA 2 is a very potent proaggregatory and vasoconstrictory metabolite formed in the platelets. We investigated plasma 11-dTXB 2 and 5-hydroxytryptamine (5-HT) levels in patients with migraine during headache-free periods and in patients with chronic TH. The mean value of plasma 11 -dTXB 2 levels in migrainous patients was significantly higher than those in TH patients and healthy controls. The mean value of plasma 5-HT levels in TH patients was significantly lower than those in migrainous patients and healthy controls. There was no correlation between plasma 11-dTXB 2 levels and plasma 5-HT levels in any group. The results suggest the existence of continuous platelet activation in migrainous patients.
 
The etiology of transient global amnesia (TGA) remains unclear, and flow disturbances in the mesial temporal lobes secondary to venous congestion have been proposed as a potential cause. The occurrence of TGA during a migraine attack is a rare condition. This 11-year retrospective study in one French center describes patients' characteristics, type of migraine, investigations, treatment with vasoconstrictor during the TGA/migraine attack, and outcome in patients who had TGA during a migraine attack. Among 8821 new patients, 6 cases of TGA occurring during a migraine attack were identified. For a majority of patients, TGA occurs after the beginning of the attack. TGA always occurs during a severe migraine attack, with vomiting or vomiting efforts. Vomiting or vomiting efforts always precede a TGA episode. TGA occurring during a migraine attack is rare. Since a Valsalva maneuver, such as forceful vomiting, is frequently described at the origin of the attack, blocking venous return through the superior venous cava may allow brief retrograde transmission of high venous pressure from the arms to the cerebral venous system, resulting in venous ischemia to the diencephalon or mesial temporal lobes and causing TGA. © 2015 American Headache Society.
 
To assess the efficacy, tolerability, and patient satisfaction with almotriptan 12.5 mg across multiple migraine attacks in routine clinical settings. The efficacy and tolerability of almotriptan have been well-documented in clinical trials. Less information is available about patient acceptance of therapy under normal prescribing conditions in routine practice. This was a prospective, open-label surveillance study conducted on 899 adults with documented attacks fulfilling the IHS criteria for migraine in medical practices of 307 neurologists and primary care physicians across Germany from June 2001 to April 2002. Patients were eligible for inclusion in the study if they were being treated for the first time with almotriptan. Main outcome measures were pain relief, pain free, consistency, tolerability, and satisfaction with almotriptan 12.5 mg when used to treat multiple migraine attacks. A total of 899 patients with migraine treated 1 (18.4%), 2 (25.9%), or 3 (55.6%) migraine attacks with almotriptan for a total of 2131 attacks. Pain relief at 2 hours was achieved in 84.5% of attacks; pain free was achieved in 41.4%. Consistency of almotriptan 12.5 mg (at least 2 out of 3 attacks successfully treated) was 87.3%. Most patients (88.5%) indicated that they were "satisfied" or "very satisfied" with their treatment with almotriptan and 80.3% of patients expressed that almotriptan 12.5 mg therapy was better than their prior therapy. Physicians' global assessment of the efficacy of almotriptan 12.5 mg was judged to be "good" and "very good" in 87.6% of the patients, and tolerability was considered to be "good" and "very good" in 96.3% of patients. More than 92% of physicians indicated that they would continue to prescribe almotriptan for their patients. The high levels of efficacy, consistency, and tolerability of almotriptan 12.5 mg observed in this postmarketing surveillance study are not only consistent with the findings of controlled clinical trials but also resulted in high rates of patient and physician satisfaction with almotriptan and patient preference for almotriptan over prior acute treatments, including other triptans.
 
To determine whether time-based early treatment, independent of pain intensity, is superior to a pain intensity-based treatment, where patients are asked to treat at least moderate intensity headaches, resulting in a reduction of overall migraine headache duration. Retrospective and prospective trials have reported improved outcomes when triptans were used early or to treat mild migraine headache pain. However, tolerability as well as efficacy may be 2 of several key issues that have prevented this new treatment paradigm from becoming universally accepted. In this multicenter, open-label, cluster-randomized study, patients with IHS-defined migraine were instructed to treat 2 sequential migraine headaches with almotriptan 12.5 mg using either Early Treatment (ET, ie, treat at earliest onset of headache pain, within 1 hour) or Standard Treatment (ST, ie, treat when headache pain intensity is moderate or severe). The novel trial design uses total migraine headache pain duration as the primary endpoint. Results are presented for the first headache and include an ITT population of 757 ET and 693 ST patients. Median headache duration (time from onset of headache pain until no pain) was significantly shorter in ET patients compared to ST patients (3.18 vs 5.53 hours, P < .001). An analysis of the ET subgroup treating headache pain within 1 hour of onset revealed pain intensity, ie, treating mild or moderate versus severe pain, was significantly correlated with treatment outcomes defined by total headache duration, 2-hour pain free, sustained pain free, and use of rescue medication. Multivariate analyses comparing ST subgroups that treated within 1 hour versus greater than 1 hour after headache onset, demonstrate that both pain intensity, ie, treating moderate versus severe headache pain, and treating early versus late, were significantly correlated with total headache duration, 2-hour pain free, sustained pain free, and use of rescue medication. The overall incidence of adverse events was low; nausea and dizziness were the only adverse events with an incidence > or =1% in either treatment group (nausea: 2.5% and 1.7% and dizziness 1.1% and 0.7%, in the ET and ST groups, respectively). Total headache duration was significantly shorter in the early treatment group compared to the standard treatment group. Considering time to treatment within a relatively early range of 1 hour or less, efficacy results when treating mild versus moderate pain were similar and both were associated with better outcomes than treatment of severe pain. When considering the prognostic variables of time to treatment and headache pain intensity (limited to moderate vs severe), both were independent predictors, with time to treatment a better predictor of headache duration and rescue medication use, and pain intensity a better predictor of 2-hour pain free and sustained pain free.
 
This study evaluated the long-term safety of oral almotriptan 12.5 mg for the treatment of multiple migraine episodes in adolescents over a 12-month period. Efficacy outcomes were assessed as a secondary objective. Adolescent migraineurs aged 12-17 years were enrolled in this 12-month, open-label study (Study ID CR002827). Patients were instructed to record their assessments on paper headache records whenever they experienced a migraine headache that they treated with study medication. Safety was assessed descriptively and assessments included adverse event (AE) recording, change in laboratory values, vital signs, and electrocardiogram parameters. Efficacy outcomes were assessed descriptively and outcomes included rates for 2- and 24-hour pain relief and sustained pain relief, 2- and 24-hour pain-free and sustained pain-free, and presence of migraine-associated symptoms of photophobia, phonophobia, nausea and vomiting. Overall, 67.1% of patients reported >or=1 AE over the course of the trial, 7.6% had an AE judged by the study investigator to be related to treatment with almotriptan, 2.4% discontinued because of an AE, and 1.9% reported serious AEs. The most commonly reported treatment-related AEs (occurring in >or=1% of patients) were nausea (1.4%) and somnolence (1.4%). Pain relief responses for treated migraines of moderate or severe intensity at baseline were 61.7% and 68.6%, at 2 and 24 hours, respectively; the sustained pain relief rate was 55.5%. Pain-free responses were reported for 40.5% of all treated migraines at 2 hours and 65.9% of treated migraines at 24 hours; the sustained pain-free rate was 38.4%. The proportion of migraines that achieved the pain relief, sustained pain relief, pain-free and sustained pain-free endpoints were similar in the 12- to 14-year and 15- to 17-year age groups. Treating with almotriptan 12.5 mg when headache pain was mild was associated with higher rates of pain relief and pain-free at 2 and 24 hours, and sustained pain relief and sustained pain-free, compared with treatment initiated when pain was severe. Almotriptan 12.5 mg was well tolerated in this adolescent population over a 12-month period. No unexpected safety or tolerability concerns were revealed over the course of this study. The results are consistent with almotriptan 12.5 mg being effective for the acute treatment of pain and symptoms associated with migraine in both younger and older adolescents.
 
Evaluate the long-term tolerability of almotriptan 12.5 mg for the treatment of acute migraine attacks occurring over a 6-month period. Almotriptan is a second-generation 5-HT(1B/1D) agonist that exhibits vascular selectivity for meningeal arteries and has demonstrated efficacy for the treatment of acute migraine in short-term controlled trials. This was a 6-month open-label study. Adults (18 years of age or older) were required to have a diagnosis of acute migraine with or without aura (according to the diagnostic criteria of the International Headache Society), a history of at least 1 year of moderate-to-severe migraine pain with at least two and a maximum of six migraines per month, and at least 24 hours of freedom from head pain between attacks. Patients were instructed to take a single 12.5-mg dose of almotriptan at the onset of a migraine attack. If migraine pain did not disappear in 2 hours, escape medication could be taken; if relapse occurred in less than 24 hours, a second 12.5-mg dose could be taken. Tolerability was assessed from the nature and incidence of all adverse events, and efficacy was assessed according to the end point of pain relief 2 hours following almotriptan administration. Of 585 patients treated, 582 were included in the intent-to-treat population. The most frequent drug-related adverse events were nausea (3.1%) and dizziness (2.4%). No serious drug-related adverse events were reported, and no deaths occurred. Adverse events led to discontinuation of treatment in 36 patients (6.2%). Drug-related chest pain was reported in 9 patients (1.5%). Seventy-six percent of patients achieved pain relief at 2 hours for all attacks treated, and 49% were pain-free at 2 hours. After a second dose of almotriptan 12.5 mg, pain relief was achieved in 87% of attacks, and 59% were pain-free. Pain relief and pain-free rates were higher among those with moderate baseline pain. When taken at attack onset, almotriptan 12.5 mg is well tolerated, safe, and effective for the long-term treatment of acute migraine.
 
Migraine is a common neurological disorder, the origins of which remain unknown. Patent foramen ovale (PFO) is considered to have a role in migraine. The relationship between migraine and patent foramen ovale may be stronger in patients suffering from migraine with aura compared to patients with common migraine. The aim of the study was to evaluate the frequency of PFO in patients with migraine with aura (MA+) and compare it with the prevalence of PFO in migraine patients without aura (MA-), and in a healthy age-matched control group. We investigated PFO association with migraine, considering such factors as: A type of migraine aura, frequency of attacks, familial occurrence, sex and age of patients. Patients.-121 patients: 61 patients suffering from migraine with aura, 60 without aura and 65 normal controls. The group of patients with migraine with aura was divided into subgroups regarding to the type of aura. In order to detect PFO the contrast transcranial Doppler was performed during Valsalva maneuver. The presence of PFO was found in 33/61 (54%) patients with MA(+) compared to 15/60 (25%) without aura and 16/65 (25%) control subjects. The difference between MA(+) patients and MA(-) patients and the difference between MA(+) patients and control group was statistically significant (P < .05). There was no association between type of migraine aura and PFO, as well as we found no association between PFO and frequency of attacks, familial occurrence, sex and age of patients and PFO. Our findings suggest possible association of migraine with aura and PFO. It seems that PFO does not influence the type of aura and frequency of attacks of migraine as well as it is not associated with familial occurrence of migraine.
 
SYNOPSIS 123I-IMP-SPECT brain imaging was performed in patients with classic migraine (n=5) and migraine accompagnée (n =18) during the headache-free interval. A regional reduction of tracer uptake into brain was observed in all patients with migraine accompagnée, while in patients with classic migraine only one case showed an area of decreased activity. The most marked alteration was found in a patient with persisting neurological symptoms (“complicated migraine”). In most cases the areas of decreased tracer uptake corresponded to headache localization as well as to topography of neurologic symptoms during migraine attacks. It may be concluded that migraine attacks occur in connection with exacerbations of preexisting changes of cerebral autoregulation due to endogenous or exogenous factors.
 
The 5-HT(1B/1D) receptor agonist sumatriptan is highly effective in the treatment of migraine. However, some patients do not respond to sumatriptan or experience recurrence of the headache after initial relief. In addition, some patients report chest symptoms after the use of sumatriptan. To assess whether 2 genetic variants (F124C changing a phenylalanine for a cysteine and polymorphism A/T at nucleotide position -161 in the 5' regulatory region) of the 5-HT(1B) receptor play a major role in the therapeutic response to sumatriptan. The 5-HT(1B) receptor most likely mediates the therapeutic action and coronary side effects of sumatriptan, and both F124C and A-161T have relevant functional consequences on either the affinity of sumatriptan to bind to the 5-HT(1B) receptor or on receptor expression level itself, respectively. Genomic DNA of a relatively small but very well-characterized set of migraine patients with consistently good response to sumatriptan (n = 14), with no response (n = 12), with recurrence of the headache (n = 12), with chest symptoms (n = 13), and patients without chest symptoms (n = 27) was available for the genetic analyses and screened for the F124C variant and the A-161T polymorphism in the human 5-HT(1B) receptor gene. F124C was not detected in any of the patients studied. In addition, we did not observe drastic changes in allele frequencies of the A-161T polymorphism that might hint to a causal relation with the therapeutic effect of sumatriptan. We have not obtained any evidence that variants F124C and A-161T of the 5-HT(1B) receptor are major determinants in the clinical response to sumatriptan.
 
This study of headache location in migraine was performed (1) to document the location of pain in a large group of migraine patients and (2) to assess the impact of different types of migraine, gender, aura, and headache features on the location of the headache. The literature documenting the location of the pain of acute attack of migraine is sparse. A total of 1283 migraine patients (ICHD, 2004, 1.1, 1.2, 1.5.1, and 1.6) were evaluated at the 1st visit. Headache location and character were graded on a scale of 0 to 3 with 0 being none and 3 the most. Triggers were graded on a frequency scale of 0 to 3; 0 = none; 1 = less than 1/3 of time; 2 = between 1/3 and 2/3 of time; 3 = greater than 2/3 of time. Other headache features and medication responsiveness, were also recorded. Patients were stratified by migraine type and headache frequency. Combined and isolated locations, and the impact of age, gender, headache frequency, migraine types, and aura were addressed. Unremitting headache was excluded. Migraine patients reported that the highest location frequencies were in the eyes (67.1%), temporal (58.0%), and frontal (55.9%). The lowest were diffusely (17.5%) and vertex (24.1%). The intermediate were in the occipital (39.8%) and neck areas (39.7%). Other migraine types were remarkably similar. Hemi-cranial location was present in 66.6% of patients, 71.2% in episodic migraine and 61.4% in chronic migraine, 67.2% in females and 63.2% in males, 59.7% in migraine without aura and 68.9% in migraine with aura 100% of the time. Headaches were reported on the right side in 27.3%, left side 24.3%, both sides 23.7%, either side 15.0%, and in the middle of the head in 4.6% of cases. Significant differences in headache location were seen only within migraine and not other migraine types. Headache location was not correlated with lifetime duration of migraine, prodrome, response to triptan, intensity, time to peak of headache, recurrence frequency, and time to recurrence. This study provides a detailed documentation of headache location in a large cohort of patients. The commonest locations are the orbital, frontal, and temporal areas and least common sites being diffuse and the vertex. A single location is infrequent. Hemi-cranial location is present in two thirds of subjects and a quarter each are on the left side, right side, and both sides. The locations of the headache are very similar in different migraine types, but there are some differences. Under age 21 and older patients tended to show some differences in location and side. Location differences are seen with gender, headache frequency, and aura. Location shows many correlations with triggers and headache features.
 
A retrospective study was conducted on 1300 women suffering from migraine without aura referred to the Headache Centers of Parma and Pavia from 1984 to 1990. All the data concerning their reproductive life, and the modifications induced by it on the course of headache were obtained from record-charts. Migraine frequently started at menarche (10.7%); in 60% of cases the migraine attacks occurred mostly or exclusively in the perimenstrual period, in 67% of cases disappeared during pregnancy, and in 24.1% significantly (P < 0.0001) worsened with "pill" intake. This study also designated a migraine subgroup which is more influenced by changes in sexual hormones, i.e. migraine with onset at menarche. This form of migraine shows more frequently a menstrual periodicity, and usually improves during pregnancy. Furthermore, menstrual migraine patients show social and cultural characteristics with distinguish them from other women.
 
SYNOPSIS The present study reports cerebral blood flow (CBF) measurements in 11 patients during attacks of classic migraine (CM)-migraine with aura. In 6 and 7 patients, respectively, cerebral vascular reactivity to increased blood pressure and to hypocapnia was also investigated during the CM attacks. The Xenon-133 intraarterial injection technique was used to measure CBF. In this study, based in part on previously published data, methodological limitations, in particular caused by scattered radiation (Compton scatter), are critically analysed. Based on this analysis and the results of the CBF studies it is concluded: During CM attacks CBF appears to decrease focally in the posterior part of the brain to a level around 20 ml/100 g/min which is consistent with a mild degree of ischemia. Changes of CBF in focal low flow areas are difficult to evaluate accurately with the Xe-133 technique. In most cases true CBF may change 50% or more in the low flow areas without giving rise to significantly measurable changes of CBF. This analysis suggests that the autoregulation response cannot be evaluated in the low flow areas with the technique used while the observations are compatible with the concept that a vasoconstrictive state, unresponsive to hypocapnia, prevails in the low flow areas during CM attacks. The gradual increase in size of the low flow area seen in several cases may be interpreted in two different ways. A spreading process may actually exist. However, due to Compton scatter, a gradual decrease of CBF in a territorythat does not increase in size will also appear as a gradually spreading low flow area when studied with the Xe-133 intracarotid technique.
 
To study the clinical features of nummular headache (NH) and get an approach to its epidemiology. NH has been recently described as a primary disorder characterized by head pain exclusively felt in a small rounded area typically 2-6 cm in diameter. Through a 1-year period we have studied all patients referred to our neurologic clinic because of head pain exclusively felt in a small-circumscribed area, and not attributed to another disorder. All the patients had normal neurological, analytical, and neuroimaging examinations. All the patients belonged within the same regional care system comprising 220,000 inhabitants. A total of 11 females and 3 males were studied. Based in our hospital series, the incidence was 6.4/100,000/year. The mean age at the onset was 38 years (range: 13-72). Only three patients had another concurrent headache: migraine (n = 2), and trigeminal neuralgia (n = 1) which proved to have an independent course. All the patients reported head pain exclusively felt in either a rounded (n = 12) of 1-6 cm diameter, or an oval area (n = 2) of 5 x 3 cm, and 2 x 3 cm, respectively. Both size and shape of the painful area remained constant since the onset of symptoms. The location of the symptomatic area was mostly parietal (n = 7) or temporal (n = 5), but also frontal (n = 1) and in occiput (n = 1). The background pain was mostly mild-to-moderate, but also moderate-to-severe pain was reported. Exacerbations-either spontaneous or precipitated by combing hair or touching the symptomatic area-were reported by 8 patients. The temporal pattern was chronic-continuous (n = 7) and episodic (n = 7). Ten patients reported a variable combination of sensory disturbance (tenderness, hypoesthesia, hyperalgesia, and allodynia) in the symptomatic area. There were no autonomic accompaniments. Treatment was generally not necessary. When needed, standard oral doses of paracetamol usually sufficed. NH emerges as a clear-cut clinical picture. It is a noninfrequent primary headache. The particular topography suggests the pain has a probable epicranial source conveyed by, or originated in, one/a few terminal branch(es) of the cutaneous nerves of the scalp.
 
During the 14th International Headache Congress the results of several innovative studies that contribute to our understanding of headache pathophysiology and treatment were presented. Here we summarize work expected to contribute substantially to understanding headache mechanisms, while an accompanying manuscript summarizes presentations regarding the treatment of headache. This manuscript highlights research on mechanisms of photophobia and phonophobia, pharmacologic inhibition of cortical spreading depression, a proposed mechanism by which oxygen effectively treats cluster headache, identification of functional and structural aberrations in people with hypnic headache, and research on functional imaging markers of a migraine attack.
 
The 14th International Headache Congress was held in Philadelphia in September 2009. During the Congress, many important basic, translational, and patient-oriented research studies were presented. In this and an accompanying manuscript, the work that has been deemed to be among the most innovative and significant is summarized. This manuscript discusses the best clinical research, while the accompanying manuscript summarizes the top basic science research. Here, we provide background and summarize Congress presentations on novel agents for migraine treatment, botulinum toxin therapy for chronic migraine, new methods for administration of headache medications, and nerve stimulation for the treatment of medically refractory headaches.
 
The 15th Congress of the International Headache Society was held in Berlin from June 23rd to 26th of 2011. Interesting new data from several areas of the basic sciences of headache were presented. This is a review of some of the most exciting platform and poster presentations of the meeting. Research addressing 3 general areas of interest is presented in this review: pathophysiology, pharmacology, and genetics.
 
SYNOPSIS We have studied the effect of isometheptene, an indirectly acting sympathomimetic with a reported anti-migraine action, on carotid blood flow and the distribution of carotid blood flow throughout the cephalic circulation of the cat, using 15μm-microspheres. Microspheres measuring 15μm in diameter were used to separate capillary flow from flow through the arteriovenous anastomoses. Apart from decreasing carotid blood flow, isometheptene vigorously reduced the fraction of carotid blood flow shunted through the arteriovenous anastomoses. This mode of action of isometheptene may be relevant to its beneficial effect in migraine.
 
SYNOPSISThe efficacy of long acting propranolol in a dosage of 80 mg once daily in comparison to 160 mg once daily was assessed in the prophylactic treatment of migraine in a double-blind cross-over trial. 48 patients with classic or common migraine were included in the investigation, 6 patients withdrew, but only one because of side-effects. A four week run-in placebo period preceded the drug treatments, the duration of drug treatments was 12 weeks and there was a wash-out placebo period of 4 weeks between the treatments.The two long acting propranolol doses, 80 mg and 160 mg once daily seemed to be equally effective. There was no difference in the antimigraineous effect. Long acting propranolol decreased both the frequency and severity of migraine attacks. Side-effects reported during the trial were mild, both doses were well tolerated. The treatment compliance during the once daily treatment was very good.
 
(Headache 2011;51:632-636) Seventeenth-century English closets were books containing a wide repertoire of household supplies targeted at female readers. Such volumes typically included medical recipes, as early modern women also used to be responsible for preserving and restoring the health of relatives and close neighbors. A Closet for Ladies and Gentlewomen (Sir Hugh Platt, 1608), in particular, incorporates 13 medicinal remedies devised for the therapeutic management of 3 different types of headaches: head-ache, migraine and pain in the head. This article historically contextualizes the text, offers a valid classification of headaches in 17th-century England, and describes the composition of the homemade pharmaceutical forms recommended to female caregivers, the guidelines for administration and its potential pain-relieving effects.
 
SYNOPSIS An open study of verapamil in cluster headache is reported. Forty-eight patients participated in the study of whom 33 (=69%) improved more than 75%. No significant differences in response were observed between episodic and chronic cluster headache.
 
SYNOPSISM To most physicians, Thomas Willis (1621–1675) is only known for the Circle of Willis, but he achievedmuch more: he was one of the three great clinicians of 17th-century England, and the founder of modernbrain anatomy and clinical neurology. He coined the word “neurology,” discovered reflex action, and wrotethe first textbook of clinical neurology. He made use of an imaginary neurophysiological framework whichenabled him to anticipate numerous discoveries of the 19th century.The first two chapters of the clinical part of his textbook deal with headache. Wolff's hypothesis,“complete migraine,rdquo; the slow spreading of focal symptoms, the cerebral origin of vomiting, and clusterperiodicity are found to be anticipated, at least in part. The combination of hypothetical pathophysiologyand arbitrary nosology is quite suggestive of the present situation, although the system is different.The review is based on the original Latin text of 1672.
 
SYNOPSIS We report the first use of ICI 169,369, a selective S2 receptor antagonist, in acute and prophylactic treatment of migraine. Ten selected patients documented their migraine attacks over a 2-month period of open treatment with ICI 169,369, 30 mg orally, for acute therapy. They compared this treatment with others they had experience of. Four of these patients undertook a pharmacokinetic study comparing drug absorption in an acute attack to that when symptom-free. Prophylaxis was then commenced with the same drug, 30 mg bd. Patients recorded symptoms in diary cards noting the effects of treatment on the usual frequency and severity of their attacks. The pharmacokinetic study showed that drug absorption could be markedly impaired during an acute attack. Nevertheless, in 35 attacks treated acutely, half the patients reported some efficacy apparent to them. One third of patients considered ICI 169,369 to be better treatment on this one occasion than their own usual medication. Some benefit was also noted during prophylaxis. There was a statistically significant reduction in attack frequency from the baseline observed during acute therapy only, but this was arguably compatible with placebo response. S2 receptor antagonism may have some beneficial effect in acute or prophylactic treatment of migraine, but it is not marked and does not support S2 receptor activation being important in its pathogenesis.
 
We report the case of a 17-year-old boy presenting with a history of recurrent episodes of isolated visual aura later followed infrequently by indomethacin-responsive headache attacks resembling paroxysmal hemicrania.
 
The objective of this study was to investigate the prevalence and sociodemographic characteristics of headaches among Turkish adolescents aged 12 to 17 years old in Bursa province of Turkey. A multistep, stratified, cluster sampling method was used for subject selection. The estimated sample size for 12- to 14-year-old students was 1,270 and for 15- to 17-year-old students was 1,117. Our study sample included 6.5% of the secondary schools and 1.8% of the students aged 12 to 17 years old. The study was conducted in two phases; the questionnaire phase and the face-to-face interview phase. The prevalence of recurrent headache in the study population was 52.2%. Girls (59.8%) had significantly more recurrent headache than boys (45.1%) The prevalence of recurrent headache increased from 42.2% up to 60.7% by age. In multivariate logistic regression analysis age and gender differed significantly between adolescents with and without recurrent headache groups. Frequent episodic tension-type headache was the most common (25.9%) headache among Turkish adolescents, followed by migraine (14.5%). Age and gender appeared to be demographic factors increasing adolescent headache prevalence. Frequent episodic-tension type headache was the most common headache followed by migraine. Our migraine prevalence was slightly higher than most of the previously reported prevalence rates. This might be due to the new classification criteria of headache released by International Headache Society.
 
(Headache 2011;51:999-1001) Olfactory hallucinations have been reported in association with numerous neurological and psychiatric disorders, in particular as a component of partial complex seizure and psychiatric disorders, but are rarely described in migraine disease. We report the case of an adolescent who reported complex hallucinations during a migraine attack.
 
Seven hundred nineteen young patients attending 21 Italian headache care settings were evaluated by a diagnostic headache interview and a neurological examination. Headache disorders were classified according to the current 1988 criteria of the International Headache Society (IHS); 54.9% of the patients suffered from migraine, 33.9% from tension-type headache, 1.9% from secondary headache, and 3.4% had non-classifiable headache. A further 5.9% of the patients were not classified due to incomplete questionnaires. Of the 395 patients with migraine, 44.5% were affected by migraine without aura, 29.9% by migraine with aura, 1.3% from other migraine forms, and 24.3% by migrainous disorders which do not fulfill the 1988 IHS diagnostic criteria for headache. Among the 244 patients with tension-type headache, 51.6% had episodic tension-type headache, 15.2% chronic tension-type headache, and 33.2% headache of the tension-type which does not fulfill the 1988 IHS criteria for episodic and chronic tension-type headache. In young migraine patients, pain was of a pulsating type in 55.7%, severe in 57.8%, unilateral in 42.6%, and aggravated by routine physical activity in 38.9%. Tension-type headache was described as pressing in 73.8%, mild or moderate in 75.7%, bilateral in 87.4%, and not aggravated by routine physical activity in 85.5%. The duration of pain was less than 2 hours in 35% of the cases in migraine sufferers and less than 30 minutes in 26.7% of tension-type headache sufferers. Nausea, phonophobia, and photophobia were present in at least half of the migraine patients and in one third of tension-type headache patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 
SYNOPSIS In previous studies, we reported chronic hemodialysis patients who suffer with headaches to have low renin, low aldosterone, and high blood pressure. We report the role of plasma 18 Hydroxy-II-deoxycorticosterone 18 OHDOC as another mineralocorticoid responsible for such biochemical change. Plasma 18 OHDOC level was found to be low in these patients.
 
The efficacy of BMS 180048, a 5-HT1 agonist in the acute treatment of a migraine headache, was evaluated in 216 patients. Three doses of the study drug were compared to placebo. Patients received a single test dose in the physician's office while being evaluated with a Holter monitor during a headache-free day. They then treated a migraines headache with a single dose of the study drug as an outpatient. The 150 mg- and 200-mg doses of BMS were significantly superior to placebo on change in pain intensity at 2 hours. Patients treated with BMS 180048 had a longer duration of response than placebo-treated patients. At the 24-hour point, only 24% of the 150-mg group and 25% of the 200-mg group had relapsed, compared to placebo which had a 42% relapse rate. It is concluded that BMS 180048 is an effective compound for the treatment of migraine headaches with a prolonged duration of response.
 
Nitroglycerin (NTG) (glyceryl trinitrate) was synthesized by the Italian chemist Ascanio Sobrero in Paris in 1846. A very unstable explosive, Alfred Nobel while working on explosives, combined it with Kiselguhr and patented it as dynamite in 1867. NTG was introduced in 1879 in medicine in the treatment of angina pectoris by the English doctor William Murrell. NTG-induced headache was quickly recognized as an important adverse event both in the industrial use of NTG, where it was used to produce dynamite, as well as in the use of NTG as drug. This review traces the evolution of our understanding of NTG headache.
 
To investigate the familial occurrence of cluster headache in a series of French patients fulfilling the International Headache Society diagnosis criteria. One hundred eighty-six index patients and 624 first-degree relatives were surveyed. A positive family history of cluster headache was found in 20 index patients (10.75%) with 22 affected first-degree relatives (3.4%). In multiplex families 6 of the 68 second-degree relatives that were contacted had cluster headache. No precise mode of inheritance could be drawn from the observed repartition of cases within multiplex families.
 
SYNOPSISAutonomic nervous system functions were studied in 188 patients with migraine during headache free intervals by measuring cardiovascular reflex responses. Eighty-five healthy subjects served as a control group.Pulse rate (R-R- interval) variation in normal and deep breathing, during Valsalva manoeuvre and orthostatic test was diminished in migraine patients. Diastolic blood pressure rises in orthostatic test and isometric work test were lower than in the controls. The results of patients with classic and common migraine did not deviate from each other. The same was true for the results of the female and male patients.The results of the patients with frequent migraine attacks (>4/month) showed more severe disturbance than those with infrequent attacks. Disturbances gradually developed with age, being minimal or totally lacking in young migraine patients. The results confirm the development of sympathetic and parasympathetic hypofunction in migraine patients during the course of the disorder.
 
Epicrania fugax (EF) is a primary headache of recent description. We aimed to report 19 new cases of EF, and thus contribute to the characterization of this emerging headache. EF is characterized by painful paroxysms starting in a particular area of the head, and rapidly radiating forwards or backwards through the territories of different nerves. The pain is felt in quick motion along a lineal or zigzag trajectory. To date, 47 cases have been published, 34 with forward EF and 13 with backward EF. We performed a descriptive study of all EF cases attending our Headache Unit from April 2010 to December 2012. Demographic and clinical data were recorded with a structured questionnaire. Overall, there were 12 women and 7 men. Mean age at onset was 51.7 ± 16.2. Fourteen patients had forward EF, while 5 patients had backward EF. Painful paroxysms lasted 1-4 seconds. Pain intensity was usually moderate or severe, and pain quality was mostly electric. Four patients had ocular autonomic accompaniments. Pain frequency was extremely variable, and 7 patients identified some triggers. Between attacks, 13 patients had some pain or tenderness in the stemming area. Thirteen patients required therapy for their pain. Neuromodulators, indomethacin, anesthetic blockades, and steroid injections were used in different cases, with partial or complete response. EF appears as a distinct headache syndrome and could be eventually included in future editions of the International Classification of Headache Disorders.
 
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Richard Lipton
  • Albert Einstein College of Medicine
Michael L Reed
  • Vedanta Research
Stephen D Silberstein
  • Thomas Jefferson University
Dawn C Buse
  • Albert Einstein College of Medicine
Walter Stewart
  • Sutter Health