Crying migraine

Eighty-five percent of migraineurs report triggers which include a diverse array of internal and external factors. Crying as a trigger has been reported in two women, without details, in only one prior study. In the present report, the clinical history of two women (aged 38 and 41 years, respectively) with migraines triggered by crying are detailed. In both women, the migraines were triggered by crying associated with sadness or emotional upset. Crying when happy or due to cutting onions was not a trigger. Only in the second patient was crying during a sad movie or theatrical production also a trigger. Crying may be a common underrecognized migraine trigger.     

The mode of action of migraine triggers: a hypothesis

Objectives.— To review conjectured modes of action of migraine triggers and to present a new hypothesis about them.
Background.— Migraine attacks are initiated in many migraineurs by a variety of "triggers," although in some patients no external trigger can be identified. Many triggers provoke attacks with such a short latency that only some kind of neural mechanism can explain the triggering.
Results.— We present here a hypothesis that the pain of migraine has its ultimate origin in the cortex, but that the immediate generator is in the brainstem. Our hypothesis is that most migraines have triggers that produce excitation of cortical neurons and that this directly causes withdrawal of descending sensory inhibition originating in the brainstem. A wide range of evidence from the literature that cortical activation induced by a number of different mechanisms often produces headache is presented to support this notion. Several nuclei in the brainstem appear to participate in the selective control of trigeminovascular sensation through descending inhibitory mechanisms that arise in the cortex. In this review we focus on 2 of them, the periaqueductal gray matter and nucleus raphe magnus. Our own past results and those of others show that this inhibition is specific for craniovascular sensation and involves the neurotransmitter 5-hydroxytryptamine. Finally, we summarize our own recent experiments, which show that cortical activation by migraine triggers (including cortical spreading depression) inhibits neuronal discharge in the brainstem and facilitates trigeminovascular sensation.
Conclusion.— If the hypothesis can be proven and the neurotransmitters involved in the hypothetical trigger pathway can be identified, it may be possible to develop novel migraine preventative therapies.     

Frovatriptan as preemptive treatment for fasting-induced migraine

Objective.— To examine frovatriptan's efficacy as preemptive treatment for fasting‐induced migraine. Background.— Fasting is a common migraine trigger that cannot always be avoided. The development of a short‐term preemptive approach would be of benefit. Because of its longer half‐life, frovatriptan has been effectively used for short‐term daily use to prevent menstrually related migraines and might prove useful in the prevention of fasting‐induced migraine. Methods.— This was a double‐blind, placebo‐controlled, randomized, parallel‐group trial. Subjects.— With a history of fasting‐induced episodic migraine were randomly assigned to receive either frovatriptan (5.0 mg) or placebo (ratio 1:1). Subjects.— Took a single dose of study medication at the start of their 20‐hour fast. Information about headache intensity, associated symptoms, and use of rescue medication was captured at defined time points from the start of the fast through 20 hours post‐fast. Results.— Of the 75 subjects screened, 74 subjects were randomized and 71 subjects completed the study. Demographic characteristics of the placebo and frovatriptan treatment groups were not statistically different. Thirty‐three subjects received active drug. Twelve (36.4%) developed a headache between 6 and 20 hours after the start of the fast (1/33 mild, 11/33 moderate or severe). In the placebo group, 18/34 (52.9%) developed a headache (4/34 mild, 14/34 moderate or severe). The difference between the 2 treatment groups did not achieve statistical significance; Pearson chi‐square, P = .172. Kaplan‐Meier survival analysis showed no difference between the 2 treatment groups with respect to the time of onset of headache of any intensity (log rank, P = .264) and for the time of onset of a moderate or severe intensity (log rank, P = .634). Conclusion.— More subjects on placebo developed a headache than those on frovatriptan. Perhaps because of the small number of subjects involved, the differences in headache incidences observed did not achieve statistical significance.     

Possible predictive factors in the prognosis of migraine with aura

In order to identify possible predictive factors in the prognosis of migraine with aura (MA), we conducted a review at 10 to 20 years from referral on a sample of 77 MA patients (51 F, 26 M) consecutively seen for the first time at the University of Parma Headache Center. Based on the date of the last MA attack reported by these patients, we divided them into two study groups: a group of 22 patients "with remission of the disease," i.e. attack-free for at least 2 years at the end of the follow-up study; and a group of 55 patients "without remission of the disease," i.e. still having attacks in the last 2 years of the follow-up study. A comparative analysis of the MA clinical features observed in the two groups at the time of the patients' first visit to our Center enabled us to identify a number of favorable prognostic indicators, namely: a family history of parents with MA, the absence of other associated forms of primary headache, and the absence of both natural and artificial light stimulation as trigger factors.     

Reflux-triggered migraine headache originating from the upper gum/teeth

Two patients with migraine are described who also suffered from gastric reflux. The reflux triggered headaches that originated from the upper gum/teeth and responded to specific reflux treatment.     

Prospective analysis of factors related to migraine attacks: the PAMINA study

Migraine is related to numerous factors such as hormones, stress or nutrition, but information about their actual importance is limited. Therefore, we analysed prospectively a wide spectrum of factors related to headache in migraineurs. We examined 327 migraineurs recruited via newspapers who kept a comprehensive diary for 3 months. Statistical analysis comprising 28 325 patient days and 116 dichotomous variables was based on the interval between two successive headache attacks. We calculated univariate Cox regression analyses and included covariables with a P-value of <0.05 in two stepwise multivariate Cox regression analyses, the first accounting for a correlation of the event times within a subject, the second stratified by the number of headache-free intervals. We performed similar analyses for the occurrence of migraine attacks and for the persistence of headache and migraine. Menstruation had the most prominent effect, increasing the hazard of occurrence or persistence of headache and migraine by up to 96%. All other factors changed the hazard by <35%. The two days before menstruation and muscle tension in the neck, psychic tension, tiredness, noise and odours on days before headache onset increased the hazard of headache or migraine, whereas days off, a divorced marriage, relaxation after stress, and consumption of beer decreased the hazard. In addition, three meteorological factors increased and two others decreased the hazard. In conclusion, menstruation is most important in increasing the risk of occurrence and persistence of headache and migraine. Other factors increase the risk less markedly or decrease the risk.     

Is familial hemiplegic migraine a hereditary form of basilar migraine?

We studied aura symptoms in 83 patients from 6 unrelated families suffering from familial hemiplegic migraine. Fifty-five of the patients reported symptoms that allowed us to categorize them as basilar migraine (BM) patients, in accordance with the International Headache Society (IHS) criteria. In a control group of 33 patients suffering from migraine with aura and 33 patients suffering from migraine without aura, 9 patients complained of vertigo, and only one patient of diplopia during one of her attacks. None of these control patients fulfilled the IHS criteria for BM We suggest that familial hemiplegic migraine and BM may share certain pathophysiologic mechanisms, which may consist of a (genetically determined) disturbance of basilar artery blood flow.     

Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study

Background.— Though symptomatic medication overuse is believed to play a major role in progression from episodic to chronic or transformed migraine (TM), population‐based longitudinal data on these agents are limited. Objectives.— To assess the role of specific classes of acute medications in the development of TM in episodic migraine (EM) sufferers after adjusting for other risk factors for headache progression. Methods.— As a part of the American Migraine Prevalence and Prevention study (AMPP), we initially surveyed a population sample of 120,000 individuals to identify a sample of migraineurs to be followed annually over 5 years. Using logistic and linear regression, we modeled the probability of transition from EM in 2005 to TM in 2006 in relation to medication use status at baseline. Adjustments were made for gender, headache frequency and severity, and prevention medication use. Results.— Of 8219 individuals with EM in 2005, 209 (2.5%) had developed TM by 2006. Baseline headache frequency was a risk factor for TM. Using acetaminophen user as the reference group, individuals who used medications containing barbiturates (OR = 2.06, 95%CI = 1.3‐3.1) or opiates (OR = 1.98, 95%CI = 1.4‐2.2) were at increased risk of TM. A dose–response relationship was found for use of barbiturates. Use of triptans (OR = 1.25, 95%CI = 0.9‐1.7) at baseline was not associated with prospective risk of TM. Overall, NSAIDs (OR = 0.85, 95%CI = 0.63‐1.17) were not associated with TM. Indeed, NSAIDs were protective against transition to TM at low to moderate monthly headache days, but were associated with increased risk of transition to TM at high levels of monthly headache days. Conclusion.— EM sufferers develop TM at the rate of 2.5% per year. Any use of barbiturates and opiates was associated with increased risk of TM after adjusting for covariates, while triptans were not. NSAIDs were protective or inducers depending on the headache frequency.     

Single-site botulinum toxin type a injection for elimination of migraine trigger points

BACKGROUND: Botulinum toxin may be effective in suppressing migraine. Most injection regimens utilized have involved multiple sites. PURPOSE: To evaluate prospectively the effect of botulinum toxin type A injections into the corrugator supercilii muscles alone on the frequency and severity of migraine. METHODS: Twenty-nine patients (24 women, 5 men) with migraine were enrolled in the study. Average age was 45 years (range, 24 to 63). The frequency (number of migraines per month) and intensity (recorded on an analog scale of 1 to 10, 10 being most severe) of headache were recorded before and after treatment. Twenty-five units of botulinum toxin type A was injected into each corrugator supercilii muscle, for a total of 50 units. RESULTS: At 2 months, 24 (83%) of 29 patients reported a positive response to the injection of botulinum toxin type A (P <.001). Sixteen patients (55%) reported complete elimination of headache (P <.001), 8 (28%) experienced significant improvement (at least 50% reduction in frequency or intensity) (P <.04), and 5 (17%) did not notice a change in headache. The duration of efficacy of the botulinum toxin type A injections ranged from 6 to 12 weeks, with an average of 8 weeks. In patients who had improvement in migraine but not complete elimination, the headache frequency decreased from 6.4 to 2.1 per month on average (P <.04), and the intensity decreased from 8.6 to 6.1 (P <.04). CONCLUSION: These results support the hypothesis that focal injection of botulinum toxin type A may be an effective therapy for migraine.     

Assessment of migraine disability using the migraine disability assessment (MIDAS) questionnaire: a comparison of chronic migraine with episodic migraine

BACKGROUND: Chronic migraine is the most common type of chronic daily headache seen in headache tertiary care centers. Most patients with chronic migraine report their ability to function and feeling of well-being as severely impaired. OBJECTIVE: To measure the headache-related disability of patients with chronic migraine using the Migraine Disability Assessment (MIDAS) Questionnaire, comparing it with that obtained in a control group of patients with episodic migraine. METHODS: The clinical records of 703 patients with chronic daily headache treated in a headache specialty clinic were reviewed to identify 182 with chronic migraine who were evaluated using the MIDAS at their initial visit. Our control group consisted of 86 patients with episodic migraine. RESULTS: Of the 182 patients with chronic migraine, 127 (69.8%) were overusing acute-care medication. Patients were predominantly women (72.5%), with a mean age of 38.3 years. The group with episodic migraine consisted of 59 women (68.6%), with a mean age of 36.1 years. No statistically significant demographic differences were observed between the two groups. The group with chronic migraine had more total headache days over 3 months (66.7 versus 15.5, P<.001), missed more days of work or school (5.3 versus 2.3, P =.0007), had more reduced effectiveness days at work or school (11.9 versus 4.6, P =.0001), missed more days of housework (16.5 versus 3.3, P<.0001), and missed more days of family, social, or leisure activities (7.0 versus 5.5, P =.03). The group with chronic migraine was more likely to be in MIDAS grade IV (64.3% versus 43.2%, P =.001), reflecting the great likelihood of severe disability in this group. The average total MIDAS score was 34.9 in the group with chronic migraine versus 19.3 in the group with episodic migraine (P<.001). CONCLUSION: In subspecialty centers, patients with chronic migraine demonstrate remarkable impairment of their daily activities and are severely burdened by their headache syndrome, reflected by their high MIDAS scores. The chronicity and pervasiveness of migraine thus is associated with increased functional impairment as well as increase in headache frequency.     

Normobaric hypoxia and nitroglycerin as trigger factors for migraine

Migraine prevalence is increased in high-altitude populations and symptoms of acute mountain sickness mimic migraine symptoms. Here we tested whether normobaric hypoxia may trigger migraine attacks. As positive control we used nitrolgycerin (NTG), which has been shown to induce migraine attacks in up to 80% of migraineurs. Sixteen patients (12 females, mean age 28.9 +/- 7.2 years) suffering from migraine with (n = 8) and without aura (n = 8) underwent three different provocations (normobaric hypoxia, NTG and placebo) in a randomized, cross-over, double dummy design. Each provocation was performed on a separate day. The primary outcome measure was the proportion of patients developing a migraine attack according to the criteria of the International Headache Society within 8 h after provocation onset. Fourteen patients completed all three provocations. Migraine was provoked in six (42%) patients by hypoxia, in three (21%) by NTG and in two (14%) by placebo. The differences among groups were not significant (P = 0.197). The median time to attacks was 5 h. In conclusion, the (remarkably) low response rate to NTG is surprising in view of previous data. Further studies are required to establish fully the potency of hypoxia in triggering migraine attacks.     

Dihydroergokryptine versus dihydroergotamine in migraine prophylaxis: a double-blind clinical trial

Dihydroergokryptine has been evaluated in the prophylaxis of headache attacks in patients with migraine without aura. The study was controlled vs dihydroergotamine with a double-blind crossover design. After a 1-month run-in period, 30 patients were randomized into two groups and submitted to 4 months treatment with dihydroergokryptine 10 mg b.i.d. or dihydroergotamine (controlled release) 5 mg b.i.d. The treatment was repeated in crossover after 2 months washout. The clinical patients' evaluation was determined by monthly Pain Total Index recording, headache daysmonth and analgesic consumption. The patients were considered responsible when Pain Total Index decreased by 50% or more in 1 or more months of each treatment period; otherwise the patients were considered unresponsive. The response rate to dihydroergokryptine was 66% while 48% of cases were responsive to dihydroergotamine. The response rate to both treatments was 41%, while 26 % did not respond to either treatment. Seven cases unresponsive to dihydroergotamine responded positively to dihydroergokryptine while two cases only, resistant to dihydroergokryptine, responded positively to dihydroergotamine. Three cases dropped out during treatment with dihydroergotamine due to gastric pain and nausea, while they did not show any side effects during dihydroergokryptine therapy. During treatment with dihydroergokryptine there was one case of skin rash which disappeared after drug withdrawal. In conclusion, dihydroergokryptine appears to be an effective drug for the prophylaxis of migraine attacks.     

Refractory migraine and chronic migraine: pathophysiological mechanisms

Migraine is a complex disorder of the brain whose mechanisms are only now being unravelled. It is common, disabling, and economically costly. Brain imaging has suggested a role for the brainstem. While the disorder is almost certainly inherited, the degree to which this contributes to a treatment refractory state is not clear. Indeed, no specific structural or pharmacological explanation can be seen from the data as they have been generated. It is clear that patients with more frequent headache are very likely to go on to even more frequent headache, but again these data are complex. A challenge going forward is to establish the biology of these very challenging patients who undoubtedly have substantial disability.     

Early treatment of migraine with rizatriptan: a placebo-controlled study

OBJECTIVE: To evaluate the efficacy of rizatriptan when administered early during a migraine attack. BACKGROUND: Several studies indicate that triptans are more efficacious when administered early during a migraine attack, when the pain is still mild. METHODS: One hundred and twelve rizatriptan-na?ve patients aged 20 to 64 years with a history of migraine with or without aura that progressively worsened when left untreated were instructed to treat a total of three migraine attacks with either rizatriptan 10 mg or placebo as early as possible during each attack. Seventy-four patients (68 women and 6 men) were assigned to use the active drug and 38 (35 women and 3 men) to placebo. The primary efficacy endpoint was pain-free response at 2 hours after administration of the study drug. Secondary efficacy measures were pain-free response at 1 hour and sustained pain-free response lasting between 2 and 24 hours. RESULTS: A total of 216 attacks were treated in the rizatriptan group and 109 in the placebo group. Pain-free response at 2 hours after early treatment was noted in 151 (70%) of attacks in the rizatriptan group and in 24 (22%) in the placebo group (P < .01). Pain-free response at 1 hour occurred in 97 (45%) and 9 (8%) attacks, respectively (P < .01). When the attacks were categorized by headache severity at the time of treatment, the pain-free response at 2 hours was higher for mild attacks than for moderate or severe attacks (P < .01). Sustained pain-free response after treatment was significantly higher for attacks treated with rizatriptan (60%) than for those treated with placebo (17%) (P < .001). Adverse events were observed in 62 patients in the rizatriptan group and 15 in the placebo group. Only 1 patient taking rizatriptan discontinued the study because of adverse events, and no serious adverse events were reported. CONCLUSIONS: Rizatriptan is significantly more likely than placebo to produce a pain-free response within 2 hours when the drug is administered early in the migraine attack, when pain is mild rather than moderate or severe.     

Water-deprivation headache: a new headache with two variants

OBJECTIVES: To describe a new type of headache induced by water deprivation. BACKGROUND: Two medical students experienced headache over the previous 7 (C.A.K.) and 9 (J.M.S.) years when deprived of drinking water. In a tutorial on headache, they mentioned this precipitant, not recognized by the tutor (J.N.B.) or described in the medical literature. Dialysis and post-alcohol headaches are widely attributed to dehydration, but simple water deprivation has not been documented as a headache precipitant. METHODS: Family members, colleagues, and acquaintances were asked whether they experienced a headache when deprived of fluids. If they had, information was obtained regarding the location and quality of the headache, whether activity or posture influenced the pain, and what amount of fluid and time was needed to relieve symptoms. RESULTS: Approximately 1 in 10 interrogated subjects experienced water-deprivation headache, aching in the majority and accentuated by head movement, bending down, or walking. The 34 subjects were divided into 2 groups according to the time taken to relieve the headache by drinking water: total relief within 30 minutes by drinking 200 to 1500 mL (mean, 500) occurred in 22 subjects, and within 1 to 3 hours by drinking 500 to 1000 mL (mean, 750) in 11 subjects; 1 subject required sleep in addition to fluid intake. Surprisingly, the Internet revealed many references to water deprivation inducing headaches. CONCLUSIONS: Water-deprivation headache is common, recognized by the public, but not described in the medical literature. Here we delineate it as a primary headache, postulating that the pain arises from the meninges; that the brain is also involved is indicated by impaired concentration and irritability, although not studied in detail in this preliminary survey. We speculate that water deprivation may play a role in migraine, particularly in prolonging attacks. Further studies of serum osmolality could prove illuminating.     

Is chronic migraine one end of a spectrum of migraine or a separate entity?

Chronic migraine is associated with abnormalities in the periaqueductal grey that may be progressive. The condition is also associated with a greater degree of impairment in cortical processing of sensory stimuli than episodic migraine, perhaps due to more pervasive or persistent cortical hyperexcitability. These findings fit with the model of migraine as a spectrum disorder, in which the clinical and pathophysiological features may progress over time. This progression may result from changes in nociceptive thresholds and ensuing central sensitization caused by recurrent migraine in susceptible individuals. This may lead to changes in baseline neurological function between headaches, evident not only in electrophysiological and functional imaging studies, but also as psychological and somatic complaints that occur after years of episodic migraine. From current research and migraine models, a conceptualization of chronic migraine is emerging in which relatively permanent and pervasive central changes have occurred that warrant novel and tolerable treatments.     

Nitric oxide synthase inhibition: a new principle in the treatment of migraine attacks

Glyceryl trinitrate, an exogenous nitric oxide (NO) donor, and histamine, which causes NO formation in vascular endothelium, have been shown to trigger migraine attacks. However, it remains uncertain whether NO is involved in the subsequent phase of migraine attacks. To answer this question we studied the effect of L-NGmethylarginine hydrochloride (546C88), a NO-synthase inhibitor, on spontaneous migraine attacks. In a double-blind study design, 18 patients with migraine without aura randomly received 546C88 (6 mg/kg) or placebo (5% dextrose) iv given over 15 mm for a single migraine attack (546C88 placebo, 15:3). Furthermore, 11 placebo-treated patients from previous double-blind trials with almost identical design were added to the placebo group in the statistical evaluation. Two hours after the infusion, 10 of 15 L -N^Gmethylarginine hydrochloride-treated patients experienced headache relief compared to 2 of 14 placebo-treated patients ( p =0.0l). Symptoms such as phono- and photophobia were also significantly improved. A similar trend for nausea was not significant. We conclude that NO may be involved in the pain mechanisms throughout the course of spontaneous migraine attacks.