Migraine-like Attacks Research Articles

Prostaglandin E2 induces immediate migraine-like attack in migraine patients without aura

Prostaglandin E(2) (PGE(2)) has been suggested to play an important role in the pathogenesis of migraine. In the present experiment we investigated if an intravenous infusion of PGE(2) would induce migraine-like attacks in patients with migraine. Twelve patients with migraine without aura were randomly allocated to receive 0.4 µg/kg/min PGE(2) (Prostin(®)E2, dinoprostone) or placebo over 25 minutes in a two-way, crossover study. Headache intensity was recorded on a verbal rating scale, middle cerebral artery blood flow velocity (V(MCA)) was measured by transcranial Doppler (TCD) and diameter of the superficial temporal artery (STA) was obtained by c-series scan (Dermascan C). In total, nine migraine patients (75%) experienced migraine-like attacks after PGE(2) compared to none after placebo (p = 0.004). Seven out of 9 (58%) patients reported the migraine-like attacks during the immediate phase (0-90 min) (p = 0.016). Only two patients experienced the delayed migraine-like attacks several hours after the PGE(2) infusion stop (p = 0.500). The V(MCA) decreased during the PGE(2) infusion (p = 0.005) but there was no significant dilatation of the STA (p = 0.850). The migraine-like attacks during, and immediately after, the PGE(2) infusion contrast with those found in previous provocation studies, in which the other pharmacological compounds triggered the delayed migraine-like attacks several hours after the infusion. We suggest that PGE(2) may be one of the important final products involved in the generation of migraine attacks.

Clinical Reasoning: A 62-year-old migraineur with a new kind of headache attacks

A 62-year-old man presented with novel headache attacks with acute onset 4 weeks previously strictly confined to the right side. The attacks occurred almost daily, often after midnight, lasting 1 to 3 hours, occasionally longer. The pain was localized around and behind the right eye. The pain intensity was excruciating and the pain quality pulsatile. Ipsilateral lacrimation, conjunctival injection, and prominence of the temporal artery accompanied these attacks. During the attacks, the patient reported a sense of restlessness. Alcohol consumption and physical activity provoked attacks. No recent major trauma was identified. In his personal history, the patient had had tension-type headache and mainly left-sided migraine-like headache attacks for many years. The latter were of a hammering quality, irradiating from the occipital to the frontal region, and accompanied by nausea, photophobia, and phonophobia. In comparison, the new onset current attacks clearly differed from the previous attacks in terms of location, pain quality, intensity, frequency, duration, and attendant symptoms. Ancillary diagnoses included arterial hypertension, treated with amlodipine, and α-1 antitrypsin deficiency. Family history revealed a twin brother, who died of aneurysmal subarachnoid hemorrhage 6 years previously. Several relatives had migraine. On clinical examination, reduced width of the palpebral fissure on the right side compared to the left (ptosis), right miosis, and anhidrosis of the forehead (figure 1, A and B) were noticed. These findings persisted during the pain-free interval. Figure 1 Complete right Horner triad (A) Right eye “ptosis” (or, more correct, reduced width of the palpebral fissure on the right side compared to the left) and miosis. (B) Right forehead anhidrosis, visualized using ponceau dye. ### Questions for consideration: 1. How would you classify these new onset headache attacks? 2. Are there any atypical features or red flags pointing to a secondary headache? GO TO SECTION 2 At first glance, the patient's complaints and clinical findings match the criteria of the International …

Unequal gains of function are a headache for migraine mechanisms

Unequal gains of function are a headache for migraine mechanisms

Differential vasoactive effects of sildenafil and tadalafil on cerebral arteries –relevant to migraine?

BackgroundPhosphodiesterase 5 (PDE5) is associated with migrainepathophysiology, stroke recovery and vasospasm treat-ment [1,2]. We have shown previously that vasodilata-tion was not a prerequisite for migraine induction;sildenafil elicited migraine-like attacks in migrainepatients without measurable changes in intra- or extra-cerebral artery diameter. Further, sildenafil was found tonot affect neurovascular response or excitability [3].However, dural artery responses were not accounted forin the human studies and minor vascular changes offunctional importance may not have been detected.The potential vascular interplay of PDE5 inhibitors sil-denafil, tadalafil and UK-114,542 were studied by intra-versus extra-luminal administration in rat middle cere-bral arteries (MCA) in vitro and on middle meningealarteries (MMA) in vivo.AimTo examine a possible vascular site of action, if any, ofeach of sildenafil and tadalafil by investigating 1) theeffects of PDE5 inhibitors in vitro dilatation of the mid-dle cerebral artery (MCA) with controlled luminal orextra-luminal application of the drugs and 2) the in vivoeffects of intravenous PDE5 inhibitors on the middlemeningeal artery (MMA) dilatation in a closed cranialwindow model in rats.MethodsRat MCA diameter was investigated using pressurisedarteriography, applying UK-114,542, sildenafil, andtadalafil intra- or extra-luminally. Effects on MMA werestudied in the in vivo closed cranial window model.ResultsAt high concentrations, abluminal sildenafil and UK-114,542, but not tadalafil, induced dilatation. Luminalapplication elicited a contraction of 4 % (sildenafil, p =0.03) and 10 % (tadalafil, p = 0.02).In vivo, sildenafil,but not tadalafil, dose-dependently dilated MMA conco-mitant to blood pressure reduction (1-3 mg/kg);1 mg/kgsildenafil inducing 60 ± 14 % (p = 0.04) and vehicle(DMSO) 13 ± 6 % dilatation.ConclusionPDE5 inhibitors applied luminally had contractile effecton MCA. Abluminal sildenafil induced MCA dilatationabove therapeutic levels. In vivo, sildenafil dilated MMA.Tadalafil had no dilatory effects. PDE5 inhibitors showdifferential vascular activity in arteries, although clini-cally the potential for headache induction appears simi-lar. Such findings support clinical studies showing novasodilatory effects of sildenafil on cerebral arteries inhealthy subjects.

Calcitonin Gene‐Related Peptide Does Not Cause Migraine Attacks in Patients With Familial Hemiplegic Migraine

Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP triggers migraine-like attacks in patients with migraine with aura and without aura. In contrast, patients with familial hemiplegic migraine (FHM) with known mutations did not report more migraine-like attacks compared to controls. Whether CGRP triggers migraine-like attacks in FHM patients without known mutations is unknown. In the present study we therefore examined the migraine-inducing effect of CGRP in FHM patients without known mutations and healthy controls. Eleven patients suffering from FHM without known mutations and 11 controls received an intravenous infusion of 1.5 µg/minute CGRP over 20 minutes. The study design was a balanced and controlled provocation study. Headache and other migraine symptoms were scored for 1 hour and self-recorded hourly thereafter until 13-hour postinfusion. We found no difference in the incidence of migraine-like attacks between the 2 groups, with 9% (1 of 11) of patients and 0% (0 of 10) of controls reporting migraine-like headache (P = 1.00). CGRP infusion did not induce aura symptoms in any of the participants. There was no difference in the incidence of CGRP-induced delayed headaches between the groups (P = .18). In contrast to patients suffering from migraine with aura and without aura, CGRP infusion did not induce more migraine-like attacks in FHM patients without known mutations compared to controls. It seems that the majority of FHM patients with and without known mutation display no sensitivity to CGRP signaling compared to common types of migraine.

Unilateral Agenesis of the Internal Carotid Artery in CHARGE Syndrome

CHARGE syndrome is a multisystemic disorder comprising colobomas, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies and deafness. The CHD7 gene on chromosome 8q12.1 was recently shown to be a major gene involved in the etiology of this syndrome. We describe a girl with CHARGE syndrome who had a novel mutation of CHD7 associated with agenesis of the left internal carotid artery. She had presented with recurrent episodes of photophobia and vomiting since the age of 6 years. Since her symptoms were well controlled by cyproheptadine, migraine-like attacks were considered. CHD7 molecular confirmation in this patient provides further evidence to support the occurrence of a vascular anomaly suggested from animal models of CHARGE syndrome with molecular delineation. We report this case to emphasize the importance of neurologic signs of photophobia and to highlight the broad clinical variability in this pleiotropic disorder.

What have we learnt from triggering migraine?

This review presents what we have learnt from triggering migraine. Experimental studies have shown that glyceryl trinitrate (GTN), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase activating polypeptide-38 (PACAP38) and prostaglandin I2 (PGI2) induce migraine-like attacks in migraine suffers indistinguishable from their spontaneous attacks. These studies point to two key pathways to play an important role in migraine pathophysiology: cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP). At present, no valid experimental model exists to reproduce aura episodes in migraine with aura patients. Familiar hemiplegic migraine patients seem to be less sensitive to GTN and CGRP provocation compared with common types of migraine. Advances in recent imaging studies suggest neuronal mechanisms to be behind migraine attacks. The experimental headache models have resulted in development and an ongoing search of new migraine targets. Human models of migraine offer unique possibilities to study mechanisms responsible for different migraine subtypes and to explore the mechanisms of action of existing and future antimigraine drugs. Adding advanced imaging techniques to the models may lead to a better understanding of the complex events that constitutes a migraine attack and thereby more targeted ways of intervention.

Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura

Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP infusion triggers delayed migraine-like attacks in patients with migraine without aura (MO). In contrast to patients with MO, in prior studies patients with familial hemiplegic migraine (FHM) did not report more migraine-like attacks compared to controls. Whether CGRP triggers migraine in patients with typical (non-hemiplegic) migraine with aura is (MA) unknown. In the present study we examined the migraine inducing effect of CGRP infusion in patients suffering from MA and healthy controls. Fourteen patients suffering exclusively from migraine with typical aura (MA) and 11 healthy volunteers received a continuous intravenous infusion of 1.5 µg/min CGRP over 20 minutes. Headache and other migraine symptoms were scored every 10 minutes for one hour and self recorded hourly thereafter and until 13 hours post-infusion. CGRP infusion induced significantly more delayed headaches in MA patients (12 out of 14) than in controls (2 out of 11) (p = 0.001). Furthermore, significantly more MA patients (57%; 8 out of 14) fulfilled criteria for an experimentally induced migraine attack after CGRP than controls (0%; 0 out of 11) (P = 0.003). Four patients (28%) reported aura symptoms after CGRP infusion. CGRP triggered migraine-like attacks without aura in patients suffering exclusively from MA. It also triggered a typical aura in 28% of the patients. These data indicate similar neurobiological pathways responsible for triggering migraine headache in MA and MO patients, and suggest differences between MA/MO and FHM.

The PACAP Receptor: A Novel Target for Migraine Treatment

The origin of migraine pain has not yet been clarified, but accumulating data point to neuropeptides present in the perivascular space of cranial vessels as important mediators of nociceptive input during migraine attacks. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in sensory trigeminal neurons and may modulate nociception at different levels of the nervous system. Human experimental studies have shown that PACAP-38 infusion induces marked dilatation of extracerebral vessels and delayed migraine-like attacks in migraine patients. PACAP selectively activates the PAC(1) receptor, which suggests a possible signaling pathway implicated in migraine pain. This review summarizes the current evidence supporting the involvement of PACAP in migraine pathophysiology and the PAC(1) receptor as a possible novel target for migraine treatment.

Calcitonin gene related peptide (CGRP)–provoked migraine-like attacks

Calcitonin gene related peptide (CGRP)–provoked migraine-like attacks

Prolonged left homonymous hemianopsia associated with migraine-like attacks in a child with Sturge–Weber syndrome

We report a patient with Sturge–Weber Syndrome (SWS) who developed migraine-like headaches followed by cerebral infarction. SWS without facial nevus was diagnosed based on calcification detected by CT and pial angioma detected by enhanced MRI. His migraine-like headaches were preceded by left homonymous hemianopsia, which persisted for more than 60 min. Although homonymous hemianopsia disappeared with cessation of the headache until 13 years of age, from age 14 years onward, this homonymous hemianopsia persisted after the headaches ended. Moreover, reduced cerebral blood flow was seen in the right occipital area on SPECT. At first, his left homonymous hemianopsia persisted for several months after the headache disappeared, but it had recovered completely. However, the durations of episodes of left homonymous hemianopsia, which persisted after headache disappearance, gradually became longer. At last one year after his first admission, the visual defect had become permanent. SWS is well known to be associated with migraine attacks and hemianopsia. However, the course of our present patient, i.e. recurrent homonymous hemianopsia, associated with migraine-like headaches becoming permanent, is rare. The pathophysiological mechanism underlying this clinical course is uncertain. The efficacy of valproate and propranolol as preventive therapy has been inadequate, to date.

Carbachol induces headache, but not migraine-like attacks, in patients with migraine without aura

Carbachol induces headache in healthy subjects, but the migraine eliciting effect of carbachol has not previously been studied. We hypothesized that the cholinomimetic agonist carbachol would induce headache and migraine-like attacks in migraineurs. Carbachol (3 µg/kg) or placebo was randomly infused into 18 patients with migraine without aura in a double-blind crossover study. Headache was scored on a verbal rating scale from 0 to 10. Velocity in the middle cerebral artery (V(MCA)) and diameter of the superficial temporal artery (STA) were recorded. Fifteen patients experienced headache after carbachol compared with eight after placebo (P = 0.039). There was no difference in incidence of migraine-like attacks after carbachol (n = 8) compared with placebo (n = 6) (P = 0.687). Carbachol caused a decrease in V(MCA) (P = 0.044), but no change in STA (P = 0.089) compared with placebo. The study demonstrated that carbachol provocation is not a good model for experimental migraine.

Prostaglandin I2 (epoprostenol) triggers migraine-like attacks in migraineurs

Prostacyclin [prostaglandin I(2) (PGI(2))] activates and sensitizes meningeal sensory afferents. In healthy subjects PGI(2) triggers headache in healthy subjects. However, the migraine-eliciting effect of PGI(2) has not been systematically studied in patients with migraine. We hypothesized that intravenous infusion of the stable prostacyclin analogue epoprostenol would trigger migraine-like attacks in migraineurs. We infused 10 ng kg(-1) min(-1) PGI(2) or placebo over 25 min in 12 migraineurs without aura in a controlled, double-blind, cross-over study and recorded headache intensity and associated symptoms, velocity in the middle cerebral artery (V(MCA)) and diameter in the superficial temporal artery. In the period 0-14 h, 12 subjects reported headache on PGI(2) day compared with three subjects on placebo day (P = 0.004), and six subjects fulfilled the criteria for an experimentally induced migraine-like attack compared with two subjects on placebo (P = 0.219). During infusion and post-infusion phases the AUC under the headache curve on PGI(2) was significantly larger than on placebo (P < 0.05). There was a significant V(MCA) decrease (P = 0.015) and superficial temporal artery diameter increase (P < 0.001) on PGI(2) compared with placebo. In conclusion, PGI(2) may trigger a migraine-like attack in migraine sufferers. We suggest sensitization of perivascular nociceptors and arterial dilation as the mode of action of PGI(2)-induced headache and migraine-like attacks.

CGRP receptors in the control of pain and inflammation

Calcitonin gene related peptide (CGRP) has been proposed to contribute to pain transmission and inflammation and for these reasons to the mechanism of migraine. CGRP is, in fact, expressed in and released from a subset of polymodal primary sensory neurons of the trigeminal ganglion. Release of CGRP in the dorsal spinal cord has been associated to nociceptive transmission, and release from perivascular nerve endings causes neurogenic vasodilatation. CGRP levels increase in the cranial circulation during migraine attacks, and GRP injection in migraineurs results in migraine-like attacks. Most importantly, two chemically unrelated CGRP-receptor antagonists, the parenteral agent, olcegepant, and the orally available telcagepant demonstrated efficacy in the treatment of migraine attacks, thus supporting CGRP as an important mediator in migraine.

PACAP38 induces migraine-like attacks in patients with migraine without aura

Experimental studies have shown that infusion of vasoactive neurotransmitters may trigger headache or migraine-like attacks in man. Pituitary adenylate cyclase activating peptide-38 (PACAP38) is a strong vasodilator found in trigeminal sensory and parasympathetic perivascular nerve fibers. We therefore hypothesized that infusion of PACAP38 would cause headache in healthy subjects and migraine-like attacks in migraine patients. Twelve healthy subjects and 12 migraine patients were examined in two separate studies. All subjects were allocated to receive 10 pmol/kg/min PACAP38 and placebo in a randomized, double-blind crossover study design. Headache was scored on a verbal rating scale (VRS) during hospital (0-2 h) and post-hospital (2-12 h) phases. Mean blood flow velocity in the middle cerebral artery (V(MCA)) by transcranial Doppler (TCD) and diameter of the superficial temporal artery (STA) by high resolution ultrasonography were recorded during hospital phase in migraineurs. PACAP38 infusion caused headache in all healthy subjects and 11 out of 12 migraine patients. Seven migraine patients experienced migraine-like attacks after PACAP38 and none after placebo (P = 0.016). Most of attacks (6 out of 7) occurred during the post-hospital phase [mean time 6 h (range 2-11)]. Two healthy subjects reported migraine-like attacks after PACAP38 during the hospital phase and none during the post-hospital phase. In the hospital phase, the area under the curve (AUC) for headache score was larger during PACAP38 infusion compared to placebo in healthy subjects (P = 0.005) and tended to be larger in migraineurs (P = 0.066). In the post-hospital phase, the AUC for headache was larger after PACAP38 infusion compared to placebo in both healthy subjects (P = 0.005) and migraine patients (P = 0.013). In migraine patients, PACAP38 caused a peak decrease of 16.1% in V(MCA) and a 37.5% increase in STA diameter at 20 min after start of infusion. In conclusion, PACAP38 infusion caused headache and vasodilatation in both healthy subjects and migraine patients. In migraine sufferers, PACAP38 caused delayed migraine-like attacks. The findings stimulate further investigation of the neuronal and vascular mechanisms of PACAP38.

Painful Stimulation of the Temple During Optokinetic Stimulation Triggers Migraine-Like Attacks in Migraine Sufferers

To determine whether motion sickness induced by optokinetic stimulation would trigger migraine-like attacks, 27 migraine sufferers and 23 controls attended the laboratory up to three times at intervals of at least 3 weeks. On one occasion subjects experienced up to 15 min of optokinetic stimulation, followed by three 30-s applications of ice to the temple at 4-min intervals. On another occasion, the ice applications preceded and accompanied optokinetic stimulation. On a third occasion, one hand was immersed in ice water for 30 s, three times at 4-min intervals before and during optokinetic stimulation. Subjects recorded headache activity in a diary over the course of the study. None of the controls experienced a migraine-like attack at any stage of the experiment. In migraine sufferers, the incidence of migraine-like attacks was greater than the expected daily incidence of 8% after sessions that involved painful stimulation of the temple during or after optokinetic stimulation (44% and 28% of the group, respectively) (P<0.001). In contrast, migraine-like attacks developed in only 13% of migraine sufferers after the session that involved immersing the hand in ice water during optokinetic stimulation (not significant). The development of nausea and headache during optokinetic stimulation increased the likelihood of migraine-like attacks afterwards. These findings indicate that motion sickness and head pain increase susceptibility to migrainous attacks in migraine sufferers, and suggest that the symptoms of migraine build upon each other in a vicious circle. Thus, targeting multiple symptoms should be more effective than targeting individual symptoms, both for preventing and treating attacks of migraine.

Migraine-like attacks in child with Sturge-Weber syndrome without facial nevus

The Sturge-Weber syndrome was recently subdivided into type I (facial and leptomeningeal angioma, possible glaucoma), type II (facial angioma, without evident endocranial involvement), and type III (exclusive leptomeningeal angioma). Thus far in the literature only 24 cases of Sturge-Weber syndrome type III have been reported. This study presents a case of a 2-year 9-month-old child with normal psychomotor development and skin free (no angiomas), who presented repeated episodes of severe headache, vertiginous symptoms, vomiting, and drowsiness, separated by complete recovery. The cranial computed tomography and magnetic resonance imaging with gadolinium revealed left occipital leptomeningeal angiomatosis with calcifications, suggesting a diagnosis of Sturge-Weber syndrome type III. Considering the normal psychomotor development, the improved electroencephalographic reports between the episodes, and the absence of hypoperfusion areas on single-photon emission computed tomography at 30 months of follow-up, the symptomatology appears an expression of migraine-like symptoms resulting from vasomotor disturbances within and around the angioma, more than an expression of partial seizures arising through an epileptic focus in the ischemic region around the vascular malformation.

Frequent Migraine and Migraine Status Without Tension-Type Headaches: an Unusual Presentation of Rebound Headaches

Rebound headaches usually present as daily or almost daily, prolonged, generalized tension-type headaches with superimposed migraine-like attacks. The latter are more frequent, more intense, and longer than any episodic migraine that the patient might have experienced prior to the development of the chronic daily headaches. Rebound presenting as migraine without tension-type pain has been mentioned in a few previous articles on chronic daily headache, but there have been no previous articles stressing that frequent migraine might relate to the analgesics that are being used. These case histories are presented to illustrate that frequent migraine and migraine status without tension-type headaches may be manifestations of rebound and improve when the offending analgesic agents are stopped. If the clinician fails to recognize this unusual presentation of rebound headache, the patient might be placed on unnecessary and often ineffective medications for prophylaxis instead of stopping the offending pain relief medications.

Post-traumatic Headache.

Headache is the most common symptom after closed head injury, persisting for more than 2 months in 60% of patients. Rarely does headache occur in isolation. Cervical pain is a frequent accompaniment. Post-traumatic headache is often one of several symptoms of the postconcussive syndrome, and therefore may be accompanied by additional cognitive, behavioral, and somatic problems. Acute post-traumatic headaches may begin at the time of injury and continue for up to 2 months post-injury. Although onset proximate to the time of injury is most common, any new headache type occurring within this period of time is referred to as an acute post-traumatic headache. If such headaches persist beyond the first two months post-injury, they are subsequently referred to as chronic post-traumatic headaches. Over time, post-traumatic headaches may take on a pattern of daily occurrence. If aggressive treatment is initiated early, posttraumatic headache is less likely to become a permanent problem. Once "windup" of post-traumatic headaches occurs, the cycle of ongoing headaches is more difficult to interrupt. The mechanism of post-traumatic headache is poorly understood. Trauma-induced headaches are usually heterogeneous in nature, often including both tension-type pain and intermittent migraine-like attacks. Rebound-headaches may develop from overuse of analgesic medications, and the occurrence of such may complicate significantly the diagnosis of post-traumatic headache. Adequate treatment typically requires both "peripheral" and "central" measures. Understanding the general principles of treatment, especially appropriate use of preventive and abortive medications, will most usefully guide treatment. There is scant literature with which to direct treatment selection for post-traumatic headache. Consequently, treatments for post-traumatic headache are based on those prescribed for phenomenologically similar but etiologically distinct headache disorders. Delayed recovery from post-traumatic headache may be a result of inadequately aggressive or ineffective treatment, overuse of analgesic medications resulting in analgesia rebound phenomena, or comorbid psychiatric disorders (eg, post-traumatic stress disorder, insomnia, substance abuse, depression, or anxiety).

Genetic Heterogeneity of Familial Hemiplegic Migraine

Familial hemiplegic migraine (FHM) is a distinctive form of migraine with an autosomal dominant mode of inheritance. The migraine-like attacks are associated with transient hemiparesis. A locus for FHM has recently been assigned to chromosome 19 by linkage mapping. In the present study, five unrelated pedigrees with multiple members suffering from hemiplegic migraine were investigated. In two of the pedigrees additional symptoms, cerebellar ataxia and benign neonatal convulsions, respectively, were observed in affected members. Three pedigrees showed linkage to loci D19S391, D19S221, and D19S226 at chromosome 19p13. Haplotyping suggested a location of a FHM gene between D19S391 and D19S221. In the two remaining families, evidence against linkage was found. These results confirm the localization of a gene for familial hemiplegic migraine to the short arm of chromosome 19, but locus heterogeneity not corresponding to the observed clinical heterogeneity is likely to exist.