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Background Perimenstrual migraine attacks in women with menstrual migraine is difficult to treat. This post-hoc analysis evaluated the efficacy of lasmiditan, a high affinity and selective 5-HT1F receptor agonist, for perimenstrual attacks. Methods Patients from two randomized, double-blind, placebo-controlled clinical trials (MONONOFU and CENTURION) were instructed to treat an attack with a single dose of study medication within four hours of pain onset. After dosing, the proportion of patients who achieved freedom from migraine-related head pain, most bothersome symptom, and disability was reported at baseline up to 48 hours after dose and pooled data were evaluated. Results A total of 303 patients (MONONOFU N = 78; CENTURION N = 225) treated perimenstrual migraine attacks with lasmiditan 50 mg (N = 24), 100 mg (N = 90), 200 mg (N = 110), and placebo (N = 79). More patients achieved migraine-related head pain freedom with lasmiditan 200 mg versus placebo at all time points assessed. At 2 hours, 33.6% of patients in the 200-mg group (p Conclusions Lasmiditan treatment of perimenstrual migraine attacks was associated with freedom from migraine-related head pain at two hours, early onset of efficacy, and sustained efficacy. Clinical Trial registration: NCT03962738 and NCT03670810

The digiti quinti sign (DQS), described originally as a clinical indication of subtle motor deficit, consists of a relatively greater abduction of the fifth finger on the affected side when both arms are extended forwards. This sign was previously observed interictally in three consecutive hemiplegic migraine (HM) patients. Patients and methods: To verify whether the DQS specifically discriminates HM from non-hemiplegic migraine (nHM), the angle between the fourth and fifth fingers (ANG) was measured interictally in 10 HM patients, 44 migraine with aura and migraine without aura patients, and 45 healthy controls. Results: The ANG was significantly wider at the symptomatic side in HM as compared with nHM and controls. The differences between the symptomatic and non-symptomatic (for HM) or between the right and left sides (absolute values for nHM and controls) were, respectively, 10.10° ± 9.58°, 4.15° ± 3.95° and 5.37° ± 4.74° ( p = .007). The optimal cutoff point for ANG was 15° at the symptomatic side (sensitivity and specificity of 80.0% and 72.2%, respectively), 10.5° at the non-symptomatic side (sensitivity and specificity of 60.0% and 52.3%), and 3° for the difference between sides (sensitivity and specificity of 90.0% and 79.5%). Conclusion: Data show that the DQS discriminates HM from nHM and controls.

The digiti quinti sign (DQS) was described as an indication of mild hemiparesis. It consists of a wider space between the fourth and fifth fingers at the affected side when the patient extends both arms horizontally to the front with the palms down. The three successively examined sporadic hemiplegic migraine patients presented herein disclosed no other neurological abnormality except the interictally present DQS on the same side of the motor deficits. This sign is perhaps clinically useful for the diagnosis of hemiplegic migraine.

Whiplash is a controversial concept. The real nature and prevalence of whiplash-related headaches are not known. To address this issue, the history of severe trauma was collected from occipital/nuchal headache-cervicogenic headache, migraine and tension-type headache patients attending a neurology office. The two last groups of patients had significantly less history of trauma in their medical records, with longer time span between the injury and the headache onset. Whiplash may induce preferably cervicogenic and tension-type headaches.

Since visual aura is usually described as expanding zigzag lines, neurones involved with the perception of line orientation may initiate this phenomenon. A visual incongruent line stimulation protocol was developed to obtain functional magnetic resonance images (fMRI) interictally in 5 female migraine patients with typical fortification spectra and in 5 normal matched controls. Activation in the visual cortex was present contralateral to the side of stimulation in 4 of 5 patients, notably in the extrastriate visual cortex. In 4 of 5 controls activation was observed in the medial and anterior orbitofrontal cortex. In one of them additional activation at the right nucleus accumbens/ventral striatum and right ventral pallidum was present. In the remaining control subject activation was present in the left primary visual cortex. The enhanced interictal reactivity of the visual cortex in migraineurs supports the hypothesis of abnormal cortical excitability as an important pathophysiological mechanism in migraine aura, though the role of specific regions of the visual cortex remains to be explored.

Proposals for the diagnostic criteria for hemicrania continua (HC) and also for the nosological status of HC are set forth. The clinical constellation of symptoms and signs making up HC consists of: unilaterality without side shift; absolute indomethacin effect; and long-lasting repetitive attacks of varying duration, eventually with a chronic pattern, the pain being mild to severe. For the typical clinical picture of HC, including a positive ‘indotest’, we propose the term hemicrania continua vera. More or less analogous, but ‘indotest-negative’ clinical pictures have provisionally been termed hemicrania generis incerti (of undetermined nature). At the present level of knowledge, the diagnosis of hemicrania generis incerti should be made mostly by exclusion. HC may possibly best be classified along with chronic paroxysmal hemicrania (CPH) as this is the only other headache absolutely responsive to indomethacin. The bond between these two headaches on the one hand and cluster headache on the other should, at most, be a loose one. Interrelationships of these four classifiable headaches are briefly discussed.

Cervicogenic headache (CEH) is a neck-generated headache syndrome. Attacks may be similar to migraine (M) or tension-type headache (TTH). In order to test the accuracy of the IHS diagnostic criteria for M and episodic TTH and of the criteria for CEH of Sjaastad et al., 33 CEH, 65 M, and 29 TTH were evaluated according to the CEH criteria, and CEH patients were tested for M and TTH according to the IHS criteria. Only 30% of the CEH patients met the criteria for M, 3% met the criteria for TTH, and 66% were neither M nor TTH. The mean number of criteria met, sex, age, and age of onset were also analysed, and the results indicate an inequality among these three headache types. The most important differentiating aspects were the site and radiation of the pain, the temporal pattern, and the induction of attacks from neck posture, movements, and/or digital pressure. CEH clearly differs from M and TTH. Existing criteria adequately distinguish the three headaches.

Sumatriptan, a 5-hydroxytryptamine (5HT)1-like receptor agonist, is a new antimigraine drug which is also effective in cluster headache (CH), a disorder with marked ocular circulatory abnormalities. Sumatriptan could putatively exert a therapeutic effect in this vascular bed. The present study is an attempt to assess sumatriptan's vasoactivity in isolated porcine ophthalmic artery (POA) and to verify whether it has similar activity to 5HT, and whether it interferes with the vasodilation induced by calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP). In contrast to 5HT, sumatriptan induced only slight contraction in POA at high concentrations. However, in some artery segments pre-contracted with PGF22a, sumatriptan induced a slight and short-lasting but marked relaxation. In addition, relaxations induced by VIP were inhibited significantly by sumatriptan, whereas CGRP effects were not influenced by the drug. Such reactions suggest that sumatriptan's effect in CH is probably unrelated to direct ocular arterial vasoconstriction.

Although it is known that pain in the forehead may be induced by neck abnormalities, the actual neck-head connections responsible for development of pain in trigeminal areas are poorly understood. Vasoactive neuropeptides released from sensory fibres, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been considered as important elements in headache pathophysiology. The levels of CGRP-like immunoreactivity (LI) were measured bilaterally in the jugular blood (52 rats) and intraocular aspirates (66 rats) following electrical stimulation of the left greater occipital nerve, and in the jugular blood of 13 control animals. One-third of the stimulated rats had varying combinations of conjunctival injection, tearing, diminished eye aperture and miosis or mydriasis on the stimulated side. The other two-thirds exhibited no ocular signs. Significantly lower levels of CGRP-LI were present in the jugular blood on the stimulated side in comparison with control rats. There was comparatively lower CGRP-LI on the non-stimulated side as well, but to a lesser extent. Significant differences between the stimulated and the non-stimulated side were present, particularly in the tearing/diminished eye cleft group. It is proposed that stimulation of the rat GON inhibits the trigeminal system (reduction of CGRP-LI) and possibly activates parasympathetic fibres (ocular changes).

Our group has previously reported significant changes in the incorporation of precursors into glycerophos-pholipids, particularly phosphatidylserine, in polymorphonuclear cells obtained from the peripheral blood of cluster headache patients, when compared with controls. The potential of these results led to further work using both the previous methodology and a modified isolation technique to obtain polymorphonuclear cells in as pure a state as possible. Neither the new results obtained using the original technique, nor the results with high purity polymorphonuclear cells from controls and cluster headache patients, confirm the marked changes in precursor uptake into glycerophospholipids originally reported.