Cluster headache: state of the art of pharmacological treatments and therapeutic perspectives.

Cluster headache (CH) is the most common form of trigeminal autonomic cephalalgia. Current treatments have several limitations, and new drugs are required. This article first briefly reviews present acute and preventive treatments in CH, their mechanism of action and limitations, then describes the state of the art in recent clinical drug trials since 2015, and ends with a critique of trials in the CH field. Research is limited by lack of knowledge of pathophysiology and lack of animal models. In the past 5 years, no brand-new treatment has emerged, but promising drugs, such as CGRP(R) antibodies, are under study. According to the literature and guidelines, clinicians and researchers should be aware of many limitations in study protocols: concomitant medication, patient sample size, patients' protocol compliance, and study designs that tend to restrict patient recruitment.

Attention orienting dysfunction with preserved automatic auditory change detection in migraine.

OBJECTIVE: To investigate automatic event-related potentials (ERPs) to an auditory change in migraine patients. METHODS: Auditory ERPs were recorded in 22 female patients suffering from menstrually-related migraine and in 20 age-matched control subjects, in three sessions: in the middle of the menstrual cycle, before and during menses. In each session, 200 trains of tone-bursts each including two duration deviants were presented in a passive listening condition. RESULTS: In all sessions, duration deviance elicited a mismatch negativity (MMN) showing no difference between the two groups. However, migraine patients showed an increased N1 orienting component to all incoming stimuli and a prolonged N2b to deviance. They also presented a different modulation of P3a amplitude along the menstrual cycle, which tended to normalise during migraine attacks. None of the studied ERP components showed a default of habituation. CONCLUSIONS: This passive paradigm highlighted increased automatic attention orienting to auditory changes but normal auditory sensory processing in migraineurs. SIGNIFICANCE: Our observations suggest normal auditory processing up to attention triggering but enhanced activation of attention-related frontal networks in migraineurs.

Exacerbated attention orienting to auditory stimulation in migraine patients.

OBJECTIVE: To investigate long-term (LTH) and short-term (STH) habituation of auditory event-related potentials (ERPs) during a migraine cycle, using a classic habituation paradigm. METHODS: In 22 patients suffering from menstrually-related migraine and in 20 age-matched control subjects, auditory ERPs were recorded in 3 sessions: in the middle of the menstrual cycle, before menses, and during menses. In 12 patients, a migraine attack occurred during one of the peri-menses sessions. In each session, 200 trains of stimuli were presented, with an average of 10 stimuli per train. RESULTS: In response to the first stimuli of the trains, migraineurs exhibited in all sessions a larger orienting component of N1 than matched controls and a larger P3a in the interictal session, which normalized during attacks. They also showed a residual orienting component in response to the subsequent stimuli inside the trains. In contrast, the sensory component of N1 showed no difference between the two groups, with similar STH and LTH. CONCLUSIONS: Migraineurs show an exacerbated attention orienting to auditory stimulation, without any habituation deficit. SIGNIFICANCE: Previous migraine studies reported interictal habituation deficits of ERPs, but demonstrated in the auditory modality only in paradigms testing intensity dependence. Previous and current results can be interpreted as an increased attention orienting, possibly relying on an abnormal involvement of frontal cortex in auditory processing.