Migraine/Headache

Hemiplegic migraine (HM) is a rare form of migraine characterized by the presence of a motor and other types of aura. HM can be sporadic or familial. Familial hemiplegic migraine (FHM) is an autosomal dominant disorder, classified into 3 subtypes, based on the gene involved (CACNA1A in FHM1, ATP1A2 in FHM2 and SCN1A in FHM3). The clinical presentation is highly heterogeneous and some attacks may be severe. We report the clinical characteristics and genetic analysis of 12 patients belonging to a family with CACNA1A-p.Thr501Met gene mutation.

Biofeedback is effective in treating migraines. It is believed to have a beneficial effect on autonomous nervous system activity and render individuals resilient to stressors that may trigger a migraine. However, widespread use of biofeedback is hampered by the need for a trained therapist and specialized equipment. Emerging digital health technology, including smartphones and wearables (mHealth), enables new ways of administering biofeedback. Currently, mHealth interventions for migraine appear feasible, but development processes and usability testing remain insufficient.

The existence of a trigeminocervical complex (TCC) has been suggested based on animal data, but only indirect evidence exists in humans. We investigated the functional relationship between the trigeminal and the occipital region by stimulating one region and measuring electrical pain thresholds (EPTs) of the corresponding opposite region. This study consists of two single-blinded, randomized protocols. 40 healthy participants were recruited in the propaedeutic Protocol I. EPTs were measured on the V1 and the greater occipital nerve (GON) dermatome bilaterally as well as on the left forearm longitudinally before and after application of topical capsaicin. Protocol II was then online pre-registered and, additionally, the ipsilateral trigeminal dermatomes V2 and V3 were tested. GON stimulation increased the EPT ipsilateral at V1 after 20 minutes (p=0.006) compared to baseline, whereas trigeminal stimulation increased the EPT at the ipsilateral (p=0.023) as well as the contralateral GON (p=0.001) following capsaicin application. Protocol II confirmed these results and additionally showed that GON stimulation with capsaicin increased EPTs ipsilateral at all three trigeminal dermatomes and that trigeminal stimulation on V1 led to an ipsilateral increase of EPTs at GON, V2 and V3. Our data suggest a strong functional interplay between the trigeminal and occipital system in humans. The fact that stimulation of one of these dermatomes increases the electrical pain threshold of the respective other nerve could be explained by segmental inhibition on brainstem level.

The pharmacological block of the greater occipital nerve has been proven effective in numerous headache and facial pain syndromes. This clinical effect supports the hypothesis of a strong functional interaction between the occipital and trigeminal nerves which has been proposed in neurophysiological in vivo experiments in rodents. Although it is likely that the interaction has to occur in the central nervous system, the exact site and the mechanisms of the interaction remain largely unknown.

Chronic migraine (CM) is a disabling neurologic disorder that affects approximately 2% of the general population. Neuroimaging studies show functional involvement of trigeminal structures, such as the trigeminal spinal nucleus (Sp5) in migraine. However, structural changes in the Sp5 and the afferent trigeminal spinal tract (sp5) have never been found. The aim of this study was to test the hypothesis that white matter changes in the sp5 are a key feature of brain alterations in CM patients. We used diffusion Magnetic Resonance Imaging (dMRI) and polarized light imaging (PLI) of post mortem brainstem specimens from healthy controls (n = 5) and CM patients (n = 5) to study white matter alterations in the sp5. Within the sp5, dMRI metrics included fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) values. PLI was used to assess myelin density by measure of the retardance values in the sp5. The present study provides histological evidence that structural alterations occur in the sp5 in CM patients as compared to healthy controls. Myelin-density, as assessed by retardance values, showed to be higher and a corresponding increase in FA-values was observed. In addition, accompanying decreases in MD-, AD- and RD-values were observed. This study shows that the sp5 undergoes neuroplastic changes, a feature which substantiates evidence for the hyperactivity of the Sp5 in migraine patients. More insights are needed to observe whether these changes only occur in CM patients.

A large proportion of headache sufferers do not routinely seek medical care. App-based technologies permit the collection of real-world data over time and between countries that can help assess true burden of headache. This study used a mobile phone application to collect information on real-world burden of self-diagnosed headache and to describe its impact on daily life in headache sufferers who do not routinely seek medical advice.