The migraine–stroke connection: A genetic perspective

Background A complex relationship between migraine and vascular disease has long been recognized. The pathophysiological basis underlying this correlation is incompletely understood. Aim The aim of this review is to focus on the migraine–vascular disorders connection from a genetic perspective, illustrating potentially shared (molecular) mechanisms. Results We first summarize the clinical presentation and genetic basis of CADASIL and other monogenic vascular syndromes with migraine as a prominent disease manifestation. Based on data from transgenic mouse models for familial hemiplegic migraine, we then discuss cortical spreading depression as a potential mechanistic link between migraine and ischemic stroke. Finally, we review data from genome-wide association studies, with a focus on overlapping findings with cervical artery dissection, ischemic stroke in general and cardiovascular disease. Conclusion A wealth of data supports a genetic link between migraine and vascular disease. Based on growing high-throughput data-sets, new genotyping techniques and in-depth phenotyping, further insights are expected for the future

Hemicrania Continua Associated with Classic Scintillating Scotoma

Hemicrania continua (HC) is a rare primary headache disorder, characterized by persistent unilateral pain associated with cranial autonomic symptoms and prompt response to indomethacin. While migrainous features (including aura) have been recognized in cluster headache, there have been only single reports of HC with aura. Here, we report the case of a 53-year-old man with constant right-sided headache and superimposed exacerbations to severe pain lasting for several hours. Secondary etiologies were excluded, and a diagnosis of HC was established after prompt and complete response to treatment with indomethacin. During an episode of pain exacerbation, for the first time the patient experienced an episode of transient visual disturbances compatible with scintillating scotoma. We propose a potential link between HC and visual aura, which parallels similar observations in other trigeminal autonomic cephalalgias and more specifically confirms previous observational data on aura in HC, thus highlighting potentially shared pathophysiological mechanisms

Human Cerebrospinal fluid promotes long-term neuronal viability and network function in human neocortical organotypic brain slice cultures

Abstract Pathophysiological investigation of CNS-related diseases, such as epilepsy or neurodegenerative disorders, largely relies on histological studies on human post mortem tissue, tissue obtained by biopsy or resective surgery and on studies using disease models including animal models, heterologous expression systems or cell culture based approaches. However, in general it remains elusive to what extent results obtained in model systems can be directly translated to the human brain, calling for strategies allowing validation or even primary investigation in live human CNS tissue. In the work reported here, we prepared human organotypic slice cultures from access tissue of resective epilepsy surgery. Employing different culture conditions, we systematically compared artificial culturing media versus human cerbrospinal fluid (hCSF) obtained from patients with normal pressure hydrocephalus (NPH). Presented data demonstrates sustained cortical neuronal survival including not only maintenance of typical cellular electrophysiological properties and activity, such as robust action potential generation and synaptic connectivity, but also preservation of tonic and phasic network activity up to several weeks in vitro. As clearly delineated by immunocytochemistry, single cell patch clamp and extracellular recordings, we find that in contrast to artificial culturing media, hCSF significantly enhances neuron viability and maintenance of network activity