Abstract
Introduction: Migraine is a debilitating primary headache disorder with a poorly understood aetiology. An extensive body of literature supports the theory of migraine as a systemic vascular inflammatory disorder characterised by endothelial dysfunction. It is also well-known that chronic inflammation results in an excessive burden of oxidative stress and therefore cellular dysfunction. In this study the effects of excessive oxidative stress through the phases of female migraine-with-aura (FMA) were evaluated by examining the health of the systems of haemostasis.Methods: Blood was obtained from 11 FMA patients at baseline and during the headache phase of migraine, as well as from 8 healthy age-matched female controls. Samples were analysed using thromboelastography (TEG) to evaluate viscoelastic profiles, light microscopy for erythrocyte morphology, Scanning Electron Microscopy (SEM) for erythrocyte and fibrin clot structure, confocal microscopy for β-amyloid detection in fibrin clots.Results: Viscoelastic profiles from platelet poor plasma showed decreased clot reaction times in FMA at baseline (95% CI [5.56, 8.41]) vs. control (95% CI [7.22, 11.68]); as well as decreased time to maximum thrombus generation for the same comparison (95% CI [6.78, 10.20] vs. [8.90, 12.96]). Morphological analysis of erythrocytes indicated widespread macrocytosis, poikilocytosis and eryptosis in the migraineurs. Analysis of fibrin networks indicated that this hypercoagulability may be a result of aberrant fibrin polymerisation kinetics caused by the adoption of a β-amyloid conformation of fibrin(ogen).Conclusion: The results reaffirm the hypercoagulable state in migraine, and would suggest that this state is most likely a result of a systemic inflammatory state which induces oxidative damage to both erythrocytes and fibrin(ogen) in female episodic migraine-with-aura. Furthermore, if the amylodogenic changes to fibrin(ogen) were observed in a larger cohort, this would support theories of micro-embolisation in migraine-with-aura.
Highlights
Migraine is a debilitating primary headache disorder with a poorly understood aetiology
Morphological analysis of the whole blood of female migraineurs with aura is suggestive of a systemic inflammatory state both at baseline and during the headache phase characterised by macrocytosis, poikilocytosis and eryptosis
The observed variations in erythrocyte size, shape and distribution are most likely a result of oxidative stress. This observed inflammatory pathology is the likely cause of the known hypercoagulability in female migraine-with-aura (FMA), which was most prominently observed in this cohort during the headache phase
Summary
Migraine is a debilitating primary headache disorder with a poorly understood aetiology. An extensive body of literature supports the theory of migraine as a systemic vascular inflammatory disorder characterised by endothelial dysfunction. It is well-known that chronic inflammation results in an excessive burden of oxidative stress and cellular dysfunction. CSD results from a release of the neurotransmitter glutamate in a domino effect, which results in a wave of glutamatergic neuron excitation followed by a wave of inhibition This results in the vasodilation of the meningeal vasculature with release of inflammatory neuropeptides, such as calcitonin gene-related peptide, substance P, and neurokinin A [3, 6]. The end result is the sensitisation of the peripheral nociceptors of the trigeminovascular system and the headache phase of migraine, characterised by pulsating pain that is aggravated by any activity that increases intracranial pressure [7,8,9,10,11]
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