Abstract
We systematically reviewed the literature to evaluate the prevalence of phosphenes and the phosphene threshold (PT) values obtained during single-pulse transcranial magnetic stimulation (TMS) in adults with migraine. Controlled studies measuring PT by single-pulse TMS in adults with migraine with or without aura (MA, MwA) were systematically searched. Prevalence of phosphenes and PT values were assessed calculating mean difference (MD) and odds ratio (OR) with 95 % confidence intervals (CI). Ten trials (277 migraine patients and 193 controls) were included. Patients with MA had statistically significant lower PT compared with controls when a circular coil was used (MD −28.33; 95 % CI −36.09 to −20.58); a similar result was found in MwA patients (MD −17.12; 95 % CI −23.81 to −10.43); using a figure-of-eight coil the difference was not statistically significant. There was a significantly higher phosphene prevalence in MA patients compared with control subjects (OR 4.21; 95 % CI 1.18–15.01). No significant differences were found either in phosphene reporting between patients with MwA and controls, or in PT values obtained with a figure-of-eight coil in MA and MwA patients versus controls. Overall considered, these results support the hypothesis of a primary visual cortex hyper-excitability in MA, providing not enough evidence for MwA. A significant statistical heterogeneity reflects clinical and methodological differences across studies, and higher temporal variabilities among PT measurements over time, related to unstable excitability levels. Patients should therefore be evaluated in the true interictal period with an adequate headache-free interval. Furthermore, skull thickness and ovarian cycle should be assessed as possible confounding variables, and sham stimulation should be performed to reduce the rate of false positives. Phosphene prevalence alone cannot be considered a measure of cortical excitability, but should be integrated with PT evaluation.
Highlights
Several aspects in the pathophysiology of migraine are still unknown, an altered cortical excitability has been proposed as an important factor predisposing to the spontaneous cortical spreading depression which is thought to represent the pathophysiological basis of the migraine with aura [1]
We systematically reviewed the literature to evaluate the prevalence of phosphenes and the phosphene threshold (PT) values obtained during single-pulse transcranial magnetic stimulation (TMS) in adults with migraine
No statistically significant difference was found either in phosphene reporting between patients with migraine without aura and controls, or in PT values obtained by figure-of-eight coil Transcranial magnetic stimulation (TMS) in subjects with migraine with/without aura versus controls
Summary
Several aspects in the pathophysiology of migraine are still unknown, an altered cortical excitability has been proposed as an important factor predisposing to the spontaneous cortical spreading depression which is thought to represent the pathophysiological basis of the migraine with aura [1]. Neurophysiologic evidence for inter-ictal primary visual cortex hyper-excitability is controversial, with some studies demonstrating amplitude differences of visual evoked responses in patients with migraine compared with controls [4,5,6], and other studies not confirming such results [7, 8]. Important discrepancies among different studies do, exist, with some groups reporting increased, and others decreased inter-ictal PT. These studies produced conflicting results regarding prevalence of stimulation-induced phosphenes in migraineurs compared with healthy controls. These discrepancies make it very difficult to reach a definite conclusion by simple summation of previous results. We decided to undertake a systematic review and a meta-analysis of studies evaluating phosphene prevalence and inter-ictal PT values during single-pulse TMS in adults
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