Abstract
Listening to patients tell of the visual experiences that so prominently characterize their migraine aura rarely fails to evoke the fascination of most clinicians and even patients themselves. Gratifyingly, this fascination has extended to a small but select body of contemporary visual scientists that has contributed thoughtful and rigorous analysis of visual cortex function in migraine sufferers (1–5), systematically addressing the notion that ‘the occipital cortex is to migraine what the temporal lobe is to epilepsy’. Attention to altered function of primary visual cortex between and during attacks of migraine aura began with Airey's observations on fortification spectra in the late nineteenth century (6). Detailed descriptions of migraine aura by Richards (7), and his suggestion that the event began with activation of linear detector neurones in primary visual cortex, was followed by systematic investigations of stripe-induced visual discomfort in migraine sufferers by Marcus and Sosa (2). Visual stress, particularly repetitive linear and specifically angulated visual stimuli, may evoke an ‘exhaustion’ phenomenon in responding susceptible specialized line detector neurones of the visual cortex to account for the illusion of fortification spectra as part of the aura.
Precise mechanisms underlying the unique, complex, and variable visual disturbances of migraine aura remain to be determined. Wilkins, whose paper in the current Cephalagia prompted this Editorial, in earlier neurophysiological studies had demonstrated that stressful linear stimuli could excite visual cortex epileptiform discharges (5). In support, psychophysical studies by Wray, Mijovic-Prelec and Kosslyn revealed abnormally sensitive ‘low-level’ visual processing in subjects with migraine with aura that they attributed to hyperexcitability caused by dysfunction of an intracortical GABA-ergic inhibitory system that plays a major role in linear detection (1). This group has confirmed hyperexcitability in both V1 and V5 most recently using transcranial magnetic stimulation (TMS) (8), thus contributing to an increasing body of evidence to support occipital cortex hyperexcitability using this technique (9, 10), although not all studies agree (11). Nevertheless, using different techniques, magneto-encephalography (MEG) and fMRI-BOLD, Bowyer et al. (12) and Cao et al. (13), respectively, confirmed that linear visual stress activates widespread regions of hyperexcitable visual and association cortex in migraine patients.
Collectively, the studies referred to above either anticipated or highlighted the concept of CNS hyperexcitability as the basis of migraine susceptibility (14), made more logical as contemporary methods of brain imaging indicate the basis of aura to be a depolarizing neuroelectric and metabolic event likened to the spreading depression (SD) of Leao (12, 13, 15). Incomplete restoration of ionic homeostasis and intracellular potential in stressed hyperexcitable neurones might cause excess extra cellular K+ accumulation sufficient to initiate SD. Abnormalities have been reported in migraine sufferers that, alone or in combination, might account for occipital cortex hyperexcitability. In addition to impaired GABA-ergic inhibition referred to above (1), these include mitochondria defects (16), disturbance in magnesium metabolism (17), calcium channelopathy (18), and disturbances of neuromodulation involving serotonin projections from dorsal raphe nucleus (19).
In the context of strong visual stimuli and cortical excitability, Wilkins and his colleagues, in the current issue of Cephalalgia, have rigorously evaluated visual function in migraine patients with complaints of visual triggering of their attacks, perceptual disturbance and photophobia during headache, or spatial or chromatic distortion of text or blurring during reading. First choosing the colour of light that improved such perceptual distortion or discomfort, patients subsequently were provided glasses to wear with spectral filters that optimized these conditions. In a clever experimental paradigm, ‘control’ glasses had an undetectable difference in tint that was other than the optimal colour chosen. A double-masked randomized controlled study with crossover design assessed the effectiveness of the optimal ophthalmic tint in headache prevention. Reduction in headache frequency was marginally significant when the optimal tint was worn (P=0.08). Although a disappointing level of significance, it should not have been surprising in the population studied. Of 17 patients, five had migraine without aura, and of those with aura its nature was not precisely described. Possibly there are symptom complexes that might yield more effective results on subpopulation analysis with greater numbers. Most importantly, patients remained on a variety of preventive medications known to reduce excitability of neurones, the premise upon which the study was based. Marginally significant benefit still was obtained, however, even though this confound skewed against the effectiveness of the optimal tinting arm of the study.
Wilkins and colleagues attribute the beneficial headache response to the coloured filters reducing pattern glare. As is the case for linear stimuli, neurones in excitable regions of visual cortex fire inappropriately when the excitation is strong, as for example reading texts that evoke pattern glare, leading to perceptual distortion and headache. Certain coloured tints might redistribute the excitation from these hyperexcitable cortical regions, reducing abnormal neuronal firing. In practical terms of patient care, it seems worthy of exploring coloured visual filters for individuals with a strong history of perceptual problems or visual triggers of headache, but predicated upon appropriate optometric assessment. Although it is commonly assumed that migraine patients wear dark glasses to counteract photophobia, perhaps some are relieving visual discomfort due to occipital cortex hyperexcitability.