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Arquivos de Neuro-Psiquiatria

Print version ISSN 0004-282X

Arq. Neuro-Psiquiatr. vol.72 no.12 São Paulo Dec. 2014

https://doi.org/10.1590/0004-282X20140200 

Articles

Aura-like features and photophobia in sightless migraine patients

Características de fenômenos aura-relacionados e da fotofobia em enxaquecosos deficientes visuais

Greice Cardoso de Carvalho Silva 1  

Cristiana Pessoa de Queiroz Faria Góes 2  

Maurice Borges Vincent 2  

1Hospital Naval Marcílio Dias, Rio de Janeiro RJ, Brasil;

2Faculdade de Medicina, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ, Brasil.


ABSTRACT

Migraine is a central nervous system disorder frequently expressed with paroxysmal visual dysfunctions.

Objective

To test the hypothesis that normal visual input is vital for the migrainous aura and photophobia.

Method

We studied the migraine-related visual disturbances in 8 sightless migraineurs identified among 200 visually impaired subjects.

Results

The main findings were the visual aura and photophobia disappearance along with blindness development, the oddness of aura – too short, colourful (e.g. blue or fire-like), auditory in nature or different in shape (round forms) – and the lack of photophobia.

Conclusion

We propose that the aura duration should be accepted as shorter in visually impaired subjects. The changes in aura phenotype observed in our patients may be the result of both cerebral plasticity induced by the visual impairment and/or the lack of visual input per se. Integrity of visual pathways plays a key role in migraine visual aura and photophobia.

Key words: migraine with aura; low vision; blindness; visual aura; photophobia

RESUMO

A enxaqueca é doença neurológica frequentemente associada a anormalidades visuais transitórias.

Objetivo

Testar a hipótese de que a visão normal é importante para o fenótipo da aura e da fonofobia.

Método

Estudamos 8 enxaquecosos deficientes visuais identificados em uma população de 200 indivíduos com visão subnormal.

Resultados

Os principais achados foram: o desaparecimento da aura visual e da fotofobia com o início da cegueira; a ocorrência de aura atípica – muito curta, colorida (p. ex. azul ou cor de fogo) auditiva ou diferente na forma (arredondadas); e a ausência de fotofobia.

Conclusão

Propomos que a duração da aura possa ser admitida como mais curta em pessoas com deficiência visual. As mudanças no fenótipo da aura observadas nos nossos pacientes pode ser o resultado da plasticidade cerebral induzida pela deficiência visual e/ou a deficiência visual em si. A integridade da via visual desempenha um papel crucial na aura enxaquecosa e na fotofobia.

Palavras-Chave: enxaqueca com aura; visão subnormal; cegueira; aura visual; fonofobia

Migraine is a neurological disorder that frequently involves cortical paroxysmal dysfunction expressed as aura1. The most frequent aura type is visual, sometimes experienced as fortification spectra, known as teichopsia. This typical zigzag, horseshoe-shaped expanding bright perception, usually perceived as complex interlacing lines named “chevaux de frises” by Gowers followed by a bean-shaped loss of visual acuity strongly suggests involvement of visual processing areas. Clinical, experimental and neuroimaging evidence demonstrate that cortical spreading depression (CSD) is the phenomenon underlying the pathophysiology of bizarre visual perceptions among migraineurs. Computerized models simulating a CSD wave passing through cortical area V1 convincingly reproduce the teichopsia pattern2.

The cortical function is deeply dependent on neuronal input. Depriving the cortex of its natural input might influence the cerebral function and change the cortical maps both locally and distantly3. In blind individuals, the occipital cortex is critical for tactile Braille reading4. Since the visual cortex is pivotal in the pathophysiology of the migraine aura, the objective of the present study was to investigate whether the phenotype of migraine-related visual phenomena would change in amaurotic patients.

Method

Two hundred visually impaired adult subjects (VIS) were randomly recruited at the Instituto Benjamin Constant (IBC), a Brazilian reference treatment and education centre for the unsighted located in Rio de Janeiro. One of the authors (GCCS), a fully trained neurologist, personally interviewed and examined all the VIS from October 2010 to May 2011, and March to July 2012. Study procedures included the headache and visual impairment history recording, neurological examination, and IBC medical records review for access to full ophthalmological and clinical data. This descriptive, observational study was approved by the Hospital Naval Marcílio Dias (HNMD) ethics committee (56/2010) and authorized by the IBC board in 10 August 2010. All VIS who volunteered to participate signed or fingerprinted an informed consent.

A standardized interview was used to espy migraine patients among the VIS. The International Classification of Headache Disorders version II (ICHD-II)5 was applied to distinguish migraineurs fulfilling the criteria for the following disorders: migraine without aura, typical aura with migrainous headache, typical aura with non migrainous headache, typical aura without headache, probable migraine without aura and probable migraine with aura, present for at least one year prior to the interview. Visual phenomena not necessarily meeting the ICHD-II criteria for typical aura, either atypical in form, colour and/or duration; occurring without, before or during the headache, being migrainous or not, were also considered. VIS had to suffer from acquired or congenital amaurosis according to the 10th revision of the International Classification of Diseases (ICD-10) code H54, corresponding to vision impairment categories 3, 4 or 5 (WHO Study Group on the Prevention of Blindness, Geneva, 6-10 November 1972, WHO Technical Report Series no. 518, 1973).

Exclusion criteria comprise ICHD-II familial hemiplegic migraine, sporadic hemiplegic migraine, basilar-type migraine, retinal migraine, migraine complications, chronic migraine, migrainous status, persistent aura without infarction, migrainous infarction, seizure triggered by migraine and probable chronic migraine, migraine onset after the age of 50, comorbidities systemic or not potentially causing or manifesting as a migraine-like disorder.

Results

From the 200 individuals initially interviewed, 9 were excluded: three refused to participate, four because of cognitive impairment, one because of a brain tumour and one due to marijuana addiction. Among the 191 remaining VIS, 63 fulfilled criteria for amaurosis. In this subgroup, 35 (55.5%) referred recurrent headaches, mostly of the migrainous type (23-37.0%), as opposed to 12 (19%) with other headache disorders and 28 (44%) headache free subjects. Eight (12.7%, 6 females, 40.00±13.06 y-o, range 25-56) migraine with aura patients were selected and studied in further detail (Table), of which seven presented with visual aura not necessarily fulfilling.

Internacional Headache Society (IHS) diagnostic criteria5 (in four, the aura lasts less than 5 min), and one referred auditory aura (uncharacteristic noise). In the majority of our population the headache started before the visual impairment.

Among the seven amaurotic patients with visual aura, five failed to present aura following the sightlessness onset. In patient 1, diagnosed as typical aura with headache not fulfilling migraine criteria, and patient 7, with atypical aura – auditory – the migraine with aura started after the visual impairment. Patient 4 used to perceive scintillations in some headache attacks prior to blindness, changing to perceptions in colour and forms after vision loss. Regardless of the headache type, visual aura symptoms were atypical because of length (too short) colour (blue, silver or fire-like); and/or shape (round shapes).

Photophobia, referred by all patients in whom the headache preceded the blindness in time (n=6), disappeared after the visual impairment. The remaining two subjects denied this symptom.

Discussion

In this study, we looked for the lifetime prevalence of migraine in a population of visually impaired subjects in order to address the disease phenotype in this particular population. After blindness, only one patient continued to express aura as before. This suggests that normal visual input and processing is crucial for aura expression in migraine. Besides, in one patient who became blind years before the migraine attacks, auditory rather than visual phenomena emerged, possibly reflecting an aura-like symptom. Photophobia is clearly dependent on vision, as it is not present concomitantly with total blindness.

Kowacs et al. looked for migraine among visually impaired and found a 6 months prevalence ratio of 14.28% (37% in our material). In their series, four subjects had aura: one totally blind patient presented auditory aura and two subnormal vision individuals referred atypical visual aura lasting 2-4 min. In the last patient aura symptoms disappeared as the vision impairment progressed6. Noseda et al. reported on 6 (2 with aura) totally blind and 14 (5 with aura) visually impaired (light perception) migraineurs, but aura details were not provided7.

Aura is supposed to be the clinical counterpart of CSD, a neurophysiological wave of excitation followed by depression of cortical activity8. Migraine has been related with cortical hyperexcitability9, and the migrainous occipital cortex is particularly responsive to interictal visual stimulation10. There are limited data on CSD provoked by stimuli either then seizure induction or direct chemical/mechanical stimulation, but it is well known that migraine attacks may be triggered by visual stimuli such as sunlight11, red-green flickering12 or particular striped patterns13. Exercise was used to induce a migraine aura during which a CSD-like wave was detected in the brain14. In rats, darkness seems to reduce the CSD propagation15. Sound may trigger CSD in rats16 and light was also reported to precipitate CSD in rabbits hyperexcited by subconvulsive doses of pentylenetetrazol17. Thus, there is clinical and experimental evidence that increased neuronal excitability renders the migrainous cortex more vulnerable to CSD.

Plasticity is an intrinsic endowment of the brain18 and blindness induces substantial cerebral reorganization19. Blind individuals may compensate the lack of sight by developing hyper-effective non-visual senses. Although tactile input activates the visual cortex in sighted individuals20, blinds activate their primary visual areas V1 and V2 during Braille reading as a compensatory cross-modal strategy4. Blind subjects develop auditory abilities beyond controls21 and absolute pitch is more prevalent in blind musicians22. Sightless people detect much more efficiently moving sounds23.

Therefore, in theory, non-cortical blindness should not preclude CSD from occurring in a migraineous brain, as the cortex remains functional and is activated by various inputs. Since the occipital cortex may change from processing visual information to processing other sensory modalities in sightlessness, we hypothesized that the lack of visual input would render the visual cortex less susceptible to CSD, leading to the cessation of the visual auras. Likewise, as sight deteriorates before blindness subnormal vision would partially reduce CSD susceptibility, possibly explaining the atypical visual auras, mostly too short or expressing colour changes not commonly seen in ordinary migraine. Alternatively, the cortical reorganization induced by the lack of vision could still allow CSD but change just its clinical expression, leading to the discontinuation of visual phenomena. If this hypothesis is correct, the auditory aura referred by patient 7 could be the result of an aberrant activation as a result of blindness.

It is noteworthy that visual phenomena were significantly shorter in many VIS. According to the ICHD-II, aura should develop gradually over 5-20 minutes and last for less than 60 minutes. Each aura symptom lasts, by definition, ≥5 and ≤60 minutes5. These time restrictions are maintained in the present ICHD-3 beta version24. In half of our cases the visual symptoms possibly reflecting aura were shorter than 5 minutes. Based in these results, we suggest that the 5-60 minutes aura limit should not encompass VIS. More subnormal vision subjects must be studied to confirm this finding. The reason as why aura is shorter the VIS is not known, my may be the result of cortical plasticity and/or lack of visual input to the visual cortex.

Auditory aura is rarely seen in migraine, but auditory hallucination has been reported as a type of acoustic aura25. Our case and the one described by Kowacs et al.6 in small sightless populations contrast with the rarity of this phenomenon in ordinary migraine, indicating that acoustic aura might be significantly more common among blind subjects. Speculatively, if the lack of vision result in overactivation of cortical areas related to hearing, this could favour auditory aura in this population.

Photophobia is present in >80% of migraine patients26 and seems to be closely inter-related with trigeminal pain. Painful27 and optokinetic simuli28 increase light discomfort in migraineurs. In controls, luminous stimulation at certain intensities did not produce activation of the visual cortex without concomitant pain as detected by positron emisson tomography, but in migraineurs cortical activation occurred at the same luminous stimulation levels without simultaneous pain, which in turn potentiated the light activation even further29.

The pathophysiology of photophobia is largely unknown and may involve non-image formation visual pathways. The fact that mice lacking rods and cones showed normal suppression of pineal melatonin in response to monochromatic light was the first evidence of an additional ocular photoreception in mammals. Melanopsin, an opsin/vitamin A-based photopigment sensitive to blue stimuli present in some retinal ganglion cells30 may play a key role in migraine photophobia. In contrast with the present findings, sensitivity to light was referred by blind migraineurs who had preservation of pupillary light response and circadian photoentrainment, but in patients with bilateral enucleation or damage to the optic nerves photophobia was absent7, indicating that image formation input is not obligatory for photophobia. As shown in rats, it is possible that retina originated fibres projecting to the thalamus induce retinal photoactivation in a discrete area at the posterior thalamus where dura-sensitive fibres converge7. In our cases, no blind patient admitted pain exacerbation or discomfort by light. This is probably due to the fact that rod, cone and melanopsin perceptions were all damaged in our cases.

The small number of subjects and the lack of congenitally blind subjects are limitations of this study. We are fully aware that memory biases could have interfered with our results somehow. Reviewing the medical records was the possible way to minimize this drawback. However, we are confident that the cases reported herein do suggest that visual function is crucial for both the expression of migraine aura and photophobia, regardless of the visual cortex integrity.

Table Blind patients with migraine and aura-like symptoms. 

      Headache Blindness
        Aura   Cause
Patient Gender Age Age at onset (years) Nau Vom Photo Phono Type Duration (minutes) Age at onset (years) Right eye Left eye
1 Male 32 23 (after blindness) - - - + Short-lasting teichopsia Few 23 CG RD
2 Female 49 18 + - +* + Photopsia, round white or blue bright shapes. Round lights moving as fireworks. Bright pink light before 45 y-o 1 Left: congenital right: 29 y-o Myopia and RD CD and glaucoma
3 Female 55 14 + - +* + Photopsia, teichopsia always to the left hemifield, 2h duration. Headache within 1h after the visual aura* Up to 120 38 Myopia and RD Glaucoma
4 Female 56 26 + - +* + Short-lasting photopsia* "fire-coloured waves" and "gun bullets passing in the air" 1-5 51 PR and cataract Enucleated
5 Female 28 Childhood + - +* + Decreased visual acuity* teichopsia*, scintillations* and photopsia* 5-60 26 CG, phthisis bulbi Megalocornea
6 Female 54 Adolescence - - +* + 1-5 minutes silver or blue scintillations*. Headache within one hour after visual aura 1-5 44 Glaucoma Buphthalmos
7 Male 25 Adolescence + - - + Non-specific noise Unknown 5 ONA, RD
8 Female 52 32 + - +* + White scintilations 5-10 34 Glaucoma and cataract

Acknowledgment

We are indebted to Instituto Benjamin Constant for their cooperation with this study.

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Received: December 16, 2013; Received: August 30, 2014; Accepted: September 18, 2014

Correspondence: Maurice Vincent; Av. das Américas, 1155 / 504; 22631-000 Rio de Janeiro RJ, Brasil; E-mail: vincent@ufrj.br

Conflict of interest: There is no conflict of interest to declare.

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