Self-reported photophobic symptoms in migraineurs and controls are reliable and predict diagnostic category accurately

OBJECTIVES: To assess the reliability of self-reported photophobia across different patient populations and to examine how visual stress thresholds and photophobic symptoms may be predictive of diagnosis. BACKGROUND: Relatively little is known about interictal photophobia in migraine. In particular, the variability of photophobia across different patient groups has not previously been studied, and a pathophysiological hypothesis to account for the symptoms is not agreed upon. METHODS AND RESULTS: Study 1 compared 99 self-selected Dutch patients and 101 headache-free controls using survey methods. Patients both with and without aura were significantly more likely to report symptoms, such as the wearing of sunglasses in normal daylight, consistent with interictal photophobia. Study 2 replicated these findings in a series of consecutive referrals to a headache clinic in the United States. Study 3 used a specially designed laboratory test to examine the threshold for visual stress in those patients who had participated in study 2. Visual stress thresholds were significantly lower in patients than in controls. A discriminant function analysis of data from both studies 2 and 3 showed that diagnostic category (migraine; control) could be predicted from photophobic symptoms and visual stress thresholds at a level significantly better than chance. CONCLUSIONS: We suggest that interictal photophobia is common in migraine and similar across different patient populations. One pathophysiological hypothesis is that interictal photophobia is associated with cortical hypersensitivity to stimulation. The predictive validity of interictal photophobic symptoms suggests that clinical diagnosis may be aided by questioning the patient about light sensitivity in the period between attacks.     

The influence of pattern interference on performance in migraine and visual discomfort groups

Performance in migraine with and without visual aura, non-specific headache and headache-free control groups was measured using a visual search task. Data from groups with high and low visual discomfort were also gathered. No pattern, 2 c/deg, 15 c/deg and a grey field were used in different background conditions. Presentation of patterned backgrounds slowed performance for all groups with the 2 c/deg pattern producing greatest interference. Performance of headache groups did not differ from that of the control group in any condition. The high visual discomfort group responded significantly more slowly than other groups with the 2 c/deg background. It was concluded that the presence of visual discomfort, reported on an everyday basis was a better indicator of heightened sensory sensitivity than the occurrence of migraine with or without aura.     

Tryptophan depletion increases nausea, headache and photophobia in migraine sufferers

Sensitivity to light was investigated 5 and 8 h after consumption of an amino acid drink which contained L-tryptophan (balanced amino acid condition: 19 controls and 22 migraine sufferers) or which produced a short-term reduction in brain serotonin synthesis by omitting L-tryptophan (tryptophan depletion condition: 16 controls and 16 migraine sufferers). Migraine sufferers reported more intense nausea, headache, glare- and light-induced pain than controls. In addition, glare- and light-induced pain were greater in the tryptophan depletion condition than in the balanced amino acid condition, in both migraine sufferers and controls. Eight hours after the amino acid drink, after participants had completed tests of pain sensitivity and motion sickness provocation, tryptophan depletion augmented headache in migraine sufferers and aggravated nausea in migraine sufferers and controls. These findings suggest that a reduction in brain synthesis of serotonin intensifies photophobia and other migrainous symptoms and thus might contribute to the pathogenesis of migraine.     

Influence of disease duration on visual evoked potentials in migraineurs

OBJECTIVE: To determine the possible influence of the duration of migraine on pattern-reversal visual evoked potentials. METHODS: An investigation was conducted in 49 patients with migraine without aura according to the International Headache Society criteria. Twenty-two of these patients had had migraine for 2 years or less (group 1), and the other 27 patients had had the disease for 10 years or more (group 2). The control group consisted of 17 healthy subjects. RESULTS: Comparison of the mean P100 latency and amplitude showed no significant difference among the groups. There was, however, a good negative correlation between age and latency (r = -0.59, P =.003) in group 1, but no such correlation was observed for group 2 or the control group. CONCLUSIONS: It was concluded that the duration of migraine has no influence on pattern-reversal visual evoked potentials and that the pathogenesis of early- and late-onset migraine may be different.     

Frequent analgesics consumption in migraineurs: comparison between chronic and episodic migraineurs

Abstract To assess the frequent consumption of symptomatic medications in migraineurs, we consecutively recruited 536 migraineurs from a headache clinic. Among them, 194 (36.2%) had chronic migraine and 342 had episodic migraine. When grouped according to duration of headache, the proportion of patients with chronic migraine increased from 25.5% to 50.9% as headache history increased from <1 to >20 years. The percentage of patients with frequent analgesics consumption also increased with the duration of headache, in patients with both chronic migraine (from 25.0% to 85.7%) and episodic migraine (from 20.0% to 59.3%). Nonetheless, patients with chronic migraine had a higher prevalence of frequent consumption of abortive medications than patients with episodic migraine regardless of duration of headache history, and the common odds ratio across strata of headache duration was 2.8 (95% confidence interval, 1.9–4.1). However, we found that a long headache history is an important risk factor for frequent consumption of symptomatic medications in migraineurs in patients with both episodic migraine and chronic migraine.     

Interictal executive dysfunction in migraineurs without aura: relationship with duration and intensity of attacks

Subjects with migraine are at increased risk of subcortical white matter lesions (WML). Reports of cognitive testing in adults with migraine have yielded inconsistent results. We performed a cross-sectional study to assess whether migraine without aura (MwA) is associated with impairment in executive functioning, a typical cognitive correlate of subcortical WML. Forty-five subjects with MwA and 90 controls, matched for age and education, underwent a cognitive battery of tests evaluating executive functions. The following migraine characteristics were collected: age at onset and length of migraine history, and frequency, duration and intensity of attacks. Subjects with MwA performed significantly lower than controls in tests evaluating complex, multifactorial executive functions. After multiple adjustments, the duration and intensity of migraine attacks significantly predicted cognitive disturbances. In the interictal phase of MwA there is evidence of mild executive dysfunction. The cumulative effects of repeated migraine attacks on prefronto-cerebellar loop probably account for our results.     

The wavelength of light causing photophobia in migraine and tension-type headache between attacks

OBJECTIVE: To ascertain the wavelength of light that patients with migraine and tension-type headache find uncomfortable between attacks. BACKGROUND: Photophobia is an abnormal perceptual sensitivity to light experienced by most patients with headache during and, also, between attacks. METHODS: We examined the discomfort threshold to light of low, medium, and high wavelengths in a group of patients with migraine (n=21), patients with tension-type headache (n=19), and healthy controls (n=21). RESULTS: The results indicate that the migraine group had significantly lower discomfort thresholds at the low (P=.001) and high (P=.031) wavelengths compared with both the tension-type headache and control groups; the latter two groups had similar average discomfort levels at these two wavelengths. With the medium wavelength, the control group had significantly higher discomfort thresholds than the migraine (P=.002) and tension-type headache (P=.031) groups; the latter two groups had similar discomfort levels at this wavelength. With unfiltered (white) light, the migraine group had the lowest discomfort threshold and the control group the highest (P=.026), whereas the tension-type headache group had an intermediate discomfort threshold. CONCLUSIONS: There were significant differences between migraineurs, patients with tension-type headache, and healthy controls in the wavelengths that are uncomfortable between attacks.     

The use of questions to determine the presence of photophobia and phonophobia during migraine

Objective.— To investigate whether the use of more detailed close‐ended questions as part of the routine headache history is helpful when patients initially deny that they are sensitive to light and noise during migraine headaches. Background.— According to the International Headache Society 2004 criteria, the diagnosis of migraine requires the presence of at least one of the following during a headache: (1) nausea and/or vomiting, (2) photophobia and phonophobia. Evans anecdotally noted that many patients answer the question, “does light or noise bother you during a headache,” with a “no” when the answer is really “yes” if they are asked more detailed close‐ended questions. Methods.— Consecutive patients fulfilling International Headache Society 2004 criteria for migraine or probable migraine presenting to a headache clinic and a neurology clinic were asked the following questions: “does light bother you during a headache?” If “no,” they were then asked, “during a headache, would you prefer to be in bright sunlight or in a dark room?”“does noise bother you during a headache?” If “no,” they were then asked, “during a headache, would you prefer to be in a room with loud music or in a quiet room?” Results.— Eighty‐five consecutive patients with migraine or probable migraine were questioned, 71 females (83.5%) and 14 males (16.5%). There was denial of light and sound sensitivity in 24% of patients with routine questioning and then awareness of sensitivity in 93% with the further questioning. A total of 7.1% of the patients were diagnosed with probable migraine. However, if the additional questions were not asked, 8% more of the patients with definite migraine would have been incorrectly diagnosed as probable migraine. Conclusion.— When patients initially deny light and noise sensitivity during migraine headaches, additional questions should be asked to ensure that their answer is accurate. Not asking the additional questions may result in the over‐diagnosis of probable migraine.     

Light-induced discomfort and pain in migraine

Quantitative thresholds for discomfort and pain with monocular and binocular light stimuli were measured in 67 controls and 67 migraine patients 37 migraine with aura and 30 migraine without aura). Patients were more photophobic during attack than outside attack ( p <0.03), and they were more sensitive to light than controls even between attacks ( p 0001). We found no differences in light sensitivity between migraine with aura and migraine without aura ( p 0.93). Unilateral pain affected light sensitivity on both sides. When asked with a questionnaire, 74% of patients answered that they were sensitive to light outside attack and 100% were sensitive during attack. Pain thresholds were generally lower among sensitive than non-sensitive patients ( p =0.004), indicating some agreement between subjective opinion and objective measurements of photophobia. Photophobia seems to be an intrinsic property of migraineurs. It is increased by migraine pain, but seems to be unrelated to migraine characteristics such as nausea, severity of attacks, pain character and pain laterality.     

Visual system dysfunction in migraine: a review of clinical and psychophysical findings

This paper reviews both clinical and experimental literature relating to visual dysfunction in migraine, starting with the eye and progressing via the retina and visual pathways to the visual cortex. Migraine is associated with (i) a pupillary sympathetic hypofunction, and (ii) a cortical hypersensitivity to visual stimuli (perhaps only in migraine with aura), the pathogenesis of which remains to be determined. Various hypotheses are discussed, and it is proposed that the methods of visual psychophysics may represent a useful approach in the future study of cortical hyperexcitability in migraine. Paradoxically, little research has been directed towards understanding (i) the photophobia of migraine attacks, and (ii) how migraine may be triggered by visual stimuli. Research aimed at elucidating the mechanisms of these phenomena may enhance understanding of the pathogenes is of migraine.     

Altered motion perception in migraineurs: evidence for interictal cortical hyperexcitability

Much research on visual functions in migraine has pinpointed the existence of abnormal visual processing between attacks. However, it is not clear if this is due to cortical hyper- or hypoexcitability. We aimed to clarify this issue by comparing motion perception thresholds of subjects with migraine with (MA) or without aura (MoA) and control subjects. Two types of dot kinetograms were used: in the first experiment coherently moving dots were presented in an incoherent environment, while in the second only coherent motion was seen. Subjects with migraine displayed significantly impaired motion perception compared with controls when they had to detect the direction of the coherently moving dots in an incoherent environment, while they were slightly better in a direction discrimination task, where only coherent motion was presented. This pattern of results is comparable to those achieved by an external excitability enhancement of V5 induced in healthy human subjects in a former study of our group. According to this, a cortical excitability enhancement can result in an impaired focusing on a given signal against a noisy background, but improves perception of non-ambiguous stimuli. Thus we conclude that migraineurs display enhanced visual cortical excitability between attacks in V5.     

Photophobia and Phonophobia in Migraineurs Between Attacks

This study investigated whether migraineurs are more sensitive to light and sound while headache-free than are: healthy people. Fifty-two migraineurs (mean age 39 years) were selected using the International Headache Society diagnostic criteria for migraine. Forty-eight healthy controls were matched for age, sex, and race (mean age 36 years). Visual and auditory discomfort thresholds were measured by exposing subjects to increasing light and sound until then complained of discomfort. There were significant differences; between groups in both the light discomfort threshold (P<0.90005) and the hearing discomfort threshold (P<0.0005) The thresholds for both were lower in the migraineurs.
Overall, for both groups together, there was a significant negative correlation between light discomfort threshold and age (correlation coefficient -0.2276, P =0.011), but not for the hearing discomfort threshold and age ( P =0.275).
The results show that the migraineurs were significantly more sensitive to light and sound when headache-free than were healthy controls. The apparent increased intolerance to light in both groups together noted with increased age, did not apply to the migraine group.     

Cerebrovascular response to repetitive visual stimulation in interictal migraine with aura

Cortical hypersensitivity and absent habituation to different stimuli have been observed in migraine patients. These features might also be transmitted to the cerebral vasoreactivity, but results are conflicting so far. Transcranial Doppler ultrasound (TCD) was used to assess cerebral blood flow velocity (CBFV) changes in the middle (MCA) and posterior cerebral arteries (PCA) in relation to repetitive checkerboard visual stimulation. Stimulation consisted of 10 consecutive cycles, each comprising 10 s stimulation and 10 s rest. TCD recordings were analysed using stimulus-related averaging algorithm. Data of 19 interictal migraineurs with aura were compared to those of 19 headache-free healthy volunteers. The CBFV increase in PCA and in MCA during visual stimulation was significantly larger and steeper in migraineurs than in controls (P = 0.017 and P = 0.005). The response in PCA remained stable over the 10 stimulation cycles, both in migraineurs and in controls. The response in MCA was stable only in migraineurs. In controls it decreased over the last 5 stimulation cycles compared with the first 5 cycles (P = 0.04). Migraineurs with aura exhibit a larger cerebrovascular response to repetitive visual stimulation compared to headache-free subjects. A reduced adaptation to environmental stimuli in migraine is suggested, since there was no habituation in migraineurs in contrast to healthy controls.     

Functional connectivity of the visual cortex differentiates anxiety comorbidity from episodic migraineurs without aura

BackgroundMigraine is a common neurological disease that is often accompanied by psychiatric comorbidities. However, the relationship between abnormal brain function and psychiatric comorbidities in migraine patients remains largely unclear. Therefore, the present study sought to explore the correlations between the resting-state functional deficits and psychiatric comorbidities in migraine without aura (MwoA) patients.MethodsResting-state functional magnetic resonance images were obtained. In addition, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were obtained. Thereafter regional abnormalities in MwoA patients with and without anxiety (MwoA-A and MwoA-OA) were chosen as seeds to conduct functional connectivity (FC) analysis.ResultsCompared to the healthy controls (HCs), the MwoA-A and MwoA-OA patients had abnormal ALFF and ReHo values in the right lingual gyrus (LG). They also had abnormal FC of the right LG with the ipsilateral superior frontal gyrus (SFG) and middle cingulate cortex (MCC). Additionally, the MwoA-A patients showed higher ReHo values in the left posterior intraparietal sulcus (pIPS) and abnormal FC of the right LG with ipsilateral pIPS and primary visual cortex, compared to the MwoA-OA patients. Moreover, the MwoA-OA patients showed an increase in the FC with the right posterior cingulate cortex/precuneus (PCC/PCUN), left middle frontal gyrus (MFG) and left inferior temporal gyrus (ITG) relative to the HCs. Furthermore, the ALFF values of the right LG positively were correlated with anxiety scores in MwoA-A patients. The abnormal LG-related FCs with the PCC/PCUN, MFG and ITG were negatively associated with the frequency of headaches in MwoA-OA patients.ConclusionsThis study identified abnormal visual FC along with other core networks differentiating anxiety comorbidity from MwoA. This may therefore enhance the understanding of the neuropsychological basis of psychiatric comorbidities and provide novel insights that may help in the discovery of new marks or even treatment targets.     

Enhanced interictal responsiveness of the migraineous visual cortex to incongruent bar stimulation: a functional MRI visual activation study

Since visual aura is usually described as expanding zigzag lines, neurones involved with the perception of line orientation may initiate this phenomenon. A visual incongruent line stimulation protocol was developed to obtain functional magnetic resonance images (fMRI) interictally in 5 female migraine patients with typical fortification spectra and in 5 normal matched controls. Activation in the visual cortex was present contralateral to the side of stimulation in 4 of 5 patients, notably in the extrastriate visual cortex. In 4 of 5 controls activation was observed in the medial and anterior orbitofrontal cortex. In one of them additional activation at the right nucleus accumbens/ventral striatum and right ventral pallidum was present. In the remaining control subject activation was present in the left primary visual cortex. The enhanced interictal reactivity of the visual cortex in migraineurs supports the hypothesis of abnormal cortical excitability as an important pathophysiological mechanism in migraine aura, though the role of specific regions of the visual cortex remains to be explored.     

Stimulation of brainstem nuclei in the cat: Effect on neuronal activity in the primary visual cortex of relevance to cerebral blood flow and migraine

The electrical activity of single neurons was recorded in the primary visual cortex of anesthetized cats in order to test the hypothesis that changes in their activity might be the cause of the changes in blood flow seen after stimulation of the brainstem and in migraine. Discharge evoked by optic radiation stimulation was facilitated by conditioning stimulation (6 pulses over 24 msec) of the locus coeruleus (LC), whereas no consistent effect was exerted on resting discharge. No clear difference could be demonstrated between the effect on resting discharge of short-duration stimulation of the LC, midbrain reticular formation and dorsal raphe nucleus (DRN). Stimulation of these structures at 5/sec for 10 sec was also studied to ascertain whether long-term changes in neuronal activity could be produced, and to indicate whether changes in cerebral blood flow previously described with these parameters of stimulation were secondary to alterations in metabolic demand due to increased or decreased bulk neuronal activity. The vast majority of single neurons were unaltered by these parameters of stimulation, suggesting that cortical blood flow changes following LC and DRN stimulation are due to a direct action on the cortical microcirculation.     

Cerebral blood flow and CO2 reactivity in interictal migraineurs: a transcranial Doppler study

There is still some controversy about alterations in velocity of blood flow and in cerebral vasomotor reactivity of intracranial arteries in migraineurs during the interictal phase. By means of simultaneous bilateral transcranial Doppler ultrasonography we, therefore, assessed intracranial blood flow velocities and cerebrovascular reactivity to carbon dioxide of all three basal brain arteries in 20 migraineurs during the interictal phase and 30 nonheadache-prone control subjects. Mean blood flow velocities were higher in migraineurs than in controls in all three arteries on both sides, with a significant difference (P < 0.05) for the right anterior cerebral artery and middle cerebral artery under basal conditions and for the right posterior cerebral artery during hypercapnia. Similarly, the cerebrovascular reactivity to carbon dioxide was always higher in patients than in controls, with a significant difference for the left anterior and the right middle cerebral arteries (P < 0.05) and the right posterior cerebral artery (P < 0.01). The broad overlap of cerebrovascular blood flow velocities and CO2 reactivities in patients and controls precluded identification of values diagnostic of migraine. Nevertheless, transcranial Doppler ultrasonography offers the opportunity to noninvasively monitor cerebral blood flow parameters and, therefore, represents a valuable tool for vascular research in migraine.     

Quantitative evaluation of photophobia and phonophobia in cluster headache

In order to evaluate photophobia and phonophobia in cluster headache (CH), light and sound-induced discomfort and pain thresholds were measured quantitatively in 50 patients and 50 sex-matched and age-matched headache-free controls. During bout (i.e., during the active period with attacks), CH patients were more sensitive to light and sound than controls ( p <0.00l). Outside bout they did not differ significantly from controls except for binaural stimulation. Patients were more photophobic and phonophobic during bout than in the remission period ( p 0.05). However, for those tested during bout, the sensitivity to light and sound was not related to the presence of pain during test, usual pain intensity, or pain laterality. In response to a questionnaire about their sensitivity, a significantly higher proportion of patients considered themselves sensitive during bout than outside (91% vs 46% for light [χ²=5.9, p <0.05] and 89%, vs 49% for sound [χ²=4.7, p <0.05]). These results indicate that photophobia and phonophobia are important accompanying phenomena of cluster bouts.