Posterior Ischemic Optic Neuropathy Associated With Migraine

Anterior ischemic optic neuropathy is a well-recognized clinical syndrome that has been described in patients after an episode of migraine with visual aura (classic migraine) and, less commonly, after an episode of visual aura without headache (acephalgic migraine). Little emphasis, however, has been placed on migraine associated retrobulbar or posterior ischemic optic neuropathy. We report two cases of visual loss presumed to be due to posterior ischemic optic neuropathy that occurred In the setting of otherwise typical migraine episodes. We review the English language literature on Ischemic optic neuropathy associated with migraine. Although most cases of ischemic optic neuropathy associated with migraine are of the anterior variety, posterior ischemic optic neuropathy should be considered in the differential diagnosis of any patient with acute loss of vision and evidence for a retrobulbar optic neuropathy, during or after an attack of migraine headache or following an otherwise typical episode of visual aure without headache (acephalgic migraine).     

Hemi-field pattern reversal visual evoked potentials in migraine

A study of hemi-field pattern reversal visual evoked potentials recorded in the interictal phase was carried out in 44 patients (22 with migraine with aura, 22 without aura) in order to determine whether migraine patients with or without aura and with headaches with strong unilateral predominance, either left or right, exhibit abnormalities after hemi-field stimulation. No differences of P100 latency were found between them and a group of 20 normal individuals, between patients suffering from migraine with aura and migraine without aura and between the affected and the non-affected side of the head. Only in a subgroup of 14 patients with headaches constantly lateralized to a single side, either left or right, was the P100 latency significantly shorter on the affected side (p < 0.001, t-test) compared with the contralateral non-affected side. The results indicate that in both types of migraine there is a common underlying pathogenetic mechanism and the affected retrochiasmatic optic radiation has an increased response to sensory input modulation.     

Peri-ictal normalization of visual cortex excitability in migraine: an MEG study

To delineate if the change in cortical excitability persists across migraine attacks, visual evoked magnetic fields (VEF) were measured in patients with migraine without aura during the interictal ( n  = 26) or peri-ictal ( n  = 21) periods, and were compared with 30 healthy controls. The visual stimuli were checkerboard reversals with four different check sizes (15', 30', 60' and 120'). For each check size, five sequential blocks of 50 VEF responses were recorded to calculate the percentage change of the P100m amplitude in the second to the fifth blocks in comparison with the first block. At check size 120', interictal patients showed a larger amplitude increment than controls [28.1 ± 38.3% ( s.d. ) vs. 8.7 ± 21.3%] in the second block and a larger increment than peri-ictal patients in the second (28.1 ± 38.3% vs. −3.2 ± 19.2%), fourth (22.7 ± 31.2% vs. −5.7 ± 22.3%) and fifth (20.5 ± 30.4% vs. −10.8 ± 30.1%) blocks ( P  < 0.05). There was no significant difference at other check sizes or between peri-ictal patients and controls. In conclusion, there may be peri-ictal normalization of visual cortical excitability changes in migraine that is dependent on the spatial frequency of the stimuli and reflects a dynamic modulation of cortical activities.     

Diffusion- and perfusion-weighted MR imaging in persistent migrainous visual disturbances

Pathological changes on diffusion-weighted MR scans had been described in hemiplegic migraine and perfusion changes had been demonstrated in typical migraine aura with radio-isotope studies and, more recently, MR perfusion imaging. However, there is relatively little knowledge of the pathophysiology of long-lasting migraine aura and its possibly variant phenotype, visual snow. Our aim was to investigate with advanced MR techniques whether patients with long-lasting visual disturbance showed regional alterations in cerebral water diffusion and perfusion. We have studied four patients using MR perfusion and MR diffusion imaging. Two patients had typical visual aura and two had a primary persistent visual disturbance (visual snow phenomenon). All patients had normal conventional structural MR imaging. MR diffusion-weighted images were acquired with a b-value of up to 1000 s/mm2. From the diffusion weighted images we generated maps of apparent diffusion coefficient (ADC), which were inspected visually and used for ADC measurements of predefined regions of interest, which included the visual, frontal, insular and temporal cortices. MR perfusion imaging was performed using a bolus tracking technique with dynamic susceptibility-weighted images. Colour coded maps of relative cerebral blood volume, mean transit time and bolus arrival time were generated, as well as time-signal intensity curves over the anterior, middle and posterior cerebral artery territories. The maps of the ADC and above perfusion parameters appeared symmetrical in all patients with no evidence of decreased water diffusion or cerebral perfusion in the occipital regions, or elsewhere. There was no statistically significant difference between the ADC measurements of the primary visual cortices and other cortical regions. Our findings suggest that regional changes in cerebral water diffusion and perfusion do not play an important part in the pathophysiology of persistent migraine aura or primary persistent visual disturbance.     

An association of migraine with hereditary haemorrhagic telangiectasia independently of pulmonary right-to-left shunts

Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, telangiectasia and visceral vascular manifestations. It is associated with migraine with aura due to pulmonary arteriovenous malformations (pAVMs). The aim of the study was to evaluate headache prevalence in 106 consecutive HHT patients (67 female, 39 male, age 53.5 ± 14.5 years) and age- and gender-matched controls. An extensive clinical work-up was performed and headache prevalence was determined. Lifetime prevalence of migraine was higher in HHT patients (39.6%) than in controls (19.8%) [ P  < 0.001, χ² = 12.17, odds ratio (OR) 3.0; 95% confidence interval 1.6 < OR < 5.7]. A positive association was confirmed between HHT patients with pAVMs and migraine with aura (38.5% vs. 10%). Furthermore, HHT patients without pAVMs had a higher prevalence of migraine without aura (11.5% vs. 26.3%; χ² = 11.85; d.f. = 2; P  = 0.003). We speculate that pathophysiological mechanisms, including dysfunction of the transforming growth factor-beta pathways and resulting vascular changes, contribute to the higher prevalence of migraine without aura in HHT patients without pAVMs.     

C-reactive protein in migraine sufferers similar to that of non-migraineurs: the Reykjavik Study

C-reactive protein (CRP), a marker of inflammation, has been associated with cardiovascular disease. Risk of cardiovascular disease is increased in migraineurs with aura. Results from a clinical report, case–control and a cohort study suggest that CRP is elevated in migraineurs compared with non-migraineurs. We examined the proposed association in a case–control study nested within two large population-based studies. The relationship between migraine and CRP (high-sensitivity CRP) was studied in 5906 men and women aged 55.0 ± 8.5 years in the Reykjavik Study and 1345 men and women aged 27.7 ± 5.5 years from the Reykjavik Study for the Young. A modified version of the International Headache Society's criteria was used to categorize people into migraineurs (two or more symptoms) or non-migraineurs. Migraineurs with visual or sensory symptoms were further defined as having migraine with aura (MA) or without aura (MO). Multivariable-adjusted CRP levels were similar in migraineurs and non-migraineurs for men (0.83 vs. 0.79 mg/l, P  = 0.44) and for women (0.87 vs. 0.87 mg/l, P  = 0.90). When further stratified by migraine aura and age, no differences were found between non-migraineurs, MO and MA among men. In women, CRP levels were borderline higher in those with MO compared with non-migraineurs and those with MA (1.01 mg/l vs. 0.81 and 0.75 mg/l, P  = 0.08 and P  = 0.08) in age group 19–34 years, but significantly lower in age group 60–81 years (0.52 mg/l vs. 1.07 and 1.01 mg/l, P  = 0.007 and P  = 0.03). CRP levels were not increased among migraine sufferers compared with non-migraineurs. Older women migraineurs without aura had lower CRP values than non-migraineurs and migraineurs with aura.     

Simultaneous recording of pattern reversal electroretinograms and visual evoked potentials in migraine

We recorded full-field pattern seversal electroretinograms (PERGs) and visual evoked potentials (PVEPs) simultaneously in 15 migraine with aura, 14 migraine without aura patients during the interictal period, and in 23 sex- and age-matched normal subjects. All subjects had normal visual fields. The visual aura in all patients was hemianopsia or fortification spectra. Neither migraine group showed significant differences from normal in latency and amplitude of PERGs. In migraine with aura, the amplitudes of PVEPs in classic migraine at the mid-occipital electrode were significantly ( p <0.01) higher than normal. PVEP amplitudes were significantly ( p <0.01) high or on the contralateral side of the aura than the ipsilateral side in both visual aura and normal subjects, but there was no significant difference in latency. This high amplitude and asymmetry of PVEPs may contribute to defective inhibition between interhemispheric visual occipital areas or striate and peristriate areas.     

Maturation of early visual processing investigated by a pattern-reversal habituation paradigm is altered in migraine

Evidence for a disturbed maturation of information processing in migraine came recently from evoked and event-related potential studies during childhood. In adult migraineurs, deficient habituation is proposed as principal interictal abnormality and was found inter alia for Visual Evoked Potentials (VEPs). This study investigated response and habituation to pattern-reversal VEPs and its maturation in 102 children with primary headache (migraine with and without aura, tension-type headache) and 79 healthy controls from 6 to 18 years. A reduction of N180 latency from pre- to postpubertal age reflects maturation and was clearly present in controls but lessened in migraineurs. N180 latency was prolonged in migraineurs without aura from 12 years onwards. Habituation did not differ between groups. In conclusion, diminished N180 latency reduction with age in migraineurs gives further evidence that maturation of visual information processing is altered in migraine. Deficient habituation to pattern-reversal VEPs could not be confirmed during childhood migraine.     

Perfusion weighted imaging during migraine: spontaneous visual aura and headache

Using perfusion weighted imaging, we studied 28 spontaneous migraine episodes; 7 during visual aura (n = 6), 7 during the headache phase following visual aura (n = 3), and 14 cases of migraine without aura (n = 13). The data were analyzed using a region-of-interest-based approach. During aura, relative cerebral blood flow (rCBF) was significantly decreased (27% +/- 0.07) in occipital cortex contralateral to the affected hemifield. rCBV was decreased (15% +/- 0.12) and mean transit time increased (32% +/- 0.3), persisting up to 2.5 h into the headache phase. Other brain regions did not show significant perfusion changes. During migraine without aura, no significant hemodynamic changes were observed. In one patient who experienced both migraine with and without aura, perfusion deficits were observed only during migraine with aura. These findings suggest that decremental blood flow changes in occipital lobe are most characteristic of migraine with aura.     

Vertebral artery dissection onset mimics migraine with aura in a graphic designer

Headache is the most common symptom in patients with cervical artery dissection. This symptom, however, rarely occurs in isolation, and more commonly is associated with other neurological symptoms and signs. Visual symptoms associated with vertebral artery dissection (VD) have also been observed, but do not typically mimic the migraine aura. Here, we report a young patient who presented VD, embolic ischemic lesions, and visual symptoms with the features of aura, followed by migraine headache. The suggestion of VD dissection should be kept in mind in those cases complaining of the first attack of headache that mimics migraine with aura. In these cases, an extensive neuroimaging study is advisable.     

Persistent and Repetitive Visual Disturbances in Migraine: A Review

Visual disturbances in migraineurs, such as visual aura, are typically episodic, that is, associated with the headache attack, and overlaid by head pain and other symptoms that impact the patient. In some patients, however, visual symptoms are dominant due to frequency (migraine aura status), duration (persistent migraine aura and other persistent positive visual phenomena), or complexity (visual snow syndrome). These syndromes are more rare and challenging to classify in clinical practice resulting in a lack of systematic studies on pathophysiology and treatment. We aim at describing clinical features and pathophysiological concepts of typical migraine aura with a focus on cortical spreading depression and differentiation from non‐typical migraine aura. Additionally, we discuss nomenclature and the specifics of migraine aura status, persistent migraine aura, persistent positive visual phenomena, visual snow, and other migrainous visual disturbances. The term migraine with prolonged aura might be a useful bridge between typical aura and persistent aura. Further studies would be necessary to assess whether a return of the classification category eventually helps diagnosing or treating patients more effectively. A practical approach is presented to help the treating physician to assign the correct diagnosis and to choose a medication for treatment that has been successful in case reports of these rare but disabling conditions.     

Improved description of the migraine aura by a diagnostic aura diary

We present a diagnostic aura diary for prospective recordings of migraine with aura. Three questionnaires are supplemented with sheets for drawings and plottings of visual and sensory auras. Twenty patients recorded 54 attacks of migraine with aura and 2 attacks of migraine aura without headache. The visual and sensory aura were usually gradually progressive, reaching maximum development in 15 and 25 min (median) respectively and had a total duration of 20 and 55 min (median) respectively. Approximately 13% of the attacks had acute onset of visual aura associated with other features more typical of migraine. The visual and sensory auras always preceded typical migraine headache, and headache occurring before aura symptoms was always of the tension type, The migraine headache was milder than in attacks of migraine without aura and often did not have migraine characteristics. In attacks with unilateral head pain, headache and aura symptoms were contralateral in 90% and ipsilateral in 10%.     

Influence of colors on habituation of visual evoked potentials in patients with migraine with aura and in healthy volunteers

OBJECTIVE: To investigate whether colored glasses influence the habituation of visual evoked potentials. BACKGROUND: We have previously shown that during pattern-reversal stimulations lasting 2 minutes the amplitude of the visual evoked potential increases in migraine with and without aura between attacks, whereas it decreases in healthy volunteers. Red light was found to increase visually evoked EEG fast activity only in children with migraine with aura. Wearing rose-tinted glasses for 4 months decreased attack frequency in parallel with a reduction of the visually evoked EEG fast activity. METHODS: We compared the change in amplitude of the visual evoked potential using five different tinted glasses in 12 patients with migraine with aura and in 10 healthy volunteers. During continuous stimulation at 3.1 Hz, five blocks of 50 responses were sequentially averaged using red, yellow, green, blue, and grey glasses and without glasses in a random order and analyzed in terms of latencies and N1-P1 amplitudes. Amplitude changes were calculated for each block by comparison with the first block in every condition and analyzed statistically using Zerbe's method. RESULTS: In healthy volunteers, the visual evoked potential amplitude increased with red glasses compared to without glasses (P = .05) or with green glasses (P = .03). In patients with migraine with aura, no significant difference was detected using colored glasses. Our findings in healthy volunteers are in line with earlier reports of increased excitability of the human visual cortex when exposed to red light. The lack of such a pattern in patients with migraine with aura suggests that the visual cortex is interictally hypoexcitable rather than hyperexcitable, which is consistent with studies of transcranial magnetic stimulation.     

Characteristics and prevalence of transient visual disturbances indicative of migraine visual aura

The objective of this study was to estimate the prevalence of and to compare the characteristics of transient visual disturbances (TVDs) of possible migraine origin in a clinical and a general population. Data were obtained in interviews from 100 consecutive female migraine patients (17-69 years) and 245 women (40-75 years) from the general population. The lifetime prevalences were 37% and 13%, respectively. We did not detect any differences in characteristics of TVDs between patients and women in the general population. A gradual onset of five or more minutes was stated by as few as 45% and 46%, respectively. The typical headache phase in conjunction with a TVD had more migrainous features in patients. We conclude from our data that the TVDs in this study, which do not fulfill the IHS criteria for migraine with aura, more likely represent poorly described or abortive migraine phenomena, rather than phenomena of other origin.     

Pattern reversal visual evoked potentials in migraine with aura and migraine aura without headache

Pattern reversal visual evoked potentials (PVEPs) were recorded in 20 patients with migraine with aura (MA), 19 patients with migraine without headache (migraine equivalent; ME.) during interictal periods, and 34 normal subjects. All migraine patients had hemianopsia or fortification spectra during attacks. In both MA and ME patients of less than 49 years of age, there were significant ( p <0.01) differences in amplitude of PVEPs at the mid-occipital and contralateral to visual aura electrode sites compared to normal subjects. Amplitude of PVEPs in MA and ME showed significant ( p <0.001) increases when recorded soon after attacks, especially within 10 days. There was a significant ( p <0.0l) correlation between percentage asymmetries and the duration of illness in both MA and ME. We conclude from our PVEP findings that cortical spreading depression remains the most likely explanation for the migraine visual aura.     

Genetic association study of Endothelin-1 and its receptors EDNRA and EDNRB in migraine with aura

The effect of endothelin-1 and its receptors EDNRA and EDNRB in migraine with aura (MA) susceptibility is not established yet. We studied the association between the MA end-diagnosis and three migraine trait components and 32 single nucleotide polymorphisms (SNPs) capturing the variation of endothelin genes in 850 Finnish migraine patients and 890 non-migrainous individuals. The SNPs showing evidence of association were further studied in 648 German migraine patients and 651 non-migrainous individuals. No significant association was detected. However, the homozygous minor genotype (5% in cases) of the EDNRA SNP rs2048894 showed nominal association with MA both in the Finnish sample ( P  = 0.015) and in the pooled sample [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.12–2.32, P  = 0.010] when adjusted for gender and sample origin. The trait age of onset < 20 years was also associated with rs2048894 (OR 1.69, 95% CI 1.13–2.54, P  = 0.011) in the pooled sample. To confirm this finding studies on even larger samples are required.     

MR-spectroscopic imaging during visual stimulation in subgroups of migraine with aura

Migraine pathophysiology possibly involves deficient mitochondrial energy reserve and diminished cortical habituation. Using functional magnetic resonance spectroscopic imaging (fMRSI), we studied cortical lactate changes during prolonged visual stimulation to search for different pathophysiological mechanisms in clinically distinct subgroups of migraine with aura. Eleven healthy volunteers (HV) and 10 migraine patients were investigated interictally: five with visual aura (MA) and five with visual symptoms and at least one of the following: paraesthesia, paresis or dysphasia (MAplus). Using MRSI (Philips, 1.5 T) (1)H-spectra were repeatedly obtained from a 25 mm-thick slice covering visual and non-visual cortex, with the first and fifth measurements in darkness and the second to fourth with 8-Hz checkerboard stimulation. In MAplus lactate increased only during stimulation, only in visual cortex; in MA resting lactate was high in visual cortex, without further increase during stimulation. This is compatible with an abnormal metabolic strain during stimulation in MAplus, possibly due to dishabituation, and a predominant mitochondrial dysfunction in MA.     

Recurrent Lilliputian hallucinations as visual aura symptom in migraine

Since her early 30s a 72-year-old female migraine sufferer has experienced recurrent episodes of Lilliputian hallucinations occurring at the peak of her severe migraine attacks and lasting between 2 min and 5 min, suggesting that her miniature hallucinations represent a visual migraine aura symptom. The existence of Lilliputian hallucinations of a migrainous nature is confirmed by four similar case reports reviewed from the migraine literature. The occurrence of similar Lilliputian hallucinations in the syndrome of peduncular hallucinosis, due to mesencephalic and/or thalamic lesions, supports the notion that the patient's recurrent Lilliputian hallucinations might have been aura symptoms of basilar migraine.     

Association of benign recurrent vertigo and migraine in 208 patients

The aim of this study was to determine the association of benign recurrent vertigo (BRV) and migraine, using standardized questionnaire-based interview of 208 patients with BRV recruited through a University Neurotology clinic. Of 208 patients with BRV, 180 (87%) met the International Classification of Headache Disorders 2004 criteria for migraine: 112 migraine with aura (62%) and 68 without aura (38%). Twenty-eight (13%) did not meet criteria for migraine. Among patients with migraine, 70% experienced headache, one or more auras, photophobia, or auditory symptoms with some or all of their vertigo attacks, meeting the criteria for definite migrainous vertigo. Thirty per cent never experienced migraine symptoms concurrent with vertigo attacks. These met criteria for probable migrainous vertigo. Among patients without migraine, 21% experienced either photophobia or auditory symptoms with some or all of their vertigo attacks; 79% experienced only isolated vertigo. The age of onset and duration of vertigo attacks did not differ significantly between patients with (34 ± 1.2 years) and patients without migraine (31 ± 3.0 years). In patients with migraine, the age of onset of migraine headache preceded the onset of vertigo attacks by an average of 14 years and aura preceded vertigo by 8 years. The most frequent duration of vertigo attacks was between 1 h and 1 day. Benign recurrent vertigo is highly associated with migraine, but a high proportion of patients with BRV and migraine never have migraine symptoms during their vertigo attacks. Other features such as age of onset and duration of vertigo are similar between patients with or without migraine.     

Retinal migraine reappraised

Retinal migraine is usually characterized by attacks of fully reversible monocular visual loss associated with migraine headache. Herein we summarize the clinical features and prognosis of 46 patients (six new cases and 40 from the literature) with retinal migraine based upon the International Classification of Headache Disorders-2 (ICHD-2) criteria. In our review, retinal migraine is most common in women in the second to third decade of life. Contrary to ICHD-2 criteria, most have a history of migraine with aura. In the typical attack monocular visual features consist of partial or complete visual loss lasting <1 h, ipsilateral to the headache. Nearly half of reported cases with recurrent transient monocular visual loss subsequently experienced permanent monocular visual loss. Although the ICHD-2 diagnostic criteria for retinal migraine require reversible visual loss, our findings suggest that irreversible visual loss is part of the retinal migraine spectrum, perhaps representing an ocular form of migrainous infarction. Based on this observation, the authors recommend migraine prophylactic treatment in an attempt to prevent permanent visual loss, even if attacks are infrequent. We also propose a revision to the ICHD-2 diagnostic criteria for retinal migraine.