Investigation of the relationship between thrombophilic disorders and brain white matter lesions in migraine with aura.

BACKGROUND: Migraine is associated with several genetic or acquired comorbidities. Studies conducted in recent years emphasize that the frequency of thrombophilia is high in migraine, especially migraine with aura (MA). Similarly, the presence of white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) scans has been associated with migraine for many years. OBJECTIVE: Based on the knowledge that both WMLs and thrombophilia variants are frequently observed in MA, we aimed to investigate whether there is a relationship between genetic thrombophilia and the presence of WMLs in these patients. METHODS: The levels of proteins S and C, antithrombin III activities, activated protein C (APC) resistance, antiphospholipid immunoglobulin G/immunoglobulin M (IgG/IgM) and anticardiolipin IgG/IgM antibodies were investigated in 66 MA patients between the ages of 18 and 49 years who presented no cardiovascular risk factors. The presence of WMLs and the Fazekas grade was determined from the brain magnetic resonance imaging (MRI) scans' T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequence taken from the patients. The rates of WMLs were compared in patients with and without thrombophilia. RESULTS: Thrombophilia was detected in 34.8% of the patients, and 27.3% were determined to have WMLs in brain MRI scans. The WMLs were detected in 23.3% of the patients without thrombophilia, in 34.8% of those with thrombophilia, and in 50% of the subjects with multiple thrombophilia disorders. Among the thrombophilia disorders, only APC resistance was significantly more common in patients with WMLs. CONCLUSION: The results of the present study showed that thrombophilia may be a mechanism that should be investigated in the etiology of increased WMLs in MA.

ANTECEDENTES: La migraña se asocia con una serie de comorbilidades genéticas o adquiridas. Los estudios realizados en los últimos años destacan que la frecuencia de trombofilia es elevada en la migraña, especialmente en la migraña con aura (MA). De manera similar, la presencia de lesiones de la sustancia blanca (LSB) en las imágenes por resonancia magnética (RM) del cerebro se ha asociado con la migraña hace muchos años. OBJETIVO: Con base en la información de que se suelen observar tanto LSB como variantes de la trombofilia en MA, nuestro objetivo fue investigar si existe una relación entre la trombofilia genética y la presencia de LSB en estos pacientes. MéTODOS: Se investigaron los niveles de proteína S y de proteína C, actividades de antitrombina III, resistencia a la proteína C activada (PCA), anticuerpos antifosfolípidos inmunoglobulina G/inmunoglobulina M (IgG/IgM) y anticuerpos anticardiolipina IgG/IgM en 66 pacientes con MA entre 18 y 49 años que no presentaban factores de riesgo cardiovascular. Se determinaron la presencia de LSB y el grado de Fazekas a partir de imágenes por RM del cerebro en la secuencia ponderada en T2 y recuperación de la inversión atenuada de fluido (fluid-attenuated inversion recovery, FLAIR, en inglés) obtenidas de los pacientes. Se compararon las tasas de LSB en pacientes con y sin trombofilia. RESULTADOS: Se detectó trombofilia en el 34,8% de los pacientes y LSB en el 27,3%. Las LSB estuvieron presentes en el 23,3% de los pacientes sin trombofilia, en el 34,8% de los que tenían trombofilia, y en el 50% de los que tenían múltiples trastornos trombofílicos. La resistencia a la PCA fue significativamente más común en aquellos pacientes con LSB. CONCLUSIóN: Los resultados del presente estudio mostraron que la trombofilia puede ser un mecanismo que debe investigarse en la etiología del aumento de LSB en MA.

Migraine aura discrimination using machine learning: an fMRI study during ictal and interictal periods.

Functional magnetic resonance imaging (fMRI) studies on migraine with aura are challenging due to the rarity of patients with triggered cases. This study optimized methodologies to explore differences in ictal and interictal spatiotemporal activation patterns based on visual stimuli using fMRI in two patients with unique aura triggers. Both patients underwent separate fMRI sessions during the ictal and interictal periods. The Gaussian Process Classifier (GPC) was used to differentiate these periods by employing a machine learning temporal embedding approach and spatiotemporal activation patterns based on visual stimuli. When restricted to visual and occipital regions, GPC had an improved performance, with accuracy rates for patients A and B of roughly 86-90% and 77-81%, respectively (p < 0.01). The algorithm effectively differentiated visual stimulation and rest periods and identified times when aura symptoms manifested, as evident from the varying predicted probabilities in the GPC models. These findings contribute to our understanding of the role of visual processing and brain activity patterns in migraine with aura and the significance of temporal embedding techniques in examining aura phenomena. This finding has implications for diagnostic tools and therapeutic techniques, especially for patients suffering from aura symptoms.

Retinal nerve fiber layer, ganglion cell complex, and choroidal thicknesses in migraine.

PURPOSE: To evaluate the thicknesses of the peripapillary retinal nerve fiber layer (RNFL), ganglion cell complex (GCL), and choroid layer using spectral domain optical coherence tomography (SD-OCT) for investigating the effects of vascular changes on the eye and optic nerve in patients who have migraine with aura. METHODS: Forty-five patients who had migraine with aura (migraine group) and 45 healthy individuals (control group) were enrolled in the study. Age, gender, duration after migraine diagnosis, intraocular pressure, and axial length measurements were recorded in each case. RNFL, GCL, and choroid layer thicknesses were measured using SD-OCT in all participants. RESULTS: The mean age was 36.1 ± 6.7 (20-45) years in the migraine group and 35.7 ± 8.6 (19-45) years in the control group. There was no significant difference in the RNFL thicknesses of the temporal and nasal quadrants (p >0.05). The RNFL thicknesses of the superior and inferior quadrants were significantly lower in the migraine group compared with those in the control group (p =0.001, p <0.01, respectively). Measurements for the superior and inferior GCL were not significantly different between the groups (p >0.05). Subfoveal, temporal, and nasal choroidal thickness measurements at 500 µm, 1000 µm, and 1500 µm were significantly lower in the migraine group than in the control group (p =0.001; p <0.01, respectively). CONCLUSIONS: Compared with the controls, the RNFL and choroid layer were determined to be thinner in patients who had chronic migraine with aura.

Retinal nerve fiber layer, ganglion cell complex, and choroidal thicknesses in migraine / Espessuras da camada de fibras nervosas retinianas, complexo de células ganglionares e coroide na enxaqueca

ABSTRACT Purpose: To evaluate the thicknesses of the peripapillary retinal nerve fiber layer (RNFL), ganglion cell complex (GCL), and choroid layer using spectral domain optical coherence tomography (SD-OCT) for investigating the effects of vascular changes on the eye and optic nerve in patients who have migraine with aura. Methods: Forty-five patients who had migraine with aura (migraine group) and 45 healthy individuals (control group) were enrolled in the study. Age, gender, duration after migraine diagnosis, intraocular pressure, and axial length measurements were recorded in each case. RNFL, GCL, and choroid layer thicknesses were measured using SD-OCT in all participants. Results: The mean age was 36.1 ± 6.7 (20-45) years in the migraine group and 35.7 ± 8.6 (19-45) years in the control group. There was no significant difference in the RNFL thicknesses of the temporal and nasal quadrants (p >0.05). The RNFL thicknesses of the superior and inferior quadrants were significantly lower in the migraine group compared with those in the control group (p =0.001, p <0.01, respectively). Measurements for the superior and inferior GCL were not significantly different between the groups (p >0.05). Subfoveal, temporal, and nasal choroidal thickness measurements at 500 µm, 1000 µm, and 1500 µm were significantly lower in the migraine group than in the control group (p =0.001; p <0.01, respectively). Conclusions: Compared with the controls, the RNFL and choroid layer were determined to be thinner in patients who had chronic migraine with aura.

RESUMO Objetivo: Avaliar as espessuras de camada peripapilar de fibras nervosas retinianas (RNFL), complexo de células ganglionares (GCL) e da coroide utilizando a tomografia de coerência óptica de domínio espectral (SD-OCT), a fim de investigar os efeitos das alterações vasculares no olho e nervo óptico em pacientes que apresentam enxaqueca com aura. Métodos: Quarenta e cinco pacientes que apresentavam enxaqueca com aura (grupo enxaqueca) e 45 indivíduos saudáveis (grupo controle) foram incluídos no estudo. Idade, sexo, duração da enxaqueca, pressão intraocular e medidas de comprimento axial foram registrados em cada caso. Medidas da RNFL, GCL e espessuras da coroide foram obtidas com SD-OCT em todos os participantes. Resultados: A média da idade foi de 36,1 ± 6,7 (20-45) anos no grupo enxaqueca e 35,7 ± 8,6 (19-45) anos no grupo controle. Não houve diferença significativa em espessuras RNFL nos quadrantes temporal e nasal (p>0,05). A espessura da RNFL nos quadrantes superiores e inferiores foram significativamente menores no grupo de enxaqueca em comparação ao grupo controle (p=0,001; p<0,01). Medidas da GCL superior e inferior não mostraram diferença significativa entre os grupos (p>0,05). Espessuras subfoveais, temporais e nasais da coroide (CT) a 500 µm, 1000 µm e 1500 µm foram significativamente menores no grupo de enxaqueca em relação ao grupo controle (p=0,001; p<0,01). Conclusões: Comparados aos controles, as espessuras da RNFL e coroide foram mais finas em pacientes que apresentavam enxaqueca crônica com aura.

Prevalence of patent foramen ovale in migraine patients with and without aura compared with stroke patients. A transcranial Doppler study.

The aim of this study was to investigate the prevalence of patent foramen ovale (PFO) in a consecutive unselected cohort of migraine patients (with and without aura) and compare it with a group of ischaemic young and elderly stroke patients. One hundred and forty-one migraine patients were compared with 330 stroke patients (130 young patients; 200 elderly patients) selected from our hospital stroke data bank. PFO was assessed with transcranial Doppler sonography with i.v. injection of agitated saline. The prevalence of PFO was 51.7% in migraine with aura (MA) patients, 33.7% in migraine without aura (MoA) patients, 33.8% in young stroke patients and 20.5% in elderly stroke patients (P < 0.001). The prevalence of PFO in cryptogenic stroke in young and elderly stroke patients was, respectively, 41.1% and 25% (P = 0.04). The difference between MA and MoA patients was significant (odds ratio = 2.1). The prevalence of PFO in MA patients is higher than in MoA patients and in young cryptogenic stroke patients.

Cerebral vasoreactivity in Andeans and headache at sea level.

Headache is common in Cerro de Pasco (CP), Peru (altitude 4338 m) and was present in all patients with chronic mountain sickness (CMS) in CP reported here. Forty-seven percent of inhabitants report headache. Twenty-four percent of men have migraine with aura, with an average of 65 attacks a year. We assessed vasoreactivity of the cerebral vessels to CO2 by rebreathing and to NO by the administration of isosorbite dinitrate (IDN), a nitric oxide (NO) donor, using transcranial Doppler ultrasound in the middle cerebral artery (MCA) in natives of CP, some of whom suffered from CMS. We repeated the measurements in Lima (altitude 150 m) in the same subjects within 24 h of arrival. Vasodilatation in the middle cerebral artery supply territory in response to CO2 and NO, both physiologic vasodilators, is defective in Andean natives at altitude and in the same subjects at sea level. Incapacitating migraine can occur with impaired cerebral vasoreactivity to physiologic vasodilators. We propose that susceptibility to migraine might depend in part on gene expression with consequent alterations of endothelial function.

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.