PMC:4630240 / 1616-5814 JSONTXT

{"project":"TEST0","denotations":[{"id":"26527348-152-157-1500437","span":{"begin":376,"end":377},"obj":"[\"8800932\"]"},{"id":"26527348-155-160-1500438","span":{"begin":379,"end":380},"obj":"[\"15196299\"]"},{"id":"26527348-35-40-1500439","span":{"begin":418,"end":419},"obj":"[\"1525797\"]"},{"id":"26527348-229-234-1500440","span":{"begin":908,"end":909},"obj":"[\"11595007\"]"},{"id":"26527348-232-237-1500441","span":{"begin":911,"end":912},"obj":"[\"24042483\"]"},{"id":"26527348-94-99-1500442","span":{"begin":1009,"end":1010},"obj":"[\"2285266\", \"10328249\", \"11287655\"]"},{"id":"26527348-125-130-1500443","span":{"begin":1040,"end":1041},"obj":"[\"11706963\"]"},{"id":"26527348-136-142-1500444","span":{"begin":1188,"end":1190},"obj":"[\"20592202\"]"},{"id":"26527348-140-146-1500445","span":{"begin":1192,"end":1194},"obj":"[\"21416489\"]"},{"id":"26527348-22-28-1500446","span":{"begin":1644,"end":1646},"obj":"[\"23298223\"]"},{"id":"26527348-223-229-1500447","span":{"begin":1845,"end":1847},"obj":"[\"9549502\", \"17986271\", \"23565983\", \"23899115\"]"},{"id":"26527348-146-152-1500448","span":{"begin":1999,"end":2001},"obj":"[\"16492238\"]"},{"id":"26527348-232-238-1500449","span":{"begin":2236,"end":2238},"obj":"[\"10612640\"]"},{"id":"26527348-231-237-1500450","span":{"begin":2265,"end":2267},"obj":"[\"11817265\"]"},{"id":"26527348-141-147-1500451","span":{"begin":2706,"end":2708},"obj":"[\"15955037\"]"},{"id":"26527348-114-120-1500452","span":{"begin":2825,"end":2827},"obj":"[\"19393012\"]"},{"id":"26527348-146-152-1500453","span":{"begin":2857,"end":2859},"obj":"[\"26037553\"]"},{"id":"26527348-128-134-1500454","span":{"begin":3073,"end":3075},"obj":"[\"16996036\"]"},{"id":"26527348-132-138-1500455","span":{"begin":3077,"end":3079},"obj":"[\"17408578\"]"},{"id":"26527348-195-201-1500456","span":{"begin":3140,"end":3142},"obj":"[\"1618937\"]"},{"id":"26527348-127-133-1500457","span":{"begin":3272,"end":3274},"obj":"[\"1603349\"]"},{"id":"26527348-131-137-1500458","span":{"begin":3276,"end":3278},"obj":"[\"8857754\"]"},{"id":"26527348-116-122-1500459","span":{"begin":3874,"end":3876},"obj":"[\"17986271\"]"},{"id":"26527348-120-126-1500460","span":{"begin":3878,"end":3880},"obj":"[\"23565983\"]"}],"text":"Background\nMigraine with aura (MA) is defined as attacks of neurological symptoms that last no more than 60 min and may be followed or accompanied by headache (International Classification of Headache Disorders 3beta 2013). The most common aura symptoms are visual (e.g. scintillating scotoma), while sensory and aphasic auras are present in a smaller proportion of patients [1, 2]. According to Rasmussen and Olesen [3], 51 % of migraine auras are purely visual, while 4 % comprise sensory symptoms in addition to the visual ones and 6 % language disturbances in addition to visual and sensory disturbances.\nThe most likely cause of the migraine aura, Leão’s cortical spreading depression (CSD), consists of a brief neuronal depolarisation followed by a long-lasting wave of neuronal depression that often spreads postero-anteriorly in the occipital cortex and can reach the parietal and/or temporal lobes [4, 5]. Indirect evidence for CSD occurrence in migraine patients stems from functional neuroimaging [6–8] and electrophysiological [9] studies. Although in animal models CSD is able to activate peripheral and central trigeminovascular neurons that underlie the migraine headache [10, 11], knowledge is lacking on the possible relation of CSD to interictal neural alterations that may predispose to migraine attacks.\nDuring the last decade various research groups have demonstrated significant changes of bioelectrical activity in the visual cortex of migraine patients over the migraine cycle. In particular, cortical visual evoked potentials (VEPs) are used to infer the mass activity of visual cortical neurons. Most, though not all [12], VEP, recordings have shown that the brain of migraineurs with and without aura is characterized by an interictal deficit of habituation during stimulus repetition, and by its ictal normalization [13–16].\nIt was suggested that migraine with aura is a condition with a spectrum of clinical subtypes that likely differ in pathophysiological mechanisms [17]. Distinct electrophysiological abnormalities were especially found at the neuromuscular junction in patients suffering from complex neurological auras characterized by visual symptoms followed by sensorimotor and dysphasic symptoms [18] or from prolonged auras [19]. Using 1H-MR-spectroscopy, migraine patients with visual symptoms and at least one of paraesthesia, paresis, or dysphasia had a significant lactate increase in the visual cortex during sustained visual stimulation, while this was not the case in controls and patients with exclusive visual aura. In the latter group, however, lactate levels were already elevated at baseline and remained consistently high during the visual stimulation [20]. Besides its role as energy substrate of the brain, lactate acts as a neuromodulator and interacts with glutamate [21], GABA [22], and monoamines [23], which suggest that it is important in regulating the activity of cortical neurons. Lactate may increase to attenuate the electrical activity of excessively active neurons as observed in experimental models [22, 24, 25] and in healthy humans during sustained visual stimulation [26]. Considering these data and those obtained by NMR spectroscopy showing altered metabolic homeostasis of the migraineur’s brain [27, 28], it is of interest to verify whether activity of visual cortical neurons is increased in migraine patients suffering from complex auras respective to those experiencing pure visual symptoms. We decided therefore to compare amplitude and habituation of pattern reversal VEP in healthy volunteers, migraine patients with pure visual auras, and in patients with complex neurological auras including at least one of sensory and language symptoms in addition to visual disturbances. Considering the abovementioned NMR spectroscopy studies and our prior interictal VEP studies in migraine with aura [14, 15], we reasoned that subgroups of migraine with aura patients would show both common and specific neurophysiological abnormalities. We hypothesized that VEP amplitude would be higher in migraine with complex aura than in migraine with pure visual aura, while habituation would be equally deficient in both MA subgroups."}

{"project":"2_test","denotations":[{"id":"26527348-8800932-60555176","span":{"begin":376,"end":377},"obj":"8800932"},{"id":"26527348-15196299-60555177","span":{"begin":379,"end":380},"obj":"15196299"},{"id":"26527348-1525797-60555178","span":{"begin":418,"end":419},"obj":"1525797"},{"id":"26527348-11595007-60555179","span":{"begin":908,"end":909},"obj":"11595007"},{"id":"26527348-24042483-60555180","span":{"begin":911,"end":912},"obj":"24042483"},{"id":"26527348-2285266-60555181","span":{"begin":1009,"end":1010},"obj":"2285266"},{"id":"26527348-10328249-60555181","span":{"begin":1009,"end":1010},"obj":"10328249"},{"id":"26527348-11287655-60555181","span":{"begin":1009,"end":1010},"obj":"11287655"},{"id":"26527348-11706963-60555182","span":{"begin":1040,"end":1041},"obj":"11706963"},{"id":"26527348-20592202-60555183","span":{"begin":1188,"end":1190},"obj":"20592202"},{"id":"26527348-21416489-60555184","span":{"begin":1192,"end":1194},"obj":"21416489"},{"id":"26527348-23298223-60555185","span":{"begin":1644,"end":1646},"obj":"23298223"},{"id":"26527348-9549502-60555186","span":{"begin":1845,"end":1847},"obj":"9549502"},{"id":"26527348-17986271-60555186","span":{"begin":1845,"end":1847},"obj":"17986271"},{"id":"26527348-23565983-60555186","span":{"begin":1845,"end":1847},"obj":"23565983"},{"id":"26527348-23899115-60555186","span":{"begin":1845,"end":1847},"obj":"23899115"},{"id":"26527348-16492238-60555187","span":{"begin":1999,"end":2001},"obj":"16492238"},{"id":"26527348-10612640-60555188","span":{"begin":2236,"end":2238},"obj":"10612640"},{"id":"26527348-11817265-60555189","span":{"begin":2265,"end":2267},"obj":"11817265"},{"id":"26527348-15955037-60555190","span":{"begin":2706,"end":2708},"obj":"15955037"},{"id":"26527348-19393012-60555191","span":{"begin":2825,"end":2827},"obj":"19393012"},{"id":"26527348-26037553-60555192","span":{"begin":2857,"end":2859},"obj":"26037553"},{"id":"26527348-16996036-60555193","span":{"begin":3073,"end":3075},"obj":"16996036"},{"id":"26527348-17408578-60555194","span":{"begin":3077,"end":3079},"obj":"17408578"},{"id":"26527348-1618937-60555195","span":{"begin":3140,"end":3142},"obj":"1618937"},{"id":"26527348-1603349-60555196","span":{"begin":3272,"end":3274},"obj":"1603349"},{"id":"26527348-8857754-60555197","span":{"begin":3276,"end":3278},"obj":"8857754"},{"id":"26527348-17986271-60555198","span":{"begin":3874,"end":3876},"obj":"17986271"},{"id":"26527348-23565983-60555199","span":{"begin":3878,"end":3880},"obj":"23565983"}],"text":"Background\nMigraine with aura (MA) is defined as attacks of neurological symptoms that last no more than 60 min and may be followed or accompanied by headache (International Classification of Headache Disorders 3beta 2013). The most common aura symptoms are visual (e.g. scintillating scotoma), while sensory and aphasic auras are present in a smaller proportion of patients [1, 2]. According to Rasmussen and Olesen [3], 51 % of migraine auras are purely visual, while 4 % comprise sensory symptoms in addition to the visual ones and 6 % language disturbances in addition to visual and sensory disturbances.\nThe most likely cause of the migraine aura, Leão’s cortical spreading depression (CSD), consists of a brief neuronal depolarisation followed by a long-lasting wave of neuronal depression that often spreads postero-anteriorly in the occipital cortex and can reach the parietal and/or temporal lobes [4, 5]. Indirect evidence for CSD occurrence in migraine patients stems from functional neuroimaging [6–8] and electrophysiological [9] studies. Although in animal models CSD is able to activate peripheral and central trigeminovascular neurons that underlie the migraine headache [10, 11], knowledge is lacking on the possible relation of CSD to interictal neural alterations that may predispose to migraine attacks.\nDuring the last decade various research groups have demonstrated significant changes of bioelectrical activity in the visual cortex of migraine patients over the migraine cycle. In particular, cortical visual evoked potentials (VEPs) are used to infer the mass activity of visual cortical neurons. Most, though not all [12], VEP, recordings have shown that the brain of migraineurs with and without aura is characterized by an interictal deficit of habituation during stimulus repetition, and by its ictal normalization [13–16].\nIt was suggested that migraine with aura is a condition with a spectrum of clinical subtypes that likely differ in pathophysiological mechanisms [17]. Distinct electrophysiological abnormalities were especially found at the neuromuscular junction in patients suffering from complex neurological auras characterized by visual symptoms followed by sensorimotor and dysphasic symptoms [18] or from prolonged auras [19]. Using 1H-MR-spectroscopy, migraine patients with visual symptoms and at least one of paraesthesia, paresis, or dysphasia had a significant lactate increase in the visual cortex during sustained visual stimulation, while this was not the case in controls and patients with exclusive visual aura. In the latter group, however, lactate levels were already elevated at baseline and remained consistently high during the visual stimulation [20]. Besides its role as energy substrate of the brain, lactate acts as a neuromodulator and interacts with glutamate [21], GABA [22], and monoamines [23], which suggest that it is important in regulating the activity of cortical neurons. Lactate may increase to attenuate the electrical activity of excessively active neurons as observed in experimental models [22, 24, 25] and in healthy humans during sustained visual stimulation [26]. Considering these data and those obtained by NMR spectroscopy showing altered metabolic homeostasis of the migraineur’s brain [27, 28], it is of interest to verify whether activity of visual cortical neurons is increased in migraine patients suffering from complex auras respective to those experiencing pure visual symptoms. We decided therefore to compare amplitude and habituation of pattern reversal VEP in healthy volunteers, migraine patients with pure visual auras, and in patients with complex neurological auras including at least one of sensory and language symptoms in addition to visual disturbances. Considering the abovementioned NMR spectroscopy studies and our prior interictal VEP studies in migraine with aura [14, 15], we reasoned that subgroups of migraine with aura patients would show both common and specific neurophysiological abnormalities. We hypothesized that VEP amplitude would be higher in migraine with complex aura than in migraine with pure visual aura, while habituation would be equally deficient in both MA subgroups."}