Migraine Aura Research Articles

Associations between migraine and major cardiovascular events in type 2 diabetes mellitus.

Migraine is one of the most common primary headache disorders and a well-known risk factor for cardiovascular disorders. We aimed to investigate the association between migraine and major cardiovascular outcomes, including myocardial infarction (MI), ischemic stroke (IS), and cardiovascular death (CVD) in people with type 2 diabetes. A total of 2,229,598 people from the nationwide Korean National Health Insurance Service database with type 2 diabetes but without a previous history of MI and IS were included in this study. We identified patients over 20years of age with migraine using the claim data of International Statistical Classification of Diseases Related Health Problems, Tenth Revision (ICD-10) code G43. The patients with migraine were divided according to their migraine aura status. Migraine was present in 6.3% of the study population. Cases observed for MI, IS, CVD, and all-cause death were 2.6%, 3.6%, 5.9%, and 7.9%, respectively. The diagnosis of migraine was significantly associated with an increased risk of MI, IS, and CVD. The results remained significant after adjusting for covariates, including age, sex, body mass index, alcohol intake, smoking habits, physical activity, economic status, hypertension history, dyslipidemia, and duration of type 2 diabetes (MI, adjusted hazard ratio [aHR]: 1.182, 95% confidence interval [CI]: 1.146-1.219; IS, aHR: 1.111, 95% CI 1.082-1.14; CVD, aHR: 1.143, 95% CI 1.12-1.167). In particular, the presence of aura was associated with a higher risk of MI development compared to the non-aura group. The difference became more prominent with progressing age. In this nationwide population-based study, people with type 2 diabetes and migraines were found to be at a significantly higher risk for major cardiovascular events, including MI, IS, and CVD. The risk of MI and CVD significantly increased with the presence of aura symptoms among patients with migraine.

Cortical pain induced by optogenetic cortical spreading depression: from whole brain activity mapping

BackgroundCortical spreading depression (CSD) is an electrophysiological event underlying migraine aura. Traditional CSD models are invasive and often cause injuries. The aim of the study was to establish a minimally invasive optogenetic CSD model and identify the active networks after CSD using whole-brain activity mapping.MethodsCSD was induced in mice by light illumination, and their periorbital thresholds and behaviours in the open field, elevated plus-maze and light-aversion were recorded. Using c-fos, we mapped the brain activity after CSD. The whole brain was imaged, reconstructed and analyzed using the Volumetric Imaging with Synchronized on-the-fly-scan and Readout technique. To ensure the accuracy of the results, the immunofluorescence staining method was used to verify the imaging results.ResultsThe optogenetic CSD model showed significantly decreased periorbital thresholds, increased facial grooming and freezing behaviours and prominent light-aversion behaviours. Brain activity mapping revealed that the somatosensory, primary sensory, olfactory, basal ganglia and default mode networks were activated. However, the thalamus and trigeminal nucleus caudalis were not activated.ConclusionsOptogenetic CSD model could mimic the behaviours of headache and photophobia. Moreover, the optogenetic CSD could activate multiple sensory cortical regions without the thalamus or trigeminal nucleus caudalis to induce cortical pain.

Lack of Habituation in Migraine Patients Based on High-Density EEG Analysis Using the Steady State of Visual Evoked Potential

Migraine is a periodic disorder in which a patient experiences changes in the morphological and functional brain, leading to the abnormal processing of repeated external stimuli in the inter-ictal phase, known as the habituation deficit. This is a significant feature clinically of migraine in both two types with aura or without aura and plays an essential role in studying pathophysiological differences between these two groups. Several studies indicated that the reason for migraine aura is cortical spreading depression (CSD) but did not clarify its impact on migraine without aura and lack of habituation. In this study, 22 migraine patients (MWA, N = 13), (MWoA, N = 9), and healthy controls (HC, N = 19) were the participants. Participants were exposed to the steady state of visual evoked potentials also known as (SSVEP), which are the signals for a natural response to the visual motivation at four Hz or six Hz for 2 s followed by the inter-stimulus interval that varies between 1 and 1.5 s. The order of the temporal frequencies was randomized, and each temporal frequency was shown 100 times. We recorded from 128 customized electrode locations using high-density electroencephalography (HD-EEG) and measured amplitude and habituation for the N1-P1 and P1-N2 from the first to the sixth blocks of 100 sweep features in patients and healthy controls. Using the entropy, a decrease in amplitude and SSVEP N1-P1 habituation between the first and the sixth block appeared in both MWA and MWoA (p = 0.0001, Slope = -0.4643), (p = 0.065, Slope = 0.1483), respectively, compared to HC. For SSVEP P1-N2 between the first and sixth block, it is varied in both MWA (p = 0.0029, Slope = -0.3597) and MWoA (p = 0.027, Slope = 0.2010) compared to HC. Therefore, migraine patients appear amplitude decrease and habituation deficit but with different rates between MWA, and MWoA compared to HCs. Our findings suggest this disparity between MWoA and MWA in the lack of habituation and amplitude decrease in the inter-ictal phase has a close relationship with CSD. In light of the fact that CSD manifests during the inter-ictal phase of migraine with aura, which is when migraine seizures are most likely to occur, multiple researchers have lately reached this conclusion. This investigation led us to the conclusion that CSD during the inter-ictal phase and migraine without aura are associated. In other words, even if previous research has not demonstrated it, CSD is the main contributor to both types of migraine (those with and without aura).

Sustained Effects of CGRP Blockade on Cortical Spreading Depolarization-Induced Alterations in Facial Heat Pain Threshold, Light Aversiveness, and Locomotive Activity in the Light Environment.

A migraine is clinically characterized by repeated headache attacks that entail considerable disability. Many patients with migraines experience postdrome, the symptoms of which include tiredness and photophobia. Calcitonin gene-related peptide (GGRP) is critically implicated in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, sensitizes the trigeminovascular system. In our previous study, CSD caused hypomotility in the light zone and tendency for photophobia at 72 h, at which time trigeminal sensitization had disappeared. We proposed that this CSD-induced disease state would be useful for exploring therapeutic strategies for migraine postdrome. In the present study, we observed that the CGRP receptor antagonist, olcegepant, prevented the hypomotility in the light zone and ameliorated light tolerability at 72 h after CSD induction. Moreover, olcegepant treatment significantly elevated the threshold for facial heat pain at 72 h after CSD. Our results raise the possibility that CGRP blockade may be efficacious in improving hypoactivity in the light environment by enhancing light tolerability during migraine postdrome. Moreover, our data suggest that the CGRP pathway may lower the facial heat pain threshold even in the absence of overt trigeminal sensitization, which provides an important clue to the potential mechanism whereby CGRP blockade confers migraine prophylaxis.

Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD

Spreading depolarization (SD) occurs in a plethora of clinical conditions including migraine aura, delayed ischemia after subarachnoid hemorrhage and malignant hemispheric stroke. It describes waves of near-breakdown of ion homeostasis, particularly Na+ homeostasis in brain gray matter. SD induces tone alterations in resistance vessels, causing either hyperperfusion in healthy tissue; or hypoperfusion (inverse hemodynamic response = spreading ischemia) in tissue at risk. Observations from mice with genetic dysfunction of the ATP1A2-encoded α2-isoform of Na+/K+-ATPase (α2NaKA) suggest a mechanistic link between (1) SD, (2) vascular dysfunction, and (3) salt-sensitive hypertension via α2NaKA. Thus, α2NaKA-dysfunctional mice are more susceptible to SD and show a shift toward more inverse hemodynamic responses. α2NaKA-dysfunctional patients suffer from familial hemiplegic migraine type 2, a Mendelian model disease of SD. α2NaKA-dysfunctional mice are also a genetic model of salt-sensitive hypertension. To determine whether SD thresholds and hemodynamic responses are also altered in other genetic models of salt-sensitive hypertension, we examined these variables in stroke-prone spontaneously hypertensive rats (SHRsp). Compared with Wistar Kyoto control rats, we found in SHRsp that electrical SD threshold was significantly reduced, propagation speed was increased, and inverse hemodynamic responses were prolonged. These results may have relevance to both migraine with aura and stroke.

Narrative review of peripheral nerve blocks for the management of headache.

To provide an overview of the current available literature on peripheral nerve blocks for the management of migraine and other headache disorders in adults. Peripheral nerve blocks have been commonly performed in the headache practice for migraine, cluster headache, occipital neuralgia, and other headache disorders, despite a paucity of evidence supporting their use historically. In the past decade, there has been an effort to explore the efficacy and safety of peripheral nerve blocks for the management of headache, with the greatest interest centered around greater occipital blocks. We performed a search in PubMed using key words including "occipital nerve blocks," "peripheral nerve blocks," "occipital nerve," "migraine," "cluster headache," and "neuralgia." We reviewed the randomized controlled trials (RCTs), observational studies, and case series, and summarized the anatomy, techniques, and the evidence for the use of peripheral nerve blocks in different headache disorders, with particular focus on available RCTs. Case reports were included for a detail review of adverse events. Of 12 RCTs examining the use of greater occipital nerve blocks for migraine, all but one demonstrate efficacy with reduction in headache frequency, intensity, and/or duration compared to placebo. Studies have not demonstrated a difference in clinical outcomes with the use of corticosteroids for nerve blocks compared to blocks with local anesthetic in the treatment of migraine. There are two RCTs supporting the use of greater occipital blockade for cluster headache, both showing benefit of suboccipitally injected corticosteroid. One RCT suggests benefit of greater occipital nerve blocks for cervicogenic headache. Observational studies and case series/reports show that greater occipital nerve block may be effective in prolonged migraine aura, status migrainosus, post-dural puncture headache, and occipital neuralgia. Overall, peripheral nerve blocks are well tolerated. Serious side effects are rare but have been reported, including acute cerebellar syndrome and infection. Peripheral nerve blocks, especially occipital nerve blocks, are a viable treatment option for migraine and may be helpful in cluster headache as a transitional therapy or rescue therapy. Additional prospective studies are needed to investigate the efficacy and safety of occipital nerve blocks for long-term migraine prevention, as well as for other headache disorders, such as occipital neuralgia.

Migraine aura-like symptoms at onset of stroke and stroke-like symptoms in migraine with aura.

Background and objectivesIn general, suddenly occurring neurological deficits, i.e., negative neurological symptoms, are considered symptoms of focal cerebral ischemia, while positive irritative symptoms with gradual onset are viewed as the characteristics of migraine aura. Nevertheless, cortical spreading depolarization, the pathophysiological basis of migraine aura, has also been observed in acute ischemic stroke. The aim of our study was to determine the frequency of migraine aura-like symptoms at ischemic stroke onset and stroke-like symptoms in migraine with aura.MethodsWe interviewed 350 consecutive patients with ischemic stroke and 343 with migraine with aura using a structured questionnaire. Stroke diagnosis was confirmed by imaging, and migraine with aura was diagnosed according to the current criteria of the International Headache Society. Patients with wake-up strokes or severe cognitive deficits that precluded a useful interview were excluded from the study.ResultsSeventy-eight patients with stroke (22.3%) reported visual symptoms, 145 (41.4%) sensory symptoms, 197 (56.3%) a paresis, and 201 patients (57.4%) more than one symptom, compared to 326 migraine patients with aura (95%) with visual symptoms (P < 0.001), 175 (51%) with sensory symptoms (p = 0.011), 50 (14.6%) with paresis (P < 0.001), and 211 (61.5%) with more than one symptom (p = 0.27). Among patients with stroke, migraine-like symptoms were frequent: 36 patients (46.2%) with visual disturbance and 78 (53.8%) with sensory symptoms experienced irritative sensations. Paresis-onset in stroke lasted longer than 5 min in 43 patients (21.8%). Spreading of sensory and motor symptoms occurred in 37 (25.5%) and 37 (18.8%) patients, respectively. Stroke-like negative symptoms in migraine with aura occurred in 39 patients (12%) with visual symptoms, in 55 (31.4%) with sensory symptoms, and paresis appeared suddenly in 14 patients (28%). More than one symptom in succession occurred in 117 patients with stroke (58.2%) and in 201 migraine with aura patients (95.3%; P < 0.001).ConclusionMany patients with stroke experience migraine-like symptoms at stroke onset, and many migraine with aura patients have stroke-like symptoms. Though overall the symptom frequencies of the two groups are significantly different, clarifying the differential diagnosis in an individual patient requires additional history elements, physical findings, or results of ancillary investigations.

Non-aura visual disturbance with high visual aura rating scale scores has stronger association with migraine chronification than typical aura.

To investigate the clinical correlates of visual symptoms in patients with migraine. Patients with migraine that attended our headache clinics were enrolled. Headache profiles, disability, and comorbidities were acquired with structured questionnaires. A semi-structured visual phenomenon questionnaire was also used to assess the characteristics of visual symptoms, including visual aura in patients with migraine with aura and transient visual disturbance in patients with migraine without aura. Headache specialists interviewed with the participants for the ascertainment of diagnosis and verification of the questionnaires. Migraine with aura patients with visual aura (n = 743, female/male = 2.3, mean age: 34.7 ± 12.2 years) and migraine without aura patients with non-aura transient visual disturbance (n = 1,808, female/male = 4.4, mean age: 39.4 ± 12.6 years) were enrolled. Patients with transient visual disturbance had higher headache-related disability and more psychiatric comorbidities. Chronic migraine was more common in migraine without aura than migraine with aura patients (41.9% vs. 11.8%, OR = 5.48 [95% CI: 4.33-7.02], p < 0.001). The associations remained after adjusting confounding factors. Presence of non-aura transient visual disturbance may suggest a higher migraine-related disability and is linked to higher risk of chronic migraine than typical migraine aura in migraine patients. Further studies are needed to elucidate the potential mechanism.

Pathophysiological crosstalk between migraine aura and epilepsy: Effect of lomerizine hydrochloride

AbstractA 29‐year‐old woman previously diagnosed with both migraine with aura and epilepsy visited our hospital complaining of unusual headaches. The prodromal symptoms changed from typical scintillating scotoma to short‐lasting moving lights against deja‐vu scenery. Then, loss of consciousness and urinary incontinence after headaches, and even generalized convulsion began to occur. Lomerizine hydrochloride decreased her headache attacks, urinary incontinence, loss of consciousness, and seizure. We considered her headache changed from migraine with typical aura to post‐ictal headache. Lomerizine hydrochloride may have alleviated epilepsy in addition to migraine.

Recurrent Monocular Vision Loss In A Collegiate Rower

HISTORY 21 yo F rower presenting with second episode of monocular vision loss in the last year. Her first episode in 9/2020 occurred when she was in training room doing neck rehab, when she experienced a curtain phenomenon over the peripheral vision in her right eye for about 30 minutes before spontaneous resolution, with some residual floaters and flashes afterward. Her workup for that episode is included below. She returns with recurrent symptoms. She was getting ready for practice when she experienced a “vertical cut” to her lateral right visual field. It lasted for about an hour and gradually improved. She states the medial aspect of her vision of right eye was blurry. PHYSICAL EXAMINATION: Physical exam including full neuro exam are non-focal. Fundoscopic exam after her first episode with a white area at the right inferior disc. Unchanged fundoscopic exam after this episode. DIFFERENTIAL DIAGNOSIS: 1. TIA or CVA 2. retinal arterial ischemia 3. retinal vein occlusion 4. retinal detachment 5. ocular migraine 6. vasculitis TEST AND RESULTS: 1. Visual fields normal 1. Lab findings included iron deficiency, TSH of 0.24 and CRP of 4.0 which both improved to normal on recheck. 2. EKG with sinus tachycardia previously, now shows NSR with sinus arrythmia. 3. TTE w bubble showed moderate right-to-left shunt and LA enlargement. Normal LVEF. No LV thrombus seen. TEE shows focal aneurysmal interatrial septum with transient bowing into the LA, and small R-L shunt consistent with small PFO. 4. Event monitor overall unremarkable, mostly sinus rhythm with first degree AV block and rare ectopy. 5. MR Head and Neck with and w/o contrast showed normal brain and orbits. 6. OCT of the optic nerves OU was normal FINAL WORKING DIAGNOSIS: Migraine aura without headache TREATMENT AND OUTCOMES: The athlete underwent a PFO closure after the cardiac workup following her first event. She was initiated on dual antiplatelet therapy, de-escalated to ASA daily before her repeat episode this year. She was put back on DAPT as a precaution. She has been stable without recurrence. Given the stable retinal lesion on exam, this was decided more likely to be a myelinated nerve fiber and not a cotton wool spot. She was referred to hematology to rule out coagulopathy and will follow through with this appointment soon.

Natural course of visual snow syndrome: a long-term follow-up study.

Visual snow syndrome is characterized by a continuous visual disturbance resembling a badly tuned analogue television and additional visual and non-visual symptoms causing significant disability. The natural course of visual snow syndrome has not hitherto been studied. In this prospective longitudinal study, 78 patients with the diagnosis of visual snow syndrome made in 2011 were re-contacted in 2019 to assess symptom evolution using a semi-structured questionnaire. Forty patients (51% of 78) were interviewed after 84 ± 5 months (mean ± SD). In all patients, symptoms had persisted. Visual snow itself was less frequently rated as the most disturbing symptom (72 versus 42%, P = 0.007), whereas a higher proportion of patients suffered primarily from entopic phenomena (2 versus 17%, P = 0.024). New treatment was commenced in 14 (35%) patients, of whom in seven, visual snow syndrome was ameliorated somewhat. Three (7%) experienced new visual migraine aura without headache, and one (2%) had new migraine headache. There were no differences in the levels of anxiety and depression measured by the Patient Health Questionnaire 8 and the Generalized Anxiety Disorder Scale 7. Thirty-eight patients (49%) were lost to follow-up. In visual snow syndrome, symptoms can persist over 8 years without spontaneous resolution, although visual snow itself might become less bothersome.

Clinical Diagnosis and Magnetic Resonance Imaging in Patients With Transient and Minor Neurological Symptoms: A Prospective Cohort Study.

Background:The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or minor stroke.Methods:Cohort of participants with transient or minor neurological symptoms from emergency and outpatient settings. Clinicians at different levels of training gave each participant a diagnostic probability (probable when TIA/stroke was the most likely differential diagnosis; possible when TIA/stroke was not the most likely differential diagnosis; or uncertain when diagnostic probability could not be given) before 1.5 or 3T brain MRI ≤5 days from onset. Post hoc, each clinical syndrome was defined blind to MRI findings as National Institute of Neurological Disorders and Stroke criteria TIA/stroke; International Headache Society criteria migraine aura; non-TIA focal symptoms; or nonfocal symptoms. MRI evidence of acute ischemia was defined by 2 reads of MRI. Stroke was ascertained for at least 90 days and up to 18 months after recruitment.Results:Two hundred seventy-two participated (47% female, mean age 60, SD 14), 58% with MRI ≤2 days of onset. Most (92%) reported focal symptoms. MR evidence of acute ischemia was found, for stroke/TIA clinical probabilities of probable 23 out of 75 (31% [95% CI, 21%–42%]); possible 26 out of 151 (17% [12%–24%]); and uncertain 9 out of 43, (20% [10%–36%]). MRI evidence of acute ischemia was found in National Institute of Neurological Disorders and Stroke criteria TIA/stroke 40 out of 95 (42% [32%–53%]); migraine aura 4 out of 38 (11% [3%–25%]); non-TIA focal symptoms 16 out of 99 (16% [10%–25%]); and no focal features 1 out of 29 (3% [0%–18%]). After MRI, a further 14 (5% [95% CI, 3–8]) would be treated with an antiplatelet drug compared with treatment plan before MRI. By 18 months, a new ischemic stroke occurred in 9 out of 61 (18%) patients with MRI evidence of acute ischemia and 2 out of 211 (1%) without (age-adjusted hazard ratio, 13 [95% CI, 3–62]; P<0.0001).Conclusions:MRI evidence of acute brain ischemia was found in about 1 in 6 transient or minor neurological symptoms patients with a nonstroke/TIA initial diagnosis or uncertain diagnosis. Methods to determine the clinical and cost-effectiveness of MRI are needed in this population.

Visual snow: A systematic review and a case series.

Visual Snow Syndrome is a recently recognized neurological condition presenting, continuous, tiny dots across the entire visual field, accompanied by nyctalopia, photophobia and palinopsia that persist for months. It may be part of migraine aura spectrum, yet its definition is still questionable. Diagnostic criteria for Visual Snow Syndrome are included in the supplemental material of ICHD-3. We aimed to summarize recent data to improve the understanding of Visual Snow Syndrome. After presenting four new cases, we conducted a PRISMA systematic search in PubMed/MEDLINE and Embase databases using the keyword "visual snow" with specific inclusion and exclusion criteria. From the 855 articles identified 30 were included for the qualitative analysis. These reports covered five aspects related to Visual Snow Syndrome: epidemiology, clinical features, comorbidities, pathophysiology, and treatment. We found limited data concerning Visual Snow Syndrome's epidemiology (one study). Clinical presentation (22 articles) and the comorbidities (migraine with aura and tinnitus most often, five reports) are described in detail. The pathophysiology of Visual Snow Syndrome is only approached with hypotheses, but several neuroimaging studies have been identified (seven articles). Treatment is based on single case reports only. Data for Visual Snow Syndrome are few and not strong enough to support Visual Snow Syndrome as a medical identity. Further investigation is needed.

Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia

Migraine is one of the most common pain disorders and causes disability in millions of people every year. Delta opioid receptors (DOR) have been identified as a novel therapeutic target for migraine and other headache disorders. DORs are present in both peripheral and central regions and it is unclear which receptor populations regulate migraine-associated effects. The aim of this study was to determine if DOR expressed in peripheral nociceptors regulates headache associated endpoints and the effect of delta agonists within these mouse models. We used a conditional knockout, in which DOR was selectively deleted from Nav1.8 expressing cells. Nav1.8-DOR mice and loxP control littermates were tested in models of chronic migraine-associated allodynia, opioid-induced hyperalgesia, migraine-associated negative affect, and aura. Nav1.8-DOR and loxP mice had comparable effect sizes in all of these models. The anti-allodynic effect of the DOR agonist, SNC80, was slightly diminished in the nitroglycerin model of migraine. Intriguingly, in the OIH model the peripheral effects of SNC80 were completely lost in Nav1.8-DOR mice while the cephalic effects remained intact. Regardless of genotype, SNC80 continued to inhibit conditioned place aversion associated with nitroglycerin and decreased cortical spreading depression events associated with migraine aura. These results suggest that DOR in Nav1.8-expressing nociceptors do not critically regulate the anti-migraine effects of delta agonist; and that brain-penetrant delta agonists would be a more effective drug development strategy.

Altered Cortical Trigeminal Fields Excitability by Spreading Depolarization Revealed with in Vivo Functional Ultrasound Imaging Combined with Electrophysiology.

Spreading depolarization, usually termed cortical spreading depression has been proposed as the pathophysiological substrate of migraine aura and as an endogenous trigger of headache pain. The links between neurovascular coupling and cortical craniofacial nociceptive activities modulated by SD were assessed by combining in vivo local field potential (LFP) recordings in the primary somatosensory cortex (S1) with functional ultrasound imaging of S1 and caudal insular (INS) cortices of anesthetized male rats. A single SD wave triggered in the primary visual cortex elicited an ipsilateral, quadriphasic hemodynamic and electrophysiological response in S1 with an early phase consisting of concomitant increases of relative cerebral blood volume (rCBV) and LFPs. A transient hypoperfusion was then correlated with the beginning of the neuronal silence, followed by a strong increase of rCBV, whereas synaptic activities remained inhibited.LFPs and rCBV recovery period was followed by a progressive increase in S1 and INS baseline activities and facilitation of cortical responses evoked by periorbital cutaneous receptive field stimulation. Sensitization of cortical ophthalmic fields by SD was bilateral, occurred with precise spatiotemporal profiles, and was significantly reduced by pretreatment with an NMDA antagonist. Combined high-resolution assessing of neurovascular coupling and electrophysiological activities has revealed a useful preclinical tool for deciphering central sensitization mechanisms involved in migraine attacks.SIGNIFICANCE STATEMENT A crucial unsolved issue is whether visual aura and migraine headache are parallel or sequential processes. Here, we show that a single spreading depolarization wave triggered from the primary visual cortex is powerful enough to elicit progressive, sustained increases of hemodynamic and sensory responses to percutaneous periorbital noxious stimuli recorded in S1 and insular ophthalmic fields. Sensitization of cortical ophthalmic fields by SD was bilateral, occurred with precise spatiotemporal profiles, and was significantly reduced by pretreatment with an NMDA antagonist. Combined high-resolution assessing of neurovascular coupling and electrophysiological activities has revealed a useful preclinical tool for deciphering central sensitization mechanisms involved in migraine attacks.

Migraine and peripheral pain models show differential alterations in neuronal complexity.

ObjectiveOur laboratory has recently shown that there is a decrease in neuronal complexity in head pain processing regions in mouse models of chronic migraine‐associated pain and aura. Importantly, restoration of this neuronal complexity corresponds with anti‐migraine effects of known and experimental pharmacotherapies. The objective of the current study was to expand this work and examine other brain regions involved with pain or emotional processing. We also investigated the generalizability of our findings by analyzing neuronal cytoarchitectural changes in a model of complex regional pain syndrome (CRPS), a peripheral pain disorder.MethodsWe used the nitroglycerin (NTG) model of chronic migraine‐associated pain in which mice receive 10 mg/kg NTG every other day for 9 days. Cortical spreading depression (CSD), a physiological corelate of migraine aura, was evoked in anesthetized mice using KCl. CRPS was induced by tibial fracture followed by casting. Neuronal cytoarchitecture was visualized with Golgi stain and analyzed with Simple Neurite Tracer.ResultsIn the NTG model, we previously showed decreased neuronal complexity in the trigeminal nucleus caudalis (TNC) and periaqueductal gray (PAG). In contrast, we found increased neuronal complexity in the thalamus and no change in the amygdala or caudate putamen in this study. Following CSD, we observed decreased neuronal complexity in the PAG, in line with decreases in the somatosensory cortex and TNC reported with this model previously. In the CRPS model there was decreased neuronal complexity in the hippocampus, as reported by others; increased complexity in the PAG; and no change within the somatosensory cortex.ConclusionsCollectively these results demonstrate that alterations in neuronal complexity are a feature of both chronic migraine and chronic CRPS. However, each type of pain presents a unique cytoarchitectural signature, which may provide insight on how these pain states differentially transition from acute to chronic conditions.

From spreading depolarization to epilepsy with neuroinflammation: The role of CGRP in cortex

CGRP release plays a major role in migraine pain by activating the trigeminal pain pathways. Here we explored putative additional effects of CGRP on cortical circuits and investigated whether CGRP affects cortical excitability, cortical spreading depolarization (CSD), a phenomenon associated with migraine aura, blood-brain-barrier (BBB) and microglial morphology. We used immunohistochemistry to localize CGRP and the CGRP receptor (CGRP-R) in native cortex and evaluated morphology of microglia and integrity of the BBB after exposure to CGRP. In anesthetized rats we applied CGRP and the CGRP-R antagonist BIBN4096BS locally to the exposed cortex and monitored the spontaneous electrocorticogram and CSDs evoked by remote KCl pressure microinjection. In mouse brain slices CGRP effects on neuronal activity were explored by multielectrode array. CGRP immunoreactivity was detectable in intracortical vessels, and all cortical neurons showed CGRP-R immunoreactivity. In rat cortex in vivo, topical CGRP induced periods of epileptiform discharges, however, also dose-dependently reduced CSD amplitudes and propagation velocity. BIBN4096BS prevented these effects. CGRP evoked synchronized bursting activity in mouse cortical but not in cerebellar slices. Topical application of CGRP to rat cortex induced plasma extravasation and this was associated with reduced ramification of microglial cells. From these findings we conclude that CGRP induces a pathophysiological state in the cortex, consisting in neuronal hyperexcitability and neuroinflammation. Thus, CGRP may have a pronounced impact on brain functions during migraine episodes supporting the benefit of CGRP antagonists for clinical use. However, increased cortical CGRP may end the CSD-induced aura phase of migraine.

The Responses to CGRP in the Territory of the Posterior Cerebral Artery in Migraine.

Calcitonin gene-related peptide (CGRP) is important in trigeminovascular (TMV) sensitization with neurogenic inflammation which might be involved in CGRP-induced headache (CGRP-IH). Distribution of white matter lesions, migraine aura, and functional neuroimaging indicate that posterior circulation is especially exposed to TMV sensitization. The transcranial Doppler (TCD) is able to detect changes in the posterior cerebral artery (PCA) during CGRP stimulation. Thus, we studied CGRP-induced hemodynamic changes in PCA and frequency of CGRP-IH. Twenty healthy subjects and 20 patients with migraine participated in our study. TCD was used to monitor mean arterial velocity in posterior cerebral artery (vmPCA). Simultaneously, end-tidal carbon dioxide (Et-CO2), mean arterial pressure (MAP), and heart rate (HR) were measured. During the experiment, we monitored the frequency of CGRP-IH. We determined the values of vmPCA, Et-CO2, MAP, and HR and calculate the response of vmPCA, Et-CO2, MAP, and HR to CGRP. To test the differences and relationships, statistical methods were applied using SSPS. We found significant decrease in vmPCA in migraine and control groups and found the vmPCA response to be significantly lower in migraine (p = 0.018). Et-CO2 decreases in both groups, and it is significantly lower in migraine (p < 0.001). MAP is significantly higher in migraine (p = 0.001), while HR is not significantly higher in migraine (p = 0.570). CGRP-IH is significantly associated with vmPCA responses (p = 0.003) and migraine (p < 0.001). We concluded that hemodynamic changes in PCA are significantly related to CGRP-IH. The TMV sensitization might be pronounced in posterior circulation explaining clinical and morphologic issues in migraine.

ATENOLOL IN EPISODIC MIGRAINE PROPHYLAXIS: A REVIEW

Atenolol seems to reduce blood vessel dilation, which is known to contribute to migraine. It reduces electrical activity of nervous system and reduces it excitability. Atenolol is a β1-cardioselective beta-blocker that influences the heart circulation through veins and arteries. Primarily, it is used to treat high blood pressure and heart-related chest pain. It is also used as a supplement subsequent to a heart attack to lower the risk of death. Atenolol has shown efficacy in prevention of migraines and to treat certain irregularities in heartbeats. It can be taken orally or parentally. It reduces the heart rate and workload of cardiac muscles by blocking β1-adrenergic receptors in heart. It restricted blood flow in the brain by reducing blood vessel dilation and helpful in the treatment of migraine. It reduced the electrical activity of nervous system and made it less excitable. It also repressed the waves of electric currents that proved beneficial in the treatment of migraine aura.

Migraine : Evolution of a Common Disorder

MIGRAINE is a common, chronic, incapacitating neurovascular disorder, characterized by attacks of severe headache, autonomic nervous system dysfunction, and in some patients, an aura involving neurologic symptoms. In one-third of patients the headache is preceded by transient neurological symptoms that are most frequently visual but may involve other senses and speech [migraine with aura (MA)]. Migraine is extremely prevalent [affecting 17% of females and 8% of men], very expensive ($18.5 billion Euros per year in Europe], and disabling [one of the World Health Organization's top 20 most disabling disorders]. It is consequently a public fitness hassle of exceptional effect on each the man or woman and society. Most migraine assaults begin with inside the mind, as advised through (a) the premonitory signs (e.g., issue with speech and reading, expanded emotionality, sensory hypersensitive reaction) that during many sufferers are exceptionally predictive of the attack, even though such signs arise as much as 12 h earlier than the attack, and through (b) the character of a few usual migraine triggers which includes stress, sleep deprivation, oversleeping, hunger, and extended sensory stimulation. Psychophysical and neurophysiological research have supplied clean proof that with inside the duration among assaults migraines display hypersensitive reaction to sensory stimuli and odd processing of sensory information, characterized through expanded amplitudes and decreased habituation of evoked and event-associated potentials. It is usually believed that migraine headache relies upon at the activation and sensitization of the trigeminovascular ache pathway and that cortical spreading depression (CSD) is the neurophysiological correlate of migraine aura. CSD may be precipitated in animals through focal stimulation of the cerebral cortex and includes a slowly propagating (2–6 mm min−1) wave of robust neuronal and glial depolarization; the mechanisms of initiation and propagation of CSD continue to be unclear. The mechanisms of the number one mind dysfunction(s) main to the onset of a migraine attack, to CSD susceptibility, and to episodic activation of the trigeminovascular ache pathway continue to be in large part unknown and the predominant open problem with inside the neurobiology of migraine.