Migraine and major depression: localizing shared genetic susceptibility in different cell types of the nervous systems.

Background: There is a bidirectional relationship between migraine and major depression disorder (MDD). They likely share important risk genes associated with different cell types in the central nervous system (CNS) and peripheral nervous system (PNS). Profiling the expression of these genes in specific cell types is critical in understanding the pathophysiology of the relationship between migraine and MDD. Methods: Associated genes shared by migraine and MDD were identified by consolidating multiple curations of human disease-gene associations. Subsequently, the expression of overlapping genes was profiled and compared across the different cell types in CNS, PNS and neurovascular cells using eight single cell RNA sequencing datasets, including two human CNS datasets, two mouse CNS datasets, one human PNS dataset and three mouse PNS datasets. Results: 45 shared genes between migraine and MDD were identified. Consistently found in all eight datasets, dopaminergic and serotonergic neurotransmitters were broadly expressed in CNS and PNS cell types. Glutamatergic and endocannabinoid genes were specifically expressed in CNS neurons and astrocytes. Synthesis and/or Release and Binding of Neuropeptides were specifically expressed in PNS peptidergic nociceptor (PEP). Genes related to inflammatory factors and immune responses were specifically expressed in CNS microglia. Among which, IL1B and COMT were highly expressed in CNS microglia cells. Conclusion: Single cell RNA sequencing of the CNS and PNS helps to identify the shared genes between migraine and MDD that are enriched in specific cell types. The findings provide new insight in understanding the underlying mechanism of action for the bidirectional co-morbidity between migraine and MDD.

Remotely supervised at-home tDCS for veterans with persistent post-traumatic headache: a double-blind, sham-controlled randomized pilot clinical trial.

Background: Currently, there are no FDA approved therapies for persistent post-traumatic headache (PPTH) secondary to traumatic brain injury (TBI). As such neither headache nor TBI specialists have an effective means to manage PPTH. Thus, the objective of the present pilot trial was to evaluate the feasibility and preliminary efficacy of a four-week at-home remotely supervised transcranial direct current stimulation (RS-tDCS) intervention for veterans with PPTH. Methods: Twenty-five (m = 46.6 ± 8.7 years) veterans with PPTH were randomized into two groups and received either active (n = 12) or sham (n = 13) RS-tDCS, with anodal stimulation over left dlPFC and cathodal over occipital pole. Following a four-week baseline, participants completed 20-sessions of active or sham RS-tDCS with real-time video monitoring over a period of four-weeks. Participants were assessed again at the end of the intervention and at four-weeks post-intervention. Primary outcomes were overall adherence rate (feasibility) and change in moderate-to-severe headache days per month (efficacy). Secondary outcomes were changes in total number of headache days, and PPTH-related functional outcomes. Results: Adherence rate was high with 88% of participants (active = 10/12; sham = 12/13) fully completing tDCS interventions. Importantly, there was no significant difference in adherence between active and sham groups (p = 0.59). Moderate-to-severe headache days were significantly reduced within the active RS-tDCS group (p = 0.004), compared to sham during treatment (-2.5 ± 3.5 vs. 2.3 ± 3.4), and 4-week follow-up (-3.9 ± 6.4 vs. 1.2 ± 6.5). Total number of headache days was significantly reduced within the active RS-tDCS (p = 0.03), compared to sham during-treatment (-4.0 ± 5.2 vs. 1.5 ± 3.8), and 4-week follow-up (-2.1 ± 7.2 vs. -0.2 ± 4.4). Conclusion: The current results indicate our RS-tDCS paradigm provides a safe and effective means for reducing the severity and number of headache days in veterans with PPTH. High treatment adherence rate and the remote nature of our paradigm indicate RS-tDCS may be a feasible means to reduce PPTH, especially for veterans with limited access to medical facilities.Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT04012853].

Risks of suicide in migraine, non-migraine headache, back, and neck pain: a systematic review and meta-analysis.

Objective: To conduct a systematic review and meta-analysis on suicidal ideation, attempts, and death in patients with head, neck, and back pain. Method: Search was performed using PubMed, Embase, and Web of Science from the date of the first available article through September 31, 2021. A random effects model was used to estimate the pooled odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between suicidal ideation and/or attempt and head, back/neck pain conditions. Articles describing non-migraine headache disorders and death by suicide were also reviewed but not included in the meta-analysis due to an insufficient number of studies. Results: A total of 20 studies met criteria for systemic review. A total of 186,123 migraine patients and 135,790 of neck/back pain patients from 11 studies were included in the meta-analysis. The meta-analysis showed that the estimated risk of combined suicidal ideation and attempt in migraine [OR 2.49; 95% CI: 2.15-2.89] is greater than that in back/neck pain pain [OR 2.00; 95% CI: 1.63-2.45] compared to non-pain control groups. Risk of suicide ideation/planning is 2 folds higher [OR: 2.03; 95% CI: 1.92-2.16] and risk of suicide attempt is more than 3 folds higher [OR: 3.47; 95% CI: 2.68-4.49] in migraine as compared to healthy controls. Conclusion: There is an elevated risk of suicidal ideation and attempt in both migraine and neck/back pain patients in comparison to healthy controls, and this risk is particularly higher among migraine patients. This study underscores the critical need for suicide prevention in migraine patients.

Relationship Between Headache Characteristics and a Remote History of TBI in Veterans: A 10-Year Retrospective Chart Review.

BACKGROUND AND OBJECTIVES: The objective of this work was to examine the association between deployment-related traumatic brain injury (TBI) severity, frequency, and other injury characteristics with headache outcomes in veterans evaluated at a Veterans Administration (VA) polytrauma support clinic. METHODS: We conducted a retrospective chart review of 594 comprehensive TBI evaluations between 2011 and 2021. Diagnostic criteria were based on the Department of Defense/VA Consensus-Based Classification of Closed TBI. Adjusted odds ratios (AORs) and 95% CIs were estimated for headache prevalence (logistic), headache severity (ordinal), and prevalence of migraine-like features (logistic) with multiple regression analysis. Regression models were adjusted for age, sex, race/ethnicity, time since injury, and mental health diagnoses. RESULTS: TBI severity groups were classified as sub concussive exposure (n = 189) and mild (n = 377), moderate (n = 28), and severe TBI (n = 0). Increased headache severity was reported in veterans with mild TBI (AOR 1.72 [95% CI 1.15, 2.57]) and moderate TBI (AOR 3.89 [1.64, 9.15]) compared to those with subconcussive exposure. A history of multiple mild TBIs was associated with more severe headache (AOR 2.47 [1.34, 4.59]) and migraine-like features (AOR 5.95 [2.55, 13.77]). No differences were observed between blast and nonblast injuries; however, greater headache severity was reported in veterans with both primary and tertiary blast effects (AOR 2.56 [1.47, 4.49]). Alteration of consciousness (AOC) and posttraumatic amnesia (PTA) >30 minutes were associated with more severe headache (AOR 3.37 [1.26, 9.17] and 5.40 [2.21, 13.42], respectively). The length of time between the onset of last TBI and the TBI evaluation was associated with headache severity (AOR 1.09 [1.02, 1.17]) and prevalence of migraine-like features (AOR 1.27 [1.15, 1.40]). Last, helmet use was associated with less severe headache (AOR 0.42 [0.23, 0.75]) and lower odds of migraine-like features (AOR 0.45 [0.21, 0.98]). DISCUSSION: Our data support the notion of a dose-response relationship between TBI severity and headache outcomes. A history of multiple mild TBIs and longer duration of AOC and PTA are unique risk factors for poor headache outcomes in veterans. Furthermore, this study sheds light on the poor headache outcomes associated with subconcussive exposure. Past TBI characteristics should be considered when developing headache management plans for veterans.

Suicide Attempts in US Veterans with Chronic Headache Disorders: A 10-Year Retrospective Cohort Study.

OBJECTIVES: A large-scale retrospective analysis of veterans with chronic pain was conducted to examine (1) the annual incidence of suicide attempts (SA) in veterans with chronic headache and other chronic pain conditions, and (2) the risk of SA in men and women with chronic headache and chronic headache concurrent with traumatic brain injury (TBI) as compared to non-headache chronic pain. METHODS: This retrospective study (N=3,247,621) analyzed National Veterans Affair Health Administrative data of patients diagnosed with chronic head, neck, back and other chronic pain from 2000 to 2010. Multivariable Poisson regression was used to explore the relative risks of SA in veterans with chronic headache and chronic headache concurrent with TBI as stratified by sex. RESULTS: Veterans with chronic headaches had the highest annual incidence of SA (329 to 491 per 100,000) each year among all identified types of chronic pain conditions. Compared to other non-headache chronic pain, chronic headache is associated with increased risk of SA [men RR (1.48), CI (1.37,1.59); women RR (1.64), CI (1.28,2.09)], after adjusting for demographic factors, TBI, and psychiatric comorbidities. The risk increased further when chronic headache is comorbid with TBI [men RR (2.82), CI (2.60, 3.05); women RR (2.16, CI (1.67-2.78)]. CONCLUSION: Veterans with chronic headache have a higher risk of SA than those with other chronic pain and women with chronic headache are at a higher risk than men with chronic headache. Chronic headache concurrent with TBI further heightened this risk, especially in men. Our data underscore the importance of identifying specific types of chronic pain in veterans with comorbid TBI and sex disparity associated with SA when targeting suicide prevention measures.

A Systematic Review and Meta-Analysis on the Efficacy of Repeated Transcranial Direct Current Stimulation for Migraine.

PURPOSE: Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results. We reviewed studies using repeated tDCS for longer than 4 weeks in migraine treatment, and performed meta-analysis on the efficacy of tDCS in migraine. METHODS: In this meta-analysis, we included the common outcome measurements reported across randomized controlled trials (RCTs). Subgroup analysis was performed at different post-treatment endpoints, and with different stimulation intensities and polarities. RESULTS: Five RCTs were included in the quantitative meta-analysis with a total of 104 migraine patients. We found a significant reduction of migraine pain intensity (MD: -1.44; CI: [-2.13, -0.76]) in active vs sham tDCS treated patients. Within active treatment groups, pain intensity and duration were significantly improved from baseline after tDCS treatment (intensity MD: -1.86; CI: [-3.30, -0.43]; duration MD: -4.42; CI: [-8.11, -0.74]) and during a follow-up period (intensity MD: -1.52; CI: [-1.84, -1.20]; duration MD: -1.94; CI: [-3.10, -0.77]). There was a significant reduction of pain intensity by both anodal (MD: -1.74; CI: [-2.80, -0.68]) and cathodal (MD: -1.49; CI: [-1.89, -1.09]) stimulation conditions. CONCLUSION: tDCS treatment repeated over days for a period of 4 weeks or more is effective in reducing migraine pain intensity and duration of migraine episode. The benefit of tDCS can persist for at least 4 weeks after the completion of last tDCS session. Both anodal and cathodal stimulation are effective for reducing migraine pain intensity.

Post-traumatic Headache and Mild Traumatic Brain Injury: Brain Networks and Connectivity.

PURPOSE OF REVIEW: Post-traumatic headache (PTH) consequent to mild traumatic brain injury (mTBI) is a complex, multidimensional, chronic neurological disorder. The purpose of this review is to evaluate the current neuroimaging studies on mTBI and PTH with a specific focus on brain networks and connectivity patterns. RECENT FINDINGS: We present findings on PTH incidence and prevalence, as well as the latest neuroimaging research findings on mTBI and PTH. Additionally, we propose a new strategy in studying PTH following mTBI. The diversity and heterogeneity of pathophysiological mechanisms underlying mild traumatic brain injury pose unique challenges on how we interpret neuroimaging findings in PTH. Evaluating alterations in the intrinsic brain network connectivity patterns using novel imaging and analytical techniques may provide additional insights into PTH disease state and therefore inform effective treatment strategies.

Cortical and subcortical changes following sphenopalatine ganglion blocks in chronic migraine with medication overuse headache: a preliminary longitudinal study.

OBJECTIVE: The purpose of this pilot study was to investigate potential changes in brain morphology (cortical thickness and cortical/subcortical volume) accompanying a series of sphenopalatine ganglion (SPG) blockade treatments in chronic migraine with medication overuse headaches (CMw/MOH). BACKGROUND: Local anesthetization of the SPG via intranasal application is used for the treatment for multiple types of headache disorders, including CM. Our previous longitudinal fMRI study revealed improved network connectivity after such treatment. However, the impact of SPG blocks on cortical, subcortical gray matter volume and cortical thickness has yet to be assessed. METHODS: Using magnetic resonance imaging (MRI), cortical/subcortical volume were measured in 12 chronic migraine patients before and after a series of 12 SPG blocks administered over a 6-week period (2 per week). The average time between MRI assessments was 6 weeks. Targeted, within-subjects t-tests comparing pre-treatment and post-treatment values in specific apriori brain regions of interest, including the hippocampus, amygdala, basal ganglia, somatosensory cortex, temporal cortex and occipital cortex, were used to estimate the impact of repetitive SPG blocks treatment on brain morphology in CMw/MOH. RESULTS: Compared to baseline values, the number of moderate/severe headache days per month, HIT-6, PHQ-9 scores and allodynia scores were all significantly improved at the end of treatment. Analysis of MRI data revealed that the volume of the right hippocampus and the right palladium significantly decreased following SPG block treatment, while the volume of the left nucleus accumbens significantly increased following treatment. Cortical thickness in the left temporal pole and left lateral occipito-temporal gyrus significantly decreased following SPG block treatment. CONCLUSION: Our results suggest SPG block treatment is associated with significant symptom improvement as well as significant structural brain changes in regions known to be associated with migraine and chronic pain processing in CMw/MOH.

Migraine Age of Onset and Association With Ischemic Stroke in Late Life: 20 Years Follow-Up in ARIC.

BACKGROUND AND PURPOSE: To evaluate the association between cumulative exposure to migraine and incidence of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: In this ongoing, prospective longitudinal community-based cohort, participants were interviewed to ascertain migraine history at the third visit (1993-1995), followed for ischemic stroke incidence over 20 years. We performed a post hoc analysis to evaluate the association between the age of migraine onset and ischemic stroke. RESULTS: We identified 447 migraineurs with aura (MA) and 1128 migraineurs without aura (MO) among 11,592 black and white participants. There was an association between the age of MA onset ≥50 years old (average duration = 4.75 years) and ischemic stroke when compared to no headache group (multivariable adjusted HR = 2.17, 95% CI [1.39-3.39], P < .001). MA onset <50 years old (average duration = 28.17 years) was not associated with stroke (multivariable adjusted HR = 1.31, 95% CI [0.86-2.02], P = .212). These results were consistent with our logistic regression model. MO was not associated with increased stroke regardless of the age of onset. The absolute risk for stroke in migraine with aura is 37/447 (8.27%) and migraine without aura is 48/1128 (4.25%). CONCLUSION: As compared to the no headache participants, increased stroke risk in late life was observed in participants with late onset of MA. In this cohort, longer cumulative exposure to migraine with visual aura, as would be expected with early onset of migraine, was not associated with increased risk of ischemic stroke in late life. This study underscores the importance of the age of onset of MA in assessing stroke risk in older migraineurs.

Central Executive and Default Mode Network Intranet work Functional Connectivity Patterns in Chronic Migraine.

BACKGROUND: The neural mechanisms of chronic migraine remain largely unknown but linked to the decreased connectivity to intrinsic brain networks. OBJECTIVE: To characterize the intranetwork functional connectivity within the Central Executive Network (CEN) and Default Mode Network (DMN) in chronic migraine (CM), with and without medication overuse headache (MOH). METHODS: Using functional magnetic resonance imaging, we performed post-hoc analysis of a total of 136 pairs of nodes to node functional connectivity (NTNC) within the CEN and 6 pairs of NTNC within the DMN in CM (n=13) and CMMOH (n=16) as compared to controls, and between these two subgroups. RESULTS: Connectivity between right ventrolateral prefrontal cortex (PFC) to contralateral anterior thalamus and connectivity between left dorsal PFC/frontal eye field (FEF) to dorsomedial PFC were decreased within the CEN in both CM and CMMOH subgroups. In the CEN, there was more widespread disruption in the CMMOH (n=16) versus CM (n=13), when compared to healthy controls. Within the subgroups, connectivity between right inferior frontal gyrus to left dorsolateral PFC was decreased in CMMOH compared to CM. In the DMN, only one NTNC (left lateral parietal to precuneus/PCC) was disrupted in the CMMOH group when compared to controls. CONCLUSION: There are similar patterns of NTNC dysfunction within CEN in CM regardless of MOH status. We observed more extensive intranetwork disruption in CMMOH than CM. The decreased coherence between the right inferior frontal gyrus and the left dorsolateral PFC in CMMOH is likely associated with a significant disruption in the inhibitory control and a maladaptive response in risk aversion and reward; whereas the decreased coherence between right dorsolateral and ventrolateral PFC to contralateral dorsal PFC/FEF may be related to lack of cognitive control and top-down regulation of pain in both CM and CMMOH.

Migraine with visual aura is a risk factor for incident atrial fibrillation: A cohort study.

OBJECTIVE: Migraine with visual aura is associated with cardioembolic stroke risk. The aim of this study was to test association between migraine with visual aura and atrial fibrillation (AF), in the Atherosclerosis Risk in Communities study. METHODS: In the Atherosclerosis Risk in Communities study, a longitudinal, community-based cohort study, participants were interviewed for migraine history in 1993-1995 and were followed for incident AF through 2013. AF was adjudicated using ECGs, discharge codes, and death certificates. Multivariable Cox proportional hazards models were used to study the relation between migraine and its subtypes with incident AF, compared with controls without headaches. Mediation analysis was conducted to test whether AF was a mediator of migraine with visual aura-associated stroke risk. RESULTS: Of 11,939 participants assessed for headache and without prior AF or stroke, 426 reported migraines with visual aura, 1,090 migraine without visual aura, 1,018 nonmigraine headache, and 9,405 no headache. Over a 20-year follow-up period, incident AF was noted in 232 (15%) of 1,516 with migraine and 1,623 (17%) of 9,405 without headache. After adjustment for multiple confounders, migraine with visual aura was associated with increased risk of AF compared to no headache (hazard ratio 1.30, 95% confidence interval 1.03-1.62) as well as when compared to migraine without visual aura (hazard ratio 1.39, 95% confidence interval 1.05-1.83). The data suggest that AF may be a potential mediator of migraine with visual aura-stroke risk. CONCLUSIONS: Migraine with aura was associated with increased risk of incident AF. This may potentially lead to ischemic strokes.

Resting State Functional Connectivity After Sphenopalatine Ganglion Blocks in Chronic Migraine With Medication Overuse Headache: A Pilot Longitudinal fMRI Study.

OBJECTIVE: In this pilot study, the purpose is to investigate if a series of sphenopalatine ganglion (SPG) blockade treatments modulate the functional connectivity within the salience and central executive network (CEN) in chronic migraine with medication overuse headaches (CMw/MOH ). BACKGROUND: Using intranasal local anesthesia to block the SPG for the treatment of various headache disorders has been employed in clinical practice since the early 1900s. However, the exact mechanism of how SPG modulate resting state intrinsic functional brain networks connectivity remains to be elucidated. This pilot study seeks to understand the resting state connectivity changes in salience and CENs, with emphasis on the mesocorticolimbic systems, before and after a series of SPG block treatments. METHODS: Using fMRI, resting state connectivity was derived from predefined networks of nodes (regions of interests) for the salience (27 nodes, 351 connections) and CENs (17 nodes, 136 connections). After treatments, a paired samples t-test (with 10,000 permutations to correct for multiple comparison) was used to evaluate changes in the intranetwork resting state functional connectivity within the salience and executive networks, as well as the overall network connectivity strength. RESULTS: When comparing connectivity strength at baseline to that at the end of treatment in our cohort of 10 CMw/MOH participants, there were several connections within the salience (n = 9) and executive (n = 8) networks that were significantly improved. Within the salience network, improved connectivity was observed between the prefrontal cortex and various regions of the insula, basal ganglia, motor, and frontal cortex. Additionally, changes in connectivity were observed between regions of the temporal cortex with the basal ganglia and supramarginal gyrus. Within the CEN, improved connectivity was observed between the prefrontal cortex and regions of the anterior thalamus, caudate, and frontal cortex. After treatment, the overall CEN connectivity was significantly improved (Baseline 0.00 ± 0.08; 6 weeks 0.03 ± 0.09, P = .01); however, the overall salience network connectivity was not significantly improved (Baseline -0.01 ± 0.10; 6 weeks 0.01 ± 0.12, P = .26). Additionally, after treatment, there was a significant reduction in the number of moderate/severe headache days per month (Baseline 21.1 ± 6.6; 6 weeks 11.2 ± 6.5, P < .001), HIT-6 (Baseline 66.1 ± 2.6; 6 weeks 60.2 ± 3.6, P < .001), and PHQ-9 (Baseline 12.4 ± 5.7; 6 weeks 6.1 ± 3.6, P = .008) scores. CONCLUSION: In this longitudinal fMRI study, we observed improved functional connectivity within both networks, primarily involving connectivity between regions of the prefrontal cortex and limbic (cortical-limbic) structures, and between different cortical (cortical-cortical) regions after a series of repetitive SPG blockades. The overall CEN strength was also improved. Our results suggest that recurrent parasympathetic inhibition via SPG is associated with improved functional connectivity in brain regions critical to pain processing in CMw/MOH .

Modulation of salience network intranetwork resting state functional connectivity in women with chronic migraine.

Objective To investigate the intranetwork resting state fMRI connectivity within the Salience Network of chronic migraine with and without medication overuse headache. Methods We compared 351 pairs of intranetwork connectivity in chronic migraine (n = 13) and chronic migraine with medication overuse headache (n = 16) compared to matched controls, and between each chronic migraine subgroup. Results Compared to controls, 17 pairs of intranetwork connections in chronic migraine and 27 pairs in chronic migraine with medication overuse headache were decreased. When comparing chronic migraine with medication overuse headache versus chronic migraine, connectivity between bilateral extended amygdala, and between paracingulate to right ventral tegmental area/substantia nigra were decreased in chronic migraine (chronic migraine < chronic migraine with medication overuse headache). Connectivity between left dorsolateral prefrontal cortex to bilateral ventral striatum/pallidum, to bilateral dorsal anterior cingulate cortex; left anterior prefrontal cortex to contralateral orbitofrontal insula; and left ventral striatum/pallidum to ipsilateral supplementary motor area (SMA)/preSMA were decreased in chronic migraine with medication overuse headache (chronic migraine with medication overuse headache < chronic migraine). Conclusion Both chronic migraine subgroups had shared intranetwork connectivity abnormality, however, each subgroup had unique pattern of disruption within the salience network. The results suggest that the aberrant assignment of salience to external and internal stimuli plays an important role in chronic migraine and chronic migraine with medication overuse headache interictally, mostly involving mesolimbic pathways (especially bilateral extended amygdala) in chronic migraine, and prefrontal-subcortical limbic pathways in chronic migraine with medication overuse headache.

Modulation of intrinsic resting-state fMRI networks in women with chronic migraine.

OBJECTIVE: To evaluate the intrinsic resting functional connectivity of the default mode network (DMN), salience network (SN), and central executive network (CEN) network in women with chronic migraine (CM), and whether clinical features are associated with such abnormalities. METHODS: We analyzed resting-state connectivity in 29 women with CM as compared to age- and sex-matched controls. Relationships between clinical characteristics and changes in targeted networks connectivity were evaluated using a multivariate linear regression model. RESULTS: All 3 major intrinsic brain networks were less coherent in CM (DMN: p = 0.030, SN: p = 0.007, CEN: p = 0.002) as compared to controls. When stratified based on medication overuse headache (MOH) status, CM without MOH (DMN: p = 0.029, SN: p = 0.023, CEN: p = 0.003) and CM with MOH (DMN: p = 0.016, SN: p = 0.016, CEN: p = 0.015) were also less coherent as compared to controls. There was no difference in CM with MOH as compared to CM without MOH (DMN: p = 0.382, SN: p = 0.408, CEN: p = 0.419). The frequency of moderate and severe headache days was associated with decreased connectivity in SN (p = 0.003) and CEN (p = 0.015), while cutaneous allodynia was associated with increased connectivity in SN (p = 0.011). CONCLUSIONS: Our results demonstrated decreased overall resting-state functional connectivity of the 3 major intrinsic brain networks in women with CM, and these patterns were associated with frequency of moderate to severe headache and cutaneous allodynia.

Ischemic stroke subtypes and migraine with visual aura in the ARIC study.

OBJECTIVE: To investigate the association among migraine, ischemic stroke, and stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: In this ongoing, prospective, longitudinal community-based cohort study, participants were given an interview ascertaining migraine history in 1993-1995, and were followed for all vascular events, including stroke. All stroke events over the subsequent 20 years were adjudicated and classified into stroke subtypes by standard definitions. Cox proportional hazards models adjusted for stroke risk factors were used to study the relationship between migraine and ischemic stroke, overall, as well as stroke subtypes (cardioembolic, lacunar, or thrombotic). RESULTS: We identified 1,622 migraineurs among 12,758 participants. Mean age of the study population at the 3rd clinical visit was 59 years. When compared to nonheadache participants, there was a significant association between migraine with visual aura and ischemic stroke (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2-2.6, p = 0.008). Migraine without visual aura was not significantly associated with ischemic stroke (HR 1.2, CI 1.0-1.8, p = 0.28) when compared to nonheadache participants. Among the 3 subtypes of ischemic stroke evaluated, migraine with visual aura was significantly associated only with cardioembolic stroke (HR 3.7, 95% CI 1.6-8.7, p = 0.003). CONCLUSION: In participants with migraine with visual aura in late middle age, increased risk of cardioembolic stroke was observed. Migraine with visual aura was linked to increased stroke risk, while migraine without visual aura was not, over the period of 20 years. These results are specific to older migraineurs.

Hemicrania continua may respond to repetitive sphenopalatine ganglion block: A case report.

BACKGROUND: Hemicrania continua (HC) is a chronic headache disorder characterized by a continuous, strictly unilateral head pain accompanied by cranial autonomic symptoms, which completely responds to indomethacin; however, few alternative treatment options exist for the patients with this disorder who cannot tolerate indomethacin. Sphenopalatine ganglion (SPG) block has been used for the treatment of various headaches, with the strongest evidence for efficacy in cluster headache. CASE REPORT: A 52-year-old woman with a 7-year history of HC was evaluated in our clinic for management of her headaches after she had stopped using indomethacin due to a bleeding gastrointestinal ulcer. After failing multiple pharmacologic therapies, she was treated with repetitive SPG blocks using bupivacaine (0.6 mL at 0.5%) twice a week for 6 weeks and followed by maintenance therapy. This treatment protocol resulted in significant improvement in her headaches, mood, and functional capacity. CONCLUSION: SPG block using a local anesthetic may be an effective treatment for patients with HC, specifically for those who cannot tolerate indomethacin, or when this drug is contraindicated.