Migraine is associated with high brain 5-HT levels as indexed by 5-HT4 receptor binding

Cephalalgia ◽  
2018 ◽  
Vol 39 (4) ◽  
pp. 526-532 ◽  
Author(s):  
Marie Deen ◽  
Anders Hougaard ◽  
Hanne D Hansen ◽  
Claus Svarer ◽  
Hans Eiberg ◽  
...  
Keyword(s):  
Risk Factor ◽  
Chronic Migraine ◽  
Receptor Binding ◽  
Episodic Migraine ◽  
Pet Scan ◽  
Dynamic Pet ◽  
Migraine Frequency ◽  
Slope Estimate ◽  
Migraine Pathophysiology ◽  
Made In

Introduction Serotonin (5-HT) plays a role in migraine pathophysiology, but whether brain 5-HT is involved in the conversion from episodic to chronic migraine is unknown. Here, we investigated brain 5-HT levels, as indexed by 5-HT4 receptor binding, in chronic migraine patients and evaluated whether these were associated with migraine frequency. Methods Sixteen chronic migraine patients underwent a dynamic PET scan after injection of [11C]SB207145, a specific 5-HT4 receptor radioligand. Data from 15 episodic migraine patients and 16 controls were included for comparison. Quantification of 5-HT4 receptor binding was used as a proxy for brain 5-HT levels, since 5-HT4 receptor binding is inversely related to brain 5-HT levels. Results Chronic migraine patients had 9.1% (95% CI: [−17%; −1.0%]) lower 5-HT4 receptor binding compared to controls ( p = 0.039). There was no difference in 5-HT4 receptor binding between chronic and episodic migraine patients ( p = 0.48) and no association between number of monthly migraine days and 5-HT4 receptor binding (slope estimate 0.003, 95% CI: [−0.004; 0.715], p = 0.39). Conclusion The finding of low 5-HT4 receptor binding suggests that cerebral levels of 5-HT are elevated in chronic migraine patients. This is in line with observations made in patients with episodic migraine. Elevated brain 5-HT levels may thus be an inherent trait of the migraine brain rather than a risk factor for conversion from episodic to chronic migraine.

The 1246 G/A polymorphism of the HCRTR2 gene is not associated with migraine

Cephalalgia ◽  
2007 ◽  
Vol 27 (8) ◽  
pp. 945-949 ◽  
Author(s):  
L Pinessi ◽  
E Binello ◽  
P De Martino ◽  
S Gallone ◽  
S Gentile ◽  
...  
Keyword(s):  
Risk Factor ◽  
Chronic Migraine ◽  
Genetic Risk ◽  
Migraine Without Aura ◽  
Control Design ◽  
Case Control ◽  
Healthy Controls ◽  
Experimental Animals ◽  
Significant Difference ◽  
Migraine Pathophysiology

Studies in experimental animals have suggested that the hypocretin/orexin system may be involved in migraine pathophysiology. Using a case-control design study, we genotyped 246 migraine patients and 239 healthy controls for the 1246G→A polymorphism of the hypocretin receptor 2 ( HCRTR2) gene. Genotypic and allelic frequencies of the examined polymorphism were similarly distributed between cases and controls (χ2 = 2.22, P = 0.14 and χ2 = 2.45, P = 0.29, respectively). When different migraine subgroups were compared (migraine with aura vs. migraine without aura and episodic vs. chronic migraine) no significant difference was found. Comparison of the clinical features of the disease with the 1246G→A genotypes showed no significant difference. Our data suggest that the HCRTR2 gene is not a genetic risk factor in migraine.

scholarly journals Chronic Migraine Pathophysiology and Treatment: A Review of Current Perspectives

2021 ◽  
Vol 2 ◽  
Author(s):  
Tiffani J. Mungoven ◽  
Luke A. Henderson ◽  
Noemi Meylakh
Keyword(s):  
Chronic Migraine ◽  
Current Knowledge ◽  
Treatment Options ◽  
Episodic Migraine ◽  
Current Treatment ◽  
Future Research ◽  
Socioeconomic Outcomes ◽  
Risk Factor Modification ◽  
Evidence Based Treatments ◽  
Migraine Pathophysiology

Chronic migraine is a disabling neurological disorder that imposes a considerable burden on individual and socioeconomic outcomes. Chronic migraine is defined as headaches occurring on at least 15 days per month with at least eight of these fulfilling the criteria for migraine. Chronic migraine typically evolves from episodic migraine as a result of increasing attack frequency and/or several other risk factors that have been implicated with migraine chronification. Despite this evolution, chronic migraine likely develops into its own distinct clinical entity, with unique features and pathophysiology separating it from episodic migraine. Furthermore, chronic migraine is characterized with higher disability and incidence of comorbidities in comparison to episodic migraine. While existing migraine studies primarily focus on episodic migraine, less is known about chronic migraine pathophysiology. Mounting evidence on aberrant alterations suggest that pronounced functional and structural brain changes, central sensitization and neuroinflammation may underlie chronic migraine mechanisms. Current treatment options for chronic migraine include risk factor modification, acute and prophylactic therapies, evidence-based treatments such as onabotulinumtoxinA, topiramate and newly approved calcitonin gene-related peptide or receptor targeted monoclonal antibodies. Unfortunately, treatments are still predominantly ineffective in aborting migraine attacks and decreasing intensity and frequency, and poor adherence and compliance with preventative medications remains a significant challenge. Novel emerging chronic migraine treatments such as neuromodulation offer promising therapeutic approaches that warrant further investigation. The aim of this narrative review is to provide an update of current knowledge and perspectives regarding chronic migraine background, pathophysiology, current and emerging treatment options with the intention of facilitating future research into this debilitating and largely indeterminant disorder.

scholarly journals Migraine and Complex Regional Pain Syndrome: A Case-Referent Clinical Study

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yohannes W. Woldeamanuel ◽  
Corinne Cooley ◽  
Katharine Foley-Saldena ◽  
Robert P. Cowan
Keyword(s):  
Clinical Phenotype ◽  
Pain Syndrome ◽  
Episodic Migraine ◽  
Headache Disorders ◽  
Medical Comorbidities ◽  
Medical Disorders ◽  
Migraine Frequency ◽  
Budapest Criteria ◽  
Made In

We studied clinical phenotype differences between migraineurs with CRPS (Mig + CRPS) and those without (Mig − CRPS). Mig + CRPS cases and Mig − CRPS referents aged ≥18 years were enrolled. Diagnosis was made in accordance with International Classification of Headache Disorders-3 beta (ICHD-3 beta) for migraine and Budapest Criteria for CRPS. Migraines both with and without aura were included. A total of 70 Mig + CRPS cases (13% males, mean age 48 years) and 80 Mig − CRPS referents (17% males, mean age 51 years) were included. 33% of Mig + CRPS and 38% of Mig − CRPS exhibited episodic migraine (EM) while 66% of Mig + CRPS and 62% of Mig − CRPS had chronic migraine (CM) (OR = 0.98, CI 0.36, 2.67). Median duration of CRPS was 3 years among EM + CRPS and 6 years among CM + CRPS cohort (p<0.02). Mig + CRPS (57%) carried higher psychological and medical comorbidities compared to Mig − CRPS (6%) (OR 16.7, CI 10.2, 23.6). Higher migraine frequency was associated with longer CRPS duration. Migraineurs who developed CRPS had higher prevalence of psychological and medical disorders. Alleviating migraineurs’ psychological and medical comorbidities may help lower CRPS occurrence.

scholarly journals Differences in Frontal Lobe Dysfunction in Patients with Episodic and Chronic Migraine

2021 ◽  
Vol 10 (13) ◽  
pp. 2779
Author(s):  
Sang-Hwa Lee ◽  
Yeonkyeong Lee ◽  
Minji Song ◽  
Jae Jun Lee ◽  
Jong-Hee Sohn
Keyword(s):  
Chronic Migraine ◽  
Frontal Lobe ◽  
Iowa Gambling Task ◽  
Medication Overuse Headache ◽  
Wisconsin Card Sorting Test ◽  
Episodic Migraine ◽  
Frontal Lobe Dysfunction ◽  
Card Sorting ◽  
Cross Sectional ◽  
Frontal Lobe Function

Neuroimaging and neuropsychological investigations have indicated that migraineurs exhibit frontal lobe-related cognitive impairment. We investigated whether orbitofrontal and dorsolateral functioning differed between individuals with episodic migraine (EM) and chronic migraine (CM), focusing on orbitofrontal dysfunction because it is implicated in migraine chronification and medication overuse headache (MOH) in migraineurs. This cross-sectional study recruited women with CM with/without MOH (CM + MOH, CM − MOH), EM, and control participants who were matched in terms of age and education. We conducted neuropsychological assessments of frontal lobe function via the Trail Making Test (TMT) A and B, the Wisconsin Card Sorting Test (WCST), and the Iowa Gambling Task (IGT). We enrolled 36 CM (19 CM + MOH, 17 CM–MOH), 30 EM, and 30 control participants. The CM patients performed significantly (p < 0.01) worse on the TMT A and B than the EM patients and the control participants. The WCST also revealed significant differences, with poorer performance in the CM patients versus the EM patients and the control participants. However, the net scores on the IGT did not significantly differ among the three groups. Our findings suggest that the CM patients exhibited frontal lobe dysfunction, and, particularly, dorsolateral dysfunction. However, we found no differences in frontal lobe function according to the presence or absence of MOH.

scholarly journals Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Michael Ament ◽  
Kathleen Day ◽  
Virginia L Stauffer ◽  
Vladimir Skljarevski ◽  
Mallikarjuna Rettiganti ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Migraine Headache ◽  
Randomized Clinical Trials ◽  
Episodic Migraine ◽  
Double Blind Study ◽  
Double Blind ◽  
Prodromal Symptoms ◽  
Link Type ◽  
Associated Symptoms ◽  
Severe Migraine

Abstract Background Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days compared with placebo. Here, we analyze data from 3 randomized clinical trials (2 episodic trials [EVOLVE-1, EVOLVE-2] and 1 chronic trial [REGAIN]), to examine if galcanezumab also alleviates the severity and symptoms of migraine. Methods The episodic migraine trials were 6-month, double-blind studies in patients with episodic migraine (4–14 monthly migraine headache days). The chronic migraine trial was a 3-month, double-blind study in patients with chronic migraine (≥ 15 headache days per month, where ≥ 8 met criteria for migraine). Patients (18–65 years) were randomized to placebo or galcanezumab 120 mg with a 240-mg loading dose or 240 mg. Patients recorded headache characteristics, duration, severity, and presence of associated symptoms with each headache. The outcomes analyzed were changes from baseline in number of monthly migraine headache days with nausea and/or vomiting, photophobia and phonophobia, aura, and prodromal symptoms other than aura. Additional outcomes analyzed included the number of moderate-to-severe monthly migraine headache days, number of severe migraine headache days, and mean severity of remaining migraine headache days. Change from baseline in the proportion of days with nausea and/or vomiting and the proportion of days with photophobia and phonophobia among the remaining monthly migraine headache days were also analyzed. Results Galcanezumab was superior to placebo in reducing the frequency of migraine headache days with associated symptoms of migraine such as nausea and/or vomiting, photophobia and phonophobia, and prodromal symptoms. Galcanezumab reduced the frequency of migraine headache days with aura in the episodic migraine studies. There was a significant reduction in the proportion of remaining migraine headache days with nausea and/or vomiting for the episodic and chronic migraine studies, and with photophobia and phonophobia for the episodic migraine studies. Galcanezumab was superior to placebo in reducing the number of monthly moderate-to-severe migraine headache days and the overall and monthly severe migraine headache days. Conclusions Galcanezumab reduces the frequency of migraine headache days and can alleviate potentially disabling non-pain symptoms on days when migraine is present in patients with episodic or chronic migraine. Trial registration NCT, NCT02614183 (EVOLVE-1), registered 25 November 2015; NCT, NCT02614196, (EVOLVE-2), registered 25 November 2015; NCT, NCT02614261 (REGAIN), registered 25 November 2015.

scholarly journals Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Messoud Ashina ◽  
Joshua M. Cohen ◽  
Maja Galic ◽  
Verena Ramirez Campos ◽  
Steve Barash ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Medication Use ◽  
Episodic Migraine ◽  
Inadequate Response ◽  
Open Label ◽  
Double Blind ◽  
Moderate Severity ◽  
Preventive Medication ◽  
Open Label Extension ◽  
Acute Headache

Abstract Background Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab. Methods Episodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or  ≥75% reduction in monthly migraine days were evaluated. Results Of the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: − 4.7 [5.4]; − 5.1 [4.7]; − 5.5 [5.0]), monthly headache days of at least moderate severity (− 4.5 [5.0]; − 4.8 [4.5]; − 5.2 [4.9]), days per month of acute headache medication use (− 4.3 [5.2]; − 4.9 [4.6]; − 4.8 [4.9]), days with photophobia/phonophobia (− 3.1 [5.3]; − 3.4 [5.3]; − 4.0 [5.2]), and days with nausea or vomiting (− 2.3 [4.6]; − 3.1 [4.5]; − 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation (<1%). Conclusion Fremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes. Trial registration ClinicalTrials.gov NCT03308968 (FOCUS).

scholarly journals Validation of the Headache Impact Test (HIT-6™) across episodic and chronic migraine

Cephalalgia ◽  
2010 ◽  
Vol 31 (3) ◽  
pp. 357-367 ◽  
Author(s):  
Min Yang ◽  
Regina Rendas-Baum ◽  
Sepideh F Varon ◽  
Mark Kosinski
Keyword(s):  
Chronic Migraine ◽  
Discriminant Validity ◽  
High Reliability ◽  
Reliability And Validity ◽  
Episodic Migraine ◽  
Migraine Headaches ◽  
Scale Scores ◽  
Headache Pain ◽  
Test Retest Reliability ◽  
Headache Impact

Objective: The purpose of this study was to assess psychometric properties of the six-item Headache Impact Text (HIT-6™) across episodic and chronic migraine. Methods: Using a migraine screener and number of headache days per month (HDPM), participants from the National Survey of Headache Impact (NSHI) study and the HIT-6 validation study (HIT6-V) were selected for this study. Eligible participants were categorized into three groups: chronic migraine (CM: ≥ 15 HDPM); episodic migraine (EM: < 15 HDPM); non-migraine headaches. Reliability and validity of the HIT-6 were evaluated. Results: A total of 2,049 survey participants met the inclusion/exclusion criteria for this study. Participants were identified as 6.4% CM; 42.1% EM; 51.5% non-migraine, with respective mean HIT-6 scores: 62.5 ± 7.8; 60.2 ± 6.8; and 49.1 ± 8.7. High reliability was demonstrated with internal consistency (time1/time2) of 0.83/0.87 in NSHI, and 0.82/0.92 in HIT6-V. Intra-class correlation for test-retest reliability was very good at 0.77. HIT-6 scores correlated significantly ( p < .0001) with total Migraine Disability Assessment Scale scores ( r = 0.56), headache pain severity ( r = 0.46), and HDPM ( r = 0.29). Discriminant validity analysis showed significantly different HIT-6 scores ( F = 488.02, p < .0001) across the groups. Conclusion: Results from these analyses confirm that the HIT-6 is a reliable and valid tool for discriminating headache impact across episodic and chronic migraine.

Right-to-left shunt is common in chronic migraine

Cephalalgia ◽  
2009 ◽  
Vol 30 (5) ◽  
pp. 535-542 ◽  
Author(s):  
SJ Nahas ◽  
WB Young ◽  
R Terry ◽  
A Kim ◽  
T Van Dell ◽  
...  
Keyword(s):  
General Population ◽  
Chronic Migraine ◽  
Tertiary Care ◽  
Episodic Migraine ◽  
Diagnostic Interview ◽  
Neurological Symptoms ◽  
Valsalva Manoeuvre ◽  
Clinical Implications ◽  
Severity Of Disease ◽  
Headache Clinic

Our aim was to determine the prevalence of right-to-left shunt (RtLS) in patients with chronic migraine (CM), and to correlate the presence and grade of RtLS with aura and neurological symptoms, and duration and severity of disease. The prevalence of RtLS in migraine without aura is similar to that of the general population (between 20 and 35%). In migraine with aura, the prevalence is much higher (approximately 50%). The prevalence in CM, with or without aura, is unknown. Consecutive patients between the ages of 18 and 60 years with CM attending a tertiary care specialty headache clinic over an 8-week period were eligible. There were 131 patients in the study. A structured diagnostic interview was performed. Bubble transcranial Doppler with Valsalva manoeuvre determined RtLS presence and grade. Sixty-six percent (86/131) of patients had RtLS, a statistically significantly greater rate than those reported in the general population and in migraine with or without aura ( P < 0.001). There was no difference in RtLS rate or grade between those with and those without aura. Specific headache features and the presence of neurological symptoms were similar between those with and those without RtLS. Compared with both the general population and the episodic migraine population (with and without aura), patients with CM, with or without aura, are more likely to have RtLS. The clinical implications of our findings need to be determined.

scholarly journals Routine clinical use of 15O-water cardiac PET: Initial experience with a novel automated solution

2021 ◽  
Vol 22 (Supplement_3) ◽  
Author(s):  
LP Tolbod ◽  
LC Gormsen
Keyword(s):  
Perfusion Imaging ◽  
Low Dose ◽  
Pet Scan ◽  
Clinical Use ◽  
Dynamic Pet ◽  
Initial Experience ◽  
Cardiac Perfusion ◽  
Pharmacological Stress ◽  
Push Button ◽  
Low Dose Ct

Abstract Funding Acknowledgements Type of funding sources: None. Introduction  While considered the gold standard for cardiac perfusion imaging and myocardial blood flow quantitation, the use of 15O-water has been largely restricted to research purposes. The practical hurdles associated with the ultra-short half-life of the tracer and the lack of dedicated software have hampered the routine clinical use of 15O-water and novel solutions have been sought to obviate the issues limiting its use. An innovative bedside 15O-water generator designed for simple push button operation and high patient through-put has been developed and recently installed at our institution and utilized clinically under a magistral exception. The system also includes an infusion device and a dedicated display and analysis software. We report the initial experience utilizing such solution for routine clinical use of 15O-water. Methods  The first routine human myocardial perfusion imaging tests with PET 15O-water were conducted at our institution in December 2020. The 15O-water was produced and infused using the bed-side water generator. The activity per scan was 400 MBq in 20-35 mL of saline infused at a speed of 1-2 mL/s. Each exam consisted of a low-dose CT followed by a 4 min rest dynamic PET scan and, finally, a 4 min stress dynamic PET scan. Pharmacological stress was induced using a 6 min infusion of adenosine (0.14 mg/kg/min) starting 2 min prior to the stress PET scan. The exam time (time from initiation of the low dose CT to the end of the stress PET scan) was monitored. Images were analyzed using the dedicated software. Results  Since its implementation on December 7, 2020 and as of February 23, 2021, all patients referred to the hospital for cardiac perfusion imaging have been studied with this approach. Over this period of time, a total of 295 patients have been imaged with an average of 6 patients per day (a total of 50 scan days, 3-8 patients per day). The median total exam time was 22 min (85% of the exams were within 25 min and 95% below 30 min). Conclusion   Routine clinical use of 15O-water PET has been practically implemented utilizing a novel bedside generator and infusion solution. The system has proven to be reliable and efficient. This initial experience suggests that a very high patient throughput is achievable with improved resource utilization. The expected high diagnostic accuracy of the test is being evaluated with the dedicated imaging software.

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