Cutaneous allodynia is more frequent in chronic migraine, and its presence and severity seems to be more associated with the duration of the disease

ABSTRACT Objective To evaluate cutaneous allodynia among patients with chronic and episodic migraine in a tertiary headache clinic. Methods 80 subjects with episodic migraine and 80 with chronic migraine were assessed in a tertiary hospital. The 12-item Allodynia Symptom Checklist/Brazil questionnaire was applied to classify subjects according to the presence and severity of cutaneous allodynia. Results Cutaneous allodynia was identified in 81.3% of the episodic migraine group and 92.5% of the chronic migraine group (p = 0.03). No increased association could be attributed to chronic migraine when adjusted by years with disease (PR = 1.12; 95%CI = 0.99 to 1.27; p = 0.06). The groups also did not differ in the severity of allodynia, and severe presentation was the most frequent. Discussion Both groups seemed to be similarly affected in the cephalic and extracephalic regions, with the same severity. Conclusion Cutaneous allodynia is more frequent in chronic migraine, and its presence and severity seems to be more associated with the duration of the disease.

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Right-to-left shunt is common in chronic migraine

Cephalalgia ◽

10.1111/j.1468-2982.2009.02002.x ◽

2009 ◽

Vol 30 (5) ◽

pp. 535-542 ◽

Cited By ~ 11

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.

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Identifying Cutaneous Allodynia in Chronic Migraine Using a Practical Clinical Method

Cephalalgia ◽

10.1111/j.1468-2982.2006.01255.x ◽

2007 ◽

Vol 27 (2) ◽

pp. 111-117 ◽

Cited By ~ 48

Author(s):

A Ashkenazi ◽

M Sholtzow ◽

JW Shaw ◽

R Burstein ◽

WB Young

Keyword(s):

Chronic Migraine ◽

Demographic Data ◽

Poor Response ◽

Practical Method ◽

Episodic Migraine ◽

Entire Study ◽

Clinical Method ◽

Cutaneous Allodynia ◽

History Of ◽

Acute Headache

Cutaneous allodynia is common in migraine. In the majority of previous studies on allodynia in migraine, only patients with episodic migraine (EM) were included. Little is known on patterns of allodynia in chronic migraine (CM). Since the presence of allodynia is associated with a poor response to triptans, a clinically practical method to test migraine patients for allodynia would be useful to the clinician. The aim of this study was to assess the prevalence of dynamic mechanical (brush) allodynia (BA) in CM, using a clinically practical method. Eighty-nine CM patients were prospectively recruited. Patients were given a structured questionnaire regarding demographic data and migraine characteristics. Allodynia was tested using a 10 x 10-cm gauze pad to brush various areas of the skin lightly. The prevalence of BA in the entire study population and in different patient subgroups was calculated. BA was present in 42.7% (38/89) of the patients. The presence of allodynia was unrelated to age, disease duration or to the occurrence of an acute headache exacerbation at the time of testing. Allodynia was positively associated with a history of migraine aura. BA was most common in the cephalic area, but was also seen in cervical dermatomes. BA is common in CM and, unlike in EM, is not significantly affected by the occurrence of an acute headache exacerbation. This suggests that central trigeminovascular neurons are chronically sensitized in patients experiencing migraine headache >15 days per month. The testing of BA in the clinical setting is possible using a simple and brief approach. It allows the clinician to determine whether the patient is sensitized, a diagnosis that affects treatment decisions.

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Migraine progression in subgroups of migraine based on comorbidities

Neurology ◽

10.1212/wnl.0000000000008589 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2224-e2236 ◽

Cited By ~ 14

Author(s):

Richard B. Lipton ◽

Kristina M. Fanning ◽

Dawn C. Buse ◽

Vincent T. Martin ◽

Lee B. Hohaia ◽

...

Keyword(s):

Chronic Migraine ◽

Episodic Migraine ◽

Study Data ◽

Continuous Variables ◽

Web Based ◽

Symptom Severity Scale ◽

Hazard Ratios ◽

Cutaneous Allodynia ◽

Risk Of Progression ◽

Relationship Of

ObjectiveTo test the hypothesis that statistically defined subgroups of migraine (based on constellations of comorbidities and concomitant conditions; henceforth comorbidities), previously identified using Chronic Migraine Epidemiology and Outcomes (CaMEO) Study data, differ in prognosis, as measured by rates of progression from episodic migraine (EM) to chronic migraine (CM).MethodsThe onset of CM was assessed up to 4 times over 12 months in individuals with EM and ≥1 comorbidity at baseline, based on constellations of comorbidities (comorbidity classes). The “fewest comorbidities” class served as reference. Individuals completing ≥1 follow-up survey from the web-based CaMEO Study were included. Covariates included sociodemographic variables and headache characteristics. Sex, income, cutaneous allodynia, and medication overuse were modeled as binary variables; age, body mass index, headache-related disability (Migraine Disability Assessment [MIDAS]), and Migraine Symptom Severity Scale as continuous variables. CM onset was assessed using discrete time analysis.ResultsIn the final sociodemographic model, all comorbidity classes had significantly elevated hazard ratios (HRs) for risk of progression to CM from EM, relative to fewest comorbidities. HRs for CM onset ranged from 5.34 (95% confidence interval [CI] 3.89–7.33; p ≤ 0.001) for most comorbidities to 1.53 (95% CI 1.17–2.01; p < 0.05) for the respiratory class. After adjusting for headache covariates independently, each comorbidity class significantly predicted CM onset, although HRs were attenuated.ConclusionsSubgroups of migraine identified by comorbidity classes at cross-section predicted progression from EM (with ≥1 comorbidity at baseline) to CM. The relationship of comorbidity group to CM onset remained after adjusting for indicators of migraine severity, such as MIDAS.Clinicaltrials.gov identifierNCT01648530.

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Prevalence of parafunctional habits and temporomandibular dysfunction symptoms in patients attending a tertiary headache clinic

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2010000300009 ◽

2010 ◽

Vol 68 (3) ◽

pp. 377-380 ◽

Cited By ~ 10

Author(s):

Yára Dadalti Fragoso ◽

Heloísa Helena Carvalho Alves ◽

Sidney Oliveira Garcia ◽

Alessandro Finkelsztejn

Keyword(s):

Chronic Migraine ◽

Orofacial Pain ◽

Outpatient Service ◽

Episodic Migraine ◽

Primary Headaches ◽

Further Training ◽

Analgesic Drugs ◽

Temporomandibular Dysfunction ◽

High Prevalence ◽

Headache Clinic

OBJETIVE: To investigate the most prevalent forms of headache in a tertiary outpatient service, and to assess the frequency of associated parafunctional habits and temporomandibular dysfunction symptoms (TMD). METHOD: All new patients referred to the Headache Outpatient Service in UNIMES during 2008 were prospectively assessed by the neurologist and the dental surgeon. RESULTS: Eighty new patients were assessed; chronic migraine and episodic migraine without aura were the most prevalent conditions, accounting for 66.3% of all cases. There was significantly higher use of analgesics/days for the chronic migraine patients. The prevalence of parafunctional habits was 47.5% and the prevalence of TMD symptoms was 35%. CONCLUSION: The high prevalence of primary headaches, parafunctional habits and TMD symptoms and the inadequate use of analgesic drugs suggest that primary healthcare units need further training in the field of headache and orofacial pain.

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Prevalence of right-to-left shunts on transcranial Doppler in chronic migraine and medication-overuse headache

Cephalalgia ◽

10.1177/0333102413497600 ◽

2013 ◽

Vol 34 (1) ◽

pp. 37-41 ◽

Cited By ~ 5

Author(s):

Song Guo ◽

Sarvnaz Shalchian ◽

Pascale Gérard ◽

Michael Küper ◽

Zaza Katsarava ◽

...

Keyword(s):

Chronic Migraine ◽

Transcranial Doppler ◽

Medication Overuse ◽

Medication Overuse Headache ◽

Episodic Migraine ◽

Severe Form ◽

Cross Sectional ◽

Headache Clinic ◽

Chronic Headaches ◽

Chronic Migraineurs

Background It was suggested that right-to-left shunt (RLS) may be highly prevalent in chronic migraine (CM) patients, indicating that patent foramen ovale (PFO) might be an aggravating and chronifying factor of migraine. Since a high proportion of chronic migraineurs also have medication-overuse headache (MOH), one may wonder if they have a more severe form of the disorder and more frequently a PFO. Objective The objective of this study is to determine the prevalence and grade of RLS in patients suffering from CM and MOH. Methods A cross-sectional multicenter study of air-contrast transcranial Doppler was conducted in 159 patients with CM ( n = 57) or MOH ( n = 102) attending a tertiary headache clinic. Results The prevalence of RLS in CM was 37% (11% large shunts) and in MOH patients 31% (13% large shunts). There was no difference between the two groups ( p = 0.49). Conclusion RLS prevalence in CM is within the upper range of those reported in episodic migraine without aura or in the general population, and not higher in MOH. PFO is thus unlikely to have a significant causal role in these chronic headaches.

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Salivary glutamate is elevated in individuals with chronic migraine

Cephalalgia ◽

10.1177/0333102417742366 ◽

2017 ◽

Vol 38 (8) ◽

pp. 1485-1492 ◽

Cited By ~ 6

Author(s):

Ji Hye Nam ◽

Hun Seok Lee ◽

Jiyoung Kim ◽

Jinmi Kim ◽

Min Kyung Chu

Keyword(s):

Chronic Migraine ◽

Total Protein ◽

Episodic Migraine ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Healthy Controls ◽

Glutamate Level ◽

Migraine Group ◽

Post Hoc ◽

And Control

Background Glutamate has been implicated in migraine pathogenesis, and is elevated in the plasma, cerebrospinal fluid, and saliva in migraineurs. However, no comparison of glutamate levels among chronic migraine, episodic migraine and controls has been reported. The aim is to compare salivary glutamate levels of individuals with chronic migraine with those of individuals with episodic migraine and healthy controls. Methods We investigated salivary glutamate level of 46 women with chronic migraine, 50 women with episodic migraine, and 19 healthy controls via enzyme linked immunosorbent assay. Results The salivary glutamate level of the chronic migraine group (median and interquartile range, 20.47 [15.27–30.15] pmol/mg total protein) was significantly higher than those of the episodic migraine (16.17 [12.81–20.15] pmol/mg total protein, p = 0.008) and control (12.18 [9.40–16.24] pmol/mg total protein, p = 0.001) groups. The salivary glutamate level of the episodic migraine group was marginally elevated from that of the control group (post hoc p = 0.016). Thresholds of 16.58 and 17.94 pmol/mg total protein optimize the sensitivity and specificity to differentiate chronic migraine participants from healthy controls and episodic migraine participants, respectively. Conclusions Salivary glutamate level was elevated in chronic migraine participants. These data suggest that salivary glutamate level could be an indicator of CM

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Comparison of self-reported cutaneous allodynia and brushing allodynia during migraine attacks

Cephalalgia ◽

10.1177/0333102409352910 ◽

2010 ◽

Vol 30 (6) ◽

pp. 682-685 ◽

Cited By ~ 6

Author(s):

Chi-Hsiang Chou ◽

Jong-Ling Fuh ◽

Jaw-Ching Wu ◽

Shuu-Jiun Wang

Keyword(s):

Chronic Migraine ◽

Episodic Migraine ◽

Previous Experience ◽

Head Pain ◽

Cutaneous Allodynia

This study compares the results of brushing allodynia (BA) during migraine attacks to those of self-reported cutaneous allodynia. We recruited 100 patients (20 with chronic migraine, 80 with episodic migraine) and performed a gauze-brushing test to detect BA. A previous experience of cutaneous allodynia was queried. Seventeen patients reported having allodynia before, whereas 22 patients exhibited BA. The frequency of self-reported allodynia (12.5% vs. 35.0%, p = .040) but not BA (21.3% vs. 25.0%, p = .765) differed between patients with episodic migraine and those chronic migraine. Patients with aura ( N = 8) had a higher frequency of both self-reported allodynia (62.5% vs. 12.2%, p = .003) and BA (87.5% vs. 17.6%, p < .001) than those without aura ( N = 92). Some allodynia symptoms, including avoidance of washing hair, touching the head, combing hair and lying on the site of head pain, were associated with BA (all p < .05). Our study showed that BA during migraine attacks correlated well with prior allodynia symptoms. The frequencies of BA and self-reported allodynia depend on the composition of different migraine subtypes and the timing of the gauze-brushing test.

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Efficacy of erenumab in chronic migraine patients with and without ictal allodynia

Cephalalgia ◽

10.1177/03331024211010305 ◽

2021 ◽

pp. 033310242110103

Author(s):

Richard B Lipton ◽

Rami Burstein ◽

Dawn C Buse ◽

David W Dodick ◽

Reija Koukakis ◽

...

Keyword(s):

Standard Deviation ◽

Confidence Interval ◽

Chronic Migraine ◽

Acute Treatment ◽

Acute Migraine ◽

Symptom Checklist ◽

Double Blind ◽

Cutaneous Allodynia ◽

Specific Medication ◽

Post Hoc

Background Ictal cutaneous allodynia, common in chronic migraine, is associated with reduced responses to acute treatment with triptans. Allodynia’s impact on the efficacy of newer preventive treatments such as erenumab is unknown. Methods Post-hoc subgroup analysis of a double-blind, randomized, placebo-controlled 12-week study of erenumab in chronic migraine, contrasting those with no allodynia with those with moderate-severe allodynia assessed with the Allodynia Symptom Checklist-12, was undertaken. Results Of 648 randomized individuals with baseline Allodynia Symptom Checklist-12 scores, 386 (59.6%) had no allodynia and 153 (23.6%) had moderate-to-severe allodynia. Mean (standard deviation) baseline monthly migraine days were 17.6 (4.8) and 18.9 (4.3), respectively. Compared to placebo, the erenumab group had greater reductions in monthly migraine days and monthly acute migraine-specific medication days in both no allodynia and allodynia subgroups. Mean (95% confidence interval) treatment differences in change from baseline for monthly migraine days at week 12 were −2.5 (−3.7, −1.4) in the no allodynia subgroup and −3.3 (−5.3, −1.3) in the moderate-severe allodynia subgroup. Change in acute migraine-specific medication days were −3.3 (−4.3, −2.3) and −2.5 (−4.3, −0.8), respectively. Conclusions Erenumab’s efficacy in reducing monthly migraine days and acute migraine-specific medication days in chronic migraine was not impacted by the presence of moderate-severe ictal allodynia. Trial registration: ClinicalTrials.gov NCT02066415

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

Journal of Clinical Medicine ◽

10.3390/jcm10132779 ◽

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.

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

The Journal of Headache and Pain ◽

10.1186/s10194-021-01215-9 ◽

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.

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