Risk Factors For Migraine Progression Research Articles

Migraine treatment: quo vadis? Real-world data study (2015–2022) in Spain

BackgroundMigraine is a leading cause of disability, estimated to affect one-in-ten people in Spain. This study aimed to describe the management of migraine in Spain and identify improvement areas.MethodsNon-interventional, retrospective, cross-sectional cohort study conducted using an electronic medical records database covering visits to public healthcare providers for 3% of the Spanish population. Patients with a migraine diagnosis (ICD-9 346) between 01/2015 and 04/2022 were included, as well as their demographic and clinical characteristics, prescribed migraine treatments and the specialty of the prescribing physicians.ResultsThe database included 61,204 patients diagnosed with migraine. A migraine treatment had been prescribed to 50.6% of patients over the last 24 months (only acute to 69.5%, both acute and preventive to 24.2%, and only preventive to 6.3%). The most frequently prescribed treatments were NSAIDs (56.3%), triptans (44.1%) and analgesics (28.9%). Antidepressants were the most common preventive treatment (prescribed to 17.9% of all treated patients and 58.7% of those treated with a preventive medication), and anti-CGRP monoclonal antibodies the least prescribed (1.7%; 5.7%). In 13.4% of cases, preventive medications were the first treatment: alone in 5.8% of cases and together with an acute medication in 7.6%. A fifth of patients who were initially prescribed with only acute treatment were later prescribed a preventive medication (20.7%). On average, it took 29.4 months for this change to occur. Two-thirds of patients started their preventive treatment in primary care (64.2%). The percentage of patients treated by a neurologist increased with the number of received preventive medications. However, 28.8% of patients who had already been prescribed five or more distinct preventive treatments were not treated by a neurologist. Migraine patients had between 1.2- and 2.2-times higher prevalence of comorbidities than the general population, age-gender adjusted.ConclusionsOur study emphasizes the need for improved management of migraine in Spain to reduce the risk of chronification and improve patient outcomes. More training and coordination across healthcare professionals is necessary to recognize and address risk factors for migraine progression, including multiple associated comorbidities and several lines of treatment, and to provide personalized treatment plans that address the complex nature of the condition.

Real-world opioid use among patients with migraine enrolled in US commercial insurance and risk factors associated with migraine progression.

BACKGROUND: Migraineurs may be categorized as having episodic migraine (EM: < 15 headache days/month) or chronic migraine (CM: ≥ 15 days/month for > 3 months with ≥ 8 days/month having features of migraine). Opioid use has been linked to progression from EM to CM. OBJECTIVE: To describe the utilization of opioid prescriptions among patients with migraine, to determine the association between opioid use and migraine progression, and to explore demographic and clinical risk factors for migraine progression. METHODS: This retrospective cohort study used Optum's deidentified Clinformatics Data Mart Database from January 2015 to December 2018. Adult patients with a migraine diagnosis and continuous health plan enrollment were included. Opioid use was measured by average daily morphine equivalent dose, also known as morphine milligram equivalent (MME). Descriptive statistics were used to summarize the opioid use by patient demographic and clinical characteristics. A Cox proportional hazards model with stepwise selection was used to determine the risk factors of new-onset CM. RESULTS: Overall, 35% of patients with migraine (27,331 of 78,134) received prescription opioids (> 0 MME/day) during the 12-month follow-up period. Higher opioid dosage was found in patients who had CM and comorbidities of interest. Compared with patients with EM, patients with CM were twice as likely to receive at least 20 MME/day (CM 3.8% vs EM 1.9%) and had a higher median opioid day supply (CM 20 vs EM 10) during follow-up. About 7% of patients with CM with at least 1 opioid prescription had at least 50 MME/day in any 90-day period during follow-up. A significant association was found between MME level and the likelihood of new-onset CM. Additional significant risk factors of migraine progression included younger age, female sex, South and West regions, and having a diagnosis of medication overuse headache, depression, back pain, or fibromyalgia (all P < 0.05). CONCLUSIONS: Despite guidelines and the availability of more migraine-specific treatments, opioids are still commonly prescribed to patients with migraines in real-world practice, especially for those with CM. In this study population, a higher risk of new-onset CM was associated with receiving higher opioid doses.

Headache in idiopathic intracranial hypertension. A CGRP-dependent head pain?

Headache is the most frequent and often the most severe symptom of idiopathic intracranial hypertension (IIH) clinical presentation, although pain characteristics are very variable among sufferers and the pain may even lack in some cases. Whatever the headache features, refractoriness to treatments, pain worsening in the recumbent position, and frequent awakenings with severe headache late in the night are the specific complains of such patients. However, a migraine or probable migraine headache, mostly with a chronic headache pattern, can be diagnosed in about 2/3 of the cases. In IIH cases without papilledema (IIHWOP), this leads to a high rate of misdiagnosis with primary chronic migraine (CM). Mechanisms responsible for the shared migrainous presentation of CM and IIH/IIHWOP may rely on a pathologic CGRP release from the rich trigemino-vascular innervated dural sinuses, congested in the course of raised intracranial pressure. The possible role of IIHWOP as a powerful and modifiable risk factor for migraine progression is discussed. Further studies investigating the possible efficacy of anti CGRP/receptor antibodies in IIH/IIHWOP headache treatment are needed.

SAT-108 Effects of Bariatric and Non-Bariatric Weight Loss on Migraine Headache in Obesity. A Systematic Review and Meta-Analysis

Background. Migraine and obesity are highly prevalent and chronic diseases. Evidence has shown that obesity may influence frequency and severity of migraine attacks and is a risk factor for migraine progression. Several studies have suggested that weight loss, achieved via surgical and non-surgical means, may improve migraine. Aim. To perform a meta-analysis on the effect of weight loss obtained by bariatric surgery or behavioral intervention on migraine frequency and indices of severity. Methods. A search through Pubmed/Medline, ISI-web of knowledge and Google Scholar retrieved 10 studies (n=473) that were used for meta-analysis. Selected outcomes were Headache Frequency, Pain Intensity, Disability and Attack Duration while BMI, BMI change, type of intervention (bariatric vs behavioral), type of population (adult vs pediatric) were used for moderators and meta-regression analysis. Results. Random effect meta-analysis shows that weight loss yields significant reductions in Headache Frequency (ES -0.65, 95% C.I. -0.88 to -0.42, p<0.0001), Pain Intensity (ES -0.81, 95% C.I. -1.19 to -0.44, p<0.0001), Disability (ES -0.61, 95% C.I. -0.77 to -0.45, p<0.0001) and Attack Duration (ES -0.35, 95% C.I. -0.62 to -0.08, p=0.01). Moderators and meta-regression analysis showed that improvement in migraine was not correlated either to the degree of obesity at baseline or the degree of weight reduction. In addition, the effect on migraine was similar when weight reduction was obtained with bariatric surgery or behavioral intervention and was comparable in adult and pediatric populations. Conclusions. Weight loss improves parameters of migraine headache in patients who have obesity independently of the type of intervention and the amount of weight loss. The mechanisms underlying the link between obesity, weight loss and migraine headache are still largely unclear although it is possible that alterations in chronic inflammation, adipocytokines, obesity comorbidities (i.e. OSAS), and overlapping behavioral and psychological risk factors may play a role.

The lesson of chronic migraine.

The hypothesis that central sensitization/allodynia is the common final mechanism responsible for the progression of migraine pain is supported by the possibility of tracing back to allodynic mechanisms the action of the main risk factors for chronic migraine validated by the recent literature. The comorbidity between migraine and idiopathic intracranial hypertension without papilledema is emerging as a new, commonly overlooked risk factor for migraine progression whose putative mechanism might also converge on the sensitization of central pain pathways. If headache progression always occurs at the end of a pathogenetic sequence typical of an individual susceptibility to allodynia, then the primary character of chronic migraine might be debated. Allodynia is not specific to migraine but is implied in the progressive amplification of pain after repeated stimuli, a universal adaptive phenomenon. Being largely conditioned by the individual comorbidity profile, allodynia may only in part be defined as primary in itself. Many migraine comorbid conditions, including a hidden idiopathic intracranial hypertension without papilledema, may emphasize susceptibility to allodynia and promote chronic migraine. These factors and comorbid conditions require to be individually assessed and adequately treated to optimize the therapeutic response.

General trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine progression

Migraine is a chronic disease with episodic manifestations. In a subgroup, attack frequency increases over time, leading to chronic migraine. One of the most important risk factors for migraine progression is frequency of headache attacks at baseline. Unfortunately, the actual effects of repeated activation of dural nociceptors are poorly known. We investigated the behavioral, anatomical, and electrophysiological changes induced by repeated low- and high-intensity stimulation of meningeal nociceptor by injecting an inflammatory soup in rats. Single high-intensity, but not low-intensity, stimulation produces a reversible cephalic allodynia. Upon repetition, however, low-intensity stimulation, too, induces a reversible cephalic allodynia, and high-intensity, reversible cephalic and extracephalic allodynia. Moreover, cephalic allodynia becomes, in part, persistent upon repeated high-intensity stimulation. Fos expression reveals that a single high-intensity stimulation already leads to widespread, trigeminal, and spinal central sensitization, and that such general central sensitization potentiates upon repetition. Trigeminovascular nociceptive neurons become persistently sensitized and their diffuse noxious inhibitory controls (DNIC) concomitantly impaired. Thus, compared with single stimulation, repeated dural nociceptor activation specifically leads to: 1) a gradual worsening of cutaneous hypersensitivity and general neuronal hyperexcitability and 2) spreading of cutaneous hypersensitivity superimposed on 3) persistent cephalic cutaneous hypersensitivity and trigeminal central sensitization. Such repetition-induced development of central sensitization and its consequence, cutaneous allodynia, may arise from both the general neuronal hyperexcitability that results from DNIC impairment and hyperexcitability that likely develops in trigeminal nociceptive neurons in response to their repetitive activation. These neuronal changes may in turn elevate the risk for developing chronic migraine.

Obesity and Chronic Daily Headache

Obesity may be the greatest epidemic of modern times. It leads to diabetes and heart disease and shortens lifespan. Although not a risk factor for migraine, it is associated with an increased frequency and intensity of migraine. Obesity is also comorbid with chronic daily headache and is a major risk factor for chronification of episodic migraine in adults and children. Although obesity is not a factor in the effectiveness of migraine treatment, it does increase the peripheral and central events in migraine, ultimately increasing the neurologic potential for migraine. Although evidence suggests that obesity is a modifiable risk factor for migraine progression, it is unknown if weight loss is related to decrease in headache frequency. Recent surgical results suggest that this is true. We suggest all possible effective techniques aimed at weight loss be undertaken for migraineurs, especially obese migraineurs, and that carefully monitoring weight changes should be routinely done as part of their migraine care.

Temporomandibular Disorders Are Differentially Associated With Headache Diagnoses

Temporomandibular disorders (TMDs) are considered to be comorbid with headaches. Earlier population studies have suggested that TMD may also be a risk factor for migraine progression. If that is true, TMD should be associated with specific headache syndromes (eg, migraine and chronic migraine), but not with headaches overall. Accordingly, our aim was to explore the relationship between TMD subtypes and severity with primary headaches in a controlled clinical study. The sample consisted of 300 individuals. TMDs were assessed using the Research Diagnostic Criteria for TMD, and primary headache was classified according to International Classification for Headache Disorders-2. Univariate and multivariate models assessed headache diagnoses and frequency as a function of the parameters of TMD. Relative to those without TMD, individuals with myofascial TMD were significantly more likely to have chronic daily headaches (CDHs) [relative risk (RR)=7.8; 95% confidence interval (CI), 3.1-19.6], migraine (RR=4.4; 95% CI, 1.7-11.7), and episodic tension-type headache (RR=4.4; 95% CI, 1.5-12.6). Grade of TMD pain was associated with increased odds of CDH (P<0.0001), migraine (P<0.0001), and episodic tension-type headache (P<0.05). TMD severity was also associated with headache frequency. In multivariate analyses, TMD was associated with migraine and CDH (P=0.001). Painful TMD (P=0.0034) and grade of TMD pain (P<0.001) were associated with headache frequency. TMD, TMD subtypes, and TMD severity are independently associated with specific headache syndromes and with headache frequency. This differential association suggests that the presence of central facilitation of nociceptive inputs may be of importance, as positive association was observed only when muscular TMD pain was involved.

Sinus venous stenosis-associated IIHWOP is a powerful risk factor for progression and refractoriness of pain in primary headache patients: a review of supporting evidences

Reported prevalence of idiopathic intracranial hypertension without papilledema (IIHWOP) in series of patients with chronic or transformed migraine is significantly higher than expected; yet, IIHWOP is not included among the risk factors for migraine progression. However, several studies provided evidences suggesting that IIHWOP could represent a possible, largely underestimated, risk factor for progression of pain in migraine and, possibly, in other primary headaches. Data from two recent studies, albeit aimed to different end-points, strongly support this hypothesis. In the first study, conducted on a large series of neurological patients without any sign or symptom of raised intracranial pressure (ICP), including chronic headache, the prevalence of bilateral central venous stenosis at magnetic resonance venography (MRV) was 23% and an IIHWOP at opening pressure was found in 48% of this subgroup (11% of the whole sample) while it was not detected in any of the subjects with normal MRV. This indicates that IIHWOP may be much more prevalent than believed in general population and that it can run without any symptom or sign of raised ICP in most of affected subjects. In the second paper, sinus venous stenosis-associated IIHWOP has been found in about one half of a large chronic primary headache patients series with poor response to treatments and in none of those with normal MRV. Moreover, after the diagnostic lumbar puncture, a transient improvement of headache frequency has been observed in the majority of intracranial hypertensive chronic headache subjects. Taken together, the data of these two recent papers rise the following hypothesis: (1) asymptomatic IIHWOP is much more prevalent than expected in general population; (2) IIHWOP is a powerful and largely unrecognized risk factor for progression of pain in primary headache patients; (3) sinus venous stenosis at MRV is a reliable predictor of raised intracranial hypertension also in asymptomatic patients; (4) sinus venous stenosis has a causative role in IIH pathophysiology. These assumptions share a potential high clinical impact and need to be urgently tested in adequately designed controlled studies.

Is idiopathic intracranial hypertension without papilledema a risk factor for migraine progression?

The association of chronic migraine (CM) with an idiopathic intracranial hypertension without papilledema (IIHWOP), although much more prevalent than expected in clinical series of CM sufferers, is not included among the risk factors for migraine progression. We discuss the available evidence supporting the existence of a pathogenetic link between CM and idiopathic intracranial hypertensive disorders and suggest a causative role for IIHWOP in migraine progression.

TEMPOROMANDIBULAR SYMPTOMS, MIGRAINE, AND CHRONIC DAILY HEADACHES IN THE POPULATION

Migraine is a chronic-recurrent disorder that sometimes progresses into chronic migraine, a subtype of the chronic daily headaches (CDH). Accordingly, identifying risk factors for progression is of importance.1 Most risk factors have been assessed as a dichotomous variable (present or not). More relevant is to demonstrate a dose relationship, where higher frequency or severity of exposure magnifies the risk. This has been suggested for head trauma,2 certain medications, obesity, and allodynia.1 Temporomandibular disorders (TMD) are considered to be comorbid with migraine.3,4 Since nociceptive inputs from the orofacial area may induce trigeminal sensitization,5 TMD may be a risk factor for migraine progression. Investigating associations between disorders is a prelude to the development of studies assessing causality. Accordingly, we explored the relationship between headache types and TMD, as well as number of TMD symptoms. ### Methods. This was a questionnaire-based population study, estimating prevalence rates of TMD symptoms and of primary headaches in a Brazilian urban population. Our sample (1,230 adults) was drafted from 484,422 inhabitants representative of Brazil by demographics. The 5 …

Excessive acute migraine medication use and migraine progression

Long considered a chronic disorder with a stable course, recent research demonstrates that, in a subgroup, migraine progresses to chronic migraine. Among the risk factors for migraine progression, acute symptomatic medication overuse (SMO) is regarded as one of the most important. Though SMO and chronic migraine are associated, several questions remain unanswered. First, the causal path is controversial (SMO as a cause or consequence). Second, it is unclear if specific classes of medication, as well as critical doses of exposures, are necessary. Herein we review this topic in the light of recent conducted research. Although several caveats exist and the data should be taken with caution, important findings are as follows: 1) Opiates are associated with migraine progression; critical dose of exposure is around 8 days per month, and the effect is more pronounced in men. 2) Barbiturates are also associated with migraine progression. Critical dose of exposure is around 5 days per month and the effect is more pronounced in women. 3) Triptans induced migraine progression in those with high frequency of migraine at baseline (10-14 days per month), but not overall. 4) Anti-inflammatory medications were protective in those with <10 days of headache at baseline, and, as triptans, induced migraine progression in those with high frequency of headaches. Accordingly, specific classes of medications are associated with migraine progression, and high frequency of headaches seems to be a risk factor for chronic migraine regardless of medication exposure.

From Migraine To Chronic Daily Headache: The Biological Basis of Headache Transformation

Migraine headache carries the potential of transforming into chronic daily headache (CDH) over a period of time. Although several risk factors for migraine progression to CDH have been identified, the biological basis of this transformation is unknown. In this review, the consequences of stressful life events and medication overuse, 2 risk factors associated with the development of CDH, on brain processes involved in headache are examined. The extensive overlap in both neural circuitry and cellular events that occur with stress, medication overuse, and migraine provide insight into potential mechanisms that may lead to CDH. Particular attention is devoted to the effect of stress and medication overuse on peripheral and central neuroimmune interactions that can facilitate pain signaling. These interactions include the degranulation of mast cells in the dura, causing the sensitization of primary afferent neurons, as well as the activation of glial cells in the brain that can lead to central sensitization. It is hypothesized that the biological processes involved in migraine headache are directly impacted by stress, medication overuse, and other risk factors, resulting in a reduced threshold for induction of headache and transformation of episodic migraine to CDH.

Modifiable Risk Factors for Migraine Progression (or for Chronic Daily Headaches)—Clinical Lessons

Herein we summarize clinical issues gleaned from a full peer-reviewed article on modifiable risk factors for migraine. Since migraine is progressive in some but not in most individuals, identifying patients at risk for progression is crucial. Key interventions include: (1) Decrease headache frequency with behavioral and pharmacologic interventions; (2) Monitor the body mass index and encourage maintenance of normal weight; (3) Avoid medication overuse; (4) Avoid caffeine overuse; (5) Investigate and treat sleep problems and snoring; (6) Screen and treat depression and other psychiatric comorbidities. These recommendations have not been demonstrated to improve outcomes in longitudinal studies.

When migraine progresses: transformed or chronic migraine

Migraine may be conceptualized, not just as an episodic disorder, but as a chronic recurrent and sometimes chronic progressive disorder. Transformed migraine, often referred to as chronic migraine is the result of migraine progression. This article will review the clinical features of transformed migraine, highlighting that its phenotype varies according to stage. Early in the process of transformation, attacks with migraine features are very common. As the disease evolves, most attacks lack the migraine features. The risk factors for migraine progression and the mechanisms for progression will be discussed. This review concludes with the prospects for treating transformed migraine and avoiding migraine progression.