Surgical Management of Headache Disorders - A Systematic Review of the Literature.

PURPOSE OF REVIEW: This review article critically evaluates the latest advances in the surgical treatment of headache disorders. RECENT FINDINGS: Studies have demonstrated the effectiveness of innovative screening tools, such as doppler ultrasound, pain drawings, magnetic resonance neurography, and nerve blocks to help identify candidates for surgery. Machine learning has emerged as a powerful tool to predict surgical outcomes. In addition, advances in surgical techniques, including minimally invasive incisions, fat injections, and novel strategies to treat injured nerves (neuromas) have demonstrated promising results. Lastly, improved patient-reported outcome measures are evolving to provide a framework for comparison of conservative and invasive treatment outcomes. Despite these developments, challenges persist, particularly related to appropriate patient selection, insurance coverage, delays in diagnosis and surgical treatment, and the absence of standardized measures to assess and compare treatment impact. Collaboration between medical/procedural and surgical specialties is required to overcome these obstacles.

Commentary on 2022 guidelines on clinical trial design in cluster headache and further suggestions.

BACKGROUND: New guidelines for cluster headache clinical trials were recently published. We welcome these new guidelines and raise additional considerations in trial methodologies. MAIN BODY: We present non-inferiority trials to overcome ethical issues with placebo use, and additionally discuss issues with trial recruitment. CONCLUSIONS: We highlight some possible issues and solutions to be considered with the recently published cluster headache trial guidelines.

Treatment Delay From Onset of Occipital Neuralgia Symptoms to Treatment with Nerve Decompression Surgery: A Prospective Cohort Study.

BACKGROUND: The aim of this study was to a) evaluate the time between onset of occipital neuralgia symptoms and nerve decompression surgery, b) perform a cost comparison analysis between surgical and non-surgical treatment of occipital neuralgia and c) report postoperative results of nerve decompression for occipital neuralgia. METHODS: 1,112 subjects who underwent screening for nerve decompression surgery were evaluated for occipital neuralgia. 367 (33%) patients met the inclusion criteria. Timing of occipital neuralgia symptom onset and pain characteristics were prospectively collected. Cost associated with the non-surgical treatment of occipital neuralgia was calculated for the period between onset of symptoms and surgery. RESULTS: 226 (73%) patients underwent occipital nerve decompression. The average time between onset of occipital neuralgia and surgery was 19 years (7.1-32). Postoperatively, the median number of pain days per month decreased by 17 (0-26, 57%) (p < 0.001), the median pain intensity decreased by 4 (2-8, 44%) (p < 0.001), and median pain duration in hours was reduced by 12 (2-23, 50%) (p < 0.001). The annual mean cost of non-surgical occipital neuralgia treatment was $28,728.82 ($16,419.42-$41,198.41) per patient. The mean cost during the 19-year timeframe prior to surgery was $545,847.75($311,968.90-$782,769.82). CONCLUSION: This study demonstrates that patients suffer from occipital neuralgia for an average of 19 years prior to undergoing surgery. Nerve decompression reduces symptom severity significantly and should be considered earlier in the treatment course of occipital neuralgia that is refractory to conservative treatment to prevent patient morbidity and decrease direct and indirect healthcare costs. IRB REGISTRATION NUMBER & NAME: Weill Cornell Medicine: 23-04025985, Prospective Cohort Study Investigating Long- Term Outcomes After Headache Surgery.The Massachusetts General Hospital: 2012P001527, Correlation of pre-operative pain self-efficacy and post-operative migraine-specific symptoms and disability.

The Diagnosis and Management of Posttraumatic Headache with Associated Painful Cranial Neuralgias: a Review and Case Series.

BACKGROUND: Cranial neuralgias are common in the setting of posttraumatic headache. They may exacerbate underlying primary headache disorders and therefore may be overlooked in clinical practice. Frequently, cranial neuralgias generate neuropathic symptoms such as lancinating pain and sensory dysesthesias. Cranial neuralgias are identified based on a clinical history of focal neuropathic pain and physical exam findings including tenderness with palpation and percussion, at times eliciting radiating pain or paresthesias in the corresponding sensory nerve distribution. PURPOSE OF REVIEW: This article is a brief review of the literature and a retrospective report of 2 cases of posttraumatic headache with associated painful cranial neuralgias. RECENT FINDINGS: Two patients presented with headaches that met criteria for posttraumatic headache, but their history and physical examination suggested the presence of a focal painful cranial neuralgia. One patient was diagnosed with auriculotemporal neuralgia, which was exquisitely responsive to an auriculotemporal nerve block. The second patient was diagnosed with supratrochlear neuralgia, which was effectively treated with a supratrochlear nerve block. In both cases, adequate treatment of the painful cranial neuralgia resulted in significant improvement of the baseline PTH. Painful cranial neuralgias frequently occur within the clinical spectrum of posttraumatic headache, but are often undiagnosed. Treatment options for painful cranial neuralgias are often different than those traditionally employed for posttraumatic headache without cranial neuralgias, which can include peripheral nerve blockade, neuropathic medications, and in refractory cases, peripheral nerve decompression surgery.

Non-invasive vagus nerve stimulation for primary headache: A clinical update.

BACKGROUND: Non-invasive vagus nerve stimulation (nVNS) is a proven treatment for cluster headache and migraine. Several possible mechanisms of action by which nVNS mitigates headache have been identified. METHODS: We conducted a narrative review of recent scientific and clinical research into nVNS for headache, including findings from mechanistic studies and their possible relationships to the clinical effects of nVNS. RESULTS: Findings from animal and human studies have provided possible mechanistic explanations for nVNS efficacy in headache involving four core areas: Autonomic nervous system functions; cortical spreading depression inhibition; neurotransmitter regulation; and nociceptive modulation. We discuss how overlap and interplay among these areas may underlie the utility of nVNS in the context of clinical evidence supporting its safety and efficacy as acute and preventive therapy for both cluster headache and migraine. Possible future nVNS applications are also discussed. CONCLUSION: Significant progress over the past several years has yielded valuable mechanistic and clinical evidence that, combined with the excellent safety and tolerability profile of nVNS, suggests that it should be considered a first-line treatment for both acute and preventive treatment of cluster headache, an effective option for acute treatment of migraine, and a highly relevant, practical option for migraine prevention.

Erenumab-Induced Severe Nausea Leading to Smoking Cessation: A Retrospective Case Series.

OBJECTIVE: Erenumab is a novel treatment modality with a relatively benign and safe side effect profile, currently approved for the prevention of migraine headache. We present 3 cases with chronic migraine who are cigarette smokers were prescribed erenumab, and developed an intense smoking-induced nausea which eventually led to smoking cessation. METHODS: A multicenter retrospective review of 3 cases with cigarette smoking, one of whom was also smoking marijuana, suffering from chronic migraine resistant to multiple preventive therapies was studied. All were prescribed monthly injections of erenumab 70 mg. Response in terms of headache frequency and intensity and smoking habits was obtained through medical record review. RESULTS: Out of 3 patients, 2 reported reduced headache frequency and intensity. All patients developed severe nausea while smoking cigarettes after their first dose of erenumab, leading to smoking cessation. One patient co-smoked marijuana, which did not result in nausea after being treated. CONCLUSION: To the best of our knowledge, this is the first report of severe nausea secondary to erenumab administration and smoking cigarettes, which finally resulted in complete cigarette smoking cessation. As such, further study is indicated on the benefit of erenumab and other calcitonin gene-related peptide antagonists in migraineurs who smoke to promote smoking cessation.

Getting to the Heart of the Matter: Migraine, Triptans, DHE, Ditans, CGRP Antibodies, First/Second-Generation Gepants, and Cardiovascular Risk.

PREMISE: The science of migraine pathophysiology has advanced significantly since the 1930's. Imaging techniques, neurochemical analysis, clinical trials, and the clinical experience of providers treating migraine patients have not only sharpened our understanding of the disease, but have also led to the development of novel neural-based targets. Targeted therapies such as calcitonin gene-related peptide (CGRP) antibodies and "Second Generation" CGRP receptor antagonists (Gepants) have not only demonstrated efficacy, but have not resulted in any significant cardiovascular nor other serious adverse events. "First Generation" Gepants were associated with liver toxicity. PROBLEM: Triptans and dihydroergotamine (DHE) are contraindicated in patients with hemiplegic and basilar migraine based on theories of migraine pathophysiology from the 1930s. While our understanding of migraine has evolved substantially, perceived concerns of safety from almost a century ago continue to preclude their use in certain patient populations. POTENTIAL SOLUTION: While migraine aura was once thought to be primarily due to vasoconstriction, current evidence debunks this concept. For instance, hemiplegic migraine is the consequence of genetic mutations resulting in channelopathies without evidence of cerebral ischemia or infarction. Evidence of basilar artery constriction as postulated in basilar migraine is also lacking. This recognition has led the International Headache Society to rename basilar-type migraine to migraine with brainstem aura. The following discussion reviews current literature with respect to migraine as a neuronal disorder, as well as the published data on the safety of triptans, DHE, Ditans (a novel class of 5-HT1f receptor agonists), CGRP antibodies, and Gepants.

Headache Attributed to Autonomic Dysreflexia: Clinical Presentation, Pathophysiology, and Treatment.

A patient presenting with marked elevation in blood pressure and concurrent headache often presents a diagnostic challenge for even the most seasoned clinician. When marked hypertension and headache occur in a patient with a history of upper spinal cord injury, the patient should be presumed to have autonomic dysreflexia until proven otherwise. Autonomic dysreflexia can at times trigger headaches, hypertension, and variations in pulse, as well other autonomic signs and symptoms. Autonomic dysreflexia is a medical emergency for which appropriate treatment may be life-saving. In this review, we address the historical origins, risk factors, pathophysiology, diagnostic criteria, clinical presentation, differential diagnosis, and treatment of headache attributed to autonomic dysreflexia. Included are two case presentations from the authors' clinic, which illustrate the diagnosis and treatment of headache attributed to autonomic dysreflexia.

An Analysis of UCNS Certified Headache Center Patient Intake Forms.

OBJECTIVE: Compare the similarities and differences among headache intake forms from headache centers with United Council of Neurologic Subspecialties (UCNS) accredited headache medicine fellowships in the United States. Patient intake forms establish a first communication with patients. There have been no studies evaluating them at headache centers. Analysis of these forms can provide insight into their content and potential for improvement. METHODS: This observational study involved collection and analysis of intake forms from 25 UCNS fellowship accredited headache centers from July 2014 to October 2014. Forms were compared and contrasted in terms of data fields included, response format, and use of validated assessment tools. RESULTS: Forms shared many common elements, yet were highly variable in content, style, scales, and methods of analysis. Twenty percent (5/20) of centers did not have a formal intake form. Forms ranged from 1 to 28 pages. Seventy percent (12/17) utilized a check box format, 23% (4/17) utilized an open ended/fill in the blank format, and 6% (1/17) utilized a circle the response(s) format. Family history was inquired about in 82% (14/17) of forms and past medical history (PMH) in 58% (10/17) of forms. Gender questions were asked 82% (14/17) of the time for women, 29% (5/17) for men. Eighty-eight percent (15/17) of forms had questions concerning any type of previous medication tried. DISCUSSION: Patient intake forms are useful for clinical purposes, but vary markedly between UCNS headache centers. Ultimately, a universal intake form could be generated, providing a research-based alternative to the form currently used at each center. Use of a standardized intake form by UCNS centers would streamline data collection, a good first step in the eventual generation of a headache registry.

A retrospective analysis of triptan and dhe use for basilar and hemiplegic migraine.

BACKGROUND: Patients with basilar migraine (BM) and hemiplegic migraine (HM) have been excluded from triptan and DHE clinical trials due to a potential risk of ischemic vascular events, and the FDA mandates that package labeling state that they are contraindicated in BM and HM. The objective of this study was to demonstrate that triptans and DHE can be used for the abortive treatment of BM and HM without significant adverse ischemic vascular events. METHODS: A retrospective chart review of patients with BM features or HM who received acute abortive treatment with either triptans or DHE was conducted at 4 headache centers to assess the frequency of ischemic vascular events after administration. The diagnoses of BM or HM were made by headache specialists based on The International Classification of Headache Disorders, 2nd edition (ICHD-II). Searchable terms included BM, vertigo, dysarthria, diplopia, hemiplegia/hemiparesis, facial droop, weakness, confusion, altered consciousness, confusion, ataxia, and aphasia, as well as all triptans or DHE. RESULTS: The study included 67 patients with BM features and 13 patients with HM. Among those receiving triptans, 40 were in the BM group and 5 were in the HM group. Among those receiving DHE, 27 were included in the BM group and 8 were in the HM group. No side effects of stroke or myocardial infarction were reported. In the triptan group, 5 patients reported adverse effects that included GI upset, rash, neck dystonia, nightmares, and flushing. In the DHE group, 5 patients had adverse events that included chest tightness, dystonic reaction, transient asymptomatic anterior T wave inversion, and agitation. CONCLUSION: In this retrospective study, triptans and DHE were used with no reported, subsequent acute/subacute ischemic vascular events for the abortive treatment of migraines with basilar and hemiplegic-type features. Although the small sample sizes generated theoretical statistical event rates of 4.5% for BM and 23% for HM, there has been no clear evidence that BM and HM carry an actual elevated risk for vascular events compared with migraine with aura.

No Laughing Matter: Gelastic Migraine and Other Unusual Headache Syndromes.

Primary and secondary headache disorders have established diagnostic criteria in the International Classification of Headache Disorders IIIb, as well as classic findings, which although not part of the formal criteria are often suggestive of a particular diagnosis. At times, headache disorders can involve unusual symptoms that lack an identifiable secondary cause. This review will discuss some of these unusual symptoms, including headache associated auditory and olfactory symptoms, as well as two case reports involving gelastic migraine and migrainous thoracalgia.

A tale of two systems: cardiac cephalalgia vs migrainous thoracalgia.

The practice of headache medicine is challenging, and excluding secondary causes of headaches is essential for proper diagnosis and treatment. The evaluation of secondary headaches often leads to investigations involving organ systems other than the nervous system. As such, headache, which is typically thought to be neurologic in origin, can be a manifestation of cardiac pathology in the form of cardiac cephalalgia. Conversely, chest pain, which is typically thought to be cardiac in origin, could be a manifestation of a neurologic disease process in the form of atypical migraine aura. In the presented cases, we demonstrate headaches that involve cardiac and neurologic pathology with atypical presentations.

A critical evaluation of migraine trigger site deactivation surgery.

Migraine headache trigger site deactivation surgery is a term that encompasses 4 different surgical procedures that are performed based on headache onset location for the preventative treatment of migraine headaches. Multiple studies have demonstrated some efficacy of these procedures, but closer evaluation of the methodology of these studies reveals major flaws in study design. In this article, the author provides an overview of the procedures and presurgical screening tools, as well as a critical evaluation of 2 of the major studies that have been published. In addition, the author provides his opinion on future study designs that may help to better determine the potential efficacy of these experimental procedures and potential headache subtypes (contact point headache, supraorbital neuralgia, and occipital neuralgia) that may respond to peripheral decompression surgery.

Education and decision making at the time of triptan prescribing: patient expectations vs actual practice.

BACKGROUND: Optimizing patient satisfaction with their medical care and maximizing patient adherence with treatment plans requires an understanding of patient preferences regarding education and their role in decision making when treatments are prescribed. OBJECTIVE: To assess the congruence between patient expectations and actual practice regarding education and decision making at the time a triptan is prescribed. METHODS: This multicenter cross-sectional survey was performed by headache fellow members of the American Headache Society Headache Fellows Research Consortium at their respective tertiary care headache clinics. Migraine patients who were new patients to the headache clinic and who were current triptan users (use within prior 3 months and for ≥1 year) or past triptan users (no use within 6 months; prior use within 2 years) completed questionnaires that assessed the education they received and their role in decision making at the time a triptan was first prescribed as well as their desire for education and participation in decision making when a triptan is prescribed. RESULTS: Consistent with patient preference, most participants received the majority of their education about the triptan from the prescriber's office (70.2%). In descending rank order, participants most desired to be informed about how to decide if a triptan should be taken, when during the course of migraine a triptan should be taken, possible side effects, cost, and how to obtain refills. Regarding side effects, most participants preferred to receive education about the most common side effects of a triptan rather than addressing all possible side effects. Regarding triptan dosing, participants desired to be informed in descending order of importance about taking other medications with triptans, how many doses can be taken for each migraine, how many doses can be taken each week/month, what to do if the triptan does not work, and the triptan mechanism of action. The vast majority of participants (92%) preferred that the decision to prescribe a triptan be a joint decision between the patient and the provider. In actual practice, participants were not as involved in decision making as they would like to be, with patients reporting that the prescriber was the sole decision maker 55.1% of the time. Participants had confidence in their providers (87.7%) and generally felt they did a good job educating them about the triptan (71.1%). CONCLUSIONS: Based on this study, it is clear that patients prefer the shared model approach to medical decision making in regards to the prescription of triptans. The majority of patients received education that was generally consistent with their desires. Patients preferred that the prescribing provider be the primary source of information. The most desired educational topics included when/if a triptan should be taken, the number of times a triptan can be taken for a single migraine, co-administration with other acute medications, and the most common side effects. Focusing on these topics should enhance patient satisfaction and may improve compliance.

Identifying the factors underlying discontinuation of triptans.

OBJECTIVE: To identify factors associated with triptan discontinuation among migraine patients. BACKGROUND: It is unclear why many migraine patients who are prescribed triptans discontinue this treatment. This study investigated correlates of triptan discontinuation with a focus on potentially modifiable factors to improve compliance. METHODS: This multicenter cross-sectional survey (n = 276) was performed at US tertiary care headache clinics. Headache fellows who were members of the American Headache Society Headache Fellows Research Consortium recruited episodic and chronic migraine patients who were current triptan users (use within prior 3 months and for ≥1 year) or past triptan users (no use within 6 months; prior use within 2 years). Univariate analyses were first completed to compare current triptan users to past users for: migraine characteristics, other migraine treatments, triptan education, triptan efficacy, triptan side effects, type of prescribing provider, Migraine Disability Assessment (MIDAS) scores and Beck Depression Inventory (BDI) scores. Then, a multivariable logistic regression model was selected from all possible combinations of predictor variables to determine the factors that best correlated with triptan discontinuation. RESULTS: Compared with those still using triptans (n = 207), those who had discontinued use (n = 69) had higher rates of medication overuse (30 vs. 18%, P = .04) and were more likely to have ever used opioids for migraine treatment (57 vs. 38%, P = .006) as well as higher MIDAS (mean 63 vs. 37, P = .001) and BDI scores (mean 10.4 vs. 7.4, P = .009). Compared with discontinued users, current triptan users were more likely to have had their triptan prescribed by a specialist (neurologist, headache specialist, or pain specialist) (74 vs. 54%, P = .002) and were more likely to report headache resolution (53 vs. 14%, P < .001) or a reduction in pain intensity (71 vs. 28%, P < .001) most of the time from their triptan. On a 1-5 scale (1 = disagree, 5 = agree), triptan users felt they had more: control over their migraine attacks (2.9 vs. 2.1), confidence in their prescribing provider (4.5 vs. 4.0), and were more educated about triptan use (4.2 vs. 3.7) compared with triptan discontinuers (P < .001 for all comparisons). Although both current and prior users reported similar rates of side effects (48 vs. 43%, P = .44), of those who discontinued use, the main reasons were for lack of effect (44%) and side effects (29%). Our multivariable modeling revealed that the strongest correlate of triptan discontinuation was lack of efficacy (odds ratio = 17, 95% confidence interval [8.8, 33.0]). Other factors associated with discontinuation included MIDAS > 24 (2.6, [1.5, 4.6]), BDI >4 (2.5, [1.4, 4.5]), and a history of ever using opioids for migraine therapy (2.2, [1.3, 3.8]). Having a triptan prescribed by a specialist and using at least 1 other abortive medication with the triptan were associated with a decreased likelihood of triptan discontinuation (0.41, [0.2-0.7] and 0.44 [0.3, 0.8], respectively). CONCLUSIONS: As expected, discontinuation was most correlated with lack of efficacy, but other important factors associated with those who had discontinued use included greater migraine-related disability, depression, and the use of opioids for migraine attacks. Compared with patients who had discontinued triptans, current triptan users felt more: educated about their triptan, control over their migraine attacks, and confidence in their prescribing provider. Current triptan users had their triptan prescribed by a specialist and used other abortive medications with their triptan more often compared with patients who had discontinued triptans. Given the cross-sectional nature of this study, we cannot determine if these factors contributed to triptan discontinuation or reflect the impact of such discontinuation. Interventions that address modifiable risk factors for triptan discontinuation may decrease the likelihood of triptan discontinuation and thus improve overall migraine control. Because lack of efficacy was most strongly associated with triptan discontinuation, future research should determine why triptans are effective for some patients but not others.

Injecting under pressure: the pain of low CSF pressure headache responsive to botulinum toxin injections.

Low intracranial pressure headaches can, at times, be refractory to treatment including multiple blood patches and preventative medications. Imaging studies are often unable to demonstrate a cerebrospinal fluid leak that is causing headache and other associated symptoms. Onabotulinum toxin A (BTX) injection is a treatment that has proven efficacy for the treatment of chronic migraine and potentially other headache disorders. We report a patient with a long standing history of refractory low pressure headaches with brain imaging that demonstrated brain sag, and no CSF leak could be identified. She received no sustained benefit from numerous blood patches, and was unresponsive or intolerant to multiple preventative medications. With BTX treatment, the patient continued to have daily headaches, but her pain intensity improved from an average 7/10 to 3/10. This benefit has been sustained over 7 years. This case suggests that BTX may be an effective treatment for headaches due to low intracranial pressure. It also suggests that the beneficial effects of BTX in the treatment of headaches occur through a direct modulation of the nociceptive system rather than merely induction of pericranial muscle relaxation.

New daily persistent headache and potential new therapeutic agents.

New daily persistent headache is a form of a chronic daily headache with a unique temporal profile. Patients can recall the exact day when their headache started. It can be one of the most refractory types of headache to treat. Recent publications have highlighted different subtypes and heterogeneity in presentation. Referring to it as a syndrome versus a distinct disorder has also been suggested. Several different classes of medications have been used for the treatment, with mixed results. The underlying pathophysiology of new daily persistent headache is unclear, but tumor necrosis factor may play a role. The clinical features, differential diagnosis and potential new therapeutic agents will be discussed.

Reversible cerebral vasoconstriction syndrome: updates and new perspectives.

Reversible cerebral vasoconstriction syndrome (RCVS) is an important cause of headaches that can lead to other neurological complications, including stroke, if not recognized early. Over the past few years, there has been great progress in the recognition of this entity. However, there is still much to be learned about its pathophysiology and optimal treatment strategies. RCVS occurs mostly in middle-aged adults, and there is a female preponderance with an increased incidence during the postpartum period. A consistent, predominating feature is a sudden-onset, severe headache that is frequently recurrent, usually over the span of a week. Less common presentations include seizures or focal neurological symptoms. Important causative factors include vasoactive medications, as well as illicit drugs like marijuana and cocaine. The current underlying pathophysiology is thought to be a disturbance in cerebrovascular tone leading to vasoconstriction. The diagnosis is based on history, physical examination, and cerebrovascular imaging findings that demonstrate multifocal, segmental areas of vasoconstriction in large- and medium-sized arteries. An important criterion for making the diagnosis is the eventual reversibility of symptoms and imaging findings.

Refractory occipital neuralgia treatment with nerve decompression surgery: a case series.

Background: The management of refractory occipital neuralgia (ON) can be challenging. Selection criteria for occipital nerve decompression surgery are not well defined in terms of clinical features and best preoperative medical management. Methods: In total, 15 patients diagnosed with ON by a board-certified, fellowship-trained headache specialist and referred to a plastic surgeon for nerve decompression surgery were prospectively enrolled. All subjects received trials of occipital nerve blocks (NB), at least three preventive medications, and onabotulinum toxin (BTX) prior to surgery before referral to a plastic surgeon. Treatment outcomes included headache frequency (headache days/month), intensity (0-10), duration (h), and response to medication/injectable therapies at 12 months postoperatively. Results: Preoperatively, median headache days/month was 30 (20-30), intensity 8 (8-10), and duration 24 h (12-24). Patients trialed 10 (±5.8) NB and 11.7 (±9) BTX cycles. Postoperatively, headache frequency was 5 (0-16) days/month (p < 0.01), intensity was 4 (0-6) (p < 0.01), and duration was 10 (0-24) h (p < 0.01). Median patient-reported percent resolution of ON headaches was 80% (70-85%). All patients reported improvement of comorbid headache disorders, most commonly migraine, and a reduction, discontinuation, or increased effectiveness of medications, NB and BTX. Conclusion: All patients who underwent treatment for refractory ON by a headache specialist and plastic surgeon benefited from nerve decompression surgery in various degrees. The collaborative selection criteria employed in this study may be replicable in clinical practice.

Role of Calcitonin Gene-Related Peptide on the Gastrointestinal Symptoms of Migraine-Clinical Considerations: A Narrative Review.

Calcitonin gene-related peptide (CGRP) is involved in several of the pathophysiological processes underpinning migraine attacks. Therapies that target CGRP or its receptor have shown efficacy as preventive or acute treatments for migraine. Two small-molecule CGRP receptor antagonists (rimegepant and ubrogepant) are approved for the acute treatment of migraine, and four monoclonal antibodies (eptinezumab, erenumab, fremanezumab, and galcanezumab) are approved for migraine prevention; erenumab targets the canonical CGRP receptor, the others CGRP ligand. CGRP plays a role in gastrointestinal nociception, inflammation, gastric acid secretion, and motility. Nausea and vomiting are among the gastrointestinal symptoms associated with migraine, but individuals with migraine may also experience functional upper and lower gastrointestinal comorbidities, such as gastroesophageal reflux disease, gastroparesis, functional diarrhea or constipation, and irritable bowel syndrome. Although gastrointestinal symptoms in migraine can be treatment-related, they may also be attributable to increased CGRP. In this review, we summarize the epidemiological evidence for associations between migraine and gastrointestinal disorders, consider the possible physiological role of CGRP in these associations, and review the clinical occurrence of gastrointestinal events in patients with migraine receiving CGRP-based therapies and other migraine treatments. Because patients with migraine are at an increased risk of comorbid and treatment-related gastrointestinal effects, we also propose a patient-management strategy to mitigate these effects.