Status migrainosus.

Status migrainosus is one of the recognized complications of migraine with or without aura, defined as a persistent debilitating migraine attack lasting for more than 72h with little reprieve, leading to functional disability. The individual impact of status migrainosus and the substantial healthcare burden are highlighted. Current case series which inform our understanding of this condition are examined with two groups emergent, those with classic status migrainosus and those with episodic status migrainosus. The question as to whether status migrainosus is a distinct biological state beyond the established migraine pathophysiology is examined. With the underlying pathophysiology not fully understood, attention is turned to therapeutic considerations and the available evidence informing practice. A practical approach to treatment of status migrainosus is presented. Given the severity and need for emergency care, options detailed are in line with recommendations for acute migraine care: with a staged approach initially combining subcutaneous sumatriptan with parenteral options including dopamine receptor antagonists, nonsteroidal anti-inflammatories and acetaminophen. The place of combination treatment with parenteral magnesium sulfate, dihydroergotamine, antiepileptics, corticosteroids, and anesthetic agents is outlined. With a paucity of high-quality evidence to consolidate current clinical approaches, consideration of future therapies and research questions is raised.

[Sumatriptan-naproxen sodium fix-dose combination for acute migraine treatment, a review]. / Szumatriptán­naproxén-nátrium fix dózisú kombinációja a migrén akut kezelésében ­ irodalmi áttekintés.

Migraine as a common primary headache disorder has a significant negative effect on quality of life of the patients. Its pharmacotreatment includes acute and preventative therapies. Based on the shared therapeutic guideline of the European Headache Federation and the European Academy of Neurology for acute migraine treatment a combination of triptans and non-steroidal anti-inflammatory drugs is recommended for acute migraine treatment in triptan-nonresponders. In this short review we summarized the results of the randomized controlled clinical trials evaluating the effectiveness and safety of sumatriptan (85 mg)/naproxen sodium (500 mg) fix-dose combination. It was revealed that the fix-dose combination was better than placebo for the primary outcomes of exemption of pain and headache relief at 2 hours. Furthermore the combination showed beneficial effect on accompanying symptoms of migraine attack (i.e. nausea, photo- and phonophobia). Adverse events were mild or moderate in severity and rarely led to withdrawal of the drug.
It can be concluded that sumatriptan (85 mg)/naproxen sodium (500 mg) fix-dose combination is effective, safe and well-tolerated in the acute treatment of migraine. 

Quality by design for sumatriptan loaded nano-ethosomal mucoadhesive gel for the therapeutic management of nitroglycerin induced migraine.

Migraine is a progressive neurological condition often accompanied by nausea and vomiting. Various drugs have recently been used in the treatment of migraine, including sumatriptan (SUT). However, SUT has poor pharmacological effects mainly due to its reduced permeability, blood brain barrier (BBB) effect, half-life and bioavailability. Herein, we developed SUT loaded nano-ethosomes (SUT-NEs) for intranasal (IN) delivery, after their incorporation into chitosan based mucoadhesive gel (SUT-NEsG). The observed mean particle size of SUT-NEs was 109.45 ± 4.03 nm with spherical morphology, mono dispersion (0.191 ± 0.001), negatively charged (-20.90 ± 1.98 mV) and with excellent entrapment efficiency (96.90 ± 1.85 %). Fourier-transform infrared (FTIR) spectra have depicted the compatibility of the components. Moreover, SUT-NEsG was homogeneous having suitable viscosity and mucoadhesive strength. In vitro release and ex vivo permeation analysis showed sustained release and improved permeation of the SUT-NEsG, respectively. Additionally, histopathological studies of nasal membrane affirmed the safety of SUT-NEsG after IN application. In vivo pharmacokinetic study demonstrated improved brain bioavailability of SUT-NEsG as compared to orally administered sumatriptan solution (SUT-SL). Furthermore, significantly enhanced pharmacological effect of SUT-NEsG was observed in behavioral and biochemical analysis, immunohistochemistry for NF-κB, and enzyme linked immuno assay (ELISA) for IL-1ß and TNF-α in Nitroglycerin (NTG) induced migraine model. It can be concluded that migraine may be successfully managed through IN application of SUT-NEsG owing to the direct targeted delivery to the brain.

Comparative efficacy of different treatments for menstrual migraine: a systematic review and network meta-analysis.

BACKGROUND: Menstrual migraine is a subtype of migraine disease that is typically more disabling, longer-lasting, and more challenging to treat. The purpose of this network meta-analysis (NMA) is to compare the relative efficacy of treatments for menstrual migraine. METHODS: We systematically searched databases, including PubMed, EMBASE, and Cochrane, and included all eligible randomized controlled trials in the study. We conducted the statistical analysis using Stata version 14.0, based on the frequentist framework. We used the Cochrane Risk of Bias tool for randomized trials version 2 (RoB2) to assess the risk of bias of the included studies. RESULTS: This network meta-analysis included 14 randomized controlled trials with 4601 patients. For short-term prophylaxis, frovatriptan 2.5 mg twice daily had the highest probability of effectiveness [OR = 1.87 (95% CI: 1.48 to 2.38)] compared to placebo. For acute treatment, the results showed that sumatriptan 100 mg [OR = 4.32 (95% CI: 2.95 to 6.34)] was the most effective treatment compared to placebo. CONCLUSIONS: These findings suggest that frovatriptan 2.5 mg twice daily was best for short-term prevention, sumatriptan 100 mg were best for acute treatment. More high-quality randomized trials are required to determine the most effective treatment.

Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms.

Migraine is a common, polygenic disorder that is characterized by moderate to severe headache attacks. Migraine attacks are commonly treated with triptans, i.e. serotonin receptor agonists. However, triptans are effective in ~ 60% of the population, and the mechanisms of triptans are debated. Here, we aim to expose the mechanisms of triptan using metabolomics and transcriptomics in spontaneous migraine attacks. We collected temporal multi-omics profiles on 24 migraine patients, using samples collected at a migraine attack, 2 h after treatment with a triptan, when headache-free, and after a cold-pressor test. Differential metabolomic analysis was performed to find metabolites associated with treatment. Their effect was further investigated using correlation analysis and a machine learning approach. We found three differential metabolites: cortisol, sumatriptan and glutamine. The change in sumatriptan levels correlated with a change in GNAI1 and VIPR2 gene expression, both known to regulate cAMP levels. Furthermore, we found fatty acid oxidation to be affected, a mechanism known to be involved in migraine but not previously found in relation to triptans. In conclusion, using an integrative approach we find evidence for a role of glutamine, cAMP regulation, and fatty acid oxidation in the molecular mechanisms of migraine and/or the effect of triptans.

European Academy of Neurology guidelines on the treatment of cluster headache.

BACKGROUND AND PURPOSE: Cluster headache is a relatively rare, disabling primary headache disorder with a major impact on patients' quality of life. This work presents evidence-based recommendations for the treatment of cluster headache derived from a systematic review of the literature and consensus among a panel of experts. METHODS: The databases PubMed (Medline), Science Citation Index, and Cochrane Library were screened for studies on the efficacy of interventions (last access July 2022). The findings in these studies were evaluated according to the recommendations of the European Academy of Neurology, and the level of evidence was established using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). RECOMMENDATIONS: For the acute treatment of cluster headache attacks, there is a strong recommendation for oxygen (100%) with a flow of at least 12 L/min over 15 min and 6 mg subcutaneous sumatriptan. Prophylaxis of cluster headache attacks with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy and tolerability) is recommended. Corticosteroids are efficacious in cluster headache. To reach an effect, the use of at least 100 mg prednisone (or equivalent corticosteroid) given orally or at up to 500 mg iv per day over 5 days is recommended. Lithium, topiramate, and galcanezumab (only for episodic cluster headache) are recommended as alternative treatments. Noninvasive vagus nerve stimulation is efficacious in episodic but not chronic cluster headache. Greater occipital nerve block is recommended, but electrical stimulation of the greater occipital nerve is not recommended due to the side effect profile.

Duality in response of intracranial vessels to nitroglycerin revealed in rats by imaging photoplethysmography.

Among numerous approaches to the study of migraine, the nitroglycerin (NTG) model occupies a prominent place, but there is relatively insufficient information about how NTG affects intracranial vessels. In this study we aim to assess the effects of NTG on blood-flow parameters in meningeal vessels measured by imaging photoplethysmography (iPPG) in animal experiments. An amplitude of the pulsatile component (APC) of iPPG waveform was assessed before and within 2.5 h after the NTG administration in saline (n = 13) or sumatriptan (n = 12) pretreatment anesthetized rats in conditions of a closed cranial window. In animals of both groups, NTG caused a steady decrease in blood pressure. In 7 rats of the saline group, NTG resulted in progressive increase in APC, whereas decrease in APC was observed in other 6 rats. In all animals in the sumatriptan group, NTG administration was accompanied exclusively by an increase in APC. Diametrically opposite changes in APC due to NTG indicate a dual effect of this drug on meningeal vasomotor activity. Sumatriptan acts as a synergist of the NTG vasodilating action. The results we obtained contribute to understanding the interaction of vasoactive drugs in the study of the headache pathophysiology and methods of its therapy.

The efficacy and safety of metoclopramide in relieving acute migraine attacks compared with other anti-migraine drugs: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs. METHODS: We searched online databases like PubMed, Cochrane Library, Scopus, and Web of Science till June 2022 for RCTs that compared metoclopramide alone with placebo or active drugs. The main outcomes were the mean change in headache score and complete headache relief. The secondary outcomes were the rescue medications need, side effects, nausea and recurrence rate. We qualitatively reviewed the outcomes. Then, we performed the network meta-analyses (NMAs) when it was possible. which were done by the Frequentist method using the MetaInsight online software. RESULTS: Sixteen studies were included with a total of 1934 patients: 826 received metoclopramide, 302 received placebo, and 806 received other active drugs. Metoclopramide was effective in reducing headache outcomes even for 24 h. The intravenous route was the most chosen route in the included studies and showed significant positive results regarding headache outcomes; however, the best route whether intramuscular, intravenous, or suppository was not compared in the previous studies. Also, both 10 and 20 mg doses of metoclopramide were effective in improving headache outcomes; however, there was no direct comparison between both doses and the 10 mg dose was the most frequently used dosage. In NMA of headache change after 30 min or 1 h, metoclopramide effect came after granisetron, ketorolac, chlorpromazine, and Dexketoprofen trometamol. Only granisetron's effect was significantly higher than metoclopramide's effect which was only significantly higher than placebo and sumatriptan. In headache-free symptoms, only prochlorperazine was non-significantly higher than metoclopramide which was higher than other medications and showed significantly higher effects only with placebo. In rescue medication, metoclopramide's effect was only non-significantly lower than prochlorperazine and chlorpromazine while its effect was higher than other drugs and showed higher significant effects only than placebo and valproate. In the recurrence rate, studies showed no significant difference between metoclopramide and other drugs. Metoclopramide significantly decreased nausea more than the placebo. Regarding side effects, metoclopramide showed a lower incidence of mild side effects than pethidine and chlorpromazine and showed a higher incidence of mild side effects than placebo, dexamethasone, and ketorolac. The reported extrapyramidal symptoms with metoclopramide were dystonia or akathisia. CONCLUSION: A dose of 10 mg IV Metoclopramide was effective in relieving migraine attacks with minimal side effects. Compared to other active drugs, it only showed a lower significant effect compared with granisetron regarding headache change while it showed significantly higher effects only with placebo in both rescue medication needs and headache-free symptoms and valproate in only rescue medication need. Also, it significantly decreased headache scores more than placebo and sumatriptan. However, more studies are needed to support our results.

Sumatriptan, a serotonin 5HT1B receptor agonist, acutely reduces insulin secretion and sensitivity and glucose effectiveness in overweight humans: A double-blinded placebo-controlled cross-over trial.

AIM: Evidence from mouse models suggests that brain serotonergic pathways control blood glucose. We hypothesized that sumatriptan (5HT1B -receptor agonist) would alter glucose homeostasis in humans. MATERIALS AND METHODS: We conducted a two-visit random-order double-blinded placebo-controlled cross-over trial in 10 overweight adults that were otherwise healthy. Participants received sumatriptan (single dose, 100 mg) or placebo before undergoing a 60-min intravenous glucose tolerance test, followed by a 120-min hyperinsulinaemic euglycaemic clamp. RESULTS: Glucose excursion was greater during intravenous glucose tolerance test with sumatriptan compared with placebo [iAUC0-60 min 316 (268-333) vs. 251 (197-319) min/mmol/L p = .047]. This was probably explained by a combination of reduced circulating insulin levels [iAUC0-10 min 1626 (1103-2733) vs. 2336 (1702-3269) min/pmol/L, p = .005], reduced insulin sensitivity [M/I-value 2.11 (1.15, 4.05) vs. 3.03 (1.14, 4.90) mg/kg/min per pmol/L, p = .010] and glucose effectiveness [SG 0.17 (0.12, 0.21) vs. 0.22 (0.18, 0.65)/min, p = .027]. CONCLUSIONS: 5HT1B receptors have a glucoregulatory role in humans, probably acting on insulin secretion, insulin sensitivity and glucose effectiveness.

The Efficacy of Different Triptans for the Treatment of Acute Headache in Pediatric Migraine: A Systematic Review.

BACKGROUND: Serotonin receptors 5-HT1B and 5-HT1D in the cerebral arteries are activated by the 5-hydroxytryptophan agonists (triptans) to relieve the discomfort associated with migraines. Even though triptans are often used to treat acute migraines, there is some debate over their effectiveness. OBJECTIVE: Our systematic review aimed to evaluate the effectiveness of triptans for acute treatment of migraine in young individuals. METHODS: Utilizing the databases of Google Scholar, Cochrane Library, and PubMed, a literature search was conducted, and all papers published till July 2022 were included. This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. In addition to the Boolean operators AND, OR, and NOT, the following descriptive terms were also used: "Triptans," "Pediatric Migraine," "Migraine disorders," "Headache," "Children," and "Adolescent." RESULTS: A total of 1047 studies were identified, and 25 articles were finally included in the study. 17 of them were RCTs while the remaining were non-randomized trials. Most studies recruited participants aged between 12-17 years. Among 25 studies, 7 reported sumatriptan use, 3 assessed a combination of sumatriptan and naproxen, 4 were on almotriptan, 1 on eletriptan, 6 on rizatriptan, and 4 on zolmitriptan use. CONCLUSION: We found that rizatriptan (good tolerability profile with a dose of 5 mg) and sumatriptan (nasal spray, 10 mg and 20 mg) had higher efficiency as compared to other triptans. Regardless of type or dose, all triptans are generally well tolerated by patients, but a few adverse effects such as light-headedness (sumatriptan), nasopharyngitis, and, muscular spasms (sumatriptan/ naproxen), somnolence, and dry mouth (rizatriptan), and dizziness (zolmitriptan group) were reported with the triptans.

Sumatriptan as a First-Line Treatment for Headache in the Pediatric Emergency Department.

BACKGROUND: Headache is a common presenting condition for patients seen in the pediatric emergency department (ED). Intranasal (IN) sumatriptan is a well-tolerated and safe abortive treatment for migraine headache, but it is infrequently administered in pediatric EDs. In this study we characterize an ED migraine pathway that uses IN sumatriptan as a first-line treatment. METHODS: We performed retrospective chart analysis from a single center, reviewing a cohort of patients treated on an ED migraine pathway between October 2016 and February 2020. We reviewed patient demographics, clinical characteristics, treatment patterns, change in pain scores, sumatriptan prescriptions at discharge, length of stay (LOS), ED charges, and unexpected return visits. RESULTS: A total of 558 patients (aged six to 21 years, 66% female) were included in this study. Overall, the median pretreatment pain score was 7 (interquartile range [IQR]: 5 to 8) and the median post-treatment pain score was 2 (IQR: 0 to 4). Forty-eight percent of patients received IN sumatriptan in the ED, and 36% of those who received sumatriptan were prescribed oral sumatriptan at discharge. When intravenous (IV) access was obtained for headache management, this was associated with a significantly longer LOS and higher ED charges. CONCLUSIONS: IN sumatriptan shows promise as a feasible and potentially effective first-line treatment for pediatric migraine in the ED that could reduce the need for IV therapies, shorten LOS, and lower ED charges. Further research is needed to determine the efficacy of IN sumatriptan relative to other common first-line therapies used to treat pediatric migraine in the ED.

Low-dose sumatriptan improves the outcome of acute mesenteric ischemia in rats via downregulating kynurenine.

BACKGROUND: Mesenteric ischemia has remained without effective pharmacological management for many years. Sumatriptan, an abortive medication for migraine and cluster headaches, has potent anti-inflammatory properties and ameliorated organ ischemia in previous animal studies. Similarly, inhibition of the kynurenine pathway ameliorated renal and myocardial ischemia/reperfusion (I/R) in many preclinical studies. Herein, we assessed the effect of sumatriptan on experimental mesenteric I/R and investigated whether kynurenine pathway inhibition is a mechanism underlying its action. METHODS: Ischemia was induced by ligating the origin of the superior mesenteric artery (SMA) and its anastomosis with the inferior mesenteric artery (IMA) with bulldog clamps for 30 min. Ischemia was followed by 1 h of reperfusion. Sumatriptan (0.1, 0.3, and 1 mg/kg ip) was injected 5 min before the reperfusion phase, 1-methyltryptophan (1-MT) (100 mg/kg iv) was used to inhibit kynurenine production. At the end of the reperfusion phase, samples were collected from the jejunum of rats for H&E staining and molecular assessments. RESULTS: Sumatriptan improved the integrity of intestinal mucosa after I/R, and 0.1 mg/kg was the most effective dose of sumatriptan in this study. Sumatriptan decreased the increased levels of TNF-α, kynurenine, and p-ERK but did not change the decreased levels of NO. Furthermore, sumatriptan significantly increased the decreased ratio of Bcl2/Bax. Similarly, 1-MT significantly decreased TNF-α and kynurenine and protected against mucosal damage. CONCLUSIONS: This study demonstrated that sumatriptan has protective effects against mesenteric ischemia and the kynurenine inhibition is potentially involved in this process. Therefore, it can be assumed that sumatriptan has the potential to be repurposed as a treatment for acute mesenteric ischemia.

[Integrating new migraine treatments into clinical practice (part 1) : management of acute migraine attack]. / Intégration des nouveaux anti-migraineux dans notre pratique clinique . Partie 1 : traitement de la crise de migraine.

Although migraine is one of the most common chronic diseases and is the subject of numerous studies, there is still a considerable proportion of patients who are not satisfied with their acute treatment. Left without any real new therapeutic option to offer patients since sumatriptan was introduced on the Belgian market 30 years ago, neurologists have recently seen a change in the therapeutic landscape with the advent of new specific acute treatments for migraine: gepants and ditans. Being the only ones currently available in Belgium, gepants (including the newly marketed rimegepant) bring added value to traditional treatments such as non-steroidal anti-inflammatory drugs and triptans. This is why it seemed useful to review the different therapeutic options available in Belgium today by including these new treatments and to propose a rational pharmacological approach to relieve acute migraine attack.

Bien que la migraine soit une des maladies chroniques les plus fréquentes et fasse l'objet de nombreuses recherches, il existe malheureusement encore une proportion importante de patients insatisfaits de leur traitement anti-douleur. Sans nouvelle vraie option thérapeutique à proposer aux patients depuis la mise sur le marché belge du sumatriptan voici 30 ans, le neurologue a vu récemment le paysage thérapeutique se modifier avec l'arrivée de nouveaux traitements spécifiques de la crise de migraine : les gépants et les ditans. Seuls disponibles pour le moment en Belgique, les gépants (avec notamment le rimégépant nouvellement commercialisé) apportent une plus-value aux traitements traditionnels que sont les anti-inflammatoires non stéroïdiens et les triptans. C'est la raison pour laquelle il nous a semblé utile de refaire le point sur les différentes options thérapeutiques disponibles aujourd'hui en Belgique en intégrant ces nouveaux traitements et de proposer une approche pharmacologique rationnelle pour soulager la douleur de la crise de migraine.

Post-COVID Headache: A Literature Review.

PURPOSE OF REVIEW: Post-COVID headache may be unique in presentation and mechanism, often presenting as a new phenotype in patients with a history of a primary headache disorder or resulting in a new headache syndrome in those without history of headache. This review presents a description of the literature published focused on post-COVID headache. Additionally, we discuss potential mechanisms and considerations for treatment of post-COVID headache. RECENT FINDINGS: Headache is one of the most common symptoms of COVID. Common characteristics are revealed when reviewing the phenotypes of headaches that have been described in patients with COVID-19, with most headache phenotypes resembling migraine and new persistent daily headache. Post-COVID headaches are often described as moderate to severe, persistent, and treatment refractory. This review highlights the diversity of presentation of headaches that present as a complication of COVID-19. Treatment of post-COVID headache is challenging, especially in the setting of a pandemic where resources are limited. CLINICAL CASE: A 42-year-old woman with a history of episodic migraine without aura presents over video visit with a new headache type. Her typical headaches are predominantly left sided, throbbing in nature, and associated with photophobia and phonophobia. They are fully relieved by oral sumatriptan 2 h after treatment. She describes this new headache as a constant, pulsating, holocephalic pain with no other migrainous features that have been ongoing for 6 weeks. She notes that the headache has been persistent since that time. She has tried over-the-counter acetaminophen and ibuprofen and her typical migraine abortive therapy without relief. She is debilitated and wonders if there is anything that will take the pain away. She shares that she tested positive for COVID-19 about 2 days prior to headache onset and has associated rhinorrhea, anosmia, and ageusia.

Sumatriptan prevents central sensitization specifically in the trigeminal dermatome in humans.

BACKGROUND: The exact mechanism and site of action of triptans in aborting migraine attacks remain under debate. We hypothesized that the clinical efficacy of triptans lies in aborting central sensitization and focused on the question of why triptans are headache specific, that is highly effective in migraine and cluster headache and ineffective in extracephalic pain. METHODS: Forty healthy participants were enrolled in this double-blinded, randomized, placebo-controlled study. The effect of sumatriptan (n = 20) versus placebo (n = 20) was investigated in a trigeminal (V1) versus an extracephalic dermatome (forearm) using a topical capsaicin sensitization model. Capsaicin-induced primary and secondary hyperalgesia were evaluated using quantitative sensory testing. RESULTS: After capsaicin application, primary hyperalgesia developed in both the sumatriptan and placebo groups in both dermatomes. However, sumatriptan exclusively prevented secondary hyperalgesia in the V1 dermatome but not on the forearm. Placebo exerted no effects on secondary hyperalgesia in both trigeminal and extracephalic dermatomes. Additionally, sumatriptan reduced the flare size exclusively in the V1 dermatome. CONCLUSIONS: Our data suggest that sumatriptan reduces central sensitization (secondary hyperalgesia) without modulating peripheral sensitization (primary hyperalgesia) in a human pain model of capsaicin-induced sensitization. Moreover, despite a systemic administration of sumatriptan, the modulatory effects are trigeminal specific, echoing the clinical effect of triptans in aborting headaches, but not extracephalic pain. SIGNIFICANCE: Our data suggest that triptans exert their efficacy by suppressing central sensitization. By revealing a dermatome-specific modulation, our study demonstrates a previously unrecognized interaction between the pharmacodynamics of triptans and the trigeminal nociceptive system that provides new insight into how triptans may work in aborting headache attacks.

Feasibility, Utility, and Interrater Reliability of the Cluster Headache Severity Scale, Cluster Headache Quality of Life, Cluster Headache Index, and 6-Item Headache Impact Test in Pediatric Cluster Headache.

Introduction: Cluster headache is rare in children and only a few clinical studies have systematically evaluated cluster headache in children. Methods: This study was conducted between August 2019 and December 2021 with the primary aim to evaluate the feasibility and utility of the Cluster Headache Severity Scale in determining the severity of cluster headache in patients aged less than 18 years and monitoring response to prescribed treatment. Secondary objectives were to evaluate the feasibility and utility of Cluster Headache Quality of Life, Cluster Headache Index, and 6-item Headache Impact Test in pediatric cluster headache patients to assess the quality of life, severity, and impact of cluster headache. Results: A total of 32 children (age of onset 11.9 ± 2.3 years, age of diagnosis 13.7 ± 2.4 years, 68% boys) were enrolled. Although 30 cases had their headache episodes occurring during nighttime, only 16 children had a Children's Sleep Habits Questionnaire (CSHQ) score >41 at baseline. All children responded to prednisolone as bridging therapy and 23 of 32 showed adequate pain relief after sumatriptan nasal spray for an acute attack. The average time taken for completion of Cluster Headache Index, Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test-6 scores were 5.2 ± 0.7, 5.1 ± 0.8, 27.4 ± 3.5, and 6.2 ± 0.8 minutes, respectively. The interrater reliability was good for Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test-6 (Cronbach α 0.93, 0.81, and 0.89, respectively). There was a strong positive correlation between the Cluster Headache Severity Scale score with Headache Impact Test-6 score and Cluster Headache Quality of Life score (correlation coefficient r = 0.90 and 0.98). Conclusion: Majority of pediatric cluster headache patients are likely to respond to prednisolone and sumatriptan. Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test-6 can be used for pediatric cluster headache patients for treatment monitoring.

Triptan medication use among patients with migraine with contraindications in the US.

OBJECTIVE: We sought to investigate the prevalence of triptan use among patients with migraine who have contraindications to triptan usage, and to explore specifics of the medication prescribed, dosage, and route of administration. BACKGROUND: Triptan medications are a mainstay of acute migraine therapy, but little is known about prevalence and patterns of triptan prescribing among patients with contraindications in the United States. METHODS: In this retrospective cohort study, we used data from the IBM Marketscan database to identify patients aged ≥ 18 years with migraine from January 1, 2016, to December 31, 2017, using International Classification of Diseases, Clinical Modification 10 codes. Contraindications to triptan medications were identified by review of package labels as listed on the US Food and Drug Administration website. Triptan medications were identified from the IBM Micromedex Redbook linked to prescription claims along with route of administration and dosage. RESULTS: Of 1,038,472 individuals diagnosed with migraine, 400,112 (38.5%) were prescribed triptan medication, and of those who were prescribed a triptan, 55,707 (13.9%) had at least one contraindication, with the most common contraindication being cardiac arrhythmia (33,696/400,112 individuals, 8.4%) followed by cerebrovascular disease (14,787/400,112, 3.7%) and coronary artery disease (10,236/400,112, 2.6%). Sumatriptan was the most prescribed triptan (261,736/1,038,472, 25.2%), and the subcutaneous and intranasal routes were more commonly prescribed among those with contraindications compared with those without contraindications. DISCUSSION: A substantial proportion of patients with migraine with contraindications were prescribed triptan medications. These findings call for further research on the outcomes of patients with medical contraindications who are prescribed triptan medications, and for greater clarity in prescribing guidelines about the optimal approach for acute therapy among patients with migraine.

The implementation of transcranial Doppler ultrasonography for preclinical study of migraine.

Transcranial Doppler ultrasonography is used to study intracranial blood flow changes associated with migraine in humans, but whether this method is helpful in preclinical settings is yet unknown. To identify changes in rat intracranial blood flow specific to trigeminovascular activation-a key process in migraine pathophysiology-we measured Doppler indices in the middle cerebral artery and basilar artery before, during, and after dural or somatosensory electrical stimulation. Hemodynamic changes specific to dural stimulation were tested further in separate experiments. After baseline recordings, the animals received cumulative infusions of valproate (100 mg/kg, trice), sumatriptan (0.3, 1, and 3 mg/kg), or saline, and dural stimulation with measurement of Doppler indices was repeated every 10 min for 1 h. Several parameters of blood flow in the rat middle cerebral artery underwent alterations specific to trigeminovascular activation. These changes, however, were insensitive to valproate and sumatriptan and diminished over time. These findings question the reliability of blood flow velocity variations in large intracranial vessels as biological markers of migraine-related processes and do not support the idea of using transcranial Doppler ultrasonography for preclinical screening of antimigraine treatments, at least in the model of acute trigeminovascular activation in rats.

Network meta-analysis of therapies for cluster headache: Effects of acute therapies for episodic and chronic cluster.

OBJECTIVE: We used network meta-analysis (NMA) to characterize the relative effectiveness and harms of acute treatment options for cluster headache. BACKGROUND: There are few evidence-based acute treatments available for cluster headache. As most treatments were compared only against placebos in clinical trials, few head-to-head comparisons of treatments are available. METHODS: An a priori registered scoping review was performed to identify randomized controlled trials evaluating treatments in adult patients (>18 years old) with cluster headache per accepted diagnostic criteria. Bayesian NMAs were performed to compare treatments in terms of headache relief at 15 or 30 min, and also the occurrence of adverse events. We report odds ratios (ORs) of relative treatment effects along with corresponding 95% credible intervals (CrIs), as well as measures of treatment ranking. RESULTS: A total of 13 randomized controlled trials informed NMAs. We found high flow oxygen to be the most effective therapy for headache response at 15 and 30 min (OR 9.0, 95% CrI 5.3 to 15.9 vs. placebo), with injectable sumatriptan demonstrating the next highest effect (OR 6.4, 95% CrI 3.75 to 11.1 vs. placebo). High flow oxygen was also more effective than low flow oxygen (OR 2.55, 95% CrI 1.13 to 5.8), nasal spray zolmitriptan (OR 3.75, 95% CrI 1.72 to 8.4), octreotide (OR 4.5, 95% CrI 1.64 to 12.5), and non-invasive vagal nerve stimulation (nVNS; OR 5.2, 95% CrI 2.29 to 11.9). Sumatriptan injectable was also effective for headache relief and was found to be better than nasal spray zolmitriptan (OR 2.67, 95% CrI 1.21 to 5.9), octreotide (OR 3.20, 95% CrI 1.17 to 8.8), and nVNS (OR 3.69, 95% CrI 1.63 to 8.4). Octreotide (OR 4.1, 95% CrI 1.71 to 10.5) and sumatriptan (OR 2.40, 95% CrI 1.39 to 4.2) were associated with greater risk of adverse events compared to placebo, while other treatments did not demonstrate increased risk. When focusing on patients with episodic cluster headache, nVNS was significantly better than placebo (OR 4.9, 95% CrI 1.89 to 14.1). CONCLUSIONS: Our findings suggest that high flow oxygen is more efficacious when compared to low flow oxygen for headache relief. When low flow oxygen fails in patients who can tolerate oxygen, increased flow rates should be tried. Additionally, high flow oxygen is likely more effective than zolmitriptan nasal spray, nVNS, and octreotide. Sumatriptan injectable is more likely to be effective when compared to zolmitriptan nasal spray, octreotide, and nVNS.

Efficacy of ketorolac in the treatment of acute migraine attack: A systematic review and meta-analysis.

OBJECTIVES: This review was designated to evaluate the efficacy of parenteral ketorolac in treating acute migraine headache. METHODS: We searched databases Cochrane Central Register of Controlled Trials (CENTRAL), Medline, and Google Scholar up to January 2021 and identified randomized controlled trials comparing ketorolac to any other medications in treating patients presenting with migraine headache. RESULTS: Thirteen trials were included in our review, comprising 944 participants. We derived seven comparisons: ketorolac versus phenothiazines, metoclopramide, sumatriptan, dexamethasone, sodium valproate, caffeine, and diclofenac. There were no significant differences in the reduction of pain intensity at 1 h under the comparisons between ketorolac and phenothiazines (standard mean difference [SMD] = 0.09, p = 0.74) or metoclopramide (SMD = 0.02, p = 0.95). We also found no difference in the outcome recurrence of headache (ketorolac vs. phenothiazines (risk ratio [RR] =0.98, p = 0.97)], ability to return to work or usual activity (ketorolac vs. metoclopramide [RR = 0.64, p = 0.13]), need for rescue medication (ketorolac vs. phenothiazines [RR = 1.72, p = 0.27], ketorolac vs. metoclopramide [RR 2.20, p = 0.18]), and frequency of adverse effects (ketorolac vs. metoclopramide [RR = 1.07, p = 0.82]). Limited trials suggested that ketorolac offered better pain relief at 1 h compared to sumatriptan and dexamethasone; had lesser frequency of adverse effects than phenothiazines; and was superior to sodium valproate in terms of reduction of pain intensity at 1 h, need for rescue medication, and sustained headache freedom within 24 h. CONCLUSIONS: Ketorolac may have similar efficacy to phenothiazines and metoclopramide in treating acute migraine headache. Ketorolac may also offer better pain control than sumatriptan, dexamethasone, and sodium valproate. However, given the lack of evidence due to inadequate number of trials available, future studies are warranted.