Hemicrania continua in a family: A report of two cases.

OBJECTIVE: To report two cases of hemicrania continua (HC) in a mother and daughter. BACKGROUND: HC is a rare primary headache disorder belonging to the family of trigeminal autonomic cephalalgias (TACs). Unlike migraine, familial cases of TACs are rare, and we know relatively little of their inheritance pattern and genetic mechanisms. METHODS: We present a mother and daughter with HC. We compare the similarities and differences between this family and the first report of familial HC and discuss the implications for future studies. RESULTS: Both the mother and daughter presented with a constant, side-locked headache of moderate intensity, with episodic exacerbations of more severe pain that are associated with ipsilateral cranial autonomic activation. After negative workup, both patients were started on indomethacin and achieved absolute response at different doses, confirming HC. CONCLUSIONS: Our report further corroborates other reports of familial TACs that TACs are primary headaches possibly attributable to genetic factors, albeit detailed mechanisms remain elusive. Nevertheless, whether clinical presentation and treatment responses would be substantially different between sporadic and familial HCs remain unclear.

Patient experience of telemedicine for headache care during the COVID-19 pandemic: An American Migraine Foundation survey study.

OBJECTIVE: We sought to investigate the patient experience of telemedicine for headache care during the coronavirus disease 2019 (COVID-19) pandemic. BACKGROUND: The use of telemedicine has rapidly expanded and evolved since the beginning of the COVID-19 pandemic. Telemedicine eliminates the physical and geographic barriers to health care, preserves personal protective equipment, and prevents the spread of COVID-19 by allowing encounters to happen in a socially distanced way. However, few studies have assessed the patient perspective of telemedicine for headache care. METHODS: The American Migraine Foundation (AMF) designed a standardized electronic questionnaire to assess the patient experience of telemedicine for headache care between March and September 2020 to help inform future quality improvement as part of its patient advocacy initiative. The date parameters were identified as the emergence of severe acute respiratory syndrome coronavirus 2 disease and the declaration of a national emergency in the United States. The questionnaire was distributed electronically to more than 100,000 members of the AMF community through social media platforms and the AMF email database. RESULTS: A total of 1172 patients responded to our electronic questionnaire, with 1098 complete responses. The majority, 1081/1153 (93.8%) patients, had a previous headache diagnosis prior to the telemedicine encounter. A total of 648/1127 (57.5%) patients reported that they had used telemedicine for headache care during the study period. Among those who participated in telehealth visits, 553/647 (85.5%) patients used it for follow-up visits; 94/647 (14.5%) patients used it for new patient visits. During the telemedicine encounters, 282/645 (43.7%) patients were evaluated by headache specialists, 222/645 (34.4%) patients by general neurologists, 198/645 (30.7%) patients by primary care providers, 73/645 (11.3%) patients by headache nurse practitioners, and 21/645 (3.2%) patients by headache nurses. Only 47/633 (7.4%) patients received a new headache diagnosis from telemedicine evaluation, whereas the other 586/633 (92.6%) patients did not have a change in their diagnoses. During these visits, a new treatment was prescribed for 358/636 (52.3%) patients, whereas 278/636 (43.7%) patients did not have changes made to their treatment plan. The number (%) of patients who rated the telemedicine headache care experience as "very good," "good," "fair," "poor," and "other" were 396/638 (62.1%), 132/638 (20.7%), 67/638 (10.5%), 23/638 (3.6%), and 20/638 (3.1%), respectively. Detailed reasons for "other" are listed in the manuscript. Most patients, 573/638 (89.8%), indicated that they would prefer to continue to use telemedicine for their headache care, 45/638 (7.1%) patients would not, and 20/638 (3.1%) patients were unsure. CONCLUSIONS: Our study evaluating the patient perspective demonstrated that telemedicine facilitated headache care for many patients during the COVID-19 pandemic, resulting in high patient satisfaction rates, and a desire to continue to use telemedicine for future headache care among those who completed the online survey.

Fremanezumab as Add-On Treatment for Patients Treated With Other Migraine Preventive Medicines.

BACKGROUND: Fremanezumab (formerly TEV-48125) is a monoclonal antibody directed against calcitonin-gene-related peptide (CGRP), a validated target for migraine preventive therapy. In two previous phase 2 studies, fremanezumab administered once every 28 days for 12 weeks was found to be effective and safe as a preventive treatment for patients suffering from episodic migraine (EM) and chronic migraine (CM). OBJECTIVE: To evaluate the efficacy and safety of fremanezumab as an add-on preventive therapy in individuals with EM and CM who are on stable doses of preventive migraine medications. METHODS: Two randomized placebo-controlled studies tested once-monthly subcutaneous injections of various dosing regimens of fremanezumab versus placebo in EM and CM. Headache information was captured daily using an electronic headache diary. For these post hoc analyses, data were pooled from patients who were on stable preventive medications and taking fremanezumab doses of 225 mg or 675/225 mg, or placebo. RESULTS: The sample consisted of 133 patients, (67 fremanezumab and 66 placebo). Total reduction in migraine days for the duration of the study was 12.4 for fremanezumab and 7.4 for placebo (P = .0321). There were also decreases in moderate/severe headache days (12.5 vs 7.1, P = .0058), and days using acute medication for headaches relative to placebo (11.6 vs 7.5, P = .0414). Treatment emergent adverse events were generally mild and transient, and no serious adverse events were considered to be treatment-related by the site investigators. CONCLUSIONS: The findings from these post hoc analyses suggest that fremanezumab is a safe and effective add-on treatment for migraine patients being concomitantly treated with other migraine preventive medications. Trials are registered at Clinicaltrials.gov NCT02025556 and NCT02021773.

Update on New Daily Persistent Headache.

OPINION STATEMENT: New daily persistent headache (NDPH) is an uncommon and under-recognized primary headache disorder. Clinically, NDPH may resemble migraine or tension-type headache. Unlike migraine or tension-type headaches, however, a distinguishing feature of NDPH is that the majority of patients with NDPH can pinpoint the exact date of onset of symptoms. While cases can arise de novo, in multiple reports, a viral illness precedes the onset of headache. NDPH has two temporal profiles: a self-limited form that resolves spontaneously without treatment and a refractory, persistent form in which headaches continue unabated for years. Diagnosis is predicated on first eliminating secondary mimics via diagnostic imaging and hematological studies. Lumbar puncture should be considered in patients who are refractory to treatment to search for alterations in CSF pressure or for an infectious process. There have been no randomized clinical trials utilizing acute or preventive therapies for NDPH. In clinical practice, treatment is aimed at matching the predominant headache phenotype; nonetheless, most therapies are generally ineffective or only partially effective. Not surprisingly, medication overuse is very common among patients with this disorder and should be identified, although in most patients, eliminating medication overuse does not alter the course of the illness. There have been reports of successful treatment combining doxycycline 100 mg and montelukast 10 mg, dosed BID for 3 months. Anecdotally, in our practice, this combination has occasionally provided good results. Onabotulinum toxin injections are currently under investigation and may provide a potential new effective treatment regimen.

Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is a validated target for the treatment of episodic migraine. Here we assess the safety, tolerability, and efficacy of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of high-frequency episodic migraine. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 2b study, we enrolled men and women (aged 18-65 years) from 62 sites in the USA who had migraine headaches 8-14 days per month. Using a randomisation list generated by a central computerised system and an interactive web response system, we randomly assigned patients (1:1:1; stratified by sex and use of concomitant preventive drugs) after a 28 day run-in period to three 28 day treatment cycles of subcutaneous 225 mg TEV-48125, 675 mg TEV-48125, or placebo. Investigators, patients, and the funder were blinded to treatment allocation. Patients reported headache information daily using an electronic diary. Primary endpoints were change from baseline in migraine days during the third treatment cycle (weeks 9-12) and safety and tolerability. The secondary endpoint was change relative to baseline in headache-days during weeks 9-12. Efficacy endpoints were analysed for the intention-to-treat population. Safety and tolerability were analysed using descriptive statistics. This trial is registered at ClinicalTrials.gov, number NCT02025556. FINDINGS: Between Jan 8, 2014, and Oct 15, 2014, we enrolled 297 participants: 104 were randomly assigned to receive placebo, 95 to receive 225 mg TEV-48125, and 96 to receive 675 mg TEV-48125. The least square mean (LSM) change in number of migraine-days from baseline to weeks 9-12 was -3.46 days (SD 5.40) in the placebo group, -6.27 days (5.38) in the 225 mg dose group, and -6.09 days (5.22) in the 675 mg dose group. The LSM difference in the reduction of migraine-days between the placebo and 225 mg dose groups was -2.81 days (95% CI -4.07 to -1.55; p<0.0001), whereas the difference between the placebo and 675 mg dose group was -2.64 days (-3.90 to -1.38; p<0.0001). LSM differences in the reduction of headache-days were -2.63 days (-3.91 to -1.34; p<0.0001) between the placebo group and 225 mg dose group and -2.58 days (-3.87 to 1.30; p <0.0001) between the placebo group and the 675 mg dose group. Adverse events occurred in 58 (56%) patients in the placebo group, 44 (46%) patients in the 225 mg dose group, and 57 (59%) patients in the 675 mg dose group; moderate or severe adverse events were reported for 29 (27%) patients, 24 (25%) patients, and 26 (27%) patients, respectively. INTERPRETATION: TEV-48125, at doses of 225 mg and 675 mg given once every 28 days for 12 weeks, was safe, well tolerated, and effective as a preventive treatment of high-frequency episodic migraine, thus supporting advancement of the clinical development programme to phase 3 clinical trials. FUNDING: Teva Pharmaceuticals.

Trigeminal Autonomic Cephalalgias.

PURPOSE OF REVIEW: This article reviews the clinical features of and treatment options for the trigeminal autonomic cephalalgias (TACs). RECENT FINDINGS: The TACs are a group of primary headache disorders characterized by short-lasting episodes of severe unilateral headaches that are associated with ipsilateral cranial autonomic symptoms. The best known and most commonly seen TAC in clinical practice is cluster headache. The other syndromes within this group include paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks. Although these disorders share a similar phenotype, they are distinguished by differences in attack frequency and duration. Recognition of these clinical differences is paramount because treatment options vary; paroxysmal hemicrania and hemicrania continua demonstrate an absolute response to treatment with indomethacin, while the other syndromes respond to other agents. SUMMARY: Although much less common than other headache disorders seen in clinical practice, recognition of the TACs is especially important as they are among the most severe and disabling syndromes in headache medicine.

Sumatriptan Iontophoretic Transdermal System Reduces Treatment-Emergent Nausea and Is Effective in Patients With and Without Nausea at Baseline - Results From a Randomized Controlled Trial.

OBJECTIVES: To test the hypothesis that sumatriptan iontophoretic transdermal system (TDS) is associated with lower rates of treatment-emergent nausea (TEN) relative to placebo, as well as to compare the efficacy of sumatriptan TDS in migraineurs with or without nausea at baseline. METHODS: Participants of a double-blind, randomized, parallel-group, single-attack, placebo-controlled study conducted at 38 sites in the United States were analyzed. Participants who treated their migraine attacks while nausea-free were identified. The primary endpoint was TEN over 24 hours post-treatment contrasting both treatment groups and it was assessed by regression analyses using generalized estimating equations. Secondary endpoint was headache response as a function of presence of nausea, assessed by generalized linear model. RESULTS: A total of 130 participants free of nausea at baseline were treated with sumatriptan TDS, while 109 participants free of nausea at baseline were treated with placebo TDS. The occurrence of TEN over 24 hours post-treatment was significantly lower with the sumatriptan TDS than with placebo (P = .0011). These differences were statistically significant at 1 hour (13.8% vs 9.2%, P < .01), 2 hours (13.8% vs 4.6% P < .001) and 3 hours (13.8% vs 8.5% P < .01). The efficacy of sumatriptan TDS was similar regardless of the presence or absence of nausea at baseline for all clinical parameters. CONCLUSION: Sumatriptan TDS is not associated with the emergence of nausea in migraineurs without nausea. It is equally effective in participants with or without nausea at the time of treatment.

Why triptan treatment can fail: focus on gastrointestinal manifestations of migraine.

BACKGROUND: Results of randomized, double-blind, controlled studies establish the efficacy of triptans in the acute treatment of migraine, but triptan benefits demonstrated in clinical trials have not consistently been realized in clinical practice. This paper explores the contribution of gastrointestinal manifestations of migraine--namely nausea (with or without vomiting) and gastroparesis--to triptan treatment failure. SYNTHESIS: Migraine-related nausea and vomiting and migraine-associated gastroparesis appear to be prevalent and highly impactful and have been characterized as being among the greatest challenges affecting migraine care today. These gastrointestinal signs and symptoms have not been satisfactorily taken into account in the management of migraine, which is dominated by the use of oral therapies. Oral triptans are not the optimal therapy in the presence of migraine-related nausea because nausea predicts poor response to oral triptans and because nausea can cause patients to delay oral treatment, which can further compromise therapeutic efficacy. Oral triptans are not the optimal therapy in the presence of migraine-associated gastroparesis because these agents rely on gastric motility and gastrointestinal absorption and may be ineffective or slowly or inconsistently effective in the presence of gastroparesis. Health care providers need to work with their patients to address the still-all-too-frequent problem of treatment failure in migraine. First, health care providers need to have greater appreciation of the importance of nausea, vomiting, and gastroparesis as factors affecting migraine prognosis and treatment success. Second, health care providers need to systematically assess migraine patients for gastrointestinal signs and symptoms. Finally, patients and health care providers need to be willing to practice customized migraine care, in which patients tailor the treatment and formulation to the characteristics and context of the individual migraine episode.

Migraine and vestibular symptoms--identifying clinical features that predict "vestibular migraine".

BACKGROUND: Migraine and symptoms that may suggest a vestibular disorder (referred to herein broadly as vestibular symptoms-VS) often co-exist. In part due to a lack of standardized diagnostic criteria, this relationship remains unknown to many physicians. OBJECTIVE: To determine common clinical features that may be associated with "vestibular migraine" (VM). METHODS: We retrospectively reviewed charts of patients diagnosed with VM at a headache center. In this group we recorded certain demographic and clinical features related to their disorder, including the most common triggers of the VS and the specific characteristics of the symptoms that suggested VM. RESULTS: Our sample consisted of 147 patients (68% women, mean age = 45 years, 39% with aura). Migraine onset preceded the onset of VS by a mean of 8 years. A total of 62 patients (42%) had gradual onset of VS, while in 48 (33%) symptoms began suddenly. The most commonly reported symptoms that led to the diagnosis of VM were: unsteadiness (134; 91%), balance disturbance (120; 82%), "light-headedness" (113; 77%), and vertigo (84; 57%). VS and headache occurred concomitantly in 48% of patients. A total of 67 (47%) patients had VS that were chronic from onset, 29 (21%) had episodic symptoms, and in 46 (32%) the VS had evolved from episodic to chronic (with an average duration of 7.04 years required for this evolution to occur). CONCLUSIONS: Vestibular migraine is a heterogeneous condition with varying symptomatology. As with migraine itself, symptomatic expression varies along a spectrum that extends from episodic to chronic. As the histories of many of the patients we evaluated would not meet current International Classification of Headache Disorders criteria, we suggest that new criteria which account for the heterogeneity and natural history of the disorder may be required to adequately diagnose and treat those who suffer from VM.

Hemicrania continua: a second case in which the remitting form evolved from the chronic form.

We report the case of a woman with a 15-year history of chronic hemicrania continua, which over time evolved to remitting hemicrania continua. This is the second reported case in the literature documenting this transition.

Frovatriptan for acute treatment of migraine associated with menstruation: results from an open-label postmarketing surveillance study.

AIMS: To examine the effectiveness and tolerability of acute treatment with frovatriptan in women experiencing menstrual migraine (MM) vs. female migraineurs with non-MM. METHODS: This was an open-label postmarketing surveillance study (n = 7107) conducted in Germany to assess acute treatment with frovatriptan in one to three migraine attacks. This retrospective subanalysis evaluated acute frovatriptan treatment in women who experienced >or=1 MM attack vs. those women with non-MM attacks. Effectiveness and tolerability were graded using a 4-point scale (1 = very good, 2 = good, 3 = satisfactory, 4 = poor). RESULTS: Demographics were similar in MM (n = 1931) and non-MM patients (n = 2080), except that mean age (38.3 vs 45.3 years, respectively) and number of migraine attacks per month were less in the MM group than in the non-MM group (both p < 0.001). Although 98% of women reported that their previous migraines were moderate or severe, only one third in each treatment group previously used triptans. Prestudy medications were rated as good or very good for effectiveness by 20.3% and 19.2% of the MM and non-MM groups, respectively. In contrast, the effectiveness of frovatriptan was rated as very good or good by 92.7% and 90.9% of women in the MM and non-MM groups, respectively. Forty-three percent and 96% of all women rated their previous medication and frovatriptan, respectively, as having good or very good tolerability. Among women rating their previous medication as poor or satisfactory, most (94%) rated frovatriptan as very good or good. CONCLUSIONS: Acute frovatriptan treatment improved patient ratings of treatment effectiveness and tolerability in women with migraine associated with menses.

Rebound abdominal pain: noncephalic pain in abdominal migraine is exacerbated by medication overuse.

Abdominal migraine usually has its onset during childhood or adolescence and resolves in adulthood, often being replaced by typical migraine headaches. Rarely, migraine headache and recurrent abdominal pain coexist in some patients during adulthood. We report a patient who developed abdominal migraine without headaches beginning for the first time at the age of 22 years. The abdominal symptoms increased in frequency coincident with medication overuse and resolved after the overuse was treated. Analgesic overuse may cause a worsening of noncephalic pain in patients with extra-cephalic variants of migraine.

Understanding the causes and prevention of menstrual migraine: the role of estrogen.

Menstruation increases the risk of migraine in susceptible women. In a subpopulation of women with menstrual migraine, headaches occurring in association with onset of menses may be more severe and of longer duration than headaches experienced by the same woman at other times of her menstrual cycle. Although menstrual migraines share many clinical characteristics of other types of migraines, their occurrence is predictable provided that the patient has regular menstrual cycles. Therefore, short-term prevention regimens can be considered for women whose headaches are not adequately managed with acute therapies.

Hemicrania continua: a third case in which attacks alternate sides.

Hemicrania continua (HC) is an uncommon, primary headache disorder characterized by a continuous unilateral headache of moderate intensity with superimposed exacerbations of more severe pain. HC exists in two temporal subtypes, a continuous form in which headaches persist continuously without remission periods, and a less common remitting form in which bouts of continuous headaches are separated by pain-free remissions. There have been more than 100 prior reports of HC; in the majority of which the headache is strictly unilateral and without side shift. We now report the third patient in whom headaches alternated sides during different attacks.

Cluster headaches and related disorders.

The headache disorders described here are relatively rare, but probably are more common than previously thought. These disorders cause significant pain and disability, so recognition is essential as treatment response differs from that of migraine, tension-type, and cluster headaches. Table 4 reviews the important clinical features of these syndromes and contrasts them with cluster headache, the disorder for which they are often confused.