Menstrual Migraine and Treatment Options: Review.

OBJECTIVE: A review of treatment options for menstrual migraine. BACKGROUND: Migraine affects ∼30 million people in the US. A subset of female migraineurs have migraines that are mainly associated with menstruation. Menstrual migraine (MM) is divided into pure MM and menstrually related migraine. Pure MM attacks occur only with menstruation and have a prevalence of 1%. Menstrually related migraine has a prevalence of 6-7%, and occurs both during menstruation as well as during the rest of the cycle. MM is usually without aura and is more severe, longer lasting, and more resistant to treatment due to the effects of ovarian hormones, specifically estrogen. MM treatment is divided into acute, short-term prophylaxis, and daily prevention. The best-studied acute treatments are triptans. For short-term prophylaxis, triptans, non-triptans, or combinations are used. Some preventive medications may be used daily to prevent MM. Many anti-epileptic medications used in migraine prevention can affect the efficacy of oral contraceptives and hormonal treatments, so caution is indicated when these are used. METHODS: PubMed, Scopus, Cochrane, and Embase were searched for MM and treatments. RESULTS: Many randomized, placebo-controlled, prospective studies have evaluated the efficacy of sumatriptan, rizatriptan, naratriptan, zolmitriptan, and almotriptan in MM. Reviewing numerous studies with statistically significant results, rizatriptan has the best overall evidence for acute treatment of MM, ranging from pain-free responses of 33-73% at 2 hours. Sumatriptan and rizatriptan have shown similar efficacies of 61-63% in terms of 2 hour pain freedom. Rizatriptan showed sustained pain relief between 2 and 24 hours with an efficacy of 63% and sustained pain freedom for MM between 2 and 24 hours with an efficacy of 32%. For short-term prevention of MM, there were four randomized controlled trials for frovatriptan taken twice daily, one trial for zolmitriptan taken three times daily, and two studies for naratriptan taken twice daily, all of which showed statistically significant results. Among studies on non-triptans for short-term prevention of MM, magnesium, estrogen, naproxen sodium, and dihydroergotamine all had statistically significant results. Many antiepileptic medications taken for prevention of MM can cause enzyme induction affecting oral contraceptives (OCs) and hormonal treatments to different degrees. Topiramate has the least effect on OCs at doses below 200 mg/day. Lamotrigine noticeably decreases oral contraceptive levels; however, the evidence for it as a preventive medication is not strong. CONCLUSION: MM can be very difficult to treat. For acute treatments, rizatriptan has the best overall evidence. For short-term prevention, frovatriptan, zolmitriptan, or naratriptan, as well as magnesium, estrogen, naproxen sodium, or dihydroergotamine may be useful.

Patent Foramen Ovale and Migraine: Closing the Debate--A Review.

BACKGROUND: A link between patent foramen ovale (PFO) and migraine as well as the utility of closure of PFO and its effect on migraine have been subjects of debate. The present review is an effort to gather the available evidence on this topic and formulate recommendations. METHODS: A systematic search of electronic databases (Medline, Embase, Cochrane Library) was performed. A separate search in associated reference lists of identified studies was done. Observational studies and clinical trials published in English using the International Headache Society criteria for diagnosis of migraine were included in the analysis. The search was performed in 3 categories: prevalence of migraine in patients with PFO, prevalence of PFO in migraine patients, and effect of PFO closure and its effect on migraine. The quality of evidence and strength of recommendations during review of these studies was analyzed. RESULTS: About 14 observational studies with 2602 subjects who had PFO were identified. Migraine prevalence ranged from 16% to 64%. Another 20 studies reported 2444 patients with migraine; the prevalence of PFO ranged from 15% to 90%. About 20 observational studies (1194 patients) that examined the effect of PFO closure on migraine were identified. Resolution of migraine was reported in 10% to 83% of patients, improvement in 14% to 83%, no change in 1% to 54%, and worsening in 4% to 8%. The overall quality of these observational studies was poor. Finally, 3 randomized clinical trials included a total of 238 patients who underwent PFO closure compared with 234 patients in the control groups. All 3 trials failed to meet their primary end points defined as migraine resolution and greater than 50% reduction in migraine days at 1 year. In 2 of the clinical trials, there was some benefit noted in a small subset of migraine patients with aura, but the numbers were too small to extrapolate the findings to the general migraine population. CONCLUSIONS: There is no good quality evidence to support a link between migraine and PFO. Closure of PFO for migraine prevention does not significantly reduce the intensity and severity of migraine. We do not recommend the routine use of this procedure in current practice.

Case Report of Debilitating Headaches and a Coexisting Ophthalmic Artery Aneurysm: An Indication for Treatment?

OBJECTIVE: We present a case of a patient who had severe unilateral headaches related to a small, unruptured ophthalmic artery aneurysm, who experienced complete headache cessation following endovascular coiling. BACKGROUND: Small unruptured intracranial aneurysms are generally managed and followed conservatively due to minimal risk of rupture. Headaches are frequently reported in patients with intracranial aneurysms, but these aneurysms are typically considered incidental and unrelated, given the undefined association between headaches and most aneurysms. CONCLUSION: There may be some unruptured intracranial aneurysms that can cause intractable headaches and warrant interventional treatment. Future prospective studies are needed that compare pre- and post-procedure headache character and diagnosis, aneurysm characteristics such as size, location, orientation, and shape, type of aneurysm repair with materials used, and other potential risk factors for worsening post-procedure headache in order to better predict headache association to aneurysms, as well as outcomes following endovascular aneurysm treatment.

Long-Term Outcomes and Clinical Characteristics of Hypnic Headache Syndrome: 40 Patients Series From a Tertiary Referral Center.

OBJECTIVE: Hypnic headaches (HHs) are unique because of late life onset and characteristic periodic nocturnal awakening. We retrospectively identified 40 cases at a tertiary headache referral center over the course of 6 years and assessed response to conventional treatments. METHODS: This was a retrospective study in which patients were identified using primary and secondary ICD-9 diagnostic codes of HHs (339.81) from October 2008 until December 2014 using the International Classification of Headache Disorders II and III-beta criteria for diagnosis. Baseline characteristics were collected. Primary outcome was response to medications divided into 4 categories: complete response (headaches completely gone), moderate response (≥50% decrease in frequency), partial response (<50% decrease in frequency), no response. RESULTS: Forty (40) patients (80% females) were identified with HHs, and mean follow-up was 929 days (range 42-2555). Average age of headache onset was 62 years (range 44-86). Twenty (50%) patients had previous history of migraine, 5% had bilateral cranial autonomic features, and 40% underlying sleep abnormalities. The average duration per day and frequency per month of headaches were 186 minutes (range 30-720 minutes) and 21 days (range 5-30), respectively. Among 15 different medications tried, the best response was seen with lithium (7/10 [70%] complete response and 2/10 [20%] moderate response). With caffeine, there was a complete response in 6/21 (28%) and moderate response in 9/21 (43%) subjects. A telephone follow-up survey revealed that 5 patients in the bedtime caffeine group also benefited from taking a caffeinated drink at the time of awakening. CONCLUSIONS: HH is an infrequent primary headache disorder that can present with cranial autonomic features. It can persist for years in the elderly. Lithium appeared to be the most effective treatment option, followed by caffeine at bedtime. Caffeine ingestion on awakening with an HH also demonstrated benefit. Cervicogenic headaches in the elderly and presence of active migraine are major confounders in the diagnosis of HHs.

Effect of OnabotulinumtoxinA Injection on Depression in Chronic Migraine.

OBJECTIVE: The current study retrospectively evaluated patient reported outcomes (PROs) collected before and after at least 2 sessions of onabotulinumtoxinA (onabot) injections for chronic migraine. Depression was assessed by the Patient Health Questionnaire-9. METHOD: Chronic migraineurs receiving onabot were identified. In addition to the Patient Health Questionnaire-9 (PHQ9), the European Quality of Life (QOL), 5-Dimension (EQ-5D) (QOL), Headache Impact Test (HIT6), and Pain Disability Index (PDI) were reviewed across ≥2 consecutive onabot injections for 6-12 months. Paired t-tests on patient's questionnaire scores before and after treatment were performed. Analysis of the PHQ9 was restricted to patients with pretreatment scores ≥ 10 (moderate to severe depression). Change in PHQ9 was the primary outcome, and other PROs were also evaluated. RESULTS: Four hundred twenty-nine patients met the inclusion criteria, and data were gathered from 2010 to 2014. Average age was 45 years, with 85.5% female, and 92.1% Caucasian. There were 127 patients with PHQ9 scores ≥10 at baseline. Their PHQ9 scores improved from 14.4 (high-moderate) pre-onabot to 11.3 (low-moderate) post-onabot (P <.0001, 95% CI = -4.2 to -2.1); PDI improved from 4.3 to 3.8 (P = .0078, 95% CI = -0.7 to -0.1); EQ-5D improved from 0.74 to 0.77 (P = .0078; 95%CI = 0.01 to 0.04); HIT6 improved from 63.3 to 60.5 (P <.0001, 95%CI = -3.4 to -2.2). For comparison, in the PREEMPT onabot regulatory trials, HIT6 changed from 66 to 61.2 after 5 onabot injections at 24 weeks, P < .001. CONCLUSION: Onabot injections in chronic migraine patients statistically improved depression scores in patients beginning with at least moderate depression and improved scores in headache and quality of life. Onabot injections also decreased impact of headache on daily life.

Five-year outcome of surgical treatment of migraine headaches.

BACKGROUND: This study was designed to assess the long-term efficacy of surgical deactivation of migraine headache trigger sites. METHODS: One hundred twenty-five volunteers were randomly assigned to the treatment (n = 100) or control group (n = 25) after examination by the team neurologist to ensure a diagnosis of migraine headache. Patients were asked to complete the Medical Outcomes Study 36-Item Short Form Health Survey, Migraine-Specific Quality of Life, and Migraine Disability Assessment questionnaires before treatment and at 12- and 60-month postoperative follow-up. The treatment group received botulinum toxin to confirm the trigger sites; controls received saline injections. Treated patients underwent surgical deactivation of trigger site(s). Results were analyzed at 1 year (previously published) and 5 years postoperatively (the subject of this report). RESULTS: Eighty-nine of 100 patients in the treatment group underwent surgery, and 79 were followed for 5 years. Ten patients underwent deactivation of additional (different) trigger sites during the follow-up period and were not included in the data analysis. The final outcome with or without inclusion of these 10 patients was not statistically different. Sixty-one (88 percent) of 69 patients have experienced a positive response to the surgery after 5 years. Twenty (29 percent) reported complete elimination of migraine headache, 41 (59 percent) noticed a significant decrease, and eight (12 percent) experienced no significant change. When compared with the baseline values, all measured variables at 60 months improved significantly (p < 0.0001). CONCLUSION: Based on the 5-year follow-up data, there is strong evidence that surgical manipulation of one or more migraine trigger sites can successfully eliminate or reduce the frequency, duration, and intensity of migraine headache in a lasting manner.

A placebo-controlled surgical trial of the treatment of migraine headaches.

BACKGROUND: Many of the nearly 30 million Americans suffering with migraine headaches are not helped by standard therapies, a proportion of which can harbor undesirable side effects. The present study demonstrates the efficacy of independent surgical deactivation of three common migraine headache trigger sites through a double-blind, sham surgery, controlled clinical trial. METHODS: Seventy-five patients with moderate to severe migraine headache who met International Classification of Headache Disorders II criteria were studied. Trigger sites were identified (frontal, temporal, and occipital), and patients were randomly assigned to receive either actual or sham surgery in their predominant trigger site. Patients completed the Migraine Disability Assessment, Migraine-Specific Quality of Life, and Medical Outcomes Study 36-Item Short Form Health Survey health questionnaires before treatment and at 1-year follow-up. RESULTS: Of the total group of 75 patients, 15 of 26 in the sham surgery group (57.7 percent) and 41 of 49 in the actual surgery group (83.7 percent) experienced at least 50 percent reduction in migraine headache (p < 0.05). Furthermore, 28 of 49 patients in the actual surgery group (57.1 percent) reported complete elimination of migraine headache, compared with only one of 26 patients in the sham surgery group (3.8 percent) (p < 0.001). Compared with the control group, the actual surgery group demonstrated statistically significant improvements in all validated migraine headache measurements at 1 year. These improvements were not dependent on the trigger site. The most common surgical complication was slight hollowing of the temple in the group with temporal migraine headache. CONCLUSION: This study confirms that surgical deactivation of peripheral migraine headache trigger sites is an effective alternative treatment for patients who suffer from frequent moderate to severe migraine headaches that are difficult to manage with standard protocols.

Comprehensive surgical treatment of migraine headaches.

The purpose of this study was to investigate the efficacy of surgical deactivation of migraine headache trigger sites. Of 125 patients diagnosed with migraine headaches, 100 were randomly assigned to the treatment group and 25 served as controls, with 4:1 allocation. Patients in the treatment group were injected with botulinum toxin A for identification of trigger sites. Eighty-nine patients who noted improvement in their migraine headaches for 4 weeks underwent surgery. Eighty-two of the 89 patients (92 percent) in the treatment group who completed the study demonstrated at least 50 percent reduction in migraine headache frequency, duration, or intensity compared with the baseline data; 31 (35 percent) reported elimination and 51 (57 percent) experienced improvement over a mean follow-up period of 396 days. In comparison, three of 19 control patients (15.8 percent) recorded reduction in migraine headaches during the 1-year follow-up (p < 0.001), and no patients observed elimination. All variables for the treatment group improved significantly when compared with the baseline data and the control group, including the Migraine-Specific Questionnaire, the Migraine Disability Assessment score, and the Short Form-36 Health Survey. The mean annualized cost of migraine care for the treatment group (925 dollars) was reduced significantly compared with the baseline expense (7612 dollars) and the control group (5530 dollars) (p < 0.001). The mean monthly number of days lost from work for the treatment group (1.2) was reduced significantly compared with the baseline data (4.41) and the control group (4.4) (p = 0.003). The common adverse effects related to injection of botulinum toxin A included discomfort at the injection site in 27 patients after 227 injections (12 percent), temple hollowing in 19 of 82 patients (23 percent), neck weakness in 15 of 55 patients (27 percent), and eyelid ptosis in nine patients (10 percent). The common complications of surgical treatment were temporary dryness of the nose in 12 of 62 patients who underwent septum and turbinate surgery (19.4 percent), rhinorrhea in 11 (17.7 percent), intense scalp itching in seven of 80 patients who underwent forehead surgery (8.8 percent), and minor hair loss in five (6.3 percent). Surgical deactivation of migraine trigger sites can eliminate or significantly reduce migraine symptoms. Additional studies are necessary to clarify the mechanism of action and to determine the long-term results.

Hourglass deformity after botulinum toxin type A injection.

BACKGROUND: Complications, such as eyelid ptosis, have been attributed to botulinum toxin type A. An "hourglass" deformity, which is the consequence of temporalis muscle atrophy, has not been reported previously. OBJECTIVE: To report a transient muscle deformity of the temporalis muscle caused by botulinum toxin type A. METHODS: Patients who underwent injection of 25 units of botulinum toxin type A into the temporal muscle, in a fan-shaped fashion, during an ongoing study for treatment of migraine were noted to develop temporary depression of the temples. Preinjection and postinjection photographs were taken. Patients were also sent questionnaires to verify the observed information. RESULTS: Only 26 of 92 patients who underwent injection of botulinum toxin type A into the temporalis muscle subsequently reported depression of the muscle. When examined, all 92 patients exhibited this deformity ranging from minimal to significant. Patients who seemed to have less deformity were those who had excessive soft tissue overlying the muscle due to excess weight. CONCLUSION: A newly recognized deformity is reported subsequent to the injection of botulinum toxin type A into the temporalis muscle. Informing patients of this transient deformity may minimize concern following treatment.