Search

Background Triptans are the most commonly prescribed acute treatments for migraine; however, not all triptan users experience adequate response. Information on real-world resource use and costs associated with triptan insufficient response are limited. Methods A retrospective claims analysis using US commercial health plan data between 2012 and 2015 assessed healthcare resource use and costs in adults with a migraine diagnosis newly initiating triptans. Patients who either did not refill triptans but used other non-triptan medications or refilled triptans but also filled non-triptan medications over a 24-month follow-up period were designated as potential triptan insufficient responders. Patients who continued filling only triptans (i.e. triptan-only continuers) were designated as potential adequate responders. All-cause and migraine-related resource use and total (medical and pharmacy) costs over months 1–12 and months 13–24 were compared between triptan-only continuers and potential triptan insufficient responders. Results Among 10,509 new triptan users, 4371 (41%) were triptan-only continuers, 3102 (30%) were potential triptan insufficient responders, and 3036 (29%) did not refill their index triptan or fill non-triptan medications over 24 months’ follow-up. Opioids were the most commonly used non-triptan treatment (68%) among potential triptan insufficient responders over 24 months of follow-up. Adjusted mean all-cause and migraine-related total costs were $5449 and $2905 higher, respectively, among potential triptan insufficient responders versus triptan-only continuers over the first 12 months. Conclusions In a US commercial health plan, almost one-third of new triptan users were potential triptan insufficient responders and the majority filled opioid prescriptions. Potential triptan insufficient responder patients had significantly higher all-cause and migraine-related healthcare utilization and costs than triptan-only continuers.

Purpose of Review Migraine and other primary headache disorders do not receive adequate research funding, medical resources, or other forms of structural support relative to their prevalence and the disability they cause. In recent research, scholars have argued that stigma associated with headache disorders explains some of this discrepancy. This review will discuss (1) the factors contributing to stigma toward migraine and other primary headache disorders, (2) how structural and enacted stigma may perpetuate individual disability, (3) the impact of internalized stigma, and (4) interventions to mitigate stigma toward headache disorders with an emphasis on outcome monitoring. The review will also propose new areas of stigma research in need of further investigation. Recent Findings Recent research shows that discrimination can exacerbate chronic pain. Summary Stigma profoundly affects everything from the allocation of federal research funds and healthcare resources to individual patients’ self-efficacy and ability to care for themselves. Understanding the stigma of migraine and learning how to develop effective interventions to mitigate this stigma will increase access to appropriate migraine care, improve healthcare providers’ ability to care for their migraine patients, and help advocates reverse policies that discriminate against those with migraine. It is important to closely monitor outcomes of anti-stigma efforts for both positive and negative consequences and take note of outcomes and “lessons learned” from anti-stigma campaigns for other diseases. Supplementary Information The online version contains supplementary material available at 10.1007/s11916-021-00982-z.

To review carnitine’s role in migraine and headache, present a case of a patient with intractable chronic migraine refractory to medications but exquisitely responsive to mitochondrial cofactors with a particularly prompt response to L-carnitine supplementation with dose response, and suggest scenarios where L-carnitine could be considered for prophylactic treatment in migraine and intractable headache with migraine features. Multiple treatments modalities are used to treat migraine, including nutraceutical therapies. Mitochondrial supplements are often used to treat migraine, based on controlled trials. One of the nutraceutical therapies used in neurological and non-neurological conditions is L-carnitine. A few studies have examined the effect of carnitine in patients with migraine. We present a case of a patient with chronic migraine-like headaches found to have carnitine deficiency whose headaches greatly improved with carnitine supplementation. This case suggests that secondary carnitine deficiency may cause chronic migraine. Energy deficiency states occur with migraine, and replenishment of energy substrates has demonstrated some improvement in migraine. Recent studies suggest that L-carnitine with other mitochondrial cofactors may be migraine preventives. The exact link between carnitine and migraine is unknown. Perhaps carnitine deficiency should be in the differential for refractory migraine. Supplementation with L-carnitine merits exploration as a nutraceutical treatment of chronic migraine. Our case suggests that there may be a dose-dependent response to L-carnitine.

Introduction: Triptans, the most commonly prescribed acute treatments for migraine attacks are, per FDA labeling, contraindicated in cardiovascular (CV) disease patients and have warnings and precautions for those with CV risk factors. Methods: Headache specialists, cardiologists, and health economics and outcomes researchers convened to identify diagnostic codes for: (1) CV diseases contraindicating triptans based on FDA labeling; (2) conditions comprising “other significant underlying CV disease”; and (3) CV risk factors included as warnings and precautions for triptans. A retrospective, cross-sectional analysis of commercially insured adult US migraine patients in the 2017 Optum® Clinformatics® Data Mart (CDM) and the 2017 IBM® Watson Health MarketScan® Commercial Claims database was used to estimate the proportion of migraine patients with CV contraindications and warnings and precautions to triptans. Results: Of the 56,662 migraine patients analyzed from Optum CDM, 13.5% had ≥1 CV disease as specified in triptan labeling and an additional 8.5% had ≥1 “other CV disease” judged by the panel to constitute a “significant underlying CV disease” (total: 22.0% migraine patients). Of 176 724 migraine patients analyzed from MarketScan, 12.2% had ≥1 CV disease as specified in the labeling and an additional 8.0% had ≥1 “other significant underlying CV disease” (total: 20.2% of migraine patients). An additional 25.4% and 25.1% of migraine patients had ≥2 CV risk factors in Optum CDM and MarketScan. In total, 47.4% and 45.3% of migraine patients in both databases had a CV disease specified as a contraindication, an “other CV disease” endorsed as significant, or ≥2 CV risk factors identified as warnings and precautions to triptans. Conclusions: Analyses of more than 230,000 people with migraine showed that ≥20% of commercially insured US migraine patients have a CV condition that specifically contraindicates triptan treatment, and an additional 25% have ≥2 CV risk factors identified as warnings and precautions to triptans.

Migraine is a common chronic neurological disease that disproportionately affects women. Migraine has significant negative effects on physical, emotional, and social aspects of health, and can be costly for patients, employers, and society as a whole. Growing evidence supports the roles of sex and gender in migraine risk, pathophysiology, presentation, diagnosis, treatment, and management. However, sex and gender differences in migraine have received limited attention, which can impede advancements in migraine detection, treatment, care, and education. The Society for Women's Health Research convened an interdisciplinary expert panel of researchers, clinicians, and advocates for a roundtable meeting to review the current research on sex and gender differences in migraine. This review summarizes discussions from the roundtable and prioritizes areas of need that warrant further attention in migraine research, care, and education. Examining sex and gender differences in migraine and addressing knowledge gaps will decrease the health and economic burden of migraine for both women and men.

Migraine is a prevalent disease with a substantial socioeconomic impact. However, stigma affects social attitude toward migraine, accruing additional burden on individuals with migraine and isolating them from a society that should be supporting them. PURPOSE OF THIS REVIEW: This review will discuss the following concepts: (1) the emergence of stigma toward migraine and its impact on medical care; (2) internalized stigma among those with migraine and its detrimental effect on quality of life and patient-physician relationships; (3) the structural impact of stigma on research funding, workplace support, and specialized care; and (4) strategies for "rebranding" the disease and alleviating stigma toward migraine. RECENT FINDINGS: Recent literature on condition rebranding offers strategies on how to define and communicate migraine to the public. Rebranding of migraine to alleviate societal stigma is paramount. This involves use of unified language, education, and advocacy.

Background Dual supraorbital and occipital nerve stimulation (SONS and ONS) have shown promising efficacy in treating primary headaches. However, its functional outcome is not well studied. Objective To present functional outcome studies of combined SONS and ONS for chronic migraine using verified metrics. Method Consecutive patients with both SONS and ONS assessed with Migraine Disability Assessment (MIDAS) and Beck Depression Index (BDI) both preoperatively and postoperatively were studied. Selected predictor variables included patients with ≥50% improvement of pain, disability status, number of years from diagnosis to implantation, and narcotic use. Functional outcome variables included net improvement of ranked MIDAS and BDI scores. Multivariate analysis of variance was performed to assess the correlation between the outcome and predictor variables. Results Sixteen patients (12 female; average age 52 years old) were studied. Follow-up ranged from 5 to 80 months (average 44.5; σ = 21.4 months). At most recent follow-up, eight patients had a positive response (≥50% improvement in headache), which was the only predictor of functional outcome (total MIDAS, MIDAS-B, and BDI) (p = 0.021). Of note, improvement in functional outcome was only significant during the perioperative 3–6 months period and not throughout long-term follow-up. Among the predictor variables, a strong inverse correlation was found between disability status and positive response to stimulation (r = −0.582). Conclusion There is a paucity of studies in quality of life, productivity, and psychosocial aspects with peripheral nerve stimulation therapy for headache. Patients with a positive response to SONS and ONS also reported overall improvement in their functional status as reflected by MIDAS and BDI in the perioperative period. Unfortunately, this effect waned over the long-term follow-up.

Background OnabotulinumtoxinA is effective in treating chronic migraine (CM), but there are limited data assessing how allodynia affects preventive treatment responses. This subanalysis of the 108-week, multicenter, open-label COMPEL Study assessed the efficacy and safety of onabotulinumtoxinA in people with CM with and without allodynia. Methods Patients (n = 715) were treated with onabotulinumtoxinA 155 U every 12 weeks for 9 treatment cycles. The Allodynia Symptom Checklist was used to identify patients with allodynia (scores ≥3). The primary outcome for this subanalysis was reduction in monthly headache days from baseline for weeks 105 to 108 in groups with and without allodynia. Other outcomes included assessments of moderate to severe headache days, disability (using the Migraine Disability Assessment [MIDAS] questionnaire), and health-related quality of life (Migraine-Specific Quality-of-Life Questionnaire [MSQ] v2). Adverse events and their relation to treatment were recorded. Results OnabotulinumtoxinA was associated with a significant mean (SD) reduction in headache day frequency at week 108 relative to baseline in patients with (n = 289) and without (n = 426) allodynia (− 10.8 [7.1] and − 12.5 [7.4], respectively; both P

Background OnabotulinumtoxinA is effective in preventing chronic migraine (CM); however, the benefit of onabotulinumtoxinA in patients with CM with daily headache is unknown because these patients are typically excluded from clinical trials. This subanalysis of the COMPEL Study assessed the efficacy and safety of onabotulinumtoxinA in people with CM with and without daily headache. Methods In total, 715 patients received onabotulinumtoxinA 155 U with or without concomitant oral preventive treatment. Patients who had complete daily diary records for the 28 days of the baseline period were stratified based on daily headache status. The primary outcome variable was reduction in headache-day frequency per 28-day period at 108 weeks (after 9 treatment cycles) relative to baseline. Exploratory outcomes included moderate to severe headache days, migraine disability (using the Migraine Disability Assessment [MIDAS] questionnaire), and health-related quality of life (Migraine-Specific Quality-of-Life Questionnaire v2 [MSQ]). Adverse events and their relatedness were recorded. Results Overall, 641 patients had complete daily diary records at baseline. In patients with daily headache (n = 138) versus without (n = 503), treatment with onabotulinumtoxinA was associated with a significant mean (SD) reduction in 28-day headache-day frequency relative to baseline at week 108 (− 10.5 [9.2] vs − 12.2 [6.7], respectively; both P

The following article is a Thomas Jefferson Headache Center headache rounds presentation. A 37-year-old woman, who reports a history of chronic sinusitis, developed sudden onset headache 1 1/2 years prior to her initial presentation at the Jefferson Headache Center. At that time she noted acute severe pressure-like pain bilaterally in her neck, which radiated to her forehead above her eyebrows. She denied fever, rashes, or nasal discharge at the time. The pain was much more intense than her usual “sinus headaches” and associated with a positional component, occurring only upon standing, reaching a peak intensity of 10/10 that would only last seconds and remaining as a dull milder continuous frontal pain for up to 12 hours. She had nausea and vomiting but no photophobia, phonophobia, or osmophobia. There was no rhinorrhea, conjuctival injection, or eye tearing. The pain was alleviated upon lying down. After several emergency department visits, a head computed tomography was performed revealing chronic sinus disease that led her to sinus surgery with no improvement of symptoms. For several months, she was unsuccessfully treated with preventive therapy including topiramate, duloxetine, gabapentin, onabotulinumtoxin A, and abortive therapy including triptans, nonsteroidal anti-inflammatory drugs, barbiturates, and muscle relaxants. Acupuncture and occipital nerve blocks provided limited relief. The patient denied a prior medical and family history of migraines. Since the onset of symptoms, the patient continued to have intermittent explosive frontal headaches that would be triggered by standing and improved upon lying down. As time elapsed, she also noticed suboccipital pain and neck discomfort worsened by Valsalva maneuvers such as straining and coughing. She also reported bilateral upper extremity paresthesias along with subjective weakness.

Primary headache disorders are generally characterized by the pain, time course, and associated symptoms of their attacks, but often are accompanied by milder interictal pain. Patients with chronic migraine, chronic tension-type headache, hemicrania continua, and new daily-persistent headache have constant pain more often than not. Patients with trigeminal autonomic cephalalgias such as cluster headache commonly have interictal pain as well, usually much milder and unilateral to the side of attacks. Even those with rare headache types, including hypnic headache and trigeminal neuralgia, commonly have interictal pain. This review describes the incidence of interictal pain in primary headache disorders and suggests the significance and biological meanings of this pain.

Medical language has implications for both public perception of and institutional responses to illness. A consensus panel of physicians, academics, advocates, and patients with diverse experiences and knowledge about migraine considered 3 questions: (1) What is migraine: an illness, disease, syndrome, condition, disorder, or susceptibility? (2) What ought we call someone with migraine? (3) What should we not call someone with migraine? Although consensus was not reached, the responses were summarized and analyzed quantitatively and qualitatively. Panelists participated in writing and editing the paper. The panelists agreed that "migraine," not "migraine headache," was generally preferable, that migraine met the dictionary definition for each candidate moniker, terms with psychiatric valence should be avoided, and "sufferer" should be avoided except in very limited circumstances. Overall, while there was no consensus, "disease" was the preferred term in the most situations, and illness the least preferred. Panelists disagreed strongly whether one ought to use the term "migraineur" at all or if "person with migraine" was preferable. Panelists drew upon a variety of principles when considering language choices, including the extent to which candidate monikers could be defended using biomedical evidence, the cultural meaning of the proposed term, and the context within which the term would be used. Panelists strove to balance the need for terms to describe the best science on migraine, with the desire to choose language that would emphasize the credibility of migraine. The wide range of symptoms of migraine and its diverse effects may require considerable elasticity of language.

New daily-persistent headache is a relatively uncommon type of chronic daily headache. The critical features of the original description and the subsequent Silberstein-Lipton description was the onset: daily headache starts abruptly without a background of frequent or worsening headache. In 2004, the International Headache Society classification committee excluded an abundance of migrainous features. The exclusion of patients with too many migrainous features from the International Headache Society classification was contentious from the onset and is a source of consternation for many headache experts. Many contend that the sudden onset of a daily headache raises the same issue of what turned on the headache, irrespective of the headache features. Switch-related questions about predisposing factors or precipitating events are equally valid regardless of how many migrainous features the patient has. The differential diagnosis, treatment response, or prognoses do not vary by the number of migrainous features. The current International Headache Society definition excludes more than half of patients with new onset of daily headache. This exclusion due to migrainous features could have adverse scientific, diagnostic, and treatment consequences.

Background: New daily persistent headache (NDPH) is a primary chronic daily headache that is generally considered to be difficult to treat. Migraine has been linked to comorbid psychiatric conditions, mainly mood and anxiety disorders, but NDPH has never been linked to psychiatric conditions, and never studied extensively for such an association. Case: We report nine cases (six women and three men) of patients diagnosed with NDPH and panic disorder who were treated for both conditions. Six of them (66%) had good or excellent responses. Conclusion: The spectrum of anxiety disorders, particularly panic disorder, should be considered in NDPH patients. Simultaneous treatment of both disorders may lead to good outcomes.

Occipital nerve block has been part of headache medicine for more than half a century, with injection techniques and solutions varying greatly. Most studies have been case series and many show benefit for patients with migraine, cluster headache, and postconcussive headache. A double-blind, controlled trial of cluster headache has demonstrated that injectable steroids with local anesthetics benefit cluster headache patients. A double-blind, controlled trial of nerve blocks in occipital neuralgia, which may have actually been chronic migraine, was positive.

(Headache 2010;50:769-778) Background.— Electronic medical records (EMRs) are used in large healthcare centers to increase efficiency and accuracy of documentation. These databases may be utilized for clinical research or to describe clinical practices such as medication usage. Methods.— We conducted a retrospective analysis of EMR data from a headache clinic to evaluate clinician prescription use and dosing patterns of topiramate. The study cohort comprised 4833 unique de-identified records, which were used to determine topiramate dose and persistence of treatment. Results.— Within the cohort, migraine was the most common headache diagnosis (n = 3753, 77.7%), followed by tension-type headache (n = 338, 7.0%) and cluster or trigeminal autonomic cephalalgias (n = 287, 5.9%). Physicians prescribed topiramate more often for subjects with migraine and idiopathic intracranial hypertension (P

The objective of this study was to evaluate, in patients with migraine and healthy volunteers, with and without a history of motion sickness, the degree of discomfort elicited by drifting striped patterns. Eighteen healthy volunteers (HV) and 30 migraine patients participated in the study. Discomfort was greater in migraine patients than in HV, and in individuals with a history of motion sickness than in those without, but the effect of history of migraine was independent of history of motion sickness. Generalized Estimating Equations models for binary correlated data revealed that these differences did not depend on levels of duty cycle, spatial and temporal frequencies. Visual discomfort in migraine patients was associated with worse performance. There was a significant correlation between median degree of discomfort across conditions and number of migraine attacks in the past month. Discomfort to drifting striped patterns may be related to central sensitization in migraine patients.

Allodynia is a normal part of the untreated migraine attack in most people with episodic migraine and is prevalent in chronic migraine. The extent to which allo-dynia contributes to the pain and disability of migraine attacks is unclear, as is its clinical importance. The presence of allodynia correlates with the severity and other features of migraine, including aura, migraine-associated symptoms, and motor symptoms. The development of allodynia is associated with resistance to triptan treatment. It is uncertain whether this treatment resistance is due to the accompanying increase in headache severity or whether the development of allo-dynia is the fundamental biologic event causing the new treatment-refractory state. Animal models support the relationship to allodynia. Intravenous ketorolac may be effective at treating migraine with allodynia several hours after the development of the throbbing pain, but prior treatment with opioid analgesics may confer treatment resistance. Occipital nerve blocks rapidly treat migraine pain and allodynia. Uncontrolled studies have successfully used dihydroergotamine to treat episodic and chronic migraine with allodynia.

Objective.— To describe the use of mexiletine in the treatment of chronic daily headache in a refractory headache population. Background.— Intravenous lidocaine is a novel treatment for chronic daily headache with medication overuse and SUNCT syndrome. Mexiletine is a similar but orally active anti-arrhythmic that has been demonstrated to be an effective analgesic in various types of neuropathic pain. We looked at mexiletine as a preventative treatment for headache in refractory patients. Methods.— We reviewed the medical records of all patients with an order for mexiletine. For each patient, we determined diagnosis, presence of medication overuse on initial evaluation, pain scores, and if the patient received intravenous lidocaine before starting the medication. We then contacted patients by phone to confirm their dose, to review side effects and current pain scores, and to obtain a global impression of effectiveness. Results.— We identified 9 patients with a chronic daily headache, including chronic migraine or new daily persistent headache, with significant clinical improvement while using mexiletine as a headache preventative. Each patient had failed to respond to multiple preventative and acute treatments. Seven of the 9 rated mexiletine “much more effective” and 2 “more effective” than previous preventative headache medications. The daily dose ranged from 600 mg/day to 1500 mg/day. Side effects were common and occurred in 7 patients. The majority of patients with an order for mexiletine did not respond to treatment or had intolerable side effects. Discussion.— The preliminary study suggests mexiletine is a useful preventative treatment for some patients with chronic daily headache, including refractory patients with medication overuse or those who have failed multiple preventatives in the past.

Context.— Headache is a common, disabling disorder that is frequently not well managed in general clinical practice. Objective.— To determine if patients cared for in a coordinated headache management program would achieve reduced headache disability compared with patients in usual care. Design.— A randomized controlled trial of headache management vs usual care. Setting.— Three distinctly different practice sites: an academic internal medicine practice located in a major east coast city, a staff-model managed care organization located in a major west coast city, and a community practice in a medium-sized city in the southeast. Patients.— Individuals 21 years of age or older with chronic tension-type, migraine, or mixed etiology headache and a Migraine Disability Assessment (MIDAS) score greater than 5, not receiving treatment from a neurologist or headache clinic currently or within the previous 6 months and with an intention to continue general medical care at their current location and to continue their present health insurance coverage for the next 12 months. Interventions.— Active intervention is a headache management program consisting of: (1) a class specifically designed to inform patients about headache types, triggers, and treatment options; (2) diagnosis and treatment by a professional especially trained in headache care (based on US Headache Consortium guidelines); and (3) proactive follow-up by a case manager. Participation lasted 6 months. Control patients received usual care from their primary care providers. Main Outcome Measures.— The primary efficacy measure reported in this article is a comparison of MIDAS scores of headache disability between the intervention group and the control group at 6 months. Secondary measures were response at 12 months, general health and quality of life, and satisfaction with headache care. Results.— The intervention improved (ie, decreased) MIDAS scores by 7.0 points (95% confidence interval 2.9 to 11.1) more than the control (P = .008) at 6 months. The difference was not affected by site (P = .59 for clinic by intervention interaction), and a trend toward persistent benefit at 12 months (mean difference in improvement 6.8 points, 95% confidence interval −.3 to 13.9, P = .06) was observed. Quality of life and satisfaction with headache treatment were similarly improved. Conclusions.— Coordinated headache management significantly improved outcomes for patients who, despite contact with the healthcare system for headache, had substantial unmet needs. The intervention in this trial can be implemented practically in a wide range of settings with the expectation that meaningful improvements will accrue.

Weight gain is a common side effect of drugs used for headache prevention. Weight gain can adversely affect patient health, exacerbate comorbid metabolic disorders, and encourage noncompliance. Additionally, obesity may promote the chronification of episodic migraine. Few studies have looked specifically at the effect that headache medications have on weight. The practicing physician needs accurate information about important side effects, including weight gain, when selecting appropriate pharmacologic regimens. This article discusses the potential effects the more common headache medications have on weight.

Cephalic and extracephalic allodynia are recognized as a common sign of sensory sensitization during migraine episodes. However, the occurrence of body pain in migraine has not been thoroughly explored. Here we report three patients presenting with spontaneous body pain in association with migraine attacks. A 41-year-old woman experienced face and limb pain along with migraine headaches; it started before, during or after headache, was usually ipsilateral to head pain, and could last from minutes to days. A 39-year-old woman had pain in her right limbs, back and neck for 30-60 min prior to right-sided migraine headaches. A 30-year-old woman perceived pain in her left upper limb for 24-48 h prior to left-sided migraine headaches. All patients had allodynia to mechanical stimuli over the painful areas. Spontaneous body pain may be associated with migraine attacks. Together with allodynia, this might be a consequence of central sensitization.

Objective: To characterise the clinical features of non-familial migraine with unilateral motor symptoms (MUMS) and compare these features with those of migraine without weakness. Methods: 24 patients with MUMS and 48 matched controls were identified from a tertiary care headache centre. Using a structured interview, the migraine symptoms of both groups were characterised. Results of previously administered Beck Depression Inventories (BDI), Minnesota Multiphasic Personality Inventories and psychiatric diagnoses were collected, when available, and compared between groups. Results: 9 patients had episodic migraine and 15 had chronic migraine. Patients with MUMS always had weakness involving the arm subjectively, and both arm and leg objectively. A give-way character was always present. Only 17% of patients with MUMS reported facial weakness; 58% reported persistent interictal weakness; 92% reported sensory symptoms. A rostrocaudal march of sensory and motor symptoms was frequently reported. Weakness was ipsilateral to unilateral headache in two thirds of the patients. Compared with controls, patients with MUMS had had similar pain intensities, but were more likely to report other migrainous symptoms, including allodynia. 38% of patients with MUMS were told they had had a stroke, and 17% believed they had had a stroke despite normal brain imaging. Patients with MUMS reported fewer affective disorders and more adjustment disorders than controls, and had similar BDI scores. Conclusions: A syndrome of severe migraine with accompanying give-way weakness is common in tertiary care headache centres. It is accompanied by other neurological symptoms.

Headache education for the physician begins in medical school. The American Headache Society has endorsed a curriculum and core competencies.

Allodynia has been described in migraine but has not been fully investigated for the different sensory modalities. The aim of this study was to compare the prevalence of dynamic (brush) and static (pressure) mechanical allodynia in migraine patients and to suggest a practical method of testing them in a clinical setting. Patients with International Headache Society-defined episodic migraine (EM) or with transformed migraine (TM) as defined by Silberstein and Lipton were prospectively recruited from the Jefferson Headache Center out-patient clinic. A questionnaire of migraine features and symptoms of allodynia was administered. Brush allodynia (BA) was tested by cutaneous stimulation with a gauze pad and pressure allodynia (PA) was tested using von Frey hairs (VFH). The prevalence of BA and PA in all patients and in the different subgroups was calculated and correlated with migraine features. We recruited 55 migraine patients. Twenty-five had EM and 30 had TM. BA was present in 18 (32.7±) patients and PA in 18–24 (32.7–43.6±). Allodynia to both brush and pressure was found in 13–17 (23.6–30.9±) patients. If a patient had allodynia to one modality only, it was more likely to be PA than BA. Both BA and PA were more common in patients with TM compared with those with EM [BA 46.7± vs. 16.0±; PA (differences significant for the medium and thick VFHs) 50± vs. 20± and 50± vs. 12±, respectively]. Both types of allodynia were also more common in patients with migraine with aura compared with those with migraine without aura (BA 57.1± vs. 17.6±; PA 57.1–61.9± vs. 17.6–32.7±). There was a positive correlation between allodynia score (as obtained by examination) and allodynia index (as obtained by history) for both BA and PA. The incomplete, although considerable, overlap between BA and PA suggests that allodynia to different sensory modalities is associated with sensitization of different neuronal populations. Because PA was more common than BA, it may be a more sensitive indicator of allodynia in migraine. PA can be tested clinically in a practical and systematic manner.

Objectives.—To review the mechanism of action of neuroleptics, the evidence for their efficacy, and their clinical use in headache treatment. Background.—Neuroleptics and antiemetics have long been used for headache treatment; however, they have not been widely utilized because of general unfamiliarity with them and concerns about their adverse events. With the recent advent of the atypical neuroleptics and their improved adverse event profile, our armamentarium for headache treatment has expanded. In this review, we explore the mechanism of action of these classes of drugs, their adverse events, and the evidence for their efficacy. We also detail our experience with the different drugs and how we use them as both acute and preventive headache therapy. Design.—A review of published literature was obtained through a MEDLINE search on the use of neuroleptics in headache therapy. Conclusion.—Neuroleptics have widespread evidence supporting their use in headache treatment and present an important part of the armaterium against headache.

Medication overuse headache is an important and challenging problem for clinicians and researchers. The new International Headache Society classification now gives specific limits for medication use based on the number of days of treatment per month. Medication overuse headache is increasingly recognized in children. Triptan overusers have a more migrainous phenotype than overusers of other medications, as well as a shorter period of induction and a milder and more ultimately successful medication withdrawal course. Treatment may involve weaning the overused medications or abrupt discontinuation using a transitional medication for 1 or 2 weeks. Detoxification may be performed in an inpatient or outpatient setting. Repetitive intravenous valproate, prochlorperazine, or lidocaine may be reasonable alternatives to the traditional treatment of metoclopramide and dihydroergotamine. Biofeedback-assisted relaxation training improves outcomes after detoxification at 3 years. Even aggressive treatment is unsuccessful in a significant number of cases.

Migraine is a common, disabling disorder that often requires preventive treatment. The decision to treat migraine preventively generally is based on disability, problems with acute medicines, patient preference, risk of acute medication overuse, special circumstances, and concern that high migraine attack frequency may be a risk factor for chronic daily headache. Migraine and epilepsy are comorbid episodic central nervous system disorders that can have stereotyped symptoms with negative and positive phenomena. Controlled trials have demonstrated the efficacy of anticonvulsants in migraine prevention. Valproic acid, topiramate and, to a lesser extent, gabapentin, have demonstrated efficacy in randomized, placebo-controlled trials. Lamotrigine may be effective at controlling migraine aura, but has not demonstrated effectiveness at controlling migraine headache. Anticonvulsants are a useful option for the preventive treatment of migraine.

Objective.—To characterize the temporal course of transcranial magnetic stimulation-induced phosphene thresholds in subjects with migraine and in controls. Methods.—Eleven subjects with migraine with aura, 10 subjects with migraine without aura, 9 subjects with menstrual migraine, and 15 controls (no history of migraine and without migraine during the study) were studied. Subjects were not on preventive medication. Transcranial magnetic stimulation was performed, and a phosphene threshold was measured 3 times a week over 3 weeks in a manner timed to incorporate the menstrual period in females. A headache calendar was kept during the study. Results.—Mean transcranial magnetic stimulation thresholds were lower for each migraine group compared with controls (P < .001) for each comparison. There was a trend for lower thresholds among subjects with migraine with aura compared with subjects with migraine without aura (P < .10), but not subjects with menstrual migraine. There was consistent lowering of thresholds from the first to the last stimulation in all migraine groups and in the controls. Maximum and minimum thresholds did not predict headache occurrence, nor did the occurrence of headache predict an ensuing maximum or minimum phosphene threshold. Conclusions.—Transcranial magnetic stimulation thresholds are lower in subjects with migraine compared with controls. The reported phosphene threshold is lowered with repeated measurement. Neither high nor low phosphene thresholds predict a subsequent headache, nor do migraines predict a subsequent high or low threshold.

Medication overuse headache is a common complex disorder with physical and psychologic elements. Treatment may be difficult but often is accomplished in an outpatient setting. Some patients require inpatient treatments. An option for some is day treatment with i.v medication in an infusion center over several consecutive days. The two most common classes of drugs that acutely induce headache are NO donors, typified by NTG, and PDE inhibitors, typified by sildenafil. NO donors cause a biphasic headache in migraineurs and PDE inhibitors a monophasic one.

The purpose of the research presented in this article was to characterize restless legs syndrome (RLS) in a headache population and correlate treatment induced risks with dopamine blockers. Fifty patients with severe headache who were admitted to an outpatient infusion center were enrolled. The diagnosis of RLS was established using the International Restless Legs Syndrome Study Group criteria. Patients were screened for baseline akathisia using an akathisia scale and reexamined for akathisia after receiving intravenous infusion with one of four dopamine receptor blocking agents as treatment for their headaches. A change from baseline to post-infusion assessment of two points on a global assessment of akathisia was considered positive for drug-induced akathisia. Our results indicated that 41 (82%) of patients had episodic or chronic migraine. The rest had new daily persistent headache, cluster, or posttraumatic headache. Seventeen subjects (34%) met the criteria for RLS. Nineteen (38%) of the subjects developed drug-induced akathisia. Thirteen (76.5%) of the subjects with RLS developed akathisia compared with only 6 of the 33 (18.2%) without RLS (PFinally, we concluded that headache patients with RLS are at a greatly increased risk of developing drug-induced akathisia when treated with intravenous dopamine receptor blocking agents.

The treatment of a migraine attack can be difficult when first-line medication is unsuccessful and options for parenteral "rescue" therapy are limited.A randomized, double-blind, placebo-controlled, dose-ranging, multicenter study was conducted to assess the efficacy and tolerability of droperidol 0.1 mg, 2.75 mg, 5.5 mg, and 8.25 mg for the acute treatment of moderate to severe migraine headache in adults.A total of 331 patients were enrolled; 305 were treated. Headache response at 2 hours was better (p0.002) in the treatment groups receiving droperidol IM at doses of 2.75 mg (87%), 5.5 mg (81%), and 8.25 mg (85%) compared with placebo (57%). The percent of patients achieving a pain-free response at 2 hours after treatment was significantly greater than placebo for the droperidol 2.75-mg, 5.5-mg, and 8.25-mg dose groups. The frequency of headache recurrence (within 24 hours) for patients initially responding by 2 hours was lower in patients treated with droperidol than placebo, but differences failed to reach significance. A significantly greater percentage of patients receiving droperidol 2.75 mg reported the elimination of migraine-associated symptoms (nausea, vomiting, photophobia, and phonophobia) than those who received placebo. Although most adverse events were of mild or moderate intensity, anxiety, akathisia, and somnolence were rated as severe in 30% of patients who experienced those symptoms. Hypotension was uncommon. No patient had QT prolongation.

Fatigue is a common symptom frequently reported in many disorders including headaches, but little is known about its nature. The objective was to determine the prevalence of fatigue in chronic migraine (CM) patients, to define its subtypes and its relationship with other conditions comorbid with CM. Sixty-three CM patients were analysed. The Fatigue Severity Scale (FSS), the Chalder fatigue scale and the CDC diagnostic criteria for chronic fatigue syndrome (CFS) were used. Fifty-three (84.1%) patients had FSS scores greater than 27. Forty-two (66.7%) patients met the CDC criteria for CFS. Thirty-two patients (50.8%) met the modified CDC criteria (without headache). Beck depression scores correlated with FSS, mental and physical fatigue scores. Trait anxiety scores also correlated with fatigue scales. Women had higher FSS scores than men, P < 0.05. Physical fatigue was associated with fibromyalgia, P < 0.05. Fatigue as a symptom and CFS as a disorder are both common in CM patients. Therapeutic interventions include a graded aerobic exercise program, cognitive behavioural therapy and antidepressants. Identification of fatigue and its subtypes in headache disorders and recognition of headaches in CFS patients has implications for the pathophysiology, diagnosis and treatment of these disorders.

We reviewed the electronic records of 74 migraine patients treated with topiramate for more than 6 weeks. Twenty-four patients had episodic migraine and 50 had chronic (transformed) migraine. Most (81%) started treatment at 25 mg per day and reached a dose of 100 mg twice a day (mean dose on the last follow-up visit was 208 mg). The mean headache frequency decreased from 20.6 days to 13.6 days per month ( P < 0.0001) for all headaches (9.9-5.1 ( P < 0.0001) and 25.7-17.7 ( P < 0.001) for episodic migraine and chronic migraine, respectively). The percentage of patients whose headache frequency was reduced by ≥ 50% was 44.6% for all patients; 58.3 for episodic migraine and 38.0 for chronic migraine. For all patients mean headache severity (10-point scale) was reduced from 6.2 to 4.8 ( P < 0.0001). Patients on monotherapy (20%) and polytherapy (80%) had similar reductions in headache frequency. Adverse events were usually mild to moderate and were seen in 58.1% (paresthesias in 25%, cognitive difficulties 14.9%). Mean weight loss was 3.1 ± 4 kg (3.8% of total body weight).

Background.—Olanzapine, a thienobenzodiazepine, is a new “atypical” antipsychotic drug. Olanzapine's pharmacologic properties suggest it would be effective for headaches, and its propensity for inducing acute extrapyramidal reactions or tardive dyskinesia is relatively low. We thus decided to assess the value of olanzapine in the treatment of chronic refractory headache. Methods.—We reviewed the records of 50 patients with refractory headache who were treated with olanzapine for at least 3 months. All previously had failed treatment with at least four preventative medications. The daily dose of olanzapine varied from 2.5 to 35 mg; most patients (n = 19) received 5 mg or 10 mg (n = 17) a day. Results.—Treatment resulted in a statistically significant decrease in headache days relative to baseline, from 27.5 ± 4.9 before treatment to 21.1±10.7 after treatment (P

In the United States analgesic-overuse headache is often caused by butalbital-containing analgesics. These agents can cause physical and psychological dependency, and dangerous withdrawal syndromes. Butalbital-containing analgesics have already been banned in several European countries. They are proven effective in tension-type headache, but not in migraine; there are many alternative treatments for migraine and tension-type headache. In the 20 years since analgesic overuse headache was widely recognized, butalbital overuse has remained distressingly common. It is time to ban these agents.

Chronic migraine (CM) is a disabling complication of migraine. Prevalence is high, disease-related burden is great, and medical and psychiatric comorbidity is considerable. Treatment has been unsatisfactory and rigorous trials specifically targeting CM are rare. Topiramate and botulinum neurotoxin are the only pharmacological treatments that have been proven effective in randomized, placebo-controlled trials (1–6); however, the therapeutic gain (against placebo) is only modest (Table 1). New or complementary therapeutic modalities for CM treatment are needed. Acupuncture is a widely used, non-pharmacological treatment for migraine. Although its use is still controversial, a recent Cochrane systematic review found acupuncture to be as effective as, or possibly more effective than, preventive migraine agents (7). A beneficial effect of acupuncture in migraine prophylaxis was demonstrated in a prospective randomized trial for CM (8). In a 12-week treatment period, a significantly larger decrease in the mean monthly number of moderate/ severe headache days was observed in the acupuncture group compared with the topiramate group ( 10.5 vs. 7.8 days per 4 weeks, p< 0.01). Significant differences favoring acupuncture across multiple efficacy end points, including mean change of headache days, Migraine Disability Assessment Scores (MIDAS), Hospital Anxiety and Depression Scale (HADS) scores, Short Form 36 (SF-36) scores, Beck Depression Inventory II (BDI-II) scores, mean days of acute medication use, 50% reduction in monthly moderate/severe headache days, 50% reduction in monthly headache days, and safety end points were also observed. In the context of the topiramate studies (1,9) and the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials (4–6), similar beneficial effects were also observed in patients who were overusing acute medications. Does this study identify an alternative choice for CM patients? Probably yes, but the reasons behind the positive effect could be complex. The study was designed according to the guidelines for trials of the prophylactic treatment of CM (10) and had a clearly defined acupuncture treatment procedure following the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) recommendations (11), making it possible to replicate the study and provide a basis for comparisons across disciplines. The acupoints chosen are classic acupuncture sites, which correspond to the dermatomal distribution of trigeminocervical complexes: V1 dermatome [Cuanzhu (BL 2) and Yintang (EX-HN 3)], V2 dermatome [Taiyang (EX-HN 5)], and C2 dermatome [Fengchi (GB-20)]. Traditionally, acupuncture has had its own diagnostic system and the acupoints are individualized and tailored for headaches over different meridians. In this study, the benefits from individualized acupuncture are limited by the fixed-site approach. However, even with this trade-off, the acupuncture arm still outweighed the topiramate group. The positive results of this trial seem to provide a rational mechanism linking the intervention with the pathophysiology of migraine; that is, modulating the trigeminal sensory system. While this hypothesis is possible, a second thought is required to interpret the data. The investigators provided several reasons to justify the choice of topiramate as the active comparator instead of control with sham acupuncture; however, none could offset the putatively higher placebo effect caused by the needling procedure in comparison

Background.—According to the International Classification of Headache Disorders (ICHD)-2, primary daily headaches unremitting from onset are classified as new daily persistent headache (NDPH) only if migraine features are absent. When migraine features are present, classification is problematic. Methods.—We developed a revised NDPH definition not excluding migraine features (NDPH-R), and applied it to consecutive patients seen at the Montefiore Headache Center. We divided this group into patients meeting ICHD-2 criteria (NDPH-ICHD) and those with too many migraine features for ICHD-2 (NDPH-mf). We compared clinical and demographic features in these groups, identifying 3 prognostic subgroups: persisting, remitting, and relapsing-remitting. Remitting and relapsing-remitting patients were combined into a nonpersisting group. Results.—Of 71 NDPH-R patients, 31 (43.7%) also met NDPH-ICHD-2 criteria. The NDPH-mf and the NDPH-ICHD-2 groups were similar in most clinical features although the NDPH-mf group was younger, included more women, and had a higher frequency of depression. The groups were similar in the prevalence of allodynia, triptan responsiveness, and prognosis. NDPH-R prognostic subforms were also very similar, although the persisting subform was more likely to be of white race, to have anxiety or depression, and to have a younger onset age. Conclusions.-Current ICHD-2 criteria exclude the majority of patients with primary headache unremitting from onset. The proposed criteria for revised NDPH definition not excluding migraine features (NDPH-R) classify these patients into a relatively homogeneous group based on demographics, clinical features, and prognosis. Both NDPH with too many migraine features for ICHD-2 and NDPH meeting ICHD-2 criteria include patients in equal proportions that fall into the persisting, remitting, and relapsing-remitting subgroups. Our criteria for NDPH-R should be considered for inclusion in ICHD-3.

To determine whether there are any differences in health-related quality of life between patients with migraine and those with transformed migraine.There are no published reports comparing the health-related quality of life between patients with migraine and patients with transformed migraine.We conducted a retrospective analysis examining the health-related quality of life of patients with transformed migraine and migraine seen at a specialty headache clinic. Data collected included the Short Form-36 (SF-36) and the Migraine Disability Assessment questionnaires as well as demographic information. Both of these forms are part of the initial evaluation at the headache clinic. A t test with Bonferroni correction was used to test for significant differences in the SF-36 domains between the groups.Data were collected for 90 patients, 46 with transformed migraine and 44 with migraine. There were no significant differences between groups with respect to sex, race, or age. Over the last 90 days prior to their first visit, patients with transformed migraine reported having a headache an average of 69 days compared with patients with migraine who averaged 18 days with headache (P.05). Compared with patients with migraine, patients with transformed migraine had statistically (P.05) and clinically significant (difference5 points) lower mean scores on seven of the eight SF-36 domains and both the mental and physical summary scores of the SF-36.The results of this study suggest that patients with transformed migraine have a lower health-related quality of life than patients with migraine. These findings indicate that the headache chronicity associated with transformed migraine has a significant influence on quality of life. The results highlight the importance of effective management of headaches to avoid the progression of migraine to the more disabling transformed migraine.