The Headache-Attributed Lost Time (HALT) Indices: measures of burden for clinical management and population-based research.

BACKGROUND: The burden attributable to headache disorders has multiple components: a simple measure summarising them all does not exist. The Migraine Disability Assessment (MIDAS) instrument has proved useful, estimating productive time lost in the preceding 3 months due to the disabling effect of headache. We developed adaptations of MIDAS for purposes of the Global Campaign against Headache, embracing epidemiological studies and the provision of clinical management aids. METHODS: We reviewed the structure, content, wording and scoring of MIDAS and made revisions, developing the Headache-Attributed Lost Time (HALT) Indices in three versions. Over 10 years, these were employed in multiple epidemiological and clinical studies in countries worldwide. RESULTS: In the original HALT-90, we made no changes to the structure and scoring of MIDAS, but used wording in questions 1-4 that we believed would be more widely understood and more easily translated into other languages. Of the two alternative versions, HALT-30 kept the same structure, question format and wording except that "3 months" was replaced by "1 month". HALT-7/30 was a variant of HALT-30: focusing only on lost work time for population-based studies of headache-attributed burden, it enquired into lost days in the preceding month (30 days) and week (7 days). CONCLUSIONS: Three versions of the HALT Indices serve different purposes as measures of headache-attributed burden, and offer different means of scoring. In studies using HALT as a population measure, there is no need to reflect the states of individuals, whereas a measure over shorter periods than 3 months is likely to be more reliable through better recall. Assessment of individual patients prior to treatment may best estimate impact if enquiry is made into the preceding 90 days, except in cases where headache is highly frequent. Follow-up in clinical management may be better served by assessments over 30 rather than 90 days.

The headache under-response to treatment (HURT) questionnaire, an outcome measure to guide follow-up in primary care: development, psychometric evaluation and assessment of utility.

BACKGROUND: Headache disorders are both common and burdensome but, given the many people affected, provision of health care to all is challenging. Structured headache services based in primary care are the most efficient, equitable and cost-effective solution but place responsibility for managing most patients on health-care providers with limited training in headache care. The development of practical management aids for primary care is therefore a purpose of the Global Campaign against Headache. This manuscript presents an outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire, describing its purpose, development, psychometric evaluation and assessment for clinical utility. The objective was a simple-to-use instrument that would both assess outcome and provide guidance to improving outcome, having utility across the range of headache disorders, across clinical settings and across countries and cultures. METHODS: After literature review, an expert consensus group drawn from all six world regions formulated HURT through item development and item reduction using item-response theory. Using the American Migraine Prevalence and Prevention Study's general-population respondent panel, two mailed surveys assessed the psychometric properties of HURT, comparing it with other instruments as external validators. Reliability was assessed in patients in two culturally-contrasting clinical settings: headache specialist centres in Europe (n = 159) and primary-care centres in Saudi Arabia (n = 40). Clinical utility was assessed in similar settings (Europe n = 201; Saudi Arabia n = 342). RESULTS: The final instrument, an 8-item self-administered questionnaire, addressed headache frequency, disability, medication use and effect, patients' perceptions of headache "control" and their understanding of their diagnoses. Psychometric evaluation revealed a two-factor model (headache frequency, disability and medication use; and medication efficacy and headache control), with scale properties apparently stable across disorders and correlating well and in the expected directions with external validators. The literature review found few instruments linking assessment to clinical advice or suggested actions: HURT appeared to fill this gap. In European specialist care, it showed utility as an outcome measure across headache disorders. In Saudi Arabian primary care, HURT (translated into Arabic) was reliable and responsive to clinical change. CONCLUSIONS: With demonstrated validity and clinical utility across disorders, cultures and settings, HURT is available for clinical and research purposes.

Neuroticism, depression and pain perception in migraine and tension-type headache.

OBJECTIVES: People with migraine and tension-type headache (TTH) have psychiatric comorbidities. We aimed to test differences in mental health constructs by type and frequency of primary headache and associated pain sensitivity. MATERIALS AND METHODS: Data on headache features, neuroticism (Eysenck Personality Questionnaire) and depression (Major Depression Inventory) were obtained from 547 individuals classified into chronic (≥15) or episodic (<15 headache days/month) and into pure migraine (n=43), pure tension type headache (TTH, n=97), migraine and TTH (n=83) and no headache diagnosis (controls, n=324) groups. A pericranial total tenderness score (TTS) and pressure pain thresholds (PPTs) were measured. Differences in mental health constructs were examined by headache frequency and type using generalized linear mixed models adjusting for sociodemographic covariates. RESULTS: Depression scores were highest among people with chronic headache, lower in those with episodic headache, and lowest in controls. The chronic and episodic headache groups had higher neuroticism scores than controls. Mental health construct scores were highest for the migraine and TTH group and lowest in the control group. TTS and cephalic PPTs were correlated with neuroticism and depression and were higher in the chronic headache group compared to the no headache group even when adjusted for neuroticism and depression. CONCLUSIONS: Neuroticism and depression scores are associated with headache frequency (chronic vs episodic) and are highest for migraine and TTH followed by pure TTH then migraine. Mental health constructs were correlated with but did not influence differences in TTS and PPTs between headache groups.

Validation and calibration of HeadCount, a self-report measure for quantifying heading exposure in soccer players.

The long-term effects of repetitive head impacts due to heading are an area of increasing concern, and exposure must be accurately measured; however, the validity of self-report of cumulative soccer heading is not known. In order to validate HeadCount, a 2-week recall questionnaire, the number of player-reported headers was compared to the number of headers observed by trained raters for a men's and a women's collegiate soccer teams during an entire season of competitive play using Spearman's correlations and intraclass correlation coefficients (ICCs), and calibrated using a generalized estimating equation. The average Spearman's rho was 0.85 for men and 0.79 for women. The average ICC was 0.75 in men and 0.38 in women. The calibration analysis demonstrated that men tend to report heading accurately while women tend to overestimate. HeadCount is a valid instrument for tracking heading behaviour, but may have to be calibrated in women.

Dipyridamole-induced headache and lower recurrence risk in secondary prevention of ischaemic stroke: a post hoc analysis.

BACKGROUND AND PURPOSE: Our objective was to investigate the association between recurrent stroke risk and headache induced by extended-release dipyridamole (ER-DP) when administered alone or with low-dose aspirin (ASA+ER-DP). METHODS: This was a post hoc analysis of prospectively collected data on recurrent stroke risk and headache as an adverse event or reason for treatment discontinuation from the PRoFESS (N = 20,332) and ESPS2 (N = 6602) trials. Hazard ratios (HRs) for recurrent stroke were calculated using the Cox model. RESULTS: In PRoFESS, the 2.5-year recurrent stroke risk in patients receiving ASA+ER-DP was 8.2% in those with headache within 7 days of starting treatment and 9.4% in those without [HR 0.85, 95% confidence interval (CI) 0.73-0.98; P = 0.03]. Recurrent stroke risk was 5.0% in patients who discontinued ASA+ER-DP due to headache by day 90 versus 9.2% in those who did not (HR 0.52, 95% CI 0.35-0.77; P = 0.001). No such difference was observed in clopidogrel-treated patients. In ESPS2, risk of recurrent stroke was 6.2% in patients who discontinued ASA+ER-DP due to headache by day 90 versus 9.8% in patients who did not (HR 0.62, 95% CI 0.31-1.27; P = 0.19) and 7.3% in patients who discontinued ER-DP due to headache by day 90 versus 13.2% in those who did not (HR 0.53, 95% CI 0.27-1.04; P = 0.06). CONCLUSIONS: Patients taking ASA+ER-DP in PRoFESS who developed headache had significantly reduced stroke recurrence risk versus those without headache. Similar (non-significant) findings for ASA+ER-DP and ER-DP in ESPS2 suggest that dipyridamole-induced headache may reflect better cerebrovascular function.

OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program.

OBJECTIVE: Chronic migraine (CM) is a prevalent and disabling neurological disorder. Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program assessed efficacy and safety of onabotulinumtoxinA (BOTOX(®)) for prophylaxis of headaches in adults with CM. This secondary analysis assessed patients who received all five treatment cycles and completed the study. MATERIALS AND METHODS: PREEMPT (two phase III studies: 24-week double-blind, placebo-controlled [DBPC], parallel-group phase, followed by 32-week open-label [OL] phase) evaluated the efficacy and safety of onabotulinumtoxinA in CM (≥15 days/month with headache lasting ≥4 h a day). Patients were randomized (1:1) to onabotulinumtoxinA or placebo every 12 weeks for two cycles, followed by onabotulinumtoxinA for three cycles. Multiple headache symptom measures were evaluated. Results for the completer (five cycles) subgroup of patients are reported. RESULTS: Of 1384 total PREEMPT patients, 1005 received all five treatment cycles (513 received onabotulinumtoxinA only [onabotulinumtoxinA/onabotulinumtoxinA (O/O)] and 492 received two cycles of placebo then three cycles of onabotulinumtoxinA [placebo/onabotulinumtoxinA (P/O)]). Demographics were similar between treatment groups. At Week 56, after all patients were treated with onabotulinumtoxinA, there continued to be significant between-group differences favoring the O/O vs P/O group for the following headache symptom measures: LS mean change from baseline in frequencies of headache days (-12.0 O/O, -11.1 P/O; P = 0.035), migraine days (-11.6 O/O, -10.7 P/O; P = 0.038), and moderate/severe headache days (-11.0 O/O, -10.1 P/O; P = 0.042). For other measures (cumulative hours of headache on headache days, frequency of headache episodes, and percentage with severe Headache Impact Test (HIT)-6 score, and total HIT-6 and Migraine-Specific Quality of Life Questionnaire scores), there were also large mean improvements from baseline. The percent of patients with a ≥50% reduction from baseline in frequency of headache days was significantly greater for the onabotulinumtoxinA-only group at Week 56 (69.6% O/O, 62.8% P/O; P = 0.023). The treatment-related adverse event rate was 28.5% for onabotulinumtoxinA vs 12.4% for placebo in the DBPC phase and 34.8% for patients treated with onabotulinumtoxinA for all five cycles throughout the 56-week trials. CONCLUSIONS: This subgroup analysis demonstrated improvements with onabotulinumtoxinA treatment (five cycles) vs placebo (two cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA had better outcomes. These findings demonstrate the continued need and cumulative benefit over time with continued prophylaxis, an important and clinically pragmatic observation for clinicians and patients.

Associations of Stages of Objective Memory Impairment with Cerebrospinal Fluid and Neuroimaging Biomarkers of Alzheimer's Disease.

OBJECTIVE: To investigate cerebrospinal fluid (CSF) and neuroimaging correlates of Stages of Objective Memory Impairment (SOMI) based on Free and Cued Selective Reminding Test (FCSRT) performance, and to evaluate the effect of APOE ε4 status on this relationship. METHODS: Data from 586 cognitively unimpaired individuals who had FCSRT, CSF, and volumetric magnetic resonance imaging (MRI) measures available was used. We compared CSF measures of ß-amyloid (Aß42/Aß40 ratio), phosphorylated tau (p-Tau181), total tau (t-Tau), hippocampal volume, and PIB-PET mean cortical binding potential with partial volume correction (MCBP) among SOMI groups in the whole sample and in subsamples stratified by APOE ε4 status. RESULTS: Participants had a mean age of 67.4 (SD=9.1) years, had 16.1 (SD=2.6) years of education, 57.0% were female, and 33.8% were APOE ε4 positive. In the entire sample, there was no significant difference between SOMI stages in Aß42/Aß40 ratio, p-Tau181, t-Tau, or PIB-PET MCBP when adjusted for age, sex, and education. However, higher SOMI stages had smaller hippocampal volume (F=3.29, p=0.020). In the stratified sample based on APOE ε4 status, in APOE ε4 positive individuals, higher SOMI stages had higher p-Tau181 (F=2.94, p=0.034) higher t-Tau (F=3.41, p=0.019), and smaller hippocampal volume (F=5.78, p<0.001). There were no significant differences in CSF or imaging biomarkers between SOMI groups in the APOE ε4 negative subsample. CONCLUSION: Cognitively normal older individuals with higher SOMI stages have higher in-vivo tau and neurodegenerative pathology only in APOE ε4 carriers. These original results indicate the potential usefulness of the SOMI staging system in assessing of tau and neurodegenerative pathology.

Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS).

Migraine is a disabling neurological disease that affects 14.7 % of Europeans. Studies evaluating the economic impact of migraine are complex to conduct adequately and with time become outdated as healthcare systems evolve. This study sought to quantify and compare direct medical costs of chronic migraine (CM) and episodic migraine (EM) in five European countries. Cross-sectional data collected via a web-based survey were screened for migraine and classified as CM (≥15 headache days/month) or EM (<15 headache days/month), and included sociodemographics, resource use data and medication use. Unit cost data, gathered using publicly available sources, were analyzed for each type of service, stratified by migraine status. Univariate and multivariate log-normal regression models were used to examine the relationship between various factors and their impact on total healthcare costs. This economic analysis included data from respondents with migraine in the UK, France, Germany, Italy, and Spain. CM participants had higher level of disability and more prevalent psychiatric disorders compared to EM. CM participants had more provider visits, emergency department/hospital visits, and diagnostic tests; the medical costs were three times higher for CM than EM. Per patient annual costs were highest in the UK and Spain and lower in France and Germany. CM was associated with higher medical resource use and total costs compared to EM in all study countries, suggesting that treatments that reduce headache frequency could decrease the clinical and economic burden of migraine in Europe. Comparing patterns of care and outcomes among countries may facilitate the development of more cost-effective care, and bring greater recognition to patients affected by migraine.

Chronic migraine: classification and comparisons.

OBJECTIVE: The objective of our study was to field test different chronic migraine (CM) criteria and compare CM epidemiological profiles, which include demographic, personal, and lifestyle characteristics, with high-frequency episodic migraine (HFEM) and low-frequency episodic migraine (LFEM). METHODS: Questionnaires were mailed to a random sample of 18,000 18-65-year-olds in demographically diverse regions of Germany. The epidemiological data for the three classifications of CM, LFEM and HFEM were assessed using descriptive statistics, Pearson Chi-square, and analysis of variance tests. RESULTS: Among 9350 respondents, CM_I was the most restrictive (N = 37, 0.4%), followed by CM_II (N = 45, 0.5%) and CM_III (N = 185, 2.0%). CM groups did not differ in distribution by age, gender, body mass index, education or smoking and alcohol consumption. Compared to those with LFEM and HFEM, those with CM (CM_III) had significantly different epidemiological profiles. CONCLUSIONS: CM prevalence varies by case definition. The epidemiological profiles of the three CM groups are similar but differ significantly from those of HFEM and LFEM. Optimal definitions for clinical practice and epidemiological research require additional field testing.

Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the International Burden of Migraine Study (IBMS).

BACKGROUND: Migraine imposes significant burden on patients, their families and health care systems. In this study, we compared episodic to chronic migraine sufferers to determine if migraine status predicted headache-related disability, health-related quality of life (HRQoL) and health care resource utilization. METHODS: A Web-based survey was administered to panelists from nine countries. Participants were classified as having chronic migraine (CM), episodic migraine (EM) or neither using a validated questionnaire. Data collected and then analyzed included sociodemographics, clinical characteristics, Migraine Disability Assessment, Migraine-Specific Quality of Life v2.1, Patient Health Questionnaire and health care resource utilization. FINDINGS: Of the respondents, 5.7% had CM and 94.3% had EM, with CM patients reporting significantly more severe disability, lower HRQoL, higher levels of anxiety and depression and greater health care resource utilization compared to those with EM. INTERPRETATION: These results provide evidence that will enhance our understanding of the factors driving health care costs and will contribute to development of cost-effective health care strategies.

Sociodemographic and comorbidity profiles of chronic migraine and episodic migraine sufferers.

OBJECTIVE: To characterise and compare the sociodemographic profiles and the frequency of common comorbidities for adults with chronic migraine (CM) and episodic migraine (EM) in a large population-based sample. METHODS: The American Migraine Prevalence and Prevention (AMPP) study is a longitudinal, population-based, survey. Data from the 2005 survey were analysed to assess differences in sociodemographic profiles and rates of common comorbidities between two groups of respondents: CM (ICHD-2 defined migraine; > or =15 days of headache per month) and EM (ICHD-2 defined migraine; 0-14 days of headache per month). Categories of comorbid conditions included psychiatric, respiratory, cardiovascular, pain and 'other' such as obesity and diabetes. RESULTS: Of 24 000 headache sufferers surveyed in 2005, 655 respondents had CM, and 11 249 respondents had EM. Compared with EM, respondents with CM had stastically significant lower levels of household income, were less likely to be employed full time and were more likely to be occupationally disabled. Those with CM were approximately twice as likely to have depression, anxiety and chronic pain. Respiratory disorders including asthma, bronchitis and chronic obstructive pulmonary disease, and cardiac risk factors including hypertension, diabetes, high cholesterol and obesity, were also significantly more likely to be reported by those with CM. DISCUSSION: Sociodemographic and comorbidity profiles of the CM population differ from the EM population on multiple dimensions, suggesting that CM and EM differ in important ways other than headache frequency.

Migraine prevalence by age and sex in the United States: a life-span study.

The present study assessed age- and sex-specific patterns of migraine prevalence in a US population of 40,892 men, women, and children who participated in the 2003 National Health Interview Survey. Gaussian mixture models characterised the relationship between migraine, age, and sex. Migraine prevalence was 8.6% (males), 17.5% (females), and 13.2% (overall) and showed a bimodal distribution in both sexes (peaking in the late teens and 20s and around 50 years of age). Rate of change in migraine prevalence for both sexes increased the fastest from age 3 years to the mid-20s. Beyond the age of 10 years, females had a higher prevalence of migraine than males. The prevalence ratio for females versus males was highest during the female reproductive/child-bearing years, consistent with a relationship between menstruation and migraine. After age 42 years, the prevalence ratio was approximately 2-fold higher in women.

Patterns of medication use by chronic and episodic headache sufferers in the general population: results from the frequent headache epidemiology study.

Though symptomatic medication overuse is believed to play a role in progression from episodic headaches (EH) to chronic daily headaches (CDH), population-based data on this topic are limited. Our objective was to describe patterns of medication use among CDH and EH sufferers in a general population sample. We compared medications used to treat headache in CDH cases and EH controls identified from a large population-based computer-assisted telephone interview survey. CDH began within 5 years of the computer-assisted telephone interview. Questions on medication use focused on treatment prior to the onset of CDH for cases and on an equivalent period in the past for controls. We asked about the likelihood of treating, time waiting to treat, number of different medications used, first, second and third most frequently used headache pain medication, and total treatment days. Questions were also asked about the use of medication for non-headache pain. Current treatment patterns and past treatment patterns were assessed. Likelihood of use of specific medications was compared between CDH cases and EH controls after adjusting for age, sex, primary headache type and number of medications taken to treat pain. Our sample consists of 206 CDH cases and 507 EH controls. CDH subjects were more likely than EH controls to use over-the-counter/caffeine combination products, triptans, opioid compounds and 'other' prescription pain medications. Use of aspirin was protective. After adjustment, aspirin and ibuprofen were (negatively) associated with CDH [OR = 0.5 (0.3-0.9), OR = 0.7 (0.5-1.0)] and opioids remained positively associated with CDH [OR = 2.3 (1.3-3.9)]. For past use, CDH was positively associated with over-the-counter/caffeine combination products and opioid compounds and was negatively associated with use of aspirin. Only ibuprofen remained (negatively) associated with CDH after adjustment [OR = 0.6 (0.4-0.9)]. After adjusting for demographic factors, primary headache type and number of medications taken, CDH sufferers are more likely to use opioid-combination analgesics, and less likely to use aspirin or ibuprofen, than EH sufferers.

The use of migraine preventive medications among patients with and without migraine headaches.

The aim was to describe the use of and adherence to migraine preventives among insured patients meeting the International Classification of Headache Disorders, 2nd edn (ICHD-II) criteria for migraine headaches. A retrospective, case-control study was conducted using data from a telephone interview linked with health insurance claims data. Subjects were health plan enrollees aged 18-55 years who had incurred at least one encounter between June 2000 and November 2001. Interview responses were used to identify cases meeting the ICHD-II criteria for strict and probable migraine and a random sample of controls. Pharmacy claims data were used to construct measures of use and adherence. Differences in outcomes by adherence status were evaluated using generalized linear models. We identified 2517 cases and 941 controls. Among cases, the prevalence of antidepressant use was 4%, anticonvulsant use was 1.9%, antihypertensive use was 8.9%. Combined use was 13.4% among cases and did not differ significantly from that observed among controls (12.4%). Mean adherence rate between the first and last dispensing during the year was high (88%) and did not differ by migraine status. When the entire 12-month period is considered, adherence was substantially lower (56%). Patients who were adherent between dispensings reported significantly less migraine-related disability and incurred higher prescription drug costs, but did not differ in their total medical care costs. Patients with migraine are unlikely to be users of preventive medications. Among users, few are taking preventive medications continuously. Patients with migraine-especially those without a medical diagnosis for migraine or headaches-are not receiving the benefits available from existing pharmacotherapy options.

Association between migraine, anxiety and depression.

Logistic regression was used to evaluate the relationship between self-reported medical diagnosis of migraine, self-reported depressive symptomology (RDS) and self-reported anxious symptomology (RAS) in the National Health Interview Survey (n = 30 852). Semipartial squared correlations evaluated the population-level variability between RDS, RAS and migraine impairment. Migraine prevalence was 15.2% (overall), 20.5% (women) and 9.4% (men). Migraine risk was higher in participants with RAS [odds ratio (OR) 2.30, 95% confidence interval (CI) 2.09, 2.52), with RDS (OR 2.23, 95% CI 1.93, 2.58), who smoked (OR 1.19, 95% CI 1.09, 1.30), or who consulted a mental health provider (OR 1.45, 95% CI 1.27, 1.65). Although migraine risk was increased in both women (OR 1.93) and men (OR 2.42) with RAS (P < 0.001), men with RAS had a higher migraine risk than did women with RAS (P < 0.001). Only 7% of the variability in migraine impairment (population level) was predicted by variability in RDS and/or RAS.

Temporomandibular disorders and cutaneous allodynia are associated in individuals with migraine.

The objective of this study was to estimate and contrast the occurrence of ictal and interictal cutaneous allodynia (CA) in individuals with migraine with and without temporomandibular disorders (TMD). Both TMD and CA are common in migraine and may be associated with migraine transformation from episodic into a chronic form. Herein we hypothesize that TMD contributes to the development of CA and to more severe headaches. In a clinic-based sample of individuals with episodic migraine, the presence of TMD was assessed using the research diagnostic criteria for myofascial or mixed (myofascial and arthralgic) TMD. Ictal CA was quantified using the validated Allodynia Symptom Checklist (ASC-12). The ASC-12 measures CA over the preceding month by asking 12 questions about the frequency of allodynia symptoms during headaches. Interictal CA was assessed in the domains of heat, cold and mechanical static allodynia using quantitative sensory testing. Our sample consists of 55 individuals; 40 (73%) had TMD (23 with myofascial TMD and 17 with the mixed type). CA of any severity (as assessed by ASC-12) occurred in 40% of those without TMD (reference group), 86.9% of those with myofascial TMD (P = 0.041, RR = 3.2, 95% CI = 1.5-7.0) and in 82.3% of those with mixed TMD (P = 0.02, RR = 2.5, 95% CI = 1.2-5.3). Individuals with TMD were more likely to have moderate or severe CA associated with their headaches. Interictally (quantitative sensory testing), thresholds for heat and mechanical nociception were significantly lower in individuals with TMD. Cold nociceptive thresholds were not significantly different in migraine patients with and without TMD. TMDs were also associated with change in extra-cephalic pain thresholds. In logistical regression, TMD remained associated with CA after adjusting for aura, gender and age. TMD and CA are associated in individuals with migraine.

Global prevalence of chronic migraine: a systematic review.

The aim of this review was to summarize population-based studies reporting prevalence and/or incidence of chronic migraine (CM) and to explore variation across studies. A systematic literature search was conducted. Relevant data were abstracted and estimates were subdivided based on the criteria used in each study. Sixteen publications representing 12 studies were accepted. None presented data on CM incidence. The prevalence of CM was 0-5.1%, with estimates typically in the range of 1.4-2.2%. Seven studies used Silberstein-Lipton criteria (or equivalent), with prevalence ranging from 0.9% to 5.1%. Three estimates used migraine that occurred ≥15 days per month, with prevalence ranging from 0 to 0.7%. Prevalence varied by World Health Organization region and gender. This review identified population-based studies of CM prevalence, although heterogeneity across studies and lack of data from certain regions leaves an incomplete picture. Future studies on CM would benefit from an International Classification of Headache Disorders consensus diagnosis that is clinically appropriate and operational in epidemiological studies.

OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial.

OBJECTIVES: This is the second of a pair of studies designed to evaluate the efficacy and safety of onabotulinumtoxinA (BOTOX) for prophylaxis of headaches in adults with chronic migraine. METHODS: PREEMPT 2 was a phase 3 study, with a 24-week, double-blind, placebo-controlled phase, followed by a 32-week, open-label phase. Subjects were randomized (1:1) to injections of onabotulinumtoxinA (155U-195U; n = 347) or placebo (n = 358) every 12 weeks for two cycles. The primary efficacy endpoint was mean change in headache days per 28 days from baseline to weeks 21-24 post-treatment. RESULTS: OnabotulinumtoxinA was statistically significantly superior to placebo for the primary endpoint, frequency of headache days per 28 days relative to baseline (-9.0 onabotulinumtoxinA/-6.7 placebo, p < .001). OnabotulinumtoxinA was significantly favoured in all secondary endpoint comparisons. OnabotulinumtoxinA was safe and well tolerated, with few treatment-related adverse events. Few patients (3.5% onabotulinumtoxinA/1.4% placebo) discontinued due to adverse events. CONCLUSIONS: The results of PREEMPT 2 demonstrate that onabotulinumtoxinA is effective for prophylaxis of headache in adults with chronic migraine. Repeated onabotulinumtoxinA treatments were safe and well tolerated.

OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial.

OBJECTIVES: This is the first of a pair of studies designed to assess efficacy, safety and tolerability of onabotulinumtoxinA (BOTOX) as headache prophylaxis in adults with chronic migraine. METHODS: The Phase III REsearch Evaluating Migraine Prophylaxis Therapy 1 (PREEMPT 1) is a phase 3 study, with a 24-week, double-blind, parallel-group, placebo-controlled phase followed by a 32-week, open-label phase. Subjects were randomized (1:1) to injections every 12 weeks of onabotulinumtoxinA (155 U-195 U; n = 341) or placebo (n = 338) (two cycles). The primary endpoint was mean change from baseline in headache episode frequency at week 24. RESULTS: No significant between-group difference for onabotulinumtoxinA versus placebo was observed for the primary endpoint, headache episodes (-5.2 vs. -5.3; p = 0.344). Large within-group decreases from baseline were observed for all efficacy variables. Significant between-group differences for onabotulinumtoxinA were observed for the secondary endpoints, headache days (p = .006) and migraine days (p = 0.002). OnabotulinumtoxinA was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. CONCLUSIONS: There was no between-group difference for the primary endpoint, headache episodes. However, significant reductions from baseline were observed for onabotulinumtoxinA for headache and migraine days, cumulative hours of headache on headache days and frequency of moderate/severe headache days, which in turn reduced the burden of illness in adults with disabling chronic migraine.

Migraine is comorbid with multiple sclerosis and associated with a more symptomatic MS course.

The objectives of this study were: (1) to assess relative frequency of migraine in multiple sclerosis (MS) patients using the validated self-administered diagnostic questionnaire, and to compare the migraine rates in MS outpatients to age- and gender-matched historical population controls; (2) to compare clinical and radiographic characteristics in MS patients with migraine and headache-free MS patients. We conducted a cross-sectional study to assess the demographic profiles, headache features and clinical characteristics of MS patients attending a MS clinic using a questionnaire based on the American Migraine Prevalence and Prevention (AMPP) study. We compared the relative frequency of migraine in MS clinic patients and AMPP cohort. We also compared clinical and radiographic features in MS patients with migraine to an MS control group without headache. Among 204 MS patients, the relative frequency of migraine was threefold higher than in population controls both for women [55.7 vs. 17.1%; prevalence ratio (PR) =3.26, p<0.001] and men (18.4 vs. 5.6%; PR=3.29, p<0.001). In a series of logistic regression models that controlled for age, gender, disease duration, ß-interferon use, and depression, migraine in MS patients was significantly associated (p<0.01) with trigeminal and occipital neuralgia, facial pain, Lhermitte's sign, temporomandibular joint pain, non-headache pain and a past history of depression. Migraine status was not significantly associated with disability on patient-derived disability steps scale or T2 lesion burden on brain MRI. Migraine is three-times more common in MS clinic patients than in general population. MS-migraine group was more symptomatic than the MS-no headache group.