Sylvia Lucas

Botulinum Toxin Type A for the Prophylactic Treatment of Chronic Daily Headache: A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVESnTo identify a treatment-responsive population for botulinum toxin type A (BoNTA) and to evaluate the safety and efficacy of 3 different doses of BoNTA as prophylactic treatment of chronic daily headache (CDH).nnnPATIENTS AND METHODSnA randomized, double-blind, placebo-controlled study of BoNTA in patients with CDH was conducted from July 6, 2001, through November 7, 2003, at 28 North American study centers. Eligible patients were injected with BoNTA at 225 U, 150 U, 75 U, or placebo and returned for additional masked treatments at day 90 and day 180. Patients were assessed every 30 days for 9 months. The primary efficacy end point was the mean change from baseline in the frequency of headache-free days at day 180 for the placebo nonresponder group.nnnRESULTSnFor this study, 702 patients were enrolled and randomized. The primary efficacy end point was not met. Mean improvements from baseline at day 180 of 6.0, 7.9, 7.9, and 8.0 headache-free days per month were observed in the placebo nonresponder group treated with BoNTA at 225 U, 150 U, 75 U, or placebo, respectively (P=.44). An a priori-defined analysis of headache frequency revealed that BoNTA at 225 U or 150 U had significantly greater least squares mean changes from baseline than placebo at day 240 (-8.4, -8.6, and -6.4, respectively; P=.03 analysis of covariance). Only 27 of 702 patients (3.8%) withdrew from the study because of adverse events, which generally were transient and mild to moderate.nnnCONCLUSIONSnAlthough the primary efficacy end point was not met, all groups responded to treatment. The 225 U and 150 U groups experienced a greater decrease in headache frequency than the placebo group at day 240. The placebo response was higher than expected. BoNTA was safe and well tolerated. Further study of BoNTA prophylactic treatment of CDH appears warranted.

Post-traumatic headaches in civilians and military personnel: a comparative, clinical review.

Post‐traumatic headache (PTH) is the most frequent symptom after traumatic brain injury (TBI). We review the epidemiology and characterization of PTH in military and civilian settings. PTH appears to be more likely to develop following mild TBI (concussion) compared with moderate or severe TBI. PTH often clinically resembles primary headache disorders, usually migraine. For migraine‐like PTH, individuals who had the most severe headache pain had the highest headache frequencies. Based on studies to date in both civilian and military settings, we recommend changes to the current definition of PTH. Anxiety disorders such as post‐traumatic stress disorder (PTSD) are frequently associated with TBI, especially in military populations and in combat settings. PTSD can complicate treatment of PTH as a comorbid condition of post‐concussion syndrome. PTH should not be treated as an isolated condition. Comorbid conditions such as PTSD and sleep disturbances also need to be treated. Double‐blind placebo‐controlled trials in PTH population are necessary to see whether similar phenotypes in the primary headache disorders and PTH will respond similarly to treatment. Until blinded treatment trials are completed, we suggest that, when possible, PTH be treated as one would treat the primary headache disorder(s) that the PTH most closely resembles.

Headache Management in Concussion and Mild Traumatic Brain Injury

Headache is one of the most common symptoms after traumatic brain injury (TBI), and posttraumatic headache (PTH) may be part of a constellation of symptoms that is seen in the postconcussive syndrome. PTH has no defining clinical features; currently it is classified as a secondary headache based on its close temporal relationship to the injury. A growing number of studies are characterizing PTH by using primary headache classifications. Moderate to severe PTH that is often disabling may be classified as migraine or probable migraine and is found in substantial numbers of individuals. Recent data from civilian adult, pediatric, and military populations all find that PTH may be more of a chronic problem than previously thought, with a prevalence of close to half of the injured population. In addition, if PTH definitions are strictly adhered to, then many cases of PTH may be missed, thus underestimating the scope of the problem. New headaches may be reported well after the 7 days required for diagnosis of PTH by the guidelines of the International Classification of Headache Disorders, 2nd edition. A history of headache before a head injury occurs and female gender are possible risk factors for headache after TBI. Treatment of PTH may be acute or preventive, and recommendations are made for the use of migraine‐specific acute therapy when indicated. Preventive therapy may be considered when PTH is frequent, disabling, or refractory to acute therapies. Comorbid conditions should be considered when choosing an appropriate preventive therapy. The symptom of headache as a “return to play” or “return to duty” barrier must be viewed in the context of other symptoms of mild TBI.

Use of Common Migraine Treatments in Breast-Feeding Women: A Summary of Recommendations

Breast‐feeding has important health and emotional benefits for both mother and infant, and should be encouraged. While there are some data to suggest migraine may improve during breast‐feeding, more than half of women experience migraine recurrence with 1 month of delivery. Thus, a thorough knowledge base of the safety and recommended use of common acute and preventive migraine drugs during breast‐feeding is vital to clinicians treating migraine sufferers. Choice of treatment should take into account the balance of benefit and risk of medication. For some of the medications commonly used during breast‐feeding, there is not good evidence about benefits.

Vascular Risk in Migraineurs: Interaction of Endothelial and Cortical Excitability Factors

Migraine is a common primary headache disorder occurring predominantly in a young, relatively healthy population.

The Pharmacology of Indomethacin

Over 50 years ago, indomethacin emerged as an extremely potent non‐steroidal anti‐inflammatory drug (NSAID) during a massive effort to find effective anti‐inflammatory and analgesic medications. The 1960s saw acetic acid derivatives developed into indomethacin, diclofenac, and sulindac, and propionic derivatives into ibuprofen, naproxen, and ketoprofen. Indomethacin was likely the most potent of these compounds and one of the earliest to enter clinical trials. It is not surprising that indomethacin was among the first of the NSAID medications to be used in treatment of migraine and for headaches that eventually became known as “indomethacin‐responsive” headache disorders. Potential pharmacokinetic and bio‐mechanistic differences between indomethacin and other NSAIDs are of great clinical and research interest to explain this observation.

Sport-Related Headache

Headache occurring in a sports setting may be primary or secondary headache. Headache is the primary symptom reported after concussion. Cumulative incidence and prevalence of posttraumatic headache (PTH) are higher following mild traumatic brain injury (TBI) compared with moderate to severe TBI. Frequency is higher in those with more severe PTH. Migraine or probable migraine is the most common headache type after any severity TBI using primary headache disorder criteria. Management is empiric. Expert opinion recommends treating PTH according to clinical characteristics of primary headache. The most important factor in this approach is the recognition of the severity of headache.

Aspirin resistance is common in premenopausal women with migraine

Jill T. Jesurum, PhD, Cindy J. Fuller, PhD, Natalia Murinova, MD, Elisa A. McGee, BS, Lisa E. Hales, BS, Ernesto Tolentino, MS, Sylvia M. Lucas, MD, PhD Swedish Heart & Vascular Institute, Swedish Medical Center; Department of Neurology and Center for Women’s Health & Gender Research, University of Washington, Seattle, WA Background Women with migraine, particularly those with aura (MA) and frequent headache, are at increased risk of stroke1; the risk remains high even after migraine symptoms have abated in later life2. Acetylsalicylic acid (aspirin, ASA) is the recommended first-line antiplatelet agent for prevention of cerebrovascular events; however, ASA’s efficacy for stroke prevention in migraine is unknown. “Aspirin resistance” refers to inadequate platelet inhibition to ASA treatment manifested as high on-ASA platelet reactivity in laboratory testing, and has been associated with inconsistent therapeutic effects and poor clinical outcomes in patients with cardiovascular disease3. A recent study 4 reported that 24% of migraineurs, all women, were resistant to ASA 325 mg; however, the study lacked placebo control and was not designed to test women. The objective of this exploratory study was to determine the prevalence of ASA resistance in women with migraine on daily ASA 81 mg, as recommended by the US Preventive Services Task Force5 for primary prevention of stroke. Methods Design: This study is listed on clinicaltrials.gov as Aspirin Resistance in Women with Migraine (NCT01257893). The Swedish Medical Center Institutional Review Board approved the study; all subjects granted written informed consent. Data were collected using a randomized, double-blind, placebo-controlled, crossover design. Target Population: Non-probability, convenience sampling was used to enroll women from the University of Washington. Enrollment criteria are listed below.

Posttraumatic Headache: Classification by Symptom-Based Clinical Profiles: Headache

There are currently no accepted therapies for posttraumatic headache (PTH). In order to meet the urgent need for effective therapies for PTH, we must continue to address fundamental gaps in our understanding of the clinical course and impact of PTH. Here we examine the existing schema used to characterize the clinical characteristics of PTH, including the International Classification of Headache Disorders (ICHD). There remain unresolved questions about whether to classify patients based on the extent of brain injury or on clinical symptom profiles. There also remain problematic issues of definition such as continuous headache, and chronic daily headache with features of “embedded” migraine‐type within these headaches, which will need to be studied further. We make the case that a symptom‐based classification is needed to begin an examination of these unresolved questions, and to establish clinically relevant endpoints for research and clinical trials for effective therapies.

Post-Traumatic Headache

Headache is one of the most common symptoms after traumatic brain injury (TBI). With an estimated 2.5 million TBIs per year in the US alone, increased attention has been directed to the diagnosis, management, and prevention of this problem, heightened by awareness of high-profile sports-related injuries and by the high prevalence of TBI in returning military personnel from war. Recent studies of post-traumatic headache (PTH) over 1 year after injury show a high cumulative incidence of 71% after moderate or severe TBI, and 91% after mild TBI (mTBI). Prevalence remains high at over 44% throughout the year after moderate or severe TBI, and over 54% after mTBI. A prior history of headache is associated with a higher risk for PTH, whereas older age appears to be protective. Most PTH has the phenotype of migraine or probable migraine, followed by tension-type headache. While there are no evidence-based treatment guidelines for PTH management, expert opinion has suggested treating the headache using primary headache diagnostic criteria and treatment recommendations.