Migraine Disorders: Dodick DW

Silberstein S, Tfelt-Hansen P, Dodick DW, Limmroth V, Lipton RB, Pascual J, Wang SJ, Anonymous00408. · Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. [corrected] · Cephalalgia. · Pubmed #18294250 No free full text.

Abstract: In 1991 the Clinical Trials Subcommittee of the International Headache Society (IHS) developed and published its first edition of the Guidelines on controlled trials of drugs in episodic migraine because only quality trials can form the basis for international collaboration on drug therapy, and these Guidelines would 'improve the quality of controlled clinical trials in migraine'. With the current trend for large multinational trials, there is a need for increased awareness of methodological issues in clinical trials of drugs and other treatments for chronic migraine. These Guidelines are intended to assist in the design of well-controlled clinical trials of chronic migraine in adults, and do not apply to studies in children or adolescents.

Dodick DW. · No affiliation provided · Cephalalgia. · Pubmed #17970983 No free full text.

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Dodick DW, Silberstein S, Dahlöf CG. · No affiliation provided · Headache. · Pubmed #12005269 No free full text.

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Schwedt TJ, Dodick DW. · Department of Neurology and Anesthesiology, Washington University Headache Center, Washington University School of Medicine, St Louis, MO, USA. · Lancet Neurol. · Pubmed #19446275 No free full text.

Abstract: Advanced neuroimaging has helped to increase our knowledge about migraine pathophysiology. Our perception of migraine has transformed from a vascular, to a neurovascular, and most recently, to a CNS disorder. Functional imaging has confirmed the importance of cortical spreading depression (CSD) as the pathophysiological mechanism of migraine aura in human beings, whereas novel animal studies are unravelling the mechanistic underpinnings of CSD. Altered cerebral blood flow and neurotransmitter systems have been identified during and between headaches in migraine with and without aura. Advanced neuroimaging has identified mechanisms involved in the transformation of migraine from an episodic disorder to one with near continuous symptomatology. Questions regarding the secondary effects of migraine on brain structure and function, possibly related to attack frequency and duration of illness, have been raised. New imaging techniques could lead to novel diagnostic and therapeutic interventions that will help to improve the lives of millions of patients with migraine. In this Review, we summarise the most important findings from current imaging studies of migraine.

Vargas BB, Dodick DW. · Center for Neurosciences, 2450 East River Road, Tucson, AZ 85718, USA. · Neurol Clin. · Pubmed #19289226 No free full text.

Abstract: Chronic daily headache (CDH) represents a therapeutic challenge for many clinicians. Treatment strategies should be aimed at correctly identifying the presence of CDH. In addition, an effective prophylactic regimen should be initiated; the presence of medication overuse must be addressed, and the offending medication being overused must be discontinued. Aside from analgesic overuse, other modifiable risk factors associated with the development of chronic migraine and CDH must be addressed including obesity and caffeine use and the effective management of comorbid conditions such as depression, anxiety, and sleep-related breathing disorders.

Dodick DW, Schwedt T. · Department of Neurology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA. · Lancet Neurol. · Pubmed #19081504 No free full text.

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Diener HC, Schorn CF, Bingel U, Dodick DW. · Department of Neurology, University Duisburg-Essen, Essen, Germany. · Cephalalgia. · Pubmed #18727647 No free full text.

Abstract: The best way to appreciate the efficacy of drug and behavioural therapy in the acute and prophylactic treatment of headache is to perform placebo-controlled randomized trials. In order to plan and conduct these studies in the most appropriate way, it is desirable to know which factors influence the placebo response. This paper reviews factors which influence the placebo response in clinical trials, such as expectation, blinding, route of application of drugs and age, gender and geographical distribution. Response rates of placebo in the treatment of acute headache episodes are higher than in headache prophylaxis. Invasive procedures such as injections have a higher placebo response compared with oral drugs. Variables known to influence the placebo response have to be taken into consideration to calculate properly the power of planned randomized trials.

Dodick DW. · Mayo Clinic, Scottsdale, AZ, USA. · Cephalalgia. · Pubmed #18715332 No free full text.

Abstract: The Act when Mild (AwM) Study has illustrated the benefits to migraineurs of taking triptan medication when their migraine pain is still mild and within 1 h of the onset of symptoms. Yet many patients wait until the attack has fully developed before taking their medication, with potentially inferior outcomes. In order to reproduce the benefits of early intervention using the AwM paradigm in daily practice, a number of key barriers need to be addressed at both the physician and patient level. Notable physician-related barriers to be overcome, particularly at the primary care level, include accuracy of an early diagnosis of migraine in newly presenting patients, communication skills that generate a therapeutic engagement with migraine patients and enhance patient confidence, the application of knowledge about up-to-date strategies to optimize treatment outcomes, and the setting of achievable goals to avoid unrealistic expectations. Patient-related obstacles that need to be identified and overcome encompass patient attitude, expectations, and behaviour. Migraine patients may be reluctant to consult their physician, and, of those who do, many stop consulting because they perceive that physicians can do little to improve their situation. For this reason, migraine patients need to be counselled about the most appropriate medication for their level of symptoms. Moreover, patients need to be confident before they will adhere routinely to the advice they receive, and high in the priority of advice is the use of medication, particularly triptans, at the first sign of a migraine attack, rather than waiting until their attack has progressed to moderate or severe intensity. Patients who adhere to this advice are likely to experience a notable reduction in the pain, disability and time lost that they would otherwise suffer. The beneficial effects of early triptan intervention illustrated in the AwM Study can therefore be best reproduced in the clinic if the correct advice given to patients is not only accepted and applied by them, but also followed up by their physician.

Vargas BB, Dodick DW, Wingerchuk DM, Demaerschalk BM. · Department of Neurology, Mayo Clinic Hospital, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA. · Curr Atheroscler Rep. · Pubmed #18706284 No free full text.

Abstract: Migraine, cardiovascular disease, and stroke are three highly prevalent and disabling conditions that exert a significant socioeconomic impact. The association between migraine and a twofold risk of stroke and myocardial infarction has been the topic of much debate. The mechanism underlying this link is largely unknown but may be the result of an increased prevalence of other conditions such as vasculopathies, hypercoagulable states, and patent foramen ovale seen in migraine with aura. Although many prior studies have demonstrated increased risks in women with migraine with aura, an emerging body of evidence is showing similar risks in men. These risks are further compounded with increased migraine frequency, smoking, and the use of oral contraceptive pills. Because the overall risk for stroke and myocardial infarction in migraineurs remains relatively low, recommendations at this time are limited to the modification of cardiovascular risk factors, such as smoking cessation and the avoidance of oral contraceptive pills, especially in women suffering from migraine with aura.

Dodick DW. · Department of Neurology, Mayo Clinic Arizona, Phoenix, AZ, USA. · Headache. · Pubmed #18549360 No free full text.

Abstract: This review considers current debate surrounding refractory migraine and poses the question, why do some patients fail to improve with currently available therapies?

Dodick DW. · Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA. · Headache. · Pubmed #18377395 No free full text.

Abstract: A debate is presented that examines whether it is the blood vessel or the brain that determines the essence of migraine.

Schwedt TJ, Demaerschalk BM, Dodick DW. · Washington University School of Medicine, Washington University Headache Center, St Louis, MO, USA. · Cephalalgia. · Pubmed #18355348 No free full text.

Abstract: Initial studies indicate an increased prevalence of patent foramen ovale (PFO) in migraineurs with aura, and an increased prevalence of migraine and migraine with aura in persons with PFO. Retrospective analyses of PFO closure suggest clinically significant improvements in migraine patterns. The aim of this study was to examine the prevalence of migraine in patients with PFO, the prevalence of PFO in migraineurs, and the effect of PFO closure on migraine. We conducted a quantitative systematic review of articles on migraine and PFO that met inclusion criteria, then reviewed, appraised, and subjected them to data extraction. Of 134 articles identified, 18 met a priori selection criteria. The estimated strength of association between PFO and migraine, reflected by summary odds ratios (ORs), was 5.13 [95% confidence interval (CI) 4.67, 5.59], and between PFO and migraine with aura the OR was 3.21 (95% CI 2.38, 4.17). The grade of evidence was low. The association between migraine and PFO was OR 2.54 (95% CI 2.01, 3.08). The grade of evidence was low to moderate. Six studies of PFO closure suggested improvement in migraine, but had a very low grade of evidence. The low-to-moderate grade of evidence from observational studies supports an apparent association between PFO and migraine. Although PFO closure seemed to affect migraine patterns favourably, the very low grade of available evidence to support this association precludes definitive conclusions.

Dodick DW, Silberstein SD. · Department of Neurology, Mayo Clinic Arizona, Scottsdale, Arizona 85259, USA. · Pract Neurol. · Pubmed #18024778 No free full text.

Abstract: Preventive medications reduce migraine frequency and severity, and improve migraine-specific quality of life. Recent evidence also suggests that these same medications enhance the patient's response to acute migraine therapies, and may also reduce the likelihood of developing chronic daily headache. However, many patients who should receive or be offered preventive treatment are not. Most patients can be successfully managed when patient and physician expectations are realistic and aligned, the selection of preventive medications is individualised, and the initiation and titration strategy is appropriate and carefully followed. Rational combinations of preventive medications may also be useful. This review provides an evidence and experience-based approach to the preventive treatment of migraine.

Goadsby PJ, Dodick DW, Almas M, Diener HC, Tfelt-Hansen P, Lipton RB, Parsons B. · Institute of Neurology, London, UK. · Cephalalgia. · Pubmed #17381558 No free full text.

Abstract: If treatment-emergent central nervous system (CNS) symptoms following triptan therapy represent direct pharmacological effects of the drug, they should occur independent of response to active drug. However, if they represent unmasking of neurological symptoms of the migraine attack after pain is relieved, they should be more common in responders both to active drug and to placebo. To explore this issue, we evaluated the relationship between the CNS adverse events and treatment response following triptan or placebo treatment. We used pooled data from seven double-blind, placebo-controlled trials involving eletriptan 20 mg (E20, n = 402), eletriptan 40 mg (E40, n = 1870), eletriptan 80 mg (E80, n = 1393), sumatriptan 100 mg (S100, n = 275) and placebo (Pbo, n = 1024). Somnolence was more prevalent among 2 h headache responders than non-responders for all treatments, including E80 (8.8% vs. 5.0%; P < 0.05), E40 (6.4% vs. 5.0%; NS), E20 (4.0% vs. 2.0%; NS), S100 (4.7% vs. 3.2%; NS) and Pbo (7.6% vs. 3.0%; P < 0.05). Similarly, the incidence of asthenia was higher among patients who responded to treatment compared with those who did not respond to E80 (15.2% vs. 7.8%; P < 0.05), E40 (6.5% vs. 3.6%; P < 0.05), E20 (6.5% vs. 1.0%; P < 0.05), S100 (10.1% vs. 4.7%; NS) and Pbo (4.4% vs. 2.7%; NS). The generally higher rates of somnolence and asthenia in patients who respond to treatment suggests that these treatment-emergent neurological symptoms may represent the unmasking of CNS symptoms associated with the natural resolution of a migraine attack, rather than simply representing drug-related side-effects. The rate of somnolence in placebo responders is comparable to that in responders to E40 and E80, indicating that somnolence is related, at least in some important part, to headache relief and not treatment.

Schwedt TJ, Dodick DW. · Department of Neurology, Mayo Clinic College of Medicine, 13400 E. Shea Blvd, Scottsdale, AZ 85259, USA. · Headache. · Pubmed #16643562 No free full text.

Abstract: There is increasing interest in the relationship between migraine and patent foramen ovale (PFO). PFO is more common in migraineurs with aura, and migraine with aura is more prevalent in patients with PFO. Retrospective analyses of PFO closure for stroke prevention and decompression illness in divers have suggested that migraineurs with and without aura may derive significant benefit from PFO closure, but to date no prospective, randomized, sham-controlled study to confirm this has been completed. Herein we review published data regarding the relationship between migraine and PFO and discuss the rationale, justification, and important factors to consider in the conduct of prospective, controlled, clinical trials designed to evaluate the efficacy and safety of percutaneous device closure of PFO for migraine prevention.

Boes CJ, Black DF, Dodick DW. · Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. · Semin Neurol. · Pubmed #16628534 No free full text.

Abstract: There is considerable overlap in the mechanisms mediating migraine headache pain and sustained opioid-induced paradoxical pain. Both involve upregulation of calcitonin gene-related peptide and increased excitability of dorsal horn neurons. Descending facilitation from the rostral ventromedial medulla may contribute to this increased excitability. Using special magnetic resonance imaging techniques, high iron levels were found in the periaqueductal gray of patients with chronic daily headache with medication overuse. The periaqueductal gray is the center of a powerful descending antinociceptive neuronal network and projects to the rostral ventromedial medulla and subsequently to the dorsal horn. The periaqueductal gray is also involved in the behavioral response to opiate withdrawal. Dysfunction in the periaqueductal gray may explain why frequent analgesic use can result in medication overuse headache in migraineurs. Management of transformed migraine with medication overuse involves patient education, biobehavioral therapy, withdrawal of overused acute medications, bridge therapy for withdrawal headache, initiation of preventive medication, and close follow-up.

Dahlöf CG, Pascual J, Dodick DW, Dowson AJ. · Institute of Clinical Neuroscience, Gothenburg Migraine Clinic, Gothenburg, Sweden. · Cephalalgia. · Pubmed #16556240 No free full text.

Abstract: A meta-analysis of pooled individual patient data from four randomized, placebo-controlled, double-blind trials comparing several doses of almotriptan (n = 1,908) with placebo (n = 386) was used to investigate the efficacy, speed of onset and tolerability of almotriptan in the acute treatment of migraine. As early as 30 min after dosing, almotriptan 12.5 mg was significantly more effective than placebo for pain relief (14.9% vs. 8.2%; P < 0.05) and pain free (2.5% vs. 0.7%; P < 0.05). At 2 h, pain-relief rates were 56.0%, 63.7% and 66.0% for almotriptan 6.25, 12.5 and 25 mg, respectively, compared with 35% for placebo; 2-h pain-free rates were 26.7%, 36.4% and 43.4% compared with 13.9% for placebo. All almotriptan dosages were significantly more effective than placebo in eliminating migraine-associated symptoms (P < 0.05) and in achieving sustained pain relief up to 24 h (P < 0.05). The incidence of adverse events after almotriptan 6.25 mg and 12.5 mg was not significantly different from that of placebo. This meta-analysis confirms the findings of individual clinical trials, while demonstrating for the first time, significant pain-free efficacy at 30 min compared with placebo.

Dodick DW. · Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, Ariz 85259, USA. · N Engl J Med. · Pubmed #16407511 No free full text.

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Cady RK, Dodick DW, Levine HL, Schreiber CP, Eross EJ, Setzen M, Blumenthal HJ, Lumry WR, Berman GD, Durham PL. · Headache Care Center, Primary Care Network, Inc, 3805 S Kansas Expressway, Springfield, MO 65807, USA. · Mayo Clin Proc. · Pubmed #16007896 links to  free full text

Abstract: Sinus headache is a widely accepted clinical diagnosis, although many medical specialists consider it an uncommon cause of recurrent headaches. The inappropriate diagnosis of sinus headache can lead to unnecessary diagnostic studies, surgical interventions, and medical treatments. Both the International Headache Society and the American Academy of Otolaryngology-Head and Neck Surgery have attempted to define conditions that lead to headaches of rhinogenic origin but have done so from different perspectives and in isolation of each other. An interdisciplinary ad hoc committee convened to discuss the role of sinus disease as a cause of headache and to review recent epidemiological studies that suggest sinus headache (headache of rhinogenic origin) and migraine are frequently confused with one another. This committee reviewed available scientific evidence from multiple disciplines and concluded that considerable research and clinical study are required to further understand and delineate the role of nasal pathology and autonomic activation in migraine and headaches of rhinogenic origin. However, this group agreed that greater diagnostic and therapeutic attention needs to be given to patients with sinus headaches.

Porter A, Gladstone JP, Dodick DW. · University of Toronto, Division of Neurology, 1333 Sheppard Avenue East, Suite 122, M2J 1V1, Toronto, Ontario, Canada. · Curr Pain Headache Rep. · Pubmed #16004847 No free full text.

Abstract: Patients with migraine are at increased risk for white matter hyperintensities detected on magnetic resonance imaging. The presence of nonspecific white matter hyperintensities may cause uncertainty for physicians and anxiety for patients. The pathophysiology and long-term consequences of these lesions are unknown. Occasionally, white matter lesions in a migraineur may indicate an underlying disease such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), or central nervous system vasculitis. The ability to distinguish between nonspecific and disease-specific patterns of white matter hyperintensities in migraine sufferers is important for the practicing clinician.

Dowson AJ, Dodick DW, Limmroth V. · King's Headache Service, King's College Hospital, London, UK. · CNS Drugs. · Pubmed #15962999 No free full text.

Abstract: Medication overuse headache (MOH) is a common medical condition that is associated with considerable long-term morbidity and disability. Patients experiencing MOH have primary headache disorders (migraine, tension-type headache [TTH] or the combination of migraine and TTH) that change to a pattern of daily or near-daily headaches over a period of years or decades following the overuse of symptomatic headache medications. Overused drugs include analgesics, ergot alkaloids, serotonin 5-HT(1B/1D) receptor agonists ('triptans') and medications containing barbiturates, codeine, caffeine, tranquillisers and mixed analgesics. Affected patients usually have a long history of primary headache, overuse of medications and MOH before they consult a physician for care. Patients with MOH are usually managed in specialist centres by withdrawal of the overused drugs and treatment of withdrawal symptoms (on an inpatient or outpatient basis), headache prophylaxis and limited use of symptomatic acute medications. Most patients respond to this therapy, although the prognosis is not always good and >or=50% may lapse over an initial 5-year follow-up period. The best practical strategy at present is to prevent the overuse of drugs in the first place by patient education and formal management approaches conducted in primary care to treat the primary headache before it changes to MOH. The quality of the clinical evidence on MOH is suboptimal and further biological and clinical research is urgently required to help facilitate the management of these patients more effectively in the future.

Sadovsky R, Dodick DW. · Department of Family Practice, SUNY Downstate Medical Center, Brooklyn, New York 11203, USA. · Am J Med. · Pubmed #15841883 No free full text.

Abstract: Migraine disorders are largely unrecognized and untreated, despite the heavy burden they impose on individuals and society. Studies have shown that the symptom severity and disability associated with undiagnosed migraine are as burdensome as those associated with diagnosed migraine. Of those persons with migraine identified in population-based surveys, many were previously unaware that they had migraine. Furthermore, coexisting headache types and comorbid conditions contribute to misdiagnosis among those who consult a physician for headache. Patients who do seek medical attention for headaches usually visit their primary care providers. The purpose of this review is to highlight the distinguishing characteristics of migraine compared with other headache disorders, based on the new International Classification of Headache Disorders. To aid in diagnosis, simple screening tools, such as ID Migraine (Pfizer Inc., New York, NY), are recommended. The clinical interview and headache diary aid in refining the diagnosis or suggesting the need for further evaluation. Improved recognition of migraine in primary care will increase the rate of successful treatment with effective migraine-specific therapies. This will result in improved functionality and decreased pain, and may help prevent disease progression.

Gladstone JP, Dodick DW. · Mayo Clinic College of Medicine, Department of Neurology, 13400 E. Shea Blvd., Scottsdale, AZ 85259, USA. · Neurologist. · Pubmed #15631641 No free full text.

Abstract: BACKGROUND: Patients with migraine are at an increased risk for white matter lesions, typically multiple, small, punctate hyperintensities in the deep or periventricular white matter, best observed on magnetic resonance imaging utilizing T2-weighted or FLAIR sequences. The underlying pathogenesis of white matter lesions in migraineurs is unknown, and the lesions are usually nonspecific and of unclear clinical significance. REVIEW SUMMARY: Often the presence of white matter lesions causes uncertainty for physicians and anxiety for patients and may lead to a variety of diagnostic tests and treatments. Occasionally, white matter lesions may represent a secondary cause for headaches such as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). CADASIL is underrecognized and underdiagnosed; it should be suggested by (i) 1 or more of recurrent subcortical ischemic strokes (especially before age 60 and in the absence of vascular risk factors), migraine (especially with aura, including atypical or prolonged auras) and/or early cognitive decline or subcortical dementia; (ii) bilateral, multifocal, T2/FLAIR hyperintensities in the deep white matter and periventricular white matter with lesions involving the anterior temporal pole, external capsule, basal ganglia, and/or pons; and (iii) an autosomal-dominant family history of migraine, early-onset stroke, or dementia. The clinical spectrum of CADASIL is broad, and there is a poor genotype-phenotype correlation. In certain individuals or families, migraine may be the only clinical manifestation. CONCLUSIONS: While the prevalence of nonspecific white matter lesions in migraineurs is increased, the white matter lesions may occasionally represent a secondary cause for headache such as CADASIL. Greater awareness of the unique clinical, neuroimaging, and pathologic features, as well as the availability of diagnostic genetic testing, should enhance the recognition and diagnosis of this fascinating condition.

Dodick DW, Lipton RB, Ferrari MD, Goadsby PJ, McCrory D, Cutrer FM, Williams P. · Department of Neurology, Mayo Clinic Scottsdale, AZ 85259, USA. · Curr Pain Headache Rep. · Pubmed #15509456 No free full text.

Abstract: Seven oral triptans, which differ on a range of attributes important for treatment selection, are now available for treating migraine. US neurologists were surveyed to assess the relative importance of treatment attributes, prespecified by clinical relevance and availability of controlled study data, for selecting among oral triptans. Using a multiattribute decision model, we combined these data on the importance of treatment attributes with information on the relative performance of the oral triptans derived from a recent meta-analysis of controlled clinical trials.

Gladstone JP, Dodick DW. · Department of Neurology, Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA. · Curr Pain Headache Rep. · Pubmed #15228894 No free full text.

Abstract: Painful ophthalmoplegia is an important presenting complaint to emergency departments, ophthalmologists, and neurologists. The etiological differential diagnosis of painful ophthalmoplegia is extensive and consists of numerous sinister etiologies including vascular (eg, aneurysm, carotid dissection, carotid-cavernous fistula), neoplasms (eg, primary intracranial tumors, local or distant metastases), inflammatory conditions (eg, orbital pseudotumor, sarcoidosis, Tolosa-Hunt syndrome), infectious etiologies (eg, fungal, mycobacterial), and other conditions (eg, microvascular infarcts secondary to diabetes, ophthalmoplegic migraine, giant cell arteritis). A systematic approach to the evaluation of painful ophthalmoplegia can lead to prompt recognition of serious disorders that if left untreated, can be associated with significant morbidity or mortality. Inflammatory conditions such as Tolosa-Hunt syndrome and orbital pseudotumor are highly responsive to corticosteroids, but should be diagnoses of exclusion.