Fred Michael Cutrer

Mayo Foundation for Medical Education and Research | MMS · Department of Neurology

Objective: "Pain interference" and "headache impact" refer to negative consequences that pain and headache have on one's life. This study investigated determinants of these negative impacts in a large patient cohort who have chronic migraine with medication overuse. Methods: Six hundred and eleven adults were enrolled from 34 headache, neurology...

Background Currently, there is no biologically based rationale for drug selection in migraine prophylactic treatment. Methods To investigate the genetic variation underlying treatment response to verapamil prophylaxis, we selected 225 patients from a longitudinally established, deeply phenotyped migraine database (N = 5983), and collected uninterr...

Transient disturbances in neurologic function are disturbing features of migraine attacks. Aura types include binocular visual, hemi-sensory, language and unilateral motor symptoms. Because of the gradual spreading quality of visual and sensory symptoms, they were thought to arise from the cerebral cortex. Motor symptoms previously included as a ty...

The development of postconcussion syndrome after traumatic brain injury can result in a wide range of potentially debilitating symptoms that includes headaches, cognitive dysfunction, and mood disorders. Unfortunately, data on helpful medications are quite limited, particularly on the treatment of persistent headaches attributed to trauma. This ret...

Background Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome predominantly in women without usual cardiovascular risk factors. Many have a history of migraine headaches, but this association is poorly understood. This study aimed to determine migraine prevalence among SCAD patients and assess differences in clinica...

Background: Migraine is a common and disabling disorder. Fibromyalgia has been shown to be commonly comorbid in patients with migraine and can intensify disability. The aim of this study was to determine if patients with co-morbid fibromyalgia and migraine report more depressive symptoms, have more headache related disability, or report higher int...

Background: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction (MI) occurring most often in young women without cardiovascular disease (CVD) risk factors. SCAD is associated with fibromuscular dysplasia (FMD), pregnant/postpartum state, and extreme mental stress or physical exertion. Migraine headac...

Migraine patients have varied descriptions of their headaches. In most cases, the pain is sufficient to disrupt normal activities, although the intensity ranges from merely annoying to disabling. The International Headache Society (IHCD) has codified the characteristics of the migraine headache into a set of diagnostic criteria for migraine without...

Premise: Migraine can present with a wide range of neurological symptoms. Problem: Based on currently available data, the symptoms of typical migraine aura are most likely related to cortical spreading depression (CSD), and evidence supports that CSD can lead to trigeminovascular activation resulting in the headache phase of migraine. Potential...

Objective To report a case series of a novel migraine subtype, which we term as episodic status migrainosus (ESM), characterized by attacks of migraine exclusively lasting more than 72 hours. We hypothesized that this would represent a novel nosologic entity, possibly an unstable migraine phenotype with a high conversion rate to chronic migraine (C...

The aim of this study was to identify structural and functional brain changes that accompanied the transition from chronic (CM; ≥15 headache days/month) to episodic (EM; <15 headache days/month) migraine following prophylactic treatment with onabotulinumtoxinA (BoNT-A). Specifically, we examined whether CM patients responsive to prophylaxis (respon...

Background Cutaneous allodynia (CA) is a common feature of migraine, which has a complex underlying pathophysiology that is not well understood. In addition to pain, photophobia, phonophobia, osmophobia, nausea, and vomiting, CA can contribute to the overall disability caused by migraine. The presence of CA can be established via a validated questi...

We have designed Mayo Clinic Neurology Board Review to assist both physicians-in-training who are preparing for the initial American Board of Psychiatry and Neurology certification examination and neurologists who are preparing for recertification. Trainees and other physicians in related specialties such as psychiatry, neurosurgery, or physiatry m...

This report reviews a series of 3 patients who developed superficial siderosis following posterior fossa operations in which dural closure was incomplete. In all 3 patients, revision surgery and complete duraplasty was performed to halt the progression of superficial siderosis. Following surgery, 2 patients experienced resolution of their CSF xanth...

Migraine aura consists of fully reversible focal neurologic symptoms that may precede or coexist with headache in a significant minority of migraine patients. Typical aura symptoms include visual, sensory, and language disturbances. The most recent International Classification of Headache Disorders, 3rd edition (beta version) has added other aura t...

Low intracranial pressure headaches can, at times, be refractory to treatment including multiple blood patches and preventative medications. Imaging studies are often unable to demonstrate a cerebrospinal fluid leak that is causing headache and other associated symptoms. Onabotulinum toxin A (BTX) injection is a treatment that has proven efficacy f...

Cough, exercise, and sex headaches are underrecognized distinct but related syndromes, triggered by rapid rises in intra-abdominal pressure. All may occur as a manifestation of a possible underlying, symptomatic etiology, and additional diagnostics should typically be pursued to rule out serious causes. Cough headaches may be more common in certain...

The frequency of not being able to self-report pain after a stroke has not been previously assessed in a population-based sample. We studied the epidemiology of this problem using a cohort of patients hospitalized after a stroke in Olmsted County, Minnesota, from June 1, 2008, to June 1, 2012. Overall, 52 of 388 (13.4%) individuals were unable to p...

Background Isolated neuralgic pain in the deep ear may arise from either nervus intermedius (NIN) or glossopharyngeal (GPN) neuralgias. Current International Headache Society (IHS) International Classification of Headache Disorders, second edition (ICHD-2) criteria for these cranial neuralgias require the presence of a characteristic trigger.AimThe...

Migraine is a complex trait in which multiple genetic loci, as well as environmental factors, likely contribute to its clinical manifestation. Many genetic associations reported in previous studies either have not been replicated to date or showed only marginal statistical significance, possibly due to the genetic heterogeneity of the common forms...

Background: While the association between migraine and depression has been well established, there is very little information as to whether effective prophylactic treatment of migraine correlates with improvement in comorbid depression. Methods: We analyzed initial visit data from migraine headache patients (n = 961) in the Mayo Headache Registr...

The expansion of technologies available for the study of migraine pathophysiology has evolved greatly over the last 15 years. Two areas of rapid progress are investigations focusing on the genetics of migraine and others utilizing novel functional neuroimaging techniques. Genetic studies are increasingly focusing on sporadic migraine and the utiliz...

The 15th Congress of the International Headache Society was held in Berlin from June 23rd to 26th of 2011. Interesting new data from several areas of the basic sciences of headache were presented. This is a review of some of the most exciting platform and poster presentations of the meeting. Research addressing 3 general areas of interest is presen...

To evaluate the efficacy of MAP0004, an orally inhaled dihydroergotamine, for acute treatment of migraine when administered at various time points from within 1 hour to more than 8 hours after migraine onset. This post hoc subanalysis was conducted using data from 902 patients enrolled in a randomized, double-blind, placebo-controlled, 2-arm, phase...

To investigate the relationship between clinical mast cell activity and primary headache syndromes. We surveyed individuals with systemic mastocytosis, an uncommon disorder associated with increased mast cell activity. Diagnoses of primary headache syndromes in addition to the relationship of headache and symptoms of mastocytosis were ascertained....

To identify complications of mastocytosis that impact the nervous system across a large cohort. In this retrospective series, we reviewed the electronic medical records of adult patients with a diagnosis of mastocytosis who were referred to a Neurologist at Mayo Clinic in Rochester, MN from January 1, 1999 to December 31, 2008. Thirty patients were...

Trigeminal neuropathies are a group of clinical disorders that involve injury to primary first-order neurons within the trigeminal nerve. We review the spectrum of etiologies underlying both painful and non-painful trigeminal neuropathies, with attention to particularly dangerous processes that may elude the clinician in the absence of a meticulous...

Migraine headache represents a diverse group of disorders that includes migraine with and without aura, childhood periodic syndromes, retinal migraine, complications of migraine, and probable migraine. The criteria as proposed by the International Headache Society (IHS) have standardized the diagnosis of migraine headache for use within clinical an...

This case-control study shows a strong association between migraine history and development of ovarian hyperstimulation syndrome (OHSS). We hypothesize there may be a similar gene variant that predisposes women to both migraines and OHSS and identification will lead to optimal therapy, not only for OHSS, but also for women who suffer from migraines...

Migraine is a common intermittently debilitating neurovascular disorder that affects younger adults, especially women. The diagnosis is generally made based on clinical criteria, with neuroimaging used in some cases to exclude secondary causes of headache. This article reviews current understanding of the mechanisms underlying migraine and approach...

Our understanding of migraine pathophysiology is a work in progress. As more is learned about migraine, it seems that the probability of identifying a single unifying explanation for this common disorder becomes less and less. Although the neuroanatomy and elements of pain physiology underlying migraine attacks are probably shared pathophysiologic...

Neurologic symptoms are a prominent and often disturbing component of the migraine syndrome in many patients. Collectively termed "aura," migraine-related neurologic symptoms include visual, sensory, language, and motor disturbance. They occur in about one quarter of migraine patients, are classically transient, and are thought to occur as the resu...

To compare patient recall of migraine headache frequency and severity over 4 weeks prior to a return visit as reported in an interval questionnaire vs a daily diary. Many therapeutic decisions in the management of migraine patients are based on patient recall of response to treatment. As consistent completion of a daily headache diary is problemati...

There is accumulating evidence of a neurogenic basis of migraine. This evidence arises from both the clinical and experimental domains. Many of the well known clinical features of migraine attacks including the prodrome are not explained by changes in vascular caliber. Despite the fact that ergotamines and triptans are vasoactive does not provide s...

Over the past two decades, the development of new functional neuroimaging techniques has improved our understanding of the brain events underlying several primary headache disorders. In migraine and cluster headache, the advent of these techniques has shifted the emphasis in pathophysiological research away from the vessel and back to the brain.

Recurrent episodes of transient focal neurologic symptoms, known as aura, occur in association with migraine headache in about 11.9 million people in the United States. At present, the International Headache Society has recognized 3 "typical" auras: visual, sensory, and language. Increasing evidence from investigations in human subjects suggests th...

Increasingly sophisticated neuroimaging techniques have allowed researchers to begin to define functional and anatomical characteristics of migraine. This paper reviews current knowledge and techniques employed. Assessing present-day knowledge limitations it concludes that with parallel advances in the technology of imaging and the pathophysiologic...

Exertional headaches may under certain conditions reflect coronary ischemia. We report the case of a patient seen in a neurology referral practice whose exertional headaches, even in the face of two normal electrocardiographic stress tests and in the absence of underlying chest pain were the sole symptoms of coronary ischemia as detected by Tc-99m...

The physician treating patients with migraine is now able to choose from among seven triptans-almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. These differ, to greater or lesser degrees, on a range of clinical attributes important for treatment selection. To outline the basic principles of Multiattribut...

In treating migraine sufferers, physicians can choose from among seven triptans with different attributes. To develop a system for selecting an oral triptan based on treatment priorities of migraine sufferers, neurologists, and primary care physicians (PCPs) in the United States, and evidence-based performance of triptans in clinical trials. The TR...

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 multi...

Physicians treating patients with migraine can now choose from among 7 triptans, which differ on a range of attributes that may be important for treatment selection. The aims of this study were to determine the relative importance of treatment attributes of the available triptans and assess their impact on deciding the most appropriate treatment fo...

Seven oral triptans are available for treating acute migraine. We surveyed US migraine sufferers on the relative importance of treatment attributes for choosing among oral triptans. A multiattribute decision model was used to combine data on the relative importance of efficacy, consistency, and tolerability of acute treatment (determined by 206 tri...

Neuronal Expression and Regulation of CGRP Promoter Activity Following Viral Gene Transfer into Cultured Trigeminal Ganglia Neurons We examined the regulation of calcitonin gene‐related peptide (CGRP) promoter activity in primary cultures of rat trigeminal ganglia neurons. A viral vector was used to circumvent the potential complication of examinin...

Possible Antimigraine Mechanisms of Action of the 5HT1F Receptor Agonist LY334370 This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10(−5) M) had no vasoconstrictor effects on human cerebral ar...

Cough, exertional, and sex headaches are three relatively rare and distinct but related syndromes, all of which are triggered in the context of rapid rises in intra-abdominal pressure. Cough headache occurs after single or brief series of such rises, whereas exertional and sexual headache typically arise after more prolonged provocations. All three...

Neurologic signs of increased parasympathetic outflow to the head often accompany migraine attacks. Because increased parasympathetic outflow to the cranial cavity induces vasodilation of cerebral and meningeal blood vessels, it can enhance plasma protein extravasation and the release of proinflammatory mediators that activate perivascular nocicept...

The pathophysiology of migraine is not fully understood. Recent studies have shed light on the neuronal events mediating the aura and headache phases of migraine. Cortical spreading depression appears to underlie the aura phase in patients with migraine with aura, and it may also precede headache in patients with migraine without aura. Recent evide...

To evaluate the effectiveness of rizatriptan for acute migraine treatment and patient satisfaction with the drug in usual clinical practice settings. Although rizatriptan has been shown to effectively relieve migraine symptoms in clinical trials, we wished to assess its utility in typical patient care settings. Design.-Multicenter, open-label desig...

The safety and tolerability of medications used to treat acute migraine attacks are summarized, the classification of headaches and the causes of and diagnostic criteria for migraine are reviewed, and the clinical tolerability profiles and therapeutic benefits of second-generation triptans are presented. Migraine is a paroxysmal disorder characteri...

Antiepileptic drugs (AEDs) are promising agents for the prevention of migraine and other head pain. Migraine and epilepsy share several clinical features and respond to many of the same pharmacologic agents, suggesting that similar mechanisms may be involved in their pathophysiology. The mechanisms of action of AEDs are not fully understood, and a...

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demo...

Recently, we showed that most migraine patients exhibit cutaneous allodynia inside and outside their pain-referred areas when examined during a fully developed migraine attack. In this report, we studied the way in which cutaneous allodynia develops by measuring the pain thresholds in the head and forearms bilaterally at several time points during...

Research into migraine pathophysiology has been hampered by the episodic nature and unpredictable onset of migraine attacks. Recently, newer imaging techniques have been providing noninvasive methods of studying metabolism and hemodynamics in the brains of migraineurs during and between acute attacks. 133Xe blood flow techniques, transcranial Doppl...

We examined the effects of butalbital (30, 100, and 1000 micrograms/kg) on the number of cells expressing c-fos-like immunoreactivity (c-fos-LI), a marker of neuronal activation, within lamina I, IIo of the trigeminal nucleus caudalis and the nucleus of the solitary tract 2 hours after the intracisternal injection of capsaicin (0.1 mL; 15.25 mg/mL)...

Using perfusion weighted imaging, we studied 28 spontaneous migraine episodes; 7 during visual aura (n = 6), 7 during the headache phase following visual aura (n = 3), and 14 cases of migraine without aura (n = 13). The data were analyzed using a region-of-interest-based approach. During aura, relative cerebral blood flow (rCBF) was significantly d...

We studied the effects of PNU-109291 [(S)-(-)-1-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]-N-methyl-isoc hroman-6-carboxamide], a receptor agonist showing 5000-fold selectivity for primate 5-HT1D versus 5-HT1B receptors (Ennis et al., J. Med. Chem. 41, 2180-2183), on dural neurogenic inflammation and on c-fos like immunoreactivity within trigemin...

New functional imaging techniques, including positron emission tomography, transcranial magnetic stimulation and functional magnetic resonance imaging, promise to allow the noninvasive study of haemodynamic, metabolic and activation parameters during acute migraine attacks in humans. These techniques are currently being applied to the study of the...

We examined the effects of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzol[f]quinoxaline-7-sulphonamide (NBQX), the kainate receptor antagonists γ-(R-)-glutamylaminomethanesulphonic acid (GAMS) and 6,7,8,9-tetrahy...

New functional imaging techniques, including positron emission tomography, transcranial magnetic stimulation and functional magnetic resonance imaging, promise to allow the noninvasive study of haemodynamic, metabolic and activation parameters during acute migraine attacks in humans. These techniques are currently being applied to the study of the...

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-i mine hydrogen maleate (MK-801) was examined on c-fos-like immunoreactivity (c-fos-LI) in urethane-anesthetized Sprague-Dawley rats using a polyclonal antibody. C-fos, an indicator of neuronal activation, was asse...

Perfusion- and diffusion-weighted magnetic resonance imaging was performed during spontaneous visual auras in four migraineurs. Alterations in relative cerebral blood flow (16-53% decrease), cerebral blood volume (6-33% decrease), and tissue mean transit time (10-54% increase) were observed in the gray matter of occipital cortex contralateral to th...

Five years as a migraine researcher, 8 years as a neurologist, 10 years as a physician, and 25 years as a migraineur have prompted this article. The focus is on the impact of migraine as experienced first by a teenager, then by a college student, then by a neurologist, and finally, by a headache researcher. Migraine attacks as experienced from both...

Valproate has been shown to be an effective prophylactic treatment in migraine. Investigation of the mechanism of its antimigraine action is difficult due to the broad range of its biochemical effects and the complex nature of migraine pathophysiology. Valproate increases brain GABA levels and, in doing so, may suppress migraine-related events in t...

The aim of this study was to examine whether GR-127,935, a 5-HT1B/1D receptor antagonist, blocks the inhibitory effects of sumatriptan, CP-122,288 and 5-carboxamidotryptamine (5-CT) on plasma protein extravasation, within guinea pig and rat dura matter, following electric stimulation of the trigeminal ganglion. Binding studies first established tha...

Gamma-aminobutyric acid (GABA) receptors are ubiquitous inhibitory receptors in the central and peripheral nervous systems. Valproic acid (2-propylpentanoic acid), which enhances GABA synthesis and blocks degradation, is useful in migraine treatment and may act through activation of GABA receptors to modulate trigeminal nociceptive neurons innervat...