Bio

Bio


Robert Cowan, MD, FAAN is Professor of Neurology and Chief of the Division of Headache Medicine at Stanford University. Prior to coming to Stanford he was ta senior clinical research scientist in molecular neurobiology at Huntington Medical Research Institutes (Pasadena, CA). Dr. Cowan attended University of Southern California, Keck Medical School, completed a residency program at USC Department of Neurology and served on faculty there until 2000. He is Board Certified in the areas of: Psychiatry and Neurology and Pain Medicine. He also holds subspecialty certification in Headache Medicine. Dr. Cowan is widely published in various scientific journals, including the Journal of the American Medical Association Cephalalgia, and Headache. He has authored book chapters lectures both nationally and internationally on a variety of headache topics, and has appeared on NBC, CBS and has been featured in articles ranging from the San Francisco Chronicle to Vogue Magazine.

Dr. Cowan has held several nationally elected positions, including chair of the sections on Chronic Daily Headache and In-office Patient Education for the American Headache Society. He is immediate past President of the Headache Cooperative of the Pacific, is a fellow of the American Academy of Neurology and the American Headache Society. He is on the boards of the Alliance for Headache Diseases Advocacy, the Headache Cooperative of the Pacific, the American Headache and Migraine Association, and the American Council for Headache Education. He is a reviewer for several peer-reviewed journals, including Headache and Cephalalgia. He is an editor for Headache Currents. Dr. Cowan is the author of The Keeler Migraine Method (Penguin/Avery, 2008).

Along with Dr. Alan Rapoport, Professor of Neurology at UCLA School of Medicine, Dr. Cowan co-founded BonTriage which develops computer-based tools to aid in the diagnosis, education, and care of people with chronic medical conditions. Dr. Cowan’s primary iresearch nterest is the pathophysiology of chronic daily headache, utilizing functional imaging, body fluid analysis and deep phenotyping. He has been the recipient of NIH, foundation, industry and individual grants and gifts for his research, .

Clinical Focus


  • Headache Medicine
  • Neurology

Academic Appointments


Administrative Appointments


  • Program Director, Headache Cooperative of the Pacific (2007 - 2011)
  • Vice President, Headache Cooperative of the Pacific (2007 - 2012)
  • Chair, Refractory Headache Special Interest Section, American Headache Society, American Headache Society (2012 - Present)
  • Director,Stanford Headache Program, Stanford University School of Medicine (2011 - Present)
  • President, Headache Cooperative of the Pacific (2012 - Present)

Honors & Awards


  • Magna Cum Laude, Clark University, Worcester, Massachusetts (1972)
  • Woodrow Wilson Scholar, Clark University, Worcester, Massachusetts (1972)
  • Chief Resident, LAC/USC, Los Angeles, California (1989)
  • Fellow, American Academy of Neurology (2006)
  • Fellow, American Headache Society (2010)

Boards, Advisory Committees, Professional Organizations


  • Member, Board of Directors, Alliance for Headache Disorders Advocacy (2009 - Present)
  • Member, Board of Directors, Headache Cooperative of the Pacific (2007 - Present)
  • Member, Advisory Committee, NCAA Select committee on headache in collegiate atheletes (2013 - Present)
  • Member,, American Headache Society (1995 - Present)
  • Member, American Academy of Neurology (1990 - Present)
  • Member, International Headache Society (2010 - Present)

Professional Education


  • Residency:LACplusUSC Neurology Residency (1990) CA
  • Internship:LACplusUSC Medical Center Internal Medicine Residency (1987) CA
  • Medical Education:University of Southern California Keck School of Medicine Registrar (1986) CA
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (1994)
  • Board Certification, Unified Council of Neurologic Subspecialties, Headache Medicine (2008)
  • Board Certification, American Academy of Pain Medicine (2000)

Community and International Work


  • AHDA

    Topic

    Funding for Headache Research

    Populations Served

    Headache Researchers, Clinicians, and Patients

    Location

    US

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • AHMA

    Topic

    Patient Advocacy

    Partnering Organization(s)

    American Headache Society

    Populations Served

    Patients with Headache

    Location

    US

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


Current interest focus on patient education technology and patient/physician communication with a particular emphasis on tools which increase encounter efficiency and improve outcomes. Basic research focuses on mechanisms of action in Chronic Daily Headache, with a particular emphasis on New Daily Persistent Headache. Techniques include fMRI, biomarker investigation and evoked potentials. Clinical research includes clinical trials of novel treatments for episodic and chronic headache forms.

Projects


  • Chronic Daily Headache Project, SunStar Foundation (8/15/2013)

    Investigation into the basic mechanisms and biomarkers associated with various form of chronic daily headache. Resting state and structural imaging, analysis of blood and CSF for biomarker identification, and evoked action potentials are utilized to better characterize the pathophysiology of chronic headache.

    Location

    Stanford University and other headache centers in U.S. and abroad.

Teaching

2019-20 Courses


Publications

All Publications


  • Patient preference for and satisfaction with fremanezumab following completion of a 1-year extension study Cowan, R. P., Gandhi, S. K., Cohen, J. M., Cloud, B., Buse, D. C., Ramirez-Campos, V., Ahn, A. H., Lipton, R. B. SAGE PUBLICATIONS LTD. 2019: 264–65
  • Evaluation of the 6-Item Identify Chronic Migraine (ID-CM) Screener in a Large Medical Group Pavlovic, J. M., Yu, J. S., Silberstein, S. D., Reed, M. L., Kawahara, S. H., Cowan, R. P., Dabbous, F., Campbell, K. L., Pulicharam, R., Viswanathan, H. N., Lipton, R. B. SAGE PUBLICATIONS LTD. 2019: 283–84
  • Patient preference for dosing regimen and perception of dosing flexibility with fremanezumab for migraine: results from a patient survey following completion of a 1-year extension study Cowan, R. P., Gandhi, S. K., Cloud, B., Cohen, J. M., Buse, D. C., Ramirez-Campos, V., Ahn, A. H., Lipton, R. B. SAGE PUBLICATIONS LTD. 2019: 263–64
  • Remote electrical neuromodulation (REN) in the acute treatment of migraine: a comparison with usual care and acute migraine medications. The journal of headache and pain Rapoport, A. M., Bonner, J. H., Lin, T., Harris, D., Gruper, Y., Ironi, A., Cowan, R. P. 2019; 20 (1): 83

    Abstract

    BACKGROUND: There is a significant unmet need for new, effective and well tolerated acute migraine treatments. A recent study has demonstrated that a novel remote electrical neuromodulation (REN) treatment provides superior clinically meaningful pain relief with a low rate of device-related adverse events. The results reported herein compare the efficacy of REN with current standard of care in the acute treatments of migraine.METHODS: We performed a post-hoc analysis on a subgroup of participants with migraine from a randomized, double-blind, parallel-group, sham-controlled, multicenter study on acute care. The original study included a 2-4weeks run-in phase, in which migraine attacks were treated according to patient preference (i.e., usual care) and reported in an electronic diary; next, participants entered a double-blind treatment phase in which they treated the attacks with an active or sham device. The efficacy of REN was compared to the efficacy of usual care or pharmacological treatments in the run-in phase in a within-subject design that included participants who treated at least one attack with the active REN device and reported pain intensity at 2h post-treatment.RESULTS: Of the 252 patients randomized, there were 99 participants available for analysis. At 2h post-treatment, pain relief was achieved in 66.7% of the participants using REN versus 52.5% participants with usual care (p<0.05). Pain relief at 2h in at least one of two attacks was achieved by 84.4% of participants versus 68.9% in usual care (p<0.05). REN and usual care were similarly effective for pain-free status at 2h. The results also demonstrate the non-inferiority of REN compared with acute pharmacological treatments and its non-dependency on preventive medication use.CONCLUSION: REN is an effective acute treatment for migraine with non-inferior efficacy compared to current acute migraine therapies. Together with a very favorable safety profile, these findings suggest that REN may offer a promising alternative for the acute treatment of migraine and could be considered first line treatment in some patients.TRIAL REGISTRATION: ClinicalTrials.gov NCT03361423 . Registered 18 November 2017.

    View details for DOI 10.1186/s10194-019-1033-9

    View details for PubMedID 31331265

  • Deep Brain Stimulation for Chronic Cluster Headache: A Review NEUROMODULATION Vyas, D. B., Ho, A. L., Dadey, D. Y., Pendharkar, A. V., Sussman, E. S., Cowan, R., Halpern, C. H. 2019; 22 (4): 388–97

    View details for DOI 10.1111/ner.12869

    View details for Web of Science ID 000471831000003

  • Subarachnoid Hemorrhage and Headache. Current pain and headache reports Ogunlaja, O. I., Cowan, R. 2019; 23 (6): 44

    Abstract

    PURPOSE FOR REVIEW: Subarachnoid hemorrhage is a serious and life-threatening medical condition which commonly presents with an acute headache. Unfortunately, it remains frequently misdiagnosed at initial presentation with dire consequences in terms of patient morbidity and mortality. The goal of this paper is to review salient features in the clinical history, as well as recently developed clinical decision rules, which can help determine which patients warrant further investigation for subarachnoid hemorrhage when the initial presentation is that of an acute headache.RECENT FINDINGS: A recent prospective observational study showed that occipital location, stabbing quality, presence of meningism, and onset of headache during exertion were characteristics in the clinical history that can distinguish the headache of SAH from other causes. The Ottawa headache rule is a clinical decision tool which was developed to help identify patients presenting to the ED with acute non-traumatic headache who require investigation to rule out subarachnoid hemorrhage. Using this tool, it is recommended that patients who meet any one of the following 6 criteria are investigated further: Onset greater than or equal to 40years, presence of neck pain or stiffness, witnessed loss of consciousness, onset during exertion, thunder clap headache (pain peaking within 1s), or limited neck flexion on exam. An informed and thoughtful approach that takes into account the timing, presentation, risk factors, and resources, as discussed here, should help distinguish between the patient that warrants further evaluation and intervention for SAH and one who does not. The Ottawa SAH rule is a useful clinical decision tool for young inexperienced clinicians in order to avoid missed diagnoses. However, its clinical value is limited by its low specificity. Clinical decision tools with higher specificity are needed.

    View details for DOI 10.1007/s11916-019-0785-x

    View details for PubMedID 31123920

  • Physician and patient preferences for dosing options in migraine prevention JOURNAL OF HEADACHE AND PAIN Cowan, R., Cohen, J. M., Rosenman, E., Iyer, R. 2019; 20
  • Toward a Philosophy of Migraine HEADACHE Cowan, R. P. 2019; 59 (4): 481–83

    View details for DOI 10.1111/head.13517

    View details for Web of Science ID 000465079700001

  • Toward a Philosophy of Migraine. Headache Cowan, R. P. 2019; 59 (4): 481–83

    View details for PubMedID 30973195

  • Development of a claims-based algorithm to identify potentially undiagnosed chronic migraine patients. Cephalalgia : an international journal of headache Pavlovic, J. M., Yu, J. S., Silberstein, S. D., Reed, M. L., Kawahara, S. H., Cowan, R. P., Dabbous, F., Campbell, K. L., Shewale, A. R., Pulicharam, R., Kowalski, J. W., Viswanathan, H. N., Lipton, R. B. 2019: 333102418825373

    Abstract

    OBJECTIVE: To develop a claims-based algorithm to identify undiagnosed chronic migraine among patients enrolled in a healthcare system.METHODS: An observational study using claims and patient survey data was conducted in a large medical group. Eligible patients had an International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) migraine diagnosis, without a chronic migraine diagnosis, in the 12 months before screening and did not have a migraine-related onabotulinumtoxinA claim in the 12 months before enrollment. Trained clinicians administered a semi-structured diagnostic interview, which served as the gold standard to diagnose chronic migraine, to enrolled patients. Potential claims-based predictors of chronic migraine that differentiated semi-structured diagnostic interview-positive (chronic migraine) and semi-structured diagnostic interview-negative (non-chronic migraine) patients were identified in bivariate analyses for inclusion in a logistic regression model.RESULTS: The final sample included 108 patients (chronic migraine=64; non-chronic migraine=44). Four significant predictors for chronic migraine were identified using claims in the 12 months before enrollment: ≥15 versus <15 claims for acute treatment of migraine, including opioids (odds ratio=5.87 [95% confidence interval: 1.34-25.63]); ≥24 versus <24 healthcare visits (odds ratio=2.80 [confidence interval: 1.08-7.25]); female versus male sex (odds ratio=9.17 [confidence interval: 1.26-66.50); claims for ≥2 versus 0 unique migraine preventive classes (odds ratio=4.39 [confidence interval: 1.19-16.22]). Model sensitivity was 78.1%; specificity was 72.7%.CONCLUSIONS: The claims-based algorithm identified undiagnosed chronic migraine with sufficient sensitivity and specificity to have potential utility as a chronic migraine case-finding tool using health claims data. Research to further validate the algorithm is recommended.

    View details for PubMedID 30854881

  • Physician and patient preferences for dosing options in migraine prevention. The journal of headache and pain Cowan, R., Cohen, J. M., Rosenman, E., Iyer, R. 2019; 20 (1): 50

    Abstract

    Adherence to a therapy, though a key factor for successful treatment, is low among patients with chronic conditions such as migraine. Dose frequency plays a major role in adherence. This study evaluated the impact of having flexible dosing options on acceptance of and adherence to a new migraine preventive therapy class among adults with migraine.In this observational study, two 20-min online surveys were completed: one by physicians currently treating adult patients with migraine and the other by adults with migraine. Both surveys presented the participants with three scenarios: 1) only monthly, 2) only quarterly, and 3) both dosing options of the new medication are available. Physicians estimated the proportion of their migraine patients who would receive the new medication in each scenario. Patients were asked about their dosing preference when either or both options are available. Respondents were asked to rate the likelihood of their acceptance of and adherence to the therapy.400 physicians and 417 US adults with migraine completed the surveys. The availability of both dosing options yielded a significant increase in the proportion of patients expected to receive the new medication. The overall proportion of patients favoring monthly dosing (35%) was similar to the proportion favoring quarterly dosing (40%). Among those who preferred monthly dosing (n = 147), a greater proportion indicated they are more likely to fill the prescription (77% vs 56%, P < 0.05) and remain adherent (80% vs 57%, P < 0.05) when only monthly is available versus when only quarterly is available. Similarly, among those who preferred quarterly dosing (n = 166), a greater proportion indicated they are likely to fill (63% vs 55%, P < 0.05) and remain adherent (62% vs 54%, P < 0.05) when only quarterly is available compared with when only monthly is available.Physicians anticipated that the proportion of patients to receive the new medication would increase when both dosing options are available. Patients stated that they are more likely to fill the prescription and adhere to the new therapy when their preferred dosing regimen is available.

    View details for PubMedID 31072307

  • On Making a Headache Medicine Rotation Mandatory in Neurology Training. Headache Zhang, N., Cowan, R. P. 2019

    View details for DOI 10.1111/head.13667

    View details for PubMedID 31562640

  • Endogenous Na+, K+-ATPase inhibitors and CSF [Na+] contribute to migraine formation. PloS one Gross, N. B., Abad, N., Lichtstein, D., Taron, S., Aparicio, L., Fonteh, A. N., Arakaki, X., Cowan, R. P., Grant, S. C., Harrington, M. G. 2019; 14 (6): e0218041

    Abstract

    There is strong evidence that neuronal hyper-excitability underlies migraine, and may or may not be preceded by cortical spreading depression. However, the mechanisms for cortical spreading depression and/or migraine are not established. Previous studies reported that cerebrospinal fluid (CSF) [Na+] is higher during migraine, and that higher extracellular [Na+] leads to hyper-excitability. We raise the hypothesis that altered choroid plexus Na+, K+-ATPase activity can cause both migraine phenomena: inhibition raises CSF [K+] and initiates cortical spreading depression, while activation raises CSF [Na+] and causes migraine. In this study, we examined levels of specific Na+, K+-ATPase inhibitors, endogenous ouabain-like compounds (EOLC), in CSF from migraineurs and controls. CSF EOLC levels were significantly lower during ictal migraine (0.4 nM +/- 0.09) than from either controls (1.8 nM +/- 0.4) or interictal migraineurs (3.1 nM +/- 1.9). Blood plasma EOLC levels were higher in migraineurs than controls, but did not differ between ictal and interictal states. In a Sprague-Dawley rat model of nitroglycerin-triggered central sensitization, we changed the concentrations of EOLC and CSF sodium, and measured aversive mechanical threshold (von Frey hairs), trigeminal nucleus caudalis activation (cFos), and CSF [Na+] (ultra-high field 23Na MRI). Animals were sensitized by three independent treatments: intraperitoneal nitroglycerin, immunodepleting EOLC from cerebral ventricles, or cerebroventricular infusion of higher CSF [Na+]. Conversely, nitroglycerin-triggered sensitization was prevented by either vascular or cerebroventricular delivery of the specific Na+, K+-ATPase inhibitor, ouabain. These results affirm our hypothesis that higher CSF [Na+] is linked to human migraine and to a rodent migraine model, and demonstrate that EOLC regulates them both. Our data suggest that altered choroid plexus Na+, K+-ATPase activity is a common source of these changes, and may be the initiating mechanism in migraine.

    View details for DOI 10.1371/journal.pone.0218041

    View details for PubMedID 31173612

  • The impact of offering monthly and quarterly dosing options for a new class of migraine preventive therapy on likelihood of acceptance and adherence in adults with migraine (vol 19, pg P137, 2018) JOURNAL OF HEADACHE AND PAIN Cowan, R., Cohen, J., Rosenman, E., Fitzgerald, T., Iyer, R. 2018; 19
  • The Future of Migraine Prevention HEADACHE Cowan, R. P. 2018; 58: 291–97

    View details for DOI 10.1111/head.13418

    View details for Web of Science ID 000449847000006

  • The Future of Migraine Prevention. Headache Cowan, R. P. 2018

    Abstract

    Barring unforeseen circumstances, we anticipate the arrival of the first mechanism-specific class of molecules for migraine prevention in 2018. Despite many ground-breaking advances in the field over the last several years, these agents, broadly identified as calcitonin gene-related peptide-based pharmaceuticals, have captured the imagination and attention of the lay press and much of the headache community. This paper will address the factors, both class-specific and systems-based, that are likely to affect the launch, access, compliance, and adherence related to this new class, as well as attempt to place these novel medications in context of the current state and anticipated changes in headache medicine.

    View details for PubMedID 30311219

  • Deep Brain Stimulation for Chronic Cluster Headache: A Review. Neuromodulation : journal of the International Neuromodulation Society Vyas, D. B., Ho, A. L., Dadey, D. Y., Pendharkar, A. V., Sussman, E. S., Cowan, R., Halpern, C. H. 2018

    Abstract

    OBJECTIVES: Cluster headaches are a set of episodic and chronic pain syndromes that are sources of significant morbidity for patients. The standard of care for cluster headaches remains medication therapy, however a minority of patients will remain refractory to treatment despite changes to dosage and therapeutic combinations. In these patients, functional neuromodulation using Deep Brain Stimulation (DBS) presents the opportunity to alleviate the significant pain that is experienced by targeting the neurophysiological substrates that mediate pain.MATERIAL AND METHODS: We review the literature on chronic cluster headache, including the growing number of DBS case reports and series that describe the alleviation of pain in a majority of patients through conventional or endoventricular targeting of the posterior hypothalamus and ventral tegmental area, with a minimal side effect profile.RESULTS: In this review, the history and outcomes of DBS use for medication-refractory cluster headaches are examined, with discussion on future directions for improving this novel treatment modality and providing efficacious, longer-lasting pain relief in headache patients.CONCLUSION: In patients with chronic cluster headache, functional neuromodulation using DBS presents the opportunity to alleviate the significant pain that is experienced by targeting the neurophysiological substrates that mediate pain.

    View details for PubMedID 30303584

  • American Headache Society Survey About Urgent and Emergency Management of Headache Patients HEADACHE Minen, M. T., Ortega, E., Lipton, R. B., Cowan, R. 2018; 58 (9): 1389–96

    Abstract

    Emergency department (ED) visits for migraine are burdensome to patients and to the larger healthcare system and society. Thus, it is important to determine strategies used to prevent ED visits and the common communication patterns between headache specialists and the ED team.We sought to understand: (1) Whether headache specialists use headache management protocols. (2) The strategies they use to try and reduce the number of ED visits for headache. (3) Whether protocols are used in the EDs with which they are affiliated. (4) The level of satisfaction with the coordination of care between headache physicians and the ED.We surveyed via SurveyMonkey members of the American Headache Society Emergency Department/Refractory/Inpatient (EDRI) Section to understand their practice regarding patients who call their office to be seen urgently, and to understand their communication with their local EDs.There were 96 eligible AHS members, 50 of whom responded to questionnaires either by email or in person (52%). Of these, 59% of respondents reported giving rescue treatment to their patients to manage acute attacks. Fifty-four percent reported using standard protocols for outpatients not responding to usual acute treatments. In the event of a request for urgent care, 12% of specialists reported bringing patients into the office most or all of the time, and 20% reported sending patients to the ED some or most of the time for headache management. Thirty-six percent reported prescribing a new medicine and 30% reported providing telephone counseling some/most/all of the time. Sixty percent reported that their ED has a protocol for migraine management. Overall, 38% were usually or very satisfied with the headache care in the ED.A substantial number of headache specialists are dissatisfied with the care their patients receive in the ED. More standardized protocols for ED visits by patients with known headache disorders, and clear guidelines for communication between ED providers and treating physicians, along with better methods for follow-up following discharge from the ED, might appear to improve this issue.

    View details for DOI 10.1111/head.13387

    View details for Web of Science ID 000448841600005

    View details for PubMedID 30207384

  • The impact on physician prescribing of monthly and quarterly dosing options for a new class of migraine preventive therapy Cowan, R., Rosenman, E., Fitzgerald, T., Cohen, J., Iyer, R. SPRINGEROPEN. 2018
  • Evaluation of the Identify Chronic Migraine (ID-CM) Screener in a Large Medical Group Yu, J. S., Pavlovic, J. M., Silberstein, S. D., Reed, M. L., Kawahara, S. H., Cowan, R. P., Dabbous, F., Campbell, K., Pulicharam, R., Viswanathan, H. N., Lipton, R. B. LIPPINCOTT WILLIAMS & WILKINS. 2018
  • Development of a Claims-Based Algorithm for Use in Patients with Migraine to Identify Potentially Undiagnosed Chronic Migraine Patients Pavlovic, J., Yu, J. S., Silbertsein, S. D., Reed, M. L., Kawahara, S. H., Cowan, R. P., Dabbous, F., Campbell, K., Shewale, A. R., Pulicharam, R., Kowalski, J. W., Viswanathan, H. N., Lipton, R. B. LIPPINCOTT WILLIAMS & WILKINS. 2018
  • American Headache Society Survey about Urgent and Emergency Management of Headache Patients Minen, M., Ortega, E., Lipton, R., Cowan, R. LIPPINCOTT WILLIAMS & WILKINS. 2018
  • Migraine Action Plan (MAP). Headache Peretz, A. M., Minen, M. T., Cowan, R., Strauss, L. D. 2018; 58 (2): 355–56

    View details for PubMedID 29411363

  • Introducing the Migraine Action Plan HEADACHE Peretz, A. M., Minen, M. T., Cowan, R., Strauss, L. D. 2018; 58 (2): 195

    View details for PubMedID 29411373

  • Clinical Features Contributing to Cortical Thickness Changes in Chronic Migraine - A Pilot Study. Headache Woldeamanuel, Y. W., DeSouza, D. D., Sanjanwala, B. M., Cowan, R. P. 2018

    Abstract

    The objectives of this cross-sectional pilot study were threefold: to identify regions of cortical thickness that differentiate chronic migraine (CM) from controls, to assess group differences in interregional cortical thickness covariance, and to determine group differences in associations between clinical variables and cortical thickness.Cortical thickness alterations in relation to clinical features have not been adequately explored in CM. Assessment of this relationship can be useful to describe cortical substrates for disease progression in migraine and to identify clinical variables that warrant management emphasis.Thirty CM cases (mean age 40 years; male-to-female 1:4) and 30 sex-matched healthy controls (mean age 40 years) were enrolled. Participants completed self-administered and standardized questionnaires assessing headache-related clinical features and common psychological comorbidities. T1-weighted brain images were acquired on a 3T MRI. A whole-brain cortical thickness analysis was performed. Additionally, correlations between all brain regions were assessed to examine interregional cortical thickness covariance. Interactions were analyzed to identify clinical variables that were significantly associated with cortical thickness.The whole brain cortical thickness analysis revealed no significant differences between CM patients and controls. However, significant associations between clinical features and cortical thickness were observed for the patients only. These associations included the right superior temporal sulcus (R2  = 0.72, P = .001) and the right insula (R2  = 0.71, P = .002) with distinct clinical variables ie, longer history of CM, posttraumatic stress disorder (PTSD), sleep quality, pain self-efficacy, and somatic symptoms. Higher interregional cortical covariance was found in CM compared to controls (OR = 3.1, CI 2.10-4.56, P < .0001), such that cortical thickness between regions tended to be more correlated in patients, particularly in the temporal and frontal lobes.CM patients have significantly greater cortical covariance compared to controls. Cortical thickness in CM patients was predominantly accounted for by CM duration, PTSD, and poor sleep quality, while improved pain self-efficacy buffered cortical thickness. While it is important to address all CM features and comorbidities, it may be useful to emphasize optimizing the management of certain clinical features that contribute to cortical abnormalities including managing PTSD, early management to shorten duration of CM, and improving pain self-efficacy and sleep quality.

    View details for PubMedID 30468246

  • Migraine Treatment Patterns and Opioid Use Among Chronic and Episodic Migraine Patients Identified by a Clinician-Administered Semi-Structured Diagnostic Interview Yu, J. S., Pavlovic, J. M., Silberstein, S. D., Reed, M. L., Kawahara, S. H., Cowan, R. P., Dabbous, F., Campbell, K. L., Pulicharam, R., Viswanathan, H. N., Lipton, R. B. SAGE PUBLICATIONS LTD. 2017: 365–66
  • Evaluation of the Identify Chronic Migraine (ID-CM) screener in an accountable care organization Yu, J. S., Pavlovic, J. M., Silberstein, S. D., Reed, M. L., Kawahara, S. H., Cowan, R. P., Dabbous, F., Campbell, K., Pulicharam, R., Viswanathan, H. N., Lipton, R. B. SAGE PUBLICATIONS LTD. 2017: 188–89
  • Use of Most Bothersome Symptom as a Co-Primary Endpoint in an Acute Treatment of Migraine Trial Dodick, D. W., Tepper, S. J., Friedaman, D., Gelfand, A., Cowan, R. P., Schmidt, P., Engels, J., Rapoport, A., Kellerman, D. J. SAGE PUBLICATIONS LTD. 2017: 361–62
  • Effect of Educating the Primary Care Physician About Headache to Help Reduce "Trivial" Referrals and Improve the Number and Quality of "Substantial" Referrals that Truly Need Subspecialty Headache Medicine Care. Current treatment options in neurology Cowan, R., Barad, M. 2017; 19 (7): 25-?

    Abstract

    Technology is likely to play an increasingly important role in the delivery of healthcare as the disparity between provider availability/expertise and patient numbers/needs increases. This article is intended to lend insight into the ways in which technology can facilitate the evaluation of patients with headache disorders and improve the ongoing monitoring of disease progression and response to therapy, following proper diagnosis. While it is not possible to prognosticate the impact of technologies not yet available, the article addresses potential novel usage of currently existing technology to standardize intake, expedite evaluations, ensure adequate history and documentation, and monitoring of patient care.

    View details for DOI 10.1007/s11940-017-0462-5

    View details for PubMedID 28536899

  • Comprehensive Headache Experience in Collegiate Student-Athletes: An Initial Report From the NCAA Headache Task Force HEADACHE Seifert, T., Sufrinko, A., Cowan, R., Black, W., Watson, D., Edwards, B., Livingston, S., Webster, K., Akers, D., Lively, M., Kontos, A. P. 2017; 57 (6): 877–86

    Abstract

    The prevalence of primary headache disorders in the general population provides a unique challenge in the evaluation of headache occurring in the context of sport. Despite a wealth of studies exploring the epidemiology of headache in the layperson, little is known about the prevalence and nature of headaches in collegiate student-athletes. These scenarios are challenging in the return to play context, as it is often unclear whether an athlete has an exacerbation of a primary headache disorder, new onset headache unrelated to trauma, or has suffered a concussive injury.To establish the prevalence and nature of headaches in collegiate student-athletes.Retrospective cross-sectional survey.This cross-sectional survey evaluated the characteristics and prevalence of headache in 834 student-athletes from four NCAA Division-I institutions. Because headache occurrence may vary by sport (collision, contact, non-contact), by sex, and medical history, our sample included male and female athletes in a variety of sports, with differing degrees of contact exposure. The 20 question survey collected data on personal and family history of headache, as well as concussion history.A total of 23.7% (n = 198) of participants reported having a personal history of migraine, 25.2% (n = 210) history of sinus headache, and 12.3% (n = 103) history of tension type headache. Among athletes with a prior history of concussion, 46.3% (n = 25) of females reported a history of migraine, while only 32.2% of males reported history of migraine (χ2  = 3.421, P = .064).The etiology of increased prevalence of migraine in our study is unclear. Whether this is due to increased awareness of headache disorders, a consequence of contact exposure, or a predisposition for migraine development in this age group remains unclear. Further studies are indicated.

    View details for PubMedID 28480575

  • Migraine affects 1 in 10 people worldwide featuring recent rise: A systematic review and meta-analysis of community-based studies involving 6 million participants JOURNAL OF THE NEUROLOGICAL SCIENCES Woldeamanuel, Y. W., Cowan, R. P. 2017; 372: 307-315

    Abstract

    To study the weighted average global prevalence of migraine at the community level.A systematic review using advanced search strategies employing PubMed/MEDLINE, Scopus, and Web of Science was conducted for community-based and non-clinical studies by combining the terms "migraine", "community-based", and names of every country worldwide spanning all previous years from January 1, 1920 until August 31, 2015. Methods were in accordance with PRISMA and MOOSE guidelines. A meta-analysis with subgroup analysis was performed to identify pooled migraine prevalence and examine cohort heterogeneity.A total of 302 community-based studies involving 6,216,995 participants (median age 35years, male-to-female ratio of 0.91) were included. Global migraine prevalence was 11.6% (95% CI 10.7-12.6%; random effects); 10.4% in Africa, 10.1% in Asia, 11.4% in Europe, 9.7% in North America, 16.4% in Central and South America. When the pooled cohort was stratified, the prevalence was 13.8% among females, 6.9% among males, 11.2% among urban residents, 8.4% among rural residents, and 12.4% among school/college students. Our result showed a pattern of rising global migraine prevalence.Migraine affects one in ten people worldwide featuring recent rise. Higher prevalence was found among females, students, and urban residents.

    View details for DOI 10.1016/j.jns.2016.11.071

    View details for Web of Science ID 000393002500060

    View details for PubMedID 28017235

  • Migraine and Complex Regional Pain Syndrome: A Case-Referent Clinical Study. BioMed research international Woldeamanuel, Y. W., Cooley, C., Foley-Saldena, K., Cowan, R. P. 2017; 2017: 5714673

    Abstract

    We studied clinical phenotype differences between migraineurs with CRPS (Mig + CRPS) and those without (Mig - CRPS). Mig + CRPS cases and Mig - CRPS referents aged ≥18 years were enrolled. Diagnosis was made in accordance with International Classification of Headache Disorders-3 beta (ICHD-3 beta) for migraine and Budapest Criteria for CRPS. Migraines both with and without aura were included. A total of 70 Mig + CRPS cases (13% males, mean age 48 years) and 80 Mig - CRPS referents (17% males, mean age 51 years) were included. 33% of Mig + CRPS and 38% of Mig - CRPS exhibited episodic migraine (EM) while 66% of Mig + CRPS and 62% of Mig - CRPS had chronic migraine (CM) (OR = 0.98, CI 0.36, 2.67). Median duration of CRPS was 3 years among EM + CRPS and 6 years among CM + CRPS cohort (p < 0.02). Mig + CRPS (57%) carried higher psychological and medical comorbidities compared to Mig - CRPS (6%) (OR 16.7, CI 10.2, 23.6). Higher migraine frequency was associated with longer CRPS duration. Migraineurs who developed CRPS had higher prevalence of psychological and medical disorders. Alleviating migraineurs' psychological and medical comorbidities may help lower CRPS occurrence.

    View details for PubMedID 29214172

    View details for PubMedCentralID PMC5682894

  • Spontaneous extracranial hemorrhagic phenomena in primary headache disorders: A systematic review of published cases CEPHALALGIA Peretz, A. M., Woldeamanuel, Y. W., Rapoport, A. M., Cowan, R. P. 2016; 36 (13): 1257-1267
  • Journal Club: Change in brain network connectivity during PACAP38-induced migraine attacks. Neurology DeSouza, D. D., O'Hare, M., Woldeamanuel, Y. W., Cowan, R. P. 2016; 87 (16): e199-e202

    View details for PubMedID 27754916

  • Journal Club: Exacerbation of headache during dihydroergotamine for chronic migraine does not alter outcome. Neurology Woldeamanuel, Y. W., O'Hare, M., DeSouza, D. D., Cowan, R. P. 2016; 87 (16): e196-e198

    Abstract

    Transient headache exacerbation during IV dihydroergotamine (DHE) therapy of migraine may prompt clinicians to prematurely discontinue DHE therapy, potentially depriving patients of the full benefit of DHE infusion. In a recent Neurology® article, Eller et al. evaluated whether or not worsening headache during DHE infusion was associated with suboptimal medium-term headache outcomes.

    View details for PubMedID 27754915

  • Migraine and Complex Regional Pain Syndrome: A Case-Referent Clinical Study Woldeamanuel, Y. W., Cooley, C., Foley-Saldena, K., Cowan, R. P. WILEY-BLACKWELL. 2016: S169
  • Severe Headache or Migraine History Is Inversely Correlated With Dietary Sodium Intake: NHANES 1999-2004: A Response HEADACHE Pogoda, J. M., Gross, N. B., Arakaki, X., Fonteh, A. N., Cowan, R. P., Harrington, M. G. 2016; 56 (7): 1216–18

    View details for PubMedID 27432628

  • Worldwide Migraine Epidemiology: Systematic Review and Meta-Analysis of 302 Community-Based Studies Involving 6,216,995 Participants Woldeamanuel, Y., Cowan, R. LIPPINCOTT WILLIAMS & WILKINS. 2016
  • The impact of regular lifestyle behavior in migraine: a prevalence case-referent study JOURNAL OF NEUROLOGY Woldeamanuel, Y. W., Cowan, R. P. 2016; 263 (4): 669-676

    Abstract

    Regular lifestyle behaviors (RLBs) of sleep, exercise, mealtime pattern and hydration status independently affect migraine occurrence. We aimed herein to evaluate the differences in migraine occurrence among participants who do and do not maintain the RLB triumvirate. Cases of chronic migraine (CM) and referents of episodic migraine (EM) ≥aged 15 years with charts regularly documenting RLB notes were continuously enrolled from a retrospective case-referent cohort study performed on electronic chart review from January 1, 2014 to January 1, 2015 at the Stanford Headache and Facial Pain Program. Association between RLB prevalence and migraine occurrence was studied. 175 CM and 175 EM patients were enrolled (mean age 44.4 years, 22 % males). Migraine was diagnosed according to the ICHD-3 beta criteria, and was confirmed by a Headache Specialist attending the Clinic. The CM cohort (22 %) exhibited less RLB than the EM cohort (69 %), with crude odds ratio of 0.13 (95 % confidence interval or CI 0.08-0.21). The adjusted odds ratio and adjusted relative risk between RLB+, Meds+ (those taking medication) and CM were 0.67 (95 % CI 0.32-1.40) and 0.74 (95 % CI 0.43-1.28), indicating no significant effect modification. Engaging in regular lifestyle behavior helps quell chronic migraine.

    View details for DOI 10.1007/s00415-016-8031-5

    View details for Web of Science ID 000373742600006

    View details for PubMedID 26810728

  • Severe Headache or Migraine History Is Inversely Correlated With Dietary Sodium Intake: NHANES 1999-2004 HEADACHE Pogoda, J. M., Gross, N. B., Arakaki, X., Fonteh, A. N., Cowan, R. P., Harrington, M. G. 2016; 56 (4): 688-698

    Abstract

    We investigated whether dietary sodium intake from respondents of a national cross-sectional nutritional study differed by history of migraine or severe headaches.Several lines of evidence support a disruption of sodium homeostasis in migraine.Our analysis population was 8819 adults in the 1999-2004 National Health and Nutrition Examination Survey (NHANES) with reliable data on diet and headache history. We classified respondents who reported a history of migraine or severe headaches as having probable history of migraine. To reduce the diagnostic conflict from medication overuse headache, we excluded respondents who reported taking analgesic medications. Dietary sodium intake was measured using validated estimates of self-reported total grams of daily sodium consumption and was analyzed as the residual value from the linear regression of total grams of sodium on total calories. Multivariable logistic regression that accounted for the stratified, multistage probability cluster sampling design of NHANES was used to analyze the relationship between migraine and dietary sodium.Odds of probable migraine history decreased with increasing dietary sodium intake (odds ratio = 0.93, 95% confidence interval = 0.87, 1.00, P = .0455). This relationship was maintained after adjusting for age, sex, and body mass index (BMI) with slightly reduced significance (P = .0505). In women, this inverse relationship was limited to those with lower BMI (P = .007), while in men the relationship did not differ by BMI. We likely excluded some migraineurs by omitting frequent analgesic users; however, a sensitivity analysis suggested little effect from this exclusion.This study is the first evidence of an inverse relationship between migraine and dietary sodium intake. These results are consistent with altered sodium homeostasis in migraine and our hypothesis that dietary sodium may affect brain extracellular fluid sodium concentrations and neuronal excitability.

    View details for DOI 10.1111/head.12792

    View details for Web of Science ID 000374696100006

    View details for PubMedID 27016121

    View details for PubMedCentralID PMC4836999

  • Spontaneous extracranial hemorrhagic phenomena in primary headache disorders: A systematic review of published cases. Cephalalgia Peretz, A. M., Woldeamanuel, Y. W., Rapoport, A. M., Cowan, R. P. 2015

    Abstract

    Head pain is a cardinal feature of primary headache disorders (PHDs) and is often accompanied by autonomic and vasomotor symptoms and/or signs. Spontaneous extracranial hemorrhagic phenomena (SEHP), including epistaxis, ecchymosis, and hematohidrosis (a disorder of bleeding through sweat glands), are poorly characterized features of PHDs.To critically appraise the association between SEHP and PHDs by systematically reviewing and pooling all reports of SEHP associated with headaches.Advanced searches using the PubMed/MEDLINE, Web of Science, Cochrane Library, Google Scholar, and ResearchGate databases were carried out for clinical studies by combining the terms "headache AND ecchymosis", "headache AND epistaxis", and "headache AND hematohidrosis" spanning all medical literature prior to October 10, 2015. Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were applied.A total of 105 cases of SEHP associated with PHDs (83% migraine and 17% trigeminal autonomic cephalgias) were identified (median age 27 years, male to female ratio 1:2.3); 63% had epistaxis, 33% ecchymosis, and 4% hematohidrosis. Eighty-three percent of studies applied the International Classification of Headache Disorders diagnostic criteria. Eighty percent of the reported headaches were episodic and 20% were chronic. Twenty-four percent of studies reported recurrent episodes of SEHP.Our results suggest that SEHP may be rare features of PHDs. Future studies would benefit from the systematic characterization of these phenomena.

    View details for PubMedID 26611681

  • Comparison of parenteral treatments of acute primary headache in a large academic emergency department cohort. Cephalalgia McCarthy, L. H., Cowan, R. P. 2015; 35 (9): 807-815

    Abstract

    The objective of this article is to compare acute primary headache patient outcomes in those initially treated with parenteral opiates or non-opiate recommended headache medications in a large academic medical emergency department (ED).Many acute primary headache patients are not diagnosed with a specific headache type and are treated with opiates and nonspecific pain medications in the ED setting. This is inconsistent with multiple expert recommendations.Electronic charts were reviewed from 574 consecutive patients who visited the ED for acute primary headache (identified by chief complaint and ICD9 codes) and were treated with parenteral medications.Non-opiate recommended headache medications were given first line to 52.6% and opiates to 22.8% of all participants. Patients given opiates first had significantly longer length of stays (median 5.0 vs. 3.9 hours, p < 0.001) and higher rates of return ED visits within seven days (7.6% vs. 3.0%, p = 0.033) compared with those given non-opiate recommended medications in univariate analysis. Only the association with longer length of stay remained significant in multivariable regression including possible confounding variables.Initial opiate use is associated with longer length of stay compared with non-opiate first-line recommended medications for acute primary headache in the ED. This association remained strong and significant even after multivariable adjustment for headache diagnosis and other possible confounders.

    View details for DOI 10.1177/0333102414557703

    View details for PubMedID 25366551

    View details for PubMedCentralID PMC4417651

  • Prevalence of migraine headache and its weight on neurological burden in Africa: a 43-year systematic review and meta-analysis of community-based studies. Journal of the neurological sciences Woldeamanuel, Y. W., Andreou, A. P., Cowan, R. P. 2014; 342 (1-2): 1-15

    Abstract

    Headache burden is not adequately explored in Africa. Here, we measured weighted migraine prevalence from community-based studies in Africa.PubMed search was employed using terms 'headache in Africa' AND/OR 'migraine in Africa' for published literature from 1970 until January 31, 2014. PRISMA was applied for systematic review. Forest-plot meta-analysis, inter-study heterogeneity, and odds ratio were used to measure weighted prevalence, inter-gender, and urban-rural differences. Disability adjusted life years (DALYs) for migraine and other neurologic disorders in Africa were extracted from Global Burden of Diseases (GBD) 2000-2030.Among 21 community-based studies included (n=137,277), pooled migraine prevalence was 5.61% (95% CI 4.61, 6.70; random effects) among general population; while 14.89% (14.06, 15.74; fixed effects) among student cohorts. Female students had weighted OR of 2.13 (1.34, 3.37; p=0.0013). Prevalence of migraine was higher among urban population compared to rural settings. Migraine burden is bound to increase by more than 10% DALYs within the next decade.Africa has a crude estimate of 56 million people suffering from migraine. By virtue of mainly afflicting the younger working-age group, migraine disability has wider socioeconomic implications. Improving early headache management access points at community-level, training and research at facility-level, and healthy lifestyle modification among urban residents can help reduce this costly and disabling chronic progressive health problem.

    View details for DOI 10.1016/j.jns.2014.04.019

    View details for PubMedID 24814950

  • Prevalence of migraine headache and its weight on neurological burden in Africa: A 43-year systematic review and Meta-analysis of community-based studies JOURNAL OF THE NEUROLOGICAL SCIENCES Woldeamanuel, Y. W., Andreou, A. P., Cowan, R. P. 2014; 342 (1-2): 1-15

    Abstract

    Headache burden is not adequately explored in Africa. Here, we measured weighted migraine prevalence from community-based studies in Africa.PubMed search was employed using terms 'headache in Africa' AND/OR 'migraine in Africa' for published literature from 1970 until January 31, 2014. PRISMA was applied for systematic review. Forest-plot meta-analysis, inter-study heterogeneity, and odds ratio were used to measure weighted prevalence, inter-gender, and urban-rural differences. Disability adjusted life years (DALYs) for migraine and other neurologic disorders in Africa were extracted from Global Burden of Diseases (GBD) 2000-2030.Among 21 community-based studies included (n=137,277), pooled migraine prevalence was 5.61% (95% CI 4.61, 6.70; random effects) among general population; while 14.89% (14.06, 15.74; fixed effects) among student cohorts. Female students had weighted OR of 2.13 (1.34, 3.37; p=0.0013). Prevalence of migraine was higher among urban population compared to rural settings. Migraine burden is bound to increase by more than 10% DALYs within the next decade.Africa has a crude estimate of 56 million people suffering from migraine. By virtue of mainly afflicting the younger working-age group, migraine disability has wider socioeconomic implications. Improving early headache management access points at community-level, training and research at facility-level, and healthy lifestyle modification among urban residents can help reduce this costly and disabling chronic progressive health problem.

    View details for DOI 10.1016/j.jns.2014.04.019

    View details for Web of Science ID 000338414500001

  • CAM in the Real World: You May Practice Evidence-Based Medicine, But Your Patients Don't. Headache Cowan, R. P. 2014; 54 (6): 1097-1102

    Abstract

    Complementary and Alternative Medicine (CAM) approaches are widely used among individuals suffering from headache. The medical literature has focused on the evidence base for such use and has largely ignored the fact that these approaches are in wide use despite that evidence base.This article focuses on the uses of CAM by patients and suggests strategies for understanding and addressing this use without referring back to the evidence base. The rationale for this discussion pivots on the observation that patients are already using these approaches, and for many there are anecdotal and historical bases for use which patients find persuasive in the absence of scientific evidence.Until such time as the body of scientific literature adequately addresses non-conventional approaches, physicians must acknowledge and understand, as best as possible, CAM approaches which are in common use by patients. This is illustrated with a case study and examples from practice. This article does not review the evidence base for various CAM practices as this has been done well elsewhere.

    View details for DOI 10.1111/head.12364

    View details for PubMedID 24766436

  • Does exercise make migraines worse and tension type headaches better? Current pain and headache reports Hindiyeh, N. A., Krusz, J. C., Cowan, R. P. 2013; 17 (12): 380-?

    Abstract

    Many non-pharmacological treatments have been implicated in the treatment of primary headache, with exercise being a common recommendation. In this review we first provide an overview of the relationship between exercise and primary headaches. We then review the physiology of pain modulation, with focus on the endogenous opioids, endocannabinoids, and neuropeptides calcitonin gene-related peptide (CGRP) and brain-derived neurotrophic factor (BDNF), and their associations with primary headache and exercise. Finally, we summarize current literature evaluating effects of exercise on primary headache in an effort to understand the benefits and disadvantages of exercise in primary headaches.

    View details for DOI 10.1007/s11916-013-0380-5

    View details for PubMedID 24234818

  • Does exercise make migraines worse and tension type headaches better? Current pain and headache reports Hindiyeh, N. A., Krusz, J. C., Cowan, R. P. 2013; 17 (12): 380-?

    Abstract

    Many non-pharmacological treatments have been implicated in the treatment of primary headache, with exercise being a common recommendation. In this review we first provide an overview of the relationship between exercise and primary headaches. We then review the physiology of pain modulation, with focus on the endogenous opioids, endocannabinoids, and neuropeptides calcitonin gene-related peptide (CGRP) and brain-derived neurotrophic factor (BDNF), and their associations with primary headache and exercise. Finally, we summarize current literature evaluating effects of exercise on primary headache in an effort to understand the benefits and disadvantages of exercise in primary headaches.

    View details for DOI 10.1007/s11916-013-0380-5

    View details for PubMedID 24234818

  • Executive Function Changes before Memory in Preclinical Alzheimer's Pathology: A Prospective, Cross-Sectional, Case Control Study PLOS ONE Harrington, M. G., Chiang, J., Pogoda, J. M., Gomez, M., Thomas, K., Marion, S. D., Miller, K. J., Siddarth, P., Yi, X., Zhou, F., Lee, S., Arakaki, X., Cowan, R. P., Thao Tran, T., Charleswell, C., Ross, B. D., Fonteh, A. N. 2013; 8 (11)

    Abstract

    Early treatment of Alzheimer's disease may reduce its devastating effects. By focusing research on asymptomatic individuals with Alzheimer's disease pathology (the preclinical stage), earlier indicators of disease may be discovered. Decreasing cerebrospinal fluid beta-amyloid42 is the first indicator of preclinical disorder, but it is not known which pathology causes the first clinical effects. Our hypothesis is that neuropsychological changes within the normal range will help to predict preclinical disease and locate early pathology.We recruited adults with probable Alzheimer's disease or asymptomatic cognitively healthy adults, classified after medical and neuropsychological examination. By logistic regression, we derived a cutoff for the cerebrospinal fluid beta amyloid42/tau ratios that correctly classified 85% of those with Alzheimer's disease. We separated the asymptomatic group into those with (n = 34; preclinical Alzheimer's disease) and without (n = 36; controls) abnormal beta amyloid42/tau ratios; these subgroups had similar distributions of age, gender, education, medications, apolipoprotein-ε genotype, vascular risk factors, and magnetic resonance imaging features of small vessel disease. Multivariable analysis of neuropsychological data revealed that only Stroop Interference (response inhibition) independently predicted preclinical pathology (OR = 0.13, 95% CI = 0.04-0.42). Lack of longitudinal and post-mortem data, older age, and small population size are limitations of this study.Our data suggest that clinical effects from early amyloid pathophysiology precede those from hippocampal intraneuronal neurofibrillary pathology. Altered cerebrospinal fluid beta amyloid42 with decreased executive performance before memory impairment matches the deposits of extracellular amyloid that appear in the basal isocortex first, and only later involve the hippocampus. We propose that Stroop Interference may be an additional important screen for early pathology and useful to monitor treatment of preclinical Alzheimer's disease; measures of executive and memory functions in a longitudinal design will be necessary to more fully evaluate this approach.

    View details for DOI 10.1371/journal.pone.0079378

    View details for Web of Science ID 000327308500055

    View details for PubMedID 24260210

    View details for PubMedCentralID PMC3832547

  • Phospholipase C activity increases in cerebrospinal fluid from migraineurs in proportion to the number of comorbid conditions: a case-control study JOURNAL OF HEADACHE AND PAIN Fonteh, A. N., Pogoda, J. M., Chung, R., Cowan, R. P., Harrington, M. G. 2013; 14

    Abstract

    Migraineurs are more often afflicted by comorbid conditions than those without primary headache disorders, though the linking pathophysiological mechanism(s) is not known. We previously reported that phosphatidylcholine-specific phospholipase C (PC-PLC) activity in cerebrospinal fluid (CSF) increased during migraine compared to the same individual's well state. Here, we examined whether PC-PLC activity from a larger group of well-state migraineurs is related to the number of their migraine comorbidities.In a case-control study, migraineurs were diagnosed using International Headache Society criteria, and controls had no primary headache disorder or family history of migraine. Medication use, migraine frequency, and physician-diagnosed comorbidities were recorded for all participants. Lumbar CSF was collected between the hours of 1 and 5 pm, examined immediately for cells and total protein, and stored at -80°C. PC-PLC activity in thawed CSF was measured using a fluorometric enzyme assay. Multivariable logistic regression was used to evaluate age, gender, medication use, migraine frequency, personality scores, and comorbidities as potential predictors of PC-PLC activity in CSF.A total of 18 migraineurs-without-aura and 17 controls participated. In a multivariable analysis, only the number of comorbidities was related to PC-PLC activity in CSF, and only in migraineurs [parameter estimate (standard error) = 1.77, p = 0.009].PC-PLC activity in CSF increases with increasing number of comorbidities in migraine-without-aura. These data support involvement of a common lipid signaling pathway in migraine and in the comorbid conditions.

    View details for DOI 10.1186/1129-2377-14-60

    View details for Web of Science ID 000321647800001

    View details for PubMedID 23826990

    View details for PubMedCentralID PMC3704687

  • Chronic daily headache NEUROPSYCHIATRY OF HEADACHE Cowan, R. P., Green, M. W., Muskin, P. R. 2013: 95–105
  • Cerebrospinal fluid phosopholipase C activity increases in migraine. Cephalalgia Alfred N Fonteh, Rainbow Chung, Tara L Sharma, R Danielle Fisher, Janice M Pogoda, Robert Cowan, Michael G Harrington 2011; 31 (4): 456-462
  • Capillary Endothelial Na+, K+, ATPase Transporter Homeostasis and a New Theory for Migraine Pathophysiology. Headache Harrington, M.G., Fonteh, A.N., Arakaki, X., Cowan, R.P., Ecke, L.E., Foster, H., Huhmer, A.F., & Biringer, R. 2010; 50 (3): 459-78
  • The morphology and biochemistry of nanostructures provide evidence for synthesis and signaling functions in human cerebrospinal fluid. Cerebrospinal Fluid Res. Harrington MG, Fonteh AN, Oborina E, Liao P, Cowan RP, McComb G, Chavez JN, Rush J, Biringer RG, Huhmer AF. 2009: 6:10
  • Prostaglandin D Synthase Isoforms from Cerebrospinal Fluid Vary with Brain Physiology. Disease Markers Harrinton MG, Fonteh AN, Biringer RG, Huhmer AF, Cowan RP. 2006; 22 (1-2): 73-81
  • Cerebrospinal Fluid Sodium Increases in Migraine Headache Harrington MG, Fonteh AN, Cowan RP, Perrine K, Pogoda JM, Biringer, RG, Huhmer AFR. 2006; 46 (7): 1128-1135