The Stanford Headache Program Research

Overview

At Stanford we have tremendous resources at our disposal and we are using them to explore novel approaches to understanding headache medicine. We have taken on the challenge of understanding why some patients have occasional headaches throughout their life while others go on to have headaches that become daily or almost daily, causing enormous suffering and expense to patients and their families. Through generous gifts from patients as well as other funding, we are making significant discoveries about headaches, and their treatment. We have three working groups, which are described below:

Working Groups:

Functional imaging

Through the use of advanced imaging, some of which is only available at a few institutions around the world, we are able to see how the migraine brain processes pain and other stimuli and compare it to the brain processing of patients with other pain conditions and people without ongoing pain. We are fortunate to have the talented imaging scientist, Dr. Danielle DeSouza heading this group along with other researchers from across the Stanford Campus.

Deep phenotyping 

Deep phenotyping just means collecting tons of information about patients – far more detail than is normally gained from a doctor’s visit. We then take this detailed information and compare it with what we see in our functional imaging and -omics analysis (see below) in hopes of identifying subgroups of headache sufferers who are more likely to respond to one treatment or another or more likely to follow one clinical course or another. Yohannes Woldeamanuel, MD, a gifted scientist and clinicisan, leads our efforts to better understand the characteristics that make subgroups of headache sufferers unique.

Proteomics/genomics 

In this part of our research, we collect fluids (blood and spinal fluid) from our amazing patients and others who want to help us better understand headache. The information we extract from these fluids, when combined with the imaging and phenotyping described above will lead us to identifying patients who are at risk or are more likely to respond to a treatment, or even to have a different diagnosis than what they may have thought or  been told.

Researchers

Robert Cowan, MD, FAAN

Dr. Cowan’s clinical research focuses on the use of technology to improve encounter efficiency and outcomes in headache medicine. Present projects include development of on-line tools to generate detailed patient histories and delineation of diagnostic impressions based on established criteria, and app-based tools for monitoring headaches, trigger exposure, lifestyle decisions and integrating them with predictive modeling, deep phenotyping, and big data to help patients and their doctors to better manage headache disorders.

His basic research focuses on translational approaches to better understand the chronification process in headache. Utilizing technologies ranging from resting state imaging to microanalysis of cerebrospinal fluid and blood, his team is looking at changes present in patients who suffer with headache more days than not. The goal is to identify ways that these changes, in conjunction with novel therapies such as transcranial magnetic stimulation, new pharmacologic therapies, and interventional techniques will result in fewer, less severe headaches.


Danielle D. DeSouza, PhD

Dr. DeSouza's research focuses on neuroimaging methods to examine brain structure and function and treatment-related plasticity in individuals with chronic pain. Her current research projects aim to identify biomarkers of headache subtypes using multimodal neuroimaging methods, including structural and functional connectivity, diffusion tensor imaging, magnetic resonance spectroscopy, and voxel- and surface-based brain morphometry, combined with behavioral assessments. 

Her additional ongoing projects aim to understand the central mechanisms of chronic pain associated with Lyme disease using magnetic resonance imaging and quantitative sensory testing and the role of neuroinflammation in the chronic facial pain disorder, trigeminal neuralgia.


Yohannes Woldeamanuel, MD

Dr. Woldeamanuel's clinical research focuses on exploring naturally-occurring cohorts of headache sufferers. He utilizes unsupervised methods of data-reduction modeling to study multidimensional dataset including clinical phenotypes, biofluid multi-omics analysis, and brain imaging. His goal is to generate clinically meaningful results to help management of headache sufferers. 

Select Publications

2019

Development of a claims-based algorithm to identify potentially undiagnosed chronic migraine patients. Pavlovic JM, Yu JS, Silberstein SD, Reed ML, Kawahara SH, Cowan RP, Dabbous F, Campbell KL, Shewale AR, Pulicharam R, Kowalski JW, Viswanathan HN, Lipton RB. Cephalalgia. 2019 Mar 9:333102418825373. doi: 10.1177/0333102418825373. [Epub ahead of print]

Clinical Features Contributing to Cortical Thickness Changes in Chronic Migraine - A Pilot Study. Woldeamanuel YW, DeSouza DD, Sanjanwala BM, Cowan RP. Headache. 2019 Feb;59(2):180-191. doi: 10.1111/head.13452. Epub 2018 Nov 23.

2018

The Future of Migraine Prevention. Cowan RP. Headache. 2018 Nov;58 Suppl 3:291-297. doi: 10.1111/head.13418. Epub 2018 Oct 12. Review.

Deep Brain Stimulation for Chronic Cluster Headache: A Review. Vyas DB, Ho AL, Dadey DY, Pendharkar AV, Sussman ES, Cowan R, Halpern CH. Neuromodulation. 2018 Oct 10. doi: 10.1111/ner.12869. [Epub ahead of print] Review.

American Headache Society Survey About Urgent and Emergency Management of Headache Patients. Minen MT, Ortega E, Lipton RB, Cowan R. Headache. 2018 Oct;58(9):1389-1396. doi: 10.1111/head.13387. Epub 2018 Sep 12.

Introducing the Migraine Action Plan. Peretz AM, Minen MT, Cowan R, Strauss LD. Headache. 2018 Feb;58(2):195. doi: 10.1111/head.13256.  

Migraine Action Plan (MAP). Peretz AM, Minen MT, Cowan R, Strauss LD. Headache. 2018 Feb;58(2):355-356. doi: 10.1111/head.13255. No abstract available.

High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression. Williams NR, Sudheimer KD, Bentzley BS, Pannu J, Stimpson KH, Duvio D, Cherian K, Hawkins J, Scherrer KH, Vyssoki B, DeSouza D, Raj KS, Keller J, Schatzberg AF. Brain 2018 141(3): e18.

2017

Migraine and Complex Regional Pain Syndrome: A Case-Referent Clinical Study. Woldeamanuel YW, Cooley C, Foley-Saldena K, Cowan RP. Biomed Res Int. 2017;2017:5714673. doi: 10.1155/2017/5714673. Epub 2017 Oct 30.

Introducing the Australian Hearing Hub. McAlpine D, McMahon C, Dillon H, Leigh G, Hungerford J, Patrick J, Cowan R, Dodd L. Trends Hear. 2017 Jan-Dec;21:2331216517722920. doi: 10.1177/2331216517722920.

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. Cowan R, Barad M. Curr Treat Options Neurol. 2017 Jul;19(7):25. doi: 10.1007/s11940-017-0462-5. Review.

Comprehensive Headache Experience in Collegiate Student-Athletes: An Initial Report From the NCAA Headache Task Force. Seifert T, Sufrinko A, Cowan R, Scott Black W, Watson D, Edwards B, Livingston S, Webster K, Akers D, Lively M, Kontos AP. Headache. 2017 Jun;57(6):877-886. doi: 10.1111/head.13104. Epub 2017 May 7.

Migraine affects 1 in 10 people worldwide featuring recent rise: A systematic review and meta-analysis of community-based studies involving 6 million participants. Woldeamanuel YW, Cowan RP. J Neurol Sci. 2017 Jan 15;372:307-315. doi: 10.1016/j.jns.2016.11.071. Epub 2016 Dec 3. Review.

Comparison of Diffusion-Weighted MRI Reconstruction Methods for Visualization of Cranial Nerves in Posterior Fossa Surgery. Behan BT, Chen DQ, Sammartino F, DeSouza DD, Wharton-Shukster E, Hodaie M. Frontiers in Neuroscience 2017 11:554. doi.org/10.3389/fnins.2017.00554.

Headache in Resource-Limited Settings. Woldeamanuel YW. Curr Pain Headache Rep. 2017 Nov 16;21(12):51

2016

Structural magnetic resonance imaging can identify trigeminal system abnormalities in classical trigeminal neuralgia. DeSouza DD, Hodaie M, Davis KD. Frontiers in Neuroanatomy 2016 10:95. doi:10.3389/fnana.2016.00095.

Journal Club: Change in Brain Network Connectivity During PACAP38-Induced Migraine Attacks. DeSouza DD, O’Hare M, Woldeamanuel YW, Cowan RP. Neurology 2016 87:e199-202.

Journal Club: Exacerbation of Headache During Dihydroergotamine for Chronic Migraine Does Not Alter Outcome. Woldeamanuel YW, O’Hare M, DeSouza DD, Cowan RP. Neurology 2016 87:e196-98.

Diffusivity Signatures Characterize Trigeminal Neuralgia Associated with Multiple Sclerosis. Chen DQ, DeSouza DD, Hayes DJ, Davis KD, O’Connor P, Hodaie M. Multiple Sclerosis Journal 2016 22(1):51-63.

Development, Validation, and Field-Testing of an Instrument for Clinical Assessment of HIV-Associated Neuropathy and Neuropathic Pain in Resource-Restricted and Large Population Study Settings. Woldeamanuel YW, Kamerman PR, Veliotes DGA, Phillips TJ, Asboe D, Boffito M, et al. PLoS ONE 2016 Oct 20;11(10):e0164994. doi:10.1371/journal.pone.0164994 

Case Fatality of Adult Tetanus in Africa: Systematic Review and Meta-analysis. Woldeamanuel YW, Andemeskel AT, Woldeamanuel MW, Woldeamanuel W. Journal of the Neurological Sciences; 2016 Sep; 368:292-299 

The impact of regular lifestyle behavior in migraine: a prevalence case-referent study. Woldeamanuel YW, Cowan RP.  Journal of Neurology; 2016 Apr;263(4):669-676.

Indomethacin Responsive Headaches: Exhaustive Systematic Review With Pooled Analysis and Critical Appraisal of 81 Published Clinical Studies. Bordini EC, Bordini CA, Woldeamanuel YW, Rapoport AM. Headache. 2016 Feb;56(2):422-35. 

Spontaneous extracranial hemorrhagic phenomena in primary headache disorders: A systematic review of published cases. Peretz AM, Woldeamanuel YW, Rapoport AM, Cowan RP. Cephalalgia. 2016 Nov;36(13):1257-1267