Development of Unique Serum Biomarkers with Mass Spectroscopy for Diagnosis of Veterans with Chronic Posttraumatic Headache versus Idiopathic Chronic Migraine
Abstract
Chronic migraine (CM) is a syndrome manifested by headache that occurs >/= 15 days/month with at least 8 of these being migraine days and may continue for years. CM occurs in 1%-2% of the general population; however, CM is a problem seen in 20%-40% of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans who have suffered a deployment-related traumatic brain injury (D-TBI) and may continue for >12 years in some subjects. D-TBI occurred in 15%-20% of OEF/OIF Veterans, and 20%-40% of these may have ongoing CM years after injury. For individuals with CM, this syndrome interferes significantly with employment, family responsibilities and relationships, and leisure pursuits. Currently, there are no biomarkers for the CM syndrome. This study will attempt to provide biomarkers that can help determine if idiopathic CM (I-CM) and post-traumatic CM (PT-CM) are the same or different diseases and provide information about pathophysiology of CM and possible treatments for the problem. Regardless of the causal mechanism for the CM syndrome, the fact that the chronic headache may continue for years suggests a pathologic process or mechanism that sustains or continually regenerates the ongoing chronic headache. Such a process could involve inflammation within the brain or its neighboring tissues, degeneration of neural tissue, a body or brain defense mechanism, or some as yet undefined process. Multiple mechanisms could contribute to ongoing occurrence of CM. Theoretically, these pathophysiologic or stress/defense mechanisms could result in production of unique biomolecules that may be shed or secreted from the site of action, then cross the blood-brain barrier and enter the blood stream. In this project, high resolution and high accuracy electrospray ionization mass spectrometry (ESI-MS) will be employed to analyze unfractionated serum samples from TBI and control subjects to look for mass profiles of biomolecules that will be specific for CM and can serve as biomarkers. Further work with these biomarkers could lead to identification of the pathophysiologic origin of CM and development of treatments for CM. This project will involve recruiting 300 Veterans from Operation New Dawn, a program of the Department of Veterans Affairs for OEF/OIF Veterans with 10,000 members in our area. We will recruit 75 Veterans who suffered (D-TBI) and manifest ongoing CM since injury (PT-CM), and 75 will be Veterans who have not had a D-TBI but developed CM since deployment (Idiopathic CM or I-CM). The remainder will be control subjects (CS) who are OEF/OIF Veterans without D-TBI or CM who will be matched by age, sex, race, and time of deployment for each PT-CM or I-CM subject. All subjects will be contacted by telephone and the following questionnaires filled out: (1) TBI and health, (2) Headache questionnaire, (3) Beck Depression Inventory 2, (4) PTSD (post-traumatic stress disorder) Civilian questionnaire, and (5) Montreal cognitive assessment. These will establish the clinical features of each subject and confirm presence or absence of D-TBI and CM. An in-person examination by a neurologist will follow with obtaining a 5 cc peripheral blood sample. The serum from this blood will be analyzed by the ESI-MS technique to look for evidence of biomolecule mass peaks profiles representing signatures that are unique to PTH. The clinical data for headache will consist of frequency, duration, and intensity of headache. The diagnosis of CM will require the following: headache occurring >/=15 days/month with >/=8 migraine days for >3 months for ICM. For PT-CM diagnosis, the same headache criteria continuing since D-TBI will be required. The data will be analyzed by comparing the serum mass profiles for the groups as follows: (1) All PT-CM vs. their CS, (2) All I-CM vs their CS, and (3) All PT-CM vs I-CM. The PT-CM will then be subdivided by time since TBI at 2-6 years and 7-12 years and these subgroups compared to determi
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610295
Entities
People
- J.R. Couch
Organizations
- United States Army
- University of Oklahoma Health Sciences Center