Clinical Characteristics and Pathophysiology of Post-Traumatic Headache

Clinical Characteristics and Pathophysiology of Post-Traumatic Headache

To better understand the clinical characteristics and complex pathophysiological events that constitute persistent post-traumatic headache (PPTH) and to identify possible calcitonin gene-related peptide (CGRP) hypersensitivity in PPTH patients.

The present project will embark upon identifying novel PTH-specific biomarkers by incorporating a plethora of scientific approaches. First, clinical biomarkers will be assessed by deep phenotyping of clinical characteristics and associated comorbidities using a semi-structured interview and multiple validated questionnaires. Second, biochemical biomarkers will be determined by plasma levels measurements of blood markers for headache hypersensitivity and neuronal/axonal damage. Third, imaging biomarkers will be established by magnetic resonance imaging (MRI) to assess structural and functional changes in the brain. Lastly, molecular biomarkers will be identified by examining whether intravenous infusion of calcitonin gene-related peptide (CGRP) provokes headache attacks mimicking the usual headache phenotype in subjects with PTH. This would determine whether PTH patients exhibit hypersensitivity to CGRP (molecular biomarker) and advance our understanding of the complex pathophysiological events that constitute the headache phenotypes in PTH sufferers.

Inclusion Criteria for PPTH patients:

• 18-65 years of age
• Subject has PPTH in accordance with the diagnostic criteria of the International Headache Society (IHS)
• Concussion (mild traumatic brain injury) occured > 12 months ago
• Subject, who are fertile women, must be on safe contraceptives

Exclusion Criteria for PPTH patients:

• Pre-trauma existing primary headache disorder (maximum 1 day/per month with tension-type headache) and medication-overuse headache
• > 1 episode with a sustained concussion
• Whiplash
• Pregnant or lactating women
• Cardiovascular disease of any kind
• Hypertension on the experimental day
• Hypotension on the experimental day
• Pre-trauma existing psychiatric disorder of any kind - unless well-regulated
• Any anamnestic or clinical signs of any kind deemed relevant for the study by the physician examining the subject
• Any MRI contraindication and a wish of not being informed about unexpected MRI changes