Distinguishing persistent post-traumatic headache from migraine: Classification based on clinical symptoms and brain structural MRI data

Abstract

Background Persistent post-traumatic headache most commonly has symptoms that overlap those of migraine. In some cases, it can be clinically difficult to differentiate persistent post-traumatic headache with a migraine phenotype from migraine. The objective of this study was to develop a classification model based on questionnaire data and structural neuroimaging data that distinguishes individuals with migraine from those with persistent post-traumatic headache. Methods Questionnaires assessing headache characteristics, sensory hypersensitivities, cognitive functioning, and mood, as well as T1-weighted magnetic resonance imaging and diffusion tensor data from 34 patients with migraine and 48 patients with persistent post-traumatic headache attributed to mild traumatic brain injury were included for analysis. The majority of patients with persistent post-traumatic headache had a migraine/probable migraine phenotype (77%). A machine-learning leave-one-out cross-validation algorithm determined the average accuracy for distinguishing individual migraine patients from individual patients with persistent post-traumatic headache. Results Based on questionnaire data alone, the average classification accuracy for determining whether an individual person had migraine or persistent post-traumatic headache was 71.9%. Adding imaging data features to the model improved the classification accuracy to 78%, including an average accuracy of 97.1% for identifying individual migraine patients and an average accuracy of 64.6% for identifying individual patients with persistent post-traumatic headache. The most important clinical features that contributed to the classification accuracy included questions related to anxiety and decision making. Cortical brain features and fibertract data from the following regions or tracts most contributed to the classification accuracy: Bilateral superior temporal, inferior parietal and posterior cingulate; right lateral occipital, uncinate, and superior longitudinal fasciculus. A post-hoc analysis showed that compared to incorrectly classified persistent post-traumatic headache patients, those who were correctly classified as having persistent post-traumatic headache had more severe physical, autonomic, anxiety and depression symptoms, were more likely to have post-traumatic stress disorder, and were more likely to have had mild traumatic brain injury attributed to blasts. Discussion A classification model that included a combination of questionnaire data and structural imaging parameters classified individual patients as having migraine versus persistent post-traumatic headache with good accuracy. The most important clinical measures that contributed to the classification accuracy included questions on mood. Regional brain structures and fibertracts that play roles in pain processing and pain integration were important brain features that contributed to the classification accuracy. The lower classification accuracy for patients with persistent post-traumatic headache compared to migraine may be related to greater heterogeneity of patients in the persistent post-traumatic headache cohort regarding their traumatic brain injury mechanisms, and physical, emotional, and cognitive symptoms.