Follow-Up of Post-Traumatic Headache Patients: A Multicenter Prospective Study on Headache Phenotype and Impact after...

Post-traumatic headache (PTH) is one of the most disabling sequelae of mild traumatic brain injury (mTBI); however, its clinical determinants and long-term trajectories remain poorly defined. We conducted a large, multicenter, prospective follow-up study to characterize the phenotypic spectrum of persistent PTH, identify predictors of persistence, and explore the role of pre-existing migraine in shaping headache outcomes after mTBI. A total of 478 adults (52.1% male, mean age 40.5 ± 18.7 years) with mTBI were recruited and evaluated by experienced neurologists at two time points: immediately after mTBI and at 6 months post injury. Demographic data and detailed headache features were collected using clinical examination and standardized questionnaires, administered face-to-face during the first visit and either face-to-face or by phone at the 6-month follow-up by physicians. Headache-related disability, depression, and insomnia were assessed using the Headache Impact Test (HIT-6), Beck Depression Inventory (BDI), and Insomnia Severity Index (ISI), respectively. Statistical analyses included classification tree analysis to identify predictors of persistent PTH and K-means clustering to delineate phenotypic subgroups. Overall, 22.6% of patients developed persistent PTH at 6 months. Pre-existing headache (PH) was reported in 31.4% of participants, predominantly migraine (57.3%). Patients with pre-existing migraine more frequently exhibited migraine-like PTH features (throbbing quality, unilateral localization, longer headache attack duration, and associated symptoms such as nausea, photophobia, and phonophobia) and scored significantly higher on the HIT-6, numeric rating scale (NRS) for headache severity, ISI, and BDI, indicating greater disability, pain severity, insomnia, and depressive symptoms (p < 0.01 for all). Classification tree analysis revealed two robust predictors of persistent PTH: acute PTH lasting more than 30 consecutive days and an initial HIT-6 score greater than 45. Furthermore, cluster analysis of patients with persistent PTH identified two phenotypic groups. Cluster 1 (n = 47) comprised patients with ≥ 180 days of continuous headache, high disability, and poor sleep quality, whereas Cluster 2 (n = 60) included patients with shorter headache duration following mTBI (<180 days), lower disability, and infrequent, shorter headache attacks. This study demonstrates that nearly one in four patients with mTBI experiences persistent PTH. Early indicators of persistence, particularly prolonged continuous headache and higher disability, may help identify high-risk individuals who warrant early aggressive, targeted interventions. Recognition of distinct PTH clusters reflects the heterogeneity of this frequent but under-investigated disorder with high burden and highlights the need for early and tailored management strategies.