Barrett, Kevin M.

Abstract Background Post-traumatic headache (PTH) is a common acute and persistent symptom following mild traumatic brain injury (mTBI). Symptoms of cutaneous allodynia and presence of nociceptive sensitization might be associated with acute PTH and its persistence. The objectives of this study were to compare allodynia symptoms and cutaneous heat pain thresholds amongst males and females with acute PTH to healthy controls (HC) and determine if pain thresholds and allodynia symptoms are associated with PTH outcomes. Methods This prospective longitudinal study enrolled 139 adults with acute PTH attributed to mTBI as defined by the International Classification of Headache Disorders and 95 HC. All PTH participants completed a baseline research visit near PTH onset and a follow-up visit three to four months later. All PTH participants and a subset of HC completed the Allodynia Symptom Checklist (ASC-12) at each research visit. A different subset of the participants underwent quantitative sensory testing (QST) during baseline, 4-week, and 16-week research visits to quantify cutaneous heat pain thresholds at the forehead and forearms. Data from daily headache diaries were used to determine longitudinal PTH improvement versus non-improvement at three months. ASC-12 score and pain threshold comparisons were made between PTH and HC groups, PTH improved versus non-improved cohorts, and between PTH males and females. Results Participants with PTH had an average age of 42.6 years and 64.0% were female. HC had an average age of 40.0 years and 65.3% were female. At the first visit, PTH participant ASC-12 scores averaged 3.6 versus 0.1 amongst HC, p < 0.001. 44.8% of PTH participants had headache improvement at 3 months. ASC-12 scores were higher in the PTH non-improved versus improved group at baseline (4.0 versus 2.4, p = 0.038) and 3-month follow-up (3.4 versus 1.9, p = 0.012). ASC-12 scores were higher in females than males at baseline (4.7 versus 1.6, p < 0.001) and 3-months (3.9 versus 1.2, p < 0.001). Cutaneous heat pain thresholds at the forehead and forearm did not differ between any group. Conclusions PTH attributed to mTBI is associated with symptoms of cutaneous allodynia. Greater allodynia symptoms are present in females with PTH compared to males and may be associated with PTH non-improvement.

Background and Objectives: It is unclear whether induced hypertension in acute ischemic stroke (AIS) may improve long-term outcomes. We conducted a systematic review and meta-analysis to compare the safety and efficacy of induced hypertension vs standard medical care in patients presenting with acute ischemic stroke within 72 hours of symptom onset. Methods: Two reviewers systematically searched PubMed using the prespecified terms “induced hypertension” or “blood pressure augmentation” plus “ischemic stroke” for clinical trials that reported functional independence (mRS 0-2) at 90 days. The safety outcome was symptomatic intracranial hemorrhage (sICH). Pooled odds ratio (OR) and 95% CI across trials were synthesized using fixed-effect model based on Mantel-Haenszel methods. Forest plots were constructed. Results: Three clinical trials with 270 AIS patients treated with induced hypertension (n=126) or standard medical care (n= 144) were included. Mean age was 66.6 years, 35.2% were women, and the mean initial NIHSS was 7.5. The rate of functional independence at 90 days was higher in patients treated with induced hypertension (70.6%) versus control (54.9%) (OR 1.88; 95% CI 1.13-3.11; p=0.01). sICH did not differ between patients treated with induced hypertension (<1%) versus control (<1%) (OR 1.03; 95% CI 0.14-7.45; p=0.98). Discussion: Among patients presenting with acute ischemic stroke with 72 hours of symptoms onset, induced hypertension resulted in better functional outcome at 90 days than standard medical care and did not increase risk of sICH. Large RCTs to test this observation are ongoing and needed to guide clinical practice.