Brennan, K. C.

Abstract Objective To examine whether sensory hypersensitivity contributes to headache‐related disability in a secondary analysis of patients with post‐traumatic headache. Background Up to one‐third of individuals with traumatic brain injuries report persistent headache 3 months post‐injury. High rates of allodynia and photophobia have been observed in clinical studies and animal models of post‐traumatic headache, but we do not fully understand how sensory amplifications impact post‐traumatic headache‐related disability. Methods We identified a cross‐sectional sample of patients from the American Registry for Migraine Research database with new or worsening headaches post‐head injury from 2016 to 2020 and performed a secondary analysis of those data. We modeled the relationship between sensory sensitivity and Migraine Disability Assessment scores using questionnaires. Candidate variables included data collection features (study site and year), headache‐related and general clinical features (headache frequency, migraine diagnosis, abuse history, sex, age, cognitive and affective symptom scores), and sensory symptoms (related to light, sound, and touch sensitivity). Results The final sample included 193 patients (median age 46, IQR 22; 161/193, 83.4% female). Migraine Disability Assessment scores ranged from 0 to 260 (median 47, IQR 87). The final model included allodynia, hyperacusis, photosensitivity, headache days per month, abuse history, anxiety and depression, cognitive dysfunction, and age ( R 2 = 0.43). An increase of one point in allodynia score corresponded to a 3% increase in headache disability (95% CI: 0%–7%; p = 0.027), an increase of one‐tenth of a point in the photosensitivity score corresponded to a 12% increase (95% CI: 3%–25%; p = 0.002), and an increase of one point in the hyperacusis score corresponded to a 2% increase (95% CI: 0%–4%; p = 0.016). Conclusions Increased photosensitivity, allodynia, and hyperacusis were associated with increased headache‐related disability in this sample of patients with post‐traumatic headache. Symptoms of sensory amplification likely contribute to post‐traumatic headache‐related disability and merit an ongoing investigation into their potential as disease markers and treatment targets.

Abstract Objective To investigate the impact of having headaches prior to traumatic brain injury (TBI) on headache features and long‐term patient health outcomes. Background and Methods This was an exploratory analysis of patients with TBI who were enrolled in the American Registry for Migraine Research (ARMR), a multicenter, prospective, longitudinal patient registry composed of patients with International Classification of Headache Disorders, 3rd edition (ICHD‐3)–defined headache diagnoses. The ARMR study enrolled 2,707 patients between February 1, 2016 and May 6, 2020, 565 of whom qualified for this analysis. Those with headaches prior to their TBI were compared to those without headaches prior to their TBI for ICHD‐3 diagnoses, headache frequency and intensity, headache‐related disability (Migraine Disability Assessment score), symptoms of anxiety (General Anxiety Disorder [GAD‐7]), depression (two items from Patient Health Questionnaire‐9), post‐traumatic stress disorder (PTSD), cutaneous allodynia (12‐item Allodynia Symptom Checklist [ASC‐12]), cognitive dysfunction (Migraine Attacks Subjective Cognitive Impairments Scale [Mig‐SCog]), pain interference (Patient‐Reported Outcomes Measurement Information System‐Pain Interference), and work productivity (Work Productivity and Activity Impairment). Results Among 565 participants with TBI, 350 had headaches prior to their TBI. Those with pre‐TBI headaches were less likely to receive a diagnosis of post‐traumatic headache (PTH; 14/350 [4.0%] vs. 21/215 [9.8%], p = 0.006), even though 25.7% reported new or worsening headaches within 7 days of their TBI. Those with pre‐TBI headaches had higher ASC‐12 scores (2.4 ± 3.5 vs. 1.8 ± 3.4, p = 0.030), Mig‐SCog scores (9.3 ± 4.7 vs. 8 ± 4.9, p = 0.004), and GAD‐7 scores (6.9 ± 5.1 vs. 6.2 ± 5.4, p = 0.039), and were more likely to have a migraine diagnosis (335/350 [95.7%] vs. 192/215 [89.3%], p = 0.003). Conclusions Those with headaches prior to TBI are less likely to receive a diagnosis of PTH. They have more severe symptoms of cutaneous allodynia, cognitive impairment, and generalized anxiety. This analysis suggests that pre‐TBI headaches might impact post‐TBI headache diagnoses and associated features.

Objective To assess photophobia and allodynia in subjects with post-traumatic headache and examine how these sensory hypersensitivities associate with clinical measures of disease burden. Background Post-traumatic headache is the most frequent and disabling long-term consequence of mild traumatic brain injury. There is evidence of sensory dysfunction in acute post-traumatic headache, and it is known from other headache conditions that sensory amplifications correlate with more severe disease. However, systematic studies in post-traumatic headache are surprisingly scarce. Methods We tested light and tactile sensitivity, along with measures of disease burden, in 30 persistent post-traumatic headache subjects and 35 controls. Results In all, 79% of post-traumatic headache subjects exhibited sensory hypersensitivity based on psychophysical assessment. Of those exhibiting hypersensitivity, 54% exhibited both light and tactile sensitivity. Finally, sensory thresholds were correlated across modalities, as well as with headache attack frequency. Conclusions In this study, post-traumatic headache subjects with both light and tactile sensitivity had significantly higher headache frequencies and lower sensitivity thresholds to both modalities, compared to those with single or no sensory hypersensitivity. This pattern suggests that hypersensitivity across multiple modalities may be functionally synergistic, reflect a higher disease burden, and may serve as candidate markers of disease.