Clinical predictors of poor 30-day headache outcomes after an emergency department visit for acute post-traumatic headache.

PURPOSE: We investigated clinical risk factors that predict poor 30-day headache outcomes among patients evaluated in the emergency department (ED) for post-traumatic headache (PTH). METHODS: This was an analysis of data from a randomized, placebo-controlled study of IV metoclopramide + diphenhydramine for acute PTH. Patients were enrolled during an ED visit and received telephone follow-up with a structured questionnaire 30 days later. The primary outcome was frequency of headaches 30 days after ED discharge. We used multivariable logistic regression models to determine which clinical variables were associated with frequent headaches at 30 days. RESULTS: In total, 160 patients were enrolled in the study. 134 (84%) patients completed the 30-day questionnaire and were included in the analysis, including 90 females and 44 males. 30 patients (22%, 95% CI = 0.16 to 0.30) reported frequent headaches at 30-day follow-up. In the multivariable analysis, female sex (OR = 4.03, 95% CI = 1.23±13.13), patients who blamed themselves for their injury (OR = 0.13, 95% CI = 0.04±0.45), and patients who were unsure if they sustained loss of consciousness during the traumatic incident (OR = 5.63, 95% CI = 1.89±16.78) were found to be associated with poor 30-day outcomes. Medication received in the ED and age were not associated. CONCLUSIONS: More than 1 out of five patients treated in the ED for acute PTH experienced frequent headaches 30 days later. Women and patients who were uncertain as to whether they had experienced loss of consciousness were at increased risk of frequent PTH. Blaming oneself for the head trauma was associated with less frequent PTH.

Activity-Induced Synaptic Structural Modifications by an Activator of Integrin Signaling at the Drosophila Neuromuscular Junction.

Activity-induced synaptic structural modification is crucial for neural development and synaptic plasticity, but the molecular players involved in this process are not well defined. Here, we report that a protein named Shriveled (Shv) regulates synaptic growth and activity-dependent synaptic remodeling at the Drosophila neuromuscular junction. Depletion of Shv causes synaptic overgrowth and an accumulation of immature boutons. We find that Shv physically and genetically interacts with ßPS integrin. Furthermore, Shv is secreted during intense, but not mild, neuronal activity to acutely activate integrin signaling, induce synaptic bouton enlargement, and increase postsynaptic glutamate receptor abundance. Consequently, loss of Shv prevents activity-induced synapse maturation and abolishes post-tetanic potentiation, a form of synaptic plasticity. Our data identify Shv as a novel trans-synaptic signal secreted upon intense neuronal activity to promote synapse remodeling through integrin receptor signaling.SIGNIFICANCE STATEMENT The ability of neurons to rapidly modify synaptic structure in response to neuronal activity, a process called activity-induced structural remodeling, is crucial for neuronal development and complex brain functions. The molecular players that are important for this fundamental biological process are not well understood. Here we show that the Shriveled (Shv) protein is required during development to maintain normal synaptic growth. We further demonstrate that Shv is selectively released during intense neuronal activity, but not mild neuronal activity, to acutely activate integrin signaling and trigger structural modifications at the Drosophila neuromuscular junction. This work identifies Shv as a key modulator of activity-induced structural remodeling and suggests that neurons use distinct molecular cues to differentially modulate synaptic growth and remodeling to meet synaptic demand.