Pain Trajectories Following Subarachnoid Hemorrhage are Associated with Continued Opioid Use at Outpatient Follow-up.

BACKGROUND: Subarachnoid hemorrhage (SAH) is characterized by the worst headache of life and associated with long-term opioid use. Discrete pain trajectories predict chronic opioid use following other etiologies of acute pain, but it is unknown whether they exist following SAH. If discrete pain trajectories following SAH exist, it is uncertain whether they predict long-term opioid use. We sought to characterize pain trajectories after SAH and determine whether they are associated with persistent opioid use. METHODS: We reviewed pain scores from patients admitted to a single tertiary care center for SAH from November 2015 to September 2019. Group-based trajectory modeling identified discrete pain trajectories during hospitalization. We compared outcomes across trajectory groups using χ2 and Kruskal-Wallis tests. Multivariable regression determined whether trajectory group membership was an independent predictor of long-term opioid use, defined as continued use at outpatient follow-up. RESULTS: We identified five discrete pain trajectories among 305 patients. Group 1 remained pain free. Group 2 reported low scores with intermittent spikes and slight increase over time. Group 3 noted increasing pain severity through day 7 with mild improvement until day 14. Group 4 experienced maximum pain with steady decrement over time. Group 5 reported moderate pain with subtle improvement. In multivariable analysis, trajectory groups 3 (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.5-8.3) and 5 (OR 8.0; 95% CI 3.1-21.1), history of depression (OR 3.6; 95% CI 1.3-10.0) and racial/ethnic minority (OR 2.3; 95% CI 1.3-4.1) were associated with continued opioid use at follow-up (median 62 days following admission, interquartile range 48-96). CONCLUSIONS: Discrete pain trajectories following SAH exist. Recognition of pain trajectories may help identify those at risk for long-term opioid use.

Bhlhb5::flpo allele uncovers a requirement for Bhlhb5 for the development of the dorsal cochlear nucleus.

Auditory information is initially processed in the cochlear nuclei before being relayed to the brain. The cochlear nuclei are subdivided into dorsal, anterior ventral, and posterior ventral domains, each containing several subtypes of neurons that are thought to play discrete roles in the processing of sound. However, the ontogeny of these neurons is poorly understood, and this gap in knowledge hampers efforts to understand the basic neural circuitry of this nucleus. Here, we reveal that Bhlhb5 is expressed in both excitatory (unipolar brush cells) and inhibitory neurons (cartwheel cells) of the DCN during development. To gain genetic access to Bhlhb5-expressing neurons in the DCN, we generated a Bhlhb5::flpo knockin allele. Using an intersectional genetic strategy, we labeled cartwheel cells, thereby providing proof of concept that subpopulations of Bhlhb5-expressing neurons can be genetically targeted. Moreover, fate-mapping experiments using this allele revealed that Bhlhb5 is required for the proper development of the DCN, since mice lacking Bhlhb5 showed a dramatically diminished number of neurons, including unipolar brush and cartwheel cells. Intriguingly, the Bhlhb5::flpo allele also genetically labels numerous other regions of the nervous system that process sensory input, including the dorsal horn, the retina, and the nucleus of the lateral olfactory tract, hinting at a more general role for Bhlhb5 in the development of neurons that mediate sensory integration.

Comparison of induction agents for rapid sequence intubation in refractory status epilepticus: A single-center retrospective analysis.

Endotracheal intubation, frequently required during management of refractory status epilepticus (RSE), can be facilitated by anesthetic medications; however, their effectiveness for RSE control is unknown. We performed a single-center retrospective review of patients admitted to a neurocritical care unit (NCCU) who underwent in-hospital intubation during RSE management. Patients intubated with propofol, ketamine, or benzodiazepines, termed anti-seizure induction (ASI), were compared to patients who received etomidate induction (EI). The primary endpoint was clinical or electrographic seizures within 12 h post-intubation. We estimated the association of ASI on post-intubation seizure using logistic regression. A sub-group of patients undergoing electroencephalography during intubation was identified to evaluate the immediate effect of ASI on RSE. We screened 697 patients admitted to the NCCU for RSE and identified 148 intubated in-hospital (n = 90 ASI, n = 58 EI). There was no difference in post-intubation seizure (26 % (n = 23) ASI, 29 % (n = 17) EI) in the cohort, however, there was increased RSE resolution with ASI in 24 patients with electrographic RSE during intubation (ASI: 61 % (n = 11/18) vs EI: 0 % (n = 0/6), p =.016). While anti-seizure induction did not appear to affect post-intubation seizure occurrence overall, a sub-group of patients undergoing electroencephalography during intubation had a higher incidence of seizure cessation, suggesting potential benefit in an enriched population.

Pain Control and Anxiolysis After Subarachnoid Hemorrhage Using Immersive Virtual Reality: A Case Report.

Debilitating headache persists after acute aneurysmal subarachnoid hemorrhage (SAH). Despite high prevalence, little is known regarding optimal treatment strategies for SAH-related headache. Nonpharmacologic adjunctive therapies are emerging as tools to help treat pain and limit opioid exposure in the hospital. Virtual reality (VR) is an immersive audiovisual experience that has been shown to reduce pain perception in other patient populations. The role of VR in acute brain injury is unknown. Here we report a patient with SAH who suffered from persistent headache during her hospitalization despite escalation of analgesic pharmacotherapy. A trial of VR was used as an adjunct to medication over four days. The patient reported subjective improvement in pain and anxiety. VR may provide additional analgesia and anxiolysis over pharmacologic measures alone and warrants further study in patients with acute brain injury.

Association of Refractory Pain in the Acute Phase After Subarachnoid Hemorrhage With Continued Outpatient Opioid Use.

OBJECTIVE: Little is known about the prevalence of continued opioid use following aneurysmal subarachnoid hemorrhage (aSAH) despite guidelines recommending their use during the acute phase of disease. We sought to determine prevalence of opioid use following aSAH and test the hypothesis that acute pain and higher inpatient opioid dose increased outpatient opioid use. METHODS: We reviewed consecutively admitted patients with aSAH from November 2015 through September 2019. We retrospectively collected pain scores and daily doses of analgesics. Pain burden was calculated as area under the pain-time curve. Univariate and multivariable regression models determined risk factors for continued opioid use at discharge and outpatient follow-up. RESULTS: We identified 234 patients with aSAH with outpatient follow-up. Continued opioid use was common at discharge (55% of patients) and follow-up (47% of patients, median 63 [interquartile range 49-96] days from admission). Pain burden, craniotomy, and racial or ethnic minority status were associated with discharge opioid prescription in multivariable analysis. At outpatient follow-up, pain burden (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.5-2.4), depression (OR 3.1, 95% CI 1.1-8.8), and racial or ethnic minority status (OR 2.1, 95% CI 1.1-4.0) were independently associated with continued opioid use; inpatient opioid dose was not. CONCLUSION: Continued opioid use following aSAH is prevalent and related to refractory pain during acute illness, but not inpatient opioid dose. More efficacious analgesic strategies are needed to reduce continued opioid use in patients following aSAH. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that continued opioid use following aSAH is associated with refractory pain during acute illness but not hospital opioid exposure.

Early Multicenter Experience With the Neuroform Atlas Stent: Feasibility, Safety, and Efficacy.

BACKGROUND: The Neuroform Atlas stent™ (by Stryker, Fremont, California) represents the most recent widely available upgrade to intracranial stenting, providing a laser cut open cell stent with a diameter of 3.0 to 4.5 mm that is delivered through an 0.017-inch microcatheter. OBJECTIVE: To report our initial multicenter experience of the safety, efficacy, and feasibility of the Atlas stent used for treating aneurysms, as well as one case of intracranial stenosis and one carotid artery dissection as well as other pathologies. METHODS: A retrospective multicenter study of subjects treated with Atlas stent during the period 2018 to 2019. RESULTS: The total number of patients included in our analysis was 71 patients. The stent was utilized to treat 69 aneurysm cases. Of the aneurysms, 36% presented with acute rupture and 56% of the ruptured aneurysms were high grade. Mean aneurysm dimension was 7 mm with an average neck width of 4.1 mm. Around 30% had received prior treatment. Telescoping or Y-stent was used in 16% of cases. We did not observe any symptomatic major complications in our series. Asymptomatic major complications were seen in 7 patients (10.1%); technical complications occurred in 4.3%. Immediate modified Raymond-Roy-occlusion-outcome class I/II was observed in 87%, and this increased to 97.7% at latest follow-up, which was at 4 mo; 91.8% of patients achieved favorable clinical outcome, and mortality rate was 1.4%. CONCLUSION: Our series demonstrates the safety, feasibility, and efficacy of the Atlas stent. The low complication rate and the high obliteration rate managing complex aneurysms, even in an acute ruptured setting, are notable.

Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord.

Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5(-/-) mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch.

Physiological, behavioral and maternal factors that contribute to size variation in larval amphibian populations.

Size variance among similarly aged individuals within populations is a pattern common to many organisms that is a result of interactions between intrinsic and extrinsic traits of individuals. While genetic and maternal effects, as well as physiological and behavioral traits have been shown to contribute to size variation in animal populations, teasing apart the influence of such factors on individual growth rates remain a challenge. Furthermore, tracing the effects of these interactions across life stages and in shaping adult phenotypes also requires further exploration. In this study we investigated the relationship between genetics, hatching patterns, behaviors, neuroendocrine stress axis activity and variance in growth and metamorphosis among same-aged larval amphibians. Through parallel experiments we found that in the absence of conspecific interactions, hatch time and to a lesser extent egg clutch identity (i.e. genetics and maternal effects) influenced the propensity for growth and development in individual tadpoles and determined metamorphic traits. Within experimental groups we found that variance in growth rates was associated with size-dependent foraging behaviors and responses to food restriction. We also found an inverse relationship between glucocorticoid (GC) hormone levels and body mass and developmental stage among group-reared tadpoles, which suggests that GC expression plays a role in regulating differing within-population growth trajectories in response to density-dependent conditions. Taken together these findings suggest that factors that influence hatching conditions can have long-term effects on growth and development. These results also raise compelling questions regarding the extent to which maternal and genetic factors influence physiological and behavioral profiles in amphibians.