Roles for substance P and gastrin-releasing peptide as neurotransmitters released by primary afferent pruriceptors.

Recent studies support roles for neurokinin-1 (NK-1) and gastrin-releasing peptide (GRP) receptor-expressing spinal neurons in itch. We presently investigated expression of substance P (SP) and GRP in pruritogen-responsive primary sensory neurons and roles for these neuropeptides in itch signaling. Responses of dorsal root ganglion (DRG) cells to various pruritogens were observed by calcium imaging. DRG cells were then processed for SP, GRP, and isolectin B-4 (IB4; a marker for nonpeptidergic neurons) immunofluorescence. Of pruritogen-responsive DRG cells, 11.8-26.8%, 21.8-40.0%, and 21.4-26.8% were immunopositive for SP, GRP, and IB4, respectively. In behavioral studies, both systemic and intrathecal administration of a NK-1 receptor antagonist significantly attenuated scratching evoked by chloroquine and a protease-activated receptor 2 agonist, SLIGRL, but not histamine, bovine adrenal medulla peptide 8-22 (BAM8-22), or serotonin. Systemic or intrathecal administration of a GRP receptor antagonist attenuated scratching evoked by chloroquine and SLIGRL but not BAM8-22 or histamine. The GRP receptor antagonist enhanced scratching evoked by serotonin. These results indicate that SP and GRP expressed in primary sensory neurons are partially involved as neurotransmitters in histamine-independent itch signaling from the skin to the spinal cord.

Rescue therapy after thrombectomy for large vessel occlusion due to underlying atherosclerosis: review of literature.

In this review article, we summarized the current advances in rescue management for reperfusion therapy of acute ischemic stroke from large vessel occlusion due to underlying intracranial atherosclerotic stenosis (ICAS). It is estimated that 24-47% of patients with acute vertebrobasilar artery occlusion have underlying ICAS and superimposed in situ thrombosis. These patients have been found to have longer procedure times, lower recanalization rates, higher rates of reocclusion and lower rates of favorable outcomes than patients with embolic occlusion. Here, we discuss the most recent literature regarding the use of glycoprotein IIb/IIIa inhibitors, angioplasty alone, or angioplasty with stenting for rescue therapy in the setting of failed recanalization or instant/imminent reocclusion during thrombectomy. We also present a case of rescue therapy post intravenous tPA and thrombectomy with intra-arterial tirofiban and balloon angioplasty followed by oral dual antiplatelet therapy in a patient with dominant vertebral artery occlusion due to ICAS. Based on the available literature data, we conclude that glycoprotein IIb/IIIa is a reasonably safe and effective rescue therapy for patients who have had a failed thrombectomy or have residual severe intracranial stenosis. Balloon angioplasty and/or stenting may be helpful as a rescue treatment for patients who have had a failed thrombectomy or are at risk of reocclusion. The effectiveness of immediate stenting for residual stenosis after successful thrombectomy is still uncertain. Rescue therapy does not appear to increase the risk of sICH. Randomized controlled trials are warranted to prove the efficacy of rescue therapy.

Impact of an automated large vessel occlusion detection tool on clinical workflow and patient outcomes.

Purpose: Automated large vessel occlusion (LVO) tools allow for prompt identification of positive LVO cases, but little is known about their role in acute stroke triage when implemented in a real-world setting. The purpose of this study was to evaluate the automated LVO detection tool's impact on acute stroke workflow and clinical outcomes. Materials and methods: Consecutive patients with a computed tomography angiography (CTA) presenting with suspected acute ischemic stroke were compared before and after the implementation of an AI tool, RAPID LVO (RAPID 4.9, iSchemaView, Menlo Park, CA). Radiology CTA report turnaround times (TAT), door-to-treatment times, and the NIH stroke scale (NIHSS) after treatment were evaluated. Results: A total of 439 cases in the pre-AI group and 321 cases in the post-AI group were included, with 62 (14.12%) and 43 (13.40%) cases, respectively, receiving acute therapies. The AI tool demonstrated a sensitivity of 0.96, a specificity of 0.85, a negative predictive value of 0.99, and a positive predictive value of 0.53. Radiology CTA report TAT significantly improved post-AI (mean 30.58 min for pre-AI vs. 22 min for post-AI, p < 0.0005), notably at the resident level (p < 0.0003) but not at higher levels of expertise. There were no differences in door-to-treatment times, but the NIHSS at discharge was improved for the pre-AI group adjusted for confounders (parameter estimate = 3.97, p < 0.01). Conclusion: Implementation of an automated LVO detection tool improved radiology TAT but did not translate to improved stroke metrics and outcomes in a real-world setting.

Impact of COVID-19 on Acute Stroke Presentation at a Comprehensive Stroke Center.

Background: COVID-19 has impacted healthcare in many ways, including presentation of acute stroke. Since time-sensitive thrombolysis is essential for reducing morbidity and mortality in acute stroke, any delays due to the pandemic can have serious consequences. Methods: We retrospectively reviewed the electronic medical records for patients presenting with acute ischemic stroke at a comprehensive stroke center in March-April 2020 (the early months of COVID-19) and compared to the same time period in 2019. Stroke metrics such as incidence, time to arrival, and immediate outcomes were assessed. Results: There were 48 acute ischemic strokes (of which 7 were transfers) in March-April 2020 compared to 64 (of which 12 were transfers) in 2019. The average last known well to arrival time (±SD) for stroke codes was 1,041 (±1682.1) min in 2020 and 554 (±604.9) min in 2019. Of the patients presenting directly to the ED with a known last known well time, 27.8% (10/36) presented in the first 4.5 h in 2020, in contrast to 40.5% (15/37) in 2019. Patients who died comprised 10.4% of the stroke cohort in 2020 (5/48) compared to 6.3% in 2019 (4/64). Conclusions: During the first 2 months of COVID-19, there were fewer overall stroke cases who presented to our hospital, and of these cases, there was delayed presentation in comparison to the same time period in 2019. Recognizing how stroke presentation may be affected by COVID-19 would allow for optimization of established stroke triage algorithms in order to ensure safe and timely delivery of stroke care during a pandemic.

Opposing effects of cervical spinal cold block on spinal itch and pain transmission.

Inactivation of descending pathways enhanced responses of spinal dorsal horn neurons to noxious stimuli, but little is known regarding tonic descending modulation of spinal itch transmission. To study effects of cervical spinal cold block on responses of dorsal horn neurons to itch-evoking and pain-evoking stimuli, single-unit recordings were made from superficial dorsal horn wide dynamic range and nociceptive-specific-type neurons in pentobarbital-anesthetized mice. Intradermal histamine excited 17 units. Cold block starting 1 minute after intradermal injection of histamine caused a marked decrease in firing. The histamine-evoked response during and following cold block was significantly lower compared with control histamine-evoked responses in the absence of cold block. A similar but weaker depressant effect of cold block was observed for dorsal horn unit responses to chloroquine. Twenty-six units responded to mustard oil allyl isothiocyanate (AITC), with a further significant increase in firing during the 1-minute period of cold block beginning 1 minute after AITC application. Activity during cold block was significantly greater compared with the same time period of control responses to AITC in the absence of cold block. Ten units' responses to noxious heat were significantly enhanced during cold block, while 6 units' responses were reduced and 18 unaffected. Cold block had no effect on mechanically evoked responses. These results indicate that spinal chemonociceptive transmission is under tonic descending inhibitory modulation, while spinal pruriceptive transmission is under an opposing, tonic descending facilitatory modulation.

Involvement of TRPV4 in Serotonin-Evoked Scratching.

Several thermosensitive transient receptor potential channels (transient receptor potential vanilloid type-1, -3; transient receptor potential cation channel, subfamily A, member 1) have been implicated in itch. In contrast, the role of transient receptor potential vanilloid type-4 (TRPV4) in itch is unknown. Therefore, we investigated if TRPV4, a temperature-sensitive cation channel, plays an important role in acute itch in mice. Four different pruritogens, including serotonin (5-hydroxytryptamine [5-HT]), histamine, SLIGRL (protease-activated receptors 2/mas-related G-protein-coupled receptor C11 agonist), and chloroquine (mas-related G-protein-coupled receptor A3 agonist), were intradermally injected into mice and itch-related scratching behavior was assessed. TRPV4 knockout mice exhibited significantly fewer 5-HT-evoked scratching bouts compared with wild-type mice. Notably, no differences between TRPV4 knockout and wild-type mice were observed in the number of scratch bouts elicited by SLIGRL and histamine. Pretreatment with a TRPV4 antagonist significantly attenuated 5-HT-evoked scratching in vivo. Using calcium imaging in cultured primary murine dorsal root ganglion neurons, the response of neurons after 5-HT application, but not other pruritogens, was significantly lower in TRPV4 knockout compared with wild-type mice. A TRPV4 antagonist significantly suppressed 5-HT-evoked responses in dorsal root ganglion cells from wild-type mice. Approximately 90% of 5-HT-sensitive dorsal root ganglion neurons were immunoreactive for an antibody to TRPV4, as assessed by calcium imaging. These results indicate that 5-HT-induced itch is linked to TRPV4.