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      Facial nerve stimulation as a future treatment for ischemic stroke

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          Abstract

          Stimulation of the autonomic parasympathetic fibers of the facial nerve system (hereafter simply “facial nerve”) rapidly dilates the cerebral arteries and increases cerebral blood flow whether that stimulation is delivered at the facial nerve trunk or at distal points such as the sphenopalatine ganglion. Facial nerve stimulation thus could be used as an emergency treatment of conditions of brain ischemia such as ischemic stroke. A rich history of scientific research has examined this property of the facial nerve, and various means of activating the facial nerve can be employed including noninvasive means. Herein, we review the anatomical and physiological research behind facial nerve stimulation and the facial nerve stimulation devices that are in development for the treatment of ischemic stroke.

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          Collateral circulation.

          David Liebeskind (2003)
          The collateral circulation plays a pivotal role in the pathophysiology of cerebral ischemia. Current knowledge of the collateral circulation remains sparse, largely because of prior limitations in methods for evaluation of these diminutive routes of cerebral blood flow. Anatomic descriptions of the collateral circulation often focus on more proximal anastomoses at the circle of Willis, neglecting secondary collateral pathways provided by leptomeningeal vessels. Pathophysiological recruitment of collateral vessels likely depends on the temporal course of numerous compensatory hemodynamic, metabolic, and neural mechanisms. Subsequent endurance of these protective vascular pathways may determine the severity of ischemic injury. Characterization of the collateral circulation with advanced neuroimaging modalities that provide angiographic information and perfusion data may elucidate critical determinants of collateral blood flow. Such information on the status of the collateral circulation may be used to guide therapeutic interventions. Prognostication and risk stratification may also be improved by routine evaluation of collateral blood flow. Contemporary understanding of the collateral circulation may be greatly enhanced through further refinement of neuroimaging modalities that correlate angiographic findings with perfusion status, providing the basis for future therapeutic and prognostic applications.
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            Good clinical outcome after ischemic stroke with successful revascularization is time-dependent.

            Harsh Khatri, Barry J. Broderick, S Yeatts … (2009)
            Trials of IV recombinant tissue plasminogen activator (rt-PA) have demonstrated that longer times from ischemic stroke symptom onset to initiation of treatment are associated with progressively lower likelihoods of clinical benefit, and likely no benefit beyond 4.5 hours. How the timing of IV rt-PA initiation relates to timing of restoration of blood flow has been unclear. An understanding of the relationship between timing of angiographic reperfusion and clinical outcome is needed to establish time parameters for intraarterial (IA) therapies. The Interventional Management of Stroke pilot trials tested combined IV/IA therapy for moderate-to-severe ischemic strokes within 3 hours from symptom onset. To isolate the effect of time to angiographic reperfusion on clinical outcome, we analyzed only middle cerebral artery and distal internal carotid artery occlusions with successful reperfusion (Thrombolysis in Cerebral Infarction 2-3) during the interventional procedure (<7 hours). Time to angiographic reperfusion was defined as time from stroke onset to procedure termination. Good clinical outcome was defined as modified Rankin Score 0-2 at 3 months. Among the 54 cases, only time to angiographic reperfusion and age independently predicted good clinical outcome after angiographic reperfusion. The probability of good clinical outcome decreased as time to angiographic reperfusion increased (unadjusted p = 0.02, adjusted p = 0.01) and approached that of cases without angiographic reperfusion within 7 hours. We provide evidence that good clinical outcome following angiographically successful reperfusion is significantly time-dependent. At later times, angiographic reperfusion may be associated with a poor risk-benefit ratio in unselected patients.
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              Safety of tPA in stroke mimics and neuroimaging-negative cerebral ischemia.

              Mariana A Barreto, Sean I. Savitz, Jazmin I. Acosta … (2010)
              Patients with acute neurologic symptoms may have other causes simulating ischemic stroke, called stroke mimics (SM), but they may also have averted strokes that do not appear as infarcts on neuroimaging, which we call neuroimaging-negative cerebral ischemia (NNCI). We determined the safety and outcome of IV thrombolysis within 3 hours of symptom onset in patients with SM and NNCI. Patients treated with IV tissue plasminogen activator (tPA) within 3 hours of symptom onset were identified from our stroke registry from June 2004 to October 2008. We collected admission NIH Stroke Scale (NIHSS) score, modified Rankin score (mRS), length of stay (LOS), symptomatic intracerebral hemorrhage (sICH), and discharge diagnosis. Among 512 treated patients, 21% were found not to have an infarct on follow-up imaging. In the SM group (14%), average age was 55 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. The most common etiologies were seizure, complicated migraine, and conversion disorder. In the NNCI group (7%), average age was 61 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. Nearly all SM (87%) and NNCI (91%) patients were functionally independent on discharge (mRS 0-1). Our data support the safety of administering IV tissue plasminogen activator to patients with suspected acute cerebral ischemia within 3 hours of symptom onset, even when the diagnosis ultimately is found not to be stroke or imaging does not show an infarct.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Brain Circ
                Journal ID (iso-abbrev): Brain Circ
                Journal ID (publisher-id): BC
                Title: Brain Circulation
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 2394-8108
                ISSN (Electronic): 2455-4626
                Publication date (Print): Oct-Dec 2016
                Publication date (Electronic): 06 December 2016
                Volume: 2
                Issue: 4
                Pages: 164-177
                Affiliations
                [1] Centro Nacional de Investigación en Imagenología e Instrumentación Médica, Universidad Autónoma Metropolitana, Iztapalapa, Mexico City, Mexico, NeuroSpring, Dover, Delaware, USA
                Author notes
                Address for correspondence: Dr. Mark K Borsody, NeuroSpring, 8 The Green, Suite #4676 Dover, DE 19001, USA. E-mail: mborsody@ 123456neurospring.org
                Article
                Publisher ID: BC-2-164
                DOI: 10.4103/2394-8108.195281
                PMC ID: 6126226
                PubMed ID: 30276294
                SO-VID: 6fac6a58-9e12-4d0b-9680-5b7711b8e14a
                Copyright © Copyright: © 2016 Brain Circulation
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                Date received : 06 June 2016
                Date revision received : 10 August 2016
                Date accepted : 14 August 2016
                Categories
                Subject: Review Article

                Keywords: facial nerve stimulation,future treatment,ischemic stroke
                Data availability:
                Keywords: facial nerve stimulation, future treatment, ischemic stroke

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