Guidelines for TMS/tES Clinical Services and Research through the COVID-19 Pandemic
UMass Chan AffiliationsDepartment of Neurology at UMMS-Baystate
Document TypeAccepted Manuscript
non-invasive brain stimulation
transcranial alternating current stimulation
transcranial direct current stimulation
transcranial electrical stimulation
transcranial magnetic stimulation
Health Services Administration
Nervous System Diseases
Psychiatry and Psychology
MetadataShow full item record
AbstractBACKGROUND: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain relevant expertise spanning NIBS technology, clinical services, and basic and clinical research - with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.
Bikson M, Hanlon CA, Woods AJ, Gillick BT, Charvet L, Lamm C, Madeo G, Holczer A, Almeida J, Antal A, Ay MR, Baeken C, Blumberger DM, Campanella S, Camprodon J, Christiansen L, Colleen L, Crinion J, Fitzgerald P, Gallimberti L, Ghobadi-Azbari P, Ghodratitoostani I, Grabner R, Hartwigsen G, Hirata A, Kirton A, Knotkova H, Krupitsky E, Marangolo P, Nakamura-Palacios EM, Potok W, Praharaj SK, Ruff CC, Schlaug G, Siebner HR, Stagg CJ, Thielscher A, Wenderoth N, Yuan TF, Zhang X, Ekhtiari H. Guidelines for TMS/tES Clinical Services and Research through the COVID-19 Pandemic. Brain Stimul. 2020 May 12:S1935-861X(20)30109-1. doi: 10.1016/j.brs.2020.05.010. Epub ahead of print. PMID: 32413554; PMCID: PMC7217075. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/27499
Full author list omitted for brevity. For the full list of authors, see article.
RightsCopyright © 2020 Published by Elsevier Inc. This is a PDF file of an accepted manuscript that has been accepted for publication and posted with a 12-month embargo and CC BY-NC-ND license as allowed by the publisher's author rights policy at https://www.elsevier.com/about/policies/sharing.
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Interferon-gamma and granulocyte/monocyte colony-stimulating factor production by natural killer cells involves different signaling pathways and the adaptor stimulator of interferon genes (STING)Souza-Fonseca-Guimaraes, Fernando; Parlato, Marianna; DeOliveira, Rosane B.; Golenbock, Douglas T.; Fitzgerald, Katherine A.; Shalova, Irina N.; Biswas, Subhra K.; Cavaillon, Jean-Marc; Adib-Conquy, Minou (2013-04-12)Natural killer (NK) cells are important for innate immunity in particular through the production of IFN-gamma and GM-CSF. Both cytokines are important in restoration of immune function of tolerized leukocytes under inflammatory events. The expression of TLRs in NK cells has been widely studied by analyzing the mRNA of these receptors, rarely seeking their protein expression. We previously showed that murine spleen NK cells express TLR9 intracellularly and respond to CpG oligodeoxynucleotide (CpG-ODN) by producing IFN-gamma and GM-CSF. However, to get such production the presence of accessory cytokines (such as IL-15 and IL-18) was required, whereas CpG-ODN or accessory cytokines alone did not induce IFN-gamma or GM-CSF. We show here that TLR9 overlaps with the Golgi apparatus in NK cells. Furthermore, CpG-ODN stimulation in the presence of accessory cytokines induces the phosphorylation of c-Jun, STAT3, and IkappaBalpha. IFN-gamma and GM-CSF production requires NF-kappaB and STAT3 activation as well as Erk-dependent mechanisms for IFN-gamma and p38 signaling for GM-CSF. Using knock-out-mice, we show that UNC93b1 and IL-12 (produced by NK cells themselves) are also necessary for IFN-gamma and GM-CSF production. IFN-gamma production was found to be MyD88- and TLR9-dependent, whereas GM-CSF was TLR9-independent but dependent on STING (stimulator of interferon genes), a cytosolic adaptor recently described for DNA sensing. Our study thereby allows us to gain insight into the mechanisms of synergy between accessory cytokines and CpG-ODN in NK cells. It also identifies a new and alternative signaling pathway for CpG-ODN in murine NK cells.
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