Neuromodulation for COVID-19, Neuromodec update 8: Encouraging news

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Neuromodulationg for COVID-19: Encouraging News

1. Breakthrough trial treats Long-Covid fatigue with targeted wearable neuromodulation and rehabilitation.

In a study published in the prestigious Brain Stimulation journal, a multi-national team reports results from a controlled clinical trial treating fatigue, anxiety, and quality of life on PASC-related fatigue. The trial combines targeted brain stimulation using High-Definition transcranial Direct Current Stimulation (HD-tDCS) and personalized rehabilitation. After just 10 sessions of the intervention patient reports significant reduction in fatigue compared to sham, with no significant side-effects.

The study led by a Dr. Suellen Andrade included members of the team that previously reported a landmark trial shows non-invasive brain stimulation in critically ill COVID-19 patients increases days alive and free of mechanical ventilation. Indeed, both trials used High-Definition tDCS, however the trial differed critically in which brain regions were targeted by HD-tDCS, the nature of targeted rehabilitation, and other factors such as patient inclusion. Dr. Andrade explains:

“We selected High-Definition tDCS because it is uniquely targeted, portable, and brain plasticity boosting. For each application in COVID or Long-Covid, brain targeting is critical to active the implicated brain region in combination with specific rehabilitation protocols. Portability is critical to deploy into diverse environments and for combination with rehabilitation protocols. The plasticity produced by tDCS combines with that driven by rehabilitation.”

Dr. Suellen Andrade will be a plenary speaker at 5th International Brain Stimulation Conference in Feb 2023 addressing neuromodulation for COVID disorders. The importance of targeted protocols was also explained by study collaborator Dr. Marom Bikson on twitter.

Full citation: Brain Stimulation. 2023 Jan 21;16(1):100-107. doi: 10.1016/j.brs.2023.01.1672. Non-invasive brain stimulation for fatigue in post-acute sequelae of SARS-CoV-2 (PASC) Kelly Santana, Eduardo França, João Sato, Ana Silva, Maria Queiroz, Julia de Farias, Danniely Rodrigues, Iara Souza, Vanessa Ribeiro, Egas Caparelli-Dáquer, Antonio L Teixeira, Leigh Charvet, Abhishek Datta, Marom Bikson, Suellen Andrade. PMID: 36693536 PMCID: PMC9867562 DOI: 10.1016/j.brs.2023.01.1672

2. Perspective on prospects to treat symptoms and enhance cognition in Long COVID using auricular transcutaneous Vagus Nerve Stimulation.

Published in the Journal of Clinical Medicine, a multi-national reviews the potential of auricular transcutaneous vagus nerve stimulation (atVNS) to compensate for the cognitive decline and to ameliorate affective symptoms caused by long COVID. The perspective concludes:

“Long COVID has been considered a complex condition likely to be triggered by multiple causes, which might likely require and benefit from an approach encompassing multiple treatments. Two of these causes might be persistent brainstem dysfunction and disrupted vagal signaling. So far, the pharmaceutical agents proposed for long COVID target neurological, but not affective and cognitive outcomes at the same time. The current position paper proposes the potential application of atVNS as an ADD-ON instrument to enhance cognition and ameliorate affective symptoms in long COVID… If this approach will be successful in treating long COVID, it will prove the causal involvement of a disrupted vagal signaling in this condition…Furthermore, considering that the earphone-like electrodes are comfortable to wear in day-to-day life similar to regular in-ear headphones, atVNS has the potential to turn out to be an optimal EMI to boost affective and cognitive outcomes in long COVID. In view of the fact that atVNS is contactless and can be applied at home by the patients themselves without the help of trained specialists, this method will assure accessibility and continuity of treatment without any risk of reinfection that might exacerbate long COVID.”

Full citation: Colzato, L.S.; Elmers, J.; Beste, C.; Hommel, B. A Prospect to Ameliorate Affective Symptoms and to Enhance Cognition in Long COVID Using Auricular Transcutaneous Vagus Nerve Stimulation. J. Clin. Med. 2023, 12, 1198. https://doi.org/10.3390/jcm12031198

3: Case series: TMS for transcranial magnetic stimulation for treatment post-COVID-19 cognitive impairment and depressive symptoms.

Early results from the Non-Invasive Neurostimulation Therapies Laboratory at the University of British Columbia report using TMS:

“This case report outlines improved post-COVID-19 cognitive dysfunction and depression following treatment with rTMS. Post-COVID-19 neuropsychiatric symptoms are purported to be primarily as a result of indirect immune-inflammatory-mediated changes in the central nervous system (CNS)…The left dorsolateral prefrontal cortex (DLPFC) is one of the main stimulation targets for rTMS due to its association with various executive function processes including planning, attention, and working memory…Given the implication of impaired vagal activity with COVID-19 infection, rTMS may improve cognitive dysfunction and depressive symptoms by not only changing functional connectivity between prefrontal circuits, but also by increasing vagal tone and decreasing inflammatory cytokine activity. This case report demonstrates the potential role of rTMS in treating neuropsychiatric manifestation of COVID-19 infection. Further research is warranted to ascertain efficacy of non-invasive neuromodulation interventions for this condition.

Partial citation: Brain fog fix: case report of repetitive transcranial magnetic stimulation for treatment of post-COVID-19 cognitive impairment and depressive symptoms Anastasia Dikareva, Jay C. Wang, Fidel Vila-Rodriguez

4: Pre-print explains interventions or best practice are there to support people with Long COVID, or similar post-viral conditions.

A new pre-print from researchers at Bangor Institute for Health and Medical Research, Bangor University (Wales, UK) and the Wales COVID-19 Evidence Centre notes:

“Long COVID fatigue management by exercise therapy, electrical nerve stimulation, sleep and touch therapy, and behavioural self-management may be beneficial when: physical and psychological support is delivered in groups, people can plan their functional response to fatigue, strengthening rather than endurance is used to prevent deconditioning, fatigue is regarded in the context of an individual’s lifestyle and home-based activities are used” and

“Electrical nerve stimulation, sleep and touch therapy, and behavioural self-management may be beneficial when; physical and psychological support is delivered in groups, people can plan their functional response to fatigue, strengthening rather than endurance is used to prevent deconditioning, fatigue is regarded in the context of an individual’s lifestyle, and home-based activities are used”

Full pre-print citation: What interventions or best practice are there to support people with Long COVID, or similar post-viral conditions or conditions characterised by fatigue, to return to normal activities: a rapid review Llinos Haf Spencer, Annie Hendry, Abraham Makanjuola, Bethany F Anthony, Jacob Davies, Kalpa Pisavadia, Dyfrig Hughes, Deb Fitzsimmons, Clare Wilkinson, Rhiannon Tudor Edwards, Ruth Lewis, Alison Cooper, Adrian Edwards. medRxiv 2023.01.24.23284947; doi: https://doi.org/10.1101/2023.01.24.23284947

5: NIH: Studying Long COVID can help others with post-viral fatigue ailments.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) shares symptoms in common with long COVID, a group of symptoms some people who have had COVID-19 experience for weeks or months after their initial illness. Symptoms of long COVID include fatigue, post-exertional malaise, breathing problems, and heart palpitations. Indeed, some of the leading efforts to treat Long-Covid (PASC) with neuromodulation has come from centers (like NYU Langone tDCS service) with existing experience managing complex lingering symptoms. The National Institutes of Health (NIH) comment on this overlap between these indications.


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