In the United States, more than 795,000 people have a stroke every year. Motor impairment after a stroke is common and can be debilitating. To date, there remain few treatments available to help improve motor recovery after a stroke, making this an important area of research. Novel use of neuromodulation such as Invasive Vagus Nerve Stimulation (VNS) has been shown to improve motor recovery in stroke patients. Vagus nerve stimulation (VNS), in which the nerve is stimulated with electrical pulses, has demonstrated success for a variety of conditions, including inflammation, depression, cognitive dysfunction, chronic fatigue, headaches/migraines, pain, insomnia, and cardiovascular issues. Very recently, non-invasive options have been developed and might be a promising alternative. The research in this area is still very limited and much more research is needed to investigate non-invasive/trancutaneous auricular vagus nerve stimulation (taVNS) related biomechanisms and to further support its efficacy in acute patients. The purpose of this study is to build upon the current research to investigate changes in electrical brain activity (using electrophysiology) and genetic markers related to improvements in both motor and cognitive recovery following the use of taVNS vs. sham in acute stroke patients.
First-time Cerebrovascular Accident (Ischemic or Hemorrhagic)
Within a month post-injury
Presence of motor impairments (FMA-U≤62)
Advanced cardiac, pulmonary, liver, or kidney disease
Bradycardia (Resting HR < 60)
Presence of Apraxia, Aphasia or confusion
Other musculoskeletal or neurologic diseases that could interfere with the outcome measures
Parallel
Transcutaneous vagus nerve stimulation
DeviceThe Parasym Plus device (https://parasym.io) is a transcutaneous auricular vagus nerve stimulator that has been deemed non-significant risk (NSR) by the FDA. Transcutaneous auricular vagus nerve stimulator is a non-significant risk device, as it involves electrical stimulation of the external ear using an ear clip, with no invasive components. The stimulation parameters will be limited to the confines of existing published data. tVNS is safe and well tolerated at doses tested in research studies. The Parasym device is considered low risk when used in accordance with the instructions for use. Participants will be properly trained to use the device, and those with contraindications will be excluded for extra precaution. A low incidence of skin irritation has been reported. No serious adverse events have been reported.
Resting state electroencephalogram (EEG)
Resting state electroencephalogram (EEG) will be recorded with eyes open during 15 minutes using our 64 electrodes cap (actiCHamp Plus; brainproducts.com). Spectral analysis will be performed on consecutive, artifact-free, epochs of awake EEG signal. The selected epochs will be filtered (1-70 Hz, 12 db/octave), followed by a 60 Hz notch filter to suppress the noise of the electrical power line, reformatted against the linked Cz reference. In order to remove blink-artifacts, we will apply an ICA-artifact rejection algorithm. Then, the selected EEG activity will be divided into non-overlapping 2 s segments and analyzed using the fast Fourier transform. Power spectral density (PSD) will be evaluated in the delta (1-4 Hz), theta (5-8 Hz), alpha (9-12 Hz), and beta (13-30 Hz) bands. Primary measure will nevertheless be PSD ratio of fast (alpha) to slow (delta) frequencies. Such ratios will be compared just before starting and just after the last taVNS session.
Fugl-Meyer Assessment - Upper extremity
Fugl-Meyer Assessment for Upper extremity evaluates and measures recovery in post-stroke hemiplegic patients. The motor portion scores range from 0-66. The higher the score, the better the function.
DNA Data
Frequency of polymorphisms per marker (BDNF,COMT) will be estimated. These values will be used as a cofactor in a repeated measures 2x2 ANOVA framework with behavioral data as dependent variable, time as a within-subjects variable (pre/post) and group (taVNS, Sham) as a between subjects variable.
The modified Rankin Scale
The modified Rankin Scale is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. Its scores range from 0 to 5 (lower scores reflecting better outcome). It has become the most widely used clinical outcome measure for stroke clinical trials and can be administered reliably over the phone.
The Montreal Cognitive Assessment
The Montreal Cognitive Assessment is a brief screening instrument originally designed to identify mild cognitive impairment in elderly patients attending a memory clinic. It is a 1-page test with scores ranging from 0 to 30 (higher scores reflecting better outcome), administrable in around 10 minutes, which evaluates different domains: visuospatial abilities, executive functions, short-term memory recall, attention, concentration, working memory, language, and orientation to time and space. This test has alternate versions that allow serial assessments and has been adapted to phone interview.
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Casa Colina Hospital and Centers for Healthcare
Lead sponsor
Foundation for Physical Medicine and Rehabilitation
Collaborator
