Effect of Transcutaneous Auricular Vagus Nerve Stimulation Combined with Conventional Rehabilitation to Improve Motor and Cognitive Function in stroke patients Randomized controlled trial

INTRODUCTION

As a fatal disease, stroke is currently the second most common cause of disability. Movement problems of the limbs are among the many functional deficits that frequently follow a stroke. The major symptoms are increased muscular tone, decreased muscle strength, or aberrant movement patterns. These can have a serious impact on the quality of life for patients and their families, as well as heavily burden society. Five Clumsiness, slowness of movement, or loss of limb movement are the symptoms of the patient’s damaged side muscle. The normal function of a healthy limb may also be impacted by the decreased bilateral limb synergy. Relying too much on the healthy upper limb might result in secondary injuries from overusing the healthy limb or in the affected limb becoming inactive The treatment of upper limb motor dysfunction has expanded in recent years, with new approaches including neuromodulation, acupuncture, rehabilitation training, and other therapies. [2]

About 50–80% of people with stroke experience upper limb disability during the acute phase, and 40–50% during the chronic phase.[6].

Following a stroke, it is common to see both physical and cognitive problems. Specifically, lower and upper limb motor impairments are linked to global cognition, executive dysfunction, and memory impairment. Depending on factors such as stroke type (ischemic or hemorrhagic), pre-stroke dementia, and temporal distance from the acute event, the prevalence of post-stroke neurocognitive problems varies from 7 to 67.3%.[6]

In the world today, stroke continues to rank among the principal causes of death and adult-onset disability. Despite physiotherapy and rehabilitation, a considerable fraction of people who survive chronic stroke retain long-term disability. Neurological deficiencies encompass a range of symptoms such as spasticity, loss of coordination, dysphasia, weakness, visual field dysfunction, and cognitive impairment. Beyond immediate expenditures like medical bills, the broader socioeconomic effects of stroke include indirect costs like missed productivity at work and the strain of caring for a loved one. Neuroprotective drugs for acute stroke and innovative treatment approaches that encourage neuroplasticity for chronic stroke are therefore unmet needs. [5]

Eighty percent of the vagus nerve’s fibers are afferent, while just twenty percent are efferent. It is vital to the preservation of autonomic tone. everywhere in the abdomen, thorax, and brain [3]

One such focused approach supports the recovery of upper limb function following a chronic stroke by enhancing plasticity and utilizing short bursts of Vagus Nerve Stimulation (VNS) in conjunction with rehabilitation. Acetylcholine and norepinephrine, two neuromodulators that promote plasticity throughout the cortex, are released when the vagus nerve is stimulated. When neuromodulators are timed to fire in tandem with motor training, the motor cortex experiences task-specific plasticity that enhances function and serves as the foundation for paired vector neurostimulation therapy. Compared to rehabilitative training without VNS, a number of studies using preclinical models of ischemic stroke showed that VNS in combination with training greatly enhanced the recovery of forelimb motor function Improvements were linked to remaining motor neurons controlling the damaged forelimb being recruited and cortical motor networks being reorganized synaptic ally, indicating potential neurobiological pathways driving motor function recovery.[9]

Transcutaneous auricular vagus nerve stimulation (taVNS) was first introduced in the year 2000. The term "neuroscience" describes a range of interventional techniques intended to control the neurological system and produce desired results. In order to effectively stimulate the auricular vagus nerve and aid in clinical application and healthcare, transcutaneous auricular vagus nerve stimulators are defined as devices that are based on the corresponding electrical output parameter with pulse width, frequency, intensity, and attached leads and electrodes.[4]

Over the course of more than 20 years of research and application, taVNS has been used to treat 31 different types of diseases or disorders. These include Parkinson’s disease, schizophrenia, post-traumatic stress disorder, epilepsy, depression, insomnia, diabetes, impaired glucose tolerance, pain, migraine, stroke, poststroke rehabilitation, anxiety, fear, cognitive impairment, atrial fibrillation, myocardial infarction, heart failure, arrhythmia, tachycardia, tinnitus, Prader-Willi Syndrome (PWS), obesity, gastrointestinal dysfunction, postoperative intestinal obstruction, inflammatory bowel disease, colon cancer, and dystonia  [4]

There are two ways to approach transcutaneous VNS: by stimulating the auricular branch or the cervical bundle. Clinicians in several professions say that transcutaneous VNS can be applied to a larger group of patients and is even comfortable for patients with non-life-threatening diseases because there is no need for surgical treatments. A more recent delivery method called transcutaneous auricular vagus nerve stimulation (taVNS) makes use of an electrical transcutaneous stimulation device. positioned at the tragus or concha of the ear[3]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive method of VNS via transcutaneous stimulation of the peripheral auricular branch of the vagus nerve and regarded as a potentially safer, better-tolerated method for sensory and motor recovery in chronic stroke [7]

Similar to implanted vagal nerve stimulation (iVNS), transcutaneous auricular VNS (TAVNS) stimulates vagal projections and vagally mediated pathways in a safe, well-tolerated, non-invasive manner. At the cymba and cavum conchae, the auricular branch of the vagus nerve (ABVN) is the only branch of the vagus to reach the skin. [1]

In individuals who have had a persistent stroke, TaVNS in conjunction with rehabilitation has been shown to enhance upper limb motor dysfunction and raise UE-FM scale scores.[2]

TaVNS has been shown to increase Growth differentiation factor 11 (GDF11) expression in the peri-infarct cortex. GDF11 is a member of the transforming growth factor-β (TGF-β) superfamily. GDF11 has been shown to increase markers of neurogenesis and angiogenesis to improve neurological function after stroke. These results suggest that TVNS can improve upper limb motor dysfunction after stroke to some extent and may be an adjunctive intervention for recovery of limb function after stroke. TVNS’s safety, affordability, ease of use, and noninvasive nature make it a potential novel strategy for motor sensory rehabilitation in chronic stroke patients.[2]

As a result of the electrode placement, local skin irritation, headaches, and nasopharyngitis are the only moderate side effects of transcutaneous vagus nerve stimulation, according to the author’s conclusion [3]

NEED FOR THE STUDY:

Patients who have experienced a stroke disrupt their motor function as well as their cognitive function. While some studies have demonstrated the effects of transcutaneous auricular vagus nerve stimulation in conjunction with conventional rehabilitation, very few have examined the combined effects of these two interventions. This study takes an innovative approach to improving both motor and cognitive function in stroke rehabilitation

RESEARCH QUESTION

Is there any effect of transcutaneous auricular vagus nerve stimulation on recovery of upper limb motor and cognitive function in stroke patients?

AIM AND OBJECTIVES:

AIM:

To find out the effect of transcutaneous auricular vagus nerve stimulation on recovery of upper limb motor and cognitive function in stroke patients

OBJECTIVES:

To find out the effectiveness of transcutaneous auricular vagus nerve stimulation on motor function along with conventional rehabilitation

To find out the effectiveness of transcutaneous auricular vagus nerve stimulation on cognitive function along with conventional rehabilitation

Hypotheses

Null Hypothesis (H0):

There will not be significant effect of transcutaneous auricular vagus nerve stimulation on recovery of upper limb motor and cognitive function in stroke patients.

 Alternative Hypothesis (H1):

There will besignificant effect of transcutaneous auricular vagus nerve stimulation on recovery of upper limb motor and cognitive function in stroke patients.

MATERIAL AND METHODOLOGY

Study setting:  The study will be conducted at department of Neuroscience Physiotherapy, Dr. A.P.J Abdul Kalam college of physiotherapy, Loni.

Study Design:  Randomized controlled trial

Study Duration: 2 years

Sampling Method: Simple random sampling

Sample size: 36

OUTCOME MEASURES

Outcome measures used for this study will be as follows,

1.     Montreal cognitive assessment [0.92, p<0.001]

2.     Action reach arm test for assess upper extremity performance [0.996-0.998]

3.     Stroke impact scale [ICC=0.07 to 0.92]

SELECTION CRITERIA**:**

Inclusion criteria:

Ø  Patient with subacute stroke

Ø  Brunnstrom recovery stage 2

Ø  Difficulty in upper limb movement

Ø  MMSC score more than 24

Ø  Ability to give informed consent

Ø  Males and females

Ø  Age 18 to 60 years

 E****xclusion criteria:

Participants excluded will be:

Ø  Participants who are not willing to participate in study

Ø  Patients having addiction

Ø  Currently taking medication to improve cognitive function

Ø  Any metabolic disorder

Ø  Other neurological or musculoskeletal problem

Ø  Cochlear implant

Procedure

INTERVENTION:

**GROUP A [**TaVNS +CONVENTIONAL THERPAY]

For TaVNS

Duration 4 week [20 Working day]

5 times week

Stimulation parameter: 0.3ms square pulses at 20HZ for 30 second

For conventional

·       Motor component:

a.      Patient education

b.     Weight bearing

c.      proprioceptive neuro muscular facilitation

                            Congnitive component: Task oriented exercise

 GROUP B [CONVENTIONAL THERPAY]

·       Motor component:

1.     Patient education

2.     Weight bearing

3.     proprioceptive neuro muscular facilitation

 Congnitive component: Task oriented exercise

REFERENCE

1.     1 Li ZD, Qiu HJ, Wang XQ, Zhang CC, Zhang YJ. Protocol: Transcutaneous auricular vagus nerve stimulation in poststroke cognitive impairment: protocol for a randomised controlled trial. BMJ Open. 2022;12(10).

2.     Yan L, Qian Y, Li H. Transcutaneous Vagus Nerve Stimulation Combined with Rehabilitation Training in the Intervention of Upper Limb Movement Disorders After Stroke: A Systematic Review. Neuropsychiatric Disease and Treatment. 2022 Jan 1:2095-106.

3.     Kim AY, Marduy A, de Melo PS, Gianlorenco AC, Kim CK, Choi H, Song JJ, Fregni F. Safety of transcutaneous auricular vagus nerve stimulation (taVNS): A systematic review and meta-analysis. Scientific Reports. 2022 Dec 21;12(1):22055.

4.     Wang L, Wang Y, Wang Y, Wang F, Zhang J, Li S, Wu M, Li L, Rong P. Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Expert Review of Medical Devices. 2022 Jan 2;19(1):43-61.

5.     Baig SS, Kamarova M, Ali A, Su L, Dawson J, Redgrave JN, Majid A. Transcutaneous vagus nerve stimulation (tVNS) in stroke: the evidence, challenges and future directions. Autonomic Neuroscience. 2022 Jan 1;237:102909.

6.     Colombo M, Aggujaro S, Lombardi N, Pedrocchi A, Molteni F, Guanziroli E. Motor and cognitive modulation of a single session of transcutaneous auricular vagus nerve stimulation in post stroke patients: a pilot study. IEEE Open Journal of Engineering in Medicine and Biology. 2023 Apr 21.

7.     Wu D, Ma J, Zhang L, Wang S, Tan B, Jia G. Effect and safety of transcutaneous auricular vagus nerve stimulation on recovery of upper limb motor function in subacute ischemic stroke patients: a randomized pilot study. Neural Plasticity. 2020 Oct;2020

8.     Li JN, Xie CC, Li CQ, Zhang GF, Tang H, Jin CN, Ma JX, Wen L, Zhang KM, Niu LC. Efficacy and safety of transcutaneous auricular vagus nerve stimulation combined with conventional rehabilitation training in acute stroke patients: a randomized controlled trial conducted for 1 year involving 60 patients. Neural regeneration research. 2022 Aug;17(8):1809.

9.     Engineer ND, Kimberley TJ, Prudente CN, Dawson J, Tarver WB, Hays SA. Targeted vagus nerve stimulation for rehabilitation after stroke. Frontiers in neuroscience. 2019 Mar 29; 13:280.

10.  Smith T, Gildeh N, Holmes C. The Montreal Cognitive Assessment: validity and utility in a memory clinic setting. The Canadian Journal of Psychiatry. 2007 May;52(5):329-32.

11.  Duncan PW, Wallace D, Lai SM, Johnson D, Embretson S, Laster LJ. The stroke impact scale version 2.0: evaluation of reliability, validity, and sensitivity to change. Stroke. 1999 Oct;30(10):2131-40.

12.  McDonnell M. Action research arm test. Aust J Physiother. 2008 Jan 1;54(3):220.