The Upper Limb and Stroke
Arm weakness is common after stroke and its treatment is recognised as an area of considerable need.1 Approximately 85% of patients with stroke present with arm weakness2 and 60% of stroke survivors with poorly functioning arms at one week do not recover meaningful function by six months.3 Arm weakness is a major factor contributing to disability following stroke.4Current treatment for arm weakness typically comprises intensive, task-specific and repetitive rehabilitative interventions or occasionally methods such as constraint induced movement therapy and robotic therapy.5 A recent meta-analysis and large-scale trials show the effects of current treatments for arm weakness to be modest.6,7 Improvement in arm function should improve quality of life for stroke survivors, reduce co-morbidities associated with loss of independence, and reduce cost to the health care system.8
Neuroplasticity and Recovery
Neuroplasticity is the brain’s ability to form new neural pathways in response to injury or disease. It has been a target for the treatment of many neurological disorders including epilepsy and tinnitus. Recent studies have suggested that augmentation of neuroplasticity is required to more fully recover motor function.9 Novel techniques that drive the growth of new neural pathways related to motor function are needed; vagus nerve stimulation (VNS) may achieve this.
Vagus Nerve Stimulation
VNS is the delivery of small electrical impulses to the vagus nerve (Figure 1). VNS activates neurons in the basal forebrain and locus coeruleus and results in the release of acetylcholine and norepinephrine. These neurotransmitters are known to facilitate the reorganisation of cortical networks.10 VNS is already used to treat patients with medically refractory epilepsy, with studies showing a reduction in seizure frequency of 50% in 24.5 to 46.6% of patients.11,12,13 In excess of 75,000 patients with refractory epilepsy have been implanted with VNS devices.14 The concept of using VNS to restore normal neuronal activity / drive neuroplasticity is under investigation in other chronic neurological conditions.
In noise induced tinnitus, cochlear trauma can lead to a disorganised auditory cortex resulting in chronic symptoms.15,16,17 The severity of tinnitus is related to the degree of map re-organisation in the auditory cortex.15,16,17 In pre-clinical studies, pairing auditory tones with brief pulses of VNS has been shown to cause re-organisation of auditory cortex maps specific to that tone.18 Further, noise-exposed rats were noted to have a significant reduction in startle response, presumably due to tinnitus, and pairing VNS with multiple tones reversed this effect.18 Thus, VNS paired with a specific stimulus may drive neuroplasticity specifically for that stimulus, thereby restoring auditory cortex architecture and reducing tinnitus. Studies suggest that VNS may help humans with tinnitus.19 Ten patients known to have unilateral or bilateral tinnitus for over a year received four weeks of VNS paired with auditory tone therapy (using MicroTransponder Inc’s Serenity© system). Subjective and objective primary outcome measures were identified in the form of the Tinnitus Handicap Inventory (THI) and the Minimum Masking Level (MML). In patients who had not been taking drugs which could interfere with VNS (muscarinic antagonists, noradrenergic reuptake inhibitors and γ-amino butyric acid agonists), a significant fall in THI of 28.17% was seen following VNS paired with auditory tones.19 Three out of five such patients had a clinically meaningful decrease in THI (44.3% decrease).19 Similar results were seen in the MML test which detects the lowest level of noise required to “drown out” the tinnitus. Results of a recently completed and larger, double blind and randomised study of VNS paired with auditory tones in tinnitus are eagerly awaited. Another study looked at the use of transcutaneous vagus nerve (t-VNS) stimulation in tinnitus. When used in combination with sound therapy t-VNS was found to modulate auditory cortical activation, resulting in reduced tinnitus and tinnitus associated distress.20