Cryoneurolysis for Spasticity Treatment: Long-term Clinical Outcomes and Mechanisms in the Central Nervous System

Spasticity can make regular daily activities difficult or impossible. Cryoneurolysis is a new technique to treat spasticity that is currently being tested. For this technique, a needle is inserted alongside a nerve implicated in spasticity. The needle then freezes and causes the nerve to break down. The nerve breaking down seems to provide relief for spasticity. The investigators are interested in testing the long-term effects of cryoneurolysis on the function of the brain over six months after treatment. The investigators are testing the brain's function using transcranial magnetic stimulation (TMS) which involves a magnet activating specific parts of the brain that cause muscles to fire; magnetic resonance imaging (MRI) which uses to examine brain structure; functional near-infrared spectroscopy (fNIRS) to examine brain function. The investigators believe that there will be a change in these measures that are related to the long-lasting effects of cryoneurolysis. Cryoneurolysis is not a part of standard care after stroke but is approved in Canada for patients. It has been used extensively in the past for treating pain. TMS is a way of studying how the brain sends signals to muscles to make movement. During these sessions, a researcher will use a magnet to turn on specific neurons in the brain that will cause muscles to contract. The investigators can study the way eyes and muscles respond to better understand how the brain is sending information about moving the body to the muscles. FNIRS is a new way of studying how the brain works. During these sessions, a researcher will fit the participant with a cap that has several lights on it. The light travels through hair, scalp, and skull where it interacts with blood in the brain. By studying the changes in the colour of the blood in the brain, researchers can understand which parts of the brain are active during specific tasks. Magnetic Resonance Imaging (MRI) involves a powerful magnet that takes very detailed pictures of the brain. These images help the investigators to understand how a stroke is related to spasticity. Also, these images are helpful to make the stimulation with TMS more accurate. Study participation will require five visits to the Parkwood Institute Main Building and one visit to St. Joseph's Hospital. The entire study will take place over roughly six months. The investigators are recruiting 25 people with stroke who are eligible for cryoneurolysis to participate in the study.

Spasticity is the result of an overactive stretch reflex after an upper motor neuron injury that results in affected muscles being constantly, involuntarily contracted.1 A failure to treat spasticity can result in contracture - a permanent shortening of the muscle and inert tissues often necessitating surgical intervention.2 There are several treatment options available to those affected by spasticity. Pharmaceutical remedies include diazepam, clonidine, and baclofen, which can be administered orally or intrathecally, and target the GABA-B receptors within the brain and spinal cord to alleviate spasticity.3 Because of the central effects, it is impossible to direct the effects towards specific musculature, making this approach most beneficial for patients with widespread spasticity, especially non-ambulatory patients for whom systemic weakness is less of a concern. For those affected by focal spasticity (spasticity that affects specific regions), there are a number of selective treatments available. By far the most common approach is denervation with botulinum-A neurotoxin. Toxin injections are administered at the neuromuscular junction and act to prevent the release of acetylcholine, thereby reducing the ability of the muscle to fire.4 Botulinum toxin is one of the most potent neurotoxins available but is also one of the most expensive substances on the planet. Since each muscle has many neuromuscular junctions, it is impossible to completely denervate a muscle with this technique. Furthermore, peak effects do not generally endure beyond 90 days and the procedure must be repeated frequently. Recent developments have led to new treatments for focal spasticity. With ultrasound guidance, clinicians are now able to easily visualize individual nerves, creating a new target for intervention. Chemical neurolysis is a developing technique being performed in a small number of clinics worldwide. The procedure involves the selective injection of a diluted phenol solution into or near motor neurons that innervate muscles implicated in spasticity. Phenol neurolysis has been shown to be effective for relieving spasticity in several locations.5-7 Phenol, however, is not selective to nerves and therefore surrounding tissues and structures are not immune to the injections. Nevertheless, chemical neurolysis has a low incidence of side effects.8,9 Chemical neurolysis is much cheaper than toxin injections, but also must be repeated frequently for long-term spasticity alleviation.10 A second, similar approach is neurolysis by pulsed radiofrequency. While phenol lyses targeted nerves with chemicals, pulsed radiofrequency heats nerves with radio-waves to ablate targeted axons. Radiofrequency ablation has been shown to have a very low incidence of side effects, and reduction in spasticity symptoms has been shown to endure six months.11 Cryoneurolysis, another emerging technique for spasticity management, is more cost effective than other techniques, and the effects ou trial.show_full_description

Inclusion Criteria: * have increased range of motion or reduced spasticity with diagnostic nerve block, * have no undesired loss of function with a diagnostic nerve block, * score 2 or higher in the Modified Ashworth scale, * have at least flickers of movement in the upper extremity, * have not received botulinum-A neurotoxin within the past 3 months, * if on anti-spastic medication, maintaining anti-spastic medications on a stable schedule over the course of the follow up period, and * they can understand and follow instructions in English. Exclusion Criteria: * have contraindications to TMS (i.e., history of seizure, pregnancy) or 3T MRI (i.e., certain metallic implants), * are unable to provide informed consent (i.e., severe cognitive impairment), * receive any toxin injections for spasticity (Botulinum-A Toxin or equivalent) within 3 months of initial baseline assessments or at any time over the course of the follow-up period. * Have previously undergone any nerve-specific interventions (phenol neurolysis, radio-frequency ablation, or cryoneurolysis) for spasticity on a nerve that will be targeted for this study.