Objective: The aim of the study was to investigate novel, minimally invasive cryoneurolysis for refractory or plateaued upper limb spasticity. Design: This was a repeated-measures, single-center, observational pilot study (NCT04670783). Percutaneous cryoneurolysis was applied to the upper limb nerves and intramuscular branches of 59 adults with upper limb spasticity refractory to or plateaued on botulinum therapies. Maximal passive range of motion (V1), active ROM, and modified Ashworth scale score were measured during shoulder flexion, abduction, and external rotation and elbow and wrist extension at baseline and follow-up to 1 yr. Additional outcomes included pain, participant satisfaction, and upper limb disability. Results: Overall, 59 participants received cryoneurolysis in ≥1 region targeting nerves that innervate muscles supporting shoulder (n = 47), elbow (n = 33), wrist (n = 18), and fingers/thumb (n = 29) movement. At 12 mos, there was significant change from baseline in V1, active ROM, and modified Ashworth scale score for shoulder flexion and abduction and in V1 and modified Ashworth scale score for external rotation. Similar results were observed for elbow extension V1, active ROM, and modified Ashworth scale score and wrist extension modified Ashworth scale score. Average daily pain, participant satisfaction, and upper limb disability improved. Conclusions: Participants with plateaued or refractory spasticity had improvements in upper limb regions; future evaluations of cryoneurolysis treatment for spasticity are warranted.

Spasticity of the knee extensors is a common presentation among patients with multiple sclerosis. The resulting stiff leg gait can result in increased risk of falls, heightened energy expenditure during gait, lowered gait speed, and compensatory gait mechanisms that increase wear on the hips. Cryoneurolysis is a novel percutaneous, minimally invasive treatment for focal spasticity. A single patient with multiple sclerosis was treated with cryoneurolysis of the femoral nerve branch to rectus femoris. The patient was followed for 15 months. Spasticity severity, gait speed, and patient reported outcomes were collected at each follow-up. Spasticity severity as per the Modified Ashworth Scale was reduced at 1 month, with change persisting up to 15 months post-procedure. Range of motion as per the Modified Tardieu Scale showed gradual improvement over the 15-month period. Gait speed increased after the procedure from 21.15 seconds to 12.49 seconds for the 10 m walk test 1 month post-procedure, then slowed to baseline after 15 months. The patient's confidence in their gait improved and their independence was maintained throughout the follow-up period. Because of the regression in the 10 m walk test, the patient elected to have the procedure repeated after 15 months. Immediately after the procedure, the 10 m test time improved to 16.20 seconds. Cryoneurolysis of the femoral nerve may be an effective, long-lasting treatment for spasticity causing stiff knee gait in patients with multiple sclerosis.

Osteoarthritis is a leading cause of disability, typically treated with exercise, analgesics, injections, or surgeries. Cryoneurolysis is an established technique for the treatment of pain, including osteoarthritis that may provide an alternative for patients in whom surgery is not appropriate and conservative measures have failed. We present our experience with a 78-year-old man with severe pain from bilateral glenohumeral osteoarthritis. Their condition is complicated by several concurrent diagnoses, leaving them ineligible for surgical intervention, despite pharmacologic treatments proving insufficient to manage their pain. As an alternative, bilateral cryoneurolysis of the suprascapular nerve was performed at the suprascapular notch. Pain and disability scores both lessened on the Brief Pain Inventory Score, Disabilities of the Arm Shoulder and Hand (change of 9 points after 170 days) as well as the Shoulder Pain and Disability Index (change of 19 points after 170 days). The patient had improved active and passive range of motion for flexion, abduction, and external rotation of the shoulder. Improvements endured to follow-up at 170 days. There were no negative side effects as a result of the procedure.

Toe clawing in patients with upper motor neuron disorders is often attributed to the flexor digitorum longus (FDL) and is a common presentation among patients with multiple sclerosis (MS). This movement may be painful because of the altered pressure distribution and may increase the risk of falls, heighten energy expenditure during gait, and lower gait speed. Cryoneurolysis is a minimally invasive treatment that may be beneficial for pain and focal muscle hypertonicity. An ambulatory patient with MS was treated bilaterally with cryoneurolysis to the superficial fibular nerves for pain on the dorsum of the foot, and to the intramuscular tibial nerve motor branch to FDL for toe clawing. The patient felt that toe clawing was immediately reduced during gait and noted the ability to voluntarily spread their toes. The patient stated that the neuropathic pain on the dorsum of the foot was fully eliminated immediately post procedure. The patient reported improved confidence in their gait, maintained independence, and reduced toe clawing during a structured interview 12 weeks after treatment. The effects lasted for 5.5 months before symptoms returned. Retreatment at 6 months reproduced the benefits. The patient reported a positive experience with cryoneurolysis for toe clawing and dorsal foot pain.

Shoulder spasticity is a common consequence of upper motor neuron lesions and may be associated with soft tissue contractures, limiting functional recovery. While both cryoneurolysis and tendon lengthening procedures are used individually in refractory cases, their combined effect has not been clearly established. It is consequently necessary to assess the efficacy of combining cryoneurolysis and percutaneous pectoral tenotomy in reducing shoulder spasticity and improving passive range of motion in patients with refractory shoulder spasticity and contracture. This retrospective, single-centre cohort study included 15 adults (≥19 years) with chronic shoulder spasticity and clinically confirmed musculotendinous contracture, previously treated with botulinum toxin injections without sufficient functional response, and free of pharmacological effects (last injection >4 months prior). All patients underwent cryoneurolysis targeting motor branches to the pectoral muscles. Outcomes included Modified Ashworth Scale (MAS) and shoulder Passive Range Of Motion (PROM). The combined approach provided significant improvements in spasticity severity for shoulder flexion (p < 0.01) and abduction (p < 0.01), and significant improvements in maximum PROM for shoulder flexion (p < 0.0001) and abduction (p < 0.0001). Combining cryoneurolysis and pectoral tenotomy appears feasible, safe, and clinically beneficial in selected patients with both spasticity and tendon contracture. Cryoneurolysis addresses the neural component, while tenotomy may restore mechanical excursion. This sequential diagnostic and therapeutic approach may enhance personalized management of mixed spastic–contracture shoulder limitations and could be applicable to other joints.

The application of non-invasive brain stimulation (NIBS) often relies on proxy estimates of cortical excitability (CE), such as the resting motor threshold (rMT), measured through transcranial magnetic stimulation (TMS). However, estimating the rMT is not always possible, as it requires an intact corticospinal pathway for neural signals to travel from the cortex to the periphery. To broaden the application of NIBS there is a need for additional CE measures. In three experiments combining TMS, transcranial direct current stimulation (tDCS), and eye-tracking, we measured TMS-induced pupil dilations as a potential CE proxy. We present Bayesian evidence (Experiment 1: BF > 9; Experiment 2: BF > 46; Experiment 3: BFs > 6) that TMS-induced pupil dilations serve as an objective CE proxy, with larger pupil size reflecting higher CE. We also show that these effects are not due to auditory, muscle, or sensory confounds. The introduction of this novel measure paves the way for a deeper understanding of CE by enabling objective NIBS measures beyond the motor cortex. Moving away from the reliance on the motor cortex would allow NIBS research and therapy to become more inclusive, allowing access to populations that are affected by damage along the corticospinal pathway.