Cryoneurolysis of the Femoral Nerve for Focal Spasticity in an Ambulatory Patient

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusion

Cryoneurolysis of the femoral nerve may be an effective, long-lasting treatment for spasticity causing stiff knee gait in patients with multiple sclerosis.

Spasticity of the lower limb is common among patients with multiple sclerosis (MS) and, when the rectus femoris is implicated, can lead to reduced knee flexion.¹ The resulting stiff-legged gait presents with an early swing toe drag which greatly increases the risk of falls.² Compensatory mechanisms such as hip circumduction or contralateral vaulting are frequently adopted, further increasing the exertion of walking.² Moreover, recurrent knee recurvatum during the stance phase can give rise to further pain and deformity which may have a profound effect on patients’ functional ability.³

The rectus femoris is innervated by the femoral nerve. The femoral nerve originates from the anterior rami of nerve roots L2, L3, and L4. The nerve travels through the psoas major and supplies the iliacus and pectineus muscles before passing underneath the inguinal ligament to enter the femoral triangle where it courses lateral or deep to the femoral artery depending on the individual.⁴ Distal to the femoral triangle, the nerve branches into anterior and posterior divisions. The anterior division branches to the sartorius and pectineus; the posterior division branches to the saphenous nerve and the quadriceps femoris.⁵

Conventional treatments for spasticity of the knee extensors involve the use of botulinum toxin (BoNT) injections. BoNT inhibits acetylcholine release from the presynaptic neuromuscular terminals, resulting in chemical denervation and paralysis of the muscle.⁶ Alternatively, neurolytic interventions can be considered for spasticity management. These approaches target the axon of the nerve implicated in spasticity as opposed to the neuromuscular junction. Neurolytic techniques including chemical neurolysis and radiofrequency neurolysis have been effectively applied to the femoral nerve to rectus femoris for knee extensor spasticity.^7,8

Cryoneurolysis is a minimally invasive alternative neurolytic intervention for spasticity. Cryoneurolysis involves the application of cold at temperatures ranging from -60°C to -88°C to nerves implicated in problematic spasticity. Under ultrasound guidance, the cryoprobe is inserted in close proximity to the target peripheral nerve. The rapidly generated ice ball causes axonotmesis.⁹ The epineurium and perineum are preserved and serve as a tunnel for the treated axon's regeneration.^10,11 Recent case studies have shown that the reduction in spasticity and improvement in range of motion (ROM) can endure beyond the nerve's regeneration, for months to years.12, 13, 14 Targeting afferent nerves for cryoneurolysis has been used for analgesic purposes for decades.¹⁵ Cryoneurolysis for spasticity seems to have manageable, minor side effects.¹⁶

We present a patient with MS who underwent cryoneurolysis of the femoral nerve branch to the rectus femoris. A video accompanying this article will illustrate the procedures and patient outcomes and includes a second patient's pre- and post-cryoneurolysis gait.

Case Report

This study follows the Case Reports (CARE) guidelines and reports the required information accordingly. Institutional research ethics board approval was not required.

A 70-year-old woman with a history of progressive MS was assessed for lower limb spasticity management. Over the last 30 years, her MS has progressed to involve both upper and lower limbs. She has a history of sensory axonal distal polyneuropathy and other musculoskeletal problems attributable to osteoarthritis, lumbar spondyloarthropathy, and left sacroiliac joint dysfunction. She provided written informed consent for the publication of this study. She is a high functioning woman who is independent in all her daily activities despite difficulties with ambulation. She uses a 4-wheeled walker and a hip flexion assist brace to remain stable during gait. In addition to BoNT injections and oral baclofen medication, she had undergone cryoneurolysis of the tibial nerve trunk at the level of popliteal fossa 18 months prior to representing to our clinic, for the treatment of pain, spasticity, and the equinus position of the foot. She indicated significant improvement in ankle function with respect to dorsiflexion and reported marked improvement in her ability to walk after the procedure.

During her physical examination, reduced gait speed was notable. Also, her right leg tended to move into external rotation of the hip with reduced knee flexion throughout the swing phase and compensatory hip hiking with a circumduction gait pattern. A supplemental video is included showing the patient's gait during the 10 m walk test. Knee extensors’ tone was increased to at least grade 3 of Modified Ashworth Scale (MAS). The ankle and foot tone were low, indicative of ongoing effectiveness of her prior tibial trunk cryoneurolysis. Right knee flexion maximum passive ROM (V1) was 115° compared with 145° in the left side. The catch angle with quick knee flexion movement (V3) was 70° relative to full extension. The catch angle in sitting position against gravity (V2) was 35°. She completed a 10-meter walk test with and without her hip flexion device. Results were 20.14 seconds (0.49 m/s) and 21.15 seconds (0.47 m/s), respectively. A complete summary of the pre-treatment findings is reported in figure 1. Three goals were established for the Goal Attainment Scale (GAS) and are reported in table 1.

Fig 1.

Baseline and follow-up range of motion, gait speed, and MAS. V1, V2, and V3 are measures from the Tardieu Scale. V1 indicates the maximum passive range of motion for a specific movement when the limb is moved as slowly as possible V1 was assessed in a supine lying position. V2 indicates the passive range of motion for a specific movement when the limb is moved by gravity. V2 was measured in a seated position and as such ranges from 0 to 90 degrees. V3 represents the maximum passive range of motion for a movement when the limb is moved as quickly as possible. V3 was assessed in a supine lying position. MAS is a 5-point ordinal scale of spasticity severity ranging from 1 to 4. *Indicates changes in gait speeds from baseline that are greater than or equal to the MDC for the 10 m walk test.¹⁷

Table 1.

Patient's evaluation of progress toward a priori goals using the Goal Attainment Scale

Goal	Baseline Score	Change After 3 Months	Change After 15 Months
1. Increase walking confidence and lessen the cognitive demand of walking;	−1	−0.5	−0.5
2. Increase gait speed;	−1	+1	0
3. Straighten the leg during gait.	−1	+1	0

NOTE. The patient set 3 goals prior to cryoneurolysis. The baseline score is -1. A score of 0 indicates achieving the goal as well as expected. A score of -0.5 indicates improvement compared with the baseline, but not as much as expected. A score of +1 indicates achieving the goal much better than expected.

Methods

Clinical evaluation and diagnostic nerve block

After careful clinical examination, the rectus femoris was deemed to be implicated in the pattern of spasticity and was the ideal target to address spastic knee extension. The femoral nerve intramuscular branch to rectus femoris was visualized on ultrasound and a diagnostic nerve block (DNB) was performed. The DNB involved the injection of 1.5 mL of a 2% lidocaine solution and provided a result like the final effects of cryoneurolysis, a reduction in motor neuron excitation, although it only lasted a few hours. There was no undesirable loss of sensation or function because of the DNB. No adverse event was reported.

Cryoneurolysis for spasticity

The patient consented to cryoneurolysis of the femoral nerve to the rectus femoris with a handheld free-standing unit that uses liquid nitrous oxide capsules.^a There is no drug treatment. The skin around the injection site was prepared with chlorhexidine swabs to lower the risk of infection. The entry point was first anesthetized with local infiltration of 1% lidocaine. A 16-gauge angiocatheter was inserted to guide the Smart Tip (Pacira BioSciences, Inc), to increase ultrasound echogenicity, and to protect the skin from frostbite. The cryoprobe was inserted through the catheter and the target nerve was located using known anatomy. The treatment site was confirmed prior to each cycle using electrical stimulation of less than 1 mA at 1 Hz. Three lesions of 106 seconds each were performed at different sites along the nerve. The procedure was well-tolerated, and no adverse event reported. Figures 2 and 3 demonstrate the anatomy of the rectus femoris and surrounding area as visualized with ultrasound during the procedure.

Fig 2.

Anatomy of the femoral nerve as visualized on ultrasound. The sartorius is visualized in the center of the image with several fascial planes passing through and around it; the rectus femoris lies deep to the sartorius. The femoral nerve is visualized proximal to the femoral artery as part of the neurovascular bundle. Intramuscular branches to rectus femoris are seen branching from the nerve trunk and are targeted for cryoneurolysis.

Fig 3.

Periprocedural ultrasound image of femoral nerve cryoneurolysis. The superficial aspect of the ice ball is visualized in the center of the image. The ice ball casts a large hyperechoic shadow.

Results

Knee extensor tone showed improvement on the MAS after 1 month. The maximum knee flexion ROM (V1) and fast-catch angle (V3) remained the same as baseline after 1 month. Catch angle against gravity (V2) showed improvement after 1 month. ROM improvements were consistent across all follow-ups every 3 months up to 15 months. The 10 m walk test showed a large improvement with and without her brace and shoes. Initially her gait speed was 0.50 m/s without assists, and 0.47 m/s with; improving to 0.76 m/s without assists and 0.80 m/s with assists 1 month post treatment; improvement of 0.26 m/s and 0.33 m/s, respectively. The minimum detectable change (MDC) in 10-m walk test gait speed is 0.26 m/s.¹⁷ Gait speed gradually slowed over time, returning approximately to baseline without braces after 15 months. Changes in gait speed were greater than or equal to the MDC for 6 months with her brace, and 1 month without her brace. Although ROM improvements were maintained throughout the follow-up period, the patient decided to repeat the procedure to improve gait speed at 15 months. After re-treatment, the 10 m walk test without braces or shoes improved to 16.20 seconds. Figure 1 displays the comprehensive set of outcome assessments completed at each stage of follow-up.

Patient reported experience

The patient did not report any complications from the procedure. She reported significant progress toward her a priori goals (table 1). After 3 months, she reports that the treatment “immediately made walking easier. . . the right leg swung easier making [her] walking smoother”. Furthermore, she reported a new ability to tap her toes and raise her heels on the treated side. She had a nerve injury unrelated to treatment on the contralateral side affecting her gait speed at the 3 month follow-up. Nevertheless, she reports that the treatment “is the best thing that has improved [her] quality of life. . .kept [her] walking so [she] still has [her] independence”. The patient was offered to repeat the cryoneurolysis after 1 year, as the gait speed without the brace had returned to baseline. She declined the need as felt her walking was still easier. She ultimately decided to repeat the procedure after 15 months because of the decrease in gait speed.

Discussion

To our knowledge, our paper is the first to report improved gait speed in an ambulatory patient after cryoneurolysis of the rectus femoris motor branch in a patient with MS. From the patient's perspective, the immediate reduction in muscle tone is 1 of the greatest advantages of cryoneurolysis. The patient's gait without her hip flexion device returned to baseline after 15 months. We surmise that this was due to the weakness in the hip flexors as the hip flexion device aided in her speed. While limited improvement was noticed in the MAS and Tardieu scales, gait speed increased further than or equal to the MDC for 1 month without her brace, and 6 months with her brace.¹⁷ The patient indicated that she had achieved her goals of increasing gait speed and straightening the leg during gait and reported that her confidence had not improved as much as she had anticipated.

Several interventions have described the efficacy of targeting the rectus femoris for spastic knee extension. A recent randomized-controlled trial of stiff-knee spasticity treated with BoNT denervation of the femoral nerve to rectus femoris in ambulatory patients showed that there were significant improvements in knee flexion ROM and walking endurance compared with placebo.¹⁸ Also, a recently published case report from Pascoal et al⁸ described a non-ambulatory patient with spastic paraplegia after a spinal stroke. Rectus femoris and adductor spasticity were addressed by performing ultrasound-guided radiofrequency thermal ablation of the motor branches to the rectus femoris of the femoral nerve and anterior and posterior branches of the obturator nerve. The patient still had significantly reduced spasticity 1 year after the treatment. As the patient was non-ambulatory, gait was not an outcome measure. One potential advantage of cryoneurolysis over alternative neurolytic techniques is the absence of surrounding tissue damage, notably including surrounding musculature. As such, cryoneurolysis may be favorable for ambulatory patients because of its conservative nature; further study is required. Furthermore, as opposed to radiofrequency thermal ablation, neuroma formation is not an expected side effect of the treatment⁹; only temporary, treatable adverse events have been reported after cryoneurolysis for spasticity.¹⁶

Stiff-knee gait, characterized by abnormally increased activity of the rectus femoris, is frequently seen in patients with MS.¹ Cryoneurolysis is an option that can be considered as part of a multimodal approach to managing stiff knee gait in patients who have not had good results with other modalities. There remains hesitancy to address the rectus femoris due to concerns it will cause weakness and instability about the knee. Our clinical protocol of triaging the patient with a DNB gives a temporary prediction of the effect of cryoneurolysis and its effect on strength, spasticity, and in this case, gait.

Limitations

The reported case describes our experience with a single patient, and therefore may not be representative of the entire patient population. Furthermore, MS is a progressive and variable condition that is highly individualized and as such, patients with this affliction may respond differently to treatment. Larger studies should be conducted to further establish the feasibility and efficacy of this technique in this population. Additionally, future studies should consider the use of superior gait evaluation techniques, such as motion capture or gait mat.

Conclusions

Cryoneurolysis of the femoral nerve motor branches may improve the gait pattern and may be maintained for up to 12 months. The procedure can be considered for ambulatory patients and may lead to improvements in gait speed. Cryoneurolysis is a treatment option for spasticity that can be considered in patients who have achieved suboptimal results from other modalities.

Supplier

• a.Iovera System 190 Smart Tip; Iovera, Pacira.