Cryoneurolysis for Managing Spasticity in Multiple Sclerosis: A Case Report Demonstrating Sustained Functional Gains and Cost-Effectiveness

Abstract

Cryoneurolysis is a minimally invasive procedure that induces secondary axonotmesis while preserving the nerve’s supportive structures, offering an alternative approach to managing spasticity in multiple sclerosis (MS)—a condition affecting up to 90% of patients with MS and often leading to contractures, pain, and reduced mobility. In this case report, a 48-year-old woman with progressive MS who previously experienced side effects and limited benefits from prior botulinum toxin-A injections underwent ultrasound-guided percutaneous cryoneurolysis on targeted nerves to spastic muscles identified using the response to diagnostic nerve blocks. Range of motion and spasticity were assessed using the Modified Ashworth Scale, Modified Tardieu Scale, and numerical pain ratings. The patient demonstrated marked, sustained improvements in range of motion (shoulder flexion, abduction, and external rotation and elbow extension up to 11mo and knee flexion up to 7mo) and a reduction in spasticity (at 11mo for shoulder and elbow, 4mo for knee). The patient then experienced a progressive MS crisis, and a second treatment was offered at 1 year. There were additional gains after the second round of cryoneurolysis. The procedure showed 15-fold annual cost savings in their jurisdiction compared with botulinum toxin-A, underscoring the potential economic benefits of cryoneurolysis. These findings suggest that cryoneurolysis is a promising treatment for upper and lower limb spasticity in MS, providing significant, sustained improvements in range of motion, pain, and spasticity. Further research with larger cohorts is needed to confirm the long-term efficacy, broader applicability, and fully substantiate the cost-effectiveness of this emerging treatment modality.

There are an estimated 2.8 million people worldwide currently living with multiple sclerosis (MS).¹ MS is a neurodegenerative, chronic, autoimmune disease impacting various body systems leading to sensorimotor impairments of the lower limb that affect mobility in 75% of patients with MS and upper limb impairments that affect 66% of patients with MS.^2,3 Spasticity is considered one of the most disabling symptoms, found in up to 90% of patients with MS and contributes to pressure ulcers, infection, pain, and contractures, leading to a reduction in mobility and ability to complete tasks of daily living.^4,5 The pathophysiology of spasticity in patients with MS is associated with axonal degeneration and demyelination causing dysregulation of the spinal tracts and imbalance within excitatory and inhibitory spinal and supraspinal neural circuits.⁶ Correlation between spasticity in MS and a lower quality of life has been found.⁷ Common treatments include botulinum toxin (BoNT) injections and oral or intrathecal antispasmodic agents.⁶ However, many treatment options have low efficacy and adverse side effects.⁸ The cost of BoNT can be prohibitive in both the developing world and North America.^9,10

Percutaneous cryoneurolysis is a minimally invasive spasticity treatment that can improve pain and focal muscle hypertonicity, including patients with MS.11, 12, 13 This procedure uses ultrasound guidance and e-stimulation where a specialized cryoprobe operating at a temperature range of −60 to −88°C at the tip will create an ice ball from interstitial fluid in and around the peripheral nerve to cause secondary axonotmesis.^12,13 The epineurium and perineurium remain intact, allowing the damaged axon to regenerate.¹² Cryoneurolysis was found to lead to an increased range of motion (ROM), reduced spasticity, and reduced pain of targeted joints in patients with upper limb spasticity, and it was maintained for a 1-year follow-up in a cohort of 59 patients including 2 patients diagnosed with MS.¹² Three additional published case reports, which included patients with MS, have shown the positive outcomes of cryoneurolysis for spasticity in the lower extremity of patients with MS.13, 14, 15 We now present a patient with upper and lower limb spasticity to examine the patient outcomes and cost compared to prior care with onabotulinum toxin-A (onaBoNT-A).

Methods

This study follows the case reports guidelines and reports the required information accordingly. Institutional research ethics approval from the local research ethics board was collected [H23-00533]. The patient’s medical chart was reviewed to collect all data regarding cryoneurolysis and any assessments before and after the procedure.

Case report

A 48-year-old woman was diagnosed in 2018 with primary progressive MS. Her magnetic resonance imaging revealed multiple T2 hyperintensities in the brain and cervical spine. She was referred to an outpatient clinic for spasticity management of the left shoulder, elbow, and both legs. Because of the disease severity, she sat in a power wheelchair most of the day, and she was only able to take a few steps with a walker and transferred independently. Intense pain in her left shoulder and hand weakness made holding the walker difficult. Her MS was treated with alemtuzumab injections. The patient had previously been treated with onaBoNT-A injections, an average of 600 units, 4 times a year to both the upper and lower limbs, with the last dose to the bilateral pectoralis major, quadriceps, gastrocnemius, and soleus muscles, 1 year before the referral for cryoneurolysis. The onaBoNT-A caused weakness and dysphonia with little effect on reducing her symptoms of spasticity. She then enquired about novel treatments.

The physical examination revealed severe spasticity in the left quadriceps, shoulder adductors, and elbow flexors with a score of 3-4 based on the Modified Ashworth Scale (MAS), with a slight increase in tone in the wrist, fingers, and ankle flexors¹⁶ (Table 1, Table 2, Table 3). There was pain with passive ROM of the left shoulder, with an average pain score of 6 out of 10 based on a numerical rating scale. The left arm and leg had minimal active movements. The right arm was normal for tone and strength. There was active but weak movement on the right leg.

Table 1.

Upper limb range of motion.

Post-Cryo (d)	Shoulder Flexion (X)V1	Shoulder Flexion (X)V3	Shoulder Flexion AROM	Shoulder Flexion MAS	Shoulder Abduction (X)V1	Shoulder Abduction (X)V3	Shoulder Abduction AROM	Shoulder Abduction MAS	Shoulder External Rotation (X)V1	Shoulder External Rotation (X)V3	Shoulder External Rotation AROM	Shoulder External Rotation MAS
Baseline	90	65	45	4	75	70	70	4	30	No V3	−15	4
1.5 mo	110	No V3	45	1	115	No V3	30	1+	60	No V3	20	1
4 mo	125	No V3	75	1	135	No V3	85	1	70	No V3	20	1
7 mo	135	No V3	50	1+	120	No V3	65	1+	65	No V3	25	1+
11 mo	125	45	45	2	130	70	40	2	65	25	No active movement	2
Second Round of Cryo Completed
New baseline-1 mo later	95	70	50	2	95	80	55	2	65	No V3	No active movement	(no measurements)
2 mo	110	75	70	2	125	95	80	2	60	10	No active movement	(no measurements)
6 mo	110	No V3	45	2	100	No V3	60	1+	20	0	−20	2

Post-Cryo (d)	Elbow Extension (X)V1	Elbow Extension (X)V3	Elbow Extension AROM	Elbow Extension MAS
Baseline	−45	−90	No active movement	3
1.5 mo	0	−75	−70	1+
4 mo	−10	−70	−75	1+
7 mo	−20	−70	−80	2
11 mo	−15	−80	−100	2
Second Round of Cryo Completed
New baseline-1 mo later	−50	−80	−85	3
2 mo	−30	−60	−95	2
6 mo	−50	−70	−90	2

Abbreviations: AROM, active range of motion; MAS, Modified Ashworth Scale.

Table 2.

Lower limb range of motion.

Post-Cryo (d)	Knee Flexion (X)V1	Knee Flexion (X)V3	Knee Flexion AROM	Knee Flexion MAS
Baseline	130	20	0	3
1.5 mo	150	75	0	2
4 mo	145	110	No active movement	1+
7 mo	145	30	No active movement	4
11 mo	130	30	No active movement	4
Second Round of Cryo Completed
New baseline-1 mo later	115	40	No active movement	No measurement
2 mo	140	55	No active movement	No measurement
6 mo	125	No measurement	No active movement	1+

Abbreviations: AROM, active range of motion; MAS, Modified Ashworth Scale.

Table 3.

Knee range of motion.

Post-Cryo (d)	Knee Flexion (X)V1	Knee Flexion (X)V3	Knee Flexion AROM	Knee Flexion MAS
Baseline	130	20	0	3
1.5 mo	150	75	0	2
4 mo	145	110	No active movement	1+
7 mo	145	30	No active movement	4
11 mo	130	30	No active movement	4
Second Round of Cryo Completed
New baseline-1 mo later	115	40	No active movement	No measurement
2 mo	140	55	No active movement	No measurement
6 mo	125	No measurement	No active movement	1+

Abbreviations: AROM, active range of motion; MAS, Modified Ashworth Scale.

Baseline measurements of the shoulder, elbow, and knee were documented for the patient’s active ROM, maximum passive ROM, V1, and angle of catch with fast movement V3 based on the Modified Tardieu Scale and spasticity severity based on MAS (supplemental video S1, available online only at http://www.archives-pmr.org/).

Interventional procedure

On clinical assessment, potential muscles contributing to her left upper and lower limb spasticity were identified as follows: (1) the medial and lateral pectoral nerves to pectoralis minor and major; (2) musculocutaneous nerve to brachialis; (3) radial nerve to brachioradialis; (4) femoral nerve to rectus femoris. Diagnostic motor nerve blocks (DNB) were then performed on these targets using ultrasound and e-stimulation with 1 cc of 2% lidocaine to the motor nerve trunk or intramuscular motor branches to the targeted muscle. On completion of the procedure, improvement in shoulder pain, shoulder, elbow, and knee ROM and MAS was noted. The patient could take more steps with their walker. With the improved ROM and reduction in pain, they were informed about cryoneurolysis as a treatment option. The patient consented to cryoneurolysis.

Cryoneurolysis

Six weeks later, in March 2022, percutaneous cryoneurolysis was planned and performed for the same targets as the DNB. The cryoneurolysis procedure uses the Iovera Handheld system, a free-standing unit that uses nitrous oxide capsules.^a The site of injection was prepared using chlorhexidine, and subcutaneous 1% lidocaine was used to anesthetize the insertion point. A 16-gauge angiocatheter was then inserted to guide the cryoprobe, increase ultrasound echogenicity, and protect the skin from cold temperatures.^12,13 For each targeted nerve, 1-2 lesions were created for 106 seconds in a freezing and thawing cycle. Ultrasound guidance and a nerve stimulator were used to ensure accuracy and protect the vasculature.¹⁵

Once the cryoneurolysis of the musculocutaneous nerve to the brachialis was completed, the brachioradialis muscle showed little tone. In contrast, retraction and shortening of the biceps brachii were noted and were treated instead. The patient experienced severe cramping during the brachialis treatment and was offered heat and massage, which resolved the discomfort.

Follow-up measurements after cryoneurolysis were documented up to 364 days postprocedure.

Results

In May 2022, 1.5 months posttreatment, there was full passive extension of the elbow with significant improvement in V1, V3, and MAS of the shoulder in all directions and knee flexion with a noted decreased pain with an average pain score of 5 (numerical rating scale) (Table 1, Table 2 and Table 1, Table 2). The patient’s results were maintained at 7 months with a significant decrease in the average pain score (3 of 10). The patient returned at 11 months because of the rapid progression of MS and increasing stiffness, mainly in knee extensors, associated with a decrease in knee flexion V1. The improvement of shoulder and elbow V1 was maintained, and the average pain score was recorded as 4 out of 10. A repeat cryoneurolysis was offered to manage the increased tone. Within 1 month of this appointment, the patient was seen by her neurologist for rapidly declining function; she could no longer transfer and was moving to a long-term care facility. She contacted our clinic for a repeat procedure because of her advancing tone and pain.

In March 2023, 1 year after the first treatment, the tone in the shoulder and elbow had worsened over the month, new baseline measurements were documented, and cryoneurolysis was repeated to the following: (1) the pectoral nerves, with the addition of new intramuscular lesions; (2) the axillary approach to the thoracodorsal nerve to latissimus dorsi and subscapularis nerve to subscapularis¹⁷; (3) the musculocutaneous branch to the biceps; (4) the femoral nerve motor branches to the rectus femoris.

A 2-month follow-up in May 2023 revealed a significant increase in V1 for shoulder abduction and flexion, elbow extension, and knee flexion (Table 1, Table 2, Table 3). Six months later, in September 2023, the final follow-up showed a maintained shoulder abduction and flexion and knee flexion V1 (fig 1). The patient was instructed to return to the clinic if the tone returned, but she did not.

Fig 1.

Shoulder flexion (X) V1 and AROM baseline and postprocedure follow-up measurements. Abbreviation: AROM, active range of motion.

Cost analysis

In Canada, a provincial ministry of health quotes a cost of CAD 9400 for 600 units of BoNT, 4 times a year.¹⁸ The cost of BoNT therapy in the United States varies with insurers and institutions. In 2019, a review of a Veteran’s Affairs/Department of Defense usage indicated that 200 units of onaBoNT-A costs USD 899.87 per 200 unit vial, or USD 10,798.44 for 2400 units.¹⁰ The wholesale acquisition cost price is currently listed at USD 646.00 for 100 units or USD 15,504 for 2400 units.¹⁹ However, physicians contacted by the authors have reported that institutions in the United States are adding surcharges of up to USD 1500 per 100 units, thus up to USD 36,000 for 1 year of treatment at this dose. This cost does not include institutional facility fees or injection fees. The cryoprobe and gas cartridges used in the case cost USD 430 for the single treatment required each year.

Discussion

This case report studied the effects of cryoneurolysis on treating upper and lower limb spasticity in a patient with primary progressive MS who reached a plateaued response to onaBoNT-A and experienced side effects. There is a direct correlation between disease progression and spasticity; contractures, increased pain, and decreased functioning can result when not adequately treated.⁶

Although often treated for spasticity, MS is not a typical target in spasticity studies because of the changeable nature of the disease.²⁰ This was demonstrated within the case study because the patient experienced an MS crisis after their 11-month follow-up. Despite the worsening function, they had a second positive response to cryoneurolysis.

Pharmacologic interventions for spasticity, such as baclofen, tizanidine, or diazepam, have been found to have many adverse side effects as well as low satisfaction and effectiveness.^6,8 Another spasticity treatment, BoNT injections, inhibits acetylcholine from being released from presynaptic terminals, leading to chemical denervation and muscle paralysis.¹⁴ However, in studies using BoNT for shoulder girdle muscles in patients with poststroke, conflicting evidence on efficacy has been found, which could be because of dose and dilution variation for injections.²⁰ In addition, because of the upper limit doses of BoNT, there is a limitation in the number of muscles that can be targeted for treatment, and many of the muscles we treated, in the shoulder and lower leg, are considered to be off-label for BoNT injection.¹³

A comprehensive review by Dressler noted the lack of studies assessing spasticity in MS, with only 3 randomized controlled trials, 2 having <10 patients.²⁰ Furthermore, Dressler noted that MS is not a registered indication for BoNT in most countries.²⁰ Cryoneurolysis is a novel approach for spasticity treatment that results in axonotmesis and poses less risk to damaging surrounding tissue than chemodenervation through phenol or alcohol.²¹ A 2025 published study by Hashemi et al¹² showed statistically significant improvement in shoulder ROM and shoulder and elbow MAS in spastic patients because of different underlying diseases, including stroke, MS, cerebral palsy, and spinal cord injury, up to 1-year after cryoneurolysis, which is compatible with the findings of this study. Another case study by Winston et al¹³ studied a pregnant patient with MS who had a cryoneurolysis performed on the left tibial nerve because her BoNT injections were contraindicated during pregnancy. This resulted in improved active and passive ankle dorsiflexion ROM with a faster step through gait and decreased pain and calf cramping.¹³

Study limitations

Because the case report consists of 1 individual, generalizability to the entirety of the MS demographic with spasticity is not possible because of variations in symptoms, severity of the disease, and experiences.

Conclusions

In this case report, a patient with MS received cryoneurolysis as a treatment for spasticity, leading to an increase in ROM for the shoulder, elbow, wrist, and knee. After a second round of cryoneurolysis at 1 year posttreatment, improvements in passive ROM for the shoulder and knee were noted up to the final follow-up date of 185 days postprocedure. Spasticity was also decreased overall after 2 rounds of cryoneurolysis for all measurements. This demonstrates that cryoneurolysis can effectively treat upper and lower limb spasticity in a patient with MS. Further studies are required to continue examining this treatment’s long-term efficacy and generalizability; the considerable cost savings demonstrate that further cost analysis is merited.

Supplier

• a.Iovera System190 SmartSip; Pacira Biosciences.

Disclosure

M.H. has received traveling support from Pacira Biosciences. P.W. has received honorarium and educational grants from Pacira Biosciences, Abbvie, Ipsen, and Merz. The other authors have nothing to disclose.