Multisite treatment with percutaneous cryoneurolysis for the upper and lower limb in long-standing post-stroke spasticity

Stroke is the leading cause of disability worldwide. Stroke causes damage to the pyramidal tract and parapyramidal fibers,¹ resulting in the upper motor neuron syndrome and spasticity.² Up to 20% to 40% of stroke survivors will develop spasticity, impacting health status, pain, function, and quality of life.³

Spastic hemiplegia may affect all muscles crossing joints in the upper and lower limbs, impairing functional capability, mobility, impacting daily life activities, and restricting social participation. The main treatment is focal botulinum toxin injections to reduce spasticity which is effective for a limited period and requires injections up to four times a year, indefinitely. A more permanent treatment of spasticity is achieved by highly specialized surgical neurotomy, the sectioning of a part of the nerve to reduce the overactivity of the spastic muscles but with surgical invasiveness and complications.⁴ An alternative for both long-lasting treatment and a minimally invasive approach has been recently introduced: “percutaneous cryoneurolysis”.⁵

Ultrasound and e-stimulation guided percutaneous cryoneurolysis is a minimally invasive procedure involving a probe that generates an ice ball due to rapidly freezing temperatures ranging from -60 °C to -88 °C depending on the cryogen agent. The ice ball forms from interstitial fluid near a peripheral nerve, causing secondary axonotmesis. Cryoneurolysis of afferent nerves is an established pain management technique that has been used for decades.⁶

Percutaneous cryoneurolysis could represent a new compromise between botulinum toxin iterative injections and radical surgery in terms of invasiveness and complications and the long-term benefit ratio on spasticity and function.

A 43-year-old man with severe spastic right hemiparesis after left MCA stroke syndrome prior 12 years, caused by endocarditis, in the chronic phase, was referred for refractory spasticity in both upper and lower limbs. The predominant spasticity score using Modified Ashworth Scale (MAS) was 3, involving the shoulder adductors and internal rotators, elbow flexors, forearm pronators, wrist flexors, finger flexors and ankle plantar flexor muscles (Table I). He used an ankle-foot orthosis to assist with an independent transfer. He self-propelled a wheelchair for mobility. He had good static balance with sitting. He was independent in toileting, dressing, hygiene, and basic meal preparation but he lived in a living facility for the rest of his care. He had access to physiotherapy as needed.

Table I. —Spasticity and Range of motion of targeted segments before and after cryoneurolysis treatment.

Parameter		Baseline	2-month follow-up	4-month follow-up
Shoulder flexion	V1	85°	110°	130°
	V3	55°	70°	70°
	AROM	55°	75°	60°
	MAS	3	1+	2
Shoulder abduction	V1	85°	130°	130°
	V3	60°	75°	80°
	AROM	70°	70°	90°
	MAS	3	2	2
Shoulder external rotation	V1	55°	65°	45°
	V3	25°	No	25°
	AROM	30°	45°	20°
	MAS	2	1+	2
Elbow extension	V1	-50°	-30°	-15°
	V3	-90°	-50°	-80°
	AROM	-60°	-40°	-45°
	MAS	4	2	2
Wrist extension	V1	+25°	+60°	+60°
	V3	+10°	-15°	-5°
	AROM	No active movement	No active movement	No active movement
	MAS	3	2	3
Ankle dorsiflexion (knee flexed)	V1	-40°	+10°	+10°
	V3	No	No	+5°
	MAS	4	2	3
Ankle dorsiflexion (knee extended)	V1	-40°	-20°	-20°
	V3	No	-45°	-30°
	MAS	4	3	3

Tardieu Modified Scale V1 and V3, AROM: active range of motion. Modified Ashworth Scale, Flex: flexion, Ext: extension.

He had been maintained on onabotulinum toxin A injection program only in his right upper limb for several years, every 4-month, with 300 units: brachialis 50 units, brachioradialis 25 units, pronator teres 50 units, flexor carpi radialis 50 units, flexor digitorum superficialis 50 units, flexor carpi ulnaris 25 units, flexor digitorum profundus 50 units, at 2:1 dilution using anatomical landmarks and electromyographic guidance. He used no oral antispasmodics.

The patient requested a longer lasting treatment as he had plateaued with toxin injections. His primary goals were to facilitate: 1. dressing of his right upper extremity, 2. fitting of a right forearm wrist hand orthosis, 3. increase the range of motion (ROM) of the ankle to better accommodate the orthosis to assist with transfers.

On examination, severe spasticity MAS Grade 3 was observed, in the right upper limb at all joints tested and in the right ankle. The limitation of shoulder abduction and external rotation was due to the combined hypertonicity and shortening of the pectoralis, subscapularis and latissimus dorsi muscles. The muscles involved in elbow flexion spasticity were biceps brachialis and brachialis, without the brachioradialis muscle. The forearm pronation, wrist and finger flexion showed there was a preferential involvement of muscles innervated by the median nerve: pronator teres, flexor carpi radialis, flexor digitorum superficialis and flexor digitorum profundus. The muscles involved in equinus were gastrocnemius and soleus.

To confirm the clinical hypothesis, diagnostic nerve blocks (DNB) were performed, after obtaining informed consent. The targeted nerves included:

• the medial and lateral pectoral nerves to pectoralis major and minor;

• the thoracodorsal nerve to latissimus dorsi;

• the intramuscular branches of the subscapular nerve to teres major and subscapularis;

• the musculocutaneous nerve branches to the biceps brachii, and brachialis muscles;

• the mixed sensorimotor trunk of the median nerve above the elbow crease;

• the tibial nerve trunk at the popliteal fossa.

Each target underwent an injection of 1cc of 2% lidocaine in each site and using ultrasound guidance and e-stim. Lidocaine provides a temporary result that predicts the final effects of cryoneurolysis.^{5, 7} There was no undesirable loss of sensation or function after the DNB. No adverse events were reported.

After the DNBs, the patient demonstrated an immediate improvement in tone and an increase in passive ROM in all related joints. The DNB fulfilled the objectives set with the patient.

After obtaining informed consent, the patient consented to cryoneurolysis procedure for the treatment of his spastic hemiplegia of the same targets using the Iovera handheld system (Iovera-190-Smart-Tip, Pacira Biosciences) on a later date. This is a free-standing handheld unit that uses liquid nitrous oxide capsules. The skin around the injection site was prepared with chlorhexidine swabs. The entry point was anesthetized with local infiltration of 1% lidocaine. A 16-gauge angiocatheter was inserted to guide the Smart Tip and protect the skin from potential cold-related adverse events. The cryoprobe was inserted through the catheter and the targeted nerve was located using known anatomy and under ultrasound guidance. The targets were confirmed using electrical stimulation of less than 1 mA at 1 Hz. One to two lesions were created along each nerve, though the tibial trunk received three lesions each lasting 106-second freezing and thawing cycle (Figure 1, 2, 3, 4, 5, 6).

Figure 1.

—Cryoneurolysis for the treatment of subscapularis and thoraco-dorsal nerves.

Figure 2.

—Cryoneurolysis for the treatment of lateral pectoralis nerves.

Figure 3.

—Cryoneurolysis for the treatment of biceps brachialis nerve.

Figure 4.

—Cryoneurolysis for the treatment of brachialis nerve.

Figure 5.

—Cryoneurolysis for the treatment of the median nerve trunk.

Figure 6.

—Cryoneurolysis for the treatment of the tibial nerve trunk.

Immediately after cryoneurolysis, the patient described less tone and spasticity and increased ROM in his shoulder, elbow, wrist, fingers, and ankle both passively and actively (Table I).

The clinical results before and after the procedure is shown in the additional video material. Spasticity score and ROM in all related joints showed improvement compared to baseline measures at the 2- and 4-month follow-up (Table I) (Supplementary Digital Material 1: Supplementary Video 1, 40.7 MB, 3 min 27 s).

As his arm was not functional, no functional motor skills were gained, however the caregiver noted significant ease in passive movements to facilitate dressing and personal care and donning the upper and lower extremity orthoses.

After long term treatment with botulinum toxin, cryoneurolysis appears to be a possible percutaneous, minimally invasive alternative, with previously demonstrated longer-lasting effects and minimal side effects.⁸ We note that neither chemodenervation with phenol or alcohol nor surgical neurectomy have been described to have such widespread use as our targets, nor are they offered for the whole mixed nerve trunks.^9-11 The localization of the upper and lower limb nerves using ultrasound and neuro-stimulation in this case study, are readily achievable according to recent research.⁷

A concern of chemoneurolysis is that the treatment will lead to undesirable weakness or sensory loss. This type of adverse event may arise due to the spread of the neurolytic agent, such as phenol away from the targeted structures, poor localization of target nerves, or poor treatment specificity.

Cryoneurolysis involves the formation of an ice ball; there is no risk of liquid spreading to undesirable nerves. Ultrasound guidance and electrical stimulation for motor targets facilitates precise localization. Finally, using a DNB prior to cryoneurolysis reduces the risk of adverse events from poor specificity by informing the treatment pathway before any long-lasting intervention. This process complements the clinical evaluation to ensure that only nerves innervating muscles directly implicated in the pathology are treated.

Cryoneurolysis has been well tolerated by most patients with adverse events being described as mostly mild in severity.^{12, 13} A recent secondary cohort analysis of patients treated with cryoneurolysis of mixed and primarily motor nerves showed side effects occurring in 1% of treatments for primarily motor nerves and none for intramuscular nerve branches.⁷ The most reported adverse events are dysesthesia and paresthesia. A recent study of 277 nerves treated by cryoneurolysis highlighted the potential side effects of this technique: one patient had a local skin infection, two patients had bruising or swelling; all resolved within one month, nine reported nerve pain or dysesthesia (two motor, seven mixed motor sensory nerves). Moreover, 96.75% of nerve treatments had no pain or dysesthesias beyond treatment.⁸

The patient treated in the present case study did not report any side effects or adverse events after cryoneurolysis.

The described case report is based on the experience of a single patient.

Further research is needed to validate objective measures of treatment efficacy. Future studies should include well-designed randomized controlled trials to understand the efficacy of this treatment compared to other options.

Cryoneurolysis of multiple nerves to treat upper and lower limb spasticity of a patient after stroke was associated with decreased spasticity and increased range of motion of all targeted joints. Percutaneous cryoneurolysis could be used as a complementary treatment option between botulinum toxin injections and surgical neurotomy. Further studies are required to understand the efficacy and safety of the treatment.

Supplementary Digital Material 1

Supplementary Video 1

Clinical results before and after the procedure.