Cryoneurolysis

Cryoneurolysis, also referred to as cryoanalgesia, cryoneuromodulation, or cryoneuroablation, is a procedure used to temporarily block nerve conduction along peripheral nerve pathways. The procedure, which involves insertion of a small probe to freeze the target nerve, allows for the complete regeneration of the structure and function of the affected nerve. While other treatments for nerve-associated pain, such as oral medications, chemical injections, or surgery, can fail or lead to more serious side effects cryoneurolysis is minimally invasive and associated with minimal side-effects. Cryoneurolysis has been used to treat a variety of painful conditions including: phantom limb pain, intercostal nerve pain, foot neuromas, ilioinguinal nerve pain and occipital neuralgia.

History

The use of cold for pain relief and as an anti-inflammatory has been known since the time of Hippocrates (460-377 B.C). Since then there have been numerous accounts of ice used for pain relief including from the Ancient Egyptians and Avicenna of Persia (A.D.982–1070). In 1812 Napoleon's Surgeon General noted that half-frozen soldiers from the Moscow battle were able to tolerate amputations with reduced pain and in 1851, ice and salt mixtures were promoted by Arnott for the treatment of nerve pain. Campbell White, in 1899, was the first to employ refrigerants for medical use and Allington, in 1950, was the first to use liquid nitrogen for medical treatments. In 1961, Cooper et al. created an early cryoprobe, which reached a temperature of -190 °C using liquid nitrogen. Shortly thereafter, in 1967, an ophthalmic surgeon named Amoils used carbon dioxide and nitrous oxide to create a cryoprobe which reached a temperature of -70 °C.

Mechanisms of Action

Nerve Anatomy

See Nerve

Each nerve is composed of a bundle of axons. Each axon is surrounded by the endoneurium connective tissue layer. These axons are bundled into fascicles which are surrounded by the perineurium connective tissue layer. Multiple fascicles are then surrounded by the epineurium, which is the outermost connective tissue layer of the nerve. The axons of myelinated nerves have a myelin sheath made up of Schwann cells that coat the axon.

Nerve Injury Classification

See Peripheral nerve injury classification

File:Nerve injury classification table of temperatures required for injury.png

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The classifications of nerve damage have been well-defined by Sir Herbert Seddon and Sunderland and are still in use today. The table at the right details the forms (neurapraxia, axonotmesis and neurotmesis) and degrees of nerve injury that occur as a result of exposure to various temperatures.

Cryoneurolysis treatments which utilize nitrous oxide (boiling point of -88.5 °C) as the coolant fall in the range of an axonotmesis injury, or 2nd degree injury according to the Sunderland classification system. Treatments of the nerve in this temperature range are reversible. Nerves treated in this temperature range experience a disruption of the axon, with Wallerian degeneration occurring distal to the site of injury. The axon and myelin sheath are affected, but all of the connective tissues (endoneurium, perineurium, and epineurium) remain intact. Following Wallerian degeneration the axon regenerates along the original nerve path at a rate of approximately 1–2 mm per day.

Cryoneurolysis treatments which utilize liquid nitrogen (boiling point of -195.8 °C) as the coolant fall into the range of a neurotmesis injury, or 3rd degree injury according to the Sunderland classification. Treatments of the nerve in this temperature range are irreversible. Nerves treated in this temperature range experience a disruption of both the axon and the endoneurium connective tissue layer.

Procedure

Cryoprobe

Cryoneurolysis is performed with a cryoprobe, which is composed of a hollow cannula that contains a smaller inner lumen. The pressurized coolant (nitrous oxide or liquid nitrogen) travels down the lumen and expands at the end of the lumen into the tip of the hollow cannula. No coolant exits the cryoprobe. The expansion of the pressurized liquid causes the surrounding area to cool (known as the Joule-Thomson effect) and the phase change of the liquid to gas also causes the surrounding area to cool. This causes a visible iceball to form and the tissue surrounding the end of the cryoprobe to freeze. The gas form of the coolant then travels up the length of the cryoprobe and is safely expelled. The tissue surrounding the end of the cryoprobe can reach a temperature as low as -88.5 °C when nitrous oxide is used as the coolant and can reach a temperature as low as -195.8 °C when liquid nitrogen is used as the coolant.

Cryoneurolysis Devices

The Endocare PerCryo® Percutaneous Cryoablation device (HealthTronics, Austin, TX, USA) utilizes liquid nitrogen as a coolant and can be used with 4 different single cryoprobe configurations with a diameter of either 1.7 mm (~16 gauge) or 2.4 mm (~13 gauge) in diameter .

The Myoscience Iovera°® is a handheld device (Myoscience, Redwood City, CA, USA) that uses nitrous oxide as a coolant and can be used with a three-probe configuration with a probe diameter of 0.4 mm (~27 gauge).

Nerve Localization and Treatment

In order for the cryoneurolysis treatment to be effective it is necessary for the target nerve to be precisely located. The first step in locating the correct nerve is palpation and guidance based on anatomical landmarks. When necessary, a variety of localization techniques including percutaneous electrical nerve stimulation (PENS), live ultrasound or fluoroscopic guidance are used.

Electrical nerve stimulation is the most commonly used form of nerve localization. Once the nerve is located by palpation, a local anesthetic is injected into the skin and a sharp stimulating needle is introduced. In some instances patients may be mildly sedated but must be capable of providing the feedback used for localization. Once it is confirmed that the needle is stimulating the target nerve a blunt cryoprobe is passed through the stimulating needle and the needle is withdrawn to expose the tip of the cryoprobe. Cryoneurolysis then begins when the coolant is allowed to flow to the end of the cryoprobe.

One unique aspect of the Iovera device is the ability to treat certain nerves using only anatomical landmarks, which eliminates the need to use other visualization techniques, such as ultrasound and fluoroscopy. Once the treatment lines are drawn to find the nerve using anatomical landmarks, a local anesthetic is applied and the cryoprobes (which are sharp) are inserted into the skin. Cryoneurolysis then begins when the coolant is allowed to flow to the end of the cryoprobe.

Treatment Applications

Cryoneurolysis has been shown to effectively treat both motor and sensory nerves. Below are brief summaries of studies conducted on a variety of nerves and nerve-related conditions.

Motor Nerves

A recent animal study demonstrated that full functional and structural recovery following cryoneurolysis of the sciatic nerve in a rat occurs within 16 weeks. Results from a related animal study demonstrate that repeated treatments to the sciatic nerve of the rat do not diminish its capacity for regeneration. In addition, nerves treated multiple times regenerate completely each time they are treated, but they do so on the same time scale as nerves treated only once.

Forehead Wrinkles

To reduce the appearance of dynamic forehead wrinkles, cryoneurolysis can be applied to the temporal branch of the facial nerve, a motor nerve of the face. This nerve can be located using only anatomical landmarks. Treatment of the nerve results in a lack of movement of the frontalis and corrugator supercilli muscle groups. Results typically last for approximately 3 months.

Sensory Nerves

Knee Pain Secondary to Osteoarthritis

Osteoarthritis is a degenerative disease of joints, and can lead to chronic pain. This pain can be treated by performing cryoneurolysis on two of the sensory nerves innervating the knee: the infrapatellar branch of the saphenous nerve and the anterior femoral cutaneous nerve. These two branches can be targeted using anatomical landmarks only. By treating these nerves and reducing or eliminating the pain associated with osteoarthritis, the patient can then start exercising the knee to restore functionality or to prepare for a knee replacement surgery. Quality of life can be much improved by reducing the amount of pain in the knees. Care must be taken to ensure patient does not develop a Charcot knee or related deinnveration-related injury to the joint.

Phantom Limb Pain

Phantom limb pain, sensations of pain perceived in a missing amputated limb, is understood to be caused by interactions between the central nervous system and the peripheral nervous system. The associated pain can range anywhere from mild to severe. The pain sensations have been described as sharp, burning, cramping, shocking, shooting, or like pins and needles. Patients who have pain prior to amputation are more likely to have pain in their phantom limb. Upper extremity phantom limbs have been more likely to cause pain than lower extremity. In an attempt to cure phantom limb pain, Ramachandran created a mirror box in order to trick the brain into seeing the limb. While this helped some patients relieve pain by unclenching a fist or scratching a hand, it did not provide lasting relief. Cryoneurolysis has been used to treat phantom limb pain with moderate success.

Post-Thoracotomy Pain

Post-thoracotomy pain is caused by the intercostal nerves after an incision into the pleural space of the chest. A thoracotomy is a very painful procedure because of the incision, the interruption of muscle and ligamentous structures, and pleural irritation from the chest tube. Respiratory function is often altered, but could be improved by effective analgesia. The current treatments for post-thoracotomy pain are opiates, epidural analgesia, and intercostal nerve blocks. An intercostal nerve block can be a short-term anesthetic block, a longer lasting neurolytic block, or a permanent neurectomy. These treatments are easily available, but have unwanted side effects. There are studies that showed cryoneurolysis on intercostal nerves help reduce pain associated with those nerves.

Zygapophyseal Joint Pain

An estimated 80% of people will have lower back pain at some point in their lifetime. Most of the time, the pain is resolved in six to twelve weeks and does not return. However, many people develop chronic lower-back pain with recurring episodes. A specific characteristic of lumbar facet joint syndrome (a primary cause of lower back pain) is that the pain is difficult to localize, and the pain often radiates into the leg. Walking or carrying heavy things is known to worsen the pain, thus limiting a patient’s ability to perform these and other tasks. Current treatments include physiotherapeutic exercise, behavioral therapy, and medical treatments. Another form of treatment is denervation of the joint using radiofrequency or cryoneurolysis.