Biomechanical and morphological foundations of the pathogenesis of cubital canal syndrome

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According to statistical data, tunnel syndromes (TS) account for about 25% of all diseases of the peripheral nervous system [1, 2]. About 30 types of TS have been described in the literature [3], with about 6 being of greatest importance in clinical practice [4, 5]. The incidence of cubital tunnel syndrome (CuTS) is 20.9–30.0 per 100,000 population [6, 7, 8], with the majority of cases occurring in people of working age — from 40 to 50 years [8].

The cause of CuTS is a nerve-canal conflict [9], which develops against the background of overstrain (more often occupational) of the muscular-ligamentous apparatus due to frequently repeated flexion-extension movements or prolonged forced positioning of the arm in a flexed state at the elbow joint, which allows CuTS to be classified as an overuse syndrome [10].

The professional risk group includes athletes (weightlifters, baseball players, tennis players), construction workers, programmers, jewelers, carpenters, packers, etc. (2.8–6.8%). Individuals whose professional activity is associated with exposure to vibration (42.5%) are most susceptible to developing CuTS [1, 6]. Trauma to the ulnar nerve can occur with prolonged leaning on the elbow while sitting, which is often observed among drivers and office workers whose work involves computer use [10].

Among the causes of rare cases of bilateral CuTS are predisposing factors such as metabolic disorders, systemic diseases, diabetes mellitus, alcoholism, vitamin deficiency, anemia, neurological pathology [11, 12], and professional activity [1, 10]. Cases of bilateral CuTS have been described in pizza cooks, where the ulnar nerves are subjected to significant biomechanical stress due to repeated forceful movements of the hands and elbows [10, 13], in a patient with psoriatic arthritis taking naproxen [14], and with long-term use of first-generation antipsychotics [10, 15].

The ulnar nerve can be compressed at various levels along its course, but about 70% of all cases occur in the cubital tunnel (CuT) region. The majority of CuTS cases are idiopathic [1, 16].

Understanding the pathogenetic mechanism of ulnar nerve compression is important not only for establishing the causes of CuTS development but also for choosing the optimal surgical approach in each specific case to achieve the best treatment outcome.

For this purpose, it is important to consider the anatomical features of the elbow joint structure, the specifics of the cubital tunnel structure, and the features of biomechanics (the anatomy of muscular tension and movement) – the functional anatomy of the elbow joint.

Topographic Features of the Cubital Tunnel.

The cubital tunnel (Mouchet's canal) is formed by Osborne's ligament, the elbow joint capsule, the posterior portion of the medial collateral ligament of the joint, and the medial epicondyle.

Fig.1. Anatomy of the cubital tunnel

The anatomical features of the ulnar nerve course determine the most typical sites of possible compression (Figure 1) at the level of the arcade of Struthers, the medial intermuscular septum, the medial epicondyle of the humerus, in Mouchet's canal, and in the flexor-pronator aponeurosis region [1, 17, 18, 19, 20, 21].

Fig. 2. Course and compression sites of the ulnar nerve

The arcade of Struthers is a musculofascial band running between the medial head of the triceps, approximately 8-10 cm proximal to the medial epicondyle, and the medial intermuscular septum, up to 2 cm wide. Compression at the level of the medial epicondyle of the humerus is more common in humeral fractures. Osborne's ligament is an arcuate ligament stretched between the medial epicondyle of the humerus and the olecranon of the ulna; it then continues into the thickened fascia of the m. flexor carpi ulnaris. Cases of multilevel compression of the ulnar nerve at the joint level have been described, where the extent of compression can range from 3 to 10 cm [22, 23].

Anatomical features of the cubital tunnel structure that contribute to the development of CuTS include [1, 2, 24, 25, 26, 27, 28]:

· The vulnerability of the superficially located ulnar nerve, protected only by thin soft tissue structures, making the nerve particularly susceptible to traumatic impact.
· The peculiarities of the ulnar nerve's location within rigid osteofibrous and fibromuscular canals, aponeurotic slits, foramina, and ligaments, which contribute to its constant trauma from bony structures during elbow joint movements.
· The presence of changes in the area of the medial epicondyle of the humerus that impede the process of free nerve gliding, potentially leading to its compression.
· Dislocations and subluxations of the ulnar nerve from the retroepicondylar groove, caused by underdevelopment or posterior positioning of the humeral epicondyle, as well as weakness of the ligament forming the superior wall of the canal. This facilitates the displacement of the ulnar nerve onto the anteromedial surface of the medial epicondyle of the humerus during elbow flexion.
· The presence, in 3-16% of CuTS cases, of the M. anconeus epitrochlearis instead of Osborne's ligament. This muscle, characteristic of primates, originates from the medial border of the olecranon and inserts into the medial epicondyle.

Biomechanical Features of N. Ulnaris

During movement, the nerve is subjected to a number of mechanical factors such as compression, longitudinal stretching, and transverse shear. The magnitude and direction of movement are determined by the anatomical relationship between the nerve and the axis of rotation.

Protection from deformation and damage is provided by factors such as elasticity, resistance, the characteristic undulating (serpentine) course in a relaxed state, and the specifics of nerve gliding (positioning) relative to the joint during movement.

The undulating course within the epineurial sheaths is characteristic not only of the nerve trunk but also of each individual nerve fiber. The length of the nerve trunk and nerve fibers significantly exceeds the linear distance between two fixed points on the limb. This protective mechanism helps reduce compressive forces on the nerve during joint movement, as the nerve fibers only begin to experience tension after the undulation is eliminated. Further stretching negatively affects the nerve trunk, initially leading to slowed conduction and eventually to a complete block in case of rupture of nerve fibers within the trunk. The perineurium is considered the structure most protected from overstretching; its undulating structure allows it to effectively neutralize traction forces during elbow joint movement. Upon relaxation, the nerve can return to its original undulating state only if it glides freely within the canal, in the absence of adhesions and fibrosis [29, 30].

Features of the Course and Position of the Ulnar Nerve Relative to the Joint

Most peripheral nerves cross the flexor side of the joint (the "inner part" when the joint is flexed) during movement. In this case, the range of joint flexion far exceeds the range of extension, allowing the nerve to remain relaxed during flexion and stretch only slightly during extension.

The ulnar and sciatic nerves cross the extensor side of the joint during flexion, leading to their excessive stretching and significant tension, while they are in a relaxed state during extension. This feature places the nerve at a disadvantage in terms of exposure to mechanical forces generated during limb movement.

In the case of the sciatic nerve, during full flexion where it crosses the extensor aspect of the hip joint, it is surrounded by sufficiently robust epineurial tissue, accounting for about 88% of the nerve's cross-sectional area. This tissue serves as a special protective mechanism [29].

The ulnar nerve, protected only by thin soft tissue structures, lacks such a protective mechanism. The ability of the nerve to undergo transverse displacement to assume an optimal position during movement somewhat reduces excessive stretching.

One of the important properties of peripheral nerves is elasticity, which allows the nerve to restore its original shape or size after the load is removed. Elasticity has threshold values; exceeding these values when stretching the nerve prevents it from returning to its initial state and leads to deformation of the nerve trunk.

The primary anatomical structure providing this property is the perineurium. Due to the corrugated form of the perineurial sheath and the undulating course of axons, nerve fibers can stretch without violating anatomical integrity [29, 30].

At the moment when the undulation of the nerve fiber disappears as it stretches, it is the perineurium that protects the nerve from further stretching, ensuring the protection of fibers within the fascicle. With increasing compression, the axons elongate along the perineurium, the cross-sectional area of the trunk decreases, nerve fibers are compressed, and intraneural pressure rises. These processes negatively affect blood supply, disrupt the trophism of nerve fibers, and lead to rupture not only of the perineurium but also of the fibers inside the nerve trunk. Continued compression results in damage to blood vessels and the epineurium. In experiments, stretching the nerve trunk by 5-10% led to the development of venous stasis, and by 11-18% to a complete block of intraneural blood flow.

Features of Elbow Joint Biomechanics Contributing to the Development of Cubital Tunnel Syndrome (CuTS)

During flexion-extension in the elbow joint, gliding of the ulnar nerve occurs with displacement of up to 10 mm in the proximal direction and up to 6 mm in the distal direction [1, 31, 32, 33].

· Flexion of the elbow joint by every 45 degrees causes a 5 mm stretch of Osborne's ligament and relaxation of the medial collateral ligament with its medial shift. This leads to a change in the canal's shape from ellipsoidal in extension to slit-like during flexion, with a reduction in cross-sectional area by 55% [1, 6, 34, 35, 36, 37].

· During elbow flexion or isometric contraction of the m. flexor carpi ulnaris [10], a 7-fold increase in pressure occurs [34, 35, 36] between the ulnar nerve and the overlying arch, reaching up to 200 mm Hg, while the average pressure during extension is about 19 mm Hg [10, 34, 35, 36, 38, 39].
· Repeated flexion movements in the elbow joint cause the n. ulnaris to stretch by 4.5–8 mm from its initial length [10, 21, 40, 41, 42], leading to its pinching in the cubital tunnel.
· Increased tension of the epicondylo-olecranon ligament and the fascia of the flexor carpi ulnaris during elbow flexion leads to direct nerve compression [1, 43].
· During forearm rotation and pronation, compression of the nerve and accompanying artery occurs due to increased pressure in the groove behind and distal to the medial epicondyle, which are more superficial than the postcondylar groove [1, 44].

Pathophysiological Mechanisms of Cubital Tunnel Syndrome

The development of compression-ischemic neuropathy is based on three key pathophysiological phenomena occurring against the background of chronic compression of the n. ulnaris in the cubital tunnel [8, 45]:

1. Impairment of venous outflow;
2. Demyelination;
3. Ischemia.
   The role of the trigger mechanism is attributed to trauma to the nerve trunk [46], against which edema of the surrounding tissues and the nerve itself forms, followed by the development of vascular disorders in the compression zone [29].

It has been experimentally established that a pressure of 20-30 mm Hg disrupts venous outflow in the epineurium. An increase in pressure to 40-50 mm Hg impairs capillary blood flow in the endoneurium, leading to the formation of venous congestion and the development of intraneural edema [47] with impaired axonal transport. Hypertension of 60-80 mm Hg and above completely disrupts microcirculation processes in the ulnar nerve, and only if the compression duration does not exceed 2 hours does microcirculation recover immediately after compression ceases [31, 37].

A pressure of 200-400 mm Hg sustained for 2 hours causes endoneurial edema; after 6 hours, the edema spreads to the central part of the nerve. Compression for 2 hours at a pressure of 400 mm Hg leads to persistent impairment of blood circulation [48]. After compression ceases, endoneurial edema persists for 28 days, and microcirculatory disturbances for up to 7 days. Impaired blood flow and edema of the nerve trunk negatively affect the processes of oxygen exchange between capillaries and nerve fibers, leading to hypoxia [29, 30].

Long-term chronic nerve compression and endoneurial edema increase the production of interleukin-6, stimulating fibroblast proliferation in synovial tendon sheaths and nerve sheaths [2, 49]. This promotes the development of scar changes in the nerve and the formation of epineurial-adhesive fusion within the cubital tunnel, intensifies nerve fixation, and limits its mobility. The scar-adhesion process contributes to constant nerve trauma during movement, exacerbating venous congestion and impairing blood supply [47].

A vicious circle typical of compression-ischemic neuropathies forms: compression → ischemia → edema → increased intraneural pressure → venous and lymphatic stasis → further increase in intraneural pressure → impaired arterial blood flow → ischemia → damage to the nerve trunk [30, 47, 50].

Pathophysiological Changes in the Nerve Trunk under Compression

Most authors agree that only prolonged compression causes nerve demyelination and axonal damage [43, 47]. The degree of damage depends not only on the force and duration of trauma but also on the size of the nerve fiber, its position within the nerve trunk, and the number and size of nerve fiber fascicles. It is proven that fibers at the periphery of the nerve trunk are damaged more severely than those located centrally, and thick myelinated nerve fibers are more susceptible to damage. Nerves consisting of a small number of large fascicles suffer more than nerves composed of many small fascicles, as they contain more connective tissue.

Compression and the accompanying edema lead to structural changes in the nerve. Pressure of up to 80 mm Hg for 2 hours initiates processes of Schwann cell swelling and disintegration of the cytoplasmic reticulum, which continue for 28 days after compression ceases. The single factor of compression, even under low intracanal pressure as low as 10 mm Hg, is sufficient to initiate demyelination processes [30]. Three degrees of conduction disturbance in a nerve due to injury are distinguished: Grade I – a rapidly reversible physiological block; Grade II – a local demyelination block; Grade III – Wallerian degeneration.

The demyelination process can occur along two main pathways:

1. Paranodal demyelination – develops under compression, characterized by preservation of the myelin sheath in the internodal segment.
2. Segmental demyelination – develops against a background of ischemia, characterized by homogeneous demyelination [47, 51].

Compression over 2 weeks stimulates Schwann cell proliferation. There is an opinion that Schwann cells may possess mechanosensitive properties, and the initiation of proliferation occurs via internal stimuli [38]. Proliferation leads to local demyelination and remyelination of the myelin sheath, reorganization of the Nodes of Ranvier occurs, and the myelin in the internodal region, where it is most unstable, changes. A number of authors hypothesize that the decrease in conduction velocity in nerve fibers is precisely related to the appearance of fibers with thin myelin sheaths and shortened internodal segments [52].

Simultaneously with proliferation, the process of apoptosis occurs, which has a biphasic character: the first phase during active proliferation and the second in the late period of morphological changes. While the late stage of apoptosis is associated with hypertrophy of connective tissue, the cause of the early stage of apoptosis remains unknown to this day. The processes of proliferation and apoptosis of Schwann cells are initiated even in the absence of morphological signs of degeneration, structural changes in the neuromuscular synapse, and preservation of the general motor potential. If at the early stage of the disease morphological changes are reversible, then at later stages axonal degeneration develops at the level of compression with classic Wallerian degeneration in the distal segment of the nerve trunk [53], denervated muscles degenerate with the development of atrophy and proliferation of connective tissue within them [54, 55].

Impairment of axonal transport under nerve compression conditions directly depends on the duration and force of impact. Experiments have established that a pressure of 20 mm Hg for 2 to 8 hours does not affect fast axonal transport; with an increase in pressure to 30 mm Hg and impact duration up to 8 hours, its slowing occurs. With pressure exceeding 50 mm Hg, a reversible block of fast axonal transport forms, which recovers 24 hours after pressure normalizes. At pressures of 200-400 mm Hg, recovery occurs only after 3 and 7 days, respectively. A similar pattern is observed when studying the effect of compression on slow axonal transport. Pressure on the nerve of 20 mm Hg for 8 hours does not cause any disturbances in slow axonal transport, while a force of 30 mm Hg leads to fluid accumulation and the formation of edema proximal to the compression site [30, 56].

The combination of compression and ischemia negatively affects the state of intraneural tissues, damaging not only Schwann cells and nerve bundles but also intraneural vessels. Phagocytosis processes slow down, fatty infiltration of cellular elements of the endoneurium and perineurium develops. Under conditions of impaired microcirculation of nerve fibers with alternating periods of ischemia and reperfusion, the permeability of cell membranes increases, leading to an increased transport of proteins from the vascular bed into the nerve. As a result, intraneural edema persists even after ischemia ceases and blood flow is restored, lasting for 28 days [57, 58]. Edema becomes permanent first in the epineurium and then in the endoneurium. Constant edema and increased pressure in the canal ultimately lead to a decrease in intraneural blood flow with activation of fibroblasts and the formation of scar tissue inside and around the nerve.

Pathophysiological Changes in the Nerve Trunk under Stretching

One of the important properties of peripheral nerves is elasticity, which allows the nerve to restore its original shape or size after the load is removed. Elasticity has threshold values; exceeding these during stretching will prevent the nerve from returning to its initial state and will lead to deformation of the nerve trunk. The elasticity and strength of nerve trunks during stretching depend on the perineurium, while the epineurium provides protection against compression. Thanks to the corrugated form of the perineurial sheath and the undulating course of axons, nerve fibers can stretch without violating anatomical integrity. At the moment when the undulation of the nerve fiber disappears as it stretches, it is precisely the perineurium that protects the nerve from further stretching, ensuring the protection of fibers within the fascicle. With increasing compression, axons elongate along the perineurium, the cross-sectional area of the trunk decreases, nerve fibers are compressed, and intrafascicular pressure increases [29, 30].

These processes negatively affect blood supply, disrupt the trophism of nerve fibers, and lead to the rupture of not only the perineurium but also the fibers within the nerve trunk. Continued compression causes damage to blood vessels and the epineurium. In experiments, stretching the nerve trunk by 5-10% leads to the development of venous stasis, and by 11-18% to a complete block of intraneural blood flow. If the elastic limit is not exceeded during stretching, the nerve restores its original length and elastic properties upon load removal. However, if the elastic limit is exceeded, the original length is not restored, and nerve fiber deformation occurs. The function of specific shock absorbers lies with the epineurium and perineurium, and only a breach in the integrity of the perineurium leads to a loss of elasticity due to the destruction of nerve fibers [8, 30].

During stretching, the cross-sectional area decreases, and nerve fibers are compressed and deformed, with the compression force being highest in the center of the elongated nerve segment. Nerve stretching negatively impacts intraneural blood flow, impairing nerve function. Stretching up to 10% of the original length does not cause significant structural changes in the nerve; conduction disturbances are functional and reversible. As stretching increases, nerve function begins to suffer, venous stasis forms with pronounced disturbances in intraneural blood flow. Elongation of the nerve by 15% leads to complete intraneural ischemia, which is reversible upon relaxation. An increase of 20% typically exceeds the nerve's elastic threshold, causing ruptures in thinner nerve fibers, and the recovery of conduction can take from 10 to 15 minutes, during which the nerve's excitation threshold increases from an initial value of 0.5 mA to 8-10 mA. In cases of stretching by 25-30% of the original length, not only nerves but also vessels are damaged, leading to the formation of paraneural and intratrunk hematomas. Complete anatomical transection of the nerve can occur with stretching of 35-38% of the original length [30, 47].

Vascular disturbances in the compression zone in the form of transient ischemia and reperfusion lead to the development of oxidative stress in cells and tissues [45, 59], which triggers a process of biochemical changes in the nerve fiber. The main damage affects lipid-rich myelinated fibers. Under conditions of ischemia and cell damage, the secretion of prostaglandin E2 increases, causing vasodilation and increasing the sensitivity of nerve endings to chemical and mechanical stimuli, sensitizing nociceptive receptors to pain mediators such as histamine and bradykinin [60, 61, 62].

The ulnar nerve is mixed; differences in the structure of its fascicles determine their varied responses to compression and ischemia, demonstrating a wide spectrum of predominant disturbances in specific fibers: metabolic disorders, demyelination (neurapraxia), axonal degeneration (axonotmesis) [47]. Functional recovery depends on the severity of morphological changes.

Pathophysiological Features of Nerve Fiber Regeneration

Studying the pathophysiological features of peripheral nerve regeneration is also important for correctly constructing a rehabilitation algorithm for patients with Cubital Tunnel Syndrome (CuTS) [63, 64, 65].

The rehabilitation prognosis directly depends on the duration of the disease. It has been experimentally proven that after 2 months, the ability of axons to regenerate decreases, and signs of denervated muscle atrophy appear [65]. Initial signs of fibrosis are observed as early as the 3rd week of the disease [63, 65]. Over the subsequent 12-18 months, pronounced fibrosis of denervated muscles develops [63, 66, 67, 68]. After 18-24 months post-injury, the likelihood of successful axonal regeneration is practically reduced to zero due to the development of fibrosis and obliteration of the Schwann cell sheaths in the distal nerve segment [63, 65, 70, 71].

Consequently, it can be concluded that surgical treatment is advisable within the first 4-6 months in cases of moderate to severe CuTS [63, 65, 67, 72].

However, the success of both conservative and surgical treatment directly depends on the severity of CuTS. The risk of unfavorable outcomes and possible recurrences significantly increases with severe forms and a prolonged course of the disease, and recovery times are substantially extended.

About the authors

Leila Edilgireeva

First Moscow State Medical University I.M. Sechenov (Sechenov University)

Author for correspondence.
Email: snickers_192000@mail.ru
ORCID iD: 0000-0001-6067-8962
SPIN-code: 9623-4500
Scopus Author ID: 57568022200
ResearcherId: PDW-9099-2025

аспирант

Russian Federation, Trubetskaya St., 8, building 2

References

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