Diagnostic Considerations in Compressive Neuropathies

Abstract

Peripheral nerve compression of the upper extremity is a common pathology often necessitating surgical intervention, much is known, but much more is left to understand. For the more common pathologies, carpal tunnel syndrome, cubital tunnel syndrome, and ulnar tunnel syndrome, research and clinical efforts directed toward standardization and reduction of resource use have been attempted with varied success. Diagnosis of many of these syndromes is largely based on a proper history and physical examination. Electrodiagnostic studies continue to have value, but proportionally less than previous decades. In addition, emerging technologies, including magnetic resonance neurography, novel ultrasound evaluation techniques, and ultrasound-guided diagnostic injections, are beginning to demonstrate their ability to add value to the diagnostic algorithm, particularly when less common compressive neuropathies are present and/or the diagnosis is in question.

Peripheral nerve compression syndromes are common conditions that should be considered for any patient presenting with upper extremity pain, paresthesia, dysesthesias, and/or muscle weakness.¹ Carpal tunnel syndrome (CTS) and cubital tunnel syndrome (CuTS) are the most common nerve compressive neuropathies in the upper extremity. Carpal tunnel syndrome occurs in 1% to 5% of the general population, and CuTS has an incidence of 30 per 100,000 person-years.2, 3, 4, 5 However, physicians must also be well-versed in the diagnosis of less prevalent nerve compression syndromes that are becoming increasingly recognized as symptom generators; such as pronator syndrome, anterior interosseous nerve (AIN) syndrome, radial tunnel syndrome, and posterior interosseous nerve syndrome (PIN).⁶

The American Academy of Orthopedic Surgery (AAOS) has clinical practice guidelines (CPGs) for the diagnosis of CTS.⁷ However, for most compressive neuropathies, there is no true diagnostic gold standard, and diagnosis relies on a combination of clinical presentation, physical examination findings, as well as use of certain imaging modalities and electrodiagnostic studies (EDSs); in some cases, even diagnostic injections.⁸ Understanding the diagnostic approach to each compressive neuropathy of the upper extremity is imperative for successful management. An ineffective clinical algorithm will likely make all interventional and conservative strategies lead to less than ideal care.

Carpal Tunnel Syndrome

Clinical presentation

Phalen’s original description of CTS, published in 1966, states that clinical assessment alone is usually sufficient to make an accurate diagnosis.⁹ In his study, Phalen describes his primary findings as being related to sensory disturbances both “subjectively and objectively” being related to the median nerve distribution distal to the wrist, typically involving numbness and tingling that is worse at night and worse with activity. In addition, his primary examination findings were a positive Tinel sign over the wrist, and the wrist flexion examination, which he described (Phalen test). Patients with CTS often present with intermittent symptoms, nocturnal pain, and paresthesia in the median nerve distribution. The distribution includes the volar thumb, index, middle, and radial one-half of the ring fingers.⁹ Paresthesia of the thenar eminence is absent because the palmar cutaneous branch of the median nerve traverses the wrist superficial to the transverse carpal ligament. Nocturnal pain is the most sensitive predictor of CTS.¹⁰

Physical examination

Numerous provocative maneuvers have been described for diagnosing CTS. The AAOS does not support the use of any single physical examination maneuver in isolation because moderate and strong evidence exists that each examination alone has a poor predictive value for diagnosing CTS.¹¹ Using electrodiagnostic testing as the reference standard, Makanji et al¹² assessed numerous examination maneuvers and found the following sensitivities and specificities, respectively: scratch collapse test: 0.31 and 0.61; Phalen: 0.67 and 0.33; Durkan: 0.77 and 0.18; Tinel: 0.43 and 0.56; thumb abduction weakness: 0.37 and 0.73 and thenar atrophy: 0.18 and 0.96.4 The CTS-6 is a validated and widely used diagnostic tool based on a consensus of expert opinion that predicts the probability of CTS based on weighted diagnostic criteria (Fig. 1). Numbness in the median nerve distribution, nocturnal symptoms, thenar weakness/atrophy, a positive Tinel sign, a positive Phalen test, and the loss of 2-point discrimination comprise the CTS-6 criteria. A score greater than 5 indicates a 25% probability of CTS, whereas a score greater than 12 confers an 80% probability.

Figure 2.

Diagnostic parameters of the provocative tests used in CTS.¹⁴ Table adapted from Makanji et al¹² depicting the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for common provocative tests used in CTS.

Figure 1.

Carpal tunnel syndrome-6. From Fowler JR et al.¹³

Electrodiagnostic studies

Electrodiagnostic studies encompass both nerve conduction studies (NCSs) and EMG. They have been found to be a significant driver of cost in the diagnosis of CTS.¹⁵ Electrodiagnostic studies are most helpful in the diagnosis of CTS when differentiating between other causes of neuropathy. The AAOS CPG supports the use of EDS when differentiating among alternative diagnoses when surgical management is being considered.¹¹ The primary findings in the electrodiagnostic assessment of CTS are paranodal demyelination of the median nerve at the wrist, focal slowing across the wrist along with increased distal conduction latencies with respect to the motor and sensory fibers. Reduced median nerve action potential across the wrist, as well as electrical instability of the abductor policis brevis muscle membrane, occur in more severe cases and indicate that axonal loss may be present. In quantifying axonal loss, the compound muscle action potential can be compared with the normal contralateral side.^16,17

Because increased carpal tunnel pressure causes median nerve compression and entrapment, there is a decrease in microcirculation and biochemical disturbances within the nerve. Further progression leads to disturbances in endoneural blood flow and edema because of the increased permeability of endoneural blood vessels. As edema increases, the diffusion distance for oxygen increases, driving hypoxia and resulting in axonal degeneration. Early demyelination is common before progression to full axonal loss and is a typical finding in CTS.¹⁸ The American Association of Neuromuscular and Electrodiagnostic Medicine has its clinical practice guide describing the use of EDS in CTS as a “validated and reproducible clinical laboratory study” with a sensitivity >85% and specificity of 95%.¹⁹ A prospective, blinded study evaluating the utility of EDS in 143 patients diagnosed with CTS based on CTS-6 criteria found the average change in probability of a correct diagnosis to be −0.02 and −0.06 when stringent and lax criteria were used, respectively. This demonstrated that EDS is of little diagnostic value in patients with a high CTS-6 score.¹⁴ The same study included a number of sensitivities and specificities for provocative tests used in CTS (Fig. 2).^12,14

Figure 5.

Possible sites of compression in pronator syndrome. A Ligament of Struthers (Arcade VIII). B Pronator teres. C Bicipital aponeurosis. D Fibrous arcade from the proximal margin of the FDS to the middle finger.

Imaging

The American Academy of Orthopedic Surgery CPGs does not support routine radiographic imaging in patients suspected of having CTS.¹¹ Exceptions occur in the setting of acute CTS associated with fracture or CTS in patients with a history of distal radius fractures.²¹ Indications for ultrasound (US) are not well defined; however, studies have demonstrated an increase in median nerve cross-sectional area at the level of the wrist in patients with CTS, with a maximal cross-sectional area of >0.12 mm² being abnormal. During US image acquisition, swelling of the median nerve proximal to the site of compression, loss of the normal fascicular architecture (“honeycomb appearance”), and flattening with compression by the transverse carpal ligament can also indicate CTS. Further, comparative cross-sectional measurement of the median nerve at the carpal tunnel as compared with the pronator quadratus has been shown to be diagnostic, in which a difference in median nerve area by 2 mm has been found to be 99% accurate.¹⁹

Ultrasound is highly specific and with a high-positive predictive value when clinical suspicion is high.²² Conversely, US has a low-negative predictive value. Thus, one cannot rule out CTS in the setting of a normal median nerve cross-sectional area.²² Ultrasound has an additional modality in CTS in relation to postoperative care. Nerve area again can be observed, as well as the absence of the transverse carpal ligament. Additionally, scarring necessitating revision may be observed along with perineural fibrosis with changes in nerve gliding during dynamic observation.^23,24,25 In combination with each other, US and EDS are useful diagnostically, with 1 study reporting 100% sensitivity and 92.5% specificity.²⁶

Magnetic resonance imaging (MRI) is indicated when there is clinical suspicion for a space-occupying lesion, nerve-based tumor, or history of trauma. Magnetic resonance imaging can also show the secondary effects of nerve compression, including muscle denervation patterns, as well as enlargement, flattening, or injury to the nerve.²⁷ Magnetic resonance neurography is a related modality that may be used to better observe nerve pathology. Separate acquisition modalities, including fat saturation (short tau inversion recovery) and flow suppression, are used to highlight neurologic structures. Magnetic resonance neurography allows for additional measurements, including the flattening ratio (width/height) and multiplanar reconstructions to grade nerve compression. Prestenotic changes may be observed in the nerve, including swelling and hyperintensity. Distal to compression, a decreased signal may be observed. One study found significant changes in swelling, flattening ratio, proximal hyperintensity, and distal hypointensity compared with controls.²⁸ Diffusion tensor imaging can also be used. It harnesses the unique axoplasmic flow of nerves to capture images of individual axonal pathways and has depicted changes in fractional anisotropy and the apparent diffusion coefficient.²⁹

Considering EDS and imaging modalities as a whole, CTS diagnosis can often be made in the presence of confounding clinical findings (Fig. 3).⁸

Figure 3.

Diagnostic parameters for EDS, US, and MRI, in CTS. Summary of diagnostic tests used in CTS. The most common standard of practice EDS measurements from the American Association of Electrodiagnostic Medicine.⁸ Ultrasound and MRI findings based on the literature review.

Injections

Corticosteroid injections have both diagnostic and therapeutic value in the management of CTS. Green et al³⁰ performed a retrospective study of 281 corticosteroid injections performed in 233 patients with suspected CTS who ultimately underwent carpal tunnel release. They found a strong correlation between the success of injection with eventual improvement after carpal tunnel release.³⁰ In a subsequent study, Hofer et al³¹ found in a randomized prospective trial that patients given 80 mg methylprednisolone were less likely than the placebo group to undergo surgery within 5 years. Another study by Atroshi et al also showed 80 mg of methylprednisolone to be superior to 40 mg, as well as the placebo group. In their study, the 1-year postinjection rates of surgery were 73%, 81%, and 92% for the 80 mg, 40 mg, and placebo groups, respectively.³² With time to surgery included, the 80 mg and 40 mg groups had a lower likelihood of surgery.³² Platelet rich plasma (PRP) has also been shown to provide an analgesic effect though further studies are warranted.^33,34

Cubital Tunnel and Ulnar Tunnel Syndrome

Clinical presentation

Ulnar nerve neuropathy can occur from compression at the elbow in CuTS or at Guyon canal of the wrist with ulnar tunnel syndrome (UTS). Patients with ulnar nerve compression present with pain, dysesthesias, and/or paresthesia in the ulnar nerve distribution, comprising the ulnar one-half of the ring finger and the little finger, as well as the ulnar aspect of the hand. Disease progression can often involve hand weakness as well as difficulty with fine motor skills. It is important to understand the motor distribution of the nerve as it also innervates the flexor digitorum profundus and flexor carpi ulnaris. In the hand, the ulnar nerve innervates the hypothenar muscles, medial lumbricals, adductor pollicis, interossei muscles, and palmaris brevis. Differentiating between the motor distributions above and below Guyon canal may be beneficial in differentiating CuTS from UTS on presentation and physical examination if differences are present. Similar to CTS, nocturnal and early morning symptoms are usually more prominent, and symptoms can often be related to elbow position in the case of CuTS.

Physical examination

An ulnar nerve compression syndrome is often elicited with a thorough history and physical examination. However, the diagnosis is often difficult to elucidate early in the disease process because most provocative maneuvers are negative. Ulnar tunnel syndrome can present as either an isolated motor, isolated sensory, or mixed neuropathy based on the zone of compression within Guyon canal. Cubital tunnel syndrome presents with mixed ulnar neuropathy. Unopposed abduction of the little finger, known as the Wartenburg sign, occurs secondary to decreased strength of the palmar interossei and overpull by the abductor digiti minimi (ADM). Froment sign is a compensatory thumb interphalangeal joint flexion via flexor pollicis longus (FPL) with attempted lateral pinch secondary to first dorsal interosseous (FDI) weakness. The Masse sign is loss of volar convexity secondary to significant atrophy of the hypothenar muscles and loss of the volar metacarpal arch. The scratch collapse test has also been used as a diagnostic tool. The ulnar nerve at the elbow is “compressed” with a scratch of the skin during external shoulder rotation, with transient loss of shoulder external rotation strength indicating a positive test.³⁵ Huynh et al³⁶ performed a systematic review and meta-analysis. The scratch collapse test was found to have poor sensitivity and moderate specificity. It was ultimately not found to be an adequate examination maneuver.

Although a positive Tinel sign is often elicited either at the elbow or at Guyon canal, the diagnostic value of provocative maneuvers in ulnar neuropathy is often debated. For instance, Novak et al³⁷ performed a prospective study of provocative testing in 32 patients with electrodiagnostically confirmed CuTS. They found the following sensitivities for 4 provocative tests: 0.70 for Tinel sign, 0.32 for elbow flexion, 0.55 for pressure provocation, and 0.91 for the elbow flexion-compression test.³⁷ A similar study conducted by Beekman et al³⁸ found the sensitivity and specificity of Tinel sign to be 0.62 and 0.53, respectively. Furthermore, Kuschner et al³⁹ demonstrated a positive Tinel sign in 34% of elbows at 180 seconds when examining 200 asymptomatic patients. All aforementioned studies concluded that the diagnostic value of provocative clinical tests in ulnar neuropathy is inadequate for confirming the diagnosis.

Electrodiagnostic studies

The use of electrodiagnostic testing for suspected compressive ulnar neuropathy is similar to that of CTS, because EDS is most useful when discerning the diagnosis from other underlying and potentially superimposed causes of neuropathy. Proper EDS evaluation relies on knowledge of the most common areas for nerve entrapment. Most ulnar compressions occur at the retroepicondylar groove and the humeroulnar arcade, although compression while exiting from the flexor carpi ulnaris and at the medial intermuscular septum can also occur. Further, the fibers destined for the flexor carpi ulnaris, palmar ulnar cutaneous branch, and dorsal ulnar cutaneous branch lie in individual fascicles at the elbow in a deep dorsolateral position, making them less susceptible to compression at the elbow. This increases the difficulty when differentiating between CuTS and UTS. When taking anatomic variation into account, the differential becomes more convoluted. The diagnostic “yield” is less for ulnar entrapment than for median nerve entrapment, and often nontraditional techniques must be used. The American Association of Electrodiagnostic Medicine recommendations are moderate flexion between 70° and 90° with a 10 cm across the elbow distance. Findings consistent with CuTS include nerve conduction velocity from above the elbow (AE) segment to below the elbow (BE) segment less than 50 m/s, AE to BE greater than 10 m/s, slower than BE to the wrist segment, a decrease in the compound muscle action potential negative peak amplitude from BE to AE greater than 20%, a significant change in the action potential between AE and BE, as well as multiple consistent abnormalities.⁴⁰

Ulnar tunnel syndrome diagnosis relies on conduction velocities to the FDI muscle and ADM. Determining the absolute distal motor latency in regard to the ADM and FDI, the difference on the ipsilateral side and their differences from the contralateral side help make the diagnosis. The clinical yield is more “conclusive” as compared with the CuTS.^41,42 Diagnosis of ulnar neuropathy should still be considered with a normal EDS, especially when clinical suspicion is high. Patients with early and mild ulnar nerve compression are more likely to have a false-negative EDS. Tomaino et al⁴³ performed in situ ulnar nerve release with medial epicondylectomy in 18 elbows of 16 patients who presented with symptomatic CuTS with normal EDS testing. They found complete resolution of paresthesia at long-term follow-up in all cases, thus demonstrating the prevalence of false positivity with EDS in CuTS.⁴³

Imaging

Radiographs are not recommended for routine evaluation of patients presenting with cubital tunnel symptoms. However, radiographs are obtained in patients for acute trauma, history of trauma, severe osteoarthritis or inflammatory arthropathy, or if a mass is suspected. Radiographs should be obtained in the setting of acute or previous trauma or when medial elbow ganglions or the presence of osteophytes are suspected, because all can be the underlying etiology of compressive symptoms. Previous studies have shown that 50% of patients having undergone surgical fixation of a distal humerus fracture will demonstrate symptoms of ulnar neuropathy. Anterior transposition of the ulnar nerve is thought to protect against scarring or impingements that may occur because of hardware friction. Chen et al⁴⁴ in a retrospective study of 137 patients undergoing fixation for distal humerus fractures, found that 33% (16/48) patients experienced ulnar neuritis when the ulnar nerve was transposed compared with 9% (8/89) when the nerve was returned to the groove. They recommended against routine transposition.⁴⁴ It is important to recognize that nerve evaluation at the time of the procedure may impact the decision to transpose the nerve. In another study by Dehghan et al⁴⁵ 58 patients were randomly placed into groups for distal humeral fracture fixation involving transposition and in situ placement. They found no difference between the 2 modalities and a very high rate of ulnar neuropathy at the time of the index procedure.⁴⁵ Although the prevalence of postoperative CuTS after distal humerus fracture is multifactorial, the nature of the fracture pattern may predispose to ulnar neuropathy.

The role of US is also supported in the literature as an accurate and potentially easily applied diagnostic test. The evaluation of ulnar nerve instability is invaluable when delineating between subluxation and dislocation of the ulnar nerve. Elbow flexion driving tightening of the retinaculum increases pressure on the ulnar nerve, potentially inhibiting intraneural blood flow and driving the pathophysiology of the compressed nerve, as previously discussed.^46,47 Further, medial displacement of the ulnar nerve exposes it to the deforming forces of the humeral medial epicondyle, and shear forces may be present related to the humeral retroepicondylar groove.^48,49 Ultrasound can be used to directly determine the degree of subluxation by holding the probe at the cubital ulnar tunnel with the elbow flexed to 45°, observing full flexion and medial deviation of the nerve—subluxation is defined as medial deviation without displacement over the apex of the medial epicondyle (12 o’ clock position), displacement past the apex is defined as a dislocation.⁴⁹ Direct visualization of the nerve allows for visualization of neuropathologic signs, such as hypofasicularity, swelling, and hyperemia; although cross-sectional area remains the gold standard.50, 51, 52 Elastography and pain threshold modalities are becoming more popular; however, more research is needed before their true benefit may be determined as a diagnostic standard.^53,54 In a large study of healthy volunteers, Cornelson et al⁵² demonstrated a large number of subclinical ulnar nerve instability, with increases in cross-sectional area present. Ulnar nerve–subluxation is a well-documented factor predisposing to ulnar neuropathy and CuTS. This subclinical population may be one of the factors driving CuTS being the second leading upper extremity entrapment syndrome.^55,56

There is renewed interest in US for the diagnosis of CuTS given its’ improved technology, the ability to assess for dynamic instability, as well as identify specific areas of compression.⁵⁷ Ultrasound offers the distinct advantage of identifying external compression, the target of surgical intervention, which may improve surgical decision-making.⁵⁷ Ultrasound has been widely accepted as a reliable additional test when diagnosing CuTS.⁵⁸ However, measurements in relation to ulnar thickness have had varying results, with sensitivities between 46% and 100% and specificities between 43% and 97%.59, 60, 61, 62, 63 Chang et al⁶⁴ performed a meta-analysis examining the cross-sectional area of the ulnar nerve. They concluded that a maximal cross-sectional area of 10 mm² can be used as a cut-off point for diagnosing ulnar nerve entrapment at the elbow. This recommendation has gained widespread acceptance.⁶⁴

With respect to EDS, US is generally less accurate, specifically in relation to its sensitivity in diagnosing CuTS when a conduction block is present. However, in instances when short-segment EDS are negative, US has a higher diagnostic yield.^65,66 Further, US is more accurate in diagnosing CuTS when axonal loss has occurred, because EDS studies are typically nonlocalizing. Concomitantly, both diagnostic modalities improve the reliability of CuTS diagnosis and may be beneficial in difficult cases when the appropriateness of surgical intervention is unclear. In regard to UTS, EDS has similarly been found to be superior as compared with US. There is, however. a propensity to question the accuracy of EDS results in the distal extremity, especially when the results are not consistent with the clinical presentation.⁶⁷ In these instances, US can be useful. Along with identifying associated echogenic and fascicular changes, a cross-sectional area is again typically the standard validated modality for diagnosis.⁶⁸ Additional findings may be present in the hand, including space-occupying lesions, anatomic variants of hypothenar muscles, and vascular anomalies.

Elastography is another measurement modality that may improve diagnostic yield, specifically shear-wave elastography. The added benefit of an objective numerical measurement (kPa) allows for reference and pathologic stiffness ranges to be determined.^54,69,70 In a recent study by Paluch et al⁶⁹ compromising 46 patients with UTS and 39 controls, a 100% sensitivity and specificity when using shear-wave US to identify UTS was found.

Finally, similar to the diagnostic value of MRI for CTS, MRI should be considered when space-occupying lesions are suspected, as in the case of ganglions, nerve sheath tumors, or vascular malformations of the medial elbow or within Guyon canal. Considering EDS, US, and MRI findings, discerning between CuTS and UTS can be made with a higher degree of certainty (Fig. 4).

Figure 4.

Differentiating pronator syndrome and AIN syndrome from CTS. Differential diagnosis table adapted from Lee et al depicting diagnostic findings between CTS, pronator syndrome, and AIN syndrome.²⁰

Injections

Ultrasound-guided diagnostic corticosteroid injections are rarely performed for the treatment of CuTS. A recent randomized, double-blinded, placebo-controlled trial could not demonstrate a subjective change in symptoms at 3 months superior to the placebo group, despite a decrease in nerve maximal cross-sectional area on US postinjection. This may be partially explained by the lack of tenosynovium generally surrounding the ulnar nerve compared to the median nerve at the wrist and the maximal cross-sectional area as a sign of the disease rather than the pathologic entity itself. Conversely, vanVeen et al⁷¹ supports the use of a diagnostic injection in patients with atypical symptoms or a negative NCS. Gronbeck et al⁷² performed US-guided cubital tunnel injections in 66 elbows with mild ulnar nerve symptoms. Thirty-eight patients demonstrated complete or partial relief after injection, and 13 subsequently proceeded to surgical decompression, with 11 (84.6%) reporting complete resolution of their symptoms. Eighteen patients saw no difference or worsening symptoms following injection, and 4 of them proceeded to surgical decompression, with only 1 demonstrating complete relief (25.0%). They concluded that relief of symptoms from a diagnostic US-guided corticosteroid injection had prognostic value for surgical decompression.⁷²

Hydrodissection is another injection modality gaining popularity. The treatment is meant to add pressure between 2 tissue planes creating separation and removing adhesions.⁷³ Hydrodissection has been used in prostatectomies and ophthalmic procedures, as well as in other scenarios where a low margin of error dissection exists.74, 75, 76 Applications in CuTS are limited in the literature, but early findings show promise. A cadaveric study showed that the ulnar nerve could be displaced from the medial epicondyle and from the surrounding tissues.⁷⁷ One study by vanVeen et al⁷¹ demonstrated no difference in clinical outcomes between corticosteroid and 1 ml of saline hydrodissection in 55 patients with CuTS. Considering uncontrolled blood glucose, hydrodissection may be of substantial benefit where traditional corticosteroid injection would be contraindicated. In regard to ulnar tunnel hydrodissection, it is an area that needs further evaluation, and the literature is scarce at this time.

Pronator Syndrome and AIN Compressive Neuropathy

Clinical presentation

The underlying etiology of both pronator syndrome and AIN compressive neuropathy involves compression of the median nerve. A thorough history and physical examination, along with an appropriate diagnostic work-up is imperative in identifying these neuropathies. Pronator syndrome is compression of the median nerve in the forearm at the Ligament of Struthers, lacertus fibrosus, between the 2 heads of the pronator teres, or at the arch of the flexor digitorum superficialis (Fig. 5). Patients present with aching pain in the proximal volar forearm, paresthesia in the median nerve distribution, as well as paresthesia in the palmar cutaneous branch distribution. The latter separates pronator syndrome from CTS and AIN syndrome.⁷⁸ Anterior interosseous nerve syndrome is isolated compression of the AIN at the pronator teres or flexor digitorum superficialis (FDS), secondary to a thrombosed vessel or via an accessory head of the FPL known as Gantzer’s muscle. Anterior interosseous nerve syndrome typically presents with motor dysfunction or weakness of the AIN-innervated muscles without pain. The exception to this is in the case of AIN syndrome secondary to a Parsonage-Turner syndrome (PTS), which is increasingly being described as a potential etiology for isolated AIN or PIN dysfunction.

Recent literature reviews have further described the AIN syndrome occurring in PTS as an immunomodulatory pathology rather than having a compressive etiology. The pathology inherent in this condition has been recently described as neuralgic amyotrophy rather than brachial plexus neuritis, reflecting a better understanding of this disease as one of the peripheral nerve rather than the plexus.⁷⁹ Differentiating PTS from traditional AIN syndrome involves understanding additional findings inherent within PTS. Parsonage-Turner syndrome may also involve spinal accessory, phrenic, suprascapular, long thoracic, axillary, musculocutaneous, radial, and PINs.^80,81 The disease progression is typically described as prodromal pain, with a subsequent palsy and complete denervation happening days later.^82,83 The axonal loss can be diagnosed with EDS.⁸⁴

A strong differential is paramount in differentiating pronator syndrome and AIN syndrome from CTS. An explanation of the physical examination differences will follow in the next section.

Physical examination

Pronator syndrome is suspected in patients with sensory abnormalities in the median nerve distribution, especially in the distribution of the palmar cutaneous branch. A Tinel sign may be elicited over the median nerve in the area of compression. Motor weakness is generally not observed; however, subjective weakness may be present secondary to pain. Physical examination maneuvers that increase pressure at the area of nerve constriction may elicit pain, including resisted elbow flexion in supination (lacertus fibrosis), resisted pronation with the elbow extended (pronator teres), or resisted proximal interphalangeal joint flexion (arch of FDS).⁷⁸ In contrast, AIN syndrome presents with motor deficits of the FPL, FDP to the index and long finger, and pronator quadratus without associated sensory deficits.⁷⁸

In relation to a specific differential from CTS, differentiating muscle atrophy/weakness may be helpful. Whereas CTS involves the abductor pollicis brevis, opponens pollicis, and the flexor pollicis brevis; pronator syndrome may additionally involve the FPL, flexor digitorum profundus of the index and middle fingers, pronator quadratus, and flexor carpi radialis; AIN syndrome will only involve the FPL, flexor digitorum profundus of the index and middle fingers, and the pronator quadratus. Tinel sign will occur at the carpal tunnel for CTS, pronator teres more than 50% for pronator syndrome, and will be negative for AIN syndrome.⁸⁵ A direct compression test will also have similar findings to those for Tinel sign. Phalen test will only be positive for CTS (Fig. 6).²⁰

Figure 6.

Differentiating between CuTS and UTS. Electrodiagnostic studies practice guidelines by the American Association of Electrodiagnostic Medicine listed for CuTS and UTS. Ultrasound and MRI findings based on the literature review.

Electrodiagnostic studies

In pronator syndrome, EMG and NCS are frequently negative but may show concomitant underlying CTS or other causes of neuropathy that may indicate a double-crush phenomenon. Electrodiagnostic studies are more often positive in AIN syndrome in which abnormal latencies can be seen at the area of compression as well as denervation of AIN-innervated muscles, especially in the case of PTS-induced AIN neuropathy.⁸⁶

Imaging

Elbow radiographs should be obtained in the work-up of pronator syndrome to evaluate for the presence of a supracondylar process, an osseous protrusion located on the anteromedial aspect of the distal humerus, which is present in 0.1% to 2.7% of the population. A fibrous Ligament of Struthers can connect the supracondylar process to the medial epicondyle of the humerus, serving as a potential site for compression of the median nerve. Magnetic resonance imaging is indicated in the work-up of both pronator syndrome and AIN syndrome when there is a concern for a space-occupying lesion. Magnetic resonance neurography also plays a role in inconclusive cases of AIN syndrome because it may demonstrate muscle edema, muscle atrophy, and/or fatty infiltration. In the case of AIN neuropathy secondary to PTS, MR neurography and US can reveal hourglass-like constrictions of the nerve, confirming the diagnosis of PTS (Fig. 7).^86,87

Figure 7.

Clinical photograph and corresponding MR neurography demonstrating the hourglass compressions pathognomonic for PTS affecting the radial nerve.

Injections

The literature regarding the use of diagnostic injections in the work-up of pronator syndrome and AIN compression is limited. One study evaluated 14 patients who underwent US-guided perineural hydrodissection and steroid injection for pronator syndrome. Of these, 10 patients (71.4%) reported a 75% improvement in symptoms at 3 months.⁸⁸ The value of using this data for diagnostic purposes has yet to be elucidated.

Radial Tunnel Syndrome and PIN Syndrome

Clinical presentation

Radial tunnel syndrome and PIN syndrome are compressive neuropathies involving the PIN. Sites of compression for radial tunnel and PIN syndrome are within the proximal forearm. They include fibrous bands anterior to the radial head, radial recurrent vessels (leash of Henry), the medial edge of the extensor carpi radialis brevis, the proximal aponeurotic arch of the supinator muscle (Arcade of Frohse), and the distal edge of the supinator. Clinically, PIN syndrome and radial tunnel syndrome present differently. The hallmark of radial tunnel syndrome is a deep aching pain in the lateral forearm approximately 3–5 cm distal to the lateral epicondyle that can worsen with activity. Radial tunnel presents as pain without PIN motor dysfunction or sensory deficits. Radial tunnel differentiates from lateral epicondylitis by the location of pain in the proximal dorsal forearm as opposed to directly over the lateral epicondyle.

The ‘Rule-of-Nine’ test can be used to improve the diagnostic accuracy of radial tunnel syndrome. The test is based on anatomic studies mapping the course of the PIN. These studies found that when the volar proximal forearm is divided into 9 squares (3 columns, 3 rows), the PIN is consistently mapped within the lateral 3 squares.⁷⁸

Posterior interosseous nerve syndrome is purely a motor neuropathy involving PIN-innervated muscles. Patients present with finger and thumb extension weakness. Occasionally, patients will subjectively endorse dorsal wrist pain. Posterior interosseous nerve syndrome can also present secondary to PTS with neuropathic pain preceding motor weakness. However, advances in peripheral nerve imaging techniques (US and MRI) can differentiate these pathologies into 2 distinct entities because of the pathognomonic findings of hourglass constrictions in PTS (Fig. 7).⁸⁷

Physical examination

Physical examination findings in radial tunnel syndrome include pain with palpation over the patient’s lateral forearm in the area of PIN compression. Provocative maneuvers, such as resisted supination and long finger extension, can exacerbate pain, whereas pronation can alleviate pain. Weakness can be present secondary to pain, but sensory loss is not a characteristic of radial tunnel syndrome. Physical examination findings in PIN syndrome are related to weakness in PIN-innervated muscles. They include decreased strength of wrist extension, finger extension, and thumb extension. Radial deviation with wrist extension is often observed secondary to preserving the innervation to the extensor carpi radialis longus, which is innervated proximal to the site of PIN compression.⁷⁸ Tenodesis effect should be checked to rule out tendon rupture as the underlying cause of observed weakness. As in radial tunnel syndrome, PIN syndrome does not involve subjective or objective sensory deficits. When considering the specific findings inherent within both radial tunnel and PIN syndromes, the diagnostic algorithm can be simplified (Fig. 8).

Figure 8.

Radial tunnel and PIN syndromes. Differential findings for radial tunnel and PIN syndromes focused on clinical presentation, physical examination, EDS, and injections.

Electrodiagnostic studies

Electrodiagnostic studies for the diagnosis of radial tunnel syndrome and PIN syndrome may be helpful. However, they are typically used to exclude other pathologies. The use of EDS in radial tunnel syndrome has yielded mixed results. Kupfer et al⁸⁹ performed a study that compared motor latencies between patients with the clinical diagnosis of radial tunnel syndrome and asymptomatic controls. They found a greater than average latency among the symptomatic group (0.44 ± 0.12 vs 0.12 ± 0.01 ms, P < .001).⁸⁹ Other studies, however, have found no such EDS abnormalities in radial tunnel syndrome.⁹⁰ A case report of PIN compression by Bevelaqua et al⁹¹ demonstrated EDS changes with a slowed radial motor conduction velocity, prolonged distal latency, and reduced amplitude compared with the contralateral arm.

Imaging

Radiographs of the elbow should be obtained in patients with PIN symptoms in the setting of trauma. The PIN is most often compressed by the radial head in the setting of Bado type 2 Monteggia fractures; however, it can be present in all types of Monteggia fracture- dislocations. Similar to all other neuropathies, MRI is useful for ruling out space-occupying lesions. Extensive elbow synovitis in rheumatoid arthritis can also lead to PIN compression and be diagnosed with an MRI (Fig. 9). Magnetic resonance imaging can also show muscle denervation via edema, fatty infiltration, and atrophy within the PIN-innervated muscles in PIN syndrome. Similar to AIN syndrome, PIN syndrome as a result of PTS can demonstrate hourglass-like constrictions on MR neurography (Fig. 7).⁹²

Figure 9.

Example of abundant radiocapitellar synovitis resulting in PIN compression on axial (A), and sagittal (B) MRI and clinical photograph (C).

Injections

Injections of the PIN results in a PIN motor palsy but may also relieve pain and assist with the diagnosis of radial tunnel syndrome. Sarhadi et al⁹³ performed local anesthetic injections in 26 arms with clinical suspicion of radial tunnel syndrome. They found complete relief of symptoms in all patients thus confirming their diagnosis.

In conclusion, compressive neuropathies of the upper extremity are common pathologies that must be considered in patients presenting with pain, paresthesia, or motor dysfunction. Although no true diagnostic gold standard exists for each entity, a combination of clinical presentation and physical examination can often be diagnostic. In many cases, further imaging, EDS, or diagnostic injections are indicated to elucidate the diagnosis. Further study to define and validate diagnostic criteria against surgical outcomes for the most common compressive neuropathies is of the utmost importance.