Median Nerve Mononeuropathies

Disease/ Disorder

Definition

The most common median nerve mononeuropathy from chronic compression at the level of the wrist¹ is carpal tunnel syndrome. For more information on carpal tunnel syndrome, please see the subsequent subsection for this topic. More proximal lesions of the median nerve can occur due to various factors, mostly from compression at the elbow or at the forearm. Median nerve mononeuropathy symptoms due to conditions occurring at the level of the elbow are often grouped under the term “Pronator Syndrome.” Symptoms from conditions affecting a motor-only branch of the median nerve in the forearm are referred to as “Anterior Interosseous Syndrome.” High median nerve lesions in the shoulder and proximal humerus can occur but are uncommon and usually secondary to trauma.

Etiology

Pronator syndrome

• Compression at the following sites²
  • Under the ligament of Struthers, an anomalous structure between the supracondylar process of the humerus and the medial epicondyle.
  • Between the two heads (ulnar and humeral) of the pronator teres muscle
  • Under the lacertus fibrosus (biceps aponeurosis) in the antebrachial fossa
  • Under the proximal arch of the flexor digitorum superficialis (FDS) (sublimis arch).
• Trauma
• Inflammatory conditions

Anterior interosseous syndrome

• Compression at the following sites²
  • Tendinous edge of the deep head of the pronator teres muscle (most common)
  • The proximal edge of the flexor digitorum superficialis (FDS) arch (the FDS arcade)
  • Gantzer’s muscle (accessory head of the FPL muscle)
  • Radial or ulnar artery due to thrombosis
  • Lacertus fibrosus (biceps aponeurosis)
  • Enlarged biceps tendon bursa
• Trauma
• Compartment Syndrome
• Inflammatory conditions (Idiopathic brachial neuritis resulting in AIN)
• Post-infectious (CMV, Zoster, Hepatitis E infections)

Epidemiology including risk factors and primary prevention

Pronator syndrome

• Less than 1% of all median nerve entrapments³
• Second most common entrapment site of the median nerve after the carpal tunnel⁴
• Most common in ages 40 to 50 years⁴
• Risk factors include the following:
  • Female sex
  • Repetitive use of elbow, wrist, and hand
  • Volar forearm muscle hypertrophy, specifically the pronator teres

Anterior interosseous syndrome

• Incidence is rare
• Risk factors include the following:
  • Anomalous fibrous bands arising from the pronator teres or FDS muscles
  • Compression at Gantzer muscles (variant muscles located in anterior forearm inserting into the flexor pollicis longus)
  • Trauma
  • Inflammatory process (e.g., idiopathic brachial neuritis)
  • Multifocal motor neuropathy

Patho-anatomy/physiology

• As the median nerve descends through the medial arm it runs beneath the ligament of Struthers, an anomalous ligament present in a small percentage of the population – which attaches from a supracondylar bony spur to the medial epicondyle.⁵ Branches to the pronator teres and flexor carpi radialis (FCR) may arise slightly proximal to the elbow.
• The median nerve continues its journey by diving beneath the lacertus fibrosus (biceps aponeurosis) and further descends between the two heads of the pronator teres.
• Four to six cm distal to the medial epicondyle, the AIN divides from the main trunk of the median nerve. The anterior interosseous branch contains no superficial sensory branches. It dives posteriorly to provide innervation to the flexor pollicis longus (FPL), flexor digitorum profundus (FDP) (index/middle), and pronator quadratus muscles.
• The median nerve then passes deep to the FDS muscle and its aponeurotic tendinous edge, known as the sublimus bridge⁶
• The median nerve innervates the FCR and FDS and continues through the forearm to the hand to innervate the abductor pollicis brevis (APB), opponens pollicis (OP), flexor pollicis brevis superficial head and first and second lumbricals.
• Proximal to the wrist, the palmar cutaneous branch divides and provides sensation to the thenar eminence. Terminal fibers of the median nerve provide sensation to the palmar surface of the thumb and second, third, and radial half of the fourth digit.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Disease progression depends on etiology.

• Compression
  • Insidious onset
  • Pain is less severe and worsened by repetitive activity
  • Slowly progressive weakness, loss of dexterity, clumsiness, and fatigue
  • Surgical decompression may provide relief^6,7
• Other etiologies are rarely described in the literature and often have a variety of onset and severity patterns

Some advocate that conservative treatment be considered for a year or more because late spontaneous recovery can occur.^8,9 However, functional recovery in a conservative setting is often incomplete, with many patients suffering from residual weakness and sensory defects.

Essentials of Assessment

History

Pronator syndrome

• Insidious onset
• Symptoms are not typically worse at night and paresthesias not as well localized as in carpal tunnel syndrome⁶
• Aching discomfort in the forearm, can be described as tiredness or heaviness
• Mild weakness
• Exacerbation by repeated or resisted forearm pronation and/or resisted or repeated proximal interphalangeal flexion of digits 2 and 3⁶

Anterior interosseous syndrome

• Compressive¹
  • Slow onset of symptoms
  • Pain is often not severe and localized to the forearm
  • Deficits are strictly confined to the AIN: no sensory changes
• Inflammatory: focal neuritis or part of acute brachial plexus neuropathy¹
  • Acute onset of severe pain in the forearm (if part of brachial plexopathy, pain can involve the shoulder and/or elbow)
  • Pain typically precedes weakness
  • May have sensory symptoms if more than the AIN is involved

Physical examination

• Cervical spine, shoulder, elbow, and wrist evaluation
• Findings may be normal in mild cases
• Sensory findings
  • Pronator syndrome/entrapment at ligament of Struthers
    • Sensory deficits may be detected in the entire median territory including thenar eminence which is spared in carpal tunnel syndrome (palmar cutaneous branch leaves median nerve proximal to carpal tunnel)
  • Anterior interosseous syndrome
    • No sensory deficits
• Motor findings
  • Pronator syndrome/entrapment at ligament of Struthers
    • Weakness may be detected in entire median territory
    • Pronator teres muscle weakness is usually spared in pronator syndrome (There is variable innervation to the pronator teres with the main branch of the median nerve providing innervation either proximal to or within the muscle itself.¹)
    • Significant weakness rare, mild weakness of FPL and APB most common⁶
    • Muscle bulk of pronator teres may be greater in symptomatic volar forearm
  • Anterior interosseous syndrome
    • Weakness may be detected in the FPL, pronator quadratus, and FDP (index and middle finger)
    • OK sign: inability to flex first digit interphalangeal joint and second digit distal interphalangeal joint

Functional assessment

• Review type of work performed, including tools used, forceful gripping, or twisting forearm movements
• Assess recreational activities that may involve repetitive use including, but not limited, to the following
  • Racquet sports
  • Rowing
  • Weightlifting
  • Chopping wood
  • Throwing

Laboratory studies

Laboratory studies may be used to evaluate for conditions that may predispose to compressive/inflammatory neuropathies.

Imaging

Magnetic resonance imaging (MRI)

• MRI allows visualization of mass lesions and nerve enlargement or inflammation^10,11
• Signal changes or atrophy of the muscle innervated by the nerve in question is also seen on MRI¹²
• Recent studies have not found increased diagnostic accuracy with MRI vs Ultrasound with measuring the median nerve at the wrist¹³

Ultrasound

• Less expensive than MRI
• Can be more easily accessed when done in the office
• Can detect mass lesions and nerve enlargement
• Can provide dynamic imaging

Supplemental assessment tools

Electrodiagnostic Testing

Nerve Conduction Studies/ Needle Electromyography (EMG)

• Include routine median sensory nerve conductions to the digits and at least one median vs ulnar comparison at the wrist to exclude carpal tunnel.
• Include routine median motor studies at wrist and antecubital fossa to the APB. Stimulation at the axilla may be needed if there is a question of entrapment at ligament of Struthers.
• Consider medial antebrachial cutaneous nerve conduction studies to rule out lower trunk/median plexopathy.
• Consider radial sensory and lateral antebrachial cutaneous nerve conduction studies to rule out upper trunk/lateral cord lesions.
• Perform needle EMG of the APB, pronator teres, and one of the following: FPL, FCR, or FDS.⁵
• If the APB is abnormal, rule out lower trunk brachial plexopathy, polyneuropathy, or C8-T1 radiculopathy by testing other nonmedian lower trunk/C8-T1 muscles.
• If the proximal median muscles are abnormal, rule out proximal brachial plexopathy or C6-C8 radiculopathy by testing nonmedian C6-C7 and C7-C8 muscles.

Pronator syndrome

• Reduced median compound muscle action potentials (CMAPs) and/or sensory nerve action potentials (SNAPs) amplitudes with relatively normal distal latencies.⁵
• Conduction block/temporal dispersion or marked conduction velocity slowing between the wrist and elbow or between the elbow and axilla, with relatively normal CMAP distal latency.
• Prolonged median F waves despite a relatively normal distal CMAP and distal latency.
• Muscles distal to the lesion should demonstrate abnormalities on needle EMG

Anterior interosseous syndrome

• Routine median SNAPs and CMAPs are normal.
• Median motor study to the pronator quadratus may demonstrate evidence of demyelination and/or axon loss.¹
• Needle EMG abnormalities seen in the pronator quadratus, FPL, and FDP of digits 2 and 3.

The following limitations exist

• If nerve conduction studies show a nonlocalized median neuropathy, needle EMG can only localize a lesion if motor axon damage is involved.
• Variability of pronator teres innervation complicates lesion localization.
• Axonal injury may result in distal conduction slowing via loss of fastest axons.
• Concomitant median neuropathy at the wrist challenges localization of proximal lesion.

Early predictions of outcomes

None reported.

Environmental

• Controversy remains regarding the role of muscle hypertrophy and overuse in developing pronator syndrome.
• Controversy remains regarding true entrapment of the AIN versus inflammatory etiology (focal neuritis, acute brachial plexus neuropathy) given the lack of abnormalities intraoperatively and variable response with surgery.¹

Rehabilitation Management and Treatments

Available or current treatment guidelines

No official guidelines.

At different disease stages

Pronator syndrome

• New onset/acute
  • Avoidance of provocative activity
  • Splinting to neutralize forearm pronation/supination and elbow flexion
  • Physical therapy: modalities for inflammation and swelling, soft tissue mobilization, gentle range of motion, and graduated strengthening
  • Patient education
• Subacute
  • Corticosteroid injections have been reported to give relief¹⁵
• No clinical improvement after conservative treatment with median nerve dysfunction
  • Extensive surgical exploration and decompression after failing conservative treatment at intervals of 9-12 months¹
  • Surgery may be expedited if blunt trauma or space-occupying lesions are derivatives.

Anterior interosseous syndrome

• New onset/acute
  • Same as above
• No clinical improvement after conservative treatment
  • Surgical exploration and decompression
    • Timing for surgical intervention varies from after 8 weeks to up to 12 months^7,8,9

Patient & family education

• Ergonomics education
• Modification of recreational and work-related activities

Emerging/unique interventions

• Impairment-based measurement
  • American Medical Association’s Guides to the Evaluation of Permanent Impairment
• Measurement of patient outcomes
  • Disabilities of the Arm, Shoulder, and Hand score¹⁶

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

• Thenar eminence sensory changes should warrant proximal investigation due to the palmar cutaneous branch of the median nerve (PCBMN) entering the wrist proximal to the transverse carpal ligament.
• Check the “OK” sign for thumb and index finger weakness. This test evaluates the anterior interosseous nerve by testing the strength of the flexor pollicis longus and flexor digitorum profundus. Anterior interosseous nerve deficits will result in flattening at the distal interphalangeal joint and weakness of the muscles of apposition.
• Resisted pronation and supination reproducing median nerve compression by the pronator teres or lacertus fibrosus.
• Resisted pronation when the elbow is fully flexed for pronator quadratus weakness in AIN ¹⁷
• Resisted flexor digitorum superficialis (FDS) of the middle finger as the median nerve can be compressed at the aponeurotic arch of the FDS muscle (can also be positive in CTS).¹⁷
• Tenodesis effect of active wrist extension and/or manual forearm flexor compression rule out tendon rupture.¹⁷ 
• Pronator teres compression test (or Tinel’s sign) with manually applied pressure proximal and lateral to the pronator teres muscle belly volar to the forearm with positive test producing pain within 30 seconds.¹⁷
• In anterior interosseous syndrome, when a Martin-Gruber anastomosis is present, there may be an associated weakness of the second- and fifth-digit abduction and adduction of the first digit because of the ulnar fiber cross-over.
• A normal physical exam does not rule out proximal median mononeuropathies.

Cutting Edge/ Emerging and Unique Concepts and Practice

• High-frequency ultrasound is becoming the imaging modality of choice for peripheral nerves and may be an additional tool to aid in diagnosis.¹⁸
• Ultrasound has been able to identify stenotic lesions of the AIN. Nagano¹⁶ reported good recovery in patients who underwent surgical neurolysis of these lesions. Closer attention to identifying these lesions may lead to better patient outcomes.
• Endoscopically assisted release,¹⁹ lacertus fibrosus release,¹⁴ and deep fascial release²⁰ of the superficial pronator teres are novel surgical techniques being explored.

Gaps in the Evidence-Based Knowledge

More outcome studies are needed to guide management. One area which may be particularly useful to the clinician are longitudinal studies outlining residual nerve and muscular defects in those managed conservatively versus interventionally. Ultrasound may also play a role in diagnosing proximal median nerve entrapments in individuals with normal EDX studies (analogous to EMG-negative carpal tunnel syndrome).

References

1. Stewart JD. Focal Peripheral Neuropathies. Philadelphia, PA: JBJ Publishing; 2010.
2. Aljawder A, Faqi MK, Mohamed A, Alkhalifa F. Anterior interosseous nerve syndrome diagnosis and intraoperative findings: A case report. Int J Surg Case Rep. 2016;21:44-7. doi: 10.1016/j.ijscr.2016.02.021. Epub 2016 Feb 20. PMID: 26921536; PMCID: PMC4802332.
3. Mercier LR. Practical Orthopedics. St Louis, MO: Mosby; 2005.
4. Lee, MJ, LaStayo, PC. Compressions that mimic carpal tunnel syndrome. J Orthop Sports Phys Ther. 2004; 34:601-609.
5. Preston DC, Shapiro BE. Electromyography and Neuromuscular Disorders. Philadelphia, PA: Elsevier; 2005.
6. Hartz CR, Linscheid RL, Gramse RR, Daube JR. The pronator teres syndrome: compressive neuropathy of the median nerve. J Bone Joint Surg Am. 1981; 63:885-890.
7. Nigst H, Dick W. Syndromes of compression of the median nerve in the proximal forearm (pronator teres syndrome; anterior interosseous nerve syndrome). Arch Orthop Trauma Surg.1979; 93:307-312.
8. Seror P. Anterior interosseous nerve lesion: clinical and electrophysiological features. J Bone Joint Surg Br. 1996; 78:238-241.
9. Futami T, Kobayashi A, Itoman M, Shimajiri I, Fujita T. Clinical investigation on the anterior interosseous nerve syndrome. J Jpn Soc Surg Hand. 1993;10:338-341.
10. Hersh B, D’Auria J, Scott M, Fowler JR. A Comparison of Ultrasound and MRI Measurements of the Cross-Sectional Area of the Median Nerve at the Wrist. Hand (N Y). 2019;14(6):746-750. doi:10.1177/1558944718777833.
11. Spratt JD, Stanley AJ, Grainger AJ, Hide IG, Campbell RS. The role of diagnostic radiology in compressive and entrapment neuropathies. Eur Radiol. 2002;12:2352-2364.
12. Sallomi D, Janzen DL, Munk PL, Connell DG, Tirman PF. Muscle denervation patterns in upper limb nerve injuries: MR imaging findings and anatomic basis. AJR Am J Roentgenol. 1998;171:779-784.
13. Hersh B, D’Auria J, Scott M, Fowler JR. A Comparison of Ultrasound and MRI Measurements of the Cross-Sectional Area of the Median Nerve at the Wrist. Hand (N Y). 2019;14(6):746-750. doi:10.1177/1558944718777833.
14. Hagert E.  Clinical diagnosis and wide-awake surgical treatment of proximal median nerve entrapment at the elbow: a prospective study. Hand (N Y). 2013;8(1):41–6.
15. Morris HH, Peters BH. Pronator syndrome; clinical and electrophysiological features in seven cases. J Neurol Neurosurg Psychiatry. 1976;39:461-464
16. Svernlov B, Nylander G, Adolfsson L. Patient-reported outcome of surgical treatment of nerve entrapments in the proximal forearm. Adv Orthop. 2011;2011:727689.
17. Sotereanos, Dean G., and Loukia K. Papatheodorou. Compressive Neuropathies of the Upper Extremity A Comprehensive Guide to Treatment. Edited by Dean G. Sotereanos and Loukia K. Papatheodorou. 1st ed. 2020. Cham: Springer International Publishing, 2020.
18. Kodama A, Sunagawa T, Ochi M. Early treatment of anterior interosseous nerve palsy with hourglass-like fascicular constrictions by interfascicular neurolysis due to early diagnosis using ultrasonography: a case report. J Hand Surg Eur Vol. In press.
19. Lee AK, Khorsandi M, Nurbhai N, Dang J, Fitzmaurice M, Herron KA. Endoscopically assisted decompression for pronator syndrome. J Hand Surg Am. 2012;37(6):1173–9.
20. Zancolli ER III, Zancolli EP IV, Perrotto CJ.  New mini-invasive decompression for pronator teres syndrome. J Hand Surg Am. 2012;37(8):1706–10.

Original Version of the Topic

Christie M. Lehman, MD. Median nerve mononeuropathies. Original Publication Date 9/20/2014

Previous Revision(s) of the Topic

Nassim Rad, MD. Median nerve mononeuropathies. Original Publication Date 11/5/2019

Author Disclosure

Thomas Chai, MD
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Christian Vangeison, DO
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Colton Reeh, MD
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Alex Wilkinson
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