Patients presenting with pronator syndrome will often complain of pain in the volar aspect of the forearm. This is most marked in people performing repetitive upper extremity movements. The pain or discomfort can usually be provoked by performing a specific movement. Sensory symptoms are present in the median nerve and palmar cutaneous branch distribution of the hand. These include numbness and paresthesias in the thumb, index finger, middle finger, radial side of the ring finger, thenar eminence and palm of the hand. Incomplete PS may be due to a reversed Martin-Gruber anastomosis, also called Marinacci communication [7]. Motor symptoms are not usually present in pronator syndrome, although there may be weakness of the thenar musculature. If the symptoms are present for a few months there may be a positive Tinel’s sign over the compression site.

Electrodiagnostic conduction studies may not be conclusive in PS, and can therefore not be used to predict the outcome of therapy [8, 9]. Needle examination can reveal denervation in the pronator teres and more distal muscles. Decrease in motor and sensory conduction across the pronator teres muscle may also be found. It is advisable to conduct both studies. Although these tests may not be conclusive in PS, they can be used to rule out CTS and more proximal causes of muscle denervation, i.e. cervical radiculopathy or brachial plexopathy. Extensive literature exists on the use of ultrasound studies in CTS, but hardly any papers have addressed the use of ultrasound in PS specifically. Ultrasonography has proved to be a good addition to electrodiagnostic studies in CTS [10]. It can therefore be used to rule out CTS but not to confirm PS. It is questionable whether MRI can aid in diagnosing PS. If the neuropathy has been present for several months an increased signal may be seen in the muscles innervated by the median nerve on STIR or T2-weigted fat-suppressed images. Normal anatomical structures causing compression of the nerve will be difficult to appreciate on MRI. Therefore, in absence of an anomaly, i.e. pathological mass, MRI is not helpful in locating the origin of entrapment [11].

The differential diagnosis of pronator syndrome include, amongst others, carpal tunnel syndrome, Parsonage-Turner syndrome and thoracic outlet syndrome.

Although there is considerable overlap between PS and CTS, there are a few differences that help distinguish between the two syndromes. In PS both the median nerve and the palmar cutaneous branch of the median nerve are affected. This will result in dysaesthesia, not only in the thumb, index and middle finger, as in CTS, but also in the thenar eminence and palm of the hand. Careful assessment of the extent of sensory changes in the hand will help distinguish between the two. Furthermore, there should be no positive Phalen’s test in patients with PS. There is, however, some indication that a percentage of patients with PS may have a positive Tinel’s sign at the wrist [12]. CTS often presents with nocturnal symptoms, which are seldom present in PS. While usually not conclusive in PS, electrodiagnostic conduction tests may be used to confirm CTS. In a selection of patients PS and CTS will coincide. In these patients the physical examination of the arm and hand should raise suspicion. Electrodiagnostic studies, response to corticosteroid injections at the proximal compression site and at the carpal tunnel, and response to conservative treatment may help confirm the simultaneous existence of PS and CTS. If the diagnosis is confirmed, both sites of compression may be released in one operation [13].

Parsonage-Turner syndrome, also known as neuralgic amyotrophy or brachial plexus neuralgia is a peripheral nervous system disorder affecting the upper limb [14]. There are two forms of Parsonage-Turner syndrome; hereditary autosomal dominant and idiopathic. Both forms seem to result from a vulnerability to brachial plexus injury followed by an immune-mediated response to the injured plexus. It is characterised by a sudden onset of severe pain in the shoulder or arm. This is followed by muscle weakness and atrophy. The syndrome can vary greatly in presentation and nerve involvement. In severe cases it results in complete loss of function of the muscle. A thorough medical history with specific questions concerning the onset of the symptoms and a physical examination of the shoulder and arm should aid differentiation between PS and Parsonage-Turner syndrome [14].

Neurogenic thoracic outlet syndrome occurs when the brachial plexus is compressed at the thoracic outlet. The thoracic outlet is formed by the clavicle, scapula, first rib and the anterior and middle scalene muscles. Changes in any of these structures can lead to compression of the underlying plexus. Common causes include presence of a cervical rib, clavicular callus after a fracture, cervical whiplash, congenital fibromuscular bands or muscle hypertrophy from repetitive overhead activities. Although some symptoms may mimic PS, the cause of thoracic outlet syndrome lies more proximal and will thus result in associated proximal signs. The physical exam will often include neck and shoulder pain and reveal a pattern of paresthesia of the arm not related to the innervation pattern of the median nerve [15].

Cervical radiculopathy is a descriptive term used to define a disorder in which one or more cervical nerves cause pain, weakness, numbness or clumsiness due to problems at the root of the nerve near the spinal cord, the cervical nerve itself or both. The most common cause of cervical radiculopathy is compression of the root which can result from, amongst others, degenerate changes and decreased disc height. Less frequent causes include nucleus pulposus herniation, tumors and infections. Depending on the affected nerve or nerve root, cervical radiculopathy can mimic a number of distal nerve entrapments. The history and examination of the neck, shoulder and arm will help differentiate between cervical radiculopathy and PS or AINS. Provocation test of the neck, i.e. moving the head to the affected side, the absence of reflexes and normal nerve-conduction studies all point to cervical radiculopathy [16].

Diabetes and alcohol induced neuropathy may in some cases imitate the sensory changes associated with CTS, but seldom AINS or PS. The medical history and concomitant neurologic changes in the legs and feet will usually be sufficient to tell them apart.

Unlike pronator syndrome, AINS seldom presents with sensory loss or paresthesia. Symptoms are related to the muscles innervated by the AIN, namely the flexor digitorum profundus of the index and middle finger, the flexor pollicis longus and the pronator quadratus muscles. Patients will generally complain about problems with fine motor skills such as writing, typing or pinching. Depending on whether the patients have a complete or incomplete AINS, function loss of one or more of these muscles will be present. In incomplete AINS there is usually an isolated weakness or function loss of the FPL or FDP. Variable innervation of the FDP to the middle finger by the median and ulnar nerve may cause incomplete AINS. Presence of distal interphalangeal joint flexion in the middle finger does therefore not necessarily exclude AINS.

Although conduction studies will not be useful in diagnosing AINS, needle examination can be used. The flexor pollicis longus, flexor digitorum profundus and pronator quadratus muscles may show varying degrees of denervation. Moreover, electrodiagnostic studies can help differentiate between AINS and CTS or flexor tendon ruptures [9, 17]. Ultrasound is usually not conclusive in AINS when there is no detectable cause, i.e. a tumor. This is partly due to the fact that the nerve itself is small and lies deep within the arm. In rare cases enlarged fascicles or loss of muscle tissue in established disease may be seen [18, 19]. When AINS is evaluated using MRI imaging, changes can be seen in the signal intensity of FPL, FDP and PQ muscles on STIR or axial T2-weigted fat-suppressed images. Also, if a space occupying lesion is causing AINS this will be seen on MRI. Normal anatomical structures leading to AINS are more difficult to perceive. However, a MRI made at the time of diagnosis can be used to monitor therapy related changes through additional imaging. Recovery should result in normalisation of the signal intensity whereas the development of fatty muscle atrophy signals deterioration of the neuropathy [11].

Brachial plexus neuritis or Parsonage-Turner syndrome can also mimic AINS. As with PS, a complete medical history and physical examination aids in differentiation between the two.

Incomplete anterior interosseous syndrome may be mimicked by rupture of the FPL, FDP 2 or both. The absence of sensory symptoms in particular can make differentiation problematic. Awareness of the differential diagnosis and scepticism of the diagnosis of tendon rupture in absence of an explanatory mechanism, i.e. rheumatoid arthritis or trauma, can avoid an unnecessary exploration of the FPL or FDP 2. When there is uncertainty about the aetiology, ultrasound or electrodiagnostic examination should be considered. Other disorders that can mimic AINS include flexor tendon adhesion, stenosing tenosynovitis and congenital absence of the FPL tendon.

PS and AINS originate from pressure on the median and anterior interosseous nerve, respectively. The duration and severity of the pressure will determine the degree of damage to the nerve. If the pressure is present long enough or increases over time a number of changes occur in the nerve tissue. The first change to occur is the blood-nerve barrier becoming permeable. This leads to an increased influx of fluid. The fluid causes the connective tissues to distend, leading to increased pressure on the blood flow to the nerve, causing ischemia. If the pressure exists long enough it results in demyelination of the nerve and finally in axonal degeneration. The outer nerve fascicles are more susceptible to the pressure due to their location. This may explain differences in clinical presentation.

First described by Upton and McComas [20], the double crush theory purports that proximal nerve compression will render the nerve more susceptible to damage distally. This is said to be the result of axial flow restriction in the nerve fibres. Several animal studies exist aimed at providing proof for the double crush syndrome (DCS) theory. However, they primarily showed that two nerve lesions cause a more profound neurologic deficiency than one lesion [21, 22]. No animal study to date has proved that proximal nerve compression leaves the distal nerve prone to pathological changes or has made clear what causes the DCS. Also, clinical studies show a wide variety in the percentage of a second nerve palsy in patients with CTS [23, 24]. Those authors opposed to the diagnosis DCS point out that the percentage of patients with cervical radiculopathy who also have carpal tunnel syndrome seems to be similar to the incidence of CTS in the work force, and not elevated as suggested [25]. Furthermore, they stipulate that most of the cervical roots involved in the radiculopathy do not contribute to the median nerve [26]. These lesions are then shown to be two non-related neuropathies in one individual. This may suggest that shared aetiologic factors, i.e. degeneration, repetitive labour, etc., contribute to the high frequency of co-existence of cervical radiculopathy and distal neuropathy. It is advisable to be aware of the possibility of two nerve entrapment syndromes coexisting in patients, especially manual labourers.

There are a number of causes that can lead to median nerve compression in the forearm, apart from the anatomical restriction sites which are discussed later. These include space-occupying lesions, direct trauma (i.e. bone fracture, muscle trauma), indirect muscle trauma (i.e. repetitive movements causing myotendinous strain or muscle tears), Volkmann contractures and external pressure. Masses in the upper extremity causing neuropathy include lipomas, primary tumors (e.g. sarcomas, schwannomas) and metastatic disease [27]. Although rare, greenstick fractures, supracondylar fractures of the humerus [28] and elbow dislocations [29] mainly in children may lead to damage to, or pressure on the median nerve. Iatrogenic damage to the nerve, for example after minimally invasive elbow surgery [30], is fortunately rare. Direct or indirect trauma to muscle or bone may lead to scar tissue an callus that may entrap the median nerve [31]. Volkmann contractures develop as a result of ischaemic injury to the forearm muscles due to either brachial artery injury as with fractures of the humerus or external pressure on the artery or compartment syndrome of the upper limb. Fractures of the humerus, especially supracondylar fractures result in direct pressure on the artery. External pressure applied by a tourniquet or an ill-fitting cast may also lead to raised pressure. Compartment syndrome can have a number of causes, i.e. infection, hematoma, crush injuries or burn wounds. The first consequence of elevated pressure is decreased arterial blood flow leading to tissue ischemia. This is followed by edema of the soft tissue distal to the point of compression resulting in compromised venous and lymphatic drainage. If the source of the compression cannot be removed or the compartment is not released this vicious circle leads to muscle and nerve ischemia that becomes irreversible and will ultimately result in tissue breakdown.

Sites where the nerve passes restricted anatomical structures are vulnerable to increased pressure due to the limited space. Table 13.2 lists anatomic sites where the nerve can be compressed in both PS and AINS. A frequent cause of median nerve compression is the existence of fibrous bands in the arm. At the elbow, in patients with a residual supracondylar process, the nerve can be compressed under the ligament of Struthers. This is a fibrous band that runs between the supracondylar process and the medial epicondyle. In the general population 0.7–2.7 % has a vestigial supracondylar process. Other causes of nerve compression at the elbow include a snapping brachialis tendon or an accessory bicipital aponeurosis. More distally, fibrous bands between the deep and superficial heads of the pronator teres muscle, a tendinous deep head of the pronator teres muscle and the proximal arch of the flexor digitorum superficialis muscle can restrict the nerve. The normal bicipital aponeurosis or lacertus fibrosus is another possible point of restriction. In AINS an accessory head of the flexor pollicis longus also known as Gantzer’s muscle or an aberrant vessel, such as an infrequent branch of the radial artery, may be the cause of nerve compression.