Chapter 14. Neuropathy

History

A thorough history is vital in the evaluation of neuromuscular diseases. The presentation of a peripheral neuropathy in the pediatric population may be different from that of an adult. The nature of the chief complaint helps define the type of neuropathic process. Patients may present with weakness, sensory disturbances, pain, autonomic disturbance, atrophy, ataxia, or a combination thereof. The time course of the symptoms is an important diagnostic clue, whether it is acute, subacute, or chronic (relapsing, recurrent, progressive, and so forth). Neuropathies can present with a number of different anatomic patterns. Symmetric or asymmetric, focal or diffuse, helps differentiate between a mononeuropathy, mononeuropathy multiplex, polyneuropathy, radiculopathy, polyradiculopathy, or plexopathy.1

In the history of a neuromuscular disorder, the examiner should always ask specifically about trauma, toxic exposures (including recreational drugs and alcohol), infections or vaccinations, dietary deficiencies, medications (both past and present), and concomitant medical conditions (Table 14-1).1 Constitutional symptoms such as weight loss or unexplained fever may direct the evaluation toward an underlying etiology. Family history may be extremely important in the neuropathies seen during childhood since many of these disorders have a genetic basis.

Physical Examination

A thorough physical examination is very important in the evaluation of neuromuscular disorders. The cranial nerves are rarely involved in a typical peripheral neuropathy but are commonly involved in Guillain–Barré syndrome (GBS), sarcoid, carcinomatosis, and diphtheria.1 Atrophy and its distribution can assist with certain diagnoses such as Charcot-Marie-Tooth disease with the classic champagne bottle legs. As with atrophy, the distribution of weakness guides diagnosis. Most polyneuropathies affect distal muscles of lower extremities first. Most demyelinating and certain acute motor and toxic neuropathies affect all muscles of limbs, trunk, neck, and some facial muscles. With the help of the history, try to narrow weakness into a pattern of mononeuropathy, mononeuropathy multiplex, polyneuropathy, radiculopathy, polyradiculopathy, or plexopathy.

While the sensory examination is very important in the assessment of a patient with a neuropathy, it may be very difficult to formally assess in children, especially the very young. Most peripheral neuropathies have distal, symmetric, sensory loss in lower extremities first (stocking-glove distribution). Sensory loss exceeds weakness in most toxic neuropathies.

The reflex examination usually reveals diminished or completely lost reflexes. The reflexes may be diminished out of proportion to the degree of weakness.1

A general skin and musculoskeletal examination is also of great importance. Pes cavus is often seen in hereditary neuropathies secondary to weakness of peroneal and pretibial muscles more than calf muscles. A "claw" hand may arise in the upper extremity for similar reasons. Kyphoscoliosis can occur secondary to weakness of paravertebral muscles. Skin ulcers, pressure sores, and burns are often seen secondary to analgesia. Analgesic joints become traumatized resulting in a deformity known as Charcot arthropathy. Hypertrophied nerves are seen in a number of neuropathies including chronic inflammatory demyelinating polyneuropathy (CIDP), Refsum disease, leprosy, hereditary sensory motor neuropathy (HMSN; III > II > I), acromegaly, neurofibromatosis, and amyloidosis.

Diagnostic Testing

Electrophysiologic studies (nerve conduction studies) can further categorize neuropathies as primarily demyelinating or axonal, sensory or motor, or both. This information helps to differentiate between mononeuropathy, polyneuropathy, mononeuropathy multiplex, plexopathy and radiculopathy.1

Most peripheral neuropathies are axonal and usually have symmetrical distal sensory loss with weakness, atrophy, and lost ankle jerks. The nerve conduction study shows significantly decreased amplitudes of compound motor action potential (CMAP) and sensory nerve action potential (SNAP) (often no obtainable potential), but only mild slowing without conduction block or temporal dispersion. Needle EMG shows evidence of distal denervation (frequently not performed in children).1

Demyelinating neuropathy is a less common category of peripheral neuropathy. Early generalized reflex loss, mild atrophy, proximal and distal muscle weakness, sensory loss of large fiber; small fiber modalities, motor usually; sensory involvement, tremor, and hypertrophied nerves are common physical findings in a patient with a demyelinating neuropathy. Nerve conduction studies reveal marked nerve conduction velocity slowing, conduction block, temporal dispersion, and prolonged F-wave and distal latencies. The needle EMG may show denervation, based on the chronicity of the neuropathy. GBS, CIDP, and some hereditary neuropathies are demyelinating. Many neuropathies are mixed axonal and demyelinating and mixed sensory and motor.

Laboratory studies are very important in the evaluation of neuropathy. A wide array of laboratory tests may be ordered but the exact panel depends on the history and the physical examination. Suggested laboratory studies are listed in the following sections.

Lumbar puncture is especially helpful in the diagnosis of a demyelinating neuropathy such as GBS or CIDP. In these patients, the CSF protein is elevated.

Treatment

Specific treatment modalities aimed at the underlying etiology are not possible in most neuropathies (especially chronic sensory motor polyneuropathies); nevertheless, the search for a specific, treatable cause should be undertaken. In approximately 25% of all chronic polyneuropathies, an etiology cannot be determined. Treatments for specific neuropathies, such as GBS and CIDP, are discussed later in this chapter.

Epidemiology

Acute inflammatory demyelinating polyneuropathy (AIDP) or GBS is the most frequent cause of acute generalized weakness. The incidence is 1 to 2 per 100,000 per year. It occurs in a nonseasonal, nonepidemic pattern affecting both genders, all ages, and in all parts of the world. While incidence increases with increasing age (highest ages 50-74 years), childhood cases are not unheard of.1

Two-thirds of patients have a preceding event 1 week to 1 month prior to onset (URI, 60%; GI syndrome, 20%; surgery, 5%; vaccinations, 5%).1 Antecedent infections associated with GBS are listed in Table 14-2. Lymphoma, particularly Hodgkin disease, has been associated with GBS. Surgery and spinal/epidural anesthesia may also precipitate GBS.

Etiology/Pathogenesis

Immune-mediated segmental demyelination is initiated by an undetermined antigenic reaction (possibly viral). There is a cell-mediated component in which T-cell lines are sensitized to P2, a basic protein found in peripheral nerve myelin. A clinically and pathologically indistinguishable disease called experimental allergic neuritis (EAN) develops in animals 2 weeks after immunization with a peripheral nerve homogenate containing P2.

An antibody-mediated component also occurs with immunoglobulins and complement found on myelinated fibers, and anti-peripheral nerve myelin antibodies found in some patients' serum (titers correlate with clinical course). An antibody to the GD1a ganglioside has been associated with a worsened clinical course.

Pathology specimens show perivascular mononuclear cell infiltrates early, associated with perivenular demyelination. Later, segmental demyelination and secondary Wallerian degeneration occur, affecting entire peripheral nerves, cranial nerves, dorsal and ventral roots, and dorsal root ganglia.

Clinical Presentation

Most patients present with rapidly progressive symmetrical weakness with areflexia.2 The weakness is usually ascending (distal to proximal) with the lower extremities affected first, then trunk, arms, and cranial muscles.3 In rare cases, proximal muscles can be affected first. Cranial nerves are rarely affected first, but more than 50% of patients have cranial nerve involvement, with facial diplegia being the most common deficit.

The maximum deficit typically occurs within days of onset up to maximum of 4 weeks after onset and then plateaus.3 Total motor paralysis with respiratory failure and death may occur in a few days in severe cases. Weakness is so rapid that atrophy is rarely seen. The weakness is associated with hypotonia. An acute cord lesion should be considered in patients with low back pain, areflexia, and leg paralysis. The reflexes are initially decreased and then absent in GBS.

While GBS is a motor neuropathy, sensory complaints are common.2,3 Low-back pain and myalgias occur in many patients, often involving the hips and thighs. Severe myalgias are rare and increased CPK levels should suggest other disorders. Paresthesias are a common early symptom but resolve rapidly. Objective sensory loss is usually mild and usually affects large fiber modalities (vibration and position sense).

Autonomic instability is fairly common but highly variable in expression.1-3 Patients may experience one or more dysfunctions of the autonomic system, occasionally with rapid fluctuations. Sinus tachycardia, bradycardia, other tachyarrhythmias, orthostatic hypotension, hypertension, anhidrosis, diaphoresis, sphincter dysfunction, pupil changes, gut atony, and flushing can occur. The autonomic dysfunction usually lasts less than 1 to 2 weeks. Urinary retention occurs in 15% of cases.

Clinical variants are even less common than GBS. Miller-Fisher syndrome consists of gait ataxia, ophthalmoparesis, and areflexia, with normal limbs (some patients have mild proximal limb weakness). It is associated with IgG antibody to ganglioside GQ1b and prior Campylobacter jejuni infection.4,5

Pharyngeal–cervical–brachial GBS consists of blurred vision or diplopia, ptosis, marked oropharyngeal, neck and shoulder weakness, respiratory failure, areflexia in arms only, and normal sensation (occasionally leg areflexia present). This disorder simulates botulism and diphtheria clinically. There is no dry mouth, dizziness, or GI symptoms that are typical of botulism.

Differential Diagnosis

Acute demyelinating inflammatory polyneuropathy is relatively uncommon in children and may mimic a variety of disorders making diagnosis a challenge. Rapid diagnosis is important as treatments are available that may help avoid complications. Table 14-3 outlines the differential diagnosis with differentiating factors.

Diagnostic Testing

Electrodiagnostic Studies

Nerve conduction studies reveal focal nerve conduction velocity (NCV) slowing, motor conduction block, temporal dispersion, and prolongation of F-wave and terminal latencies. All parameters may be normal for the first few days. The initial abnormality is prolonged (or absent) F-waves. Nerve conduction studies can remain normal in up to 10% of cases.9

Laboratory Studies

CSF studies typically exhibit an elevated protein with normal cell count (albuminocytologic dissociation). In rare cases, patients will have 10 to 50 cells/mm3 (mostly lymphs). Protein may remain normal for the first few days, rising to peak in 4 to 6 weeks. Unfortunately, CSF protein remains normal in 10% of patients, making diagnosis even more challenging. The opening pressure and CSF glucose are usually normal.

Blood should be sent for complete blood count, metabolic profile with Ca, Mg, Phos, hepatic studies, HIV, ESR, and Lyme disease. If suggested by history, heavy metal studies should be obtained.

Treatment

Supportive therapy is vital with respiratory assistance and careful nursing. Frequent forced vital capacity (FVC) measurements should be obtained. Intubation should be considered if the FVC falls below 12 to 15 mL/kg, regardless of arterial blood gas testing. If there is significant bulbar weakness even with a good FVC, the patient may need intubation for airway protection. Respiratory therapy should be consulted for aggressive pulmonary toilet. Tracheostomy may be necessary if the patient requires prolonged intubation.

Cardiac monitoring and frequent vital signs are important given the risk of autonomic dysfunction. As with all pediatric patients, special attention must be given to the fluid status.

Physical therapy should be consulted early in the hospital stay for range of motion, but the patient should not be pushed aggressively during therapy sessions, given the risk of respiratory insufficiency.

The patient must be monitored for the development of decubitus ulcers. The patient should be turned frequently to avoid the prolonged pressure leading to skin breakdown.

Artificial tears during the day, and lubricating gel with eye patches at night, should be used if there is significant facial weakness.

Immune Modulating Therapy

In mild cases, careful observation and supportive care may be all that is needed. Patients who are progressing, are ambulatory only with assistance or recently have become nonambulatory, or those with respiratory compromise or autonomic instability, should be considered for immune modulating therapy. Two treatment options exist for GBS: therapeutic plasma exchange and intravenous immunoglobulin.10-12

Therapeutic plasma exchange (TPE) is a common treatment in adults but has significant limitations in children.12 It is most effective if given within 7 days of disease onset and for patients who require intubation. Use of TPE results in decreased hospitalization time, mechanical ventilation time, and time until the patient walks again. The side effects include hypotension, bleeding, arrhythmias, and infection. The volume exchanged limits this treatment option in children.

Intravenous immunoglobulin (IVIg) was proven effective in one multicenter trial at dosage of 400 mg/ kg/d × 5 days. There appears to be a reduced complication rate over TPE, and less need for mechanical ventilation. The side effects include allergic reactions, renal failure, aseptic meningitis, increased serum viscosity with vasoocclusive phenomena, and headache. Always check an IgA level prior to IVIg initiation, given the increased risk of anaphylaxis in IgA-deficient patients when administered IVIg.10,11

Glucocorticoids are ineffective.

Epidemiology

Chronic inflammatory demyelinating polyneuropathy (CIDP) is also known as chronic inflammatory demyelinating polyradiculoneuropathy, chronic relapsing GBS, chronic relapsing polyneuritis, and relapsing cortico-steroid-dependent polyneuritis. The peak incidence occurs between 40 and 60 years of age, but can occur from infancy to late adulthood.1 Less than 10% have preceding viral infections. The age of onset can influence disease course, with younger patients tending to have a relapsing course, and older patients a more chronic progressive course.13

Etiology/Pathogenesis

There is immune-mediated segmental demyelination with a cell-mediated component based on mononuclear cell infiltration of spinal roots, ganglia, and proximal nerve trunks.13 The evidence for a humoral component is based on detection of IgM (less often IgG) and complement fragment C3d on myelin sheaths of sural nerve biopsies and also the fact that CIDP patients tend to respond to plasmapheresis. Pathology specimens, usually from sural nerve biopsy, show interstitial and perivascular inflammatory cell infiltrates, loss of many myelinated fibers and degeneration of others with segmental demyelination–remyelination (onion-bulb formations). Large fibers are more severely involved. In predominantly motor disease, changes in the sensory nerves may not be fully representative of the pathologic process.

Clinical Features

The onset of CIDP is typically insidious with a steady or stepwise progression of symmetric proximal and distal muscle weakness of both upper and lower extremities. Asymmetric signs are much less common. The formal diagnostic criteria for CIDP are shown in Table 14-4.1,,13,14

Weakness must be present for at least 2 months. The weakness can vary from mild to severe, requiring assisted ambulation, but rarely assisted ventilation. Proximal muscle weakness may be equal to or greater than distal weakness. This sets CIDP apart from most other neuropathies. Arms and legs are usually affected, but the legs are usually more severely involved. Neck flexor weakness may also occur, which is also a distinguishing feature of CIDP. Facial muscles are rarely involved. Reflexes are diminished or absent.1,16

Sensory findings are usually mild but sensory involvement is more prominent than in GBS. Touch, vibration, and proprioception are more commonly involved than pain/temperature. Numbness, paresthesias, and dysesthesias of the hands may be initial symptoms. Painful paresthesias are uncommon. Some patients may have severe proprioceptive loss, with ataxia, wide-based gait, and positive Romberg sign.1,16

Diagnostic Evaluation

Electrodiagnostic Testing

Nerve conduction studies usually reveal a non-uniform reduction in NCV in the demyelinating range in at least 2 motor nerves. Conduction block or abnormal temporal dispersion should be present in at least 1 motor nerve. Distal latencies should be prolonged in at least 2 nerves. F-waves are usually prolonged or absent.16

Laboratory Studies

Cerebrospinal fluid (CSF) evaluation reveals albuminocytologic disassociation. The CSF protein is elevated in most cases, with CSF protein greater than 55 mg/dL in 95% of patients. The CSF white blood cell count is usually less than 10/mm3.

Nerve biopsy results are described under "Etiology/ Pathogenesis"above.

Laboratory testing for patients with suspected or confirmed CIDP includes a wide array of tests, as outlined in Table 14-5.

Treatment

The mainstays of treatment in the adult population are prednisone and TPE. Prednisone is dosed at 1.5 mg/kg/d in children.17,18 The prednisone should be continued until significant improvement in weakness is apparent. The mean time to initial response is approximately2 months. Following improvement, the prednisone should be changed to an alternating day, single-dose regimen and continued until the patient reaches maximum therapeutic response. The prednisone should then be tapered slowly. Patients should be carefully monitored for side effects related to steroid use including increased blood pressure, hyperglycemia, and weight gain.

IVIg is administered as described earlier in the GBS treatment section. Following the initial treatment, patients may need additional treatments every 3 to 6 months depending on the clinical course.

Other treatment options include azathioprine (Imuran), cyclosporine A, or cyclophosphamide.19,20

Tick paralysis is an uncommon disorder that occurs with a tick bite. The neuropathy has a rapid onset and symptoms resolve quickly when the tick is removed. Any patient presenting with symptoms of a rapid-onset motor neuropathy (generalized paralysis) should have a thorough skin examination for ticks.

Critical illness polyneuropathy (CIP) is uncommon in children but is likely under-recognized. Critical illness polyneuropathy occurs in approximately 50% of adults in the ICU with sepsis and in approximately 70% of adults with sepsis and multiorgan system failure.21 Usually patients have been in the ICU for at least 1 week when the earliest signs develop (eg, difficulty weaning from the ventilator). Later signs include distal weakness, decreased deep tendon reflexes, and, if severe, complete quadriplegia and respiratory paralysis. CIP may occur outside the ICU in patients who develop sepsis in the course of severe renal failure. Physical signs occur in 50% of patients and the other 50% are diagnosed by NCS/EMG.

Nerve conduction studies are compatible with primary axonal degeneration, and EMG shows signs of denervation. Decreased diaphragmatic CMAPs and signs of chest wall denervation establish CIP as the cause of difficulty of weaning from the ventilator.1

There are a number of hereditary chronic polyneuropathies that tend to be more chronic than acquired, progressive, symmetrical, and degenerative. One major category presents with autonomic features (Table 14-6). These disorders are inheritable and usually appear early in life.

Friedreich Ataxia

Epidemiology

Friedreich ataxia is an autosomal recessive, triple repeat disease with a number of components.22 The disorder is described in more detail in Chapter 13.

Etiology/Pathogenesis

The sensory neuropathy associated with Friedreich ataxia occurs because of progressive degeneration of the dorsal ganglion and axon. There is some associated secondary demyelination.22 The characteristics of the hereditary neuropathies with autonomic features are outlined in Table 14-6.

Clinical Features

The primary feature of Friedreich ataxia is the gait ataxia. This ataxia is progressive and typically leads to the need for a wheelchair. The sensory neuropathy is not usually the most important component of the disorder but does add to the effect of the ataxia.

Treatment

There is no specific treatment for Friedreich ataxia. The patient is on a fall risk and appropriate safety measures should be taken. Furthermore, the patient's feet should be checked on a daily basis for cuts or blisters that might otherwise go unnoticed because of the sensory loss.

Epidemiology

The hereditary motor and sensory neuropathies also typically appear early in life, as described in Table 14-7.23 Charcot-Marie-Tooth (CMT) disease occurs in several subtypes. Type I CMT is an autosomal dominant disorder and is localized to chromosome 17 for type Ia and to chromosome 1 for type Ib (Table 14-7).24

Etiology/Pathogenesis

In Type I CMT, peripheral nerves hypertrophy and are occasionally palpable. Onion bulb formations occur in the nerve sheaths because of excessive collagen. Type II CMT, however, has no nerve hypertrophy and the onion bulb formations are rarely seen.25

Clinical Features

Type I CMT is characterized by distal muscle atrophy beginning in the lower extremities with progressive weakness of the anterior tibialis and peroneus muscles. This atrophy results in the classic "champagne bottle" legs. Similar changes in the upper extremities result in a clawed hand deformity. Distal sensory loss, paresthesias, and diminished or absent deep tendon reflexes also occur. Patients often develop skeletal changes as well, including an equinovarus deformity and kyphoscoliosis. The muscle atrophy and weakness are much less pronounced in type II CMT.

Diagnostic Testing

Nerve conduction studies reveal demyelinating range slowing even in infants. Over time, the amplitude seems to decrease with increasing age. Nerve biopsies reveal the demyelination, nerve hypertrophy and onion bulb formations in Type I CMT.

Treatment

Treatment is supportive. Aggressive splinting can help avoid the clawed hand deformity. Patients may also benefit from orthotics for the feet because of the equinovarus deformities.

Other Considerations

There exist a group of inherited neuropathies that in addition to neuropathy present with non neural tissue involvement.26,27 Some of them are related with a specific inherited metabolic disorder, Table 14-8 outlined main neuropathies. Diagnostic testing include metabolic, genetic and nerve biopsy. There exist treatment for some disorders. Hereditary and acquired peripheral neuropathies show a wide range of sympathetic and parasympathetic nerve fiber lesions.28,29Table 14-9 described principal clinical autonomic dysfunction.

Brachial Plexus Neuritis/Parsonage-Turner Syndrome/Neuralgic Amyotrophy

Epidemiology

Brachial plexus neuritis is relatively uncommon in the pediatric population. There is a seasonal variation in the incidence since the disorder is often related to viral infections. There are also sporadic cases related to surgery or trauma.

Etiology/Pathogenesis

Most cases of brachial plexus neuritis are felt to be related to post-infectious inflammation.1 The disorder has not been linked to a single virus but, on the contrary, has been associated with a wide variety of infections. There have also been reports of brachial plexus neuritis occurring after anesthesia, injection of serum, vaccination, antibiotic administration, IV heroin injection, unaccustomed vigorous exercise, trauma, asthmatic attack in children (Hopkins syndrome), or Lyme disease.

Clinical Presentation

The distribution of the symptoms depends on the portion of the brachial plexus involved. There is usually local pain at the shoulder described as a boring or toothache- like pain. Weakness then develops in the affected muscles 3 to 10 days after the onset of pain. Some muscles may become completely paralyzed which is uncommon in radiculopathies. Over time, atrophy develops in the weakened muscles. Sensory changes are also possible occurring most commonly in the axillary region.

Differential Diagnosis

Diagnostic Testing

Cerebrospinal spinal fluid testing is unremarkable. Blood testing may reveal antibodies against the causative agent (viral etiologies, Lyme disease, and so on).

Electrodiagnostic testing (NCV/EMG) is helpful in the diagnosis but may be normal if tested too early in the course of the syndrome. The two most useful NCVs are the latency from the Erb point to shoulder girdle muscles and sensory NCV from Erb point through brachial plexus. Needle EMG is best means of confirming diagnosis with fibrillation potentials/positive sharp waves and MUP changes indicative of denervation in affected limb muscles, with paraspinous muscles usually normal (as distinguished from radiculopathies).

Treatment

Approximately 80% of patients completely recover within 2 years. Treatment with steroids may help the pain. Treatment is primarily supportive.

Erb-Duchenne syndrome or upper radicular syndrome involves injury to the C4, C5, and C6 nerve roots, or the upper trunk of the brachial plexus.1 This syndrome typically occurs following a hard blow to the neck or a birth injury. The signs consist of loss of arm abduction, elbow flexion, supination, and lateral arm rotation. The patient's arm assumes a "waiter's tip" arm position.

The middle radicular syndrome occurs following an injury of the C7 nerve root or the middle trunk of the brachial plexus. There is typically loss of radially innervated muscles except brachioradialis and part of the triceps. This syndrome can occur with the inappropriate use of crutches (crutch paralysis).

Klumpke syndrome or lower radicular syndrome occurs with an injury of the C8 and T1 nerve roots or the lower trunk of the brachial plexus.1,30 It appears clinically as a combined median and ulnar palsy. There is paralysis of the thenar muscles and flexors resulting in a flattened simian hand. The syndrome usually occurs after a sudden pull of the arm or during delivery.

Thoracic Outlet Syndrome

Thoracic outlet syndrome (TOS) occurs secondary to compression of the neurovascular bundle between the neck and axilla, causing variable hand and arm muscle weakness and wasting, pain, and vascular symptoms.

Etiology/Pathogenesis

Thoracic outlet syndrome can occur because of a number of disorders. An incomplete cervical rib with fibrous band passing from its tip to first rib is the most common cause. An elongated transverse process of C7 with fibrous bands passing to the first rib, a complete cervical rib that articulates with the first rib, and anomalies of position/insertion of the anterior and medial scalene muscles (neurovascular bundle passes between these), are other anatomic causes of TOS. Fractures of the clavicle and first rib, pseudoarthrosis of the clavicle, and traumatic injury to upper thorax can also result in TOS.

Clinical Presentation

Non-Neurogenic TOS

Non-neurogenic TOS is usually seen in slender, "droop-shouldered" females with long necks, large breasts, and often poor muscle tone. This syndrome is usually accompanied by an ill-defined pain complex, with aching discomfort in shoulder, lower neck, pectoral region, upper arm, and sometimes hands, exacerbated by pulling down on and relieved by elevating the shoulder. In more severe cases, the patient may have signs of vascular compromise: subclavian vein compression—dusky color of the arm, venous distension, edema and thrombosis of vein after exercise (effort—thrombotic syndrome of Paget and Schroetter); or subclavian artery compression—digital gangrene, Raynaud phenomenon, brittle nails, or fingertip ulceration with or without supraclavicular bruit.

Tests for vascular compression are not very sensitive or specific but may be of some diagnostic help. For the test to be considered positive, the patient's symptoms should be reproduced during the maneuver. The Adson test is performed with the patient seated with hands on the thighs; both radial pulses are palpated simultaneously, the breath is held after full and rapid inspiration, the neck is hyperextended, and the head is turned to the side. The test is positive if the radial pulse on the affected side is diminished or obliterated, with the unaffected side remaining normal.

The shoulder hyperabduction test (Wright maneuver) is performed with the arm hyperabducted and externally rotated while the radial pulse is palpated; the pulse in normal subjects diminishes. The test is positive if the pulse diminishes asymmetrically in the presence of symptoms.

In the shoulder bracing test, the shoulders are braced backwards in an "exaggerated military position." The pulse on the affected side decreases more markedly than normal in the presence of symptoms.

Nerve conduction studies and EMG in non-neurogenic TOS are usually normal.

Neurogenic TOS

Neurogenic TOS is extremely rare. The syndrome typically consists of weakness and wasting of hypothenar and thenar muscles (in severe cases, of other hand intrinsics as well as flexors of fourth and fifth digits). There is usually an aching pain and sensory loss in the C8/T1 dermatomes (lower trunk involvement). Sensory symptoms may be reproduced by applying firm supraclavicular pressure or downward traction on the arm. Reflexes are usually preserved.

Nerve conduction studies and EMG show reduced amplitude of ulnar CNAP distally and across the thoracic outlet, prolonged ulnar F-wave latency, low CMAP in the median > ulnar nerve, and signs of chronic denervation in ulnar and median hand muscles.

Evaluation for both types of TOS should include C-spine films (may show cervical rib, elongated C7 spinous process, or T2 vertebral body visible above shoulder), nerve conduction studies, EMG, and possibly somatosensory evoked potentials.

The spinomuscular atrophy (SMA) syndromes are discussed in Chapter 30.