Diseases of the Nerves

Note: Significant diseases are indicated in bold and syndromes in italics.

I. Nerve Physiology

Figure 9–1 Action potential conduction. (From Koolman J, Rohm KH. Color Atlas of Biochemistry. Stuttgart, Germany: Georg Thieme; 1996:219. Reprinted by permission.)

Figure 9–2 Peripheral nerve organization. (From Midha R, MacKay M. Principles of nerve regeneration and surgical repair. Semin Neurosurg 2001, 12:82, Fig. 1. Reprinted by permission.)

ii.   usually done with the common peroneal and posterior tibial nerves in the lower extremity, and with the medial and ulnar nerves in the upper extremity

b. sensory nerve conduction studies

i.    performed by stimulating a pure sensory nerve and measuring the amplitude and distal latency of the nerve potential (sensory nerve action potential [SNAP]); usually done with the sural nerve behind the lateral malleolus for the lower extremity, and with the median and ulnar nerves for the upper extremity

Figure 9–3 Motor nerve conduction study demonstrating partial motor conduction block. The median nerve was stimulated supra-maximally at the wrist and elbow and the motor response was recorded from the abductor pollicis brevis muscle. There is a 67% reduction in CMAD comparing distal to proximal stimulation sites. The antidronic median sensory nerve action potential recorded from the index fingers with ring electrodes was normal note differences in voltage. (From Nagale SV, Bosch EP. Multifocal motor neuropathy with conduction block. Semin Neurol 2003, 23:327, Fig. 1. Reprinted by permission.)

c. nerve conduction tests involving the spinal cord

i.    F waves: an internally-generated anterograde potential from the motoneuron soma caused by retrograde conduction of an action potential that is generated by distal, supramaximal axonal stimulation; the F waves are usually observed as a small response with a 20–50-ms delay after the CMAP that was directly activated by the stimulation {M response}

(1) useful for testing the integrity of proximal motor nerve segments

(2) can be performed on any motor nerve

ii.   H reflex: specific stimulation of a sensory nerve that causes reflex activation of motoneurons in spinal cord (equivalent to the reflex arc), > which can then be measured as a myographic response with a long-latency (30-ms delay) following the M response

(1) technically best performed by stimulating the tibial nerve while measuring gastrocnemius and soleus muscles (S1 innervation)

(2) sensitive to sensory fiber dysfunction more so than motor fiber dysfunction

(3) useful for testing integrity of proximal S1 nerve segments, therefore is good for distinguishing sciatic nerve injury from S1 radiculopathy

d. technical considerations

i.    limb temperature variations: cold extremities slows the conduction velocities, and increases amplitudes and distal latencies

ii.   patient age: slower conduction velocities and reduced amplitudes are normal in young children and in the elderly

iii.  limb position should be kept constant and compared against a reference standard that was developed for that limb position

3. Nerve biopsy

a. diagnostic in some conditions with abnormalities of

i.    axons (e.g., giant axon neuropathy)

ii.   myelin (e.g., hereditary neuropathy with liability to pressure palsies, anti-myelin-associated glycoprotein [MAG] antibody neuropathies, leukodystrophies)

iii.  connective tissue and supportive elements (e.g., vasculitis, amyloid, sarcoid, leprosy, tumor infiltration)

b. can be supportive, but not diagnostic, of Charcot-Marie-Tooth neuropathies and inflammatory demyelinating polyradiculopathies (Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy [CIDP])

c. procedure: generally involves both nerve and muscle biopsy simultaneously

i.    sites for nerve biopsy

(1) sural nerve, 15 cm above the heel: complicated by sensory loss with paresthesias and allodynia around the lateral malleolus that generally resolves over a period of years; avoid nerve biopsy at the ankle because repeated trauma from shoes causes nonspecific changes in the nerve

(2) superficial peroneal nerve, at the lower third of the anterior calf

(3) superficial radial nerve: used only when the neuropathy is limited to the upper extremities or when severe, chronic neuropathy exists in the lower extremities that would prevent useful histo-logical analysis of the nerve

(4) intermediate cutaneous nerve of the thigh, at the lower third of the anterior thigh: used mostly to confirm proximal diabetic plexopathy (i.e., diabetic amyotrophy/Bruns-Garland syndrome)

Figure 9–4 Wallerian degeneration in situ. (A) Light microscopy demonstrating ovoid myelin debris. (B) Electron microscopy demonstrating degeneration axons in cross-section (arrows). (From Tseng CY et al. Histologic analysis of schwann cell migration and peripheral nerve regeneration in the autogenous venous nerve conduit. J Reconstruct Microsurg 2003, 19:338, Fig. 14. From Oliveira EF et al. Correlation between functional index and morphometry to evaluate recovery of the rat sciatic nerve following crush injury. J Reconstruct Microsurg 2001, 17:73, Fig. 5B. Reprinted by permission.)

ii.   tissue preparation: sections of the nerve should be evaluated by

(1) formalin fixation followed by paraffin embedding, which demonstrates the connective tissue and blood vessels

(2) frozen section for immunostaining, which demonstrates leukocytes, complement components, and autoantibodies

(3) plastic embedding for high-resolution microscopy

a. supraclavicular lesions: more commonly injured than infraclavicular sites (severe trauma commonly involves all three trunks)

i.    upper trunk/C5–6 root injury

(1) pathophysiology: caused by

(a) traumatic depression of the shoulder (e.g., neck–shoulder distraction, weight-bearing compression)

(i) traction trauma more commonly affects nerve trunks than roots, in comparison with lower trunk/C8–T1 injury

(b) birth trauma: maternal obesity, multiparity, and large baby size are greater risk factors than obstetrical intervention; can occur even with normal vertex head positioning

(2) symptoms

(a) weakness in shoulder abduction (supraspinatus and deltoid) and external rotation (infraspinatus), elbow flexion (biceps and brachioradialis), and forearm supination; produces an internally rotated and adducted shoulder with extended elbow and pronated hand {waiter’s tip/Duchenne-Erb palsy}

(i)    winging of the scapula (weakness of the serratus) suggests involvement of the C5–7 nerve roots, from which the long thoracic nerve originates

(ii)   weakness of scapula elevation (rhomboid) suggests involvement of the dorsal scapular nerve, which originates from the C5 nerve root

(b) sensory loss in lateral brachium and antebrachium

ii.   middle trunk/C7 root injury

(1) pathophysiology: usually occurs in conjunction with upper or lower trunk injuries

(2) symptoms (specific for the middle trunk/C7 root)

(a) weakness in elbow extension, wrist extension, finger extension, and forearm pronation (pronator teres and quadratus); produces a decorticate-like posture

(b) sensory loss in the dorsal brachium, antebrachium, and hand

ii.   medial cord injury—symptoms include weakness in wrist flexion toward the ulnar side, finger flexion and extension, and hand intrinsic muscles including thumb flexion and opposition (similar to that of Klumpke’s palsy), as well as sensory loss along the whole medial side of the upper extremity

iii.  posterior cord injury—symptoms include

(1) weakness in shoulder abduction (deltoid) and adduction (latissimus dorsi and teres major), elbow extension, forearm supination, wrist extension, and finger extension

(2) sensory loss that is usually limited to the thumb and deltoid, but it may extend over the entire radial nerve sensory territory (i.e., dorsal web-space between the first and second digits, the dorsal brachium, and dorsal ante-brachium)

4. Diagnostic testing

a. neuroimaging: not reliable for lesion localization in the brachial plexus

i.    plain radiographs can demonstrate vertebral and clavicular fractures

ii.   CT myelography and MRI can demonstrate nerve root avulsions and traumatic injury to the meninges and spinal cord; CT myelography is superior to conventional myelography, particularly for C5–6 lesions

b. nerve conduction study: results must be interpreted carefully because the presence of injury to the plexus will hide root injuries

c. EMG: the absence of fibrillation potentials in paraspinal muscles does not rule-out nerve root injury, but their presence does confirm it

5. Treatment

a. anastomosis of transected neural elements, although this is generally ineffective for nerve roots or for injuries to lower trunk

b. destruction of the dorsal root entry zone for elimination of chronic pain of nerve root injury

Figure 9–6 Lumbosacral plexus anatomy. (From Duus P, Topical Diagnosis in Neurology. Stuttgart, Germany: Georg Thieme; 1998:24, Fig. 1.25. Reprinted by permission.)

ii.   sacral plexus lesions: pain is located in the posterior thigh, calf, or foot

b. weakness

i.    lumbar plexus lesions: weakness mostly in hip flexion and knee extension

ii.   sacral plexus lesions: weakness mostly in ankle movements and hip extension; involvement of the pudendal nerve function or S2–4 nerve roots causes bowel and bladder dysfunction (rare)

3. Diagnostic testing

a. neuroimaging: MRI and radionucleotide scanning are useful for localization of tumors; CT is useful for imaging of hematomas

b. EMG: evidence of denervation in the gluteus muscles and the muscles innervated by the sciatic nerve indicates a sacral plexopathy rather than a sciatic neuropathy

Figure 9–7 Median nerve anatomy. (From Rohkamm R. Color Atlas of Neurology. Stuttgart, Germany: Georg Thieme; 2004:35. Reprinted by permission.)

IV. Traumatic and Compression Neuropathies (“Entrapment Neuropathies”)

1. Pathophysiology: Patients with a preexisting neuropathy are at greater risk for compression neuropathies, but there is no evidence that one focal injury to a nerve increases the susceptibility of that nerve to a second focal injury

a. histology

i.    focal compression causes longitudinal sliding of the myelin layers that collect on either side of the site of compression {tomaculae}; accumulations of excess myelin layers may impair axoplasmic transport

ii.   Wallerian degeneration order of progression of historical changes

(1) Schwann cell retraction and myelin breakdown begin proximal to the injury site; accumulation of mitochondria and transport vesicles occur at the nodes of Ranvier along the length of the axon

(2) disintegration of the smooth endoplasmic reticulum in the neuronal soma

(3) breakdown of microtubule and intermediate filament structures

(4) macrophage invasion of the nerve: a late response, therefore Wallerian degeneration is not a primary inflammatory reaction

(5) persistence of Schwann cell tubes and their basal lamina {bands of Bungner}

2. Specific compression neuropathies of the upper extremity

Figure 9–8 The carpal tunnel. (From Platzere W. Atlas of Topographical Anatomy. Stuttgart, Germany: Georg Thieme; 1985:145, Fig. 153. Reprinted by permission.)

(c) sensory loss, usually limited to part of the distal median nerve sensory territory; sensory loss should not involve the thenar eminence, which is supplied by a branch of the median nerve that leaves above the carpal tunnel