Peripheral Neuropathy

Joshua Gordon

Morris A. Fisher

key points

History and physical examination are the most important steps in determining the etiology of a peripheral neuropathy.
Neuropathies can be categorized according to type of modalities involved (motor, sensory, or autonomic) and distribution (multifocal or diffuse).
A distal symmetric pattern is the most common presentation of a polyneuropathy.
Treatment of peripheral neuropathies is either directed at the underlying cause or is aimed at reducing the discomfort that is often associated with neuropathies.

CLINICAL FEATURES AND SCIENTIFIC BACKGROUND

The peripheral nervous system (PNS) starts as the pia arachnoid ends at the level of the intervertebral foramina and therefore encompasses those parts of the nervous system that lie outside the confines of the brain, brainstem, and spinal cord. It consists of those portions of the primary sensory neurons, lower motor neurons, and autonomic neurons that are outside the central nervous system (CNS). Therefore the PNS includes the cranial nerves, the spinal nerves with their roots and rami, the peripheral nerves, and those aspects of the autonomic nervous system that are outside the CNS. Because some disease processes preferentially involve the PNS, it is useful to consider this system as a nosologic entity.

All parts of the PNS are associated with Schwann cells or the comparable ganglionic cells, the satellite cells. This anatomic commonality may account for some of the pathologic aspects of the PNS. More significantly, the normal functions of all parts of the PNS are dependent on the proper functioning of the nerve cell bodies from which the motor and sensory axons originate. For example, the foot is supplied by nerve fibers whose cell bodies lie at the level of the lower thoracic/upper-lumbar vertebrae. A single neuron consists of the motoneuron and its associated motor axon innervating a foot muscle. The maintenance of this cell extending from the lower back to the foot is a complex process. There is constant anterograde transport system from the nerve cell bodies to their most distal axonal projections, and this system is necessary for maintaining
normal nerve (and muscle) function. There is also retrograde transport so that the cell bodies are influenced by distal events. This system provides the conduit by which agents such as herpes virus may reach the nerve cell body. Given the complexity and length of the structures involved, it is not surprising that the normal functioning of the PNS frequently is disturbed.

ANATOMY

Except for the cranial nerves, peripheral nerves separate at the level of the roots. The dorsal roots contain sensory afferent (sensory) fibers that are located either preganglionic or postganglionic to the dorsal root ganglion on their way to the spinal cord. The ventral roots consist of efferent (motor) fibers that originate from the lower motor neurons. The ventral and dorsal roots joining shortly after exiting the spinal cord, and the resultant mixed (motor and sensory) nerves are the structures for providing information to and from the CNS. In the thoracic and upper-lumbar region, these nerves are joined by sympathetic fibers after these fibers have synapsed in the ganglionic chain adjacent to the vertebral column. The parasympathetic outflow originates either in the cranial region (cranial nerves III, VII, IX, and X) or in the sacral region passing distally as the pelvic splanchnic nerves (Fig. 18.1).

Individual muscles and areas of skin are supplied not only by particular nerves but also by fibers that originate in particular roots. The PNS distribution in the limbs is superficially complex because of the routing that occurs in the brachial plexus for the upper limb, and the lumbosacral plexus of the lower limb.

Individual nerves are composed of bundles of individual nerve fibers called fascicles, which, in turn, are surrounded by connective tissue. All of the motor fibers and many of the sensory fibers are surrounded by myelin. Myelin is formed by foldings of Schwann cell membranes. These supporting cells are ubiquitous throughout the PNS. In myelinated fibers the gaps between myelin sheaths from two adjacent Schwann cells are referred to as nodes of Ranvier. Most sensory fibers and all autonomic fibers are either poorly myelinated or unmyelinated. Even unmyelinated nerve fibers, however, are ensheathed by Schwann cells.

FIGURE 18.1 Drawing of peripheral nerve originating from (1) ventral root with cells of origin in the anterior horn of the spinal cord and (2) dorsal root with a dorsal root ganglion. The postganglionic dorsal root fibers pass to the dorsal horn or more superiorly in the spinal cord. The posterior primary ramus extends dorsally, whereas the anterior primary ramus is the main extension of the peripheral nerve. Sympathetic fibers join the peripheral nerve by way of the sympathetic ganglion.

Nutrient arteries that arise from adjacent blood vessels supply nerves. The arterial supply is richly collateralized both to and within the nerves themselves. The result is a system resistant to large-vessel ischemia.

INDICATIONS OF NEUROPATHIC INJURY

The symptoms and signs of neuropathic injury can be predicted from the preceding discussion. If nerves to muscles are disrupted, weakness may be present, and prominent atrophy of muscle fibers can occur. Cramping with fatigue is a common symptom. Reflexes may be decreased or absent if the afferent or efferent nerves that subserve the reflex are disturbed.

A wide range of sensory disturbances are found. With complete loss of innervation, there may be total loss of feeling-anesthesia. This rarely happens because of the considerable overlap of sensory nerve supply. More commonly, alterations in sensation are found. Unusual feelings such as “pins and needles” are called paresthesias, and unpleasant sensations such as burning are called dysesthesias. A decrease in sensation on examination is referred to as hypoesthesia; an increase is called hyperesthesia. Formication refers to the crawling feeling that some patients may experience. A decrease in perception of position and vibration indicates dysfunction in larger fibers, whereas diminished pinprick and temperature sensation indicates abnormalities in smaller fibers. Autonomic dysfunction can affect cardiac, vasomotor, gastrointestinal, sweating, and sexual functions. The skin may become smooth and glossy, hair may decrease (or occasionally increase), and the nails may become thickened. Because of loss of feeling, repeated injury and inadequate repair can result in permanent losses in limbs as well as of function of joints (Charcot joints).

ANATOMIC DISTRIBUTION

Motor and sensory changes caused by PNS disease occur in the distribution of nerve roots or the peripheral nerves themselves. Charts are readily available that show these distributions. The information has been obtained indirectly based on root or nerve injury. Although superficially complex, with practice the information becomes readily usable. There is some variability between different charts, and one should not attempt to fit each patient into a rigidly circumscribed view of normal. Patterns of root and nerve distribution in a broad sense are reliable, and it is important to try to identify these patterns clinically (Fig. 18.2).

The muscles of the shoulder girdle are innervated mainly by the C5 root, those of the arm by C5 and C6 (triceps brachii, C7), those of the forearm by C7 and C8, and those of the hand by C8 and T1. In the lower extremity, the thigh muscles are supplied by the L2, L3, and L4 roots. Those muscles of the anterior leg are innervated by L4 and L5 roots, those of the posterior leg by S1, and the small muscles of the foot by S1 and S2.

FIGURE 18.2 Sequential nature of the cutaneous root distribution as shown with the individual in the quadruped position.

The root sensory distribution can be visualized with the individual in the anatomic position. In general, C1-4 innervate the back of the head, the neck, and the shoulder region; C5 innervates the lateral aspect of the arm; C6 innervates the lateral portion of the forearm extending into the hand involving the thumb and index finger; C7 innervates the midportion of the hand and ring finger; and C8 innervates the more medial portion of the hand including the little finger. The posterior aspect of the upper extremity then is supplied by T1 and T2, and the torso is innervated sequentially by T2-L1, with T5 at about the level of the nipples and T10 at the umbilicus. The anterior thigh is supplied by L1, L2, and L3; the anterior leg and foot are supplied predominantly by L4 and L5; the posterior aspect of the lower extremity is supplied by S1 and S2; and the region of the anus is supplied by S3, S4, and S5.

The three main terminal nerves of the brachial plexus in the upper extremity are the radial, median, and ulnar nerves. The radial nerve innervates the extensor muscles and provides much of the cutaneous supply to the extensor surface of the arm, forearm, and hand. The median nerve is the predominant nerve innervating the forearm flexors as well as the muscles of the thenar eminence controlling thumb movement. The ulnar nerve innervates the remaining intrinsic hand muscles. The median and ulnar nerves supply the cutaneous sensibility to the hand. The ulnar territory characteristically encompasses the little finger, half of the ring finger, and the adjacent palmar surface, whereas the median nerve provides the remaining cutaneous innervation (Fig. 18.3). Variations, however, are frequently present.

FIGURE 18.3 Cutaneous innervation of the hand by the radial (clear section), median (stippled section), and ulnar (diagonal lines) nerves.

In the lower extremity, the femoral nerve supplies the knee extensors in the thigh in addition to the cutaneous branches for the anterior thigh and medial aspect of the leg and foot (by way of the saphenous nerve). The posterior thigh muscles controlling knee flexion, as well as all the muscles of the leg and foot, are innervated by the sciatic nerve. The peroneal (anterior tibial) branch of the sciatic nerve supplies the anterior compartment of the leg—namely, those muscles that affect dorsiflexion of the ankle and toes as well as foot eversion. The tibial portion of the sciatic nerve innervates those muscles producing plantar flexion. The cutaneous distribution is comparable. Branches of the peroneal nerve supply the anterior leg and dorsum of the foot, whereas the posterior aspect of the leg and plantar aspect of the foot are innervated by branches
of the tibial nerve. The medial plantar aspect of the foot and toes is supplied by the medial plantar nerve, whereas their more lateral aspect is supplied by the lateral plantar nerve. The medial and lateral plantar nerves are the terminal equivalents of the upper-extremity median and ulnar nerves, respectively.

Table 18.1 indicates selected muscle movements with their main innervation, and Table 18.2 shows a schema of the cutaneous innervation of the limbs. These tables and the preceding discussion are designed to provide a framework for the clinical evaluation of peripheral nerve disorders. To do the examination well requires considerable experience. Obtaining the necessary information from the patients can be demanding, and the examination itself must be an active process looking fo
patterns of abnormality. As such, neurologic consultation for the evaluation of peripheral nerve disorders is frequently helpful.

TABLE 18.1 Selected Muscle Movements and Their Innervation

Joint Movement	Muscles^a	Peripheral Nerves^a	Spinal Segments^a
	Upper	Extremity
Shoulder abduction	Deltoid	Axillary	C5
Shoulder external rotation	Infraspinatus	Suprascapular	C5
Elbow flexion	Biceps brachii	Musculocutaneous	C5, C6
Elbow extensin	Triceps brachii	Radial	C7
Radial-ulnar supination	Biceps brachii	Musculocutaneous	C6
Pronation	Pronator teres	Median	C7
Wrist extension	Extensor carpi radialis	Radial	C7
Radial wrist flexion	Flexor carpi radialis	Median	C7
Ulnar wrist flexion	Flexor carpi ulnaris	Ulnar	C8
Thumb adduction	Interossei	Ulnar	T1
Thumb abduction	Abductor pollicis brevis	Median	C8
Thumb extension	Extensor pollicis	Radial	C7, C8
Thumb opposition	Opponens pollicis	Median	T1
Finger adduction	Palmar interossei	Ulnar	T1
Finger abduction	Dorsal interossei	Ulnar	T1
Finger extension	Extensor digitorum	Radial	C7, C8
Index finger extension	Extensor indicis	Radial	C8
	Lower	Extremity
Hip flexion	Iliopsoas	Femoral	L2
Hip extension	Gluteus maximus	Inferior gluteal	S1, S2
Leg adduction	Adductor magnus	Obturator	L2, L3
Leg abduction	Gluteus medius	Superior gluteal	L4, L5
Knee extension	Quadriceps	Femoral	L3, L4
Knee flexion	Biceps femoris	Sciatic	S1
Ankle dorsiflexion	Tibialis anterior	Peroneal	L4
Plantar flexion	Gastrocnemius	Posterior tibial	S1, S2
Inversion	Tibialis posterior	Posterior tibial	L5
Eversion	Peroneus longus	Peroneal	L5
Large toe extension	Extensor hallucis longus	Peroneal	L5
^aOnly main controlling muscle, nerve, and roots listed.
Joint action listed because it can be easily tested and muscle, nerve, and root control are relatively simple.
Notes: Terminal divisions of the brachial plexus can be tested at the thumb. Hip action controlled by muscles innervated by L2-S2 roots.

TABLE 18.2 Schematic Cutaneous Innervation of the Limbs

	Lateral	Anterior	Medial	Posterior
Arm	C5 axillary radial		Medial cutaneous nerve of arm T2
Forearm	C6 musculocutaneous		Medial cutaneous nerve of forearm T1
Hand and fingers	Thumb and index C6		Middle C7 Ring C8 Little C8
Thigh	Lateral femoral cutaneous	Femoral L2, L3	Obturator	Posterior cutaneous nerve S2
Leg	Peroneal L5	Peroneal L5	Saphenous L4	Sural S1, S2
Foot		Peroneal L5		Plantar nerves S1
Portions of the posterior midline areas of the arm and forearm are supplied by branches of the radial nerve. For cutaneous distribution, see Figures 18.2 and 18.3.

PATTERNS OF ABNORMALITY

Derangements of motor, sensory, and autonomic function may be present with lesions at the level of the roots, plexuses, or peripheral nerves. Sensory loss, for example, involving the lateral aspect of the leg combined with weakness of dorsiflexion of the toes would be consistent with a lesion of the L5 root; motor and sensory changes in the distribution of both the axillary and radial nerves would be compatible with injury to the posterior cord of the brachial plexus; and weakness and atrophy of intrinsic hand muscles combined with sensory loss involving the medial aspect of the palmar surface of the hand, the little finger, and adjacent half of the middle finger would indicate an ulnar nerve lesion.

The most common pattern of PNS disease is a symmetric polyneuropathy. Sensory, usually more than motor, signs and symptoms are present in a more or less symmetric, predominantly distal distribution. The signs and symptoms start distally in the legs and progress proximally. Clinical findings in the legs and arms are related to the distance from the spinal cord (i.e., from C7 in the arms and T12-L1 in the legs). Sensory loss should extend to the midlegs, for example, before such findings are present in the arms. Diabetic polyneuropathy, uremia, and drug or toxic exposure are common examples. One possible cause for this distribution may be that longer nerve fibers are more vulnerable to disturbances in nutrient transport.

▪ SPECIAL CLINICAL POINT: In most distal symmetric polyneuropathies the portions of the nerve that are farthest from the spinal cord are affected first and symptoms progress proximally.

Damage to a single nerve is called a mononeuropathy. An example would be the carpal tunnel syndrome (CTS) as a result of median nerve injury at the level of the wrist. Compressive injury is a frequent cause.

A mononeuropathy multiplex indicates dysfunction of multiple single peripheral nerves. This pattern is common in diabetes as well as vasculitides such as polyarteritis nodosa.

Plexopathies refer to injury at the level of the brachial, lumbar, or sacral plexuses. Idiopathic brachial neuritis, traumatic injury to the brachial plexus, and retroperitoneal or apical lung tumors are common causes. Radiculopathies are caused by injury to the roots. Sensory loss is in a dermatome rather than peripheral nerve distribution. Disc and vertebral bone disease are among the associated conditions.

An important clinical distinction is whether a process is diffuse or multifocal. In multifocal neuropathies, the length-dependent basis of nerve dysfunction in neuropathies is not necessarily present. Cranial nerves may be involved, the arms may be more affected than the legs, and there may be prominent differences in the degree of injury between similar nerves on the right or left or between nerves (e.g., tibial and peroneal) in comparable areas of a limb.

PATHOLOGY

Pathologic processes affecting nerves usually involve both myelin and axons, although at times the physiologic effects predominantly may reflect injury to one or the other of these structures. In demyelinating processes, myelin may be lost diffusely (e.g., inherited demyelinating neuropathies) as well as segmentally (e.g., acquired demyelinating neuropathies). There may be marked slowing and blocking of conduction. The axons may be relatively well preserved. As such, clinical recovery in the acquired demyelinating neuropathies such as the Guillain-Barré syndrome (GBS) can be both rapid and complete if remyelination occurs.

Prominent axonal degeneration is more common than primary demyelination. This is characteristic of neuropathies as a result of a large number of exogenous toxins and metabolic derangements. These processes may affect the nerve cell bodies as well as the axons and may be manifested as a dying back of the distal portion of the axon. Secondary demyelination occurs in those fibers with axonal damage. Recovery occurs by regeneration of axons, which often must then reinnervate denervated structures. As a result, recovery may be relatively slow and incomplete.

With physical injury to nerves, the injury may be limited to focal (paranodal) demyelination with associated conduction block and rapid recovery (neuropraxia). If axons are interrupted (axonotmesis), degeneration (Wallerian) of the axons and myelin may occur distal to the site of injury. If the Schwann cell basal lamina and endoneurial tissue remain intact, axonal regeneration commences promptly after injury. If both the axon and surrounding connective tissue are disrupted (neurotmesis), Wallerian degeneration is inevitable and axon regeneration may be disrupted by intervening connective tissue. Neuromas and aberrant regeneration may occur.

The potential pathologic processes that affect the PNS are similar to those that affect other systems. Metabolic or toxic derangements (e.g., vitamin deficiencies, uremia, alcoholism, heavy metals, industrial solvents, and certain medications) frequently result in nerve dysfunction. Vascular abnormalities affecting nerves usually involve the medium and small arteries, and these abnormalities may be found in rheumatoid arthritis, polyarteritis nodosa, and temporal arteritis. Diabetic mononeuropathies are probably vascular in origin, and the primary pathologic process in diabetic polyneuropathies may be a vascular-based ischemia. Idiopathic polyneuritis (Landry-Guillain-Barré syndrome) is representative of an inflammatory process. This probably has an immunologic basis, as do the neuropathies seen in paraproteinemias and paraneoplastic syndromes. Leprosy is a common infectious process affecting nerves, as are some of the neuropathies associated with human immunodeficiency virus (HIV) infection. A genetic basis for PNS dysfunction such as peroneal muscular atrophy (Charcot-Marie-Tooth disease) is also not uncommon. Schwannomas and neurofibromas are representative tumors. Trauma is a frequent cause of nerve injury. This includes entrapment neuropathies—namely, mononeuropathies resulting from vulnerability because of
anatomic features of the nerves. CTS is the most common entrapment neuropathy, but other common injuries include the ulnar nerve at the elbow and the peroneal nerve at the fibula head.

Neuropathies are common. An approach to evaluating these problems is essential in all areas of medicine. Even under the best of circumstances, the cause for a neuropathy may not be established in about one-third of these patients. As in other areas of medicine, often the important thing for management to determine is what is not the cause as much as what is the cause.

Only gold members can continue reading. Log In or Register to continue