Figure 10-1. Sensory pathways conveying touch, pressure, vibration, joint position, pain, and temperature sensation. (Reproduced with permission from Barrett KE, Barman SM, Boitano S, Brooks H. Ganong’s Review of Medical Physiology. 23rd ed. New York, NY: McGraw-Hill; 2010.)

First-order sensory neurons from the limbs and trunk have cell bodies in the dorsal root ganglia. Each of these neurons sends a peripheral process that terminates in a free nerve ending or encapsulated sensory receptor and a central process that enters the spinal cord. Sensory receptors are relatively specialized for particular sensations and, in addition to free nerve endings (pain), include Meissner corpuscles, Merkel corpuscles, and hair cells (touch); Krause end-bulbs (cold); and Ruffini corpuscles (heat). First-order sensory neurons synapse centrally at a site that depends on the type of sensation. Fibers mediating touch, pressure, or postural sensation in the limbs and trunk ascend in the posterior columns of the spinal cord to the medulla, where they synapse in the gracile and cuneate nuclei. Other fibers that mediate touch and those subserving pain and temperature appreciation in the limbs and trunk synapse on neurons in the posterior horns of the spinal cord, particularly in the substantia gelatinosa. First-order sensory neurons from the face, which have cell bodies in the trigeminal (gasserian) ganglion, travel in the trigeminal (V) nerve and enter the pons. Fibers mediating facial touch and pressure synapse in the main trigeminal (V) nerve sensory nucleus, whereas those conveying facial pain and temperature synapse in the spinal trigeminal (V) nerve nucleus.

Third-order sensory neurons project from the thalamus to ipsilateral cerebral cortex. Fibers from VPL, VPI, and VPM travel primarily to primary somatosensory cortex in the postcentral gyrus; fibers from ILa also project to striatum, cingulate gyrus, and prefrontal cortex.

HISTORY

Sensory disturbances may consist of loss of sensation, abnormal sensations, or pain. The term paresthesia is used to denote abnormal spontaneous sensations, such as burning, tingling, or pins and needles. The designation dysesthesia denotes any unpleasant sensation produced by a stimulus that is normally painless. The term numbness is often used by patients to describe a sense of heaviness, weakness, or deadness in the affected part of the body—and sometimes to signify any sensory impairment; the meaning must be clarified whenever this word is used.

In obtaining a history of sensory complaints, it is important to determine the location of the symptoms; the mode of onset and progression of the symptoms; whether the symptoms are constant or episodic in nature; whether any factors specifically produce, enhance, or relieve symptoms; and whether there are any accompanying symptoms.

The location of symptoms may provide a clue to their origin. For example, sensory disturbances involving all the limbs suggest peripheral neuropathy, a cervical cord or brainstem lesion, or a metabolic disturbance such as hyperventilation syndrome. Involvement of one entire limb, or of one side of the body, suggests a central (brain or spinal cord) lesion. A hemispheric or brainstem lesion may lead to lateralized sensory symptoms, but the face is also commonly affected. In addition, there may be other symptoms and signs, such as aphasia, apraxia, and visual field defects with hemispheric disease, or dysarthria, weakness, vertigo, diplopia, disequilibrium, and ataxia with brainstem disorders. Involvement of part of a limb or a discrete region of the trunk raises the possibility of a nerve or root lesion, depending on the precise distribution. With a root lesion, symptoms may show some relationship to neck or back movements, and pain is often conspicuous.

The course of sensory complaints provides a guide to their cause. Intermittent or repetitive transient symptoms may represent sensory seizures, ischemic phenomena, or metabolic disturbances such as those accompanying hyper-ventilation. Intermittent localized symptoms that occur at a consistent time may suggest the diagnosis or an exogenous precipitating factor. For example, the pain and paresthesias of carpal tunnel syndrome (median nerve compression at the wrist) characteristically occur at night and awaken the patient from sleep.

SENSORY EXAMINATION

PRIMARY SENSORY MODALITIES

Light Touch

Figure 10-2. Location and lamination of sensory pathways in the spinal cord. C (cervical), T (thoracic), L (lumbar), and S (sacral) indicate the level of origin of fibers within each tract.

Figure 10-3. Sensory pathways in the brainstem. In the medulla, spinothalamic fibers conveying pain and temperature sensation are widely separated from medial lemniscal fibers mediating touch and pressure; these pathways converge as they ascend in the pons and midbrain.

Pinprick & Temperature

Vibration sense is evaluated with a tuning fork (128 Hz) that is set in motion and then placed over a bony prominence; the patient is asked to indicate whether vibration, rather than simple pressure, is felt. Many healthy elderly patients have impaired appreciation of vibration below the knees.

Joint Position

Joint position sense is tested by asking the patient to indicate the direction of small passive movements of the terminal interphalangeal joints of the fingers and toes. Patients with severe impairment of joint position sense may exhibit slow, continuous movement of the fingers (pseudoathetoid movement) when attempting to hold the hands outstretched with the eyes closed. For clinical purposes, both joint position sense and the ability to appreciate vibration are considered to depend on fibers carried in the posterior columns of the cord, although there is evidence that this is not strictly true for vibration.

COMPLEX SENSORY FUNCTIONS

Romberg Test

The patient is asked to assume a steady stance with feet together, arms outstretched, and eyes closed and is observed for any tendency to sway or fall. The test is positive (abnormal) if unsteadiness is markedly increased by eye closure—as occurs, for example, in tabes dorsalis. A positive test is indicative of grossly impaired joint position sense in the legs.

Two-Point Discrimination

The ability to distinguish simultaneous touch at two neighboring points depends on the integrity of the central and peripheral nervous system, the degree of separation of the two points, and the part of the body that is stimulated. The patient is required to indicate whether he or she is touched by one or two compass points, while the distance between the points is varied in order to determine the shortest distance at which they are recognized as different points. The threshold for two-point discrimination approximates 4 mm at the fingertips and may be several centimeters on the back. When peripheral sensory function is intact, impaired two-point discrimination suggests a disorder affecting the sensory cortex.

Graphesthesia, Stereognosis, & Barognosis

Agraphesthesia, the inability to identify a number traced on the skin of the palm of the hand despite normal cutaneous sensation, implies a lesion involving the contralateral parietal lobe. The same is true of inability to distinguish between various shapes or textures by touch (astereognosis) or impaired ability to distinguish between different weights (abarognosis).

Bilateral Sensory Discrimination

In some patients with apparently normal sensation, simultaneous stimulation of the two sides of the body reveals an apparent neglect of (or inattention to) sensation from one side, usually because of an underlying contralateral cerebral lesion.

SENSORY CHANGES & THEIR SIGNIFICANCE

It is important to determine the nature and distribution of any sensory change. Failure to find clinical evidence of sensory loss in patients with sensory symptoms must never be taken to imply that the symptoms necessarily have a psychogenic basis. Sensory symptoms often develop well before the onset of sensory signs.

PERIPHERAL NERVE LESIONS

Mononeuropathy

In patients with a lesion of a single peripheral nerve, sensory loss is usually less than would have been predicted on anatomic grounds because of overlap from adjacent nerves. Moreover, depending on the type of lesion, the fibers in a sensory nerve may be affected differently. Compressive lesions, for example, tend to affect preferentially the large fibers that subserve touch.

Polyneuropathy

In patients with polyneuropathies, sensory loss is generally symmetric and is greater distally than proximally—as suggested by the term stocking-and-glove sensory loss or length-dependent neuropathy. As a general rule, the loss will have progressed almost to the knees before the hands are affected. Sensory loss may then be accompanied by a motor deficit and reflex changes. Diabetes mellitus, amyloidosis, and certain other metabolic disorders (eg, Tangier disease, a recessive trait characterized by the near absence of high-density lipoproteins) preferentially involve small nerve fibers that subserve pain and temperature appreciation; in a pure small-fiber sensory neuropathy, the tendon reflexes are unaffected and no motor deficit occurs.

ROOT LESIONS

Figure 10-4. A: Cutaneous innervation (anterior view). The segmental or radicular (nerve root) distribution is shown on the left side of the body, and the peripheral nerve distribution on the right side of the body. B: Cutaneous innervation (posterior view). The segmental or radicular (nerve root) distribution is shown on the left side of the body, and the peripheral nerve distribution on the right side of the body. For details of radial, median, ulnar, fibular (peroneal), and femoral nerves, see Appendix.

CORD LESIONS

In patients with a cord lesion, there may be a transverse sensory level. Physiologic areas of increased sensitivity do occur, however, at the costal margin, over the breasts, and in the groin, and these must not be taken as abnormal. Therefore, the level of a sensory deficit affecting the trunk is best determined by careful sensory testing over the back rather than the chest and abdomen.

Figure 10-7. Cord lesion (blue) in Brown-Séquard syndrome. Hemisection of the cord causes ipsilateral pyramidal dysfunction and impairment of posterior column sensory function below the level of the lesion, and contralateral impairment of pain and temperature sensation with an upper limit slightly below the level of the lesion.

BRAINSTEM LESIONS

Sensory disturbances may be accompanied by a motor deficit, cerebellar signs, and cranial nerve palsies when the lesion is in the brainstem.

Finally, it should be noted that sensory disturbances are often suggested to the patient by the examiner’s own expectations. Such findings can be particularly misleading because they may be neuroanatomically correct. One helpful approach is to have the patient outline on the body the extent of any perceived sensory disturbance before formal sensory testing is undertaken.

PERIPHERAL NERVE LESIONS

Table 10-1. Causes of peripheral neuropathy.

CLASSIFICATION

MONONEUROPATHY SIMPLEX

This term signifies involvement of a single peripheral nerve.

MONONEUROPATHY MULTIPLEX

In this disorder, several individual nerves are affected, usually at random and noncontiguously. Clinical examination reveals a clinical deficit attributable to involvement of one or more isolated peripheral nerves, except when mononeuropathy multiplex is extensive and the resulting deficits become confluent.

POLYNEUROPATHY

The term polyneuropathy denotes a disorder in which the function of numerous peripheral nerves is affected at the same time. This leads to a predominantly distal and symmetric deficit, with loss of tendon reflexes except when small fibers are selectively involved. Polyneuropathies are sometimes subclassified according to the primary site at which the nerve is affected.

In distal axonopathies (axonal neuropathies), the axon is the principal pathologic target; most polyneuropathies fall into this category.

Myelinopathies (demyelinating neuropathies) are conditions that involve the myelin sheath surrounding the axon. These disorders include acute idiopathic polyneuropathy (Guillain-Barré syndrome), chronic inflammatory demyelinating neuropathy, diphtheria, certain paraneoplastic and paraproteinemic states, and various hereditary conditions including metachromatic leukodystrophy, Krabbe disease, and types 1 and 3 Charcot-Marie-Tooth hereditary motor and sensory neuropathy (CMT-1 and 3).

CLINICAL FINDINGS

SENSORY DISTURBANCES

Involvement of sensory fibers can lead to numbness and impaired sensation; abnormal spontaneous sensations, such as pain and paresthesias; and perverted sensations such as hyperpathia (amplified response to a normally painful stimulus).

Pain

Pain is a conspicuous feature of certain neuropathies, especially if small fibers within the nerves are affected. The precise mechanism of its genesis is unclear. Polyneuropathies associated with prominent pain include those related to diabetes, alcoholism, porphyria, Fabry disease, amyloidosis, rheumatoid arthritis, and acquired immunodeficiency syndrome (AIDS), as well as dominantly inherited sensory neuropathy and paraneoplastic sensory neuronopathy. Pain is also a feature of many entrapment neuropathies and of idiopathic brachial plexopathy.

Dissociated Sensory Loss

Dissociated sensory loss is impairment of some sensory modalities, such as pain and temperature, with preservation of others, such as light touch, vibration, and joint position sense. Although the presence of a dissociated sensory loss often indicates a spinal cord lesion, it also occurs in peripheral neuropathies when there is selective involvement of peripheral nerve fibers of a certain size, such as occurs in amyloid neuropathy, leprous neuritis, or hereditary sensory neuropathy. Small fiber disease is commonly associated with disproportionate impairment of pain and temperature appreciation, spontaneous pain, and autonomic dysfunction. Large fiber disease, by contrast, results in defective touch, vibration, and joint position sense, early loss of tendon reflexes, and prominent motor symptoms.

MOTOR DEFICITS

The motor deficit that occurs with a peripheral nerve lesion consists of weakness of muscles innervated by the nerve, accompanied in severe cases by wasting and fasciculation. There may be difficulty in the performance of fine tasks; this is compounded by any accompanying sensory loss. The clinical findings reflect a lower motor neuron deficit, and it is the distribution of these signs and the presence of accompanying sensory and reflex changes that suggest they may be due to peripheral nerve involvement.

TENDON REFLEXES

These are impaired or lost if reflex arcs are interrupted on either the afferent or efferent side (C5-C6, biceps and brachioradialis; C7-C8, triceps; L3-L4, knee; S1, ankle). The ankle reflexes are usually the first to be lost in patients with polyneuropathies, but may also be absent in healthy elderly subjects.

AUTONOMIC DISTURBANCES

Autonomic disturbances may be particularly conspicuous in some peripheral neuropathies—especially Guillain-Barré syndrome and neuropathies related to diabetes, renal failure, porphyria, certain paraneoplastic disorders, or amyloidosis. Symptoms include postural hypotension, coldness of the extremities, impaired thermoregulatory sweating, disturbances of bladder and bowel function, and impotence.

ENLARGED NERVES

Palpably enlarged peripheral nerves raise the possibility of leprosy, amyloidosis, hereditary motor and sensory neuropathies, Refsum disease, acromegaly, or chronic inflammatory demyelinating polyneuropathy.

EVALUATION OF PATIENTS

TIME COURSE

Polyneuropathy that develops acutely over a few days usually relates to an inflammatory process, as in the Guillain-Barré syndrome. It may also relate to an underlying neoplasm, to infections such as diphtheria, to metabolic disorders such as acute intermittent porphyria, or to exposure to such toxic substances as thallium or triorthocresyl phosphate. A chronic course with a gradual evolution over several years is typical of many hereditary or metabolic polyneuropathies but also characterizes chronic inflammatory demyelinating polyneuropathy.

Mononeuropathy of acute onset is likely to be traumatic or ischemic in origin, whereas one evolving gradually is more likely to relate to entrapment (ie, compression by neighboring anatomic structures) or to recurrent minor trauma.

AGE AT ONSET

Polyneuropathy that develops during childhood or early adult life often has a hereditary basis, but may also relate to an underlying inflammatory disorder. Polyneuropathy developing in later life is more likely to result from a metabolic, toxic, or inflammatory disorder, or from an underlying neoplasm.

Mononeuropathy presenting in the neonatal period is likely to be developmental in origin or related to birth injury; one developing in later life may relate to entrapment or injury that is often occupationally determined.

Various industrial toxins can lead to peripheral neuropathy, including carbon disulfide, n-hexane, ethylene oxide, methyl bromide, acrylamide, triorthocresyl phosphate and certain other organophosphates, DDT, arsenic, lead, and thallium. A mononeuropathy is sometimes the first clinical manifestation of an occupationally related polyneuropathy, but it may also develop in response to entrapment or recurrent minor occupational trauma. For example, carpal tunnel syndrome is more common in persons who do heavy manual labor or develop repetitive motion injury as a result of computer terminal use, and a lesion of the deep palmar branch of the ulnar nerve may relate to repeated pressure on the palm of the hand by, for example, punching down heavily on a stapler or using heavy equipment such as a pneumatic road drill.

MEDICAL HISTORY

Metabolic Disorders

Peripheral neuropathy may relate to metabolic disorders such as diabetes mellitus, uremia, liver disease, myxedema, acromegaly, metachromatic leukodystrophy, or Fabry disease. That caused by diabetes is especially important and may take the form of an entrapment mononeuropathy, acute ischemic mononeuropathy, distal sensorimotor polyneuropathy, subacute proximal motor polyradiculopathy (diabetic amyotrophy), thoracoabdominal radiculopathy, or autonomic neuropathy.

Neoplasm

Table 10-2. Selected drugs inducing peripheral neuropathy.

FAMILY HISTORY

Certain polyneuropathies have a hereditary basis. These are discussed later in this chapter in the section on hereditary neuropathies.

Topical capsaicin is also helpful in neuropathic pain syndromes.

AUTONOMIC DISTURBANCES

Dysautonomic symptoms may be troublesome in several polyneuropathies, but especially in diabetic polyneuropathy. Waist-high elastic hosiery, dietary salt supplementation, and treatment with fludrocortisone 0.1 to 1 mg/d orally may help relieve postural hypotension, but the patient must be monitored carefully to prevent recumbent hypertension. Other medications that may be helpful include clonidine, midodrine, dihydroergotamine, octreotide, or beta-blockers. Instructing the patients to sleep in a semierect rather than a recumbent position is helpful because dysautonomic patients are often unable to conserve salt and water when recumbent at night.

POLYNEUROPATHIES

IDIOPATHIC INFLAMMATORY NEUROPATHIES

ACUTE IDIOPATHIC POLYNEUROPATHY (GUILLAIN-BARRÉ SYNDROME)

Guillain-Barré syndrome is an acute or subacute polyneuropathy that can follow minor infective illnesses, inoculations, or surgical procedures or may occur without obvious precipitants. Clinical and epidemiologic evidence suggests an association with preceding Campylobacter jejuni infection. Its precise cause is unclear, but it appears to have an immunologic basis. Both demyelinating and axonal forms have been recognized, with distinctive clinical and electro-physiologic features. The demyelinative form is more common in the United States, but an axonal variant is encountered occasionally (acute motor sensory axonal neuropathy). In northern China, a related axonal form occurs frequently and has been designated acute motor axonal neuropathy.

Clinical Features

Table 10-3. Diagnostic criteria for Guillain-Barré syndrome.

Investigative Studies

The cerebrospinal fluid (CSF) often shows a characteristic abnormality, termed cytoalbuminologic dissociation, with increased protein concentration but a normal cell count; abnormalities may not be found in the first week, however. Electrophysiologic studies may reveal marked slowing of motor and sensory conduction velocity or evidence of denervation and axonal loss. The time course of the electrophysiologic changes does not necessarily parallel any clinical developments. When HIV-1 infection is suspected because of the clinical context in which the neuropathy has developed or the presence of high-risk factors, appropriate serologic studies should be performed.

Plasmapheresis appears to reduce the time required for recovery and may decrease the likelihood of residual neurologic deficits. It is best instituted early, and it is indicated especially in patients with a severe or rapidly progressive deficit or respiratory compromise. Intravenous immunoglobulin (400 mg/kg/d for 5 days) appears to be equally effective and should be used in preference to plasmapheresis in adults with cardiovascular instability and in children; the two therapies are not additive.

Therapy is otherwise symptomatic, the aim being to prevent such complications as respiratory failure or vascular collapse. For this reason, patients who are severely affected are best managed in intensive care units, where facilities are available for monitoring and assisted respiration if necessary (eg, if the forced vital capacity reaches 15 mL/kg, the mean inspiratory force reaches –40 mm Hg, the patient is short of breath, or the blood oxygen saturation declines). Volume replacement or treatment with pressor agents is sometimes required to counter hypotension, and low-dose heparin may help to prevent pulmonary embolism. Corticosteroids may affect the outcome adversely or delay recovery, and are not indicated.

Prognosis

Symptoms and signs cease to progress by approximately 4 weeks into the illness. The disorder is self-limiting, and improvement occurs over the weeks or months after onset. Approximately 70% of patients recover completely, 25% are left with mild neurologic deficits, and 5% die, usually as a result of respiratory failure. The prognosis is poorer when there is evidence of preceding Campylobacter jejuni infection, and a more protracted course and less complete recovery are also likely when axonal degeneration rather than demyelination is the primary pathology. Advanced age, the need for ventilatory support, or more rapid onset of symptoms may also predict a poorer prognosis.