Chapter 5 Peripheral Nerve Disorders

By relying on clinical findings, physicians can distinguish peripheral nervous system (PNS) from central nervous system (CNS) disorders. In PNS disorders, damage to one, a group, or all peripheral nerves causes readily observable patterns of paresis, deep tendon reflex (DTR) loss, and sensory impairments. Some PNS disorders are characteristically associated with mental changes, systemic illness, or a fatal outcome.

Anatomy

The spinal cord’s anterior horn cells form the motor neurons of the peripheral nerves – the PNS’ starting point. The peripheral nerves are the final link in the neuron chain that transmits motor commands from the brain through the spinal cord to muscles (Fig. 5-1). Nerve roots emerging from the anterior spinal cord mingle within the brachial or lumbosacral plexus to form the major peripheral nerves, such as the radial and femoral. Although peripheral nerves are quite long, especially in the legs, they faithfully conduct electrochemical impulses over considerable distances. Because myelin, the lipid-based sheath generated by Schwann cells, surrounds peripheral nerves and acts as insulation, the impulses are preserved.

FIGURE 5-1 The corticospinal tracts, as discussed in Chapter 2, and as their name indicates, consist of upper motor neurons (UMNs) that travel from the motor cortex to the spinal cord. They synapse on the spinal cord’s anterior horn cells, which give rise to the lower motor neurons (LMNs). The LMNs join sensory fibers to form peripheral nerves.

When stimulated, motor nerves release packets of acetylcholine (ACh) from storage vesicles at the neuromuscular junction. The ACh packets traverse the junction and bind on to specific ACh receptors on the muscle end plate. The interaction between ACh and its receptors depolarizes the muscle membrane and initiates a muscle contraction (see Chapter 6). Neuromuscular transmission culminating in muscle depolarization is a discrete, quantitative action: ACh does not merely seep out of the presynaptic terminal as loose molecules and drift across the neuromuscular junction to trigger a muscle contraction.

Peripheral nerves also transmit sensory information, but in the reverse direction: from the PNS to the CNS. For example, pain, temperature, vibration, and position receptors – which are located in the skin, tendons, and joints – send impulses through peripheral nerves to the spinal cord.

Mononeuropathies

Disorders of single peripheral nerves, mononeuropathies, are characterized by flaccid paresis, DTR loss (areflexia), and reduced sensation, particularly for pain (hypalgesia [Greek, hypo, under + algos, pain] or analgesia [Greek, insensitivity to pain]) (Table 5-1). Paradoxically, mononeuropathies and other peripheral nerve injuries sometimes lead to spontaneously occurring sensations, paresthesias (Greek para, near + aisthesis, sensation) that may be painful, dysesthesias. Peripheral nerve injuries also convert stimuli that ordinarily do not cause pain, such as a light touch or cool air, into painful sensations, allodynia; exaggerate painful responses to mildly noxious stimuli, such as the point of a pin, hyperalgesia; or delay but then exaggerate and prolong pain from noxious stimuli, hyperpathia.

TABLE 5-1 Major Mononeuropathies

^*Compression of the radial nerve in the spiral groove of the humerus spares the triceps deep tendon reflex (DTR).

Several mononeuropathies are common, important, and readily identifiable. They usually result from penetrating or blunt trauma, compression, diabetic infarctions, or other damage to single nerves.

Compression, especially of nerves protected only by overlying skin and subcutaneous tissue rather than by bone, viscera, or thick layers of fat, occurs frequently. People most susceptible are diabetics; those who have rapidly lost weight, thereby depleting nerves’ protective myelin covering; workers in certain occupations, such as watchmakers; and those who have remained in disjointed positions for long periods, often because of drug or alcohol abuse. One of the most common compressive mononeuropathies – “Saturday night palsy” – affects the radial nerve, which is vulnerable at the point where it winds around in the spiral groove of the humerus. Thus, people in alcohol-induced stupor who lean against their upper arm for several hours are apt to develop a wrist drop (Fig. 5-2). Foot drop, its lower-extremity counterpart, often results from common fibular nerve* damage from prolonged leg crossing compressing the nerve, lower-knee injuries traumatizing the nerve, or a constrictive lower-leg cast pushing against the nerve as it winds around the head of the fibula.

FIGURE 5-2 As the radial nerve winds around the humerus, it is vulnerable to compression and other forms of trauma. Radial nerve damage leads to the readily recognizable wrist drop that results from paresis of the extensor muscles of the wrist, finger, and thumb.

Carpal tunnel syndrome, the most common mononeuropathy, results from damage of the median nerve as it travels through the carpal tunnel of the wrist (Fig. 5-3, left). Forceful and repetitive wrist movements can traumatize the nerve in that confined passage. Meat and fish processing, certain assembly-line work, and carpentry are all closely associated with carpal tunnel syndrome; however, contrary to initial claims, word processing and other keyboarding actually have a weak association with the disorder. In another mechanism, fluid retention during pregnancy or menses entraps the median nerve in the carpal tunnel. Similarly, inflammatory tissue changes in the wrist from rheumatoid arthritis may compress the median nerve.

FIGURE 5-3 Left, The median nerve passes through the carpal tunnel, which is a relatively tight compartment. In it, the median nerve is vulnerable to repetitive movement and compression from fluid accumulation. The ulnar nerve, taking a different route, passes above and medial to the roof of the tunnel, the transverse carpal ligament. It thus escapes damage from most repetitive movements and fluid accumulation. Right, The usual sensory distribution of the median nerve encompasses the palm, thenar eminence (thumb base), thumb, and adjacent two fingers. In carpal tunnel syndrome, pain shoots distally from the wrist over this area. Physicians may elicit the Tinel sign, a reliable indication of carpal tunnel syndrome, by tapping the patient’s palmar wrist surface and finding that paresthesias emanate from the wrist and radiate in the median nerve distribution.

Whatever the mechanism, carpal tunnel syndrome causes paresthesias and pains that shoot from the wrist to the palm, thumb, and adjacent two or sometimes three fingers (Fig. 5-3, right). Symptoms worsen at night and awaken the victims, who shake their hands in an attempt to find relief. Neurologists test for the syndrome’s characteristic Tinel sign by percussing the wrist: The test is positive when the percussion generates electric sensations that shoot from the wrist into the palm and fingers.

With chronic carpal tunnel syndrome, median nerve damage leads to thenar (thumb) muscle weakness and atrophy. It also leads to impaired fine movements of the thumb and adjacent two fingers, which are instrumental in precision movements, such as writing, grasping small objects, and closing buttons.

Most carpal tunnel syndrome patients respond to rest and, sometimes, splints. Diuretics and anti-inflammatory drugs are also helpful. In refractory cases, a surgeon might inject steroids into the carpal tunnel or resect the transverse carpal ligament to decompress the tunnel.

In another example of upper-extremity nerve damage, pressure on the ulnar groove of the elbow (the “funny bone”) or cubital tunnel may damage the ulnar nerve. For instance, when individuals rest the weight of their arms on their elbows, the compression often injures the ulnar nerve. These individuals develop atrophy and weakness of their hand muscles (Fig. 5-4). The ulnar nerve damage also leads to loss of sensation of the fourth and fifth fingers and the medial surface of the hand.

FIGURE 5-4 Left, With ulnar nerve injuries, the palmar view shows that intrinsic muscles of the hand, particularly those of the hypothenar eminence (fifth finger base), undergo atrophy. The fourth and fifth fingers are flexed and abducted. When raised, the hand and fingers assume the benediction sign. In addition, the medial two fingers and palm are anesthetic (numb). Right, Ulnar nerve injuries also produce a claw hand because of atrophy of the muscles between the thumb and adjacent finger (first dorsal interosseous and adductor pollicis), as well as of those of the hypothenar eminence.

Mononeuropathies can result from systemic illnesses, such as diabetes mellitus, vasculitis (e.g., lupus erythematosus, polyarteritis nodosa), and lead intoxication (see later) – as well as from trauma. In most of the systemic conditions, pain, weakness, and other symptoms have an abrupt onset. In addition, systemic illnesses often cause stroke-like CNS insults along with the mononeuropathies.

Mononeuritis Multiplex

Mononeuritis multiplex is a serious, complex PNS condition that consists of a simultaneous or stepwise development of multiple peripheral injuries, often accompanied by cranial injuries. For example, a patient might suddenly develop left radial, right sciatic, and right third cranial nerve deficits. Mononeuritis multiplex is usually a manifestation of a systemic illness, but leprosy commonly causes it in Africa and Asia.

Polyneuropathies (Neuropathies)

The most frequently occurring PNS disorder, polyneuropathy or simply neuropathy, is generalized, symmetric involvement of all peripheral nerves. Some neuropathies also attack cranial nerves. Neurologists may divide neuropathies into those that predominantly damage either the myelin (demyelinating neuropathies) or axons (axonopathies). Most cases of demyelinating neuropathies fall into the category of inflammatory illness; however, cases of axonopathy include ones from porphyria, toxins, metabolic illnesses, and nutritional deficiencies. Although psychiatrists should be aware of that distinction, they must concentrate on neuropathies associated with mental status changes.

Alternatively, neurologists divide neuropathies into sensory, motor, or mixed sensorimotor neuropathy. Patients with sensory neuropathy usually suffer predominantly or exclusively from numbness, paresthesias, or burning in their fingers and toes (i.e., stocking-glove hypalgesia: Fig. 5-5). The pain may reach intolerable proportions (see neuropathic pain, Chapter 14). When sensory neuropathy affects the feet, it may provoke leg movements, such as restless legs syndrome (see Chapter 17). Patients with motor neuropathy usually have distal limb weakness that impairs fine, skilled hand and finger movements, such as buttoning a shirt, or raising their feet when they walk, which causes a foot drop. Their neuropathy in chronic cases usually also leads to muscle atrophy and flaccidity. As with other LMN injuries, it diminishes DTRs (see Fig. 2-2C), first at the brachioradialis and Achilles’ and then at more proximal sites. Mixed sensorimotor neuropathy causes mixtures of those symptoms and signs.

FIGURE 5-5 Patients with polyneuropathy lose pain and other sensations. The loss is symmetric, more severe distally than proximally, and more severe in the legs than arms. Neurologists term this pattern of sensory loss stocking-glove hypalgesia.

Neurologists who care for psychiatric patients may meaningfully divide neuropathies into those with and those without comorbid changes in mental status (Box 5-1).

Box 5-1

Important Causes of Neuropathy

Endogenous Toxins

Acute intermittent and variegate porphyria *

Diabetes mellitus

Uremia *

Nutritional Deficiencies

Celiac disease

Combined system disease *

Starvation, malabsorption, alcoholism *

Excessive Intake

Vitamin B₆ (pyridoxine)

Medicines

Antineoplastic agents

Vitamin B₆ (pyridoxine), in high doses

Industrial or Chemical Toxins

Ciguatera fish poisoning *

Metals: arsenic, lead, mercury *, thallium

Nitrous oxide N₂O *†

Organic solvents: n-hexane,† toluene*†

Infectious/Inflammatory Conditions

Guillain–Barré syndrome

Mononucleosis, hepatitis, Lyme disease,* leprosy, syphilis,* AIDS*

Vasculitides: systemic lupus erythematosus, polyarteritis *

Genetic Diseases

Adrenoleukodystrophy *

Metachromatic leukodystrophy *

Spinocerebellar ataxias

HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome.

^*Associated with mental status abnormalities.

^†May be substances of abuse.

Neuropathies Without Comorbid Mental Status Changes

Guillain–Barré Syndrome

Acute inflammatory demyelinating polyradiculoneuropathy or postinfectious demyelinating polyneuropathy, commonly known as Guillain–Barré syndrome, is both the quintessential PNS illness and the primary example of a demyelinating neuropathy. Although often idiopathic, this syndrome typically follows an upper respiratory or gastrointestinal illness. Cases following a week’s episode of watery diarrhea are apt to be associated with a gastrointestinal Campylobacter jejuni infection and be more extensive and severe than idiopathic cases. Many cases seem to be a complication of other infectious illnesses, including human immunodeficiency virus (HIV) infection, Lyme disease, mononucleosis, hepatitis, cytomegalovirus, and West Nile virus. Although Guillain–Barré syndrome followed administration of older influenza vaccinations, it has not complicated administration of the current ones.

When first affected, young and middle-aged adults feel paresthesias and numbness in the fingers and toes. Then they develop flaccid paresis of their feet and legs with characteristically absent knee and ankle DTRs. Weakness and areflexia, which soon become a much greater problem than numbness, ascend to involve the hands and arms. Many patients progress to respiratory insufficiency because of involvement of the phrenic and intercostal nerves, and require intubation for ventilation. If weakness ascends still further, patients develop cranial nerve involvement that may lead to dysphagia and other aspects of bulbar palsy (see Chapter 4). Additional involvement causes facial weakness and then sometimes even ocular immobility. Nevertheless, possibly because optic and acoustic nerves are protected by myelin generated by the CNS – not the PNS – patients continue to see and hear.

Even if the illness worsens to the point of total paralysis, patients usually remain conscious with a normal mental status – allowing for anxiety and depressive symptoms from enduring a life-threatening illness. Completely immobile and anarthric Guillain–Barré syndrome patients, typically with preserved consciousness and mental status, exist in a locked-in syndrome (see Chapter 11). Cerebrospinal fluid (CSF) exhibits an elevated protein concentration but with few white cells (i.e., the classic albumino-cytologic dissociation) (see Table 20-1).

The illness usually resolves almost completely within 3 months as the PNS myelin is regenerated. By way of treatment, plasmapheresis (plasma exchange), which extracts circulating inflammatory mediators, particularly autoantibodies, complement, and cytokines, reduces the severity and duration of the paresis. Alternatively, administration of intravenous human immunoglobulin, which “blocks” the antibodies at the neuromuscular junction, also restores patients’ strength. Steroids will not help, which is surprising because they are helpful in other inflammatory diseases of the nervous system, such as myasthenia gravis (see Chapter 6), multiple sclerosis (MS: see Chapter 15), and the chronic form of Guillain–Barré syndrome (chronic inflammatory demyelinating polyneuropathy).

Not only is Guillain–Barré syndrome a life-threatening illness, but it also epitomizes the distinction between PNS and CNS diseases. Although paraparesis or quadriparesis might be a feature common to PNS and CNS illnesses, different patterns of muscle weakness, changes in reflexes, and sensory distribution characterize PNS and CNS illnesses (Table 5-2). Also, in Guillain–Barré syndrome, as in most neuropathies other than diabetic neuropathy (see later), bladder, bowel, and sexual functions are preserved. In contrast, patients with spinal cord disease usually have incontinence and impotence at the onset of the injury.

TABLE 5-2 Differences between Central (CNS) and Peripheral Nervous System (PNS) Signs

	CNS	PNS
Motor System	Upper motor neuron	Lower motor neuron
Paresis	Patterns*	Distal
Tone	Spastic†	Flaccid
Bulk	Normal	Atrophic
Fasciculations	No	Sometimes
Reflexes
Deep tendon reflexes	Hyperactive^‡	Hypoactive
Plantar	Babinski sign(s)	Absent
Sensory loss	Patterns*	Hands and feet

^*Examples: motor and sensory loss of one side or lower half of the body (e.g., hemiparesis or paraparesis), and hemisensory loss.

^†May be flaccid initially.

^‡May be absent initially.

Another contrast arises from the difference between demyelinating diseases of the CNS and PNS. Despite performing a similar insulating function, CNS and PNS myelin differ in chemical composition, antigenicity, and cells of origin. Oligodendrocytes produce CNS myelin, and Schwann cells produce PNS myelin. In other words, oligodendrocytes are to Schwann cells as the CNS is to the PNS. Also, each oligodendrocyte produces myelin that covers many nearby CNS axons, but each Schwann cell produces myelin that covers only one portion of a single PNS axon. From a clinical viewpoint, Schwann cells regenerate damaged PNS myelin and thus Guillain–Barré patients usually recover. In contrast, because oligodendrocytes do not regenerate damaged CNS myelin, impairments are permanent in patients who have lost CNS myelin to toxins and infections. For example, the CNS demyelination that results from toluene use represents a permanent loss.

MS appears to be a partial exception to the rule that CNS demyelinating damage is permanent. In MS, episodes of demyelination of several CNS areas, including the optic nerves, partially or even completely resolve (see Chapter 15). However, the improvement results from resolution of myelin inflammation rather than myelin regeneration. When MS-induced demyelination eventually encompasses large areas of cerebral CNS myelin, it results in permanent quadriparesis and dementia.

From another perspective, patients with uncomplicated cases of Guillain–Barré syndrome, despite profound motor impairment, should not have an altered mental status because it is a disease of the PNS. Thus, when Guillain–Barré syndrome patients develop mental changes, consulting physicians should look for complications involving the CNS, particularly cerebral hypoxia from respiratory insufficiency, “steroid psychosis” from high-dose steroid treatment (now outdated), hydrocephalus from impaired reabsorption of CSF that has an elevated protein concentration, hyponatremia from inappropriate antidiuretic hormone secretion, or sleep deprivation. Guillain–Barré syndrome patients with the most pronounced impairments – quadriparesis, dependency on artificial ventilation, and multiple cranial nerve involvement – are the ones most apt to experience a psychotic episode.

Thus, psychiatric consultants should look first for hypoxia and other life-threatening medical complications in Guillain–Barré patients who develop mental aberrations. Also, unless the patient is already on a respirator, psychiatrists should avoid prescribing medications, such as benzodiazepines and certain antipsychotics, that depress respirations.

Neuropathies With Comorbid Mental Status Changes

Although most neuropathies, as described in the previous section, may be painful, incapacitating, or even devastating to the PNS, they generally do not cause mental changes in adults. For example, most people who are old, diabetic, on hemodialysis, or receiving chemotherapy remain intelligent, thoughtful, and competent even though beset by pain, sensory loss, and weakness. In contrast, only a few diseases (see Box 5-1) cause the combination of dementia and neuropathy, which would indicate both cerebral cortex and peripheral nerve damage. An analogous combination would be dementia and movement disorders, which would indicate cerebral cortex and basal ganglia damage (see Box 18-4).

Nutritional Deficiencies

Deficiencies of thiamine (vitamin B₁), niacin (nicotinic acid, B₃), or vitamin B₁₂ (cobalamine), each produce a predominantly sensory neuropathy accompanied by dementia or other mental status abnormality (Table 5-3). From a worldwide perspective, starvation has been the most common cause of deficiencies of vitamins, their carrier fats, minerals, and other nutrients. For example, beriberi was the starvation-induced neuropathy attributable to thiamine deficiency endemic in eastern Asia. In the United States, alcoholism, bariatric surgery, and malabsorption syndromes have replaced starvation as the most common causes of nutritional neuropathies. Curiously, few patients with anorexia nervosa or self-imposed extreme diets develop a neuropathy. Their protection may lie in a selective, possibly secret, intake of food or vitamins.

TABLE 5-3 Neurologic Aspects of Vitamins

^*Includes neuropathy as part of the illness.

^†Associated with neuropathy.

Bariatric surgery remains a unique example. After its rapid introduction and widespread acceptance, postoperative “micronutrient” deficiencies caused various neurologic illnesses. Thiamine, copper, and vitamins B₁₂ and E deficiencies frequently caused neuropathy, but also occasionally encephalopathy or myelopathy (see Chapter 4), i.e., CNS problems. Routine postoperative administration of these micronutrients has prevented the problem.

Alcohol-induced neuropathy has been virtually synonymous with thiamine deficiency because most cases are found in alcoholics who typically subsist on alcohol and carbohydrate-rich foods devoid of thiamine. Nevertheless, alcohol and thiamine deficiency may not be the only culprits. Studies have shown that alcohol itself did not cause a neuropathy and that thiamine deficiency is not present in all cases of this neuropathy.

Whatever the cause, thiamine deficiency generally leads to absent DTRs and loss of position sensation. In fact, until patients walk in the dark, when they must rely on position sense generated in the legs and feet, their deficits may remain asymptomatic. In the well-known Wernicke–Korsakoff syndrome, amnesia, dementia, and cerebellar degeneration accompany the neuropathy associated with alcoholism (see Chapter 7).

In another example of vitamin deficiency causing neuropathy, niacin deficiency is associated with or causes pellagra (Italian, rough skin). This starvation-induced disorder consists of dementia, dermatitis, and diarrhea – the “three Ds.” Despite pellagra’s status as a classic illness, the role of niacin deficiency has been challenged: deficiencies of other nutrients either coexist with or are more likely to be the actual cause.

Among its many functions, vitamin B₁₂ sustains both CNS and PNS myelin. Thus, B₁₂ deficiency leads to the combination of CNS and PNS damage – combined system disease. Although its manifestations include a neuropathy, cognitive impairment and sensory loss reflecting demyelination of the posterior columns of the spinal cord (see Fig. 2-19B) predominate. Patients also develop a characteristic megaloblastic anemia. Most importantly, neurologists refer to combined system disease as a “correctable cause of dementia” because B₁₂ injections can reverse the cognitive impairment as well as the other CNS and PNS manifestations. The usual causes of B₁₂ deficiency include pernicious anemia, malabsorption, a pure vegetarian diet, or prolonged exposure to nitrous oxide, a gaseous dental anesthetic. (Nitrous oxide inactivates B₁₂ by oxidizing its cobalt.)

The screening test for B₁₂ deficiency consists of determining the serum B₁₂ level. In equivocal cases, especially when cognitive impairment or spinal cord abnormalities are not accompanied by anemia, determining the serum homocysteine and methylmalonic acid levels can corroborate the diagnosis: in B₁₂ deficiency, both homocysteine and methylmalonic acid levels rise to abnormally high levels (Fig. 5-8). Intrinsic factor antibodies, a classic finding in pernicious anemia, will be detectable in only about 60% of cases. The standard confirmatory test is the Schilling test.

FIGURE 5-8 Vitamin B₁₂, acting as a coenzyme, along with folate, facilitates the conversion of homocysteine to methionine. Other enzymes complete the cycle by converting methionine back to homocysteine. An absence of B₁₂ leads to the accumulation of both methionine and homocysteine. Whatever the cause, an elevated homocysteine level is a risk factor for neural tube defects, cerebrovascular and cardiovascular disease, and other neurologic conditions.

A variation on nutritional deficiencies causing neuropathy is celiac disease. In this condition, foods containing wheat gluten or similar protein constituents of rye and barley trigger an immune response. Affected individuals develop not only malabsorption, which is not always readily apparent, but also neuropathy and sometimes ataxia. Severely affected ones develop osteoporosis, cardiac disease, and cancer.

In contrast to malnutrition causing neuropathy, excessive intake of certain vitamins causes neurologic problems. For example, although the normal adult daily requirement of vitamin B₆ (pyridoxine) is only 2–4 mg daily, several food faddists who consumed several grams daily as part of a special diet developed a profound sensory neuropathy. Similarly, high vitamin A intake may cause pseudotumor cerebri (see Chapter 9) or induce fetal abnormalities (see Chapter 13).

Infectious Diseases

Several common organisms have a predilection for infecting the peripheral nerves and sparing the CNS. For example, herpes zoster infects a single nerve root or a branch of the trigeminal nerve, usually in people older than 65 years or those with an impaired immune system. An infection with herpes (Greek, herpes, spreading skin eruption) causes an ugly, red, painful, vesicular eruption (“shingles”) that may remain excruciating long after the skin infection has resolved (see postherpetic neuralgia, Chapter 14). As another example, leprosy (Hansen disease), infection with Mycobacterium leprae, causes anesthetic, hypopigmented patches of skin, anesthetic fingers and toes, and palpable nerves. It particularly affects the cool portions of the body, such as the nose, earlobes, and digits; however, depending on its variety, the infection strikes the ulnar or another large nerve either singly or along with others.

Some infections involve the CNS as well as the PNS. Named for the town in Connecticut where it was discovered, Lyme disease has risen to endemic levels in New England, Westchester, eastern Long Island, Wisconsin, Minnesota, and the Pacific Northwest. Infection by Borrelia burgdorferi, a spirochete whose vector is a certain tick, causes Lyme disease. The illness’ peak incidence occurs in June through September, when people spend time in tick-infested wooded areas.

Acute Lyme disease typically produces multiple problems, such as arthritis, malaise, low-grade fever, cardiac arrhythmias, and a pathognomonic bull’s-eye-shaped expanding rash, erythema migrans (Greek, erythema, flush + migrans, move), surrounding the tick bite. In addition, Lyme disease frequently causes a facial nerve paresis, similar to Bell’s palsy, either unilaterally or bilaterally (see Fig. 4-15). Its PNS manifestations range from a mild neuropathy causing only paresthesias to a severe Guillain–Barré-like illness.

With CNS involvement, patients typically have headache, delirium (see Chapter 7), and other signs of meningitis or encephalitis. Their CSF may show a pleocytosis, elevated protein, decreased glucose concentrations, and Lyme antibodies. Serologic tests for Lyme disease remain unreliable. Another confusing aspect of the diagnosis is that patients may have a biologic false-positive test for syphilis because B. burgdorferi is a spirochete (see Chapter 7).

Numerous individuals and physicians attribute years of symptoms – cognitive impairment, weakness, fatigue, and arthralgias – after an attack of adequately treated Lyme disease to a persistent Lyme infection or disordered immunologic response to it. This condition, “chronic Lyme disease,” meets with skepticism in the neurologic community because it lacks consistent clinical criteria, pathology, and test results. Moreover, chronic Lyme disease symptoms do not respond to additional antibiotic treatment (see Chapters 6 and 7).

Even though Lyme disease is common, the most widespread infection of the CNS and PNS is acquired immunodeficiency syndrome (AIDS). Although direct HIV infection probably causes neuropathy associated with AIDS, alternative potential etiologies include opportunistic infectious agents and HIV medicines, such as nucleoside reverse transcriptase inhibitors (ddI [didanosine, Videx] and ddC [zalcitabine]). AIDS-associated peripheral nerve disorder usually develops insidiously and consists of distal, symmetrical painful dysesthesias, which can be agonizing, and numbness of the soles of the feet. In contrast to the pronounced sensory symptoms, the motor symptoms consist of only relatively mild ankle and foot weakness with loss of ankle DTRs.

HIV-associated polyneuropathy generally develops late in the course of the illness when many other problems overshadow it. By then, the plasma HIV RNA titer is elevated and the CD4 count is low. In addition, depression and decreased physical function have supervened. Treatments for diabetic neuropathy often ameliorate the pain of AIDS neuropathy.