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.

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).

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.

Diabetes

Although rigid treatment of diabetes may delay or even prevent diabetic neuropathy, most patients who have diabetes for more than 10 years show its symptoms and signs. In addition, risk factors for vascular disease, such as obesity and cigarette smoking, exacerbate the neuropathy.

The classic finding is loss of sensation in a stocking-glove distribution. Strength remains relatively normal, but patients lose the DTRs in their ankles, then knees. With long-standing diabetic neuropathy, impaired sensation in their fingertips prevents blind diabetic patients from reading Braille. In addition to the distal symmetric sensory loss, diabetic patients may suffer from suddenly occurring painful mononeuropathies and mononeuritis multiplex or continuous intense burning sensations, especially in the feet. These sensations are especially distressing at night and prevent sleep. By a different mechanism – damaging blood vessels – diabetes can lead to cerebrovascular disease that eventually may cause multi-infarct (vascular) dementia.

Three groups of medicines suppress the pain of diabetic neuropathy and other neuropathies. Narcotics (opioids), but not less potent analgesics, help. Certain antiepileptic drugs (AEDs), such as gabapentin (Neurontin) and pregabalin (Lyrica), reduce pain and promote sleep. The third group, tricyclic antidepressants, in doses too low to relieve depression, reduce pain and promote sleep. Although selective norepinephrine reuptake inhibitors, such as duloxetine (Cymbalta), also help, selective serotonin reuptake inhibitors do not. In an alternative approach, a skin cream containing capsaicin, which depletes substance P, the putative neurotransmitter for pain, provides some analgesia, along with numbness, to limited areas. In contrast to their usefulness in most painful conditions, nonsteroidal anti-inflammatory drugs provide little benefit in diabetic neuropathy.

Patients with diabetic neuropathy may also have autonomic nervous system involvement that causes gastrointestinal immobility, bladder muscle contraction, and sexual dysfunction. In fact, erectile dysfunction is occasionally the first or most disturbing symptom of diabetic autonomic neuropathy (see Chapter 16).

Toxic-Metabolic Disorders

Numerous toxins, metabolic derangements, and medications frequently cause neuropathy. For example, renal insufficiency (uremia) is a common cause of neuropathy that occurs almost universally in patients undergoing maintenance hemodialysis. Also, cancer chemotherapy agents and antibiotics, including those for tuberculosis and HIV disease (see later), routinely cause neuropathy; however, antipsychotics, antidepressants, and AEDs, except for phenytoin, do not. When medications, chemicals, or other substances cause CNS or PNS damage, neurologists label them neurotoxins.

Several heavy metals cause combinations of PNS and CNS impairments. For example, lead poisoning causes a neuropathy in adults and other problems in children. Pica (craving for unnatural foods), mostly from hunger, in young children prompts them to eat lead pigment paint chips from toys or decaying tenement walls. (Lead paint on interior walls has been illegal in most cities for decades.) Even at low concentrations, lead is neurotoxic in children. Lead ingestion is associated with inattention, learning disabilities, and poor school performance. High serum concentrations are associated with seizures and mental retardation. Because lead has a different deleterious effect on the mature nervous system, adults with lead poisoning develop mononeuropathies, such as a foot drop or wrist drop, rather than cerebral impairments. Adults most often develop lead poisoning from industrial exposure, drinking homemade alcohol distilled in equipment with lead pipes (“moonshine”), or burning car batteries for heat.

Chronic, low-level intoxication by several other heavy metals causes polyneuropathy, dermatologic abnormality, and mental changes. In contrast, acute heavy metal poisoning typically leads to fatal gastrointestinal symptoms and cardiovascular collapse. Arsenic, which is tasteless and odorless, is a poison used in popular murder cases. With chronic, low-level, deliberate, accidental, or industrial intoxication, arsenic causes anorexia, malaise, and a distal neuropathy that might mimic Guillain–Barré syndrome. It also causes several characteristic dermatologic abnormalities: Mees lines on the fingernails (Fig. 5-6), hyperpigmentation, and hyperkeratosis.

FIGURE 5-6 Mees lines, white bands (arrows) that stretch across the fingernails, characteristically indicate arsenic poisoning. In addition, poisoning by other heavy metals and trauma can cause them.

Mercury intoxication is more complex than arsenic poisoning. Individuals with mercury poisoning may develop a neuropathy and various CNS deficits, including cognitive impairment, ataxia, dysarthria, and visual field changes. Their gums accumulate a telltale dark line just below their teeth (Fig. 5-7).

FIGURE 5-7 Chronic mercury poisoning causes a dark blue or black line (arrow) along the gum. Individuals with this sign usually also have neuropathy and central nervous system signs, such as ataxia and dysarthria.

Organic mercury compounds, such as methylmercury, typically enter the food chain at the lowest level and progress upward to saturate edible fish. Pregnant women who consume even modest quantities of mercury-containing food place their fetus at risk of mental retardation. Fish highest on the food chain carry the highest mercury concentrations. Thus, the fish group with the highest concentrations includes tuna (white meat), swordfish, and Chilean sea bass; the next highest, bluefish, halibut, and striped bass; the next highest, sole; and the lowest, herring and sardines.

Poisoning with inorganic mercury, widely used in industry, causes kidney damage, but only mild cognitive impairment. Studies have not established definitively safe environmental or workplace levels.

Investigators at one time proposed that mercury-based dental amalgams (“fillings”) caused Alzheimer disease and other neurodegenerative illnesses either by dissolving in saliva and allowing mercury to enter the circulation or emitting a mercury vapor those individuals inhaled. In another inquiry, because ethyl mercury was a major component of the common vaccine preservative, thimerosal, investigators suspected that routine childhood immunizations caused autism (see Chapter 13). However, statistically powerful epidemiologic studies disproved both of those suspicions. In the case of vaccinations, the original “investigators” possibly engaged in fraud.

Thallium, another heavy metal, is the active ingredient of many rodenticides. Murderers, at least in mystery novels, lace food with it. Like other chronic heavy metal intoxications, chronic thallium intoxication causes a neuropathy that might be painful. The clue to thallium poisoning is hair loss (alopecia).

Aging

As people age, they develop sensory loss – akin to a sensory neuropathy – from peripheral nerve degeneration. Almost all individuals who are older than 80 years have lost some joint position and a great deal of vibratory sensation in their feet. This sensory neuropathy, which is accompanied by absent ankle DTRs, prevents older individuals from standing with their feet placed closely together, walking normally, and walking with a heel-to-toe (tandem) gait. It also predisposes them to falling. In addition, age- and work-related degenerative changes in the lumbar spine compress the lumbar nerve roots as they exit their neural foramina (see later, lumbar spondylosis).

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.

Inherited Metabolic Illnesses

Although numerous genetically determined illnesses cause neuropathy, two also cause psychosis.

Acute intermittent porphyria (AIP), the classic autosomal dominant genetic disorder of porphyrin metabolism, causes dramatic attacks of quadriparesis and colicky, often severe, abdominal pain. In about 25–50% of attacks, AIP patients develop any of a variety of psychiatric symptoms, including agitation, delirium, depression, and psychosis. During attacks, excess porphyrins color the urine red. Quantitative tests, which replace the classic Watson–Schwartz test, readily detect urinary porphobilinogen and 5-aminolevulinic acid in urine and serum. Although barbiturates and phenytoin may exacerbate an attack, phenothiazines are relatively safe. Notwithstanding its prominence as a standard examination question, AIP is rare in the United States.

Metachromatic leukodystrophy (MLD), an autosomal recessive illness carried on chromosome 22, derives its name from the colored granules (lipid sulfatides) that accumulate in the lysosomes of the brain, peripheral nerves, and many nonneurologic organs, such as the gallbladder, pancreas, and liver. Most importantly, MLD, like MS, causes a demyelination process in the CNS white matter (leukodystrophy) and, to a lesser extent, the PNS (see Chapter 15).

MLD symptoms usually first appear in infants and children, in whom the illness pursues a rapidly fatal course. In young adults, MLD presents with personality and behavioral changes, thought or mood disorder, and cognitive impairment. MLD-induced cognitive impairments typically progress slowly to dementia. Neurologists describe MLD-induced cognitive impairment as a “frontal dementia” because of its combination of personality, behavioral, and cognitive manifestations (see Chapter 7). Peripheral neuropathy and signs of CNS demyelination – spasticity and ataxia – follow and eventually overshadow the frontal dementia.

MLD is characterized by decreased activity of the lysosomal enzyme arylsulfatase A. Neurologists diagnose the illness by demonstrating a deficiency of this enzyme in leukocytes or cultured fibroblasts and the presence of metachromatic lipid material in biopsy specimens of peripheral nerves. In many cases, appropriate stains detect metachromatic lipid material in the urine. Autopsy specimens will show metachromatic material in cerebral tissue. As in MS, magnetic resonance imaging (MRI) shows demyelinated lesions in the brain (see Chapters 15 and 20). No treatment arrests the illness, but experimental treatments with bone marrow transplant and gene therapy hold promise.

Volatile Substance Exposure

Industrial organic solvents, which are generally lipophilic and volatile at room temperature, enter the body through inhalation, absorption through the skin, or occasionally by ingestion. Workers at risk of toxic exposures are those exposed to metal degreasing agents, paint and varnish, and shoe manufacturing chemicals; however, the danger depends more on poor ventilation and inadequate safety barriers than with particular industries.

Because of their lipophilic properties, industrial solvents, such as n-hexane, toluene, ethylene oxide, and carbon disulfide, penetrate the nervous system. Although these neurotoxins readily damage the CNS, PNS, or both, industrial solvents primarily cause a neuropathy. In addition, they sometimes cause various neuropsychologic symptoms – cognitive impairment, personality changes, inattention, depression, headaches, fatigue, and even psychosis – together termed solvent-induced encephalopathy.

Some individuals self-inflict solvent-induced encephalopathy through substance abuse. Recreational inhaling of certain volatile substances, “huffing,” also damages one or both components of the nervous system. For example, in “glue sniffing,” where the intoxicating component is the common hydrocarbon solvent n-hexane, sensation seekers typically develop polyneuropathy and other PNS complications.

In contrast, recreationally inhaling toluene, a component of spray paint and marker pens, predominantly damages CNS rather than PNS myelin. In single exposures, inhaling toluene produces an alcohol-like euphoria, but chronic overexposure, whether deliberate or accidental, may cause personality changes, psychosis, and cognitive impairment that can reach the severity of dementia. Toluene-induced dementia falls into the category of subcortical dementia, in which gait is impaired but language function is relatively preserved (see Chapter 7). Toluene may also cause ataxia, spasticity, and visual impairment. MRI can detect toluene-induced CNS demyelination (leukoencephalopathy, see Chapter 15). Thus, toluene exposure’s clinical findings and MRI abnormalities mimic those of MS.

Nitrous oxide, the dental anesthetic, is also potentially toxic to the PNS and CNS, particularly the spinal cord (see above). It is readily available in both gas cartridges, which are used in production of whipped cream, and large, safeguarded medical containers. Individuals who inhale nitrous oxide experience a few minutes of euphoria and relaxation as well as anesthesia. Frequently inhaling nitrous oxide, even intermittently for several weeks, may induce a profound neuropathy as well as spinal cord damage (see above). Succumbing to nitrous oxide abuse and suffering the neurologic consequences remains an occupational hazard for dentists.

Pseudoneurotoxic Disease

Neurologists often diagnose occupational neurotoxicity when a group of workers have similar neurologic symptoms and signs, environmental tests detect elevated concentrations of a potential toxin in their workplace, the substance is an established cause of similar symptoms and signs in animals or humans, and laboratory testing of the workers shows abnormalities consistent with the symptoms. To be fair, symptoms of solvent-induced encephalopathy and other alleged neurotoxic states are usually nonspecific and largely subjective. Moreover, generally accepted diagnostic criteria often do not exist, relevant psychologic tests are often unreliable, and studies have not yet established safe exposure limits.

Sometimes workers’ disorders have an explanation other than neurotoxin exposure. In pseudoneurotoxic disease, individuals attributing an illness to a neurotoxin have actually suffered the emergence or worsening of a neurologic or psychiatric disorder – alone or in combination – coincident with a neurotoxin exposure. In other words, despite their symptoms and signs, the neurotoxin has caused no ill effects. Attributing their illness to the neurotoxin constitutes a post hoc fallacy.

Sometimes the symptoms in pseudoneurotoxic cases may represent manifestations of an unequivocal neurologic illness, such as Parkinson disease or MS, that has emerged or worsened following the exposure. Similarly, patients may attribute age-related changes and variations in normal neurologic function to a neurotoxin exposure. Alternatively, the patients may have a somatic disorder, mood disorder, alcohol abuse, or other psychiatric disturbance whose manifestations mimic solvent-induced encephalopathy or other neurotoxic disorder.

The multiple chemical sensitivity syndrome serves as a prime example of pseudoneurotoxic disease. This disorder consists of miniscule exposures to environmental chemicals, ones usually volatile and unavoidable in day-to-day life, such as commercial cleaning agents or air fresheners, allegedly producing multiple but variable symptoms. According to affected individuals, exposure to innumerable chemicals causes attacks, which are often incapacitating, consisting of headache, alterations in level of consciousness, paresis, or various physical problems. Despite these individuals’ dramatic and compelling histories and their remaining apparently free of psychiatric disturbances between episodes, scientific analysis has shown that the symptoms are unrelated to chemical exposure and have no underlying physiologic disorder.

Marine Toxicology

Shellfish, free-swimming fish, and other forms of sea life produce, carry, or become contaminated by various toxins. Ciguatera fish poisoning, the best-understood and most commonly occurring example of “marine toxicology,” produces gastrointestinal and unique neurologic symptoms. The toxin, ciguatoxin, reaches humans by moving up the food chain from toxin-producing dinoflagellates to large, edible reef fish, particularly grouper, red snapper, and barracuda. These fish inhabit the waters off Caribbean or Indian Ocean islands, where seafood diners often fall victim.

Unlike other toxins, ciguatoxin causes a prolonged opening of voltage-gated sodium channels in nerves and muscles. Individuals who ingest ciguatoxin first have nausea and vomiting, as with most food poisonings, but then many develop the characteristic symptoms of an acute painful neuropathy with paresthesias, pain, and lack of sensation in their limbs. Victims also experience a unique symptom, cold allodynia or cold reversal, in which they misperceive cold objects as feeling hot. For example, they will sense that iced tea is hot tea served in a tall glass with ice. Although victims eventually recover, malaise, depression, and headaches may persist for months.

Puffer fish, a Japanese delicacy, and some crabs on rare occasions contain tetrodotoxin. Unlike ciguatoxin, tetrodotoxin is potentially lethal. Victims first develop numbness around the mouth and face, and then flaccid quadriparesis, which leads to respiratory failure.

Motor Neuron Disorders

Amyotrophic Lateral Sclerosis

For decades, neurologists referred to amyotrophic lateral sclerosis (ALS) as “Lou Gehrig disease” because the famous baseball player Lou Gehrig succumbed to this dreadful illness. Neurologists call ALS the quintessential motor neuron disease because both upper and lower motor neurons (UMNs and LMNs) degenerate while other neurologic systems – notably mental faculties – are usually spared.

The etiology of ALS remains an enigma, but several genetic, environmental, and pathologic findings hold some promise. One is that 5–10% of patients seem to have inherited ALS in an autosomal dominant pattern. Some of them – 2% of all ALS patients – carry a mutation of a gene on chromosome 21 (Cu, Zn superoxide dismutase [SOD1]) that normally assists in detoxifying superoxide free radicals. Another promising finding is a significantly increased incidence of ALS among US veterans of the Persian Gulf War. If the epidemiologic studies hold up, the cause in those cases may be related to either trauma, including traumatic brain injury, or exposure to a toxin, such as a pesticide or heavy metal. Among all people, cigarette smoking poses an unequivocal risk. It carries up to a fourfold increase in ALS.

The pathology of ALS, characteristically an absence of a cellular reaction surrounding degenerating motor neurons, weighs against inflammatory and infectious etiologies. Many ALS patients do respond, albeit modestly, to blocking glutamate, the excitatory neurotransmitter (see Chapter 21). Putting together these clues – the lack of a cellular response and a beneficial response to glutamate blocking – suggests that glutamate excitotoxicity leads to cell death from apoptosis (see Chapters 18 and 21).

Except for the veterans, patients develop ALS at a median age of 66 years. Their first symptoms usually consist of weakness, atrophy, and subcutaneous muscular twitching (  fasciculations) – a sign of degenerating anterior horn cells – all in one arm or leg (Fig. 5-9). Surprisingly, even from these atrophic muscles, physicians can elicit brisk DTRs and Babinski signs – signs of upper motor degeneration – because damaged UMNs supply enough undamaged LMNs. The weakness, atrophy, and fasciculations spread asymmetrically to other limbs and also to the face, pharynx, and tongue. Dysarthria and dysphagia (bulbar palsy) eventually develop in most patients. When pseudobulbar palsy superimposes itself on bulbar palsy, patients’ speech becomes unintelligible and interrupted by “demonic” or “pathologic” laughing and crying, and their behavior falls into the category of involuntary emotional expression disorder (see Chapter 4). Despite their extensive paresis, they maintain control over their bladder and bowel function as well as over ocular muscle.

FIGURE 5-9 This elderly man with amyotrophic lateral sclerosis has typical asymmetric limb atrophy, paresis, and fasciculations. His tongue, which also has fasciculations, has undergone atrophy, as indicated by clefts and furrows.

Because ALS attacks UMNs and LMNs, it generally spares neurons involved in cognitive function. Except for approximately 10% of patients, ALS victims retain their cognitive and decisional capacity, remain tragically mentally competent, and have complete awareness of their plight. The small group usually has some clinical and pathological features of frontotemporal dementia, in which behavioral and emotional changes accompany cognitive impairment (see Chapter 7).

No treatment can cure or even arrest ALS. However, riluzole (Rilutek), presumably by reducing glutamate excitotoxicity, slows the progression of the illness. Multidisciplinary health care groups, some physical therapy, nutrition supplied by gastrostomy, and noninvasive ventilation, especially at night, makes ALS patients more comfortable and prolongs their life. About 80% of ALS patients receiving standard or even aggressive medical care die, usually from respiratory complications or sepsis, within 5 years from the time of diagnosis.

The suicide rate among ALS patients is six times greater than controls. Suicide occurs more frequently among relatively young ALS patients and those in the early stage of their illness.

When asked to consult, psychiatrists almost always find that ALS patients retain their “decisional capacity.” It remains intact when, as is often the case, they refuse resuscitation measures, mechanical ventilation, and other life support devices. Because patients remain lucid, competent, and usually free of sedating medications, but carry the burden of a relatively rapid demise from untreatable fatal disease, ALS has become the prime example for discussions concerning end-of-life care, patients’ right to die, physician-assisted suicide, and euthanasia. After litigation or legislation, several patients have hastened the inevitable process of ALS. In addition, psychiatrists often find that ALS patient caregivers, just as Alzheimer disease and MS caregivers, have depressive symptoms.

Benign Fasciculations

Fasciculations are commonplace, innocuous muscle twitches that are usually caused or precipitated by excessive physical exertion, psychological stress, excessive caffeine intake, or exposure to some insecticides. The diagnosis of benign fasciculations may be difficult because they mimic ALS-induced fasciculations and are sometimes associated with fatigue and hyperactive DTRs. A clinical guideline would be that, in contrast to ALS-induced fasciculations, benign fasciculations are unaccompanied by weakness, atrophy, or pathologic reflexes, and they usually last for only several days to weeks. Using this guideline will help calm fears of medical students and others acquainted with ALS. After all, the majority of individuals with benign fasciculations have had medical training.

Sometimes twitching, which mimics fasciculations, of the eyelid muscles (orbicularis oculi) creates annoying movements. Neurologists call them myokymia and blame lack of sleep, excessive caffeine, and other irritants. In a different situation – if the movements are bilateral, forceful enough to close the eyelids, or exceed a duration of 1 second – they may represent a facial dyskinesia, such as blepharospasm, hemifacial spasm, or tardive dyskinesia (see Chapter 18).

Spine Disease

Cervical spondylosis is the chronic age- and occupation-related degenerative condition, which neurologists loosely term “wear and tear,” where bony encroachment leads to stenosis of the vertebral foramina and spinal canal (Fig. 5-10). Stenosis of the neural foramina constricts cervical nerve roots, which causes neck pain with arm and hand paresis, atrophy, hypoactive DTRs, and fasciculations – signs of LMN injury. Cervical spondylosis may also create spinal canal stenosis that compresses the spinal cord to cause myelopathy with leg weakness, spasticity, hyperreflexia, and Babinski signs – signs of UMN injury.

FIGURE 5-10 Left, In cervical spondylosis, bony proliferation damages upper and lower motor neurons. Intervertebral ridges of bone (double arrows) compress the cervical spinal cord. At the same time, narrowing of the foramina (single arrows) constricts cervical nerve roots. Right, Magnetic resonance imaging shows the lateral view of cervical spondylosis. The cerebrospinal fluid (CSF) in the foramen magnum (F) and surrounding the spinal cord is bright white. The spinal cord is gray. In the mid to low cervical spine, bony protrusions and hypertrophied ligaments compress the spinal cord and its surrounding CSF, giving the spinal cord a “washboard” appearance.

Lumbar spondylosis, the lower spine counterpart and frequent accompaniment of cervical spondylosis, produces lumbar nerve root compression and low back pain; however, because the spinal cord descends only to the first lumbar vertebra (see Fig. 16-1), lumbar spondylosis cannot cause spinal cord compression. Spondylolisthesis, which may accompany spondylosis, consists of the forward slip of adjacent lumbar vertebrae or of L5 on the sacrum. Lumbar spondylosis, with or without spondylolisthesis, commonly produces chronic buttock pain that radiates down the posterior aspect of the leg (sciatica). Its other symptoms are leg and feet fasciculations, paresis, atrophy, and knee or ankle areflexia. Sometimes patients with lumbar stenosis have symptoms of pain and weakness in their legs only when they walk (neurogenic claudication).

By causing both PNS and CNS signs, cervical and lumbar spondylosis mimics ALS. The features that distinguish spondylosis from ALS are its neck or low back pain, sensory loss, and absence of abnormalities in the facial, pharyngeal, and tongue muscles.

A ramification of cervical and lumbar spondylosis is that it causes chronic pain. It deprives people of work, mobility, and leisure activities. It sometimes contributes to depression and requires strong analgesics, perhaps opioids, as well as antidepressants (see Chapter 14). Carefully selected cases of severe spondylolisthesis and lumbar spondylosis with marked, symptomatic stenosis of the spinal canal will benefit from surgery.

A related disorder is spinal intervertebral disk herniation, which neurologists abbreviate to herniated disk. Intervertebral disks are gelatinous, checker-shaped shock absorbers that typically herniate in the curved cervical or lumbosacral spine. When they suddenly press against nerve roots as they emerge through the spinal foramina, herniated disks produce acute neck or low back pain. The pain may radiate down the nerve root’s distribution. Depending on the location and size of the herniation, sensory loss or weakness may accompany the pain.

When cervical intervertebral disks herniate and compress one or more cervical nerve roots, they typically cause neck pain that may radiate down the arm. Weakness of arm or hand muscles with loss of an upper-extremity DTR sometimes accompanies the pain. Whiplash automobile injuries and other trauma are the most common causes of herniated cervical intervertebral disks. Even without trauma, probably because of degeneration, disks herniate.

More than 90% of lumbosacral disk herniations occur at either the L4–5 or L5–S1 intervertebral space. These interspaces are vulnerable because they bear the stress of the body’s weight on the lumbar spine curve. Herniated lumbar disks cause low back pain that radiates into the buttock and often down one or both legs, i.e., sciatica. They may also cause weakness of the ankle and foot muscles and loss of the ankle DTR, but infrequently the knee DTR. Large lumbar disk herniations may cause compression of all the lower lumbar and sacral nerve roots, which comprise the cauda equina (Fig. 5-11). Such herniated disks may produce the cauda equina syndrome: LMN paresis of one or both legs, perineal (“saddle area”) pain and anesthesia, incontinence, and sexual dysfunction.

FIGURE 5-11 The cauda equina (Latin, horse’s tail) consists of the bundle of lumbar and sacral nerve roots in the lower spinal canal. The nerve roots leave the spinal canal through foramina. Herniated disks might compress the nerve roots in or near those narrow passages. Compressed nerve roots usually cause pain in the low back that radiates along the distribution of the sciatic nerve. Common movements that momentarily further herniate the disk, such as coughing, sneezing, or straining at stool, intensify the pain. Large herniated disks may compress the entire cauda equina.

Poor posture and obesity, as well as the causes of cervical herniated disks, predispose individuals to lumbar herniations. Coughing, sneezing, or elevating the straightened leg – because these maneuvers press the herniated disk more forcefully against the nerve root – characteristically increase buttock and leg pain (Fig. 5-12).

FIGURE 5-12 If a patient has a herniated lumbar intervertebral disk and a physician raises the patient’s straightened leg, the maneuver will probably cause low back pain to radiate to the buttocks and perhaps further down the leg (Lasègue sign). This position draws the nerve against the edge of a herniated disk, which leads to nerve compression and irritation.

Herniated disks are rarely responsible for all the chronic pain, disability, sexual dysfunction, and multitudinous other symptoms that many individuals, especially litigants, attribute to them. In fact, herniated disks are often an innocuous, chance finding. For example, MRI studies have revealed a herniated disk in 20% of asymptomatic individuals younger than 60 years. Even more so, bulging and desiccated disks, because they do not compress nerve roots, do not cause these symptoms.

Nonopioid analgesics, superficial heat, and reduction in physical activity usually alleviate acute neck or low back pain from herniated disks. Epidural injections of steroids, which often include some lidocaine, improve acute pain from lumbar herniated disks but do not alter the outcome. The popular spinal decompression machines do not help. Although 90% of acute low back pain cases resolve in 6 weeks, about 25% of patients who recover from low back pain suffer a recurrence within 1 year and about 10% devolve into a state of chronic low back pain. Surgery is indicated, most neurologists feel, only for spinal cord compression, cauda equina syndrome, refractory objective symptoms and signs of nerve root compression, neurologic deficits, or severe disability.