Peripheral Neuropathies
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[edit] Peripheral Neuropathies
William Pryse-Phillips
T. Jock Murray
The site of primary damage to peripheral nerves may be any of their four components: the cell body and its axon (neuronal or axonal neuropathy), the Schwann cell sheath (demyelinating neuropathy), the supporting tissue (infiltrative neuropathy), or the vascular supply (ischemic neuropathy). To classify neuropathies as primarily caused by damage to one of these four components is of diagnostic value, but because the differences are not always easy to clinically determine, nerve conduction studies and nerve biopsies are necessary in most cases.
[edit] NEURONAL (AXONAL) NEUROPATHIES
In neuronal neuropathies the damage is to the cell body or to the axon itself. On the motor side, damage to the anterior horn cell clinically manifests as weakness, wasting, and perhaps fasciculations. If the process is severe or long-standing, diminution or loss of muscle stretch reflexes occurs; but this is seen at an early stage if the reflex arc is interrupted on the sensory side. Anterior horn cell damage means that the pathology is actually operating in the spinal cord, but the condition is still referred to as a neuropathy because the clinical effects are almost entirely related to peripheral nerve dysfunction. Sensory axonal neuropathies tend to affect the various modes of sensation more or less equally.
Both Wallerian degeneration and “dying-back” neuropathies lead to secondary redundancy of Schwann cells, which may disappear or become markedly reduced in numbers. This secondary demyelination must, however, be distinguished from primary demyelination in which the major damage is caused to the Schwann cells in the first place. The Schwann cells perform the same function vis-a-vis the axon as the oligodendroglia perform in the CNS; that is, they have nutritive and insulating functions. In the case of the peripheral axon, the presence of Schwann cells with interspersed nodes of Ranvier allows saltatory conduction to occur, and their absence causes a marked reduction in the speed of the passage of the nerve impulses.
[edit] DEMYELINATING NEUROPATHIES
If there is significant Schwann cell damage, the first axons to have their function impaired will be those that rely most on the insulating action of these Schwann cells, namely those with the thickest layer of myelin, the fastest conducting fibers. Clinically, the first and most severe modalities of sensation lost will be vibration, joint position sense, and tactile discrimination, although there will usually also be some diminution in thin-fiber function, too. In the case of axonal sensory neuropathies, the different sensory modes tend to be affected to a similar extent.
Demyelinating neuropathies lead to early loss of muscle stretch reflexes. Both motor and sensory nerves are commonly involved, although in most cases the sensory effects overshadow the motor findings. Spontaneous pain is not uncommon but it is not a strong diagnostic indicator of any particular type of neuropathy (nor indeed of neuropathy itself, as spontaneous pain and tenderness in muscles may occur with both neuropathy and primary muscle disease).
[edit] INFILTRATIVE NEUROPATHY
In infiltrative neuropathy, the appearances are hardly distinguishable from demyelinating types. Accumulation of extraneous material within the nerves enlarges them, causing secondary Schwann cell damage. Examples include sarcoidosis, myelomatosis, amyloidosis, and the leukodystrophies.
[edit] ISCHEMIC NEUROPATHY
Schwann cells tolerate ischemia badly because they have a high metabolic rate and are dependent on the small vasa nervorum for their blood supply. If this supply fails, the insulating capacity of the Schwann cell is damaged as it becomes metabolically embarrassed, leading to conduction block. Such failure of blood supply may occur because of occlusion of the vasa nervorum from compression, or in diabetes, collagen-vascular diseases, atheroma, or paraneoplastic vasculitis. The result is an ischemic mononeuropathy, which may affect multiple nerves. The diabetic forms are typical of them all.
[edit] APPROACH TO THE PATIENT WITH NEUROPATHY
The clinical features of greatest relevance in the diagnosis of neuropathies are included in Box 167-1.
| Box 167-1 - Clinical Features of Neuropathy |
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The clinical history should focus on the speed of onset or development of symptoms, family history, occupation and exposure to toxins/drugs, preexisting systemic illness, and trauma.
Sensory symptoms consist of paresthesias and numbness, beginning in the feet and spreading to the legs and hands. There may be dysesthetic sensations in the same distribution in the form of burning, prickling, coldness, and heaviness. Limb pain is poorly localized, often lancinating, and especially severe at night. At times, however, severe sensory loss may develop silently.
Sensory loss develops according to axonal length, so the sensory impairment is chiefly distal in the extremities in a symmetric stocking-and-glove distribution. The likely reason for this is that based on the effect of the inciting agent, the metabolism of the cell body is impaired so that it cannot easily pump axoplasm to the most distant parts of its axon. The process of “dying back” then occurs, and it is the “Outposts of the Empire” rather than the regions close to the nerve cell body that are first affected, at least as clinically seen. Afferent fibers in the legs can be over 3 feet long, whereas in the arms the distance is a good deal less; thus the first symptoms usually appear in the lower limbs. By the same token, the face is seldom affected, although stilbamidine and trichloroethylene do impair V nerve sensory function selectively. Cutaneous sensory loss extends to about the knee before it appears in the fingers. In more advanced stages it extends to the trunk so that there is hypoesthesia to pinprick on either side of the midline of the abdominal wall and lower part of the anterior chest in the shape of a teardrop.
Motor abnormalities generally follow the same distribution, with weakness or clumsiness appearing in the feet and extending to the legs and hands and, in the most severe cases, involving the proximal muscles; however, as a rule, muscles innervated by cranial nerves are spared. Eventually the wasting and weakness of affected muscles may lead to disabling bilateral footdrop and wristdrop.
In long-standing cases of polyneuropathy with sensory loss (e.g., in hereditary sensory or diabetic polyneuropathy), trophic changes appear in the feet and less often in the hands. The best known are Charcot's joints or neuroarthropathy, in which the joints undergo insidious, painless disorganization, leading to swelling and gross deformity. The foot and ankle joints are most frequently affected, but neuroarthropathy can also occur in the knee, wrist, elbow, and shoulder. Even more common are the consequences of recurrent injury to insensitive parts of the body; corns and calluses break down to punched-out chronic ulcers over the feet that may penetrate down to the bone, setting the stage for serious infection of foot spaces and gangrene. Cigarette burns are a telltale sign in the hands. Muscle stretch reflexes are typically lost early and symmetrically. In some demyelinating and infiltrative neuropathies there is visible or palpable enlargement of the greater auricular nerve on the lateral side of the neck, the superficial cutaneous branch of the radial nerve at the wrist, and the ulnar and peroneal nerves.
Autonomic disturbances coexist with many chronic polyneuropathies, such as chronic diabetic and hereditary neuropathies and primary amyloidosis. The dysautonomia is often asymptomatic, but postural hypotension, urinary retention or incontinence, impotence, generalized or regional anhidrosis, cardiac irregularities, gastroparesis, diarrhea, and impaired pupillary motility are notable manifestations. A battery of tests can be performed at the bedside to document autonomic impairment.
The diagnosis of chronic polyneuropathy is readily made on clinical grounds, although it is clear that in many patients it is subclinical. The preservation of ankle reflexes in what appears otherwise to be symmetric polyneuropathy should arouse suspicion that one is dealing with a myelopathy. Exceptionally, ankle reflexes are preserved in some familial polyneuropathies and others that preferentially affect the thin fibers subserving pain and temperature, as in amyloidosis, porphyria, and rare cases of diabetes.
The etiologic diagnosis of chronic symmetric polyneuropathy may be obvious on clinical examination and a limited routine biochemical screening. About 40% of polyneuropathies will be due to some chronic systemic medical disorder (e.g., diabetes, malignancy, collagen-vascular disease, organ failure, B12 deficiency, alcoholism or other toxic exposure, acquired immunodeficiency syndrome [AIDS], occult malignancy, or plasma cell dyscrasia), in 30% a hereditary cause will be found, and inflammatory disease will account for another 20%. AIDS is now an important cause of mononeuropathies as well.
A significant number of patients with polyneuropathy lack a specific diagnosis even after extensive investigation. Many will eventually be found to have inherited neuropathies, so examination of family members for skeletal deformities (e.g., kyphoscoliosis, pes cavus and hammer toes, and enlarged nerve trunks) and nerve conduction studies provide important clues. Nerve biopsy is a useful way of determining the etiology of some polyneuropathies, such as amyloidosis, leprosy, sarcoidosis, certain toxic neuropathies that cause giant swellings of axons, and vasculitic neuropathies.
Although classification of neuropathies by clinical presentation alone is fallacious because the same pathologic process may create different manifestations, methodical clinical evaluation can point one toward a pathologic diagnosis.
When the question of neuropathy is raised, the physician should decide first whether this is a mononeuropathy, in which the symptoms are confined to the distribution of a single nerve; a multiple mononeuropathy, in which discrete nerves are involved at various sites; or a polyneuropathy, a symmetric (usually distal) pattern of involvement. The first two groups usually are due to nerve compression or inflammation.
The clinical approach to diagnosis in the case of a patient with polyneuropathy continues with the second differentiating question: is the neuropathy motor, sensory, or mixed? After this has been decided, the fields of possible etiologies are smaller but still quite long, so further branches of the tree must be explored.
The physician should next determine whether the progression of symptoms has been acute (over hours to days), subacute (over days to weeks), or chronic (over months). Acute neuropathies, developing in less than a week, are almost all motor; porphyria, poliomyelitis, and poisoning are the most common causes. Uncommon acute sensory neuropathies are usually caused by toxic agents but sometimes occur in association with underlying malignancy. Chronic neuropathies make up the majority of cases (Boxes 167-2, 167-3, and 167-4). When there is more motor than sensory involvement, the physician should think first of motor neurone disease (e.g., amyotrophic lateral sclerosis [ALS]), poliomyelitis, hereditary motor and sensory neuropathies, chronic infectious polyneuropathy, and toxic causes. With more sensory than motor involvement, axonal neuropathies such as those caused by toxicity, vitamin B12 deficiency, hereditary sensory neuropathy, or other systemic disease, and demyelinating neuropathies related to diabetes, uremia, myelomatosis, and dysproteinemia should be considered first.
| Box 167-2 - Causes of Sensory Neuropathies by Clinical Type✢ |
Acute/Subacute
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| Box 167-3 - Causes of Sensorimotor Neuropathies by Clinical Type✢ |
Acute/Subacute
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| Box 167-4 - Causes of Motor Neuropathies by Clinical Type✢ |
Acute/Subacute
|
The fourth question to consider is whether the polyneuropathy is of axonal or of demyelinating/infiltrating type. This can usually be answered using nerve conduction studies, although the findings of marked thick-fiber function loss (e.g., vibration and joint position sense) and of enlarged nerves would strongly suggest that the pathology is demyelinating or infiltrative. Boxes 167-2, 167-3, and 167-4 list the more likely causes of polyneuropathies with these pathologies and whether they are motor, sensory, or mixed; acute/subacute or chronic; and axonal or demyelinating. At this point in the investigation, the list of likely causes should have been narrowed to a reasonable length, allowing efficient planning of further investigations.
Finally, more precision may be obtained by considering if the condition is painful and whether there is evidence of autonomic involvement or thickening of the peripheral nerves.
[edit] MONONEUROPATHIES
[edit] Asymmetric Proximal Neuropathies
Distinctive clinical syndromes of rapidly evolving painful weakness in the arm and shoulder or thigh and hip frequently occur because of involvement of the brachial or lumbosacral plexus. The pathology and pathogenesis, however, are ill-understood.
[edit] Neuralgic Amyotrophy (Idiopathic Brachial Plexus Neuropathy, Parsonage-Turner Syndrome).
Neuralgic amyotrophy is well characterized clinically, although the cause and pathogenesis are not known. It may follow immunizations and rarely is familial. The process seems to cause an acute dysfunction of multiple nerves of the brachial plexus or more distal nerve branches, usually unilaterally but occasionally bilaterally. Otherwise healthy patients between 20 and 40 years of age are usually affected. The onset is abrupt, with intense pain over the shoulder and upper arm that persists for days or a few weeks. As pain abates, weakness and atrophy appear rapidly, most often affecting the serratus anterior, deltoid, supraspinati and infraspinati, rhomboids, sternomastoids, biceps, triceps, brachioradialis, and extensors of the wrist in various combinations. Sometimes only one or two of these muscles are affected. If any sensory impairment occurs, it is confined to an area over the deltoid in the distribution of the axillary nerve.
The diagnosis is clinical. Cerebrospinal fluid (CSF) studies are unwarranted. In the acute phase of pain the diagnosis is difficult, with referred pain from gallbladder disease, local disease such as bursitis of the shoulder, or cervical disk prolapse entering into the differential diagnosis. Unlike acute disk protrusions, there is no neck spasm or limitation of neck movement. No specific treatment is available. It is a clinical impression that a short course of steroids decreases the duration of pain but does not seem to alter the course of the disease otherwise. Recovery occurs in most instances but may take up to 2 or 3 years.
[edit] Idiopathic Lumbosacral Plexopathy.
Idiopathic lumbosacral plexopathy is most often caused by diabetes, but retroperitoneal tumors, aneurysm, abscess, or vasculitis in elderly patients can produce the same picture. Patients with vasculitis will complain of severe root pain and focal deficits in the distribution of the femoral, obturator, and/or sciatic nerves. The diagnosis is seldom possible without the aid of electromyography and computed tomography (CT) scanning, but a clue may be obtained from the high erythrocyte sedimentation rate (ESR) that is generally found.
[edit] Lumbosacral Polyradiculopathy (Cauda Equina Syndrome) in Acquired Immunodeficiency Syndrome.
A rapidly evolving cauda equina syndrome may occur in patients with AIDS as a result of necrotizing vasculitis of the lumbar and sacral nerve roots of the cauda equina from cytomegalovirus (CMV) infection. Clinically, patients are in the later stages of human immunodeficiency virus-1 (HIV-1) infection and complain of numbness in the feet or sacral areas, beginning asymmetrically and progressing rapidly to areflexic, hypotonic paraparesis and urinary retention. The CSF shows a predominantly granulocytic pleocytosis of up to 1000 cells/cm with raised protein and decreased glucose. CMV can usually be cultured from the CSF. The clinical picture is supported by evidence of other foci of CMV infection, such as retinitis, pneumonitis, or encephalitis. Prompt therapy with ganciclovir based on the clinical and CSF picture while awaiting confirmation by CSF culture is essential to prevent worsening to paraplegia. A similar syndrome may evolve in a slower, subacute fashion in patients with AIDS and can be caused by leptomeningitis localized to the cauda equina from cryptococcosis, syphilis, and tuberculosis. A rare cause of a similar syndrome in which CSF abnormalities are found has been recognized in otherwise normal persons resulting from industrial exposure to dimethyl-aminoproprionitrite (DMAPN), a catalyzer in the manufacturing of polyurethane foam.
[edit] Diabetic Amyotrophy.
In diabetes, the VI, III, and IV cranial nerves and the femoral and obturator nerves are those most often affected by neuropathy. The diabetic femoral neuropathy (diabetic amyotrophy) is really a lumbosacral plexopathy. This is a syndrome caused by microinfarcts of the lumbrosacral plexus. It is seen in middle aged or elderly patients with undiagnosed or mild diabetes and a history of recent marked weight loss. The patients present with severe, persistent, deep pain in the thigh accompanied by marked weakness and wasting of the hip and thigh muscles. It is usually unilateral; when bilateral, it is asymmetric. There is severe weakness of the iliopsoas and quadriceps femoris and often there is some weakness in other muscles innervated by the femoral, gluteal, and obturator nerves. The knee jerk reflex is lost, but sensation is normal. There is often considerable weight loss, which raises the suspicion of malignancy.
The condition is easily misdiagnosed as an L4 root lesion. However, that would not produce weakness of the iliopsoas and quadriceps muscles, and sensory impairment over the inner aspect of the leg would be notable, whereas in diabetic amyotrophy, weakness spills over to muscles supplied by the obturator and sciatic nerves, outside the territory of the L4 root. The condition must be distinguished from acute femoral neuropathy caused by retroperitoneal hematoma in patients with bleeding disorders.
Treatment is symptomatic, but symptoms may last from 3 to 18 months. Initially the main problem is to provide pain relief. Diphenylhydantoin and carbamazepine are helpful for some patients, whereas others respond to amitriptyline; in intractable cases amitriptyline is combined with fluphenazine. These agents are given along with nonnarcotic analgesics such as aspirin or ibuprofen. Aspirin is preferable, when tolerated, because it has the advantage of inhibiting platelet aggregation, which might be involved in the pathogenesis. When paralysis is severe, the patient may benefit from bracing the knee.
[edit] More Distal Mononeuropathies
[edit] Diabetic Ischemic Neuropathies
[edit] Diabetic III Nerve Palsies.
Diabetic III nerve palsies frequently spare the pupil,✢✢But so do aneurysms sometimes. The Golden Rule is that there are no Golden Rules. perhaps because the parasympathetic fibers are situated around the outside of the nerve, where they can receive some blood supply from the local pia-arachnoid vessels. The initial complaints are of eye pain, headache, and diplopia that have sudden onset but usually clear after weeks or months. In diabetes, such ischemic neuropathies are often superimposed on a preexisting metabolic polyneuropathy. In forms with any of these etiologies, single or multiple nerves show acute loss of motor and sensory function, often with pain, and recovery occurs slowly as long as the original disease is successfully treated.
[edit] Diabetic Truncal Radiculopathy.
In diabetic truncal radiculopathy the thoracic nerve roots are asymmetrically affected, causing a deep burning pain felt over the upper abdomen or side of the chest for some weeks. It is often associated with anorexia and weight loss so most patients are investigated for occult malignancy without result. Diagnosis is made primarily by an awareness that this syndrome occurs in diabetic patients. Electromyography of thoracic and lumbar paraspinal muscles shows extensive signs of denervation, usually bilaterally. A myelogram may occasionally be required to rule out compressive or inflammatory lesions of the roots. This neuropathy differs from the painless form of truncal neuropathy, which is bilateral, symmetric, and causes sensory impairment over the anterior abdominal wall. In these patients there is also severe sensory loss in the limbs and often evidence of visceral autonomic neuropathy. These cases represent a very advanced stage of the common diabetic distal symmetric polyneuropathy. The pain resolves spontaneously over months, but may be alleviated as outlined under the treatment of diabetic amyotrophy.
[edit] Compression and Traction Neuropathies
Although nerve compression produces dysfunction partly through the mechanism of ischemia, compression neuropathies will be described separately because they are so common and distinctive. Any superficial nerve in the body may be stretched or compressed; even comparatively minor pressure will prompt long-lasting symptoms if the nerves have been damaged already and are thus “at risk.” This may occur in the presence of any subclinical neuropathy and also when another lesion is situated proximally (such as cervical spondylosis), where it is already decreasing axoplasmic flow from a higher level. Superficial nerves are especially liable to injury by external pressure where they overlie bone. The radial nerve in the spiral groove of the humerus, the ulnar nerve in the cubital tunnel, and the common peroneal nerve at the neck of the fibula are especially vulnerable to compression, occupationally or resulting from deep sleep or coma. Patients with generalized wasting diseases and loss of fat will have less of a subcutaneous buffer between nerves and external objects. Because patients may be lying in bed for long periods, compression neuropathies are common in such cases. Rarely, the condition is inherited.
The mechanism is one of chronic pressure on a segment of the nerve that lies in a fibroosseous tunnel close to the joint where it is vulnerable to recurrent microtrauma. The compressed segment of the nerve shows areas of demyelination chiefly affecting the thickly myelinated fibers. In most patients, the axons are preserved and remyelination eventually occurs.
The anatomic diagnosis is made by clinical examination. Measurement of nerve conduction velocities, however, is a sensitive and easy laboratory test that shows slowing across the entrapped nerve segment. In general, sensory conduction is impaired earlier than motor conduction, although the latter is more easily tested. Electromyographic examination of the muscles supplied by the affected nerve may add more data because evidence of muscle denervation indicates a substantial degree of compression.
The etiologic diagnosis is usually evident from the history of occupational, habitual, or hobby-related trauma, but diabetes, hypothyroidism, and generalized (sometimes subclinical) polyneuropathy should be excluded, which may require laboratory tests.
Awareness of the possibility of nerve injury and careful technique should obviate nerve compression resulting from the application of a tourniquet or plaster cast to limbs. Every effort should be made to prevent or minimize prolonged local pressure in patients undergoing general anesthesia and in comatose patients (Fig. 167-1). The regions of the limbs in which nerves are vulnerable to pressure must be protected. If the arm is to be immobilized on a board for intravenous (IV) infusion, it should be placed in a supine position. If it is not immobilized, it should be kept half-flexed at the elbow and across the chest so that elbows are clear of the bed. If the arm is to be kept by the side, soft pads under the arm and forearm will protect the nerve from pressure. The unconscious patient should be turned frequently so that the weight of the body does not press on the limbs for any length of time. The elbow should be prevented from pressing against the metal edge of the bed or operating table and should not be allowed to hang over the edge of the bed to avoid pressure over the radial nerve. In the legs, the peroneal nerves can be protected by soft cushions, avoiding crossing of the legs, and by care in using stirrups for the lithotomy position.
[edit] Treatment.
Treatment of hypothyroidism, acromegaly, or gout often relieves an associated carpal tunnel syndrome, but decompression is effective in a majority of cases of compressive neuropathy. Conservative therapy is attempted in most instances and is the rule in self-limited neuropathies such as the carpal tunnel syndrome of pregnancy. Occupational and habitual modification is important. Rest from heavy work with hands and wrists in a patient with carpal tunnel syndrome is helpful, but this may call for a change of jobs. The avoidance of habitual trauma is essential. For instance, the patient with ulnar entrapment must not lean on the elbows nor sleep with them flexed. Physical medicine has a useful role. A 20-degree wrist cock-up splint may abolish the nocturnal pain in carpal tunnel syndrome. A soft pad behind the elbow may ease the pain and paresthesia of mild ulnar neuropathy. Local injection of steroids (usually methylprednisolone) may decrease the interstitial edema of the nerve and of the synovial membranes surrounding it when injected in the vicinity of the entrapped nerve segment, not into the nerve itself. The techniques of injecting the carpal tunnel, for which it is most frequently used, can be learned quickly and performed in the clinic. When successful, the injection can be repeated, but if it is required more than every 2 or 3 months, surgery should be considered.
Surgery is indicated for failure of conservative measures and the presence of enduring sensory loss or weakness. The procedures are simple and direct and in principle involve decompressing the affected nerve segment by sectioning the flexor retinaculum for the carpal and tarsal tunnel syndromes. Surgery for ulnar nerve entrapment should be decompression rather than transposition, which further damages its blood supply. Surgery effectively relieves pain and paresthesia and in most cases leads to gradual recovery of sensation. Muscle weakness, if already established before surgery, is the last to recover. Disability resulting from some palsies can be minimized before natural recovery occurs. The use of appropriate splints for wrist drop and a brace for foot drop is helpful for patient comfort and for prevention of contractures. If a minor causalgic syndrome develops, the burning pain and trophic changes can last for months and can be quite distressing. The symptoms are treated with nonnarcotic analgesics, transcutaneous electrical nerve stimulation (TENS), carbamazepine or tricyclic drugs, and, in recalcitrant cases, with sympathetic blockade. There is seldom any indication for surgery in the acute phase because the palsies usually recover spontaneously. An occasional patient with postoperative ulnar neuropathy may continue to have severe weakness for 1 to 2 years, and surgical decompression of the nerve is then advisable.
[edit] Cranial Nerves.
Because all the cranial nerves leave the skull through foramina, they are also liable to compression (e.g., the VII as in Bell's palsy, the VIII in a cerebellopontine angle tumor or Paget's disease, and the III with a temporal lobe expanding lesion producing uncal herniation syndrome). Pressure on the lower cranial nerves from inflammatory, neoplastic, or vascular lesions may occur as well. Pressure on spinal nerve roots by tumors, disks, or osteophytes and so on could also be regarded as compression neuropathies.
[edit] Facial Palsy.
Facial palsy is the most common cranial mononeuropathy seen in general practice and is discussed in Chapter 162 .
[edit] Brachial Plexus.
The usual cause of Erb's palsy is a stretching injury to the C5 and C6 roots. Weakness and wasting of the deltoid, spinati, biceps, and periscapular muscles are found (Erb's palsy); lymphedema is common, but pain is unusual. Weakness of shoulder abduction and external rotation, elbow flexion and supination, and wrist and finger dorsiflexion lead to the classical Porter's tip appearance. For some reason, myokymia in the proximal muscles is also common in this condition. The upper fibers of the brachial plexus may also be compressed by fibrous tissue after radiation therapy.
The lower fibers of the brachial plexus may be infiltrated by malignant tissue, producing Horner's syndrome, pain, and mainly distal signs, such as wasting and weakness of the thenar and hypothenar muscles and reduced sensation in the distal upper limb. Damage to these fibers also occurs with acute abduction injuries of the shoulder (Klumpke's palsy), which stretch the C8 and T1 roots.
[edit] Thoracic Outlet Syndrome.
Thoracic outlet syndrome is a much disputed condition that is more a vascular than neurologic entity; although the diagnosis is often made, objective neurologic or electrical signs are rare. Symptoms ascribed to the disorder include pain in the arm, especially with heavy lifting or carrying; coldness, color change, and pain in the hands; and weakness of the forearm and hand. Symptoms may be produced or exacerbated by downward traction on the arm and sometimes by hyperabduction at the shoulder, when a diminution of the radial pulse may be found (which may be the key to the whole matter if the problem is venous or arterial compression rather than stretching of the lower fibers of the brachial plexus). Objective physical signs, such as C8-T1 sensory loss or small hand muscle wasting, are rare but many of these patients have long necks and droopy shoulders, suggesting that the symptoms stem from a disorder of posture—the droopy shoulder syndrome.
When physical signs are actually found, even if radiographs do not show cervical ribs, a fibrous band may be present between the (often large) C7 transverse process and the first rib. The scalenus anticus muscle is inserted into the first rib, just anterior to the subclavian artery and the lower trunk of the brachial plexus, and it has been suggested that hypertrophy or abnormal contraction of this muscle can be a cause of compression. In the presence of even minor vascular changes, the potential damage to the subclavian artery (dilation or thrombosis) makes surgical exploration advisable. Resection of the scalenus anticus or of the first rib, a cervical rib, or a band between them is now seldom done and it is best to advise all patients to practice shoulder-girdle strengthening exercises and to avoid surgery.
[edit] Axillary (Circumflex) Nerve.
The axillary (circumflex) nerve may be damaged when the head of the humerus is dislocated posteriorly and is less often by direct trauma. The same nerve is severely involved in the condition of neuralgic amyotrophy. Weakness and wasting of the deltoid and a small patch of sensory loss over the outer part of the shoulder are the only signs resulting from selective axillary nerve damage. This condition must be differentiated from a C5 root lesion, which will also show signs of a lower motor neuron lesion affecting the rhomboids and the supraspinati and infraspinati, as well as other muscles supplied in part by C5.
[edit] Other Brachial Plexus Branches.
Other brachial plexus branch nerves may be damaged in isolation. The long thoracic nerve to the serratus anterior fixes the scapula to the chest wall when forward pressure is exerted on the upper limb. It also brings the scapula forward when the arm is thrust forward, as in a fencer's lunge, causing injury in healthy young people who have been exercising heavily. Injury may produce pain in the shoulder that is referred to the scapular and periscapular muscles. Causes include shoulder trauma, carrying heavy weights, and neuritis after a viral respiratory illness such as coxsackievirus infections. The patient may complain of winging of the scapula when asked to push the arm forward against resistance and of pain when rotating or extending the neck, and will be unable to raise the arm over the head in the forward position. Conservative treatment with rest leads to a resolution of symptoms in most cases. Restorative surgery is possible in patients with persisting deficits. The suprascapular nerve is sometimes compressed or locally traumatized, which results in weakness of shoulder abduction and external rotation.
[edit] Ulnar Nerve.
The ulnar nerve is vulnerable in its subcutaneous position in the ulnar groove behind the elbow, behind the medial epicondyle where it is liable to compression, as well as being involved in lesions affecting the lower trunk. The most frequent site of damage is where the nerve passes under the common origin of the flexor muscles at the elbow. Everyone has experienced the disagreeable pain and electric shock sensation of banging the “funny bone” and of paresthesia in the hands when leaning on the elbows. When the elbow is flexed, the nerve is partially stretched and rises superficially, where it may well be damaged when the elbow rests on a hard surface. Weakness of the ulnar half of the flexor digitorum profundus, all of the interossei, the hypothenar muscles, and the adductor pollicis and sensory symptoms (diminution of common sensation in the little finger and the ulnar half of the ring finger) may be expected, and the Tinel's sign will be positive at the elbow. Striking wasting of the dorsal and palmar interossei may be seen.
Patients may present with tingling and numbness on the inner aspect of the palm and on the little and ring fingers, or with the gradual onset of wasting of the muscles of the hand, with clawlike deformity of the fingers but with little pain or paresthesia. Wasting and weakness of dorsal and palmar interossei and hypothenar muscles and decreased sensation over the little finger and ulnar half of the ring finger are found. The nerve may be tender at the elbow and may be enlarged above the ulnar groove.
Tardy ulnar palsy appears years after an injury to the elbow, such as supracondylar fracture of the humerus. The elbow is deformed and its movements restricted. Idiopathic ulnar palsy is the most common variety and occurs with a normal elbow. Recurrent trauma to the nerve during elbow flexion (as with frequent vigorous “arm curls” with weights for fitness training) may cause the neuropathy. Recurrent subluxation of the ulnar nerve, in which the nerve snaps out of the ulnar groove frequently with elbow flexion, is usually asymptomatic, but may cause pain and paresthesia.
In carpenters and shoemakers who use palm pressure on awls and screwdrivers, or in heavy equipment operators and truck drivers who push gears with the palm of the hand, the deep palmar branch of the nerve may be compressed medial to the pisiform bone at the wrist. This is below the origin of the superficial sensory branch to the fingers and that of the motor branch to the hypothenar eminence, so interosseous wasting and weakness of the adductor pollicis are the only signs.
[edit] Median Nerve.
Carpal tunnel syndrome, the most common compression neuropathy, is due to entrapment of the nerve in the carpal tunnel under the flexor retinaculum, where it is surrounded by the tendons and synovial sheaths of the long flexors of the fingers (Fig. 167-2).
The syndrome is particularly common in people with tenosynovitis of the flexor tendons, which lie with the nerve under the flexor retinaculum of the wrist. Synovial herniation or a simple ganglion or a lipoma may be present. Those with any abnormal degree of fluid retention (e.g., related to hypothyroidism, pregnancy, or chronic renal disease) are also susceptible, and the syndrome may also complicate Paget's disease, myelomatosis, acromegaly, and obesity. The problem is frequently bilateral, in which case it is worse in the dominant hand. The leading symptom is recurrent, painful numbness, usually worst at night. It often affects all fingers rather than being restricted to the thumb, index, and middle fingers. Pain is less evident but when it occurs it may spread up the arm, even to the shoulder. Patients may also complain of dropping objects from the hand. In the early stages, examination may be normal despite prominent symptoms.
Patients are more frequently women than men. They complain of pain in the hand that rises up the arm as far as the shoulder and characteristically awakens them at night. The syndrome also is associated with paresthesia of at least 3½ fingers (although patients sometimes may complain of tingling throughout the whole hand). When the patient wakes up early in the morning, he or she tends to rub or flick the hand to try and restore feeling. Any heavy exertion during the day, such as housework, knitting, or gripping a steering wheel, or repetitive use of the wrist at work tends to worsen the symptoms. Weakness of the thumb is manifested as clumsiness and difficulty with some fine movements. Examination reveals weakness of the thenar muscles, especially of the opponens (but not the adductor) and possibly of the two radial lumbricals so that extension at the interphalangeal joints of the second and third fingers is impaired; sometimes there is hypoesthesia of the radial side of the palm and of the palmar aspects of the first 3½ digits, a positive Tinel's sign at the wrist, and worsening of symptoms with passive compression of the volar aspect of the wrist (Phalen's sign).
Precise electrophysiologic criteria for the diagnosis of carpal tunnel syndrome have been defined, and most surgeons prefer to operate after the diagnosis has been confirmed by nerve conduction studies. The best long-term results are achieved by incision of the flexor retinaculum under regional anesthesia to relieve the pressure on the nerve. Alternatively, splints worn at night that hold the wrist in 20 degrees of extension, or an injection of 20 mg of prednisone under the flexor retinaculum may produce temporary relief. Conservative measures such as these are correctly used in pregnant women because the condition often clears after delivery.
[edit] Radial Nerve Palsy.
In radial nerve palsy the radial nerve is compressed as it lies in the spiral groove (Fig. 167-3). With damage at that site, the branches to the triceps are spared so the patient can still extend the elbow, but there is wrist drop and failure of finger extension. A small patch of sensory loss can sometimes be detected between the thumb and first finger on the dorsum of the hand. The condition is common among alcoholics, in whom there is often the added factor of preexisting alcoholic neuropathy, and in the male partner of a courting couple, as well as from improper positioning under anesthesia, wherein the arm is allowed to hang over the edge of the operating table. Rarely, it appears after heavy exertion in a very muscular individual. The patient complains of weakness of the hand, without pain, that is noted on awakening and often misconstrued as a stroke. The chief abnormality is weakness of dorsiflexion of the wrist and fingers, but sensation and the triceps reflex are usually intact.
A common pitfall is the apparent weakness of the muscles of the hand that are innervated by the ulnar and median nerves in addition to those supplied by the radial nerve, so that the entire hand appears weak. This pseudoparesis is caused by the lack of normal fixation of the wrist and fingers by the extensor muscles necessary for the optimal use of other hand muscles. The confusion can be resolved by demonstrating that these movements are in fact normal when the wrist and fingers are supported by laying them on a firm, flat surface.
When radial nerve palsy is bilateral or appears subacutely, the possibility of lead poisoning should be considered. In patients with rheumatoid arthritis, symptoms should be differentiated from those of rupture of the extensor tendons.
The posterior interosseous nerve is a major terminal branch of the radial nerve. It may be compressed by a fibrous band or by a posterior dislocation of the radial head, where it passes underneath the origin of the extensor carpi radialis longus and supinator, or it may be damaged more distally after forearm fractures. Patients complain of pain in the forearm and of tenderness just below the lateral epicondyle, as with lateral epicondylitis. Examination shows weakness of extension of the thumb and index finger, but there is no change in sensation. After electrodiagnostic confirmation of the diagnosis, surgical decompression should relieve the symptoms.
[edit] Femoral Neuropathy.
One cause of femoral neuropathy is compression of the nerve by a hematoma in the iliopsoas muscle (Fig. 167-4), although the bleeding rarely occurs directly into the nerve. Most often it affects patients receiving anticoagulant treatment or those with hemophilia. Typically, pain in the thigh and weakness of flexion of the hip and extension of the knee rapidly evolve over hours or days. The knee jerk reflex is diminished or lost. Sensation is diminished over the anterior aspect of the thigh, and bluish discoloration may be seen in the inguinal region. In patients with coagulation disorders, there should be a high degree of suspicion for this complication; CT scan of the retroperitoneal region readily visualizes an iliopsoas hematoma.
With conservative therapy of rest, discontinuation of anticoagulation, or correction of bleeding disorder in hemophiliac patients, the neuropathy should improve, recovering fully in a few weeks, although mild residual disability may remain in some patients. The role of early surgical evacuation of hematoma is unproven.
[edit] Lateral Femoral Cutaneous Nerve.
The lateral femoral cutaneous nerve (Fig. 167-5) is sometimes compressed as it passes underneath the outer edge of the inguinal ligament. Such an occurrence is common in pregnancy and in obese people, in whom the nerve is compressed by a pad of fat. Pain, burning paresthesia in the anterolateral thigh, and a small area of local sensory loss characterize this condition, known as meralgia paresthetica. Treatment includes explanation and reassurance as to the benign nature of the otherwise baffling symptoms, weight loss if appropriate, local injection of the nerve with hydrocortisone and local anesthetic, or surgical decompression if such measures fail.
[edit] Obturator Nerve.
Occasionally damage to the obturator nerve occurs in the obturator canal, usually caused by the pressure of the fetal head during parturition, or after the imprecise application of forceps. The main features are pain in the inner side of the thigh, with some sensory loss in that area, and weakness of the hip adductors.
[edit] Sciatic Nerve.
Damage to the sciatic nerve may follow a posterior dislocation of the hip or a misplaced intramuscular injection. The initial result will be paralysis of all muscles in the leg except for those innervated by the obturator and femoral nerves. Sensory loss will be complete below the knee.
[edit] Common Peroneal Nerve.
Compression of the common peroneal nerve as it winds around the neck of the fibula is a common problem. Perhaps because of the anatomic arrangement of its fibers, those that pass in the deep peroneal branch to form the anterior tibial nerve (which innervates the space between the hallux and the second toes) are sometimes spared. Those carrying sensation from the outer edge of the calf and the dorsum of the foot in the superficial peroneal nerve are usually involved, with diminution or loss of sensation in that area. The motor fibers running to the peronei and the anterior tibial muscles are also affected, producing a foot drop and failure of eversion of the foot. If foot drop is pronounced, there may be apparent weakness of inversion and plantar flexion of the foot caused by lack of fixation of the ankle, a situation analogous to that in severe radial palsy. Tinel's sign will be positive, initially at the neck of the fibula when regeneration begins. Patients placed in stirrups in the Trendelenburg's position, those who have ill-fitting plaster casts or braces applied, those who are wasted and who lie long in bed, and especially those who sit with their legs crossed for a long time are likely to develop peroneal nerve palsy.
An acute fifth lumbar (L5) root lesion causes back pain, and straight leg raising is painfully restricted. When an L5 root lesion is suspected, evidence of denervation is sought in muscles supplied by L5 but not by the peroneal nerve, such as the posterior tibial, hamstring, and gluteus medius muscles.
[edit] Posterior Tibial Nerve.
The posterior tibial nerve may be compressed when it runs behind the medial malleolus under the flexor retinaculum to supply the small foot muscles (as the medial and lateral plantar nerves) and the skin of the sole of the foot on the medial side. Some cases occur idiopathically but in most it complicates a previous fracture with deformity of the ankle. A ganglion or neurofibroma is an occasional cause. Pain, tingling, and numbness in the sole of the foot are the main manifestations, often with nocturnal exacerbations. The nerve is usually tender behind the medial malleolus, and the Tinel's sign may be elicited on tapping it. In established cases there is wasting of the abductor hallucis, causing a hollowing out of the normal bulge on the medial margin of the foot. Apart from these motor and sensory changes, pain may also be a dominant feature. Surgical decompression is usually effective.
Rather more distally, a lateral plantar nerve may be compressed by a neuroma between the heads of the third and fourth metatarsals, producing very little in the way of clinically definable sensory loss or motor weakness but causing a lot of pain. The patient has a characteristic pattern of pain in the foot while walking, often stopping to take off the shoe and rub the foot. This condition, known as Morton's metatarsalgia, is also helped by surgery.
[edit] MULTIPLE NEUROPATHIES
[edit] Multiple Mononeuropathies
In multiple mononeuropathy syndrome, palsies of individual peripheral nerves appear acutely or subacutely and are scattered over the body in an irregular pattern (e.g., a wrist drop may appear caused by radial nerve palsy, followed in a few days by a foot drop from peroneal nerve injury and later by an ulnar neuropathy or cranial nerve palsy such as facial paralysis). Rarely, multiple mononeuropathy evolves gradually over months or years. In the Western world, the syndrome is most often caused by diabetes mellitus, vasculitis, or sarcoidosis; worldwide, however, leprosy is the most common cause. The vasculitides responsible include polyarteritis nodosa, Wegener's granulomatosis, rheumatoid arthritis, and systemic lupus erythematosus (SLE). The syndrome also occurs in Waldenström's macroglobulinemia and cryoglobulinemia, but the nerve ischemia in these disorders is due to hyperviscosity of the blood. Finally, multiple mononeuropathies may be manifestations of HIV-1 infection and of Lyme disease.
Pain is a noticeable feature in many cases. Sensory perineuritis is an uncommon variant, but it is of interest because it causes recurrent, migrating, painful numbness in different parts of the body, yields no abnormal investigative results, and eventually disappears.
The diagnosis in most cases is aided substantially by the relatively limited number of causes. Nerve biopsy may show vasculitis of the vasa nervorum, granulomas of sarcoidosis, or the bacilli of leprosy. In the appropriate clinical and epidemiologic circumstances, serologic tests for HIV-1 infection and Lyme disease should be obtained. A mononuclear CSF lymphocytosis is common to both disorders.
The treatment and prognosis are of the underlying diseases. In the acute vasculitides of polyarteritis nodosa and in Wegener's granulomatosis, the neuropathy may respond to steroids and immunosuppression, but the overall prognosis is poor. In macroglobulinemia and cryoglobulinemia, the mononeuropathies may recover fully. Antibiotic therapy is essential in Lyme disease; plasmapheresis and intravenous immunoglobulin may alleviate HIV-related neuropathies.
[edit] Polyneuropathies
When a patient has symptoms of weakness, numbness, tingling, and/or pain, and shows evidence of wasting, objective loss of power, fasciculations, and sensory loss in distal centripetal distribution, the diagnosis of neuropathy is relatively easy. The next stage is to determine the etiology, and the many potential causes make this a harder task.
The approach suggested at the start of this chapter has the merit of reducing the etiologic possibilities and thus makes investigation more efficient. Differentiation between acute and chronic is the first step, and the physician should always remember that some of these disorders evolve over days, which disallows an easy determination. Clinical evidence will give a fast answer to the question of whether the neuropathy is of motor, sensory, or mixed origin.
The third step (axonal or demyelinating?) is aided by the following: enlarged nerves, little wasting, hyporeflexia or areflexia, and major deficits in thick-fiber functions (vibration, joint position sense, tactile discrimination) point toward a demyelinating cause. Marked wasting, fasciculations, lancinating pains, no loss of reflexes, and major deficits in thin-fiber function (pinprick pain, crude light touch, scratch, temperature) indicate axonal loss. However, combinations are frequently seen, and the speed of nerve conduction may be the simplest and fastest way of making the determination.
[edit] Mainly Motor Neuropathies
[edit] Acute Motor Axonal Neuropathies.
Acute acquired neuronal motor neuropathies include poliomyelitis (see Chapter 165 ), porphyria, the severe neuronal variant of acute inflammatory polyneuropathy (see below), and less commonly lymphoma and recurrent hypoglycemia. Poisoning with dapsone, n-hexane, organophosphates, lead, and thallium are other causes.
[edit] Porphyric Neuropathy.
Recurrent bouts of acute polyneuropathy are a major and serious feature of the recessively inherited hepatic porphyrias—the acute, intermittent, variegate coproporphyric types. The principal pathologic abnormality is axonal degeneration affecting the nerve roots and proximal parts of nerves, including the autonomic fibers. The pathogenesis of nerve injury is not known, although it has been suggested that the large amounts of delta-amino levulinic acid (ALA) and porphobilinogen (PBG) produced in the acute attack may be neurotoxic.
Attacks are heralded by prominent and persistent abdominal and limb pain and constipation followed by symmetric, mainly proximal limb weakness. In severe cases, bulbar and respiratory paralysis occurs. General areflexia is present, although curiously, ankle reflexes may remain intact. A distinctive feature is sensory impairment, which often takes the form of broad bands around the thighs or arms or the shape of an old-fashioned bathing suit affecting the trunk. Autonomic disturbance is a constant feature, manifested by persistent tachycardia, ileus, hypertension, postural hypotension, and cardiac arrhythmias. The neuropathy is often accompanied or preceded by neuropsychiatric disturbances in the form of emotional lability, intense anxiety, depression, or frank psychosis with seizures.
Of great importance is the precipitation of acute attacks of porphyria by drugs, especially barbiturates. Other precipitants include starvation, acute infection, and possibly menstruation. Diagnosis is established by examining urine for PBG and ALA, both of which are present in great abundance in the acute phase. The urine typically turns port-wine color on standing in light. Relatives must be screened also.
Because of the cognitive and emotional features of acute attacks, patients in the early phases of neuropathy with bilateral limb pain are often misdiagnosed as hysterical. Another common and potentially tragic situation is that of a patient with acute abdominal pain in whom an exploratory laparotomy is performed under anesthesia using barbiturates; as the patient recovers from the anesthesia, a catastrophic barbiturate-induced neuropathy develops.
Symptomatic therapy is needed for maintenance of respiratory autonomic and metabolic functions. Propranolol is well tolerated, is an effective therapy for tachycardia and hypertension, and may also suppress the overproduction of porphyrins. Specific measures include avoidance of drugs that are known to exacerbate porphyria (Box 167-5) and the provision of an adequate amount of carbohydrates that seem to suppress porphyria precursor production and have a protective effect on neuropathy. Dextrose or levulose is given via nasogastric tube or intravenously. Hematin given early in the course of the acute attack consistently suppresses the overproduction of ALA by feedback inhibition of ALA synthetase and is of major benefit in minimizing neurologic damage.
| Box 167-5 - Drugs and Porphyria |
Drugs to Be Avoided
|
Recovery from severe attacks of porphyric neuropathy is slow and often leaves substantial chronic neurologic disability. Thus prevention and early treatment assume great importance. This is especially true because the patient with porphyria is at continual risk of attacks of neuropathy throughout life. It is vital to identify relatives who may be affected and caution them against factors that could induce attacks of porphyria, especially anesthesia and drugs.
[edit] Biologic Toxins: Shellfish and Ciguatera Fish.
The ingestion of certain shellfish and ciguatera fish in endemic coastal areas can cause severe acute peripheral neuropathy. The fish accumulate potent, flagellate-elaborated neurotoxins but are themselves unaffected by them. The usual offenders among ciguatera are barracuda and red snapper along the reefs off Florida, Hawaii, and the West Indies. Among the shellfish, oysters, mussels, clams, and scallops along the coasts of New England, Alaska, and the West Coast have been implicated. The toxins directly affect the axonal nerve membrane.
Ingestion is followed by nausea and vomiting and within a few hours by an explosively evolving neuropathy. Paresthesia occurs around the face and spreads to the limbs and is accompanied in severe cases by quadriparesis with bulbar and respiratory weakness. Bizarre sensations, such as the “feeling that teeth are coming loose” or “the body is floating away” have been noted.
The diagnosis is based on clinical evidence of rapid evolution of a neuropathy shortly after ingestion of marine food in endemic areas. One should be aware that respiratory paralysis can swiftly occur. No specific treatment exists, but supportive therapy is lifesaving and neuropathy recovers over many months.
[edit] Triorthocresyl Phosphate Poisoning.
Triorthocresyl phosphate (TOCP) is a synthetic organophosphate compound used in the manufacture of hydraulic fluids, lubricants, and plastics. It is a potent neurotoxin, and thousands of cases of neuropathy have occurred from its consumption. Most outbreaks have resulted from contamination or adulteration of foods, cooking oils, or alcohol with TOCP. One of the best-known examples is the Jamaica ginger paralysis, which affected thousands in the United States during Prohibition years, when TOCP was found in illicit liquor.
Similar neuropathies occur with exposure to organophosphates used as pesticides in agriculture, such as chlorophos and mipafox (see Chapter 11 ). In these cases, a predominantly motor neuropathy evolves in a few days, leading in severe cases to flaccid quadriplegia. A distinctive feature is the latency of 1 to 2 weeks from the time of ingestion of the organophosphate to the onset of neuropathy. In the case of pesticide ingestion, cholinergic crisis precedes the neuropathy, with diarrhea, sweating, fasciculations, and convulsions. Although the acute neurologic picture is one of severe generalized polyneuropathy, as patients recover, signs of upper motor neuron dysfunction emerge. No specific therapy is available. Patients with mild or moderately severe disease make a gradual and often incomplete recovery. Severely involved patients are left with spastic weakness.
[edit] Thallium Poisoning.
Poisoning with thallium, a heavy metal, is distinctly unusual today. The most common sources are thallium-containing rodenticides such as Gizmo mouse killer, Zelio paste, or Senco corn mix, ingested accidentally by children or for suicidal purposes. The neuropathy that evolves closely resembles acute inflammatory polyneuropathy with autonomic disturbances. Nausea and vomiting may precede the neuropathy. Some patients are encephalopathic, with clouded consciousness and seizures. Alopecia, the telltale sign of thallium intoxication, appears 2 to 4 weeks after ingestion. The diagnosis is established by detecting thallium in a 24-hour collection of urine, and it can also be found in the blood and saliva.
Vigorous supportive therapy is the mainstay of treatment, as outlined in the section on acute inflammatory polyneuropathy. The chelating agents helpful in treating poisoning by other heavy metals are not effective for thallium. However, Prussian blue (potassium ferric ferrocyanote II), an ion exchange resin, is said to help prevent or minimize evolution of the neuropathy, although it is not useful once the neuropathy is established. Prussian blue forms a complex with thallium in exchange for potassium, and the complex is excreted in the gut, thus decreasing the absorption of thallium. This treatment should be combined with a laxative. Early treatment with Prussian blue has decreased severe residual neurologic disability. Alopecia recovers fully and spontaneously.
[edit] Polyneuropathy of Critical Illness.
An acute, severe, generalized axonal polyneuropathy may occur in patients critically ill with prolonged sepsis, multiple organ failure, and hypoalbuminemia. Failure to wean the patient off the ventilator often brings the weakness to attention. Examination reveals generalized areflexic quadriparesis with muscle atrophy; nerve conduction studies show an axonal neuropathy, and CSF remains normal. With supportive therapy, surprisingly good recovery of the neuropathy is the rule, although improvement may take several months. The pathogenesis is uncertain but appears to be related to complex toxic-metabolic systemic derangements.
[edit] Acute Motor Demyelinating Neuropathies
[edit] Acute Inflammatory Polyneuropathy (Guillain-Barré Syndrome).
The other important demyelinating peripheral neuropathy, and the most common form of acute polyneuropathy encountered, is that described by Landry and later by Guillain, Barré, and Strohl, and which is known as Guillain-Barré syndrome, postinfectious polyneuropathy, or acute inflammatory polyneuropathy (AIP).
[edit] Etiology.
This condition commonly follows a viral or mycoplasmal illness affecting the upper respiratory or alimentary tracts, vaccination, or surgery, or it may complicate an underlying malignancy such as Hodgkin's disease. Because infections seem to have occurred in the preceding 2 weeks in about half of the cases seen, the term postinfectious polyneuropathy is preferred by some. Increased titers of IgM antibodies to Epstein-Barr virus, CMVs, and other viruses have been reported and, rarely, connective tissue diseases such as SLE and polyarteritis nodosa and malignancies such as Hodgkin's disease trigger the autoimmune process. The syndrome has also heralded HIV-1 seroconversion. The enteric infection Campylobacter jejuni is the cause of an identical but usually very severe syndrome, with neuronal degeneration rather than demyelination as the basis. Both genders are equally involved. AIP occurs at any age but most commonly in adults over age 40. It is a polyradiculopathy, which means that the brunt of the acute allergic response is seen in the spinal (or cranial) nerve roots. Here, intense round cell infiltration is seen, extending distally in the nerves with accompanying demyelination caused by Schwann cell damage.
[edit] Clinical features.
The onset is acute or progressive over a week or two. Complaints of paresthesia, numbness, muscle tenderness, and weakness appear in that order, initially in the legs. There is no fever. Weakness is usually but not always symmetric and may progress to any degree of severity, from minimal weakness in the legs to profound quadriparesis with respiratory and bulbar failure, which occurs in about 10% of cases. The distal muscles are usually involved first and the disease normally spreads centrally, although rarely the reverse is the case. The bladder is never much affected, and although facial involvement is common, the eyes are seldom involved.
Examination shows mainly motor findings consisting of flaccid weakness peripherally with areflexia. The face is especially affected, with at least weakness of eye closure. Power also may be lessened or lost proximally in the girdle muscles, trunk, and bulbar muscles, or these areas may escape entirely. Wasting occurs early in the affected limbs. Sensory findings are minimal, but pain may be severe.
Autonomic features represent a dangerous complication. Tachycardia, postural hypotension, pupillary disturbances, hyperhidrosis, and lack of variation in the inter-beat interval (measured by the R-R interval on an electrocardiogram [ECG] with deep breathing) signifying the need for ECG and blood pressure monitoring are the most common, but paroxysmal atrial or ventricular tachycardia and various bradyrhythmias and wide swings of blood pressure have been documented. Sphincter control and mental clarity are usually retained.
In a malignant form of AIP, there is early involvement of the cranial nerves and trunk with bulbar palsies and respiratory failure. In all, up to 20% of patients develop some degree of ventilatory inadequacy caused by involvement of the diaphragm and intercostal muscles. Because it cannot be predicted who will develop this severe form of the disease and who will not, all patients with AIP must be admitted to the hospital until at least the first signs of recovery appear.
Uncommon variants of AIP produce ophthalmoplegia, ptosis, facial weakness, limb ataxia, and areflexia with little systemic weakness (Miller Fisher syndrome); an acute sensory neuropathy; acute dysautonomia; or acute ataxia of gait and limbs without weakness or sensory loss, presumably from denervation of muscle spindles.
[edit] Investigations.
The CSF protein level is initially normal but rises as the disease progresses. Protein values are often above 2 g/L eventually, but the cell count is normal, a fact serenaded by the euphonious French term dissociation cytoalbuminologique. In cases associated with HIV-1 seroconversion, moderate lymphocytosis may be found. Occasionally, the protein level exceeds 10 g/L, producing a Froin's syndrome of xanthochromic, acellular CSF that clots spontaneously. Electrodiagnostic studies show slowing or loss of late responses; later in the illness there is marked slowing of motor nerve conduction velocities.
[edit] Course.
The recovery period is prolonged; over half of the patients are completely better by 6 months and three fourths within 1 year. But continuous weakness, malaise, and easy fatigability trouble the remainder, and in a few patients recurrent attacks occur. Those patients who begin to recover in the first 2 weeks after onset usually do so completely.
Fatalities occur in 5% of cases because of ventilatory failure, pneumonia, cardiac arrhythmias, or autonomic failure. These deaths should be preventable with intensive nursing and medical care; one must be vigilant for any hint of respiratory involvement during the early stages. In any patient diagnosed as having AIP, the vital capacity should be repeatedly measured.
[edit] Differential diagnosis.
The syndrome of AIP is the most important cause of acute severe progressive motor peripheral neuropathy. Other causes include acute porphyria, diphtheria, tick paralysis, hypokalemia and hyperkalemia, and organophosphate and lithium toxicity. Note also that myasthenia gravis may present in a similar way.
[edit] Management.
In the acute stages, attention to the airway, prevention of respiratory infections, and watchfulness for autonomic disturbances (such as acute hypertension) are the most important measures. Frequent passive limb movement to prevent contractures, subcutaneous heparin injections to prevent deep vein thrombosis, and oral quinine (300 mg daily for pain) are useful. Steroids are of no benefit (they may be harmful), but both intravenous immunogammaglobulins (IVIg; 0.4 mg/kg/day, repeated over 5 days) and plasma exchange are valuable therapies. All patients with significant weakness should be considered for IVIg therapy, and if there is still progression of weakness after the treatment, plasma exchange should be considered.
Monitoring of vital functions is essential at all times in the evolution of the disease, and patients should be cared for at least within easy distance of an intensive care unit because ventilatory support is essential for the severely affected patient. A fall in vital capacity to 25% of the predicted value, or below 1000 ml, is an indication for intubation. One must also pay attention to fluid and electrolyte status and monitor for such complications as cardiac arrhythmias, inappropriate ADH secretion, and hypertension or hypotension. The latter should never should be treated with sympathomimetics because of the denervation hypersensitivity present. Endotracheal intubation should be performed promptly when pulmonary function shows deterioration or bulbar paralysis occurs. Even with modern endotracheal tubes, tracheostomy may be necessary if the ventilatory weakness persists beyond 10 days.
Nutrition is best provided through a nasogastric tube if there is any bulbar weakness. For all patients, psychologic support is essential. Some patients are unable to move at all and need tremendous attention, support, and repeated assurance that they will indeed regain muscle power. Successful management of such a case is a triumph of medical and nursing care.
In all cases, positioning of the weakened patient is important to protect against pressure palsies of the ulnar, peroneal, and sciatic nerves; otherwise the patient recovers from AIP only to be left with a drop foot or hand weakness from secondary compression. Similar care must be taken to maintain the feet in dorsiflexion to prevent contractures.
[edit] Other Acute Motor Neuropathies.
In diphtheria, lead poisoning, and porphyria the signs are almost entirely motor and often proximal.
[edit] Chronic Motor Axonal Neuropathies
[edit] Hereditary Neuropathy.
Hereditary motor neuropathy (HMN) is the term now used for what used to be called the spinal muscular atrophies, also known by the terms Werdnig-Hoffmann disease and Wohlfart-Kugelberg-Welander syndrome.
HMNs are common, have varied modes of inheritance, and share degeneration of the lower motor neuron as their primary pathology. Severity of the disorder varies with the age of onset. Infantile onset presages rapid progression and early death; the later the onset, the more benign the course.
Evidence of the condition may appear before birth. Mothers of affected infants often comment on reduced fetal movements in the last trimester of the pregnancy. The infant will show proximal or distal symmetric weakness and wasting with hypotonia and anergy, respiratory and feeding problems being marked. Fasciculations are seen in only half of the babies because the fat layer obscures them. Reflexes are depressed. Muscle contractures and aspiration pneumonitis are common complications. When the onset is in childhood, pelvic girdle weakness causes a waddling gait and problems in climbing stairs; arm weakness is due to involvement of the shoulder girdle muscles, and scoliosis is related to trunk weakness. In adults, girdle weakness and wasting with fasciculations and hyporeflexia produce similar features but progress slowly.
Diagnostic confirmation depends on muscle biopsy; an electromyogram (EMG) is of confirmatory value, but serum creatine kinase (CK) levels are only slightly elevated. Only supportive treatment is available. Without muscle biopsy, HMN is easily misdiagnosed as limb girdle dystrophy. Uncommonly, other patterns of weakness and wasting in HMN mimic fascioscapulohumeral or distal myopathies. In all adult cases, differentiation from motor neuron disease such as amyotrophic lateral sclerosis (ALS), syringomyelia, and other conditions that affect the cord, such as trauma, myelitis, and tumor (these latter damaging the anterior horn cells in the cord), is necessary. Most of these conditions are considered elsewhere in this book. The history or accompanying evidence of central nervous system (CNS) dysfunction allows a reasonable chance of making the correct diagnosis clinically, but in other cases, diagnosis is only possible with time and with the detection of corticospinal tract signs.
[edit] Acquired Neuropathy.
Acquired chronic axonal motor neuropathies are few; multiple system atrophy (see Chapter 169 ) and motor neuron disease (see Chapter 170 ) are discussed elsewhere.
[edit] Subacute Motor Neuropathy.
Subacute motor neuropathy is a rare disorder that is a mirror image of paraneoplastic sensory neuropathy. It is associated with lymphoma, rather than lung cancer, and with Waldenström's macroglobulinemia. A subacute weakness affects distal and proximal muscles of limbs and sometimes of the neck with areflexia but without sensory impairment. In contrast to the bleak prognosis of the sensory form, this neuropathy often spontaneously recovers over 1 to 3 years, independent of the activity of the underlying neoplasm.
[edit] Chronic Demyelinating Motor Neuropathies.
Motor polyneuropathies may occur in rheumatoid arthritis and polyarteritis nodosa, but multiple mononeuropathy is a more common presentation. Chronic inflammatory demyelinating neuropathy is a variant of the acute form, in which there is either recurrence after successful initial treatment or impaired response to that therapy. Multifocal motor neuropathy with conduction block presents in a manner very similar to ALS, from which it is differentiated by nerve conduction studies that show scattered slowing of motor nerve conduction velocities. The syndrome has been defined in young adults and is associated with high serum levels of antibodies against GM1 ganglioside (anti-GM1 antibodies). There are no upper motor neuron or bulbar signs, and the course is indolent. Intravenous cyclophosphamide therapy has produced significant improvement.
[edit] Mainly Sensory Neuropathies
[edit] Acute Axonal Sensory Neuropathies.
The prototype of acute axonal sensory neuropathy is the acute inflammation of dorsal root ganglion cells that occurs with herpes zoster, but this form usually affects the V nerve or a few dermatomes at most and so is really a radiculopathy or mononeuropathy. Systemic causes include polycythemia, lymphoma, carcinoma, and acute sensory neuropathy, a form of acute inflammatory polyneuropathy with mainly sensory rather than motor changes. Poisoning with cisplatin and inflammation of the dorsal root ganglion cells as a toxic effect of penicillin, Adriamycin, or mercury are other causes.
[edit] Chronic Axonal Sensory Neuropathies
[edit] Hereditary.
In most hereditary forms of chronic axonal sensory neuropathies mild but progressing centripetal sensory loss that affects thin-fiber and thick-fiber functions brings the patient to the doctor. Complaints of girdle pains, atrophic changes in the feet, and imbalance are also common. In the uncommon hereditary sensory and autonomic neuropathies (HSAN) either all forms of sensation are absent from birth (recessive variety, type 2) or pain and temperature loss develop insidiously in the second decade (dominant form, type 1). Numerous other variants with added neurologic problems are described. Lancinating pains are common in the early stages but respond to dilantin, carbamazepine, or a tricyclic. The loss of pain and position sense can lead to terrible mutilation. Motor weakness and wasting may accompany the sensory loss in the dominant form. Obsessive care of the feet and hands is the only prophylactic measure available.
Friedreich's ataxia and the other spinocerebellar degenerations involve the dorsal root ganglia also, and the degeneration of the peripheral axons could be regarded as a neuropathy.
[edit] Acquired.
When the dorsal root ganglion cells are primarily involved, one must consider tabes dorsalis, vitamin B12 deficiency (subacute combined degeneration of the cord), and a paraneoplastic syndrome (usually from an oat-cell carcinoma of the bronchus, carcinoma of the breast, or lymphoma). Acromegaly, hypothyroidism, malabsorption syndromes, polycythemia, primary biliary cirrhosis, uremia, Lyme disease and poisoning with arsenic, hydralazine, N2O, metronidazole, misonidazole, cisplatin, and pyridoxine are other causes.
[edit] Polyneuropathy of Vitamin B12 Deficiency.
Peripheral neuropathy is one neurologic syndrome resulting from vitamin B12 deficiency. The initial symptoms are sensations of pins and needles and numbness in the feet and later (seldom initially) in the hands. The initial impression is of a peripheral neuropathy, because of the depressed or absent ankle reflexes and a stocking-distribution impairment of touch and pinprick. However, there are also signs of myelopathy with loss of proprioception and pyramidal signs in the legs. Romberg's sign is positive.
The diagnosis is est