Video 51.1). Significant atrophy can occur in the affected muscles. The pain usually lessens within 3 to 6 weeks. Sensory loss and weakness improve over months, but long-term deficits may persist. The acquired form tends not to recur but the familial form can.

Differentiation from cervical radiculopathy requires cervical spine imaging. Imaging of the plexus may show signal enhancement or enlargement in the affected portions. In a plexus lesion electro diagnostic studies show acute denervation on needle EMG in limb muscles but sparing of the parapinals. The postradiation type lesion often shows myokymic discharges in the needle exam. Conduction studies show low amplitude sensory nerve action potentials in affected nerves, a finding that also helps distinguish plexopathy from radiculopathy. Sensory action potentials should be normal in radiculopathy.

2.  Treatment. The lesion is presumably inflammatory in nature but treatment with oral or intravenous corticosteroids have shown no consistent benefit in small trials. The pain is often poorly responsive to even major analgesics but should be managed symptomatically as best as possible. The pain improves over several months. Pain is usually not a prominent feature of the postradiation plexopathy. The motor and sensory deficits in this specific condition slowly worsen over many years. No specific treatment is available.

TOXIC OR METABOLIC POLYNEUROPATHIES

A.  Alcoholic neuropathy is a sensorimotor polyneuropathy that primarily affects the distal legs but can also produce mononeuropathies.

1.  Clinical features and diagnosis. The onset of the polyneuropathy is insidious, and progression takes place over months or longer. Sensory symptoms include numbness, paresthesia, and fiery pain. Motor abnormalities in the form of deficits of toe abduction or extension are present in many patients. Foot drop can occur in more advanced cases. Electro diagnostic studies show a pattern of axonal disease. Supporting laboratory findings include liver enzyme abnormalities and red cell macrocytosis.

2.  Treatment consists of discontinuance of alcohol and establishment of an adequate diet plus supplementation of the diet with thiamine at 100 mg/day. Improvement takes place over months. Unstable walking resulting from concomitant alcoholic cerebellar disease recovers less well than the neuropathy and can limit overall improvement.

B.  Critical illness polyneuropathy occurs in patients who experience severe episodes of sepsis and multiorgan failure that require days to weeks of treatment in the intensive care unit.

1.  Clinical features. The neuropathy typically becomes evident when respiratory support is withdrawn and the patient remains severely weak. Sensory loss may be found in patients with sensorium clear enough for a detailed neurologic examination. GBS is often considered in this setting. The CSF protein content tends to be normal in critical illness polyneuropathy in contrast to the latter. NCS show axonal rather than demyelinating patterns. Critical illness myopathy can also occur in this same setting. This condition is distinguished from the neuropathy by the finding of normal sensory examination and normal sensory NCS. The myopathy patients have often received high-dose corticosteroids and nondepolarizing neuromuscular blocking agents as part of the ventilator support during the critical illness.

2.  Treatment. Management is supportive. Recovery occurs over months. Aggressive management of hyperglycemia, which can occur in the acute phase of the critical illness, appears to lessen the occurrence of this neuropathy.

C.  Diabetic neuropathy can appear in several different forms, which are not mutually exclusive. Other than optimal control of blood glucose levels there is still no specific therapy for biochemical abnormalities underlying the neuropathy. The principles of general symptom management outlined in Section Symptom-Based Management should be followed.

1.  Sensorimotor polyneuropathy causing bilateral foot numbness with or without a painful component is the most common type of diabetic neuropathy. Good control of blood glucose is the foundation of management, but neuropathic symptoms may still develop.

2.  Lumbosacral plexopathy, also termed diabetic amyotrophy or radiculoplexus neuropathy, is a distinctive syndrome (see Chapter 25). The condition usually begins with spontaneous unilateral pain in the low back, hip, or proximal leg. The pain can become severe over the next week or two. A few weeks after onset of the pain, paresthesia and sensory loss appear in the thigh and at times in the medial lower leg. Weakness most often affects the quadriceps and appears about the same time as the sensory loss. Notable muscle atrophy can occur in the affected muscles. The pain is often only partially responsive to even major analgesics but tends to begin improving within a month or two after onset. Considerable weight loss may occur with this condition. Occasionally, as the initially involved side is improving, the opposite side becomes involved. The long-term prognosis tends to be good, but recovery can extend over a year or more. Some patients have persisting motor deficits. Several small series in the literature suggest that a course of IVIG or corticosteroids by the oral or intravenous route may shorten the course of this syndrome.

3.  Thoracic radiculopathy is somewhat similar to lumbosacral plexopathy in terms of onset and time course. Unilateral band-like pain in the chest or upper lumbar region is the main symptom. The pain can be severe. Cutaneous hypersensitivity that makes the touch of clothing uncomfortable in the involved area also may be reported. Localized weakness of the lateral or anterior abdominal muscles may produce localized bulging of the abdominal wall. Analgesics can provide at best partial relief. Gabapentin and tricyclic antidepressants may partially improve the pain. Local anesthetic nerve blocks or topical lidocaine patches in the involved dermatome may help to some degree, as can use of a transcutaneous electrical nerve stimulation unit. The pain persists for some months but eventually resolves or greatly improves.

MEDICATION-INDUCED POLYNEUROPATHIES

A.  Medication-induced polyneuropathy can occur during treatment for neoplasms, autoimmune disorders, chronic infections, and cardiac arrhythmia. Vincristine, paclitaxel and docetaxel, cis and carboplatinum, and bortezemab are the antineoplastic drugs most often associated with neuropathy. Colchicine, hydroxychloroquine, leflunomide, and thalidomide used for treatment of inflammatory and autoimmune disorders can cause neuropathy. The antibiotics dapsone, isoniazid, metronidazole, and nitrofurantoin have been reported to cause neuropathy. The antiarrythmic amiodarone can cause neuropathy.

1.  Clinical features. All of these except the platinum-based medications produce a sensorimotor neuropathy and the sensory deficits are usually the prominent features. The platinum compounds tend to affect only sensory neurons and can produce both sensory loss and ataxia. A significant painful component may develop with vincristine and bortezemab. If sensory deficits progress proximally to the mid-shin and fingertip levels, foot drop and weakness of the intrinsic hand muscles can occur. The occurrence and severity of chemotherapy-related neuropathy tend to be dose related and usually begin after several cycles of administration. Neuropathy may develop or worsen after completion of the chemotherapy. This pattern is termed “coasting.” Neuropathies related to antibiotics and the rheumatologic modulating agents tend to occur after prolonged exposure except for nitrofurantoin, which can produce an acute syndrome similar to GBS. Amiodarone-related neuropathies occur after prolonged exposure.

2.  Treatment. When repeated or prolonged use of the medication is required for treatment of the primary illness, lengthening of the interval between chemotherapy treatment or reduction of the dose at each treatment may allow the neuropathy to stabilize. When neuropathy is related to antibiotic, rheumatologic agent or amiodarone use the medication has to be stopped. Improvement is the expected course but the time interval may extend over many months. Symptoms should be managed as described above in Section under Symptom-Based Management.

POLYNEUROPATHIES DUE TO INFECTIONS

A.  Lyme disease can produce several different types of peripheral neuropathy. The bites of certain ticks of the Ixodes genus (e.g., Ixodes dammini, most often) transmit the infectious agent Borrelia burgdorferi. Endemic areas include southern New England and the Mid-Atlantic states, the central regions of Wisconsin and neighboring states, and north coastal California plus Oregon.

1.  Clinical features. The characteristic skin lesion erythema chronic migraines develops 3 to 20 days after the bite, as does a general flu-like syndrome of fever, malaise, and myalgia. The skin lesion occurs in approximately 80% of cases. Frank neurologic involvement occurs in approximately 15% of cases and tends to appear 1 to 3 months after the initial infection in the time frame termed the early disseminated phase of the illness. Less specific symptoms of headache occur in more than half of patients. A positive serologic result for antibodies against the infectious agent is helpful for establishing the cause, but test results may be negative for a month or so after the initial infection. An ELISA or immunofluorescence assay should be done first and if positive be followed up by an immunoblot test for IgM or IgG antibodies. The latter test helps to identify false-positive results.

2.  Treatment. Antibiotic treatment appears to relieve all of the manifestations, either by shortening the duration of episodes or by alleviating more persistent symptoms such as polyneuropathy. Oral antibiotics can be used to manage the rash and flu-like phase of the initial stage of the infection. For adults, doxycycline 100 mg twice a day, amoxicillin 500 mg three times a day, or cefuroxime 500 mg twice a day for 2 to 3 weeks are recommended. PNS and central nervous system (CNS) manifestations are best managed with intravenous penicillin G, 20 million U/day, or ceftriaxone, 2 g daily for the same 2 to 3 weeks.

3.  Types of neuropathy of the early disseminated phase.

a.  Facial nerve involvement produces typical peripheral facial nerve palsy (often resembling Bell’s palsy), including pain in the ear region. Bilateral facial nerve involvement occurs more frequently with Lyme disease than in the idiopathic form.

b.  Radiculitis producing a syndrome similar to that described for diabetic thoracic radiculopathy (see Section C.3 under Toxic or Metabolic Polyneuropathies) and consisting of dermatomal pain, which can reach a high level of intensity, sensory loss, and focal weakness. Limb as well as truncal spinal segments can be involved.

B.  Human immunodeficiency virus (HIV) infection can be associated with several types of peripheral neuropathy.

1.  Typical acute inflammatory demyelinating neuropathy (GBS) can occur early in the course of the infection. CSF pleocytosis with white cell counts of 10 or more is the only feature that distinguishes this form from the idiopathic variety. Therapy should be the same as for the idiopathic form of the disorder (see Section A.3 under Diagnosis and Management of Specific Conditions).

2.  Distal symmetrical polyneuropathy with predominant painful symptoms can also occur in up to a third of patients and is more likely when viral load becomes greater than 10,000 copies per mL. Patients report painful paresthesia consisting of pressure- or burning-type sensations in the feet and distal legs. The hands can be involved to a lesser extent. Weakness is minimal. CSF tends to be normal to minimally abnormal. NCS show a pattern of axonal damage. Management of this type of neuropathy is symptomatic only, and the general guidelines for painful neuropathy presented in Section A under Symptom-Based Management. should be followed. A similar type of neuropathy can occur in patients being actively treated with high-activity antiretroviral therapy (HAART). This type neuropathy has symptoms and signs very similar to those produced by the HIV infection. A potential clue that the neuropathy is treatment-related is its appearance after HAART has been begun. Dosage reduction or substitution of potentially less neurotoxic medications should be considered if the status of the infection permits.

3.  Polyradiculitis resulting from infection by cytomegalovirus (CMV) is another distinctive form of neuropathy that affects patients with AIDS in the advanced stage of the illness. Patients report pain and weakness in the lower extremities and the back. The onset may be asymmetrical but becomes bilateral within days to weeks. Sensory loss develops in the limbs and perineal area. Bladder and bowel incontinence are also regular features. Progression to arm involvement is infrequent. CSF shows pleocytosis and elevated protein level. Pathologic specimens show inflammation of the nerve roots of the lumbar and sacral areas. Treatment with ganciclovir and foscarnet may stabilize the condition, but this lesion tends to be a poor prognostic indicator.

C.  Inherited polyneuropathies.

A genetic etiology should always be considered in patients with neuropathies which evolve over many years and for which another etiology is not obvious.

1.  Clinical features of a length-dependent motor greater than sensory neuropathy is typical but multifocal pattern occurring over many years is seen in the hereditary liability to pressure palsy variant. Bothersome paresthesia and neuropathic pain tend to not be present. Anatomical features like abnormally high foot arches and hammer toes further support a genetic etiology. A dominant pattern of inheritance is most common but X-linked and recessive patterns also occur.

NCS tend to show demyelinating features that are often more uniform in degree from one nerve to the next in contrast to acquired demyelinating conditions in which action potential dispersion is the more common finding. Genetic studies available through commercial testing labs can help make a specific diagnosis.

2.  Treatment. Ankle bracing may be required for foot drop. Significant hand weakness may be partly compensated for by input from occupational therapy.

NEW DEVELOPMENTS IN PERIPHERAL NEUROPATHY

A.  Small fiber neuropathy. This diagnosis is being more commonly considered in the differential diagnosis for patients who have widespread pain. Fibromyalgia is often the alternate clinical diagnosis.

1.  Clinical features. A formal definition of small fiber neuropathy has not been established. The following parameters have been suggested: spontaneous and stimulus evoked pain, deficits in pain and temperature sensation on clinical examination, preservation of light touch, position and vibration sensory functions, normal limb strength and reflexes, abnormalities in the autonomic domains of cardiovagal, adrenergic and sweat gland function, abnormalities in cold and warm sensory functions in quantitative sensory testing and decrease in the number of epidermal nerve fibers in skin biopsies. Potential etiologies include glucose intolerance, autoimmune conditions like Sjögren’s syndrome, and hepatitis C. Many cases remain idiopathic.

2.  Treatment. Managing symptoms is the mainstay of treatment. Identifiable etiologies like impaired glucose tolerance and autoimmune disorders should be managed as best as possible. At this point in our knowledge of this disorder, I consider treatment of idiopathic cases by immune-modulating treatments such as IVIG to be inappropriate.

B.  Amyloid neuropathy.

Although amyloidosis is a very rare cause of polyneuropathy the advancements in the treatment of familial amyloid neuropathy (FAP) which result from mutations in the transthyretin protein provide an exciting example the potential for direct treatment of a neuropathy. FAP results from deposition of protein fibrils composed of normal and mutant transthyretin. The peripheral nerve and cardiac tissue are the most common sites of pathological accumulation. The typical neuropathy involves small and then large fiber modalities. The accompanying cardiomyopathy can be fatal. Liver transplantation has been the mainstay of therapy for reducing production of the abnormal protein but over the last 5 years several compounds have been discovered which can either alter the potential for deposition of or synthesis of the abnormal protein. The use of oligonucleotide mechanisms to suppress production of the abnormal protein by the liver is the focus of the most recent research.

Related posts:

Approach to the Patient with Gait Disturbances and Recurrent Falls Approach to the Patient with Acute Sensory Loss Multiple Sclerosis Approach to the Patient with Sleep Disorders Approach to the Patient with Chronic and Recurrent Headache Neuroimaging of Common Neurologic Conditions

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