CIDP = chronic inflammatory demyelinating polyradiculoneuropathy; CMT = Charcot-Marie-Tooth disease; HIV = human immunodeficiency virus; HNPP = hereditary neuropathy with liability to pressure palsy.

* Include diabetes mellitus, uremia, thyroid disorders.

It is important to try defining the predominant pathophysiologic mechanism of the polyneuropathy, though the clinical examination is often unable to discriminate between a primarily axonal and demyelinating polyneuropathy. Demyelinating polyneuropathies have a limited number of etiologies, while the causes of axonal polyneuropathies, particularly those that are chronic and affect the sensory and motor axons, are numerous (Table C26-2).

Table C26-2 Common Causes of Chronic Symmetrical Axonal Peripheral Polyneuropathies

CMT = Charcot-Marie-Tooth disease; HIV = human immunodeficiency virus; HTLV1 = human T lymphotropic virus type 1; MGUS = monoclonal gammopathy of unknown significance; SLE = systemic lupus erythematosus.

Alcoholic Polyneuropathy

Chronic alcoholism is a relatively common cause of generalized sensorimotor polyneuropathy. The incidence of alcoholic polyneuropathy is unknown, but is likely underestimated since many asymptomatic alcoholic patients have physical or EDX signs of polyneuropathy. The incidence ranges from 9 to 30% among hospitalized alcoholics, and up to 90% of ambulatory alcoholics may have EDX evidence of neuropathy. Alcoholic polyneuropathy almost always occurs on a background of nutritional deficiency, particularly thiamine (vitamin B1) deficiency, and its clinical features are almost identical to beriberi. A history of poor nutrition is often present, and the diet of alcoholics is usually high in carbohydrates and low in vitamins. Moreover, alcoholics have a reduced capacity to absorb thiamine. Since the total lifetime dose of alcohol is an important factor in neuropathy, a direct neurotoxic effect of alcohol on peripheral nerves remain a possibility and cannot be totally excluded.

The clinical manifestations of alcoholic polyneuropathy are typical of a length-dependent generalized, sensorimotor polyneuropathy. The neuropathy is often asymptomatic and only detected by clinical or EDX examination. The symptoms begin usually symmetrically with numbness, paresthesias, and burning feet, followed by cramps, weakness, and sensory ataxia. The symptoms are chronic and usually evolve slowly over months or years. Overt manifestations of autonomic dysfunction, such as orthostatic hypotension, are relatively uncommon. Weight loss, often in the range of 30–40 pounds or about 10% of body weight, is common but not always present. The neurological examination discloses a sensory loss to most modalities and muscle weakness in the lower extremities in a distal to proximal gradient. Allodynia and calf tenderness may also be present. Areflexia or hyporeflexia is also worse distally. Findings of other neurological alcoholic-nutritional deficiency states may coexist, such as cerebellar degeneration or Wernicke-Korsakoff syndrome. The laboratory tests are most useful in excluding other causes of polyneuropathy. Macrocytic anemia, abnormal liver function tests, and MRI evidence of cerebellar atrophy are common supportive findings for alcoholism.

Alcoholic polyneuropathy is managed by abstinence from alcohol intake and enhancing diet with vitamin supplements including thiamine. Pain control with anticonvulsant or antidepressants may be necessary is some patients. The prognosis depends on the severity and duration of symptoms; patients with mild and recent symptoms are more likely to improve or recover.

Electrodiagnosis

The EDX testing is an essential diagnostic tool in peripheral neuropathies, being most useful when utilized as a direct extension of the neurological examination. In a patient with suspected peripheral polyneuropathy, the EDX study often:

1. Provides an unequivocal diagnosis of peripheral polyneuropathy.

2. Excludes mimickers of polyneuropathies such as L5 and S1/S2 radiculopathies, tarsal tunnel syndromes, carpal tunnel syndromes, and distal myopathies.

3. Defines the anatomic distribution of a neuropathy, as a single mononeuropathy, multiple mononeuropathies, or a generalized peripheral polyneuropathy.

4. Establish the type of fiber(s) affected (sensory, motor, or both).

5. Estimate the duration and activity of the neuropathy (acute, active (ongoing) or chronic).

6. Identify the primary pathophysiologic process (axonal loss, uniform demyelination, multifocal demyelination, or conduction block).

At the completion of the EDX study, the clinician should be able to better characterize the polyneuropathy and classify its pathophysiology. This helps establish a relatively short differential diagnosis and work-up aimed at identifying the cause of the neuropathy and planning its management (Figure C26-1).

Figure C26-1 A practical approach to peripheral neuropathy. CIDP = chronic inflammatory demyelinating polyneuropathy; HNPP = hereditary neuropathy with liability to pressure palsy; GBS = Guillain-Barré syndrome.

(Adapted with revisions from Asbury AK, Gilliatt RW. The clinical approach to neuropathy. In: Asbury AK, Gilliatt RW, eds. Peripheral nerve disorders. London: Butterworths, 1994).

Analyzing conduction times (velocities and latencies), as well as CMAP amplitude, area, and duration, is an essential exercise in the EMG laboratory for establishing the primary pathologic process of a polyneuropathy. In most situations, the polyneuropathy falls in one of the two categories based on which of the two primary nerve fiber components is dysfunctional: the axon or its supporting myelin. Occasionally, such as in very mild polyneuropathies or in severe situations associated with absent sensory and motor responses, it may be difficult to establish the primary pathology based on EDX studies.

• Primary axonal polyneuropathies (axonopathies) affect the axon primarily and produce a length-dependent dying-back degeneration of axons. These findings are first observed in the lower extremities but in more severe cases, similar alterations occur in the upper extremities. The major change on nerve conduction studies is a decrease, or absence in more advanced disease, of the CMAP and SNAP amplitudes, more marked in the lower extremities (see Figure C18–4B, Case 18). In contrast, conduction times (velocities, distal latencies, and F wave minimal latencies) are normal. Sometimes, there is a slight slowing of distal latencies, conduction velocities and F wave minimal latencies when the polyneuropathy is advanced (Figure C26-2). This is explained by the fact that the loss of axons is distributed in a random fashion, which results in survival of some thickly myelinated, fast-conducting fibers. Figure C26-3 reveals the theoretical distribution of conduction velocity in motor nerves of healthy patients and patients with axonal polyneuropathy. The random axonal loss results in survival of some, fast-conducting fibers leading to normal velocities. It is only when axonal loss is severe, surpassing 80% of the total population of axons, that slight slowing of velocities occurs. In these situations, conduction velocities should be no less than 80% of the lower limit of normal and the distal latencies should be no more than 120% of the upper limits of normal.

• Primary demyelinating polyneuropathies (myelinopathies) are, in contrast, characterized by significant slowing of conduction times (velocities, distal latencies, and F wave latencies) because the pathologic process results in myelin disruption (segmental and paranodal demyelination) which impedes saltatory conduction (see Figure C18–4C, Case 18). Commonly, the CMAP amplitudes are relatively preserved distally, although conduction blocks and dispersion are common in the acquired forms (such as chronic inflammatory demyelinating polyneuropathy). With distal stimulation, the CMAP is mildly reduced in amplitude because of temporal dispersion and phase cancellation. The distal latency is slowed (>120% of upper limit of normal) because of demyelination. With more proximal stimulation, the CMAP is much lower in amplitude, which results from temporal dispersion and conduction block along some fibers. The proximal conduction velocities are markedly slow (<80% of lower limit of normal) because of increased probability for the action potentials to pass through demyelinated nerve segments (see Case 18). Caution should be taken when evaluating for conduction block and slowing in the demyelinating range in peripheral nerves with very low distal CMAPs (<20% of the lower limit of normal or <1 mV).