Laboratory Evaluation

There is no specific laboratory study or serum marker for the diagnosis of peripheral neuropathy. Information from the history and physical examination may direct specific laboratory tests (e.g., testing for specific toxins, infections, or inflammatory disorders). If the cause of neuropathy is not obvious, some screening laboratory studies should be considered: ESR, CBC, LFTs, and determination of fasting blood glucose, glycosylated hemoglobin, BUN, creatinine, serum vitamin B12, and TSH levels. Additional studies may be warranted, depending on the initial workup, such as chest radiograph to rule out sarcoidosis, pulmonary function tests for GBS, or ECG for processes that affect cardiac conduction. An LP for CSF showing an elevated protein level with normal white blood cells (WBCs) may indicate an acquired inflammatory neuropathy (GBS or CIDP).

Box 42-14 Small-Fiber Neuropathies

Diabetes HIV/AIDS

Leprosy Amyloidosis

Hereditary Alcoholism

HIV/AIDS, Human immunodeficiency virus/acquired immunodeficiency syndrome. Modified from Poncelet AN. An algorithm for the evaluation of peripheral neuropathy. Am Fam Physician 1998;57:755.

Electromyography (EMG) and nerve conduction studies (NCS) are probably the most useful laboratory studies for the evaluation of peripheral neuropathy and should be considered early. They can confirm the presence of peripheral neuropathy and provide information about the type of fibers involved (sensory, motor, or both) and whether the problem is symmetric, asymmetric, or multifocal. EMG can define entrapment neuropathies and differentiate these from more proximal radicular compression. It can also help differentiate muscle wasting caused by neuropathic or myopathic disorders from simple disuse atrophy. NCS can help define pathophysiology (axonal loss vs. demyelin-ation). EMG and NCS are useful but have limitations and should complement the history and examination. EMG is usually not as helpful in diseases that cause a diffuse small-fiber peripheral neuropathy, in which only pinprick and temperature sensation are affected (Box 42-14). In fact, the electromyogram may be normal. EMG needles also mildly inflame the muscles into which they are inserted. Thus, if a muscle biopsy is anticipated, that muscle should not be tested with EMG (Corse and Kuncl, 1999). NCS are most diagnostic with diseases affecting large, fast fibers and thus may be normal in patients with small-fiber neuropathies. Evaluation of small, proximal sensory nerves is not reliably done using EMG or NCS.

Nerve biopsy is helpful only in specific cases and is usually a last step in the workup. This includes patients with suspected amyloidosis, vasculitis, leprosy, leukodystrophies, sarcoidosis, or demyelinating disorders. Because the sural nerve, a sensory nerve, is generally used, disease affecting only motor nerves may be missed. Possible complications include permanent numbness or dysesthesia in the distribution of the excised nerve (typically lateral heel and ankle), infection, and poor wound healing.

In the evaluation of neuropathies, a carefully performed history that identifies key features of the presentation correlated with the findings of electrodiagnostic studies is the critical first step in developing a reasonable diagnosis. Questions include the following:

• Is the pattern of involvement focal or multifocal (Box 42-15)?

• Is the pattern symmetric (Boxes 42-16 and 42-17)?

• Did symptoms evolve acutely, subacutely, or chronically? Was there a predilection for the upper extremities (Box 42-18)?

• Were the extremities affected in a distal versus a proximal distribution (see Boxes 42-16 and 42-17)?

• Are the symptoms sensory, motor, or both (Box 42-19; see also Boxes 42-16 and 42-17)?

• Is there autonomic or cranial nerve involvement (Boxes 42-20 and 42-21)?

Box 42-15 Neuropathies by Pattern of Involvement

Focal

Multifocal

Common entrapment neuropathies:

Diabetes mellitus

Endocrine

Vasculitis

Myxedema

Polyarteritis nodosa

Acromegaly

Churg-Strauss syndrome

Hypothyroidism

Giant cell arteritis

Diabetes

Wegener's granulomatosis

Infection/inflammation

Rheumatoid arthritis

Septic arthritis

Sjögren's syndrome

Lyme disease

Systemic lupus erythematosus

Tuberculosis

HIV (e.g., cytomegalovirus)

Histoplasmosis

Leprosy

Sarcoidosis

Sarcoidosis

Rheumatoid arthritis

Cryoglobulinemia

Amyloidosis

Multifocal variant of CIDP

Tumors

Ganglion

Neurofibroma

Lipoma

Hemangioma

Congenital: Anatomic anomalies of

muscles, bones, vessels

Trauma

Fractures

Hematoma

Hemorrhage from anticoagulation

Pregnancy

Hemodialysis

Idiopathic

Occupational

Repetitive stress

Neoplastic infiltration or compression

Leprosy

Ischemic lesions

Diabetes mellitus

Vasculitis

GDP, Chronic inflammatory demyelinating polyneuroradiculopathy; HIV, human

1 immunodeficiency virus.

• What did the EMG and NCS show? Were other significant laboratory studies done? Taking this approach to peripheral neuropathies will prove to be more efficient and fruitful than less ordered approaches, despite the often elusive nature of these diagnoses.

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