An easy approach to evaluating peripheral neuropathy

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Applied Evidence

An easy approach to evaluating peripheral neuropathy

J Fam Pract. 2006 October;55(10):853-861

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References

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2. England JD, Asbury AK. Peripheral neuropathy. Lancet 2004;363:2151-2161.

3. Pourmand R. Evaluating patients with suspected peripheral neuropathy: Do the right thing, not everything. Muscle Nerve 2002;26:288-290.

4. Dyck PJ, Dyck PJB, Grant IA, Fealey RD. Ten steps in characterizing and diagnosing patients with peripheral neuropathy. Neurology 1996;47:10-17.

5. Barohn RJ. Approach to peripheral neuropathy and neuronopathy. Seminars Neurol 1998;18:7-18.

6. Rosenberg NR, Portegies P, de Visser M, Vermeulen M. Diagnostic investigation of patients with chronic polyneuropathy: evaluation of a clinical guideline. J Neurol Neurosurg Psych 2001;71:205-209.

7. Bromberg MB, Smith AG. Toward an efficient method to evaluate peripheral neuropathies. J Clin Neuromusc Dis 2002;3:172-182.

8. Hughes RAC, Umapathi T, Gray IA, et al. A controlled investigation of the cause of chronic idiopathic axonal polyneuropathy. Brain 2004;127:1723-1730.

9. Lacomis D. Small-fiber neuropathy. Muscle Nerve 2002;26:173-188.

10. Low PA, Vernino S, Suarez G. Autonomic dysfunction in peripheral nerve disease. Muscle Nerve 2003;27:646-661.

11. Burns TM, Taly A, O’Brien PC, Dyck PJ. Clinical versus quantitative vibration assessment: improving clinical performance. J Periph Nerv System 2002;7:112-117.

12. England JD, Gronseth GS, Franklin G, et al. Distal symmetric polyneuropathy: A definition for clinical research: Report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2005;64:199-207.

13. Thaisetthawatkul P, Collazo-Clavell ML, Sarr MG, Norell JE, Dyck PJ. A controlled study of peripheral neuropathy after bariatric surgery. Neurology 2004;63:1462-1470.

14. Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973. Diabetes Care 1978;1:168-188.

15. Singleton JR, Smith AG, Russell JW, Feldman EL. Microvascular complications of impaired glucose tolerance. Diabetes 2003;52:2867-2873.

16. Sumner CJ, Sheth S, Griffin JW, Cornblath DR, Polydefkis M. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology 2003;60:108-111.

17. Novella SP, Inzucchi SE, Goldstein JM. The frequency of undiagnosed diabetes and impaired glucose tolerance in patients with idiopathic sensory neuropathy. Muscle Nerve 2001;24:1229-1231.

18. Singleton JR, Smith AG, Bromberg MB. Painful sensory polyneuropathy associated with impaired glucose tolerance. Muscle Nerve 2001;24:1225-1228.

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21. Koike H, Mori K, Misu K, et al. Painful alcoholic polyneuropathy with predominant small-fiber loss and normal thiamine status. Neurol 2001;56:1727-1732.

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FAST TRACK

Recent evidence suggests that neuropathy can occur even in patients with impaired fasting glucose or impaired glucose tolerance

For example, laboratory testing for a distal, symmetric sensory polyneuropathy (TABLE 2) should be much different than testing for another presentation (eg, mononeuritis multiplex). TABLE 3 details some of the laboratory tests we recommend for the more common polyneuropathies that don’t typically present in a distal, symmetric sensory fashion or that are accompanied by other distinctive features. In our experience, clinicians too frequently order unnecessary and expensive tests for disorders only rarely associated with neuropathy; the rare causes of neuropathy are intentionally not the subject of this review.

TABLE 2
Common blood tests for the evaluation of a distal, symmetrical neuropathy^1,3,5,6,8

TEST	POTENTIAL CONFIRMATORY VALUE OF TESTS
Fasting glucose or 2-hour oral glucose tolerance test	Diabetes mellitus and possibly impaired glucose tolerance (“pre-diabetes”) cause neuropathy
Serum protein electrophoresis	Paraproteinemias, including monoclonal gammopathy of undetermined significance, Waldenstrom’s macroglobulinemia, and osteosclerotic myeloma, are often associated with a demyelinating neuropathy. Amyloidosis and mixed cryoglobulinemiacan also cause an axonal neuropathy
Chemistry profile	Uremic neuropathy
Hepatitis C titer	Hepatitis C is associated with neuropathy, particularly when associated with mixed cryoglobulinemia. This neuropathy usually presents asymmetrically and often as mononeuritis multiplex but sometimes as a distal, symmetrical neuropathy
Serum B₁₂ level	Vitamin B₁₂ deficiency may cause neuropathy, often in association with symptoms and signs of myelopathy

TABLE 3
Other diagnostic tests for acquired neuropathies in specific clinical situations^2,4,5,7

SUSPECTED PATHOLOGIC PROCESSES AND PERTINENT TESTS	POTENTIAL CONFIRMATORY VALUE OF TESTS
Metabolic/toxic
Complete blood count	Elevated MCV may suggest alcoholism, vitamin B₁₂ deficiency
Thiamine level	Thiamine deficiency (eg, alcoholics or following bariatric surgery)
Urine heavy metals	Heavy metal intoxication (rare; usually systemic symptoms too)
Thyroid function tests	Hypothyroid neuropathy (rare)
Inflammatory
Complete blood count	If systemic vasculitic neuropathy suspected (eg, patient presents with painful “mononeuritis multiplex”) systemic vasculitic neuropathy
Markers of vasculitis or systemic inflammation (ESR, ANCA, RF, ANA, ENA, cryoglobulins, etc)	Cryoglobulinemic neuropathy is associated with hepatitis C
Cerebrospinal fluid (CSF)	CSF protein elevation in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy
Neoplastic/paraneoplastic
Paraneoplastic serology (technique and scope of testing varies between different labs)	Neuropathy associated with cancer, especially subacute and severe neuropathic processes in smokers (eg, subacute sensory neuronopathy associated with small cell lung cancer)
Chest X-ray and other imaging for cancer	Small cell lung cancer or other malignancy
Cerebrospinal cytology	Carcinomatous or lymphomatous polyradiculopathy.
Infectious
Cerebrospinal fluid	CSF pleocytosis common in infectious polyradiculoneuropathies (Lyme, sarcoid, HIV)
Lyme titers (serum, cerebrospinal fluid)	Lyme neuroborreliosis
HIV testing	HIV-associated neuropathy
Hepatitis C (serum cryoglobulin testing)	Hepatitis C—mixed cryoglobulinemia

Common causes of distal, symmetric polyneuropathies

Distal, symmetric polyneuropathies are usually due to metabolic/toxic, inherited, or idiopathic causes (FIGURE, TABLE 2). As such, it is often unnecessary to obtain diagnostic tests searching for active infectious, autoimmune or paraneoplastic etiologies.³ In electrodiagnostic terms, these neuropathies are almost always primarily axonal rather than demyelinating, usually involving both large and small nerve fibers.

Diabetes is the most common cause of neuropathy in developed Western countries, occurring in more than 50% of patients who require insulin.¹⁴ Diabetic neuropathy typically presents as a distal, symmetric neuropathy syndrome, though diabetic lumbosacral radiculoplexus neuropathy (diabetic amyotrophy) and other presentations may be seen less commonly.

Recent evidence suggests that neuropathy—particularly a sensory and often painful, distal, symmetric “small-fiber” neuropathy—sometimes occurs in patients with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT).^15-19 The 2-hour oral glucose tolerance test has been deemed more sensitive for the early diabetic state of IGT/IFG associated with neuropathy.¹⁹ It remains to be seen whether this early diabetic state neuropathy will turn out to represent a large percentage of cases of what were previously thought of as idiopathic small-fiber neuropathy.

Alcoholism is another common cause of a distal, symmetric neuropathy that is predominantly sensory with a painful, burning sensation.^20-22 Alcohol abuse and dependence occurs in 10% to 20% of the primary care population.^23,24 The prevalence of neuropathy in alcoholics is uncertain, though 1 study of hospitalized patients admitting to daily alcohol intake of over 100 g for men or 80 g for women (10 oz of beer, 1 oz liquor and 3–4 oz wine each have 10 g of alcohol) for 2 years or more (mean of 238±120 g for a period of 22.7±10.2 years) demonstrated that one third of patients had electrophysiologic evidence of peripheral neuropathy and one fourth of autonomic neuropathy.²⁰ Most subjects in this cohort did not show any clinical or laboratory evidence of malnutrition.

Frequently alcoholic neuropathy coexists with thiamine-deficient neuropathy,²² warranting assessment of thiamine status in all alcoholics with neuropathy. Pain is a prominent complaint in alcoholic neuropathy but a less common complaint in thiamine-deficient neuropathy.²² Cobalamin (vitamin B₁₂)-deficient neuropathy is more likely to occur suddenly and to involve the hands or hands and feet simultaneously, and is less likely to be painful.²⁵ Myelopathy is frequent in cobalamin deficiency, sometimes serving as a clue to diagnosis. It may be difficult to determine whether sensory symptoms are caused by myelopathy or neuropathy. Electro-diagnostic testing, somatosensory evoked potentials, and radiological investigation may be helpful.