An easy approach to evaluating peripheral neuropathy
Ask what, where, when, and in what setting to narrow your search.
Uremic neuropathy may occur in patients with chronic renal failure on dialysis.26,27 Today it is less common by virtue of the widespread implementation of dialysis and renal transplantation. Generally reserve this diagnosis for patients with end-stage renal failure with a creatinine clearance of less than 10 mL/min. Other systemic disorders associated with renal failure must be considered; these include diabetes mellitus, amyloidosis, and vasculitis. Also consider drug-induced neuropathy in this population.
Pharmaceutical agents, industrial and environmental agents, and substances of abuse may cause neuropathy, most commonly in the form of a length-dependent axonal neuropathy. Offending chemotherapeutic agents include colchicine, pyridoxine, and amiodarone. However, toxic polyneuropathies probably represent a rather small proportion of cases.
The list of potentially offending substances is long and includes many medications and agents that the general population is commonly exposed to in low doses. Consider the inherent risk of neuropathy of the particular agent in question. To establish a causal link, verify exposure, determine that symptoms are temporally related to the toxin, and rule out other causes of neuropathy. Furthermore, some clinical improvement or at least stabilization should occur following removal of the offending agent, though this may take months to years.28
Medication-induced neuropathy is more common than industrial and environmental neuropathies. The neuropathy of heavy metal intoxication is rare, and is usually accompanied by a combination of gastrointestinal, hematologic, and central nervous system problems.
HIV neuropathy is predominantly sensory and length-dependent. It occurs in about one third of infected patients. This is an exception to the tenet that infectious neuropathies typically present in a non– length-dependent pattern. However, in almost all circumstances, the diagnosis of HIV is well established and so it usually doesn’t present a diagnostic challenge. It is not our routine practice to check for HIV in those presenting with a new-onset distal, symmetric neuropathy, though we will in the proper clinical setting. Whether HIV neuropathy should be included in the differential diagnosis depends on the incidence of HIV in your patient population and the patient’s specifics.6 Rarely, Guillain-Barré syndrome and CIDP can be the presentation of a recent HIV infection.
For inherited neuropathies, there are an overwhelming number of commercially available panels for DNA testing.3,29-31 A detailed discussion of inherited neuropathies is beyond the scope of this review, and many excellent reviews have been written on the subject. We will, however, make a few general comments.
First, Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, and it is encountered in primary care.
Second, foot deformities (eg, high arches, curled toes) commonly accompany an inherited polyneuropathy and are valuable clues.
Third, the inheritence pattern should be sought through a detailed family history and examination of other family members (including query and examination for foot deformities). Inherited neuropathies can be autosomal dominant, autosomal recessive, or X-linked, based largely on what gene harbors the mutation. Furthermore, spontaneous “de novo” mutations are not uncommon, being responsible for probably 25% of cases of CMT type 1.
Fourth, inherited neuropathies should be characterized just like acquired neuropathies, with particular attention paid to whether the neuropathy is demyelinating (eg, CMT type 1) or axonal (CMT type 2).
With respect to DNA testing of blood, focused genetic testing is almost always possible once you further characterize the inherited neuropathy and also take into account prevalence estimates of the various inherited neuropathies (eg, CMT type 1A caused by a duplication of the PMP-22 gene is responsible for the majority of cases on CMT), obviating the need for expensive, comprehensive genetic testing.
Other presentations
The evaluation of neuropathies that are not distal and symmetric can be complex and in many cases may warrant referral to a neurologist for further evaluation. With such presentations, diagnostic considerations include chest imaging and antineuronal (paraneoplastic) antibody serology for smokers with subacute neuropathies, cerebrospinal fluid analysis for an acquired demyelinating neuropathy, infectious neuropathy or a polyradiculopathy (eg, Lyme disease),3,7 and sensory nerve biopsy (eg, sural nerve) when vasculitis, amyloidosis, or sarcoidosis is suspected.
CORRESPONDENCE
Ted M. Burns, MD, University of Virginia Health System Department of Neurology, Box 800394, Charlottesville, VA 22908. E-mail: tmb8r@virginia.edu
