A Word on Polyneuropathy, by Eric Denys, M.D.
Peripheral neuropathy refers to all diseases affecting peripheral nerves. Polyneuropathies (poly=many) are but a subset affecting peripheral nerves in a symmetrical fashion. Conditions affecting a single nerve such as in a carpal tunnel syndrome or ulnar neuropathy are instead called mononeuropathies. The classification of the polyneuropathies forms a long list beyond the scope of this review. In general terms, polyneuropathies can affect the core of the nerve, the axon, or the myelin sheath, which protects and supports the axon and provides for fast conduction in the nerves. Polyneuropathies can affect movement, sensation and even autonomic function. Either damage to the myelin sheath or a break in the axon results in weakness, as well as sensory loss. But with myelin damage, the muscle remains intact, whereas with axon loss, the muscle becomes atrophic, and potential recovery will take much longer, as the axon must grow back. Polyneuropathies can affect myelin and axons to varying degrees. This brief report will highlight a number of conditions encountered in a general practice setting.
The most common polyneuropathies are predominantly axonal and are caused by diabetes, alcohol or renal disease. These neuropathies begin in the most distal part of the nerve and are hence called dying-back neuropathies. Symptoms typically begin in the toes. Dying-back neuropathies affect the longest nerves first, the legs, because the cell in or near the spine can maintain only so much nerve length. Therefore, the shorter arm nerves can stay healthier longer.
Patients describe varying degrees of numbness, tingling, burning or pain in a symmetrical fashion. Weakness occurs in some when the disease progresses. The first objective signs show up in diminished or absent ankle reflexes and impaired vibration sense. The polyneuropathy in diabetes is highly correlated with the degree of poor glycemic control. Painless ulceration is a feared complication (See reference 1).
When patients also complain of symptoms in their hands, it is readily assumed that this is part of their polyneuropathy. But, almost always, these symptoms have a separate cause, such as carpal tunnel syndrome or ulnar neuropathy.
A typical polyneuropathy caused by damage to the myelin is Guillain-Barré syndrome, a disease that presents with ascending weakness, beginning in the legs and evolving over one or two weeks to the point that it can affect respiration and hence needs urgent attention. A better name is actually polyradiculoneuropathy because the brunt of the demyelination occurs in the nerve roots; this explains the elevated protein in the spinal fluid, without cellular reaction. Plasma exchange or IVIG, if started in the first two weeks, can make a major difference.
Vitamin B12 Deficiency
Another, treatable cause of polyneuropathy is Vitamin B12 deficiency. Lack of vitamin B12 results in disease of peripheral nerves, spinal cord, and optic nerves, with symptoms accordingly. Both axonal and demyelinating forms are encountered. In acute cases, the symptoms can rapidly ascend and involve trunk paresthesiae and L’Hermitte signs, consisting of electrical sensations in the body with neck flexion. Even low normal levels of vitamin B12 can be meaningful in the presence of neuropathic symptoms and should be explored by measuring methylmalonic acid and homocysteine, which are elevated in vitamin B12 deficiency. But low normal levels in the older population in the absence of symptoms are not likely to cause neurological disease. Please note that patients with diabetes taking metformin for many years can have reduced vitamin B12 levels due to malabsorption. Keep in mind that a high intake of vitamin B6, 2-3 grams per day, has been associated with polyneuropathy as well.
Pharmaceutically Caused Polyneuropathy
Some polyneuropathies are caused by a toxic side effect of medication, such as amiodarone, metronidazole, nitrofurantoin, and HIV medications starting with the letter "D" (ddC, ddI, d4T). Chemotherapeutic agents like cisplatin and oxaliplatin, vincristine, paclitaxel and others are dose dependent and preferentially affect the dorsal root ganglia, which lack an effective blood/brain barrier.
When the polyneuropathy causes sensory loss in older patients without pain, the polyneuropathy could have an underlying hereditary predisposition, if not overt familial basis. Symptoms may slowly progress over many years, but patients will not become disabled.
The above-described polyneuropathies can also be associated autonomic dysfunction with symptoms of orthostasis, cardiac arrhythmia, gastroparesis, abnormal perspiration and disturbed bladder function. But a purely autonomic form exists, as well, with subacute presentation.
Pain can be a vexing problem in all polyneuropathies. Pain is the result of disease of the small, poorly myelinated pain fibers, and is most difficult to deal with. Some are idiopathic, no cause can be found, and treatment is symptomatic. One such entity is known by the descriptive name of Painful Small Fiber Sensory Polyneuropathy. "Nerve modulating" drugs like gabapentin, amitriptyline and others can help alleviate pain but are often insufficient. Analgesics will most often be necessary. Obviously, one must rule out other causes of pain, particularly joint pain. Many people have foot pain attributed to the polyneuropathy, whereas much of the pain originates in the metatarsal joints or plantar fascia.
Evaluation of peripheral neuropathies may require nerve conduction studies and needle electrode exam testing but should always be guided by the clinical findings (See reference 2). Screening blood tests should include a sedimentation rate, blood sugar and/or hemoglobin A1C, immunoelectrophoresis, quantitative immunoglobulins, and vitamin B12 levels. A urine analysis for heavy metals is rarely rewarding unless there are special circumstances. If checking for arsenic, make sure the patient has not consumed fish for 14 days. Recently, skin nerve biopsies have been added but still have limited application and should be left to specialists. The same is true for genetic testing.
The differential diagnosis in polyneuropathy is very complex (See reference 3). If there is no simple answer, a neurologist with special expertise should be helpful.
- The Diabetes Control and Complications Trial Research Group. (1993). "The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus." N Engl J Med. 1993 Sep 30;329(14):977-86 329 (14): 977–86. [Search Google and enter PMID 8366922.]
- Diagnostic Techniques in Neuromuscular Diseases by Jonathan Katz, M.D. California Pacific Neuroscience Institute BULLETIN. Spring 2012 Issue.
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