Neuropathy: New Concepts in Evaluation and Treatment. (Featured CME Topic: Diabetes Mellitus).

Neuropathy: New Concepts in Evaluation and Treatment (*)

NEUROPATHIES, diabetic or otherwise, can present in many different ways depending on the fiber types involved. Often, more than one fiber type is involved, which can make diagnosis difficult. Neuropathies may be proximal or distal, focal or diffuse, small fiber or large fiber. Symptoms that may be present with large-fiber neuropathies include weakness, muscle wasting, and deficits in proprioception, deep tendon reflexes, and vibratory sense. A-delta fibers may be affected, resulting in deep seated pain, numbness, and impaired cold perception. Effects of C fiber dysfunction include spontaneous pain (which is often described as a burning sensation), allodynia (interpretation of nonpainful stimuli as painful), and hyperalgesia (interpretation of minimally painful stimuli as being excruciatingly painful). This is followed by decreased sensitivity to light touch, pinprick, and heat. Small-nerve-fiber dysfunction usually precedes large-nerve-fiber damage and is manifested first in the lower limb. Small-fiber neurop athy also occurs in the autonomic nervous system. Dysfunction of autonomic small nerve fibers can cause motility problems in the gastrointestinal tract, as well as delayed gastric emptying. Orthostatic hypotension, resting tachycardia, and cutaneous blood flow dysregulation are common cardiovascular irregularities. Abnormalities such as impotence in males, unawareness of hypoglycemic states, impaired sweating, and decreased bladder tone may be present. Autonomic symptoms may be present at diagnosis or shortly thereafter; 50% of patients with peripheral neuropathy will have asymptomatic autonomic neuropathy. Patients with autonomic neuropathy have an increased mortality rate; that rate can be as high as 50% within 3 years of diagnosis.

If diagnosed early, neuropathy may be reversible, or as least controllable. There are 3 proposed stages of neuropathy:

1. Functional neuropathy: This stage is without pathology but with biochemical alteration in nerve function. It is reversible.

2. Structural neuropathy: This stage involves the loss of structural change in nerve fibers. It may be reversible.

3. Nerve death: There is critical decrease in nerve fiber density and neuronal death in this stage. It is irreversible.

There is a distal-to-proximal gradient in nerve fiber loss in diabetic neuropathy, and the potential for reversibility will likely be in a proximal-to-distal manner. Because of the differences and stage of nerve damage, proximal nerve fibers are the least affected and distal nerve fibers are more likely to have greater structural damage. Standard testing for neuropathy does not effectively evaluate the integrity of C fibers. It is proposed that quantitative sensory tests (QST), skin blood flow, and skin biopsies measuring nerve fibers positive for protein gene product 9.5 are better suited to evaluate C fibers for level of function and recovery. Routine electrophysiology is also done as a control for the effects on the function of large, myelinated fiber. Focal neuropathies include mononeuritis, a vascular lesion that resolves spontaneously, and entrapments that are progressive with the repeated minor trauma and need to be treated with rest, splints, diuretics, injections of steroids plus local anesthetic, or surgical relief.

Proximal neuropathies are, for the most part, vasculitides, chronic inflammatory demyelinating conditions, or monoclonal gammopathies. These have specific treatments. Distal sensory polyneuropathy is treated symptomatically, but there are strategies for prevention and a number of new agents are being investigated for their ability to reverse the condition.

THREE KEY QUESTIONS WITH ANSWERS

1. Proximal neuropathy is due to:

a) longstanding hyperglycemia.

b) accumulation of advanced glycation end products.

c) deficiency of antioxidants.

d) inflammation or autoimmune disease.

Answer: d) All the others are mechanism for the pathogenesis of distal sensory polyneuropathy.

2. A patient presenting with carpal tunnel syndrome should be told that:

a) there is nothing to worry about, it will go away.

b) it is due to a vascular lesion and it will resolve spontaneously.

c) it is an irreversible condition and nothing can be done.

d) an electromyogram needs to be done to see if it is due to entrapment or a mononeuritis of the median nerve.

Answer: d) One third of diabetic patients have entrapments. This is the one time that an electromyogram is helpful to distinguish mononeuritis from distal sensory polyneuropathy and entrapment. Treatment decisions are dictated based upon this distinction.

3. Pain in distal sensory polyneuropathy may be due to different mechanisms. If someone has pain in the feet, it is important to ask:

a) What type of pain is it?

b) Where in the foot is it?

c) Does it occur with exercise?

d) Is the foot hot or cold?

Answer: All of the above. Unless you make the right diagnosis, you cannot treat the condition.

(*.) Presented at the Fourth Annual Conference on Diabetes, Southern Medical Association, Destin, Fla, October 5-7, 2001.

References

(1.) Greene DA, Sima AA, Stevens MJ, et al: Complications: neuropathy, pathogenic considerations, Diabetes Care 1992; 15:1902-1925

(2.) Caputo GM, Cavanagh PR, Ulbrecht JS, et al: Assessment and management of foot disease in patients with diabetes. N Engl J Med 1994; 331:854-860

(3.) Vinik AI, et al: Epidemiology of diabetic neuropathies. Diabetes: Clinical Science in Practice. Leslie RDG, Robbins DC (eds), New York, Cambridge University Press, 1995, pp 221-287

(4.) Vinik AI: Diagnosis and management of diabetic neuropathy. Clin Geriatr Med 1999; 15:293-320

(5.) Vinik AI, Park TS, Stansberry KB, et al: Diabetic neuropathies. Diabetologia 2000; 43:957-973

Disabling peripheral neuropathies in older adults. (4)


Vasculitis  52%
CIDP        22%
MGUS        17%
Diabetes     9%

Note: Table made from pie chart

RELATED ARTICLE: IMPACT OF DIABETIC NEUROPATHY (1-5)

* The most common peripheral neuropathy in advanced nations is diabetic neuropathy.

* Neuropathy accounts for more hospitalizations than all other diabetic complications combined.

* Diabetic neuropathy causes 50% to 70% of all nontraumatic amputations in the US.

* There are 80,000 amputations in the US each year, 1 every 2 minutes; 87% are due to neuropathy. Cost is $37 billion.

FOCAL DIABETIC NEUROPATHIES

* Cranial neuropathies (cranial nerves III, IV, VI, VII)

* Radiculopathies

* Plexopathies

* Mononeuropathy (multiplex)

MONONEURITIS VS ENTRAPMENT

Mononeuritis                    Entrapment

* sudden onset                  * gradual onset
* usually single nerve, but     * single nerves exposed to
  may be multiple                 trauma
* common nerves involved:       * common nerves involved:
   cranial nerves III, VI, VII     median
   ulnar                           ulnar
   median                          peroneal
   peroneal                        medial and lateral plantar
* not progressive and resolves  * progressive
  spontaneously
* symptomatic treatment         * treatment with rest,
                                  splints, diuretics, steroid
                                  injections, and surgery for
                                  paralysis