Restoring Sensation In Diabetic Patients

Statistics from the American Diabetes Association (ADA) reveal there were 86,000 amputations due to complications from diabetes mellitus in 2000. The ADA also points out that 50 to 70 percent of these patients will develop peripheral neuropathy sometime in the course of their disease.1
The most widely believed paradigm in mainstream medicine today is that loss of sensation in diabetic peripheral neuropathy is irreversible and the only treatment available is the achievement of euglycemic control and the ancillary use of medicines such as Elavil and Neurontin.2 Sadly, this belief is wrong. Even though this type of treatment may relieve some of the pain associated with diabetic peripheral neuropathy, this does nothing to re-establish sensation, which will prevent ulceration and potential amputation.

Examining The Pathophysiology Of Diabetic Peripheral Neuropathy
Jakobsen, in 1978, demonstrated the peripheral nerve in the diabetic rat increases in size by up to 50 percent and can become 50 percent heavier in cross-sectional volume when compared to a non-diabetic peripheral nerve.3 It was also shown that the diabetic peripheral nerve is more susceptible to injury than a non-diabetic nerve. It has also been well demonstrated that glycosylation of collagen, another of the systemic sequelae of diabetes, can predispose the diabetic patient to carpal tunnel syndrome.4 This is due to the fact that with the glycosylation of collagen, normal anatomical tunnels will become smaller and more constricted than in a non-diabetic situation. With a nerve that is anatomically larger in diameter and a smaller more constricted anatomical tunnel (i.e. the tarsal tunnel), this sets up an ideal situation for a chronic nerve entrapment.4

In summary, these are two metabolic changes in the peripheral nerves of the diabetic that render the nerve susceptible to chronic compression. There is increased water content within the nerve as the result of glucose being metabolized into sorbitol and there is a decrease in the slow anterograde component of axoplasmic transport.3,5
As we can see in the first photomicrograph (see top left photo), the ulnar nerve in a type 1 diabetic primate is stunningly normal. This section was taken from an area of no compression. While there is some mild “knuckling” of myelin, the axons appear with good myelination. There is a significant amount of endoneurial edema and sub-epineurial edema, but nothing in this section would indicate there would be difficulty with transmission of action potentials in these neurons. The second photomicrograph (see middle right photo) is the same ulnar nerve, taken under a higher power.

The third photo (see bottom left photo) was taken just several centimeters distal to the section in the first and second illustration from the area of a known site of entrapment—the cubital tunnel. It is hard to believe this photomicrograph is of the same peripheral nerve, as there is a significant axonopathy and destruction of myelin. These changes are due to a chronic nerve entrapment. The same metabolic process has affected both cross sections of ulnar nerve. Therefore, it would be impossible to attribute anything but a superimposed chronic entrapment as the etiology of this neural change.

Dellon, et. al., demonstrated this in rats in 1994.6 In this study, they took non-diabetic rats and made them diabetic by injecting them with streptozotocin, which, in effect, killed their islet cells in their pancreases with resultant blood sugars of 400 gm/dl. Walking track prints of these rats’ paws were made before and after they became diabetic. There was a significant splaying degradation of the paw print after the effects of diabetes, compared to the initial prints.
The researchers performed tarsal tunnel decompressions on similar weight-controlled rats. The rats were again rendered diabetic with blood sugars of 400 and researchers monitored their walking track patterns. There was no splaying or degernation of the paw print in contrast to those rats that were not decompressed.6

What Were The Results Of Peripheral Nerve Decompression?
Several very important studies have been published documenting the success of restoring sensation in patients with diabetic peripheral neuropathy.
Initially, in 1992, Dellon published results showing a 44 percent improvement in motor function, 67 percent improvement in sensory function, and a subjective 88 percent improvement in 60 patients, accounting for a total of 154 operations.7 He also noted that no ulcers or amputations occurred in any of these decompressed patients during a 10-year follow-up period.
In 2000, Azmann, Kress and Dellon published more results in a study in which there was a blinded therapist evaluation of the patients with diabetic peripheral neuropathy who had undergone decompression to re-establish sensation.8 In 31 operations on 20 patients, they reported a 69 percent improvement in the lower extremities and an 88 percent improvement in sensation in the upper extremities.
Perhaps even more impressive are Chafee’s 1999 results. In the study—which had more liberal inclusion criteria—11 of the 36 patients had existing neuropathic ulcers and six patients had contralateral amputations. Eighteen of the 36 patients had a documented improvement in sensation. However, 24 of 28 patients (86 percent) had a significant reduction in pain.9 This particular parameter, although not evaluated by Dellon or Azmann, may be of more importance to those unfortunate patients who have unrelenting pain and burning from their neuropathy.
In 1995, Weimann and Patel reported their results dealing with both pain reduction and the restoration of sensation in 26 patients. Interestingly, they also had liberal inclusion criteria for their study and had 13 patients with existing ulcerations. In addition to achieving a 72 percent improvement in sensation, 83 percent of the ulcers healed and incredibly, 92 percent reported relief of pain at one month after the surgery.10
Significant data is now starting to be reported within podiatric medicine, as evidenced by the work of William and Michael Wood in the Midwest. In their study, which is pending publication at this time, they report an 81 percent excellent or good result in 33 patients.11 At this time, data is being collected by more than 60 podiatric surgeons who have been trained in lower extremity peripheral nerve surgery by the Institute for Peripheral Nerve Surgery in Baltimore.

Why We Should Re-Evaluate Our Evaluation Tools
Until the development of the pressure specified sensory device (PSSD) by Dellon, you could only evaluate the peripheral nervous system via clinical evaluation or neurological electrodiagnostic testing such as EMG, NCV and the Semmes-Weinstein monofilaments.
There is a widespread belief that using the 5.07 Semmes-Weinstein monofilament is an effective means of determining a patient’s loss of protective sensation. Indeed, this screening is widely advocated by the ADA and the American Podiatric Medical Association to tell us if a patient is at risk for ulceration due to loss of protective sensation.12,13 Unfortunately, the monofilament fails to give you any early assessment of the status of the patient’s neuropathy.14
The Semmes-Weinstein monofilament is, at best, a crude tool that tells us the patient is at high risk. It does not quantify or stage the level of peripheral neuropathy. These filaments only provide an estimate of range. For example, when a patient is able to feel the 5.07 monofilament but is unable to feel the 4.31 monofilament, that tells the clinician the patient can feel somewhere between 95 grams of pressure, and 33.1 grams of pressure.14 This is an astounding range of greater than 60 grams of pressure/mm.
(In addition to only being able to test one point, monofilaments have numerous inherent flaws, which include weakening of the filament after only 10 uses.)
It is imperative to understand that when a patient is no longer able to feel a single 5.07 monofilament (which equates to approximately 95 grams/mm of pressure), the success rate for restoring sensation and reducing pain from diabetic peripheral neuropathy is greatly reduced. When these patients with diabetes cannot feel the 5.07 monofilament, they are often beyond the point at which surgical intervention is possible for restoring sensation and relieving pain.
As we can see in the illustration of the PSSD report for a patient with severe diabetic peripheral neuropathy (see illustrations below), this patient would be able to feel the 5.07 Semmes-Weinstein monofilament, even with the very abnormal pressure thresholds seen in the readout. However, this patient has severe peripheral neuropathy and sadly would be placed into a category of having protective sensation, if he were only evaluated with the monofilament. Therefore, it is easy to see why we must evaluate these patients with a more specific and sensitive method, so we can potentially initiate earlier intervention before severe axonopathy occurs.

Comparing The PSSD To NCV Testing
When the peripheral nerve becomes entrapped, the a-beta sensory fiber is the first fiber group affected by the compression. By using a sensitive means of evaluating the loss of innervation density with two-point discrimination, it is possible to make a very early assessment of the status of that particular nerve.14 This is not possible with a one-point static test. Loss of innervation density, as defined by the number of sensory end-organs within a specific area of tissue, is to the sensory system as muscle atrophy is to the motor system.

Traditional electrodiagnostic tests, such as nerve conduction velocity (NCV) testing, are also limited in their ability to evaluate early stages of isolated peripheral nerve compression and peripheral neuropathy. Weber demonstrated a 33 percent false negative rate in patients with carpal tunnel syndrome, whereas in these same patients, the PSSD demonstrated a 82 percent specificity and a 91 percent sensitivity.15
This can be easily explained by looking at the diagram of a peripheral nerve under chronic nerve compression (see diagram at right). As you can see, there is near complete destruction of the fascicles near the site of compression, but there are several normal fascicles on the side away from compression. These normal fascicles will conduct electricity and therefore a NCV test will reveal a latency. Again, similar to when you would use the Semmes-Weinstein monofilament, you are left without a true assessment of that particular nerve.

Identifying Anatomical Entrapment Sites
Researchers have identified three sites of natural anatomical entrapment in the lower extremity.16 These sites include: the common peroneal nerve at the head of the fibula; the deep peroneal nerve on the dorsum of the foot where it is crossed by the tendon of the extensor hallucis brevis; and the four tunnels of the tarsal tunnel area.
The common peroneal nerve is one of the terminal branches of the sciatic nerve, which courses around the fibula just distal to the head and travels anteriorly and distally under the deep fascia of the peroneus longus muscle. Within this area, you’ll frequently see thickened and sometimes extra bands, especially in diabetic patients, which can lead to a significant entrapment of the nerve.

The deep peroneal nerve on the dorsum of the foot can also become entrapped very easily due to the minimal amount of soft tissue at the level of the first and second metatarsal cuneiform articulations, where the neurovascular bundle can become entrapped by the tendon of the extensor hallucis brevis.
Finally, it is important to note that the posterior tibial nerve, its bifurcation into the medial and lateral plantar nerve, and the medial calcaneal nerve all have separate anatomical tunnels that are well defined and can lead to entrapment. Therefore, you must identify and decompress each of these sites in order to achieve a maximum level of sensation and reduced pain.8

In Conclusion
Nothing in 16 years of clinical podiatric practice has provided me with more gratification than the ability to intervene surgically with decompression, restore sensation and eliminate the horrible burning pain so often associated with diabetic peripheral neuropathy for many of these patients. Extraordinarily, patients will often wake up in the recovery room saying they can now feel their toes. It is not unusual to see an immediate improvement of muscle strength in some of these patients after decompression.
A couple of patients had stated they were suicidal because of the relentless burning and pain they had from the neuropathy. It is difficult to quantify the sense of gratitude these patients have after the procedure. It is equally difficult to quantify the sense of fulfillment for the practitioner as well. As you can see in the PSSD reports (above), there is documentation of improved sensory nerve function after decompression.
In addition to the restored sensation and pain reduction in those patients who have had severe symptoms associated with their neuropathy, I’ve also seen restoration of sympathetic function in some patients. Further studies are now being conducted to document and quantify the level of improvement of blood flow in the diabetic patient with neuropathy who undergoes surgical decompression.
While there is much controversy regarding this subject, paradigms are radically changing with regard to diabetic peripheral neuropathy. Within the next several years, I believe thousands of lives will be changed for the better, thousands of limbs will be saved and thousands of neuropathic ulcers will be prevented. It is now well documented that you can restore sensation in the patient with diabetic peripheral neuropathy and eliminate or reduce the pain associated with the neuropathy.
There is currently an overwhelming emphasis within our profession and others on wound care. This is laudable and important for our patients. Now, however, an emphasis should be made to further incorporate this knowledge and experience of surgical decompression techniques for diabetic peripheral neuropathy so we can prevent wounds altogether.
As with any surgical technique, there must be strict inclusion criteria for patients to be candidates for this type of surgery. It is also the responsibility of every podiatric surgeon who wants to perform this type of surgery to be adequately trained and experienced in not only the surgery but the clinical management of these types of patients.

Dr. Barrett is a Fellow of the American College of Foot and Ankle Surgeons and is board-certified in podiatric orthopedics. He is the Director of Surgical Training at the Institute for Peripheral Nerve Surgery and is the Research Director for the Houston Podiatric Foundation.

References:

References

1. American Diabetes Association: “Diabetic Foot Ulcers and Amputations,” ISBN 1-58040-059-0; 2001.

2. Backonja M, Beydoun A, Edwards KR, et. al., “Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus; a randomized controlled trial.” JAMA, 280; 1831-1836, 1998.

3. Jakobsen J. Peripheral nerves in early experimental diabetes. Expansion of the endoneurial space as a cause of increased water content. Diabetologia 14:113, 1978.

4. Dellon AL, Mackinnon SE, Seiler WA IV: Susceptibility of the diabetic nerve to chronic compression. Ann Plast Surg 20:117-119, 1988.

5. Jakobsen J, Sidenious P. “Decreased axonal transport of structural proteins in streptozotocin diabetic rats.” J Clin Invest 66:292, 1980.

6. Dellon ES, Dellon AL, Seiler WA IV: The effect of tarsal tunnel decompression in the streptozotocin-induced diabetic rat. Microsurg 15:265-268, 1994.

7. Dellon AL: Treatment of symptoms of diabetic neuropathy by peripheral nerve decompression. Plast Reconstr Surg 89:689-697, 1992.

8. Aszmann OA, Kress, KM, Dellon AL: Results of decompression of peripheral nerves in diabetics: a prospective, blinded study, Plast Reconstr Surg, 106: 816-822, 2000.

9. Chafee H, Decompression of peripheral nerves for diabetic neuropathy, Plas Reconstr Surg, 106: 813-815, 2000.

10. Wieman TJ, Patel VG, Treatment of hyperesthetic neuropathic pain in diabetics; decompression of the tarsal tunnel. Ann Surg, 221: 660-665, 1995.

11. Wood W, Wood M Personal communication after review of draft article pending publication.

12. Asbury AK, Porte D Jr: American Diabetes Association Clinical Practice Recommendations 1995; Consensus Statement on Diabetic Neuropathy. Diab Care 18:53-58, Supp 1, 1995.

13. Asbury AK, Porte D Jr: American Diabetes Association Clinical Practice Recommendation 1995; Consensus Statement on Standardized Measures in Diabetic Neuropathy. Diab Care 18:59-82, Supp 1, 1995.

14. Dellon AL Somatosensory Testing and Rehabilitation, Institute for Peripheral Nerve Surgery, Baltimore, 2000.

15. Weber RA, Schuchmann JA, Albers, JH, Ortiz, J, Prospective Blinded Evaluation of Nerve Conduction Velocity Versus Pressure-Specified Sensory Testing in Carpal Tunnel Syndrome. Plastic and Reconstructive Surgery 436(3): 252-257, 2000.

16. Dellon AL, Mackinnon SE, Surgery of the Peripheral Nerve, Thieme Medical Pub Inc., 1988.