Vol. 16, Issue 4 Jul 2016

Case Management: Treatment of Painful Diabetic Neuropathy

Contributing Author: Sidhbh Gallagher, MD

ACCREDITATION STATEMENT
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Indiana University School of Medicine (IUSM) and IU Health Physicians. IUSM is accredited by the ACCME to provide continuing medical education for physicians.

DESIGNATION STATEMENT
IUSM designates this enduring material for a maximum of 1.00 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

FACULTY DISCLOSURE STATEMENT
In accordance with the ACCME Standards for Commercial Support, educational programs sponsored by IUSM must demonstrate balance, independence, objectivity, and scientific rigor. All faculty, authors, editors, and planning committee members participating in an IUSM-sponsored activity are required to disclose any relevant financial interest or other relationship with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services that are discussed in an educational activity.

The planning committee and those in a position to control the content of this activity have disclosed no relevant financial relationships.

OBJECTIVES
After reading this article, the reader should be able to:
• Identify the most common form of diabetic neuropathy.
• Describe the usual symptoms of distal symmetric polyneuropathy (DSPN).
• Summarize the nonpharmacologic and pharmacologic approaches to DSPN management.
• Explain the double crush theory of painful diabetic neuropathy.
• Discuss the role of surgical decompression in the treatment of diabetic neuropathy.

Activity Launch Date: July 2016

Expiration Date: July 2017

COMMERCIAL SUPPORT
This CME activity does not have any commercial support

A 66-year-old man with hypertension and a five-year history of type 2 diabetes managed with metformin (a recent hemoglobin A1c level was 6.2 percent) developed bilateral foot pain 2.5 years ago and was diagnosed with distal symmetric polyneuropathy. Gabapentin was initially prescribed for pain relief, then switched to pregabalin after two months; amitriptyline was subsequently added. When the effectiveness of combined anticonvulsant and antidepressant therapy waned, opioid analgesics were substituted.

The patient presents to Indiana University Health with increasingly severe burning foot pain that is worse at night. Without narcotics, he rates the pain at 10 on a scale of one to 10. He also reports clumsiness on walking, worsening balance, and decreased sensation in both feet. Collectively, these symptoms are adversely impacting his daily activities and career as a chiropractor.

Overview of Diabetic Neuropathy

Diabetic neuropathy is a heterogeneous condition that manifests in different clinical forms. Distal symmetric polyneuropathy (DSPN), a process that primarily affects distal peripheral nerves, is the most common form and is often considered synonymous with the term diabetic neuropathy. Painful DSPN occurs in 10 to 26 percent of patients with diabetes and can have a profoundly negative effect on quality of life.1 Pain occurs more often in those with poor longterm glycemic control; older age, obesity, smoking, hypertension, dyslipidemia, and peripheral artery disease are contributing factors.

Pathophysiology, Symptoms, and Clinical Presentation

The precise cause of nerve damage in DSPN is incompletely understood but appears to be associated with inflammatory reactions, excessive production of radical oxygen species, cytokine release, and peripheral nerve edema caused by hyperglycemia and dyslipidemia (the latter a frequent comorbidity of type 2 diabetes).2-4 Symptoms usually affect the feet first; progress proximally; and are predominately sensory, classified as “positive” (tingling, burning, stabbing pain, or other abnormal sensations) or “negative” (sensory loss, weakness, and numbness).5 Decreased sensation in the feet and legs predisposes to infection, ulceration, and subsequent amputation (Figure 1). The lifetime risk of a foot lesion, including an ulcer or gangrene, in persons with DSPN is 16 to 25 percent.1

Sensory loss combined with decreased proprioception results in imbalance and unsteady gait, increasing the risk for falls and the potential for laceration, fracture, and other traumatic injury. In severe cases, motor axonal loss and motor weakness may follow the destruction of sensory axons. Loss of distal motor axons results in atrophy of intrinsic foot muscles and a disparity in toe extensor and flexor strength that eventually leads to chronic metatarsalphalangea flexion, referred to a claw toe deformity (Figure 2).

The precise cause of nerve damage in DSPN is incompletely understood but appears to be associated with inflammatory reactions, excessive production of radical oxygen species, cytokine release, and peripheral nerve edema caused by hyperglycemia and dyslipidemia (the latter a frequent comorbidity of type 2 diabetes).

Diagnosis and Medical Management

The diagnosis of DSPN is primarily clinical and involves a thorough history and physical examination, with a focus on vascular and neurologic testing and a detailed assessment of the legs and feet.6 Laboratory studies to rule out reversible causes of neuropathy include testing for thyroid dysfunction, a common coexisting condition, and vitamin B deficiency, which may be associated with metformin therapy.

Management of painful DSPN involves nonpharmacologic and pharmacologic approaches to minimize disease progression and relieve symptoms. Lifestyle interventions, in particular diet and exercise, have been shown to increase intraepidermal nerve-fiber density and reduce pain in patients with neuropathy associated with impaired glucose tolerance (pre-diabetes).7 A randomized trial enrolling persons with diabetes but without neuropathy found exercise on a treadmill reduced the risk of DSPN.8 Among patients with DSPN, strength and balance training may decrease the likelihood of falls. Additionally, rational glycemic control* is recommended to manage neuropathic symptoms and prevent further damage, although the benefits appear to be greater for individuals with type 1 diabetes than for those with type 2 disease.

Topical capsaicin, anticonvulsants, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and opioid analgesics are all used in the treatment of DSPN-associated pain. Pharmacotherapy often requires careful dose adjustment every two to four weeks based on efficacy and side effects,5 and patients may not experience satisfactory relief with first-line monotherapy at maximally tolerated doses.1 Options include switching to a different agent within the same class, changing to a new class, or adding a second agent.

Surgical decompression offers another treatment option for selected patients with painful DSPN.

Role of Surgical Decompression in DSPN Management

“Some patients with diabetic neuropathy experience peripheral nerve compression owing to a ‘double crush’ phenomenon: swollen nerves resulting from the altered metabolic state are compressed within narrow anatomic canals, exacerbating symptoms,” explains Sidhbh Gallagher, MD, assistant professor of surgery at Indiana University School of Medicine. “Approximately one-third of diabetic patients have carpal tunnel syndrome, yet lower extremity nerve compression, such as tarsal tunnel syndrome, tends to go undiagnosed and untreated. Surgical decompression has the potential to alleviate pain, restore sensation, and improve function.”

In 1992, Dellon was the first to treat patients with diabetic neuropathy using lower extremity peripheral nerve decompression and reported an 85 percent improvement in patients’ sensorimotor symptoms.10 During the following two decades, multiple studies were conducted, all with promising results but lacking a prospective, randomized, controlled design.

Results from the first randomized controlled study of surgical decompression of nerves in the lower extremities were published in 2014.11 The single-center study enrolled 42 patients with painful DSPN diagnosed using the diabetic neuropathy score (Table 1) and diabetic neuropathy examination.11 After randomization, lower extremity nerves in each patient were decompressed at four sites in one limb, with the contralateral limb serving as the control. Visual analog scale scores 12 months after surgery (the primary outcome measure) significantly improved in 74 percent of the patients.12

Recently presented findings from a National Institutes of Health-funded prospective, randomized, double-blinded study of lower extremity surgical nerve decompression for diabetic neuropathy were similarly favorable.13 As compared with 27 patients in the non-surgical control group, the 40 patients who underwent surgery experienced significant pain reduction in the decompressed leg that persisted for four years of follow-up.

Lower extremity nerve decompression also improves peripheral blood flow,12 reverses claw toe deformity,14 and decreases ulceration and amputation rates.15

“Before considering surgery, patients should be medically optimized,” stresses Dr. Gallagher. “Physical examination remains the most useful tool for identifying the best surgical candidates. Nerve blocks can assist in establishing the diagnosis; nerve conduction studies, while not always indicated, may be useful in some instances.”

On examination, the patient’s symptoms are mainly isolated to the dorsum of the foot. He has evidence of bilateral peroneal nerve compression with positive Tinel signs in both feet.* Weakness in dorsiflexion of the great toe is observed: 3/5 on the right; 4/5 on the left. A diagnostic block of the common peroneal nerve is performed and provides several hours of relief, further indicating that decompressive surgery may be helpful in alleviating symptoms long-term.

In December 2015, the patient undergoes surgical decompression of the common superficial and deep peroneal nerves on the left leg and foot. The 60-minute outpatient procedure performed with intravenous sedation involves making a small incision over the compressed nerve and releasing it from the surrounding compressive structures (Figure 3). One hour after surgery, the patient is discharged home with instructions to wear a compression garment and keep his left leg elevated as much as possible for the next two weeks.

The patient is seen in the office two weeks after the first surgery, and good healing is observed (Figure 4 see page 6). Two months later, the same procedure is performed on the right leg and foot. One month after the second surgery, he is weaned off narcotics. The patient rates his pain without medication as 2/10 and reports improvement in balance and bilateral foot strength.

Peripheral nerve decompression has applications beyond diabetes, including neuropathy caused by chemotherapy16 or human immunodeficiency virus17 as well as idiopathic neuropathy.18 Considering the diagnosis of nerve compression and treating the problem in any of these patient populations may effectively treat pain and other bothersome symptoms of neuropathy.

“Surgical decompression can potentially alter the course of a condition that, for too many individuals, ultimately leads to amputation,” Dr. Gallagher concludes. “It is very gratifying to be able to offer this treatment option, which is now backed by level one scientific evidence.”

Peripheral nerve decompression has applications beyond diabetes, including neuropathy caused by chemotherapy or human immunodeficiency virus as well as idiopathic neuropathy.

CME Credit Form

Sidhbh Gallagher, MD

Plastic Surgeon, Indiana University Health
Assistant Professor of Surgery, IU School of Medicine
sgallagher1@iuhealth.org

Dr. Gallagher received her medical degree from University College in Dublin, Ireland, did a residency in general surgery at Abington Memorial Hospital in Abington, PA, and completed a plastic surgery residency at IU School of Medicine. Her areas of interest are peripheral ner ve surger y, including the surgical treatment of diabetic neuropathy and the management of traumatic nerve injuries, and transgender surgery.

A member of the Association of Extremity Nerve Surgeons and the World Professional Association of Transgender Health, Dr. Gallagher is the author of several peer-reviewed publications and has presented at numerous scientific meetings in the United States.

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