Neuropathy

Peripheral neuropathy is one of the most common long-term complications of diabetes, affecting up to 50% of patients by the tenth year of the diagnosis. It typically manifests as a mixture of sensory, motor, and autonomic involvement. The pathogenesis of diabetic neuropathy results from metabolic and vascular disorders that affect nerve blood flow and vascular endothelial function.²

Patients are usually divided into two groups: painful neuropathy or painless neuropathy. Painful neuropathy occurs in 15% of cases, with patients complaining of burning, lancinating pain, or allodynia. Various treatments exist to treat the symptoms of painful neuropathy, including antidepressants and anticonvulsants, which modulate neurotransmitters in the central nervous system. Other treatments for pain including surgical decompression, infrared light therapy, or vitamins are unproven. Painful neuropathy usually becomes painless in 2 to 3 years; therefore treatments for pain can be reduced or even eliminated at that time. Painless neuropathy or sensory neuropathy would seem to be preferable to the painful variety; however, it is this type of neuropathy that leads to the ulcerative complications in the diabetic foot. There are no accepted treatments to reverse sensory neuropathy in diabetes, and clinicians should not be lured into marketing traps by vitamin companies or surgical decompression enthusiasts who are without credible evidence to support their claims. A minority of patients have a syndrome with characteristics that are both painful and painless. In addition, ischemic rest pain symptoms induced by lower extremity arterial insufficiency in diabetes can often be difficult to distinguish from neuropathy.

A neurologic examination should be done to evaluate sensory and motor function in all patients with diabetes. Loss of protective sensation (LOPS) is a more severe form of diabetic neuropathy that increases the risk for ulceration. It is most readily revealed by applying pressure on selected dorsal and plantar areas of the foot with a deformable Semmes-Weinstein monofilament (SWMF) (Figure 59-1).²

FIGURE 59-1 Semmes-Weinstein monofilament.

If the patient is unable to feel 10 g of pressure exerted by a SWMF, they have met the criteria for LOPS. Patients should be screened annually for neuropathy. The nerve function profile of Boulton and colleagues provides a useful and reproducible baseline that has been validated as predictive of ulceration.^3,⁴

Because diabetic neuropathy affects all three divisions of the peripheral nervous system, the motor signs are sometimes subclinical but can lead to disabling disease progression manifested by muscular atrophy, fasciculation, and weakness. Intrinsic muscle weakness of the foot, once it becomes pronounced, leads to digital contractures and secondary metatarsal-phalangeal instability. The extrinsic muscles gain mechanical advantage over the intrinsic, which results in an unstable foot, prominent metatarsal heads, plantar callus formation, and ulceration. The sensory distribution is predominately of the feet and to a lesser extent the hands. Rather than following specific nerve trunks, the pattern is one of a stocking or glove. Motor neuropathy produces a pronounced clinical finding that is obvious on even cursory examination while the medical history is obtained; interosseus muscle wasting of the hands is evident, sometimes dramatically so.

Autonomic neuropathy interrupts control of arterial and capillary flow to the feet and tissues, resulting in decreased sudomotor function and dry feet, anhidrosis, noncompliant skin, and, ultimately, fissuring and painful cracking of the skin. Deep heel cracks and fissures are a common manifestation of autonomic neuropathy. This process results in an “auto-sympathectomy,” which explains why surgical ablation of the lumbar sympathetic trunk provides no benefit for diabetic ulceration. The stage is thus set for bacterial penetration and clinical infection. Autonomic control of vascular smooth muscle can also be affected, which leads to hyperemic states and possibly contributes to the development of Charcot destruction. The importance of neuropathy in diabetic foot ulceration is best encapsulated by the words of Dr. Paul Brand, considered “the patron saint of the diabetic foot.”^4a He wisely observed: “If the patient walks into your clinic with a diabetic foot ulcer and does not limp, he has neuropathy. For that reason alone the doctor should always observe the patient as he/she walks.”

Ulceration

Evaluation

A review of the clinical examination reports reveals that doctors at all levels of training who see patients for foot ulceration often fail to describe the appearance, size, and location of the lesion, or the state of infection in the presenting complaint. Patients should remove their socks and shoes during routine clinical evaluations.

The size, depth, and location of ulcers should be measured at the first examination and serially documented thereafter to track progression. The use of photographs to document ulcer size and location is recommended. Clinical findings of infection, such as the presence of malodor, exudate, and erythema, are obvious, but in diabetics, clinical manifestations can also be subtle. Clinical signs may help elicit the bacterial pathogen. Malodorous drainage suggests an anaerobic infection; creamy, yellow pus indicates a Staphylococcus species infection; and thin, watery drainage on a green base may herald infection with Pseudomonas species. Probing the depth of the ulceration with a metal probe can reveal involvement of tendon sheaths, open fascial planes, or abscess formation. Because of LOPS, this procedure rarely elicits patient complaint.

The evaluation should also identify common deformities and biomechanical abnormalities that contribute to the ulcer. For instance, ill-fitting footwear can cause ulcers to develop on the dorsum of toes, interdigitally, or on the lateral aspect of the foot. Ulcerations located on the dorsal aspect of toes may be related to contracted digits in a shallow toe box. Ankle equinus contracture, defined as ankle dorsiflexion of less than 10 degrees, causes increased pressure of the plantar forefoot and midfoot, leading to calluses and ulceration. Patients with amputations or shortened foot are susceptible to ankle equinus because the ankle flexors overpower the extensors (Figure 59-2).⁵

FIGURE 59-2 Severe equinus contracture after transmetatarsal amputation.

The Charcot foot rocker bottom deformity increases pressure at the apex of the deformity, usually at the midfoot, leading to mid-foot collapse and to the characteristic ulcer (Figures 59-3 and 59-4).

FIGURE 59-3 Plantar lateral ulceration from Charcot deformity.

FIGURE 59-4 Radiograph corresponding to Figure 59-3.

The plantar ulcerations that arise with increased ankle flexion and plantar pressure are not usually amenable to correction with footwear; the Achilles tendon is best dealt with by tendo-Achilles lengthening (TAL) or operative lengthening of the gastrocnemius muscle.⁶

The established systems to stratify the severity of foot ulceration are based on the size of ulceration (area and volume), location, tissue loss, presence of infection, and the anatomic and hemodynamic state of the arterial circulation. Three diabetic ulcer classification systems are widely used: the University of Texas (UT) classification, PEDIS, and Wagner grading.^7,⁸ The UT and PEDIS classifications were developed specifically for the diabetic foot. Wagner grades were first described for the foot known or presumed to be dysvascular but are now applied to all etiologies of lower extremity ulcerations.⁹ The UT system appears to be a better predictor of ultimate wound outcome, is often used in wound centers, and has been validated. The Wagner classification is based on the depth of penetration, the presence of osteomyelitis, or the extent of gangrene. A major shortcoming of Wagner grading is that the presence of ischemia is not specified in the consideration of the earlier stages. Because most ulcers fall into either grade I or II, the Wagner system inadequately differentiates the etiologic factors that underlie the majority of lesions. Finally, there is the (P)erfusion, (E)xtent, (D)epth, (I)nfection, (S)ensation or PEDIS classification developed by the International Consensus on the Diabetic Foot, which was devised initially as a research tool because of its relative complexity (Table 59-1).

TABLE 59-1 Table of Ulcer Classification Systems

System	Classifications
Wagner	Grade 0: Impending skin lesion, presence of predisposing bony deformity, or healed ulcer Grade 1: Superficial skin ulcer that does not involve subcutaneous tissue Grade 2: Full-thickness ulcer that exposes bone, tendon, ligaments, or joint capsule Grade 3: Full-thickness ulcer with presence of osteitis, osteomyelitis, or abscess Grade 4: Gangrenous digit Grade 5: Gangrene severe enough to necessitate foot amputation
University of Texas diabetic foot wound classification system	Grade 0: No open lesions; may have deformity A: Without infection or ischemia B: With infection C: With ischemia D: With infection + ischemia Grade 1: Superficial wound not involving tendon, capsule, or bone A: Without infection or ischemia B: With infection C: With ischemia D: With infection + ischemia Grade 2: Wound penetrating to tendon or capsule A: Without infection or ischemia B: With infection C: With ischemia D: With infection + ischemia Grade 3: Wound penetrating to tendon or capsule A: Without infection or ischemia B: With infection C: With ischemia D: With infection + ischemia Grade 4: Wound penetrating to bone or joint A: Without infection or ischemia B: With infection C: With ischemia D: With infection + ischemia
PEDIS P: Perfusion E: Extent or size D: Depth or tissue loss I: Infection S: Sensation or neuropathy	1. Wound lacking purulence or inflammation. Uninfected. 2. Presence of more than two manifestations of inflammation (purulence or erythema, pain, tenderness, warmth, or induration), but any cellulitis or erythema extends less than 2 cm around the ulcer, and infection is limited to the skin or superficial or subcutaneous tissues; no other local complications or systemic illness. Mild infection. 3. Infections as grade 2 in a patient who is systemically well and metabolically stable but who has one or more of the following: cellulitis extending >2 cm, lymphangitic streaking spread beneath the superficial fascia, deep-tissue abscess, gangrene, and involvement of muscle, tendon, joint, or bone. Moderate infection. 4. Infection in a patient with systemic toxicity or metabolic instability (e.g., fever, chills, tachycardia, hypotension, confusion, vomiting, leukocytosis, acidosis, severe hyperglycemia, or azotemia). Severe infection.

Ulcer stratification continues to loom as a major problem. Without an effective system around which investigators can find agreement and consensus, our ability to compare patient populations, understanding disease severity, and improving effectiveness of treatment will remain an unattainable goal.

Charcot Foot

Charcot neuroarthropathy was first described in tabes dorsalis in syphilis. It is now most commonly associated with diabetes but could occur as a result of any neuropathy.¹⁰ The International Task Force on the Charcot Foot stated the condition is primarily a disease of unopposed inflammation in the foot, leading to increased vascularity and bone resorption. It is a chronic and most often progressive disease of bone and joints. Common features include joint dislocation, pathologic fractures, and severe destruction of the pedal architecture, resulting in debilitating deformity, increased risk of ulceration, and increased risk for major amputation from complications of ulceration. It can lead to disability and premature retirement. The task force recommended classifying Charcot foot as active or inactive, depending on whether inflammation was present.¹¹

The most important factor in early detection and the potential to alter the outcome of patients with Charcot foot comes from retaining a high clinical suspicion in patients with the important risk factors. It can be precipitated by seemingly minor trauma. The clinical signs most associated with the disease are an erythematous, hot, and edematous foot. When these clinical findings predominate, it is easy to understand why Charcot can be mistaken for, and is treated as, a deep infection. Approximately 50% of patients have pain with their Charcot foot, which complicates its diagnosis because it is a syndrome caused by neuropathy. The diagnosis is often missed and thus delayed. The characteristic rocker bottom deformity is a late sign of the disease.¹²

Plain radiographs meant to find subtle changes or subluxations should be the initial diagnostic procedure. Magnetic resonance imaging (MRI) or bone scintigraphy can confirm the diagnosis in some cases, but usually clinical suspicion is enough to make the presumptive diagnosis and begin treatment because the consequences of undertreatment or no treatment can be devastating.

There is consensus that the cornerstone of management of acute Charcot foot is early immobilization and offloading. Judicious use of a total contact cast (TCC) or removable cast walker, crutches, walkers, knee walkers, wheelchairs, or bed rest may be appropriate in this setting (Figure 59-5).^13,¹⁴