Diabetic peripheral neuropathy (DPN) is a “diagnosis of exclusion.” Diagnostic challenges are one thing but few practitioners relish that phrase when it comes to DPN. For this condition, the practitioner needs to cast a very wide net of tests and keep an open mind regarding clinical suspicion in order to reach an accurate diagnostic conclusion. How likely is it that there could be another neuropathy-causing disease or medical condition resulting in these same lower extremity symptoms? Does the podiatric physician really need to consider thyroid problems, vitamin B12 deficiencies, nerve entrapments, lupus, kidney failure, nutritional deficiencies and alcoholism among other diagnoses? Noted Mayo Clinic researcher Peter J. Dyck, MD, strongly cautions that the physician diagnosing DPN must first eliminate the presence of other neuropathy-inducing conditions because there is an estimated 10 percent occurrence of other neurologic diagnoses in patients who have concurrent diabetes. To fail to diagnose and treat these other conditions (or make an appropriate referral to other physicians) could be catastrophic for the patient’s outcome.1 That said, it is neither an easy nor inexpensive task to eliminate that 10 percent of outlying cases. The potential list of comparisons is a long one with vague symptoms. Indeed, when you treat patients with diabetes, you likely hear these common comments: • “My feet burn.” • “I feel electric shocks in my toes.” • “My toes are numb at the end of the day.” • “I can’t get to sleep at night because my feet feel like they are on fire.” There was a time when a patient’s complaints of symptomatic or painful neuropathy led to commiseration from the physician but not much else because there were no distinctly good treatments. Now there is much more to offer than just empathy. Emerging treatments include surgical decompression of nerves, anti-seizure medications, antidepressants and even infrared light therapy, just to name a few of the leading proven treatments.2-4 Many of the treatments are not benign. Surgery has the inherent risks associated with anesthesia and potential postoperative complications of infection and scarring. Medical (pharmaceutical) treatments can have adverse effects and drug interactions. Given the fact that there is no completely benign treatment, there is a profound desire to make a definitive diagnosis prior to embarking on a treatment plan. This brings us back to the pivotal question: How does one distinguish between diabetic peripheral neuropathy and the array of other causes of these same symptoms? What The International Consensus Group Recommended While it might seem like there is a circuitous trip in reaching a diagnosis, there is usually a very distinct roadmap leading to the correct diagnosis. At least there is if one agrees with the International Consensus Group, which arose out of suggestions made by Neurodiab, a subgroup of the larger European Association for the Study of Diabetes. The internationally respected members, primarily Europeans, debated and discussed the subject for several years before agreeing on criteria required for a correct diagnosis of DPN.5 The panel of 39 experts from the European countries and Canada also had four representatives from the United States, including Lawrence B. Harkless, DPM, of the University of Texas Health Science Center at San Antonio and Aristidis Veves, MD, of the Beth Israel Deaconess Medical Center and Harvard Medical School. This panel of diabetologists, podiatrists, neurologists, diabetes specialists, nurses and primary care physicians advocated an annual assessment in order to facilitate early diagnosis of neuropathy. Once one has diagnosed the condition, the panel said it is essential to manage it aggressively and/or make appropriate referrals within the multidisciplinary team in order to minimize complications of the condition. The international and multidisciplinary panel was mindful of the limitations of available modalities that might exist in different countries. Accordingly, the panel wanted to develop an easy to follow system that would enable the podiatrist in America to have the ability to reach the same conclusion as the diabetologist in Finland. With that in mind, the International Consensus Group concentrated on developing guidelines that did not require any technologically advanced or expensive equipment to make the diagnosis.5 In regard to the panel’s recommendations for clinicians, it emphasized gathering a comprehensive history of the patient’s symptoms, his or her type of diabetes, the patient’s lifestyle and social circumstances. For the lower extremity exam, the panel recommended a subjective analysis by the examiner that assessed the health status of the skin (i.e., absence of sweating, presence of ulcerations and callosities), immobility of joints, gait and footwear. The panel recommended that clinicians perform simple tests to assess peripheral sensation. These tests include sensation to pinprick, light touch, vibration (utilizing a 128-Hz tuning fork), pressure and ankle reflexes. Pointing Out The Flaws Of Simple Tests And Subjective Patient Responses The International Consensus Group recommended simple and easily available tests for diagnosing DPN but are these tests accurate? Dr. Dyck, a Professor of Neurology at the Mayo Clinic College of Medicine, and others disagree with the group’s findings, citing the system for “major flaws.”1 Dyck points out the shortcomings of the pinprick/tuning fork regimen, noting there are more sensitive and reliable modalities available, such as the biothesiometer or the vibrometer. (However, these modalities are not universally available in all practice settings and this was a requirement of the consensus group.) Dyck also expressed concern about the variability of examiners’ judgment about anthropometric factors of age, gender, height and weight. In order to make the diagnosis of DPN, Dyck cites the presence of at least two abnormalities from the broad group of neuropathy symptoms, clinical abnormalities and emphasizes the use of nerve conduction, quantitative sensation tests (QST) or quantitative autonomic tests (QAT). This noted neurologist specifies that one of the abnormal findings must be abnormal nerve conduction in at least two separate nerves or an abnormal QAT.1 Dyck’s gold standard is a composite score he calls the “Neuropathy Impairment Score (Lower Limbs) + 7 Tests” (NIS). The NIS is an evaluation of muscle weakness, a decrease or loss of reflexes and a loss of sensation. There are also scores for the patient’s age, gender, physical fitness and anthropometric features. The “seven tests” are peroneal motor nerve conduction, velocity, peroneal compound muscle action potential, peroneal motor distal latency, sural sensory nerve action potential and tibial motor distal latency, heart-pulse rate decrease with breathing and vibratory detection threshold.1 The comprehensive system also includes algorithms for determining a quantifiable score. This quantifiable score leaves little question as to the diagnosis of DPN. However, for what this system offers in specificity, it is an impossibly difficult system for the private practitioner to utilize and would seem better suited for the specialist or researcher who needs the detail for comparison studies. A Lack Of Reproducible, Objective Techniques Yet Dyck has a point as the more commonly used examinations (pinprick, reflexes, tuning fork) result in almost entirely subjective findings.1 In addition, the results are often not reproducible, even when these techniques are performed by the same examiner. There is also the uncertainty of the response by the patient. For a variety of reasons, whether it is an attempt to please, a fear of disease or an inability to understand what is being asked, patients may respond incorrectly either knowingly or unknowingly. Are these variables the responsibility of the examiner, the patient or the testing modality? The answer is an unsatisfying “yes” to all. Unfortunately, the very nature of peripheral neuropathy is that it is a condition that is transient, intermittent and variable in its presentation.6 It is also true that there are no convenient objective testing modalities for the condition that do not also depend on the patient’s verbal response, which is always subjective. Nothing short of nerve biopsies (or if one subscribes to the reliability of EMG/NCV for diagnosis of DPN) are independent of a declaration by the patient. It is probably not surprising that DPN is often diagnosed when complications occur. Indeed, many of the most severe outcomes occur in the feet. At that point, the condition has progressed to Stage 3 with lesions and possibly subsequent amputations.5 Finding A Diagnostic Combination That Works While there seems to be a lack of true agreement about a uniform approach or system for diagnosing DPN, perhaps the most reasonable method was developed by the International Consensus Group. It does combine a comprehensive patient history (subjective) with the physician’s objective examination.5 The patient history is the best foundation for the evaluation. In addition to the standard questions in the history (nature, location, duration, onset, course, aggravation and treatment or NLDOCAT), some practitioners find value in incorporating a standardized questionnaire such as the Michigan Neuropathy Screening Instrument.7 Once again, uniformity will aid the clinician when it comes to diagnosing this condition successfully. The recommended physical examination includes a comprehensive dermatologic exam including evaluation of dyshidrosis, callosities, ulcerations and other abnormalities. One should also note any deformed or limited joints, abnormal gait and evaluate the type of footwear worn by the patient. When You Need To Go Beyond The History And Physical Exam One can augment patient history and the physician exam with available diagnostic testing (objective) such as the Peripheral Specified Sensory Device (PSSD, Sensory Management), EMG/NCV and others.4-6 PSSD. The PSSD, invented by A. Lee Dellon, MD, a Professor of Plastic Surgery and Neurosurgery at the Johns Hopkins University School of Medicine, is capable of detecting nerve damage earlier than other modalities including nerve conduction velocity examinations.8 This early, pain-free diagnostic test allows earlier intervention and possible reversal of the condition through treatments like surgical neurolysis (release of specific peripheral nerves) because it picks up degeneration of neural tissue before it is completely irreversible. EMG/NCV. Nerve conduction velocity studies record the speed at which impulses travel through nerves and measure electrical responses in a quantifiable fashion. Although the two tests are usually referred to as the EMG/NCV, one would usually order the NCV first and follow it with the EMG if necessary. It records electrical activity in muscles and allows one to differentiate between muscle disease and neurological disease. Semmes-Weinstein. Semmes-Weinstein monofilaments (SWM) are inexpensive testing devices, which are manufactured of calibrated nylon monofilaments that can generate a reproducible bending stress. The higher the number of the monofilament, the more force it will require to bend. The most commonly used device is the 5.07, which requires 10 g of force to buckle the monofilament. The theory behind the value of the SWM is that repetitive stress of the same amount of force will cause damage to the tissues, including ulcerations, leading to amputation.9-11 This modality, first developed for the Hansen’s disease patient, has been proven as an efficient, easy-to-use, inexpensive device for diabetic peripheral neuropathy screening.12,13 In Conclusion The aforementioned differential diagnosis for peripheral neuropathy includes those medical conditions that cause symmetrical loss of sensation in the extremities. These conditions include thyroid abnormalities, anemia, vitamin B12 deficiency, alcoholism, nutritional deficiencies, lupus and multiple other conditions. To rule out these medical conditions, one must order the appropriate tests for each if you suspect their presence. On occasion, the patient may require a nerve or muscle biopsy, electroencephalography, lumbar puncture and advanced imaging modalities such as MRI and CT scans in order to determine the etiology of a difficult to diagnose neuropathy. Ensuring a quick, accurate diagnosis of neuropathy can limit nerve damage and preserve the patient’s function and sensation. Dr. Satterfield is an Clinical Associate Professor at the University of Texas Health Science Center at San Antonio.
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