Abstract
Background:
The foot and ankle surgeon can see peripheral neuropathy in the treatment of foot and ankle conditions. The purpose of this study was (1) to evaluate the demographics and presenting complaints of patients diagnosed with idiopathic peripheral neuropathy during an examination by a foot and ankle surgeon and (2) to identify the type and frequency of subsequent diagnosis of medical causes of neuropathy.
Methods:
This was a retrospective study of patients diagnosed with idiopathic peripheral neuropathy in our practice between January 1997 and December 2008. Ninety-five patients were identified, and demographic data, presenting complaints, and medical comorbidities were extracted from the medical record. Examination findings of decreased sensation to Semmes Weinstein 5.07 monofilament testing were documented, and electromyogram and nerve conduction study results were reviewed when available. Laboratory values were noted, as were neurologic evaluations performed to diagnose medical conditions associated with peripheral neuropathy.
Results:
The most common presentation was foot pain, in 36 patients (38%). Ninety-one patients had Semmes Weinstein 5.07 monofilament testing, with loss of protective sensation reported in 75 of the 91 tested (82%). Only 30 of the 95 patients had electromyogram and nerve conduction study results available, with a test positive for peripheral neuropathy in 20 of the 30 tested. Thirty-two patients were evaluated by a neurologist. A specific cause was identified in 12 of the 32 seen by a neurologist. Of the total group of 95 patients, 31 patients (33%) were diagnosed with a condition that may be associated with peripheral neuropathy.
Conclusions:
Thirty-three percent of the patients presenting to our clinic and given a diagnosis of idiopathic peripheral neuropathy were ultimately diagnosed with a medical cause of neuropathy—most commonly, diabetes. For those patients with idiopathic neuropathy, a spectrum of disease was encountered, including pain, ulcer, infection, and Charcot neuroarthropathy.
Level of Evidence:
Level IV, retrospective case series.
The primary exposure of the foot and ankle surgeon to peripheral neuropathy is the diabetic patient. Diabetic peripheral neuropathy is the most common cause of peripheral neuropathy in developed countries, 10 and Charcot neuropathic arthropathy and foot ulceration in the diabetic patient frequently bring these patients to the attention of a foot and ankle surgeon. The prevalence of peripheral neuropathy has been reported to be up to 15% of people over the age of 40, and 50% of patients with diabetes ultimately develop neuropathy.7,11,14
Several reports exist in the literature regarding the appropriate identification and treatment of patients with neuropathy unrelated to diabetes, especially for the presenting complaint of pain.8,18,20 Recently, a case series drew attention to rheumatoid arthritis as an important comorbidity associated with peripheral neuropathy. 6 On many occasions, the cause of the underlying neuropathy is unknown or considered “idiopathic.” When patients present with the manifestations of neuropathy, such as neuropathic arthropathy or ulceration, the treatment course is similar to that when diabetes is the underlying cause. However, understanding the cause of neuropathy in these cases may be overlooked. It is not currently known whether peripheral neuropathy unrelated to diabetes carries the same risks after foot and ankle surgery as seen in the diabetic population, although Charcot arthropathy has been reported in patients with rheumatoid arthritis and more recently in idiopathic peripheral neuropathy.2,6,15,23
Neuropathy can present in a variety of ways. Patients may present to a foot and ankle specialist with foot pain without an obvious musculoskeletal origin. After appropriate evaluation, peripheral neuropathy can be considered as a cause of bilateral or unilateral foot pain in these patients and confirmed with further testing. In the absence of diabetes or other known causes of neuropathy, a diagnosis of idiopathic peripheral neuropathy is often given, but it may not be accurate. An approach to the diagnosis of peripheral neuropathy has been described. Electrodiagnostic testing, while useful, is not definitive in some cases. 20
Although diabetes is seen very commonly in the context of peripheral neuropathy, it does not account for all cases of neuropathy. In an epidemiologic study of 2 areas of Italy, the Italian Practitioner General Study Group found prevalence rates of 3.4% and 3.7% of polyneuropathy in people over the age of 55 with neuropathic symptoms. Diabetes was present in fewer than 50% of patients studied. 8 However, it is not clear whether the absence of a diagnosis of diabetes represents a truly idiopathic neuropathy. Glucose tolerance has been shown to be abnormal in up to 40% of patients diagnosed with idiopathic peripheral neuropathy (“impaired glucose tolerance” or “prediabetes” defined as a fasting glucose of 100 to 125 mg/dL or glucose levels of 140 to 199 mg/dL during a glucose tolerance test). 20 Normoglycemic patients with peripheral neuropathy have been reported to display features of other metabolic syndromes, such as hyperlipidemia. 19 Treatment of the underlying disease does not resolve symptoms of neuropathy in most cases.
The evaluation and subsequent treatment of a patient with idiopathic peripheral neuropathy are not clearly defined in the orthopaedic literature. In general, the same treatment considerations apply when the presenting complaint is Charcot arthropathy or ulceration whether the neuropathy is diabetes related or idiopathic. However, when the patient complains of chronic pain, treatment solutions are elusive. Painful neuropathy may also be caused by other medical conditions, such as vitamin deficiencies or hypothyroidism. The challenge for the orthopaedic surgeon is to recognize the condition and direct the patient appropriately for further diagnostic evaluation.
The purpose of this study was to evaluate the demographics and presenting complaints of patients diagnosed with idiopathic peripheral neuropathy at the time of examination by a foot and ankle surgeon and to identify the type and frequency of subsequent diagnoses of medical causes of neuropathy. We hypothesized that many patients with neuropathy of unknown origin may have an identifiable cause.
Methods
This was a retrospective study of all patients who were seen in our academic foot and ankle practice from January 1997 through December 2008 with signs or symptoms of peripheral neuropathy but no known cause. These patients were initially diagnosed with idiopathic peripheral neuropathy by a fellowship-trained foot and ankle surgeon using clinical evaluation and data available at the time of initial evaluation. Although the diagnosis of idiopathic peripheral neuropathy was given, these patients were best described as having presumed neuropathy of unknown origin. Patients presented with a variety of complaints that were not always directly related to the diagnosis of neuropathy. Approval for this retrospective review was obtained from the Institutional Review Board of our institution prior to chart review. Patients were identified through billing databases on the basis of diagnosis codes for peripheral neuropathy.
The charts of patients diagnosed with idiopathic peripheral neuropathy based on clinical evaluation were identified and reviewed retrospectively. Demographic data (age, sex, height, weight, body mass index), presenting complaints, medical comorbidities, tobacco use, and alcohol use were extracted from the medical record. Patients with diabetes mellitus or any other known cause of peripheral neuropathy were excluded. Patients were included regardless of presenting symptoms. Patients were identified as having unilateral or bilateral symptoms.
Physical examination findings of decreased sensation to Semmes Weinstein 5.07 monofilament testing were documented and electromyogram and nerve conduction study results reviewed when available. Subsequent laboratory findings were also noted, as was neurologic evaluation for possible diagnosis of a medical condition associated with peripheral neuropathy.
A total of 111 patients were identified and reviewed per billing codes for idiopathic peripheral neuropathy. According to available billing data, on average, 518 new patients per year were seen in this foot and ankle practice over the years studied. This population of patients represents approximately 2% of new patients during that period. Five patient records indicated a diagnosis of diabetes at the time of initial presentation, and these were excluded. An additional 11 patients were excluded with neuropathy in a single extremity related to a known condition causing neuropathy. The remaining 95 patients had an average age of 61.7 years. There were 50 women and 45 men. The average body mass index was 31 (data available for 91 of 95 patients). Fifteen patients (16%) reported regular tobacco use. Eleven patients (12%) indicated frequent alcohol use (more than 1 or 2 times per week), and 3 patients indicated a history of alcohol abuse. The patients reported a wide variety of medical comorbidities, with hypertension most common (52 patients, 56%). Nine patients had a known diagnosis of rheumatoid arthritis. Although the 12 patients with either a history of alcohol abuse (n = 3) or rheumatoid arthritis (n = 9) presented with conditions known to be associated with peripheral neuropathy, none had previously been diagnosed with neuropathy. At initial presentation, neuropathy in these 12 patients was not assumed or immediately recognized to be directly related to their medical conditions.
Results
The most common presenting complaint in the group of patients identified was pain, in 36 patients (38%). Twenty-four (25%) patients complained of bilateral foot pain. The next-most common presentation was ulceration, in 29 patients (31%). Ulceration, Charcot arthropathy, or infection (or some combination of those diagnoses) was seen in 41 patients. These diagnoses were considered to be a direct result of peripheral neuropathy. Other diagnoses were seen in 54 patients. Table 1 lists the presenting complaints of all patients. Given the types of presenting complaints, we identified 2 groups of patients: group 1 included patients with Charcot neuroarthropathy, ulcer, or infection (41 patients); group 2 included all other patients with a variety of complaints, most commonly pain (54 patients).
Presenting Complaints of Patients With Idiopathic Peripheral Neuropathy.
The presence of neuropathy was most consistently tested using the Semmes Weinstein 5.07 monofilament. Of the 95 patients, 91 had Semmes Weinstein 5.07 monofilament testing, and a loss of protective sensation characterized by the inability to feel the pressure of the monofilament (10 g of force) was reported in 75 of the 91 tested. Thirty patients had electromyogram and nerve conduction study results available, with a test positive for peripheral neuropathy in 20 of the 30 tested.
Although neurology evaluation was recommended to most patients, 32 pursued a formal evaluation by a neurologist for a possible cause of neuropathy. A specific cause was identified in 12 of the 32 patients. Of these 12 patients, 7 were diagnosed with diabetes. Other diagnoses were varied and included multiple sclerosis, amyloidosis, an amyotrophic lateral sclerosis variant, Parkinson disease, and vitamin B12 deficiency. Two patients had an identifiable cause in addition to a diagnosis of diabetes. Several patients were thought to have neuropathy related to previous chemotherapy or prior or current excessive alcohol use. When appropriate, the neuropathy was treated by the neurologist. The remaining 20 patients were presumed to have idiopathic neuropathy and were treated as such by the neurologist.
Of the 63 patients with no record of a formal neurology evaluation, 12 were subsequently evaluated by another physician and diagnosed with diabetes. Of the total group of 95 patients, 19 (20%) ultimately were diagnosed with diabetic peripheral neuropathy. Among all 95 patients, a total of 31 (33%) were diagnosed with a condition that caused peripheral neuropathy (Table 2).
Medical Diagnoses With Peripheral Neuropathy.
Two patients had a diagnosis of diabetes mellitus and another cause.
Based on review of hospital records, hemoglobin A1C was tested in 38 patients. The testing did not necessarily coincide with the workup for the foot pathology. Of the 38 patients, 18 had values greater than or equal to 6 (diagnosed with diabetes).
Among group 1 patients (n = 41; patients presenting with Charcot neuroarthropathy, ulcer, or infection), 26 were ultimately considered to have idiopathic peripheral neuropathy in the absence of any other diagnosis; 10 were eventually diagnosed with diabetes mellitus; and the remaining 5 patients were given other diagnoses. Among group 2 patients (n = 54; patients presenting complaints other than Charcot neuroarthropathy, ulcer, or infection), 39 were diagnosed with idiopathic peripheral neuropathy; 8 were eventually diagnosed with diabetes; and the remaining 7 patients were given other diagnoses. Table 3 outlines the comparison of these 2 groups. Between the 2 groups, it was more common for patients in group 2 to undergo evaluation by a neurologist (48% vs 6%).
Comparison of Patients by Presenting Complaints. a
Values presented in n (%), unless noted otherwise.
Mean (range).
In patients with current frequent alcohol use or a history of alcohol abuse, the alcohol use was not always identified as a causative factor. The 3 patients with a known history of alcohol abuse were considered to have idiopathic peripheral neuropathy through the course of their care. Chart review identified an additional 10 patients with frequent alcohol use: 3 of these patients were given the diagnosis of alcohol-related peripheral neuropathy; 1 of these patients was thought to have neuropathy as a result of amyloidosis; and the remaining 6 were diagnosed as having idiopathic peripheral neuropathy.
In the 9 patients with known rheumatoid arthritis, 2 were diagnosed with diabetes and thought to have diabetic neuropathy, and the remaining 7 patients maintained a diagnosis of idiopathic peripheral neuropathy despite the presence of rheumatoid arthritis.
Of the 95 patients, 65 (68%) had a final diagnosis of idiopathic peripheral neuropathy. In that group, the average age was 61 years (range, 23-91). There were 34 female and 31 male patients. The average body mass index was 31. If patients with rheumatoid arthritis, frequent alcohol use, or history of alcohol abuse who were thought to have idiopathic peripheral neuropathy are removed from this group, 49 (52%) would be considered to have a diagnosis of idiopathic peripheral neuropathy.
Discussion
Idiopathic peripheral neuropathy is a poorly understood condition that frequently presents to the foot and ankle surgeon. While pain is many times the presenting complaint, other manifestations of neuropathy are seen and may require treatment. Several studies have discussed the appropriate steps in evaluating these patients.8,18,20 In our practice, we seek to identify the presence of peripheral neuropathy and to refer these patients to an appropriate provider for further evaluation when no known cause of neuropathy exists. In the patient group studied, 31 (33%) of the 95 patients were ultimately diagnosed with a cause other than idiopathic neuropathy. Of those 32, 19 were diagnosed with diabetes.
Sixteen additional patients had either a history of alcohol abuse or a diagnosis of rheumatoid arthritis, with both conditions known to be associated with peripheral neuropathy. However, in the course of their treatment, their neuropathy was considered idiopathic or attributed to another cause. Rheumatoid arthritis has a known association with neuropathy.1,5 Underlying causative factors have been considered to be drug toxicity, vasculitis, or entrapment. However, in many cases, the presence of neuropathy in this patient population may be underappreciated. In this review of cases of neuropathy, rheumatoid arthritis was not assumed to be the cause of neuropathy and was potentially overlooked as a reasonable explanation for the patient’s condition. Similarly, alcohol abuse has been studied as a cause of peripheral neuropathy.12,13,24 Although initially thought to be related to nutritional status, more recent studies suggest toxicity of the alcohol as the causative factor. 13 In this study, alcohol abuse was identified as the possible cause of neuropathy in only 3 patients, but 9 additional patients reported a history of alcohol abuse or current frequent use. In the orthopaedic setting, it is possible that this factor is also underappreciated as a contributing factor in neuropathic conditions. Grear et al showed that Charcot neuroarthropathy occurs in the setting of rheumatoid arthritis with no other known cause of neuropathy. 6 Foot and ankle manifestations of alcohol-related neuropathy have not been extensively studied.
When considering the conditions of Charcot neuroarthropathy, ulcer and infection were not confined to the diabetic patient population in the group studied. Sixty-three percent of the patients with these conditions were those with idiopathic peripheral neuropathy. It is not currently known whether idiopathic peripheral neuropathy carries the same risk as neuropathy associated with diabetes when outcome after surgical procedures of the foot and ankle is considered. However, Charcot neuroarthropathy, ulcer, and infection occurred in patients without diabetes as a cause of neuropathy in this series. Bariteau et al recently reported a group of patients with Charcot arthropathy and idiopathic peripheral neuropathy. 2 In this study, patients were considered to have idiopathic peripheral neuropathy when no other identifiable source of neuropathy was present. The authors emphasized the importance of recognition and appropriate treatment in this patient group.
The sequelae of diabetic neuropathy have been more extensively studied.22,23 Wukich et al reported on rates of limb salvage in severe diabetic foot infections. 22 In that series, foot infections were classified according to severity. The most severe diabetic foot infections resulted in a higher rate of amputation and longer hospital stays. Other aspects of care have been investigated by multiple authors, including psychological response of patients with diabetic foot ulceration, infection and amputation, and associated health care costs.3,4,16,17,21,22 We assume that the same strategies used to manage the diabetic patient with neuropathy will be beneficial to the patient with idiopathic neuropathy or neuropathy related to other causes. In our practice, we routinely used the same protocols for diabetic neuropathy, including prolonged periods of immobilization and nonweightbearing, total contact casting, and surgical technique based on augmented fixation techniques in all neuropathic patients. 9 We choose to carefully evaluate neurovascular status preoperatively to reduce risk and adjust treatment protocols accordingly.
In this study, group 2 patients were more likely to pursue neurologic evaluation. This study did not investigate the reason for this discrepancy (48% in group 2 vs 6% in group 1). Without additional data, one possible explanation is that these patients presented a greater diagnostic and treatment challenge. Frequently they presented with pain that was not immediately appreciated to be neurologic in origin. The additional evaluation by neurology may have been one of several diagnostic maneuvers to identify the cause of pain. It is also feasible that patients with primarily neuropathic pain that was not easily treated with orthopaedic interventions were more likely to seek additional evaluation in the hope of finding successful treatment. In the case of the patient with ulcer, Charcot neuroarthropathy, or infection, the need for more immediate orthopaedic treatment may have overshadowed further evaluation of the neuropathy.
The primary limitation of this study was the retrospective nature of the evaluation. Patient data were available from 1 hospital system. Although many patients were referred for neurology evaluation, only 30 were found to have records available from that evaluation. We cannot know for certain that the remaining patients did not pursue the evaluation at another hospital system. In addition, subsequent diagnosis of diabetes may have been made at an outside facility. Further study of patients with neuropathy, with and without serious sequelae, is needed to determine whether this is a spectrum of disease or possibly 2 different conditions.
Conclusions
Idiopathic peripheral neuropathy is a cause of foot pathology presenting to the orthopaedic foot and ankle surgeon. Thirty-three percent of the patients presenting to our clinic and given a diagnosis of idiopathic peripheral neuropathy were ultimately diagnosed with an underlying cause of neuropathy—most commonly, previously undiagnosed diabetes. For those patients with idiopathic neuropathy, a spectrum of disease was encountered, including pain, ulcer, infection, and Charcot neuroarthropathy.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.