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Diabetic peripheral neuropathy: How reliable is a homemade 1-g monofilament for screening?
... An inexpensive alternative to purchasing commercially available monofilaments is to use 25-lb (0.020-inch diameter) fishing line. 24 A fishing line cut into a 4-cm segment is similar to a 10 g monofilament and an 8-cm segment is similar to a 1 g monofilament. 24 In addition, Dr. Vinik recommends that during examination the clinician look for signs of autonomic pathology, such as dry and hairless skin, distended veins, edema, and cold skin. ...
... 24 A fishing line cut into a 4-cm segment is similar to a 10 g monofilament and an 8-cm segment is similar to a 1 g monofilament. 24 In addition, Dr. Vinik recommends that during examination the clinician look for signs of autonomic pathology, such as dry and hairless skin, distended veins, edema, and cold skin. An insensate foot can result in repeated minor trauma and can cause foot ulcers. ...
At least 3 million people in the United States are living with neuropathic pain of various etiologies. 1 More than half of these people have peripheral neuropathies caused by diabetes, herpes zoster, or human immunodeficiency virus (HIV). 1 Postherpetic neuralgia (PHN), which is caused by herpes zoster infection, and diabetic peripheral neuropathy (DPN) have a combined prevalence of 1,100 per 100,000 people. 2 HIV neuropathy has a prevalence of 15 per 100,000 people but is present in 30% of HIV patients. 2,3 Despite the frequency with which these conditions occur, diagnosis and management can represent challenges for the clinician. HIV neuropathy and DPN are often underdiagnosed and/or undertreated. 4,5 The multiple presentations of pain associated with PHN can make diagnosis difficult, especially in patients who present without a defined herpes zoster rash. 6 Recognizing and treating the underlying condition can reduce the occurrence of neuropathy. Even when the underlying cause is managed appropriately, neuropathic pain can still occur. Many pharmacologic therapies are available, but they are not equally effective in treating all neuropathic pain conditions. 7 Furthermore, most patients with neuropathic pain are not receiving appropriate analgesic therapy (ie, anticonvulsants, lidocaine patch, tricyclic antidepressants, etc), but instead are given nonsteroidal anti-inflammatory agents or aspirin. 7,8 These topics were discussed at a satellite symposium that took place on January 29, 2009, during the 25th Annual Meeting of the American Academy of Pain Medicine. This CME-certified newsletter summarizes the content of that satellite symposium.
... A low cost instrument has been proven to be equivalent to the internationally accepted instrument in assessing the risk of foot ulcers in diabetes patients, and that it has the potential to become standard for detecting diabetic neuropathy [3]. As an advantage of fishing nylon in the detection of diabetic neuropathy in a case-control study in addition to its mechanical features, a feature that stood out was its economy, as well as its simplicity and the speed of conducting the test, which shows its potential in daily clinical practice [4]. ...
In this paper the fractional Kelvin-Zener model of viscoelastic body was used for modeling the behavior of monofilament and fluorocarbon during the ramp and hold type of experiment, using diferent deformation velocities. First, experimental measurements were made on 9 samples of each material. Three sample groups were tested at different deformation rates during the first phase of the experiment. Afterward, the relaxation phase was kept consistent across all samples. Riemann-Liouville fractional derivatives were approximated numerically using the Grünwald-Letnikov definition. Four model parameters have been determined for each sample by numerical procedure. Finally, the experimental results were compared with the results provided by the fractional Kelvin-Zener model.
... Monofilament tests for superficial and vibratory stimulus for deep sensation may provide early data for neuropathy. Nerve conduction studies and skin biopsy are more detailed and useful but not practical methods [5,6] . The Toronto Consensus Panel defined diagnostic guidelines based on these methods [7] . ...
Background:
Diabetic polyneuropathy is a very common complication of diabetes. Numerous studies are available in terms of pathogenesis. But examination methods with low reliability are still not standardized and generally time consuming. High-sensitive, easy-to-access methods are expected. Biochemical markers are one of the subjects of research. We aimed to discover a potential biomarker that can be used for this purpose in patients with diabetes who have not yet developed symptoms of neuropathy.
Aim:
To determine the place and availability of visfatin and thiol-disulfide homeostasis in this disorder.
Methods:
A total of 392 patients with type 2 diabetes mellitus were included in the study. The polyneuropathy clinical signs were evaluated with the Subjective Peripheral Neuropathy Screen Questionnaire and Michigan Neuropathy Screening Instrument questionnaire and examination. The biochemical parameters, oxidative stress markers, visfatin, and thiol-disulfide homeostasis were analyzed and correlated with each other and clinical signs.
Results:
Subjective Peripheral Neuropathy Screen Questionnaire and Michigan Neuropathy Screening Instrument questionnaire with examination scores were correlated with each other and diabetes duration (P < 0.005). Neuropathy related symptoms were present in 20.7% of the patients, but neuropathy related findings were observed in 43.9% of the patients. Serum glucose, glycated hemoglobin, and visfatin were positively correlated with each other. Also, these parameters were positively correlated with the total oxidative stress index. Total and native thiol was positively correlated with total antioxidant status and negatively with oxidant status. Inversely thiol-disulfide positively correlated with higher glucose and oxidant status and negatively with total antioxidant status (P < 0.005). There was no correlation between visfatin and thiol-disulphide (P = 0.092, r = 0.086). However, a significant negative correlation was observed between visfatin and total with native thiol (P < 0.005, r = -0.338), (P < 0.005, r = -0.448).
Conclusion:
Diagnosis of neuropathy is one of the issues studied in patients with diabetes. Visfatin and thiol-disulfide balance were analyzed for the first time in this study with inspiring results.
... However, those high-risk factors may be varied upon different demographic features and T2DM development. Human DPN is characterized by nerve fiber loss, axonal degeneration, and segmental demyelization with a decrease in nerve conduction velocity due to decreased intraepidermal nerve fiber density and reduced myelin thickness of the nerve sheath, so DPN is one of the most insidious, asymptomatic complications of diabetes, but it could results in irreversible foot ulcer, insensate foot injury, lower-extremity amputation and mortality in diabetic patients [6][7][8]. ...
... Diabetes and the Nervous System and 10 g monofilament; pinprick by Wartenberg wheel, Neurotips, or a pin; temperature by cold and warm objects) ( Table 5) (Haanpaa et al. 2009). For the monofilament test, a simple substitute is to use 25 lb strain fishing line cut into 4 and 8 cm lengths, which translate to 10 and 1 g monofilaments, respectively (Bourcier et al. 2006). Vibration detection threshold and 10 g monofilament have been validated for the screening of DSPN (Perkins et al. 2001). ...
Diabetic neuropathy is the most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care. It includes a set of clinical syndromes that affect distinct regions of the nervous system, singly or combined. Current research shows that diabetes can affect brain structure and function and lead to significant changes in cognition and behavior. Peripheral neuropathy may be silent and go undetected or it may present with clinical symptoms and signs including pain that can significantly affect the patients’ quality of life. It also contributes to additional risks in the aging adult. Loss of sensory perception and muscle strength, and ataxia or incoordination, leads to an increased risk of falling in the elderly. However, risk factors for falling are not simply confined to those variables associated with peripheral sensory-motor function. Cognitive decline, particularly related to executive functioning, is a contributing factor to instability. Cardiac autonomic neuropathy is a common complication of diabetes. Early diagnosis is key, as it has been shown to be an independent risk factor for cardiovascular mortality, arrhythmias, major cardiovascular event, and myocardial dysfunction. This Chapter will describe our current knowledge on central, peripheral, and autonomic nervous system alterations in response to prediabetes and type 1 and type 2 diabetes.
... Diabetes and the Nervous System and 10 g monofilament; pinprick by Wartenberg wheel, Neurotips, or a pin; temperature by cold and warm objects) ( Table 5) (Haanpaa et al. 2009). For the monofilament test, a simple substitute is to use 25 lb strain fishing line cut into 4 and 8 cm lengths, which translate to 10 and 1 g monofilaments, respectively (Bourcier et al. 2006). Vibration detection threshold and 10 g monofilament have been validated for the screening of DSPN (Perkins et al. 2001). ...
... Diabetes and the Nervous System and 10 g monofilament; pinprick by Wartenberg wheel, Neurotips, or a pin; temperature by cold and warm objects) ( Table 5) (Haanpaa et al. 2009). For the monofilament test, a simple substitute is to use 25 lb strain fishing line cut into 4 and 8 cm lengths, which translate to 10 and 1 g monofilaments, respectively (Bourcier et al. 2006). Vibration detection threshold and 10 g monofilament have been validated for the screening of DSPN (Perkins et al. 2001). ...
... 1) The monofilament testing devices can be purchased for about $0.50 each, 17 or can even be home-made from a 4 cm segment of Nylon 6 (homopolymer) or inexpensive 25# test monofilament fishing line with one cm held between the fingers. 41,42 2) When screening large populations, use a new monofilament on each patient for infection control and to avoid filament fatigue, which occurs after about 100 consecutive compressions. 43 Monofilaments regain their accuracy with rest, so the patient can keep their monofilament to test themselves. ...
Diabetic Foot Ulcers are a common chronic wound type which often have an Arterial Disease component. This heavily referenced clinical education booklet provides detailed information on the causes, prevention, and management of diabetic foot and arterial ulcers. A procedure, protocol, decision tree, and index assist clinicians in utilizing this information.
... Diabetes and the Nervous System and 10 g monofilament; pinprick by Wartenberg wheel, Neurotips, or a pin; temperature by cold and warm objects) ( Table 5) (Haanpaa et al. 2009). For the monofilament test, a simple substitute is to use 25 lb strain fishing line cut into 4 and 8 cm lengths, which translate to 10 and 1 g monofilaments, respectively (Bourcier et al. 2006). Vibration detection threshold and 10 g monofilament have been validated for the screening of DSPN (Perkins et al. 2001). ...
Diabetic neuropathy is the most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care. It includes a set of clinical syndromes that affect distinct regions of the nervous system, singly or combined. Current research shows that diabetes can affect brain structure and function, and lead to significant changes in cognition and behavior. Peripheral neuropathy may be silent and go undetected or it may present with clinical symptoms and signs including pain that can significantly affect the patients’ quality of life. It also contributes to additional risks in the aging adult. Loss of sensory perception and muscle strength, and ataxia or incoordination leads to an increased risk of falling in the elderly. However, risk factors for falling are not simply confined to those variables associated with peripheral sensory-motor function. Cognitive decline, particularly related to executive functioning, is a contributing factor to instability. Cardiac autonomic neuropathy is a common complication of diabetes. Early diagnosis is key, as it has been shown to be an independent risk factor for cardiovascular mortality, arrhythmias, major cardiovascular event, and myocardial dysfunction. This chapter will describe our current knowledge on central, peripheral and autonomic nervous system alterations in response to prediabetes and type 1 and type 2 diabetes.
... Earlier intervention would likely allow for more positive outcomes, and low-cost tools to detect symptomology before the diagnosis of PD or T2D may be useful. Several tools, such as the 128 Hz tuning fork and the 1 g and 10 g monofilaments, have been successfully used for screening and disease assessment in adults with PD and T2D [20][21][22][23][24][25][26]. The Norfolk Quality of Life Diabetic Neuropathy (QOL-DN) questionnaire, NC-stat DPNCheck, and hemoglobin A1C testing (HbA 1C ) have been validated in T2D and limited PD populations, making them likely candidates for successful early screening efforts [1,[27][28][29][30][31]. ...
Objective
Examine the effectiveness of the 128 Hz tuning fork, two monofilaments, and Norfolk Quality of Life Diabetic Neuropathy (QOL-DN) questionnaire as tools for the early detection of diabetic peripheral neuropathy (DPN) in overweight, obese, and inactive (OOI) adults or those who have prediabetes (PD) or type 2 diabetes (T2D).
Research Design and Methods
Thirty-four adults (mean age 58.4 years ± 12.1) were divided by glycemia (10 OOI normoglycemic, 13 PD, and 11 T2D). Sural nerves were tested bilaterally with the NC-stat DPNCheck to determine sural nerve amplitude potential (SNAP) and sural nerve conduction velocity (SNCV). All other testing results were compared to SNAP and SNCV.
Results
Total 1 g monofilament scores significantly correlated with SNAP values and yielded the highest sensitivity and specificity combinations of tested measures. Total QOL-DN scores negatively correlated with SNAP values, as did QOL-DN symptoms. QOL-DN activities of daily living correlated with the right SNAP, and the QOL-DN small fiber subscore correlated with SNCV.
Conclusions
The 1 g monofilament and total QOL-DN are effective, low-cost tools for the early detection of DPN in OOI, PD, and T2D adults. The 128 Hz tuning fork and 10 g monofilament may assist DPN screening as a tandem, but not primary, early DPN detection screening tools.
... Light (1.4 g) monofilament may be more sensitive than using a standard (10 g) monofilament, detecting sensory neuropathy at an earlier stage. 40,41 The symptoms of numbness and deep aching or burning pain in the legs or feet may not be specific for peripheral neuropathy in older adults in the context of B12 deficits. Peripheral nerve impairments have been shown to be largely asymptomatic in older adults, even in those with diabetes mellitus. ...
... One or more of the following can be used to assess sensory function: pinprick (using the Waardenberg wheel or similar instrument), temperature, vibration perception (using 128-Hz tuning fork) or 1 & 10-g monofilament pressure perception at the distal halluces. For this last test a simple substitute is to use 25 lb strain fishing line cut into 4 cm and 8 cm lengths, which translate to 10 and 1 g monofilaments respectively (104). The most sensitive measure has been shown to be the vibration detection threshold, although sensitivity of 10-g Semmes-Weinstein monofilament to identify feet at risk varies from 86 to 100% (105) (106). ...
Diabetic neuropathy (DN) is the most common form of neuropathy in developed countries and may affect about half of all patients with diabetes (DM), contributing to substantial morbidity and mortality and resulting in a huge economic burden. DN encompasses multiple different disorders involving proximal, distal, somatic, and autonomic nerves. It may be acute and self-limiting or a chronic, indolent condition. DN may be silent and go undetected while exercising its ravages, or it may present with clinical symptoms and signs that may mimic those seen in many other diseases. The proper diagnosis therefore requires a thorough history, clinical and neurological examinations, and exclusion of secondary causes. The distal neuropathies are characteristically symmetric, glove and stocking distribution, length-dependent sensorimotor polyneuropathies that develop on a background of long-standing chronic hyperglycemia superimposed upon cardiovascular risk factors. Diagnosis is based on a combination of signs, symptoms, and abnormal neurophysiological test results. No treatment has been approved for the prevention or reversal of DN. Even tight glycemic control at best limits the progression of neuropathy in patients with type 1 DM, but does not affect DN in patients with type 2 DM. It has been estimated that between 3 and 25% of persons with DM might experience neuropathic pain. Painful DN can be difficult to treat, and is associated with reduced quality of life, poor sleep, depression and anxiety. Treatment guidelines suggest that pregabalin, gabapentin, venlafaxine, duloxetine, tricyclic antidepressants, and opioids are the drugs with the best evidence to support their use for painful DN. Tapentadol has also received FDA approval for the treatment of painful DN. The reported prevalence of diabetic autonomic neuropathy (DAN) varies widely (7.7 to 90%) depending on the cohort studied and the methods used for diagnosis, and can affect any organ system. Cardiovascular autonomic neuropathy (CAN) is significantly associated with overall mortality and with morbidity, including silent myocardial ischemia, coronary artery disease, stroke, DN progression, and perioperative complications. Cardiovascular reflex tests are the criterion standard in clinical autonomic testing; combining these with sudomotor function tests may allow a more accurate diagnosis. Strict glycemic control, management of lipids and blood pressure as well as the use of antioxidants. and ACE inhibitors reduce the odds ratio for DAN to 0.32; treatment is otherwise symptomatic. For complete coverage of this and related areas in Endocrinology, visit the free online web-textbook, www.endotext.org.
... Early diagnosis of DSPN is imperative in preventing irreversible damage; however, 50 % of patients may be asymptomatic. A 1-g Semmes-Weinstein monofilament is useful for detecting changes in sensitivity [41], and a 10-g monofilament is useful for predicting ulcer risk. A small decrease in the duration of a vibratory stimulus sensation, assessed with a 128-Hz tuning fork, is an early indicator of neuropathy. ...
Distal symmetric polyneuropathy (DSPN), the most common form of diabetic neuropathy, has a complex pathophysiology and can be a major source of physical and psychologic disability. The management of DSPN can be frustrating for both patient and physician. This article provides a general overview of typical patient pathways in DSPN, and highlights variations in diagnosis, management, and referral patterns among different providers. DSPN is managed in several settings by primary care physicians (PCPs), specialists, and nurse practitioners. The initial clinical management of the patient is often dependent on the presenting complaint, the referral pattern of the provider, level of comfort of the PCP in managing diabetic complications, and geographic access to specialists. The primary treatment of DSPN focuses mainly on glycemic control and adjustment of modifiable risk factors, but other causes of neuropathy should also be investigated. Several pharmacologic agents are recommended by treatment guidelines, and as DSPN typically exists with comorbid conditions, a multimodal therapeutic approach should be considered. Barriers to effective management include failure to recognize DSPN, and misdiagnosis. Patient education also remains important. Referral patterns vary widely according to geographic location, access to services, provider preferences, and comfort in managing complex aspects of the disease. The variability in patient pathways affects patient education, satisfaction, and outcomes. Standardized screening tools, a multidisciplinary team approach, and treatment algorithms for diabetic neuropathy should improve future care. To improve patient outcomes, DSPN needs to be diagnosed sooner and interventions made before significant nerve damage occurs.
... In contrast to the 10-g monofilament, which is generally associated with clinical disease and predictive of foot ulceration, 57 the 1.4-g monofilament may be a more sensitive measure, detecting sensory nerve function loss at an early stage. 58,59 Since risk factors for declining muscle power in older adults are understudied, this test could potentially be used to help develop prevention strategies to preserve muscle function. ...
Objective:
To assess whether sensorimotor peripheral nerve function is associated with muscle power in community-dwelling older men.
Design:
Longitudinal cohort study with 2.3±0.3 years of follow-up.
Setting:
One clinical site.
Participants:
Participants (n=372; mean age ± SD, 77.2±5.1y; 99.5% white; body mass index, 27.9±3.7kg/m(2); power, 1.88±0.6W/kg) at 1 site of the Osteoporotic Fractures in Men Study (N=5994).
Interventions:
Not applicable.
Main outcome measures:
A nerve function ancillary study was performed 4.6±0.4 years after baseline. Muscle power was measured using a power rig. Peroneal motor nerve conduction amplitude, distal motor latency, and mean f-wave latency were measured. Sensory nerve function was assessed using 10-g and 1.4-g monofilaments and sural sensory nerve conduction amplitude and distal latency. Peripheral neuropathy symptoms at the leg and feet were assessed by self-report.
Results:
After adjustments for age, height, and total body lean and fat mass, 1 SD lower motor (β=-.07, P<.05) and sensory amplitude (β=-.09, P<.05) and 1.4-g (β=-.11, P<.05) and 10-g monofilament insensitivity (β=-.17, P<.05) were associated with lower muscle power/kg. Compared with the effect of age on muscle power (β per year, -.05; P<.001), this was equivalent to aging 1.4 years for motor amplitude, 1.8 years for sensory amplitude, 2.2 years for 1.4-g monofilament detection, and 3.4 years for 10-g detection. Baseline 1.4-g monofilament detection predicted a greater decline in muscle power/kg. Short-term change in nerve function was not associated with concurrent short-term change in muscle power/kg.
Conclusions:
Worse sensory and motor nerve function were associated with lower muscle power/kg and are likely important for impaired muscle function in older men. Monofilament sensitivity was associated with a greater decline in muscle power/kg, and screening may identify an early risk for muscle function decline in late life, which has implications for disability.
... SW monofilament has been extensively validated previously to detect neuropathy. [13][14][15][16] Autonomic, central, optic and multifocal motor neuropathies have been documented presenting asymptomatically. [17][18][19][20][21][22] Detection of asymptomatic neuropathy in foot is important for better management and care of foot in diabetic patients who are susceptible to complications and amputations. ...
Objective: To detect neuropathy in diabetics who are clinically asymptomatic, using SW monofilament and to correlate the frequency of detected neuropathy with the duration of diabetes. Methodology: Known patients of type 2 diabetes that do not have symptoms of peripheral neuropathy were included. Height, weight and duration of diabetes were measured and BMI calculated. SW monofilament was pressed perpendicular to the test site with enough pressure to bend it for one second. Comparison of frequency of SW monofilament test among gender was done by x 2 test. Bivariate correlation of SW monofilament test result with duration of diabetes was done by Kendall's test. Results: A total of 700 patients including 324 males and 376 females were examined. Asymptomatic neuropathy was detected in 14.4% of patients. The mean age of males was significantly more (50.4 ±9.0 vs 46.7 ±8.4 yrs; P < 0.0001) but BMI was lower than females (24.4 ±2.8 vs 26.2 ±4.2; P < 0.0001). No correlation of asymptomatic neuropathy with duration of diabetes was detected (P = 0.995). Conclusions: Asymptomatic neuropathy is prevalent in our diabetic population and it does not correlate with the duration of diabetes. Diabetics should be actively screened for asymptomatic neuropathy by SW monofilament.
... There was no association with deficient B12 status and ability to detect standard (10g) monofilament or peripheral neuropathy symptoms, common clinical screens for peripheral nerve problems. Light (1.4g) monofilament may be more sensitive compared to using a standard (10g) monofilament, detecting sensory neuropathy at an earlier stage [40][41] . The symptoms of numbness and deep aching/burning pain in the legs or feet may not be specific for peripheral neuropathy in older adults in the context of B12 deficits. ...
To examine whether deficient B12 status or low serum B12 levels are associated with worse sensory and motor peripheral nerve function in older adults.
Cross-sectional.
Health, Aging and Body Composition Study.
Two thousand two hundred and eighty-seven adults aged 72 to 83 (mean 76.5 ± 2.9; 51.4% female; 38.3% black).
Low serum B12 was defined as serum B12 less than 260 pmol/L, and deficient B12 status was defined as B12 less than 260 pmol/L, methylmalonic acid (MMA) greater than 271 nmol/L, and MMA greater than 2-methylcitrate. Peripheral nerve function was assessed according to peroneal nerve conduction amplitude and velocity (NCV) (motor), 1.4 g/10 g monofilament detection, average vibration threshold detection, and peripheral neuropathy symptoms (numbness, aching or burning pain, or both) (sensory).
B12-deficient status was found in 7.0% of participants, and an additional 10.1% had low serum B12 levels. B12 deficient status was associated with greater insensitivity to light (1.4 g) touch (odds ratio = 1.50, 95% confidence interval = 1.06-2.13) and worse NCV (42.3 vs 43.5 m/s) (β = -1.16, P = .01) after multivariable adjustment for demographics, lifestyle factors, and health conditions. Associations were consistent for the alternative definition using low serum B12 only. No significant associations were found for deficient B12 status or the alternative low serum B12 definition and vibration detection, nerve conduction amplitude, or peripheral neuropathy symptoms.
Poor B12 (deficient B12 status and low serum B12) is associated with worse sensory and motor peripheral nerve function. Nerve function impairments may lead to physical function declines and disability in older adults, suggesting that prevention and treatment of low B12 levels may be important to evaluate.
... A simple substitute is to use 25pound strain fishing line and cut 4-cm and 8-cm lengths, which translate to 10-and 1-g monofilaments. [26] The most sensitive one is the vibration detection threshold, but combinations of more than one test have more than 87% sensitivity in detecting DPN. [10,27] Results from longitudinal studies have shown that these simple tests are good predictors of foot-ulcer risk. ...
Objective
To review the clinical manifestations and current treatment options for diabetic neuropathies, one of the most common complications of diabetes mellitus.
Methods
We performed a MEDLINE search of the English-language literature using a combination of words (diabetic neuropathy, diabetic autonomic neuropathy, diagnosis and treatment) to identify original studies, consensus statements, and reviews on diabetic neuropathies published in the past 25 years. Emphasis was placed on clinical manifestations of distal polyneuropathy and its treatment, especially new therapies.
Results
Distal symmetric polyneuropathy, the most common form of diabetic neuropathy, usually involves small and large nerve fibers. Small-nerve fiber neuropathy often presents with pain and loss of intraepidermal nerve fibers, but without objective signs or electrophysiologic evidence of nerve damage. This type of neuropathy is a component of impaired glucose tolerance and the metabolic syndrome. The greatest risk from small-fiber neuropathy is foot ulceration and subsequent gangrene and amputation. Large-nerve fiber neuropathy produces numbness, ataxia, and incoordination, thus impairing activities of daily living and causing falls and fractures. Successfully treating diabetic neuropathy requires addressing the underlying pathogenic mechanisms, treating symptoms to improve quality of life, and preventing progression and complications of diabetes mellitus. Two new drugs, duloxetine hydrochloride and pregabalin, have recently been approved for treatment of neuropathic pain associated with diabetes mellitus.
Conclusion
Symptomatic therapy has become available and newer and better treatment modalities, based on etiologic factors, are being explored with potential for clinically significant reduction of morbidity and mortality. Preventive strategies and patient and physician education still remain key factors in reducing complication rates and mortality. (Endocr Pract. 2007;13:550-566)
Diabetic neuropathy is the most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care. It includes a set of clinical syndromes that affect distinct regions of the nervous system, singly or combined. Current research shows that diabetes can affect brain structure and function, and lead to significant changes in cognition and behavior. Peripheral neuropathy may be silent and go undetected or it may present with clinical symptoms and signs including pain that can significantly affect the patients’ quality of life. It also contributes to additional risks in the aging adult. Loss of sensory perception and muscle strength, and ataxia or incoordination leads to an increased risk of falling in the elderly. However, risk factors for falling are not simply confined to those variables associated with peripheral sensory-motor function. Cognitive decline, particularly related to executive functioning, is a contributing factor to instability. Cardiac autonomic neuropathy is a common complication of diabetes. Early diagnosis is key, as it has been shown to be an independent risk factor for cardiovascular mortality, arrhythmias, major cardiovascular event, and myocardial dysfunction. This chapter will describe our current knowledge on central, peripheral and autonomic nervous system alterations in response to prediabetes and type 1 and type 2 diabetes.
Monofilament testing has become one of the main methods used to screen people with diabetes for increased risk of neuropathic foot ulceration. There are many different types of monofilaments in use, and although the most common is the 10-g monofilaments, other available monofilaments require different force levels to bend them. This article will discuss the role of monofilaments in screening people with diabetes, and the implications of using inaccurate monofilaments.
The worldwide burden of diabetes and its complications in children continues to increase due to the rise in type 1 and type 2 diabetes. Although overt diabetic neuropathy is rarely present in children and adolescents with diabetes, subclinical diabetic neuropathy has been estimated to occur in approximately half of all children with type 1 diabetes with a duration of 5 years or longer and up to 25% of pediatric patients with newly diagnosed diabetes have abnormal findings on nerve conduction studies. The present review on the state of pediatric diabetic neuropathy covers the definition, prevalence, pathogenesis, diagnosis, risk factors, and possible treatment approaches specific to children and adolescents with diabetes. It also highlights the many unknowns in this field. Nonetheless, new emerging interventions that can either prevent or delay the progression of diabetic microvascular and macrovascular complications may become available in the near future. Until specific interventions for diabetic neuropathy are available for use in children, it will be hard to justify screening for neuropathy other than through clinical assessment. Meanwhile, the search for quicker, easily administered, and quantifiable tests for diabetic neuropathy and efforts to establish valid pediatric norms for well-established measures used in adults will need to continue.
Both peripheral and autonomic neuropathies are characterized by a progressive loss of nerve fiber function. Most peripheral neuropathy affects the extremities, particularly the lower legs and the feet, but also the hands, whereas damage to the autonomic nervous system may lead to imbalances between the sympathetic and parasympathetic nerve fibers that innervate the heart and blood vessels, as well as abnormalities in heart rate control and vascular dynamics. To prescribe or engage in exercise that is both safe and effective, health care providers and patients with diabetes mellitus need to increase their understanding of the pathophysiological nature of neuropathies and the physical activity hurdles that may arise from the presence of a neuropathy. With proper care and preventative measures, patients with diabetes mellitus that experience either type of neuropathy can benefit from regular participation in mild to moderate aerobic, resistance, and balance activities, assuming they take any potential alterations into account to ensure that exercise is safe and effective.
Clinical trials of agents for the treatment of diabetic neuropathy have been confronted with a lack of agreement on appropriate
endpoints and have generated controversy on why ample demonstration of efficacy of an agent in animal studies has not been
readily translated into success in human clinical trials. There has been a failure to recognize that the relief of symptoms
does not equate to change in the underlying biological disorder and great disagreement on indices, which can reliably measure
changes in nerve function which translate into changes in the quality of life, activities of daily living, and health of the
individual. Here, one will focus on the various measures that have been used for the evaluation of symptoms and those that
quantify nerve function and compare and contrast the reasons for failure of different measures neurological deficits, prevention
of degeneration of specific small fiber, large fiber and autonomic nerve deficits and those that have potential for reversal
of these deficits.
Diabetic foot is considered to be one of the most serious complications for patients suffering from Diabetes Mellitus (DM). Approximately 20–25% of all diabetic patients will present with lower extremity ulceration at some time in their lives. Diabetic foot is the leading cause of non-traumatic lower limb amputations in the world, resulting in an amputation risk for diabetic patients that is approximately 40 times greater than that of the general population. Post-amputation mortality is extremely high, with a three-year survival rate of 65% and a five-year survival rate of 41%. It is a health issue affecting several countries and represents a significant socioeconomic problem.1-4 In Brazil, amputation, admission, ulceration, and cost data are similar to other Western countries.5-7 Recognition of individuals at risk for ulceration, followed by adequate intervention, may reduce the chance of unfavorable results up to 80%.8
Peripheral sensory-motor neuropathy, which is responsible for the progressive loss of protective and proprioceptive sensations, is considered the main agent of the clinical abnormalities found in diabetic foot patients. It is important to consider that in the final phases of the disease the patient may present with a completely insensitive foot.9,10 One of the first studies looking to improve touch sensitivity screening dates back to 1898 and used a horsehair attached to a thorn.11 This method was refined and currently a 10g nylon monofilament, developed by Semmes and Weinstein, is accepted as the gold standard for detecting ulcer risk.12 Its reproducibility and predictive value lead the World Health Organization (WHO) and the International Diabetes Federation (IDF) to recommend its use in clinical practice.1,2
In 2006, Bourcier et al. showed the effectiveness of the “house made” monofilament, constructed from a fishing line, for screening for diabetic foot. The main characteristic of this line is that it exerts a 10 g pressure when bent (4 cm length by 500 µm diameter N° M-1425, South Bend Inc. North Brook, EUA).13 In Brazil, the 10 g monofilament is produced locally, but is not always available for purchase.
The objective of this study was to identify a similar nylon line and compare it to the commercially available one.
The purpose of this systematic review is to evaluate current evidence in the literature on the efficacy of Semmes Weinstein monofilament examination (SWME) in diagnosing diabetic peripheral neuropathy (DPN).
The PubMed database was searched through August 2008 for articles pertaining to DPN and SWME with no language or publication date restrictions. Studies with original data comparing the diagnostic value of SWME with that of one or more other modalities for DPN in patients with diabetes mellitus were analyzed. Data were extracted by two independent investigators. Diagnostic values were calculated after classifying data by reference test, SWME methodology, and diagnostic threshold.
Of the 764 studies identified, 30 articles were selected, involving 8365 patients. There was great variation in both the reference test and the methodology of SWME. However, current literature suggests that nerve conduction study (NCS) is the gold standard for diagnosing DPN. Four studies were identified which directly compared SWME with NCS and encompassed 1065 patients with, and 52 patients without diabetes mellitus. SWME had a sensitivity ranging from 57% (95% confidence interval [CI], 44% to 68%) to 93% (95% CI, 77% to 99%), specificity ranging from 75% (95% CI, 64% to 84%) to 100% (95% CI, 63% to 100%), positive predictive value (PPV) ranging from 84% (95% CI, 74% to 90%) to 100% (95% CI, 87% to 100%), and negative predictive value (NPV) ranging from 36% (95% CI, 29% to 43%) to 94% (95% CI, 91% to 96%).
There is great variation in the current literature regarding the diagnostic value of SWME as a result of different methodologies. To maximize the diagnostic value of SWME, a three site test involving the plantar aspects of the great toe, the third metatarsal, and the fifth metatarsals should be used. Screening is vital in identifying DPN early, enabling earlier intervention and management to reduce the risk of ulceration and lower extremity amputation.
To evaluate the sensitivity and specificity of 3 sensory perception testing instruments to screen for risk of diabetic foot ulceration.
This case-control study prospectively measured the degree of peripheral sensory neuropathy in diabetic patients with and without foot ulcers. We enrolled 115 age-matched diabetic patients (40% male) with a case-control ratio of approximately 1:3 (30 cases and 85 controls) from a tertiary care diabetic foot specialty clinic. Cases were defined as individuals who had an existing foot ulceration or a history of a recently (< 4 weeks) healed foot ulceration. Controls were defined as subjects with no foot ulceration history. Using receiver operating characteristic analysis, we evaluated the sensitivity and specificity of 2 commonly used nephropathy assessment tools (vibration perception threshold testing and the Semmes-Weinstein 10-g monofilament wire system) and a 4-question verbal neuropathy score to evaluate for presence of foot ulceration.
A vibration perception threshold testing using 25 V and lack of perception at 4 or more sites using the Semmes-Weinstein 10-g monofilament wire system had a significantly higher specificity than neuropathy score used. The neuropathy score was most sensitive when 1 or more answers were affirmative. When modalities were combined, particularly the monofilament wire system plus vibration perception threshold testing and the neuropathy score plus the monofilament wire system, there was a substantial increase in specificity with little or no diminution in sensitivity.
The early detection of peripheral neuropathy or loss of "protective sensation" is paramount to instituting a structured treatment plan to prevent lower extremity amputation. The results of our study suggest that all 3 sensory perception testing instruments are sensitive in identifying patients at risk for ulceration. Combining modalities appears to increase specificity with very little or no diminution in sensitivity.
The purpose of this study was to evaluate the effects of different testing sites and buckling strengths on the sensitivity and specificity of using the Semmes-Weinstein monofilament to detect patients with insensate foot. The impact on workload required to educate and follow up these high-risk individuals was estimated by modeling in our patient population with a documented status of neuropathy.
Using the 5.07/10-g monofilament, one observer tested 132 randomly selected subjects with diabetes at five sites on the right foot. The sensitivity and specificity of each site and combinations of sites in detecting vibration perception threshold > 40 was calculated. In addition, two monofilaments, one with a buckling force of 5 g and the other with a force of 15 g, were compared by testing 200 randomly selected patients. An estimate of the prevalence of insensate foot and workload was made by modeling the findings to the 5,270 patients with neuropathy status registered on our computerized database.
Specificity of the 5.07/10-g monofilament to detect insensate foot at each of the five sites is high, at approximately 90%, but there is considerably more variation and lower sensitivity, ranging from 44-71%. Data derived from the use of different combinations of sites showed that more stringent criteria are associated with lower sensitivity but higher specificity. If the foot is considered insensate when either of sites 3 and 4 (plantar aspect of the first and fifth metatarsal heads, respectively) cannot feel the monofilament, there is reasonable sensitivity and specificity (80-86%, respectively). By modeling on our diabetes center population, it can be demonstrated that the choice of different methodologies leads to different conclusions about the prevalence of severe neuropathy, ranging from 3.4 to 29.3%.
Using a combination of sites 3 and 4 for monofilament testing gives a reasonable compromise for time, sensitivity, and specificity. Minor changes in sensitivity and specificity can lead to major changes in the prevalence of neuropathy, with implications for workload.
To identify risk factors for lower-extremity amputation (LEA) in individuals with diabetes and to estimate the incidence of LEA.
This is a prospective study of 776 U.S. veterans in a general medicine clinic in Seattle, Washington. The outcome was first LEA during follow-up. Potential risk factors evaluated in proportional hazards models included, among others, peripheral vascular disease (PVD), sensory neuropathy, former LEA, foot deformities and ulcers, diabetes duration and treatment, and hyperglycemia.
Associated with an increased risk for LEA were PVD defined as transcutaneous oxygen < or = 50 mmHg (relative risk [RR] = 3.0, 95% CI 1.3-7.1), insensitivity to monofilament testing (RR = 2.9, odds ratio = 1.1-7.8), lower-extremity ulcers (RR = 2.5, CI 1.1-5.4), former LEA, and treatment with insulin when controlling for duration of diabetes and other factors in the model. PVD defined as absent or diminished lower-extremity pulses or an ankle arm index < or = 0.8 was also associated with a significantly higher risk of LEA in separate models. Foot ulcers were associated with an increased ipsilateral risk of amputation. The age-adjusted incidence among men only for LEA standardized to the 1991 U.S. male diabetic population was 11.3/1,000 patient-years.
This prospective study shows that peripheral sensory neuropathy, PVD, foot ulcers (particularly if they appear on the same side as the eventual LEA), former amputation, and treatment with insulin are independent risk factors for LEA in patients with diabetes.
The ability to perceive vibration (vibration detection) has been shown to be a good predictor of the long-term complications of diabetic peripheral neuropathy (DPN). We aimed to estimate the predicted complications and costs for the U.S. health care system associated with reduced vibration detection (vibration perception threshold >or=25 V), estimated using a quantitative sensory testing device.
A Markov model was constructed for a hypothetical cohort of people with DPN. The model was run over a 10-year period using Monte Carlo simulations to estimate disease progression, predicted costs, and complications according to vibration detection levels.
The average individual with reduced vibration detection incurs approximately five times more direct medical costs for foot ulcer and amputations, yields 0.18 fewer quality-adjusted life-years, and lives for approximately 2 months less than an average individual with normal vibration detection.
The treatment of foot ulceration and amputation is time-consuming and expensive. If individuals with reduced vibration detection could be identified, then preventative care could be concentrated on those patients, potentially saving valuable resources and improving health outcomes.
The Semmes-Weinstein monofilament has been developed for the detection of patients at risk of neuropathic ulceration. In this study we evaluated how the physical characteristics of the monofilaments can impact on their performance. Commercially purchased monofilaments from the Hansen's Disease Center (HDC) and a batch produced 'in-house' (RPAH) were calibrated using a Mettler Balance. To assess the effects of varying lengths on buckling force, the monofilaments were tested repeatedly while the length of the filament was reduced stepwise from 4.1 to 3.1 cm. The correct length of the monofilament to generate a buckling force of 10 g was also determined theoretically by applying the Euler's Buckling Equation. Results showed neither batch of monofilaments buckled at a strength of 10 g (HDC 6.8 g, CI 5.7-7.9, and RPAH 7.2 g, CI 7.1-7.3). In addition HDC showed a wide interfilament variation range, 4.1-10.3 g with CV 29 % versus corresponding figures of range 7.1-7.9 g, CV 4.9 % for the RPAH monofilaments. As predicted by Euler's Buckling Theory, buckling force can be increased by reducing the length of the filament. These results demonstrate that the physical characteristics of the monofilament are important determinants of buckling force and are not necessarily uniform in commercial filaments. The clinical relevance of variance in buckling force remains to be determined. (C) 1998 John Wiley & Sons, Ltd.
To study the use of a self-administered sensory testing tool designed to identify individuals at risk for diabetes-related foot problems and determine the inter-rater reliability between patient and provider sensory evaluations.
Nine centers in eight states with established foot prevention centers mailed 196 self-screening testing materials to randomly selected patients with diabetes scheduled for follow-up appointments. Patients were instructed to perform a sensory test using a 10-g nylon filament at specified sites on the foot and to complete a brief survey form before their appointment. During the follow-up appointment, providers retested patients using an identical sensory filament at the same sites and completed a provider survey.
Of the patients, 145 kept their appointments and completed the self-screening materials. There were 141 patient and 137 provider surveys that indicated the instructions were clear and easy to use. Sixty-eight percent of the patients reported self-testing without the assistance of another person. Patient and provider sensory test findings disagreed (P = 0.0014) in 18 of 145 cases and fair inter-rater reliability was found (kappa = 0.73). Disagreement in sensory tests was related to patient age (P = 0.012). Sensory loss, previously undetected by providers, was found in 23 case subjects.
Self-administered sensory tests provide patients an opportunity to share in the responsibility for preventing diabetes-related foot problems but should not replace routine foot evaluation by a provider.
Both vibration perception threshold (VPT) by biothesiometry and pressure perception using Semmes-Weinstein monofilaments (filaments) have been proposed to identify diabetic patients at risk of foot ulceration. The two methods were compared in 182 subjects attending a national patients conference. Both measures were made over the great toe. Filaments of three calibres were used: 4.17, 5.07 and 6.10 bending with 1, 10 and 75 g force, respectively. Pressure perception was normal (4.17) in 122 patients (group 1) whereas in 45 patients it was grade 5.07 (group 2) and 6.10 or greater in 15 (group 3). The corresponding mean VPT (+/- SD) for the three groups were 10.6 (+/- 6.7), 22.8 (+/- 12.7) and 32 (+/- 14.3), respectively. The mean VPT for the 3 groups were significantly different (P less than 0.001). The filaments were more sensitive (100%) but less specific (77.7%) in identifying patients who had foot ulcers compared to biothesiometry which was less sensitive (78.6%) but more specific (93.4%). The filaments are therefore reliable and may be superior to biothesiometry in screening for patients at risk of foot ulceration since sensitivity is the more important parameter. In addition, they are inexpensive (12 pounds) compared to the biothesiometer (400 pounds) and are simple and easy to use.
To determine the diagnostic value of various cutaneous sensory modalities in diabetic neuropathy, we studied cutaneous perception at the dominant hallux of 113 subjects (32 normal healthy controls and 81 diabetic subjects). The cutaneous sensory perception tests included warm and cold thermal perception, vibration, touch-pressure sensation, and current perception testing (CPT). The sensitivity of each modality when specificity is held greater than 90% was as follows: warm = 78%, cold = 77%, vibration = 88%, tactile-pressure = 77%, 5-Hz CPT = 52%, 250-Hz CPT = 48%, and 2000-Hz CPT = 56%. Combination thermal and vibratory gave optimum sensitivity (92-95%) and specificity (77-86%). We conclude that vibratory and thermal testing should be the primary screening tests for diabetic peripheral neuropathy. Other modalities may be of use only in specific situations.
To identify and quantify independent physiological risk factors for foot lesions in diabetic patients.
There were 352 patients enrolled in a 1-year randomized controlled trial aimed at reducing risks for lower-extremity pathology through patient education and system interventions. Inclusion criteria were as follows: being age 40 years or over, being at or above ideal body weight, and having been diagnosed with NIDDM. Participants were predominantly African-American (76%), elderly (mean 60 years of age), indigent (77% with annual income < +10,000), or women (81%) who had diabetes for 10 years. Prospective multivariate modeling used baseline clinical signs (e.g., blood pressure, dermatological characteristics, and neuropathic measures) and laboratory values (e.g., lipid profiles and measures of glycemic control) to predict foot lesions rated using the Seattle Wound Classification.
When controlling for intervention effects, only measures of neuropathy (monofilament testing [odds ratio ¿OR¿ 2.75, 95% CI 1.55-4.88] and thermal sensitivity testing [2.18, 1.13-4.21]) predicted wounds classified 1.2 (minor injury), but investigation of wounds rated at least 1.3 (nonulcerated lesions) indicated baseline wounds (13.41), 3.19-56.26), monofilament abnormalities (5.23, 2.26-12.13), and low HDL (1.63, 1.11-2.39) as predictors. Although fungal dermatitis, dry cracked skin, edema, ingrown nails, microalbuminuria, fasting blood glucose, and hemoglobin A1c were candidates for one or both of the multivariable models (P < 0.3), they were not significant multivariate predictors.
Lesions may be preventable with aggressive screening for peripheral neuropathy and abnormal lipids. Also, these results provide empirical support for the commonly held belief that foot lesions prospectively predict future wounds.
The Semmes-Weinstein monofilament has been developed for the detection of patients at risk of neuropathic ulceration. In this study we evaluated how the physical characteristics of the monofilaments can impact on their performance. Commercially purchased monofilaments from the Hansen's Disease Center (HDC) and a batch produced 'in-house' (RPAH) were calibrated using a Mettler Balance. To assess the effects of varying lengths on buckling force, the monofilaments were tested repeatedly while the length of the filament was reduced stepwise from 4.1 to 3.1 cm. The correct length of the monofilament to generate a buckling force of 10 g was also determined theoretically by applying the Euler's Buckling Equation. Results showed neither batch of monofilaments buckled at a strength of 10 g (HDC 6.8 g, CI 5.7-7.9, and RPAH 7.2 g, CI 7.1-7.3). In addition HDC showed a wide interfilament variation range, 4.1-10.3 g with CV 29% versus corresponding figures of range 7.1-7.9 g, CV 4.9% for the RPAH monofilaments. As predicted by Euler's Buckling Theory, buckling force can be increased by reducing the length of the filament. These results demonstrate that the physical characteristics of the monofilament are important determinants of buckling force and are not necessarily uniform in commercial filaments. The clinical relevance of variance in buckling force remains to be determined.
Quantitative sensory testing is a reliable way of assessing large and small sensory nerve fiber function. Sensory deficits may be quantified and the data used in parametric statistical analysis in research studies and drug trials. It is an important addition to the neurophysiologic armamentarium, because conventional sensory nerve conduction tests only the large fibers. QST is a psychophysical test and lacks the objectivity of NCS. The results are subject to changes owing to distraction, boredom, mental fatigue, drowsiness, or confusion. When patients are consciously or unconsciously biased toward an abnormal QST result, no psychophysical testing can reliably distinguish these patients from those with organic disease. QST tests the integrity of the entire sensory neuraxis and is of no localizing value. Dysfunction of the peripheral nerves or central nervous system may give rise to abnormalities in QST. As is true for other neurophysiologic tests, QST results should always be interpreted in light of the patient's clinical presentation. Quantitative sensory testing has been shown to be reasonably reproducible over a period of days or weeks in normal subjects. Because longitudinal QST studies of patients in drug trials are usually performed over a period of several months to a few years, reproducibility studies on the placebo-control group should be included. For individual patients, more studies are needed to determine the maximum allowable difference between two QSTs that can be attributed to experimental error. The reproducibility of thermal thresholds may not be as good as that of vibration threshold. Different commercially available QST instruments have different specifications (thermode size, stimulus characteristics), testing protocols, algorithms, and normal values. Only QST instruments and their corresponding methodologies that have been shown to be reproducible should be used for research and patient care. The data in the literature do not allow conclusions regarding the superiority of any QST instruments. The future of QST is promising; however, many factors can affect QST results. As is true for other neurophysiologic tests, QST is susceptible to many extraneous factors and to misuse when not properly interpreted by the clinician.