Diagnosis Of Distal Symmetric Polyneuropathy Research Articles

Fas-mediated apoptosis and peripheral polyneuropathy in type 2 diabetes mellitus

ObjectiveTo evaluate the role of soluble Fas (sFas) and soluble Fas ligand (sFasL) in the pathogenesis of distal symmetrical polyneuropathy (DSPN) in patients with type 2 diabetes mellitus, and to analyze the relationship between these apoptotic markers with clinical parameters and electrophysiologic profile of DSPN, as well as with different diabetic factors among those patients.Patients and methodsThe study included 60 Egyptians with type 2 diabetes mellitus. All patients were evaluated clinically for DSPN by using Michigan Neuropathy Screening Instrument. Electrophysiological diagnosis of DSPN was based on the criteria suggested by the European Standardized Telematic tool to Evaluate Electrodiagnostic Methods group. Diabetic patients were divided into two groups according to the electrophysiological findings: group A included patients with DSPN (N=42), and group B included patients without DSPN (N=18). The severity of DSPN among group A patients was assessed clinically using Toronto Clinical Neuropathy Score and electrophysiologically by the severity score proposed by Hidasi and colleagues. The study also included 30 healthy volunteers as a control group. Serum levels of sFas and sFasL were assessed in all the studied groups.ResultsSerum level of sFas was significantly elevated in diabetic patients with DSPN compared with diabetics without DSPN and nondiabetic control (P=0.029 and 0.000). Receiver operating characteristic (ROC) curve analysis detected that sFas was statistically significant in discriminating between diabetic patients with DSPN from those patients without DSPN with an accuracy of 66%. The cutoff point that has the highest sensitivity (61%) and specificity (62%) was 33.3 ng/ml. Serum level of sFas showed a positive significant correlation with the electrophysiological severity of DSPN (P=0.020). Serum level of sFasL did not show statistically significant difference between all the studied groups.ConclusionFas-mediated apoptosis has an important role in the development of diabetic DSPN and is correlated with its electrophysiological severity.

Bilateral nerve conduction studies in the evaluation of distal symmetric polyneuropathy.

Nerve conduction studies are used to aid in the diagnosis of distal symmetric polyneuropathy (DSP). It is unclear whether bilateral lower extremity nerve conduction studies (NCS) are needed when evaluating for suspected DSP. We retrospectively analyzed NCS from patients who presented to the University of Michigan electromyography laboratory between July 1, 2016 and December 31, 2017 with symptoms of DSP to assess agreement and correlation between left and right lower extremity NCS parameters. We found significant agreement between abnormalities in individual nerve parameters of the left and right lower extremities of 105 patients, most notably in the sural nerve. In the 53 patients with bilateral sural, peroneal, and tibial studies, there was also significant agreement between whether the left and right met electrodiagnostic criteria for DSP (κ = 0.77). Bilateral lower extremity NCS may have limited utility in the evaluation of suspected DSP. Muscle Nerve, 2019.

Update on the Management of Diabetic Neuropathy.

IN BRIEF Distal symmetric polyneuropathy (DSPN) and diabetic autonomic neuropathies, particularly cardiovascular autonomic neuropathy (CAN), are prevalent diabetes complications with high morbidity, mortality, and amputation risks. The diagnosis of DSPN is principally a clinical one based on the presence of typical symptoms combined with symmetrical, distal-to-proximal stocking-glove sensory loss. CAN is an independent risk factor for cardiovascular mortality, arrhythmia, silent ischemia, major cardiovascular events, and myocardial dysfunction. Screening for CAN in high-risk patients is recommended. Symptoms of gastroparesis are nonspecific and do not correspond with its severity. Diagnosis of gastroparesis should exclude other factors well documented to affect gastric emptying such as hyperglycemia, hypoglycemia, and certain medications. There is a lack of treatment options targeting the neuropathic disease state. Managing neuropathic pain also remains a challenge. Given the high risk of addiction, abuse, psychosocial issues, and mortality, opioids are not recommended as first-, second-, or third-line agents for treating painful DSPN.

One-stop microvascular screening service: an effective model for the early detection of diabetic peripheral neuropathy and the high-risk foot.

AimsTo evaluate the feasibility of a one‐stop microvascular screening service for the early diagnosis of diabetic distal symmetrical polyneuropathy, painful distal symmetrical polyneuropathy and the at‐risk diabetic foot.MethodsPeople with diabetes attending retinal screening in hospital and community settings had their feet examined by a podiatrist. Assessment included: Toronto Clinical Neuropathy Score evaluation; a 10‐g monofilament test; and two validated, objective and quick measures of neuropathy obtained using the point‐of‐care devices ‘DPN‐Check’, a hand‐held device that measures sural nerve conduction velocity and amplitude, and ‘Sudoscan’, a device that measures sudomotor function. The diagnostic utility of these devices was assessed against the Toronto Clinical Neuropathy Score as the ‘gold standard’.ResultsA total of 236 consecutive people attending the retinal screening service, 18.9% of whom had never previously had their feet examined, were evaluated. The prevalence of distal symmetrical polyneuropathy, assessed using the Toronto Clinical Neuropathy Score, was 30.9%, and was underestimated by 10‐g monofilament test (14.4%). The prevalence of distal symmetrical polyneuropathy using DPN‐check was 51.5% (84.3% sensitivity, 68.3% specificity), 38.2% using Sudoscan foot electrochemical skin conductance (77.4% sensitivity, 68.3% specificity), and 61.9% using abnormality in either of the results (93.2% sensitivity, 52.8% specificity). The results of both devices correlated with Toronto Clinical Neuropathy Score (P<0.001). A new diagnosis of painful distal symmetrical polyneuropathy was made in 59 participants (25%), and 56.6% had moderate‐ or high‐risk foot. Participants rated the service very highly.ConclusionsCombined, eye, foot and renal screening is feasible, has a high uptake, reduces clinic visits, and identifies painful distal symmetrical polyneuropathy and the at‐risk foot. Combined large‐ and small‐nerve‐fibre assessment using non‐invasive, quantitative and quick point‐of‐care devices may be an effective model for the early diagnosis of distal symmetrical polyneuropathy.

Characterization of small nerve fibers in painful distal symmetric polyneuropathy and healthy controls

Abstract Aims The introduction of skin biopsies to examine small nerve fiber morphology together with functional measures such as quantitative sensory testing (QST) has led to an improvement in diagnosing patients with small fiber neuropathy (SFN). Quantification of intraepidermal nerve fiber density (IENFD) is an important measure in SFN. However, the relationship between structure and function is not straightforward and the morphological and functional fiber characteristics are still unclear. This study aimed to combine structural and functional measurements to improve the diagnosis of distal symmetric polyneuropathy and small fiber involvement. Additionally, we investigated whether patients and healthy controls have differential patterns of correlations between structural and functional nerve measurements. Methods 17 patients with painful distal symmetric polyneu-ropathy (DSP) and 19 controls underwent comprehensive small fiber assessments that included quantitative sensory testing, response to topical capsaicin and analysis of skin biopsy samples (IENFD, epidermal and dermal nerve fiber length densities (eNFLD, dNFLD) and swellings). Results DSP patients had reduced sensitivity to cold and heat, diminished capsaicin response, and lower IENFD, eNFLD and dNFLD (all p &lt; 0.0003).The correlation between structural and functional parameters was better in controls than in DSP. A diagnostic approach of combined IENFD and eNFLD utilization, increased DSP diagnostic sensitivity from 82.0% to 100% and specificity from 84.0% to 89.5%. Conclusions A correlation is found between functional and structural small fiber parameters for DSP and controls, and an approach to improve diagnostic accuracy in DSP is suggested.

Mechanisms and management of diabetic painful distal symmetrical polyneuropathy.

Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical polyneuropathy (DSPN). It is estimated that 15–20% of diabetic patients may have painful DSPN, but not all of these will require therapy. In practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal studies and clinical trials, quantitative sensory testing and electrophysiological assessment are usually necessary. A number of simple numeric rating scales are available to assess the frequency and severity of neuropathic pain. Although the exact pathophysiological processes that result in diabetic neuropathic pain remain enigmatic, both peripheral and central mechanisms have been implicated, and extend from altered channel function in peripheral nerve through enhanced spinal processing and changes in many higher centers. A number of pharmacological agents have proven efficacy in painful DSPN, but all are prone to side effects, and none impact the underlying pathophysiological abnormalities because they are only symptomatic therapy. The two first-line therapies approved by regulatory authorities for painful neuropathy are duloxetine and pregabalin. α-Lipoic acid, an antioxidant and pathogenic therapy, has evidence of efficacy but is not licensed in the U.S. and several European countries. All patients with DSPN are at increased risk of foot ulceration and require foot care, education, and if possible, regular podiatry assessment.

Correction and transformation of normative neurophysiological data: Is there added value in the diagnosis of distal symmetrical peripheral neuropathy?

Despite theoretical advantages, the practical impact of mathematical correction of normative electrodiagnostic data is poorly quantified. One hundred five healthy volunteers had clinical and neurophysiological assessment. The effects of age, height, gender, weight, and body mass index were explored using stepwise regression modeling. Reference values were derived from raw and adjusted data, which were transformed to allow appropriate use of parametric statistics. The diagnostic accuracy of derived limits was tested in patients at risk of distal symmetric peripheral neuropathy (DSPN) from chemotherapy. The variability of our normative data was reduced by up to 69% through the use of regression modeling, but the overall benefits of mathematical correction were marginal. The most accurate reference limits were established using the 2.5th and 97.5th percentiles of the raw data. Stepwise statistical regression and mathematical transformation improve the distribution of normative data, but their practical impact for diagnosis of distal symmetrical polyneuropathy is small.

Neuropad: evaluation of three cut‐off points of sudomotor dysfunction for early detection of polyneuropathy in recently diagnosed diabetes

To examine the sensitivity and specificity of three cut-off points of Neuropad for the diagnosis of distal symmetric polyneuropathy and small-fibre dysfunction in patients within the first year after diagnosis of diabetes. Neuropad results were read at 10, 15 and 20 min and evaluated for diagnostic utility in distal symmetric polyneuropathy confirmed by electrophysiology and small-fibre dysfunction in 52 patients with Type 1 diabetes and 99 patients with Type 2 diabetes. The prevalence of distal symmetric polyneuropathy was 15.4% in Type 1 diabetes and 43.4% in Type 2 diabetes, while that of small-fibre dysfunction was 9.6 and 31.3%, respectively. Sensitivity of Neuropad for the diagnosis of distal symmetric polyneuropathy and small-fibre dysfunction was highest in Type 1 diabetes for the 10-min threshold reaching 87.5 and 80.0%, respectively, while it was modestly high in Type 2 diabetes at 65.1 and 67.7%, respectively. Specificity in both diabetes types was modest for the 10-min threshold (44.7-48.2%). It was highest for the 20-min threshold (83.8-89.3%) at the cost of poor sensitivity at 12.5-34.9%. Negative predictive values were relatively high for all three cut-off points in both types of diabetes (64.1-97.1%) at the cost of poor positive predictive values at 12.5-71.4%. In patients within the first year after diagnosis of diabetes, the 10-min cut-off for Neuropad provides a relatively high sensitivity and modest specificity for distal symmetric polyneuropathy and small-fibre dysfunction, rendering the test more suitable as a screening tool than the 15- and 20-min cut-offs.

Accuracy of the Neuropad Test for the Diagnosis of Distal Symmetric Polyneuropathy in Type 2 Diabetes

OBJECTIVETo estimate the accuracy of Neuropad for the diagnosis and staging of distal symmetric polyneuropathy (DPN) across different stages of neuropathy, using multiple-level likelihood ratios (LRs) to interpret the time necessary to complete the color change of the test.RESEARCH DESIGN AND METHODSWe conducted a cross-sectional, cohort-type diagnostic accuracy study in 251 consecutive adult type 2 diabetic patients with no peripheral arterial disease or other potential causes of neuropathy, who were recruited between January 2005 and December 2008 from the diabetes outpatient clinics in Alexandroupolis Hospital, Greece. Patients were tested for DPN by means of the neuropathy disability score (NDS) and Neuropad. Multiple-level LRs for time to complete color change were calculated across different stages of neuropathy.RESULTSThe areas under the curve for the diagnosis of any (NDS of ≥3), at least moderate (NDS of ≥6), or severe (NDS of ≥9) DPN were 0.91, 0.96, and 0.97, respectively. The calculation of multiple-level LRs showed that time to complete color change <360 s suggested the absence of neuropathy. Values between 360 and 1,000 s were indicative of mild neuropathy. Finally, values between 1,000 and 1,200 or >1,200 s were strongly suggestive of moderate or severe DPN, respectively.CONCLUSIONSNeuropad could be used as a triage test for the diagnosis and staging of DPN in patients with type 2 diabetes, prompting referral to specialized care setting.

59. Nerve conduction studies and intra-epidermal nerve fiber density for the diagnosis of distal symmetric polyneuropathy

59. Nerve conduction studies and intra-epidermal nerve fiber density for the diagnosis of distal symmetric polyneuropathy

The Prevalence of Neuropathy and Relationship with Risk Factors in Diabetic Patients: A Single-Center Experience

Objective: To determine the rate of distal symmetrical polyneuropathy (DSP) in patients with type 2 diabetes mellitus, to evaluate the role of history, neurological examination and the electrodiagnostic methods in the diagnosis of DSP, and to determine the association between electromyography-supported neuropathy (ESN), neuropathic complaints (NCs) and risk factors. Subjects and Methods: A total of 191 type 2 DM patients (109 female, 82 male; mean age 58.7 ± 10 years) were recruited. The NCs were recorded. All patients had electromyographic (EMG) examinations. The relationship between ESN, NCs and risk factors were evaluated. Results: Of the 191 patients, 83 (43.5%) had DSP on EMG examinations and 92 (48.2%) patients suffered from NCs. Among the ESN patients, a significant relationship existed with HbA1_c level, illness duration, smoking, male gender or insulin usage (p < 0.05) but not with age, hypertension, hypercholesterolemia or hypertriglyceridemia. The frequency of NCs was higher in patients with ESN. There was also a significant association between NCs and ESN (p < 0.05). The presence of NCs was not related to age, gender, smoking, hypertension, hypercholesterolemia and hypertriglyceridemia (p > 0.05) but NCs were correlated to HbA1_c level, illness duration and insulin usage (p < 0.05). Conclusion: Our data show that a strong association exists between the presence of DSP and illness duration, HbA1_c, smoking, thereby indicating that cessation of smoking and near normal glycemic control would be additional precautions to delay the beginning or progression of polyneuropathy.

Evidence- and Consensus-Based Definition of Distal Symmetric Polyneuropathy

Despite neurologists' familiarity with the diagnosis of distal symmetric polyneuropathy, reaching agreement on a consistent clinical definition for

Distal symmetric polyneuropathy: A definition for clinical research

The objective of this report was to develop a case definition of distal symmetric polyneuropathy to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetric polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetric polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

Distal symmetrical polyneuropathy: A definition for clinical research. A report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation

England JD, Gronseth GS, Franklin G, Miller RG, Asbury AK, Carter GT, Cohen JA, Fisher MA, Howard JF, Kinsella LJ, Latov N, Lewis RA, Low PA, Sumner AJ. Distal symmetrical polyneuropathy: a definition for clinical research. A report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. The objective of this report was to develop a case definition of “distal symmetrical polyneuropathy” to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

Distal symmetrical polyneuropathy: Definition for clinical research

The objective of this report was to develop a case definition of "distal symmetrical polyneuropathy" to standardize and facilitate clinical research and epidemiological studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiological studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach for defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiological research studies will ensure greater consistency of case selection.

Early recognition of diabetic neuropathy: evaluation of a simple outpatient procedure using thermal perception

Objective: To determine the effectiveness of Tip-therm, a temperature discriminator, in making an early diagnosis of distal symmetrical polyneuropathy in diabetic patients and to compare its effectiveness with the Semmes-Weinstein...

Simple screening tests for peripheral neuropathy in the diabetes clinic.

The utility of rapid and reliable sensory tests appropriate for the diagnosis of neuropathy in the diabetes clinic, rather than as prognostic tools for the prediction of foot complications, has been unclear because of limitations inherent in previous studies. Although clinical practice guidelines recommend annual screening for neuropathy, they are unable to support specific recommendations for screening maneuvers because of a lack of evidence for the validity of screening tests in the medical literature. The objective of this study was to assess the operating characteristics of four simple sensory screening maneuvers as compared with standardized electrophysiological tests in the diagnosis of distal symmetrical polyneuropathy. We assessed four simple tests (the 10-g Semmes-Weinstein monofilament examination [SWME], superficial pain sensation, vibration testing by the on-off method, and vibration testing by the timed method) in 478 subjects with independent blinded evaluations compared against the criterion standard of nerve conduction studies. We present receiver-operating characteristic (ROC) curves, positive and negative likelihood ratios, and sensitivity and specificity values for each test. The four simple screening maneuvers reveal similar operating characteristics. Cutoff points by ROC curve analyses reveal that a positive or abnormal test is represented by five incorrect responses of eight stimuli applied. A negative or normal test is represented by one or fewer incorrect responses of eight stimuli applied. By these criteria, the point estimates of the positive likelihood ratios for vibration testing by the on-off method, vibration testing by the timed method, the SWME, and superficial pain sensation test are 26.6, 18.5, 10.2, and 9.2, respectively. The point estimates of the negative likelihood ratios are 0.33, 0.51, 0.34, and 0.50, respectively The screening tests showed comparable sensitivity and specificity results. The 10-g SWME, superficial pain test, and vibration testing by the on-off method are rapid, each requiring approximately 60 s to administer. The timed vibration test takes longer, and the interpretation is more complicated. The combination of two simple tests (e.g., the 10-g SWME and vibration testing by the on-off method) does not add value to each individual screening test. Annual screening for diabetic neuropathy should be conducted using superficial pain sensation testing, SWME, or vibration testing by the on-off method. The reported operating characteristics for each sensory modality can be applied to positive findings on the physical examination of individual patients to predict the likelihood of neuropathy.

Simple screening tests for peripheral neuropathy in the diabetes clinic

OBJECTIVE — The utility of rapid and reliable sensory tests appropriate for the diagnosis of neuropathy in the diabetes clinic, rather than as prognostic tools for the prediction of foot complications, has been unclear because of limitations inherent in previous studies. Although clinical practice guidelines recommend annual screening for neuropathy, they are unable to support specific recommendations for screening maneuvers because of a lack of evidence for the validity of screening tests in the medical literature. The objective of this study was to assess the operating characteristics of four simple sensory screening maneuvers as compared with standardized electrophysiological tests in the diagnosis of distal symmetrical polyneuropathy. RESEARCH DESIGN AND METHODS — We assessed four simple tests (the 10-g Semmes-Weinstein monofilament examination [SWME], superficial pain sensation, vibration testing by the on-off method, and vibration testing by the timed method) in 478 subjects with independent blinded evaluations compared against the criterion standard of nerve conduction studies. We present receiver-operating characteristic (ROC) curves, positive and negative likelihood ratios, and sensitivity and specificity values for each test. RESULTS — The four simple screening maneuvers reveal similar operating characteristics. Cutoff points by ROC curve analyses reveal that a positive or abnormal test is represented by five incorrect responses of eight stimuli applied. A negative or normal test is represented by one or fewer incorrect responses of eight stimuli applied. By these criteria, the point estimates of the positive likelihood ratios for vibration testing by the on-off method, vibration testing by the timed method, the SWME, and superficial pain sensation test are 26.6, 18.5, 10.2, and 9.2, respectively. The point estimates of the negative likelihood ratios are 0.33, 0.51, 0.34, and 0.50, respectively. The screening tests showed comparable sensitivity and specificity results. The 10-g SWME, superficial pain test, and vibration testing by the on-off method are rapid, each requiring ∼60 s to administer. The timed vibration test takes longer, and the interpretation is more complicated. The combination of two simple tests (e.g., the 10-g SWME and vibration testing by the on-off method) does not add value to each individual screening test. CONCLUSIONS — Annual screening for diabetic neuropathy should be conducted using superficial pain sensation testing, SWME, or vibration testing by the on-off method. The reported operating characteristics for each sensory modality can be applied to positive findings on the physical examination of individual patients to predict the likelihood of neuropathy.