H-reflex and Clinical Examination in the Diagnosis of Diabetic Polyneuropathy

Transcription

1 The Journal of International Medical Research 2012; 40: H-reflex and Clinical Examination in the Diagnosis of Diabetic Polyneuropathy RO MILLÁN-GUERRERO 1, B TRUJILLO-HERNÁNDEZ 1, S ISAIS-MILLÁN 1, E PRIETO-DÍAZ-CHÁVEZ 1, C VÁSQUEZ 2, JR CABALLERO-HOYOS 1 AND J GARCÍA-MAGAÑA 1 1 Clinical Epidemiology Research Unit, Mexican Institute of Social Insurance, Zone 1 General Hospital of Colima, Colima, Mexico; 2 University Centre for Biomedical Research, University of Colima, Colima, Mexico OBJECTIVES: To determine among adult patients with type-2 diabetes mellitus the proportion diagnosed with diabetic polyneuropathy (DPN) by clinical evaluation and by the Hoffmann reflex (Hreflex). In addition, the predictive value of the H-reflex in the diagnosis of DPN was evaluated. METHODS: Studies were carried out on 150 adult patients referred for neuropathy screening. Diagnostic criteria for DPN were at least two abnormalities in clinical neurophysiological examinations and electrophysiological testing (H-reflex and nerve conduction velocity). Logistic regression analysis was performed to identify unique contributions of study characteristics to positive versus negative outcomes. RESULTS: H-reflex was absent in 39.3% (59/150) and latency was prolonged in 43.3% (65/150) of patients. Ulnar nerve motor branch nerve conduction showed prolonged latency in 9.3% (14/150) of patients. Logistic regression analysis indicated that the H-reflex was significantly associated with positive outcomes. CONCLUSION: The H-reflex could have a predictive value in DPN, providing more quantitative information regarding diagnosis than conventional nerve conduction studies. KEY WORDS: DIABETES MELLITUS; DIABETIC NEUROPATHY; POLYNEUROPATHY; DIAGNOSIS; HOFFMANN REFLEX; ELECTROPHYSIOLOGICAL TESTS; NERVE CONDUCTION VELOCITY Introduction Diabetic polyneuropathy (DPN) is one of the most common complications of diabetes mellitus, affecting approximately 50% of patients. 1 Diabetes mellitus is diagnosed as the cause of neuropathy by exclusion of various other conditions, such as trauma or pressure on the nerve, vitamin deficiencies (B 1, B 6, B 12, E and niacin), alcoholism, infections (Lyme disease, varicella zoster, Epstein Barr, hepatitis C and HIV/AIDS), autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis and Guillain-Barré syndrome), inherited disorders (Charcot Marie Tooth disease and amyloid polyneuropathy), tumours and exposure to poisons. 2 5 The mechanism of DPN is unclear and multifactorial, 2 and its prevalence increases with age and disease duration, with the highest rates found among patients who have had diabetes mellitus for 25 years. 3 5 Suboptimal glycaemic control is also associated with 694

2 higher rates of DPN, although DPN may occur when blood sugar levels are well controlled. 6 8 Symptoms of DPN typically occur in a symmetrical stocking and glove pattern, initially affecting the feet and lower limbs, with the hands affected later. 5,9 Patients may lose vibration and proprioceptive sensation, temperature sensitivity and, eventually, pain sensation. 10 Diabetic peripheral neuropathic pain is insidious at the onset and is usually characterized by burningtype pain, paraesthesia and numbness of mild-to-moderate severity. 5,10,11 The diagnosis, classification and management of DPN can be done on the basis of the patient s history and the results of a thorough neurophysiological examination. Diagnosis is based on the presence of at least two of the following three characteristics: abnormal sensory or motor signs, symptoms and decreased tendon reflexes. 12,13 In many cases, the diagnosis of DPN may also require electrophysiological testing. 14 One such test involves measurement of the Hoffmann reflex (H-reflex), which has been found to be more frequently altered in patients with recently diagnosed diabetes mellitus. 15 Studies have shown that alterations in the H- reflex provide an early indication of DPN, since they are apparent before any changes in motor nerve conduction velocity (NCV) occur. These findings suggest that the H- reflex may be useful as a criterion for the diagnosis of DPN. 12,15 The purpose of the present study was to determine, among adult patients with type- 2 diabetes mellitus referred for neuropathy screening, the proportion of patients with positive DPN diagnoses made by clinical evaluation or by measurement of the H- reflex. In addition, the predictive value of the H-reflex in DPN diagnosis was evaluated. Patients and methods STUDY POPULATION AND DIAGNOSTIC CRITERIA This analytical cross-sectional study was carried out from August 2009 to July 2010 in patients of both sexes with type-2 diabetes mellitus and aged years. The patients had all been referred for DPN screening from the family medicine outpatient service of the Mexican Institute of Social Insurance (IMSS), Zone 1 General Hospital of Colima, to the University Centre for Biomedical Research, University of Colima, Mexico. They were enrolled into the study sequentially 1 2 weeks after the clinical examination. Patients were excluded if they had type-1 diabetes mellitus or alcoholism, if clinical evaluation revealed severe renal complications, or if they had a pacemaker, carpal tunnel syndrome, nerve-root compression, focal mononeuropathy, pure motor or motor-predominant neuropathy, or neuropathy restricted to the upper limbs. Patients with cognitive deterioration preventing an accurate understanding of test procedures and patients with associated central nervous system abnormalities were also excluded. Clinical and neurophysio - logical evaluations were carried out in all patients to determine the presence or absence of neuropathy. The diagnostic criteria for DPN were a minimum of two abnormalities in clinical neurophysiological examinations and electrophysiological testing studies (H-reflex and NCV). Responses in the electrophysiological tests from healthy volunteers undergoing routine medical attention at the family medicine outpatient service of the IMSS, Zone 1 General Hospital of Colima were used for normal reference values. None of the healthy volunteers used for reference values had any evidence or family history of diabetes, hypertension, cardiac disease, or 695

3 cerebral vascular disease. All subjects provided written informed consent. The study was approved by the Hospital Ethics Committee, IMSS, Zone 1 General Hospital of Colima, Colima, Mexico. CLINICAL AND NEUROPHYSIOLOGICAL EXAMINATIONS The presence of neuropathy was identified using the Michigan Neuropathy Screening Instrument (MNSI) (Appendix 1). 16 This is a simple, precise, noninvasive, five-point clinical neurophysiological test for the diagnosis of diabetic neuropathy, involving the left and right feet and ankles, and has a total maximum score of 10 points. It involved examination of the appearance of the feet, the presence or absence of ulceration, tendon reflexes in the ankle, vibratory sensation in the big toe as measured by a 128 Hz tuning fork, and Semmes Weinstein monofilament test in which the skin of the extremity was touched with a filament (Touch-Test ; Stoelting, Wood Dale, IL, USA). The MNSI has been reported to have 83% specificity and 79% sensitivity. 17 Among the clinical signs suggesting autonomic neuropathy, sudomotor abnormalities and pin-sensation were evaluated. ELECTROPHYSIOLOGICAL TESTING At 1 2 weeks after the clinical and neurophysiological examinations the patients were sent to the Clinical Electrophysiological Laboratory of the University Centre for Biomedical Research, University of Colima, where another researcher (blinded to the results of the clinical evaluation) carried out electrophysiological tests using a fourchannel Nicolet Viking IV electro - myograph and disposable electrode disks (CareFusion, San Diego, CA, USA). All tests were carried out at room temperature (25 27 C). All the electro physio logical tests were performed on the patient s right side, as described below. An alteration was considered to be present when latency of the response (H-reflex and NCV) was more than two standard deviations from the normal curve, or when response was absent. NCV measurements in the ulnar nerve The NCV measurements were carried out using the Nicolet Viking IV electro - myograph and disposable electrode disks (CareFusion). With the patient in the supine position and elbow at a flexion angle of 90, stimulation was performed at the right wrist and elbow (at 4 cm proximal to the epicondylus). A ground electrode (the electrode that stabilizes application of the current and allows for better electrophysical recording) was located on the dorsal side of the right hand, an active electrode (the principal electrode for detecting the electrophysiological signal) was located at the level of the abductor muscle in the fifth finger of the right hand, and a reference electrode was located at 4 cm proximal to the same fifth finger. The stimulus intensity was in the range of V with a 0.1- ms pulse duration. The parameters measured in this response were latency (time taken for a response to the stimulus to develop, measured in milliseconds) and amplitude (size of the signal obtained, measured in millivolts). H-reflex of the tibial posterior nerve The H-reflex of the tibial posterior nerve was assessed using the Nicolet Viking IV electromyograph and disposable electrode disks (CareFusion). With the patient in the prone position and with a knee flexion of 696

4 120, a stimulus was applied to the popliteal fossa. The cathode electrode was placed proximal to the anode (for orthodromic stimulation) and the stimulus intensity was in the V range, with 1 ms pulse duration. Recording electrodes were placed: the active electrode was at the ventral side of the right pelvic twin muscle and the reference electrode was 4 cm from the active electrode. The parameters measured in this response were latency and amplitude. GRADING OF NEUROPATHY The severity of neuropathy was graded as: grade 0, no neuropathy; grade 1, asymptomatic neuropathy and abnormal NCV; grade 2, symptomatic neuropathy and abnormal NCV; and grade 3, symptomatic neuropathy, abnormal nerve examination, ulcers, deformity, nontraumatic amputation and abnormal NCV. 17 STATISTICAL ANALYSES Statistical analyses were performed using the SPSS software package, version 17 (SPSS Inc., Chicago, IL, USA) for Windows. The mean ± SD was calculated for continuous variables and the number and percentage of patients was used for categorical variables. Logistic regression analysis of the factors associated with DPN (dependent variable) was used to estimate a predictor model for unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI). Variables that were significant in bivariate analysis were included in the multivariate model as independent variables (including H-reflex, clinical examination, NCV examination, sex, glycaemia and duration of diabetes). The reliability of the model was evaluated with the Hosmer Lemeshow goodness-of-fit test, which divided the data into several groups based on P-value and then calculated a χ 2 -value from the observed and expected frequencies of subjects classified in the two categories of the binary response variable within these groups. Small χ 2 -values (and correspondingly large P-values [P > 0.05]) indicated a statistically significantly good fit for the model. Results In total, 150 patients with type-2 diabetes mellitus were screened for DPN. The demographic and clinical characteristics of these patients are shown in Table 1. For electrophysiological reference values, 20 healthy volunteers (11 women and nine men) were used. In total, 131/150 (87.3%) of the type 2 diabetes patients referred for screening were diagnosed with DPN. Based on the results of the clinical neurophysiological examinations and electrophysiological tests (H-reflex and NCV), the frequency of DPN was: according to clinical neurophysiological criteria, 75.3% (n = 113); according to altered, sensitive or motor NCV, 38.0% (n = 57); and according to H-reflex alteration (absence or prolonged latency), 71.3% (n = 107). The following abnormal criteria were found in the clinical examination: decreased strength, 1.3% (n = 2); absent tendon reflexes, 64.0% (n = 96); TABLE 1: Demographic and clinical characteristics of the 150 adult patients with type-2 diabetes mellitus referred for diabetic peripheral neuropathy (DPN) Sex Females 105 (70.0) Males 45 (30.0) Hypertension 61 (40.6) Age, years 56.9 ± 9.6 (26 80) Duration of diabetes 8.0 ± 5.7 (1 27) mellitus, years Glycaemia (mg/dl) ± ( ) Data presented as n (%) of patients or mean ± SD (range). 697

5 superficial and vibratory sensations, 64.0% (n = 96); pin sensation, 14.0% (n = 21); and trophic, vasomotor, or sudomotor abnormalities, 22.0% (n = 33). Table 2 shows the predictive value of H- reflex testing, NCV studies, duration of diabetes, sex and glycaemia testing in diagnosing DPN in patients with type-2 diabetes mellitus. Electrophysiological alterations were as follows: H-reflex was absent in 46.0% (69/150) and latency was prolonged in 25.3% (38/150) of patients. Neuropathy severity was graded as follows: grade 0, 12.7% (19/150) of patients; grade 1, 7.3% (11/150) of patients; grade 2, 77.3% (116/150) of patients; and grade 3, 2.7% (4/150) of patients. Multivariate logistic regression was performed to identify independent factors associated with DPN, and showed that abnormal H-reflex was significantly predictive of DPN in adult patients with type 2 diabetes mellitus (OR 4.3; 95% CI 1.6, 11.2; Table 2). Discussion Diabetic neuropathies are common and encompass a wide range of nerve abnormalities (mononeuropathy, sensitive polyneuropathy, motor polyneuropathy, autonomic neuropathy). 18,19 Prevalence is reported to range from 5% to 100%, 20 depending on the diagnostic criteria used. 22 H-reflex, F waves and late responses have been clinically useful for the diagnosis of DPN in a variety of settings. H-reflex measures conduction through afferent and efferent fibres in the monosynaptic reflex arc and is the result of submaximal orthodromic stimulation of type Ia sensory fibres. Abnormalities in the H-reflex have been clinically correlated with nerve root injury, plexopathy and generalized peripheral neuropathy. 23,24 In the present study, 131/150 (87.3%) patients referred for neuropathy screening were diagnosed with DPN. Similar to previous studies, the most common type was generalized sensorimotor symmetrical peripheral neuropathy, with symptoms related to altered sensation in the distal feet or hands, suggesting that both sensory and motor fibres were affected. 25 The absence of symptoms should not be equated TABLE 2: Analysis of Hoffmann (H-reflex), nerve conduction velocity (NCV), and clinical and demographic characteristics as predictors of diabetic polyneuropathy (DPN) in adult patients with type-2 diabetes mellitus Without DPN DPN a Univariate Multivariate OR Variables (n = 19) (n = 131) OR (95% CI) (95% CI) Abnormal H-reflex, yes 6 (31.5) 101 (77.1) 2.9 (1.7, 5.1) 4.3 (1.6, 11.2) Abnormal NCV studies, yes 3 (15.8) 54 (41.2) 1.9 (1.0, 3.5) 2.3 (0.7, 7.2) Duration of diabetes 5.2 ± ± (1.0, 3.8) 1.4 (0.4, 4.9) mellitus, years Sex Females 16 (84.2) 89 (67.9) 0.4 (0.1, 1.4) 31.6 (0.7, ) Males 3 (15.8) 42 (32.1) Used as Used as reference reference Glycaemia, mg/dl ± ± (1.0, 1.02) 0.9 (0.9, 1.0) Data presented as n (%) of patients or mean ± SD. Hosmer and Lemeshow adjustment dependability test: χ 2 = 4.6, degrees of freedom = 8; P = 0.7. CI, confidence interval; OR, odds ratio. 698

6 with the absence of neuropathy; up to 50% of patients with DPN may be asymptomatic but are still at risk of foot ulcers. 10 Neurophysiological examination, which may or may not include a quantitative evaluation of sensation, has long been considered by neurologists to be the standard for diagnosis of DPN. 26 The present study showed a significant association between abnormalities in the H-reflex and the presence of DPN, and suggested that the H- reflex could be used as an early diagnostic test for neuropathy. Patients with DPN are at very high risk of foot ulcers, usually as a result of loss of sensation in the foot More than half of all lower limb amputations are largely preventable with good care and other therapeutic intervention. 25,26 The present study demonstrated that measurement of the H-reflex in addition to conventional NCV studies and clinical and neurophysiological assessment in patients with type-2 diabetes mellitus may aid the diagnosis early of DPN. As such, use of the H-reflex in combination with other routine assessments could identify more patients at risk of serious DPN complications. Conflicts of interest The authors have no conflicts of interest to declare in relation to this article. Received for publication 6 May 2011 Accepted subject to revision 6 June 2011 Revised accepted 15 February 2012 Copyright 2012 Field House Publishing LLP Appendix 1 MICHIGAN NEUROPATHY SCREENING INSTRUMENT Physical Assessment (To be completed by health professional) 1. Appearance of Feet Right Left a. Normal 0 Yes 1 No a. Normal 0 Yes 1 No b. If no, check all that apply: b. If no, check all that apply: Deformities Deformities Dry skin, callus Dry skin, callus Infection Infection Fissure Fissure Other, specify: Other, specify: Right Left 2. Ulceration Absent = 0 Present = 1 Absent = 0 Present = 1 3. Ankle reflexes Present Decreased Absent Present Decreased Absent = 0 = 0.5 = 1 = 0 = 0.5 = 1 4. Vibration Normal Reduced Absent Normal Reduced Absent perception at = 0 = 0.5 = 1 = 0 = 0.5 = 1 large toe 5. Monofilament Normal Reduced Absent Normal Reduced Absent = 0 = 0.5 = 1 = 0 = 0.5 = 1 Signature: Total Score /10 points 699

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