The Clinical Identification of Peripheral Neuropathy Among Older Persons

Transcription

1 1553 The Clinical Identification of Peripheral Neuropathy Among Older Persons James K. Richardson, MD ABSTRACT. Richardson JK. The clinical identification of peripheral neuropathy among older persons. Arch Phys Med Rehabil 2002;83: Objective: To identify simple clinical rules for the detection of a diffuse peripheral neuropathy among older outpatients. Design: Observational, blinded, controlled study. Setting: A tertiary-care electrodiagnostic laboratory and biomechanics laboratory. Participants: One hundred research subjects, 68 with electrodiagnostic evidence of peripheral neuropathy, between the ages of 50 and 80 years. Interventions: Not applicable. Main Outcome Measurements: One examiner, unaware of the results of electrodiagnostic testing, evaluated Achilles and patellar reflexes, Romberg testing, semiquantified vibration, and position sense at the toe and ankle in all subjects, and unipedal stance time and the Michigan Diabetes Neuropathy Score in a subset of subjects. Results: Significant group differences were present in all clinical measures tested. Three signs, Achilles reflex (absent despite facilitation), vibration (128Hz tuning fork perceived for 10s), and position sense ( 8/10 1-cm trials) at the toe, were the best predictors of peripheral neuropathy on both univariate and logistic regression (pseudo R 2.744) analyses. The presence of 2 or 3 signs versus 0 or 1 sign identified peripheral neuropathy with sensitivity, specificity, and positive and negative predictive values of 94.1%, 84.4%, 92.8%, and 87.1%, respectively. Values were similar among subgroups of subjects with and without diabetes mellitus. When other clinicians applied the technique to 12 more subjects, excellent interrater reliability regarding the presence of peripheral neuropathy (.833) and good to excellent interrater reliability for each sign ( range, ) were shown. Conclusion: Among older persons, the presence of 2 or 3 of the 3 clinical signs strongly suggested electrodiagnostic evidence of a peripheral neuropathy, regardless of etiology. Agerelated decline in peripheral nerve function need not be a barrier to the clinical recognition of a diffuse peripheral neuropathy among older persons. Key Words: Geriatrics; Peripheral neuropathies; Nerve conduction; Physical examination; Rehabilitation; Signs and symptoms by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation From the Department of Physical Medicine and Rehabilitation, University of Michigan Medical Center, Ann Arbor, MI. Supported by the US Public Health Service (grant nos. K23 AG , 1P30 AG 08808). No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated. Reprint requests to James K. Richardson, MD, Dept of Physical Medicine and Rehabilitation, University of Michigan Medical Center, MPB D5200, Ann Arbor, MI , jkrich@umich.edu /02/ $35.00/0 doi: /apmr A DIFFUSE PERIPHERAL NEUROPATHY is relatively common, particularly among older persons. Epidemiologic studies suggest that the prevalence of diabetes mellitus and impaired glucose tolerance are increasing and affect over 40% of American citizens in the 60- to 74-year age group. 1 Other work 2 suggests that the prevalence of peripheral neuropathy in this age group is between 32% and 50% for persons with diabetes mellitus, 11% for persons with impaired glucose tolerance, and 7.1% for normoglycemic persons. Taken together, these data suggest that the prevalence of peripheral neuropathy in the 60- to 74-year age group is approximately 22%. The detection of peripheral neuropathy is an important contribution to the health care of the older person. Peripheral neuropathy contributes to or causes foot deformity, foot pain, skin ulceration, 3 lower-extremity amputation, 4 impaired lowerextremity function, 5 and falls. 6,7 Furthermore, it is often associated with treatable systemic disorders. 8 However, the clinical recognition of peripheral neuropathy in older persons is challenging. Clinical history is unreliable, 9 and physical examination is confounded by the normal decrement in peripheral nerve function that appears to occur with age. These changes in peripheral nerve have been detected clinically, 10 anatomically, 11 and electrophysiologically 12 among older persons, blurring the boundary between normal peripheral nerve function for age and peripheral neuropathy. Strategies for the clinical detection of peripheral neuropathy have been proposed previously; however, from the standpoint of the busy practitioner seeing older patients, these techniques have drawbacks. Some are lengthy and some require expertise or equipment not readily available, 13,14 whereas others are simpler but have been used only to evaluate diabetic neuropathy among relatively young persons. 15,16 For example, the mean ages of subjects in 6 recent studies that describe the clinical detection of peripheral neuropathy were 49.2, 17 53, , , , 16 and 46.1 (control subjects) and 57.2 years. 20 In 1 study, 21 the median age of subjects was 63, but the subjects were as young as 18. Furthermore, these articles were limited to subjects with peripheral neuropathy related to diabetes mellitus. Although diabetes is the leading cause of peripheral neuropathy in more highly developed countries, other causes of peripheral neuropathy are common among older persons. 22,23 Therefore, how the techniques described in these studies may apply to older persons, with and without diabetes, is uncertain. For the last several years, the author has performed neuromuscular physical examinations of older subjects, without being aware of the results of electrodiagnostic testing, by using semiquantitative techniques. The goal of the present study was to use these accumulated data to identify clinical differences between older persons with and without electrodiagnostic evidence of peripheral neuropathy and then to use these differences to develop a clinical strategy for the detection of peripheral neuropathy in this understudied population.

2 1554 IDENTIFICATION OF NEUROPATHY, Richardson METHODS Participants The control and peripheral neuropathy subjects were examined as part of a screening process for other studies that investigated the effects of peripheral neuropathy on postural stability among older persons. The majority of the peripheral neuropathy and all of the control subjects had been referred to the electrodiagnostic laboratory by their primary physicians for symptoms and/or signs consistent with a lower-extremity peripheral neurologic disorder. Reasons for referral for the 68 peripheral neuropathy subjects included suspicion of peripheral neuropathy (50 subjects) and radiculopathy, weakness or myopathy, and carpal tunnel syndrome (18 subjects). Of the 32 control subjects, 13 were referred for suspicion of peripheral neuropathy, and 19 were referred for radiculopathy, lowerextremity mononeuropathy, or weakness. A minority of the peripheral neuropathy subjects responded to local advertisements requesting subjects and then underwent electrodiagnostic testing. All subjects underwent electrodiagnostic testing in the same laboratory, by using the same techniques, by technicians certified by the American Association of Electrodiagnostic Technologists under the supervision of a physician boardcertified by the American Association of Electrodiagnostic Medicine. Inclusion criteria for peripheral neuropathy subjects were (1) to be between the ages of 50 and 80 years and (2) to have electrodiagnostic evidence of a diffuse, primarily axonal peripheral polyneuropathy as evidenced by sural responses, absent or decreased amplitude ( 6 V) with a normal or minimally prolonged distal latency ( 5.0ms) stimulating 14cm from the recording site posterior to the lateral malleolus, 24 and peroneal and/or tibial motor responses, absent or decreased in amplitude ( 2mV for peroneal, 3mV for tibial) with a normal distal latency ( 6.2ms stimulating 9cm from recording sites over the extensor digitorum brevis and 8cm from the abductor hallicus muscles). If bilateral sural responses were absent, then motor responses were not always performed. If the sural responses were present but reduced in amplitude, then motor responses were required and must have been of reduced amplitude. Needle examination was either normal or showed findings consistent with peripheral neuropathy. The inclusion criteria for the control subjects were identical to those for the peripheral neuropathy subjects except that the controls had completely normal electrodiagnostic studies. Physical Examination I performed the physical examination within 4 months of the electrodiagnostic study. At the time of the examination, I was unaware of the results of the electrodiagnostic study. The physical examination for all subjects included the following 5 procedures. Patellar and Achilles muscle stretch reflexes. Efforts to obtain the Achilles reflex included both striking the tendon itself and the plantar strike technique. The latter is reported to be more reliable among older persons. 25 Facilitation was performed by asking the subject to gently plantarflex the foot, tightly close the eyes, or pull their clasped hand apart just prior to striking. The reflex was considered present if it could be obtained with or without facilitation. Vibratory sensation. Vibratory sensation was obtained in a semiquantitative manner. To familiarize the subject with the dissipation of vibration, a 128-Hz tuning fork was maximally struck and then held against the clavicle until it was no longer felt, at which point the subject said gone to cue the examiner. This procedure was then repeated, placing the tuning fork, in order, just proximal to the nailbed of the second digit of the dominant upper extremity, and then just proximal to the nailbed of the first digit and at the medial malleolus of the lower extremities. The number of seconds between the striking of the tuning fork and the subject saying gone were recorded. Position sense. To assess position sense, the dominant great toe was grasped on the medial and lateral surfaces by the examiner s thumb and forefinger. Up and down movements were then performed with the subject s eyes open. Then, with the subject s eyes closed, a series of 10 small amplitude movements were randomly administered. The movement itself occurred over a distance of approximately 1cm and a time of about 1 second. Care was taken not to jerk or snap the toe, but to move it smoothly. A correct response occurred when the subject perceived the movement and was able identify its direction. The number of correct responses was recorded. If the subject was correct on 8 or fewer of the 10 movements, the other side was tested also. Romberg testing. Romberg testing was performed by having the subject stand with the feet close together but not touching. Initially, the subjects stood with eyes open for about 10 seconds; subjects then closed their eyes. The ability to stand without opening the eyes or taking a step for 30 seconds was considered a negative or normal test. Unipedal stance testing and the Michigan Diabetes Neuropathy Score. Some of the subjects also underwent unipedal stance (UPS) testing (n 75) and evaluation with the Michigan Diabetes Neuropathy Score (MDNS) (n 57). The subjects who received this testing were more recent participants in other balance studies, but otherwise similar to the other subjects. For UPS, subjects stood with their weight evenly distributed on both feet, which were shoulder-width apart, and arms held comfortably at the side. Subjects were then asked to balance on the foot of their choice for as long as possible to a maximum of 30 seconds. Failure occurred when the stance foot shifted in any way or the nonstance foot touched the ground. This procedure was repeated 3 times, and the number of seconds the subject was able to balance on 1 foot was recorded for each trial. The MDNS is a point scale ranging from 0 to 46 (higher score reflecting more severe peripheral neuropathy), and it correlates well with more extensive neuropathy staging scales. 15 The MDNS includes muscle stretch reflexes at the biceps, triceps, patella, and Achilles, pinprick sensation at the great toe, ability to perceive the touch of a 10-g monofilament and a 128Hz tuning fork at the great toe, strength of hand dorsal interossei, great toe extension, and ankle dorsiflexion. Statistical Analysis SPSS software version 9.0, a was used for all analyses. Descriptive statistics were generated for the subjects with and without peripheral neuropathy. Group differences in demographic variables were determined with t tests and chi-square analyses. Dichotomous physical examination variables were evaluated against the presence or absence of peripheral neuropathy by chi-square analysis. Descriptive statistics and histograms of the continuous physical examination variables were generated. Cutoff points were chosen by analyzing the histograms and determining the variable value that maximized inclusion of the peripheral neuropathy subjects and exclusion of the controls. Logistic regression was then performed by using the presence or absence of peripheral neuropathy as an outcome and age, body mass index (BMI), and the physical examination variables as predictors.

3 IDENTIFICATION OF NEUROPATHY, Richardson 1555 Table 1: Demographic Characteristics of Subjects With and Without Peripheral Neuropathy With PN (n 68) Without PN (n 32) P* Mean age SD (y) Gender, n (% women) 25/68 (36.8) 16/32 (50.0).209 Mean height SD (in) Mean weight SD (lb) Mean BMI SD (kg/m 2 ) Abbreviation: PN, peripheral neuropathy; SD, standard deviation. * 2-tailed t test. Variables that remained significant predictors, controlling for age and BMI, were then analyzed individually and collectively against the presence or absence of peripheral neuropathy by using chi-square analysis. A clinical strategy based on the number of signs of peripheral neuropathy was developed. The sensitivity, specificity, and positive and negative predictive values for this strategy were determined for all subjects and 4 subgroups. The subgroups included subjects with and without diabetes mellitus and subjects under and over the age of 65 years. RESULTS One hundred subjects were included in the analyses. Sixtyeight of the subjects were in the peripheral neuropathy group, and 32 were in the control group. Although there were no group differences in age, gender, or BMI, the peripheral neuropathy subjects were significantly taller and heavier than the control subjects (table 1). Forty-seven of the subjects (37 Table 2: Semiquantified Continuous Clinical Variables in Peripheral Neuropathy and Control Groups Without PN With PN P* Vibration at toe(s) Vibration at ankle(s) Position sense at toe (correct of 10) Position sense at ankle (of 10) UPS (of 75 subjects) MDNS (of 57 subjects) NOTE: Values are mean SD. * 2-tailed t test. peripheral neuropathy, 10 control) had diabetes mellitus, and 53 (31 peripheral neuropathy, 22 control) did not. Fifty were at or over the age of 65 years (33 peripheral neuropathy, 17 control), and 50 (35 peripheral neuropathy, 15 control) were under age 65. Table 2 shows significant group differences in continuous clinical measures between peripheral neuropathy and control subjects. Significant differences were noted for each measure. Table 3 shows the number of subjects with and without peripheral neuropathy who showed each physical examination characteristic by using selected cutoff points for continuous physical examination variables. Both age and increased BMI have been associated with decreased Achilles reflexes and vibratory sense. 26 Therefore, logistic regression was performed by using the presence or absence of peripheral neuropathy as the outcome, age, BMI, Table 3: Absence and Presence of Peripheral Neuropathy for Discrete and Continuous Clinical Variables by Using Optimal Cutoff Values for the Latter Without PN With PN P* Sensitivity (%) Specificity (%) Achilles Absent 3 49 Present Patella Absent 0 9 Present Vibration at toe Decreased ( 8s) 8 65 Normal ( 8s) 24 3 Vibration at ankle Decreased ( 12s) 5 51 Normal ( 12s) Position sense at toe Decreased ( 8/10) Normal ( 8/10) 22 8 Position sense at ankle Decreased ( 8/10) 0 14 Normal ( 8/10) Romberg Abnormal ( 30s) 0 12 Normal (30s) UPS mean (75 subjects) Decreased ( 10s) 8 46 Normal ( 10s) MDNS (57 subjects) Increased ( 10) 2 45 Normal ( 10) 7 3 * Chi-square test.

4 1556 IDENTIFICATION OF NEUROPATHY, Richardson Table 4: Results of Logistic Regression Using Age, BMI, Vibration at Toe, Achilles Reflex, and Toe Position Sense as Predictor Variables for the Presence or Absence of Peripheral Neuropathy Coefficient P OR (95% CI) Age ( ) BMI ( ) Achilles reflex ( ) Vibration at toe (4.3 to 100) Position sense at toe ( ) NOTE. The pseudo R 2 was.744. Abbreviations: OR, odds ratio; CI, confidence interval. and the 3 best performing physical examination variables from the initial analysis (Achilles reflex, vibration, position sense at the toe) as predictor variables. The 3 physical examination variables were considered as dichotomous variables by using the cutoffs (see table 3), and all 3 variables remained significant predictors of peripheral neuropathy controlling for both age and BMI (R 2.744, table 4.) Given the results of the logistic regression analysis, it was possible to develop a simplified clinical rule by using the 3 best predictors of peripheral neuropathy. The 3 signs, the absence of an Achilles reflex, decrease in vibration, and position sense at the toe, were compared with the presence or absence of peripheral neuropathy. The results (table 5) showed that the presence of 2 or 3 of these signs strongly suggested the presence of peripheral neuropathy, whereas the presence of 1 or none of these signs strongly suggested the absence of peripheral neuropathy. This clinical rule was then applied to subjects with and without diabetes mellitus and to subjects older and younger than 65 years. Reasonable sensitivities, specificities, and positive and negative predictive values were still present within these subgroups (see table 5). The greatest change (from 84.4% to 76.5%) was a decrease in the specificity of the rules when applied to the group over age 65. The clinical rule was also compared with the MDNS, among the 57 subjects who underwent that evaluation, and disagreement between the 2 techniques was found in only 5 of the subjects (table 6). Finally, a physical therapist or another physician evaluated 12 more subjects (6 with peripheral neuropathy) for the presence or absence of the 3 signs, and the results were compared with those obtained by the author. All examiners were blinded to the findings of others. There was excellent agreement regarding the presence or absence of peripheral neuropathy (.833), excellent agreement regarding the number of signs Table 6: Comparison of the Clinical Detection of Peripheral Neuropathy, Using Presence and Absence of Achilles Reflex, and Position Sense and Vibration at the Great Toe, to the MDNS MDSN 10 MDNS 10 0 or 1 sign of PN* or 3 signs of PN 1 43 * P.001 ( 2 analysis). consistent with peripheral neuropathy present (.776), and good or excellent agreement for each individual sign for each limb ( range, ) (table 7). DISCUSSION The boundary between normal peripheral nerve function and peripheral neuropathy is not always distinct, and this is particularly true for older patients. The present study identified peripheral neuropathy by using electrodiagnostic results as the standard. Although electrodiagnostic studies are imperfect, they are generally accepted and do not require sustained concentration or attention on the part of the patient, representing an advantage for the older patient population studied here. Despite evidence that nerve conduction amplitudes decrease with age, 27,28 the nerve conduction amplitudes used to define peripheral neuropathy in the present study were not adjusted for age for 2 reasons: (1) the recognition that abnormal neurologic signs are not necessarily a normal part of aging, 26 and (2) in previous work, 29,30 significant differences in peripheral neuromuscular and balance function were found based on these same electrodiagnostic criteria. Although some authors have reported that Achilles reflexes and vibratory sensation decrease markedly with normal aging, other studies report contrary findings. Two studies 31,32 found the Achilles reflex to be absent in approximately 70% and 50% of persons over the age of 70 years. However, Impallomeni et al 33 obtained Achilles reflexes in 188 of 200 patients over the age of 80 by using the plantar strike technique with reinforcement. Furthermore, they identified causes of neuropathy in 9 of the 12 patients without a reflex, suggesting that its absence had clinical significance. Similarly, vibratory sense at the malleoli was reportedly absent in 30% to 40% of subjects in 2 earlier studies. 10,31 In contrast, Kokmen et al 34 found that healthy subjects from the community between the ages of 61 and 85 years perceived a 128-Hz tuning fork at the medial malleolus for a mean of approximately 10 seconds a result similar to the cutoff value determined in the present study. Table 5: Sensitivity, Specificity, Positive and Negative Predictive Values Using the Presence and Absence of Achilles Reflex, and Position and Vibratory Sense at the Great Toe for Detecting Peripheral Neuropathy Subject Group No. of Signs of PN Without PN With PN Sensitivity (%) Specificity (%) Positive Predictive Value (%) Negative Predictive Value (%) All subjects 0 or or y 0 or or y 0 or or Diabetes present 0 or or Diabetes absent 0 or or3 4 29

5 IDENTIFICATION OF NEUROPATHY, Richardson 1557 Table 7: Interrater Reliability With 12 Additional Subjects (6 with peripheral neuropathy) for Detection of Peripheral Neuropathy and Each of the 3 Signs Used the Presence and Absence of Achilles Reflex, and Position and Vibration Sense at the Great Toe Presence/ Absence PN No. of Signs Achilles Reflex Position Sense Vibratory Sense of PN Right Left Right Left Right Left The data in the present study suggest that a combination of 3 signs is useful in the diagnosis of electrodiagnostically confirmed peripheral neuropathy among older persons. The signs include an absent Achilles reflex despite facilitation, decreased vibration sense at the great toe (a maximally struck 128-Hz tuning fork perceived for 8s), and decreased position sense at the toe (perceived correctly fewer than 8 times in 10 trials). Positive and negative predictive values for electrodiagnostic evidence of peripheral neuropathy were approximately 90% when 2 or 3 of these signs, versus 0 or 1 of these signs, were present. These data agree with previous work that suggests that Achilles reflexes and distal lower-extremity vibratory sensation do decrease with aging, but this decrease has likely been overemphasized and therefore should not necessarily be considered normal. The same clinical strategy was effective when applied to 4 subgroups: subjects age 65 to 80 and 50 to 65 years and subjects with and without diabetes mellitus. The effectiveness of the strategy among the subjects without diabetes mellitus is important considering the frequency of peripheral neuropathy from other causes in older patients. 22,23 The techniques used in the physical examination were slightly modified from those typically used and deserve highlighting. Efforts to obtain the Achilles reflex included both striking of the tendon and the plantar strike technique and facilitation techniques. The vibratory and toe position sense were semiquantified rather than just considered present or absent. The order of testing of vibratory sensation was important. The subject had 2 opportunities to perceive the presence and extinguishing of vibratory sensation (at the clavicle and the distal upper extremity) before the toe and malleolus were tested. Position sense testing at the toe was performed by smoothly moving the digit with 1-cm motions over a period of about 1 second. No verbal cues were given so that an incorrect response included an absent response as well as suggesting the digit moved the wrong direction. The MDNS correlates well with more intensive neuropathy assessment instruments among younger subjects (mean age, 47.5y) with diabetes mellitus. Feldman et al 15 used a score of 6 as the threshold that best distinguished between subjects with and without peripheral neuropathy. In the present study of older subjects, a value of 10 provided the best threshold. This threshold is consistent with a mild decrement in peripheral nerve function with age. The agreement between the clinical strategy for identifying peripheral neuropathy in this study and the MDNS supports the validity of the strategy. Romberg testing was specific for the identification of peripheral neuropathy, but its marked lack of sensitivity (17%) precluded its use to identify peripheral neuropathy. UPS showed good sensitivity, but only moderate specificity. Because both peripheral neuropathy and impaired UPS have been associated with injurious falls, UPS may best be used as a measure of how severely balance is affected among persons with peripheral neuropathy. 7,35 Position sense in the distal lower extremity appears relatively unaffected among healthy older persons. Howell 31 found that position sense at the toe was spared in the older cohort studied, and Kokmen et al 34 found little difference in toe position sense between young and healthy older subjects. Conversely, decreased proprioception at the toe has been identified among subjects with just mild pathology distal large fiber neuropathy and normal standard nerve conduction studies. 36 High technology quantitative testing of ankle proprioceptive thresholds have demonstrated minimal differences between healthy old and young subjects, 37 but sizable differences between older, age-matched subjects with and without peripheral neuropathy. 30 Taken together, these studies suggest that reduced clinical position sense at the toe is not typical among healthy older persons, and when identified is associated with a subclinical impairment in ankle proprioception which likely contributes to postural instability in patients with peripheral neuropathy. The strength of the conclusions drawn from the present study must be tempered by the study population and the examination techniques. The findings can likely be applied to the population studied, patients between the ages of 50 and 80 years referred to an electrodiagnostic laboratory with lower-extremity symptoms, but findings should be applied to other groups with caution. Because the controls were referred to the electrodiagnostic laboratory for evaluation of lower-extremity symptoms or signs, the controls were not completely normal, which increases the possibility that some had subclinical disease. Greater group differences might have been obtained, and more sensitive and specific criteria for peripheral neuropathy identified, if the control group had been completely asymptomatic. Electrophysiologic studies and the examination techniques used in this work evaluated what is considered large diameter nerve fiber function. Therefore, it would be anticipated that the clinical strategy developed here would be insensitive to small fiber neuropathy, typically identified by a decrease in distal pinprick sensation, temperature discrimination, and autonomic dysfunction. However, isolated small fiber neuropathy is not common, and among patients with diabetes there is a significant relationship between small and large fiber function. 38 CONCLUSION Peripheral neuropathy is common among older persons, and its detection is clinically relevant. This study found a strong correlation between semiquantitative physical examination techniques and the presence of peripheral neuropathy determined electrodiagnostically. However, as with all studies, these findings should be replicated by others before widespread clinical use is considered. The examination techniques described cannot replace electrodiagnostic studies that, unlike the physical examination, require no subjective input from the patient. However, it is hoped that clinicians will be able to use these findings to evaluate more accurately older persons with lower-extremity neurologic symptoms. The data suggest that the related decline in peripheral nerve function has been overemphasized, and is not a barrier to the efficient clinical identification of peripheral neuropathy among older persons. Acknowledgment: I thank Ken Guire for his patience and expertise while providing statistical consultation.

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