O R I G I N A L A R T I C L E

750 DIABETES CARE, VOLUME 23, NUMBER 6, JUNE 2000

Early detection of symmetrical distalsensorimotor polyneuropathy (PNP) isimportant in patients with diabetes

because preventive interventions can beapplied to decrease morbidity (1). Unfortu-nately, no “gold standard” exists for diag-nosing PNP, but a consensus panel hasrecommended that at least 1 measurementshould be performed in 5 different diag-

nostic categories. One of these categories isa standardized physical examination (2,3).In our opinion, diagnostic tests should ful-fill the following criteria: validation (pres-ence of an independent reference standard,adequate spectrum and number of patients,standardization, soundly based item selec-tion), predictive value, manageability(reproducibility, performance in clinical

practice), and hierarchy. Frequently usedand accepted examination scores for dia-betic neuropathy are the Neuropathy Dis-ability Score (NDS) (4), the NeuropathyImpairment Score in the Lower Limbs (NIS-LL) (5,6), various modified NDS scores(7,8), the Neuropathy Deficit Score (9), theMichigan Neuropathy Screening Instru-ment (MNSI) (10), and the Clinical Exami-nation Score of Valk (CE-V) (11).

The NDS was designed for neuropathyin general (4). Although the score is wellfounded and complete, it is difficult to per-form in clinical practice on patients with dia-betic foot problems. Precise descriptions ofhow the tests should be performed and howitems should be scored are lacking. The NIS-LL is a modification of the NDS specific fordistal PNP, although motor activity grading isthe focus and involves 64 of a maximum of88 points (5,6). The NIS-LL has not beenvalidated. Various other modified NDS scor-ing systems have been used, such as those ofVeves et al. (7) and Young et al. (8); however,these instruments also have not been vali-dated, and no information is available ontheir predictive value regarding the results ofclinical standards. The Neuropathy DeficitScore is a neurological examination scoreaimed at anatomical levels in the legs andarms (9). It has not been validated, and noinformation is available about how to inter-pret modifications, which is also the case forthe other modified NDS scoring systems(7,8). Feldman et al. (10) developed a com-bination of 2 scoring systems: the MNSI(symptom and examination score) and theMichigan Diabetic Neuropathy Score (neu-rological examination and nerve conduc-tion studies). These scores do not have aseparate examination score as advised byconsensus reports (2,3). The CE-V can beused to examine sensory functions, tendonreflexes, and muscle strength in the lowerextremities (11). The scoring systems ofFeldman et al. (10) and Valk et al. (11) havebeen validated and are easy to perform inclinical practice. None of the aforemen-tioned scores is known to be hierarchical.

The aim of this study was to adapt theNDS into a valid, easily managed, graded,and accurate scoring system for diagnosing

From the Rehabilitation Centre Beatrixoord ( J.-W.G.M., E.E.B.), Haren; the Northern Centre for Health CareResearch ( J.-W.G.M., E.v.S., J.W.G., W.H.E.), Groningen; and the Departments of Internal Medicine (A.J.S.),Rehabilitation (W.H.E.), and Endocrinology (E.E.B., T.P.L.), University Hospital, Groningen, the Netherlands.

Address correspondence and reprint requests to Jan-Willem G. Meijer, MD, Rehabilitation Centre Beat-rixoord, P.O. Box 30.002, 9750 RA Haren, the Netherlands. E-mail: j.w.meijer@beatrixoord.nl.

Received for publication 29 October 1999 and accepted in revised form 15 February 2000.Abbreviations: CE-V, Clinical Examination Score of Valk; DNE, Diabetic Neuropathy Examination; MNSI,

Michigan Neuropathy Screening Instrument; MSP, Mokken Scaling Polychotomous items; NDS, NeuropathyDisability Score; NIS-LL, Neuropathy Impairment Score in the Lower Limbs; PNP, polyneuropathy; VPT,vibration perception threshold.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversionfactors for many substances.

Diabetic Neuropathy ExaminationA hierarchical scoring system to diagnose distal polyneuropathy indiabetes

OBJECTIVE — Existing physical examination scoring systems for distal diabetic polyneu-ropathy (PNP) do not fulfill all of the following criteria: validity, manageability, predictive value,and hierarchy. The aim of this study was to adapt the Neuropathy Disability Score (NDS) todiagnose PNP in diabetes so that it fulfills these criteria.

RESEARCH DESIGN AND METHODS — A total of 73 patients with diabetes wereexamined with the NDS. Monofilaments and biothesiometry were used as clinical standards forPNP to modify the NDS.

RESULTS — A total of 43 men and 30 women were studied; mean duration of diabetes was15 years (1–43), and mean age was 57 years (19–90). A total of 24 patients had type 1 diabetes,and 49 patients had type 2 diabetes. Clinically relevant items were selected from the original35 NDS items (specific item scored positive in .3 patients). The resulting 8-item Diabetic Neu-ropathy Examination (DNE) score could accurately predict the results of the clinical standardsand is strongly hierarchical (H value 0.53). The sensitivity and specificity of the DNE at a cut-off level of 3 to 4 were 0.96 and 0.51 for abnormal monofilament scores, respectively. Forabnormal vibration perception threshold scores, these values were 0.97 and 0.59, respectively.Reproducibility as assessed by inter- and intrarater agreement was good.

CONCLUSIONS — The DNE is a sensitive and well-validated hierarchical scoring systemthat is fast and easy to perform in clinical practice.

Diabetes Care 23:750–753, 2000

JAN-WILLEM G. MEIJER, MD

ERIC VAN SONDEREN, PHD

EDDIE E. BLAAUWWIEKEL, MD

ANDRIES J. SMIT, MD, PHD

JOHAN W. GROOTHOFF, PHD

WILLEM H. EISMA, MD

THERA P. LINKS, MD, PHD

C l i n i c a l C a r e / E d u c a t i o n / N u t r i t i o n

DIABETES CARE, VOLUME 23, NUMBER 6, JUNE 2000 751

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PNP, the Diabetic Neuropathy Examina-tion (DNE) score.

RESEARCH DESIGN AND METHODS

PatientsOur study group consisted of 73 patientswith diabetes. Exclusion criteria were fac-tors that may interfere with the neurologicalcondition of the subjects other than PNP. Atotal of 50 patients were randomly selectedfrom the diabetes outpatient clinic of Uni-versity Hospital (Groningen, the Nether-lands). A total of 23 patients with obviousdiabetic foot complications or clinical neu-ropathy were selected from the Departmentof Diabetes at the Rehabilitation CentreBeatrixoord. The characteristics of these 73patients are shown in Table 1.

MethodsThe same researcher ( J.-W.G.M.) examinedall 73 patients. First, the NDS and NIS-LLwere performed followed by quantitativesensory tests that acted as a clinical standard.

NDS and NIS-LLThe NDS is the most widely used andwidely accepted scoring system for diabeticneuropathy; it has also been recommendedin consensus reports (2–4). The instrumentexamines cranial nerves, muscle weakness,reflexes, and sensation (4). The scale con-sists of 35 items for testing the left and rightsides of the body; scores range from 0 to 4.A sum score is obtained with a maximumof 280 points.

The NIS-LL is a modified version of theNDS to quantify diabetic PNP. The lower-limb items of the NDS are used comple-mented with 2 muscle power items (toeextension and toe flexion). The NIS-LL has14 items: 8 items evaluate muscle power(0–4 points), 2 items evaluate reflexes (0–2points), and 4 items evaluate sensory modal-ities (0–2 points). All items are tested onboth sides. The maximum score is 88 points.

The NDS, as the most complete andaccepted score, was used for item selectionto develop the DNE.

Clinical standardsSemmes-Weinstein monofilaments and bio-thesiometry were chosen as clinical stan-dards to study the construct validity of thescoring system for PNP. Semmes-Weinsteinmonofilaments were tested on the plantarsurface of the hallux and centrally at theheel (when necessary after removal of exces-sive calluses). This method was standard-ized according to generally acceptedguidelines (12–15). The “yes/no” methodwas used, which means that the patientsays “yes” each time he or she senses theapplication of a monofilament. Six trialswere administered; when the patient wasunable to respond correctly in more than 1trial, a heavier monofilament was used. The1-, 10-, and 75-g monofilaments were used.We present the results in 4 categories: cate-gory 1, 1-g monofilament felt; category 2,10-g monofilament felt and 1-g monofila-ment not felt; category 3, 75-g monofila-ment felt and 10-g monofilament not felt;and category 4, 75-g monofilament not felt.

Vibration perception thresholds (VPTs)were determined using a hand-held bio-thesiometer (Biomedical Instruments,Newbury, OH). VPT was tested at the dor-sum of the hallux on the interphalangealjoint. It was performed in a standardizedway (15,16). The voltage of vibration wasincreased until the patient could perceive avibration. This was done 3 times. Themean of these 3 trials was used to deter-mine the VPT.

ReproducibilityTo test reproducibility, inter- and intrarateragreement were assessed in a separatestudy of 10 patients. The 6 women and 4men with a mean ± SD age of 50.0 ± 15.9years had a wide range of neuropathyseverity. The mean duration of diabetes was11.5 ± 10.5 years; 3 participants had type 1

diabetes, and 7 participants had type 2 dia-betes. Two experienced physicians, anendocrinologist (E.E.B.) and a physiatrist( J.-W.G.M.), both experienced in diagnos-ing diabetic neuropathies, rated thesepatients twice within 1 week.

Statistical analysesThe internal consistency of the DNE wasassessed by calculating Cronbach’s a andreliability coefficient r (17), which are com-parable with a. In addition to internal con-sistency, scalability coefficient H wascomputed with the probabilistic scalingprogram of Mokken Scaling Polychoto-mous (MSP) items to assess the hierarchicalstructure of the items (17). High values ofcoefficient H increase the likelihood thatpatients with the same scale score have dif-ficulties or problems with the same items.

The statistical package SPSS-PC (Chi-cago) was used to compute the descriptivestatistics, factor analysis, reliability coeffi-cient Cronbach’s a, Pearson’s correlationcoefficient r, and Student’s t test.

Inter- and intrarater agreement wereassessed on a scale level by computingPearson’s correlation coefficients and t testvalues for differences in means.

RESULTS — Items were excluded fromthe original NDS if they conformed to thefollowing definition of clinical irrelevance:specific item scored positive in .3patients. After examining the patients, 9 ofthe original 35 items remained. No rele-vant differences were found between themeasurements made on the left and rightsides, so only the right-side items were usedin the analyses.

Factor analysis was performed on the 9items to investigate coherence. The coher-ence of the 8 items was good; only item 22(muscle strength in triceps surae) had poorcoherence compared with the other items.

Calculation of hierarchy was per-formed using the MSP items. This resultedin a hierarchical scale of 8 items. Item 22disturbed the hierarchy severely. Logisticalregression analysis was performed to studywhether item 22, in addition to the 8-itemhierarchical scale, could predict the resultsof the clinical standards VPT and monofil-aments. Item 22 did not make any signifi-cant contribution, so it was excluded.

Modification of the NDS resulted in an8-item scale, the DNE. The DNE is shownin the Appendix. The reliability of the scalewas assessed by measuring the internalconsistency. According to both Cronbach’s

Table 1—Patient characteristics

n 73Mean age (years) 56.9 ± 16.1 (19–90)Mean duration of diabetes (years) 14.9 ± 9.9 (1–43)Sex (M/F) 43/30Type of diabetes (type 1/type 2) 24/49Mean HbA1c (%) 8.7 ± 1.4 (6.6–13.5)

Data are n or means ± SD (ranges).

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a (0.78) and reliability coefficient r (0.81),the scale appears to be reliable. The H valuefor hierarchy was 0.53, which indicates thepresence of a strong hierarchical scale (17).

Table 2 shows characteristics of theDNE, NDS, and NIS-LL. As expected, thecorrelation between the DNE and the NDS(Pearson’s r = 0.96, P , 0.001) and NIS-LL(Pearson’s r = 0.92, P , 0.001) were bothhigh. The reliability of the scoring systemswas good.

The DNE is fast and easy to perform inclinical practice; application takes ,5 min.

Relationship of the NDS, NIS-LL, andDNE with the clinical standardsPearson’s correlation coefficient r formonofilaments with the NDS, NIS-LL, andDNE was similar with values of 0.76 (P ,0.001), 0.74 (P , 0.001), and 0.75 (P ,0.001), respectively. Pearson’s correlationcoefficient r for VPT with the NDS, NIS-LL,and DNE was similar with values of 0.73(P , 0.001), 0.71 (P , 0.001), and 0.75(P , 0.001), respectively. The NDS, NIS-LL,and DNE predicted the results of the clinicalstandards very accurately (P , 0.001).

At a cutoff point of 3 to 4, the sensitiv-ity and specificity of the DNE were 0.96and 0.51, respectively, for an abnormalresult using monofilaments. For an abnor-mal result using the VPT, these values were0.97 and 0.59, respectively.

ReproducibilityReproducibility of the DNE was assessed bycomparing the scores of 2 raters obtainedon 2 occasions (interval of 1 week). Theinterrater correlation was 0.97 at t1 and0.92 at t2. Differences in mean scores were,10% and were not significant (P = 0.08and P = 0.55, respectively). The intraratercorrelation was 0.89 for 1 rater and 0.99 forthe other. The mean scores of the 2 ratersdid not differ significantly at t1 and t2 (P =0.17 and P = 0.60, respectively).

CONCLUSIONS — The NDS is awidely accepted and validated physicalexamination scoring system used to diag-nose neuropathy. Its predictive value andreproducibility are high. It is well correlatedwith neurophysiological and sural nervemorphometric abnormalities in patientswith diabetes (4,18–21). Because the aim ofthe NDS is to evaluate neuropathy in gen-eral, it is not completely suitable for use atan outpatient diabetic foot clinic. Conse-quently, several other scoring systems havebeen developed, but they do not sufficiently

fulfill all of the criteria necessary for ade-quate diagnostic tests. One of these tests isthe NIS-LL (a score for distal diabetic PNP),which has 14 items. The score has not beenvalidated and focuses more on motor prob-lems than on sensory problems (5,6).

In this study, the NDS was modifiedonce again with the aim of achieving a newphysical examination scoring system fordiagnosing distal symmetrical PNP in dia-betes. The new instrument is the DNE,which is a scoring system with 8 items. Itwas validated in diabetic patients with awide spectrum of complications. The DNEis hierarchical, sensitive, fast, and easy toperform in clinical practice (application took,5 min). Hierarchy implies that patientswith the same scale score have difficulties orproblems with the same items, which makesthis scoring system able to differentiatebetween severity levels of PNP and to com-pare groups or individuals over time. TheNDS, NIS-LL, and the other instruments forevaluating PNP have not been documentedto represent a hierarchical scale.

Our modifications were validated withmonofilament measurements and VPTs.These are both semiquantitative reliablemeasurements with proven predictivevalue for the development of clinical prob-lems such as foot ulcers and amputations.They are noninvasive, patient friendly,independent, and complementary (12–16).Monofilaments and VPTs only assess largefiber function; no small fiber tests havebeen used in this study. Testing the DNE ona random sample from the outpatient clinicin addition to a set of patients with definiteneuropathy means that the results are gen-eralizable to the complete range of patientswith diabetes.

Many clinicians prefer using electro-diagnostic techniques to diagnose diabeticPNP. Although neurophysiological exami-nation is sensitive, specific, and repro-

ducible regarding the presence and severityof peripheral nerve involvement inpatients with diabetes (18), it is not suit-able for making a quick preliminary diag-nosis at a diabetes outpatient clinic. Nodata are available on the predictive valueof these techniques in relation to thedevelopment of clinical problems such asdiabetic foot disease.

Because the aim of this study was todevelop a screening instrument as a tool inthe detection and prevention of patients atrisk for diabetic foot complications, theobserved sensitivity and specificity of theDNE are satisfactory. Because sensitivity isof greater importance than specificity forscreening instruments, the chosen cutoffvalue results in the desired high sensitivitywith an acceptable specificity. A low speci-ficity might burden prevention educationprograms. The combined use of differentdiagnostic tools, as advised in consensusreports, will enhance specificity.

The selection of the muscle strength ofthe quadriceps femoris item in the DNE issurprising and suggests the presence ofmononeuropathy. Nevertheless, all patientswith quadriceps dysfunction also showedother abnormalities regarding sensations inthe feet that were not related to the sameperipheral nerves, which makes mononeu-ropathy less probable. The ankle dorsiflex-ion item was excluded because of poorcoherence and disturbance of hierarchy. Itdid not contribute to the 8 definite items.Perhaps this discrepancy in musclestrength and its assessment is because ofother factors such as limited joint mobility.

The results of validation and the pre-dictive value of the NDS, NIS-LL, andDNE were very satisfactory. The strengthsof the DNE are its manageability in clinicalpractice and its hierarchy. The DNE is themost efficient according to the criteriashown in Table 2.

Table 2—Characteristics of the NDS, NIS-LL, and DNE in our study population (n = 73)

NDS NIS-LL DNE

Mean score 19.7 ± 14.5 9.7 ± 7.9 5.0 ± 3.6Reliability (a) 0.88 0.87 0.78Items 70 28 8Maximum score 280 88 16Maximum scored 56 32 13Items not scored 44 1 0,3 scores 8 3 0

Data are n or means ± SD, unless otherwise indicated.

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In conclusion, the DNE as modifiedfrom the NDS is fast, easy to perform, hier-archical, and sensitive for PNP, and patientscores are more differentiated.

Acknowledgments — We thank Prof.H.J.G.H. Oosterhuis, Department of Neurology,University Hospital Groningen, who providedhelpful comments on this study.

APPENDIX: DIABETIC NEUROPATHY EXAMINATION

Diabetic Neuropathy ExaminationMuscle strength1. Quadriceps femoris: extension of theknee2. Tibialis anterior: dorsiflexion of the footReflex3. Triceps suraeSensation: index finger4. Sensitivity to pinpricksSensation: big toe5. Sensitivity to pinpricks6. Sensitivity to touch7. Vibration perception8. Sensitivity to joint position

Only the right leg and foot are tested.Scoring from 0 to 2:0 = Normal1 = Mild/moderate deficit

• Muscle strength: Medical ResearchCouncil scale 3–4

• Reflex: decreased but present• Sensation: decreased but present

2 = Severely disturbed/absent• Muscle strength: Medical Research

Council scale 0–2• Reflex: absent• Sensation: absent

Maximum score: 16 points

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