A Comparative study of examination scores and quantitative sensory testing in diagnosis of diabetic polyneuropathy

Int J Diab Dev Ctries | January-March 2010 | Volume 30 | Issue 1 Context: Many advances have taken place in the detection of diabetic polyneuropathy with respect to examination scores, electrophysiological techniques and quantitative sensory testing. Aim: This study aims to evaluate the discriminative power of the Diabetic Neuropathy Examination Score (DNE), 10-g Semmes-Weinstein Monofi lament Examination (SWME) and Quantitative Sensory Testing by Vibration Perception Threshold (VPT) in the diagnosis of diabetic polyneuropathy and seek an optimal screening method in diabetic clinic. Materials and Methods: Hundred consecutive patients with Type 2 diabetes were subjected to Diabetic Neuropathy Symptom Score, DNE score, Semmes-Weinstein monofilament examination, Vibration Perception Threshold and Nerve Conduction Studies; mean SD for the various characteristics were calculated. Sensitivity and specifi city for the DNE, SWME and VPT were calculated, taking NCS as gold standard. Results: Seventy one of 100 subjects had evidence of neuropathy confirmed by Nerve Conduction Studies, while 29 did not have neuropathy. The DNE score gave a sensitivity of 83% and a specifi city of 79%. The sensitivity of SWME was 98.5% and specifi city was 55%. Vibration Perception Thresholds yielded a sensitivity of 86% and a specifi city of 76%. Conclusions: A simple neurological examination score is as good as Vibration Perception threshold in evaluation of polyneuropathy in a diabetic clinic. It may be a better screening tool for diagnosis of diabetic polyneuropathy in view of the cost effectiveness and ease of applicability.


Introduction
Diabetic Polyneuropathy (DPN) is the most common of the heterogeneous group of diabetic neuropathies and contributes to 50 to 70% of nontraumatic amputations.Screening for diabetic polyneuropathy improves foot care and prevents morbidity.Current level of evidence for optimal screening method is limited.Many advances have taken place in the detection of DPN with respect to examination scores, electrophysiological techniques and quantitative sensory testing.A consensus indicates the need for abnormalities in at least two of fi ve possible modalities to make the diagnosis for research purposes. [1]This study aims to evaluate the discriminative power of the Diabetic Neuropathy Examination Score (DNE), 10-g Semmes-Weinstein Monofi lament Examination (SWME) and Quantitative Sensory Testing by Vibration Perception Threshold (VPT) in the diagnosis of diabetic polyneuropathy.The other objective was to seek an optimal screening method in diabetic clinic.The prevalence of various subtypes of neuropathy depending on the distribution was studied.

Materials and Methods
Subjects included 100 consecutive patients with Type 2 diabetes.Patients were excluded from the study if they had other causes of neuropathy such as alcoholism, liver or renal disease, toxic exposure, other endocrine, metabolic or nutritional disorders, inflammatory diseases, or monoclonal gammopathy.Age, gender,

Diabetic neuropathy examination score:
A thorough neurological examination was carried out and the neurological signs were scored following a DNE score, which is a modification of the Neuropathy Disability Score of Dyck. [4]The DNE score consists of eight items, two testing muscle strength, one a tendon refl ex, and fi ve sensations.

Semmes-Weinstein monofi lament examination
Light touch/pressure perception was assessed using a 10 g monofi lament.These were applied on both feet on the plantar surface of the hallux and centrally at the heel.The end of the fi lament was pressed on the plantar surface of the hallux and centrally at the heel with enough pressure to cause the monofi lament to buckle.This was done six times at each point and the participant was blinded to the application of the monofi lament during testing. [4]A 'yesno' method was used, meaning that the patient says yes each time he/she senses the application of a monofi lament.The ability to correctly sense the monofi lament in six trials on both locations was defi ned as normal, whereas the inability to sense the monofi lament correctly in one or more trials was defi ned as disturbed.

Vibration perception threshold
VPT was tested using a hand-held biothesiometer (Sensitometer, Dhansai Lab, Mumbai).).Aft er explaining the procedure, the butt on is applied to various parts of both the feet with the patient relaxed, in the supine position in a quiet room.The vibration is increased gradually from the minimum voltage and the transition from no vibration to the onset of perceiving vibration is taken as VPT.The Yes/No method is used.The VPT is tested on six areas on the plantar aspect of both feet-the hallux, the fi rst metatarsal head, the third metatarsal head, the fi ft h metatarsal head, the instep and the heel.An average of all the areas tested is taken as the VPT of the subject.The voltage is gradually increased until the patient senses the vibration by the Yes or No.The VPT is measured in volts.In the present study, a voltage of more than 15 V was taken as presence of neuropathy.

Nerve conduction studies
All patients underwent conventional sensory and motor nerve conduction studies using 2-channel digital electromyograph (Medicaid).The nerves tested were median, ulnar, common peroneal, tibial and sural nerves.The parameters recorded included distal latencies, amplitudes of compound motor action potentials (CMAP), duration of CMAP, F wave latencies and conduction velocities in motor nerves.In sensory nerves, latencies and amplitudes of the sensory nerve action potentials and their conduction velocities were documented.
The presence or absence of neuropathy in these subjects was defi ned as follows: The mean age, duration of diabetes and HbA1c levels between subjects with and without neuropathy are shown in Table 2.
The sensitivity and specifi city of the DNE Score, SWME, and VPT are shown in Table 3.Out of the 71 subjects who were confirmed to have neuropathy by Nerve Conduction Studies, 59 tested positive by the DNE score which gave a sensitivity of 83%.Of the 29 subjects who were considered as not having neuropathy by the same criteria, 6 had a DNE score positive for neuropathy.The specifi city of the DNE score was 79%.
Similarly, the SWME was disturbed in 68 of the 71 subjects with neuropathy yielding a sensitivity of 98.5%.SWME was disturbed in 13 of the 29 subjects without neuropathy with a specifi city of 55%.Vibration perception thresholds were abnormal in 61 of the 71 subjects with neuropathy, a sensitivity of 86%.The values were abnormal in 7 of the 29 subjects without neuropathy, a specifi city of 76%.

Parameter
No neuropathy Neuropathy

Results
One hundred patients took part in the study and their demographic characteristics are shown in Table 1.
Seventy one of 100 subjects had evidence of neuropathy confi rmed by nerve conduction studies.
The proportion of subjects who had neuropathy with diabetes duration of more than 10 years rose to 90%, compared to individuals less than 10 years (63%).
Figure 1 shows proportion of subjects with and without neuropathy based on duration of diabetes.There was a signifi cant correlation between DNE and VPT.Correlation coefficient for the DNE and VPT was 0.72 which was statistically signifi cant.(Pearson's correlation coeffi cient r ϭ 0.72 with P value of Ͻ 0.05).Figure 2 illustrates the correlation between DNE and VPT.The various subtypes of neuropathy were analyzed based on nerve conduction studies.Table 4 shows the distribution of various types of neuropathy based on NCS

Discussion
The prevalence of neuropathy in Type 2 diabetes, in the present study, was 71% taking nerve conduction studies as gold standard.Studies on prevalence of neuropathy in Type 2 diabetes had widely diff ering results, varying from 15 to 50%.The wide variability was att ributed to diff erences in patient sample, diagnostic methods and criteria adopted for diagnosis.In the San Luis Valley Diabetes Study (SLVDS), a population based study of Type 2 diabetic patients where the diagnosis of neuropathy was based on history and examination; there was an overall prevalence of 28%. [5]In another study, the prevalence of DPN in Type 2 diabetes among hospital patients in Spain was 26.7%. [6]However, the study involved assessment of only symptoms and signs for a diagnosis of DPN against a predetermined score.In an Asian hospital-based study, which analyzed the long term complications of newly diagnosed Type 2 diabetes, the prevalence of neuropathy was 25.2%. [7]he higher prevalence of neuropathy in the present study may be due to the selection of patients from the specialty diabetes mellitus clinic who were more symptomatic and tended to have more complications.Another reason for the higher prevalence in the present study could be due to the fact that the diagnosis of neuropathy was established by nerve conduction study which is a more sensitive method.Studies that used nerve conduction studies as a diagnostic marker also reported higher prevalence of neuropathy.A Figure of 45% for prevalence of neuropathy in Type 2 diabetes was reported from a population based sample from Rochester [8] and 42% from a sample of 811 t ype 2 diabetic subjects drawn from 37 UK general practices. [9]In the Rochester study, electrophysiology was used as part of the neurological assessment, but it was a population based study.None of the earlier hospital based studies used electrophysiological studies for diagnosis of DPN.
Duration of diabetes showed a signifi cant eff ect on the prevalence of neuropathy in the present study.The association between duration of diabetes and the risk of neuropathy is strong and has been confi rmed in a variety of studies.In a study from UK, the prevalence of DPN rose from 21% in those with a diabetes duration of less than fi ve years to 37% in people with a duration of over 10 years. [10]In a Spanish study, the prevalence increased from 14% at under five years' duration to 44% at duration of more than 30 years. [6]In the present study, the prevalence was 63% in those with duration less than 5 years to 90% in those with duration more than 10 years.These data probably relate to a bias inherent in a hospitalbased study where the more severely aff ected diabetic patients are taken care of.HbA1c was significantly higher in those with neuropathy in the present study.The risk of developing DPN has been calculated to rise by approximately 10-15% for every 1% rise in HbA1c. [11]e present study showed a prevalence of 13% for foot involvement, a Figure higher than reported elsewhere.In a population based study from Spain, 3.3% of the subjects had foot ulcers. [6]In an Asian hospital-based study, the ulcer rate was 2.6%. [7]However, this study recruited newly diagnosed diabetes and clinical evidence of neuropathy was seen in only 10% of subjects.The remaining 15% had evidence of neuropathy by Vibration Perception Threshold.The high prevalence of foot ulcers in our study may be due to the higher prevalence of neuropathy.All these ulcers, except in one subject, occurred in patients with neuropathy.
The present study uses the Symptom Score (DNS), and Examination Score (DNE), which were designed by Meĳ er. [2,4]These scores are simple, reproducible, fast and easy to perform and were modifi ed from the widely used Neuropathy Symptom Score and Neuropathy Disability Score of Dyck.The construct validity of these scores in relation to SWME and VPT were studied earlier. [2,4]The correlation between the DNS and DNE scores and NCS was signifi cant (rho ϭ 0.62 for DNE and 0.51 for DNS). [12]he symptom score was highly sensitive in the present study also, as in the study by Meĳ er and others.However, since many of the patients included in the study were severely aff ected they were more likely to have symptoms.Accordingly, the symptom scores were not analyzed further.The sensitivity and specifi city of the DNE score was high in this study as compared to nerve conduction studies, sensitivity being 0.83 and specifi city of 0.79.This is in concordance with the study by Meĳ er et al.-"Clinical diagnosis of DPN with the DNS and DNE scores", where both scores are strongly correlated to electro diagnostic studies. [12]The sensitivity and specifi city of DNE were 0.96 and 0.51 respectively, for an abnormal result using monofi laments.For an abnormal result using the VPT, these values were 0.97 and 0.59 respectively.Pearson's correlation r for VPT with DNE was 0.75 in Meĳ er's study [4] and the present study showed similar correlation of 0.72.
A number of cross-sectional studies have assessed the sensitivity of the 10-g monofi lament to identify feet at risk of ulceration.Sensitivity varied from 86 to 100%. [13- 15]The present study showed sensitivity of 98.5%.The specifi city of monofi lament in diagnosis of polyneuropathy varied from 45-60% in earlier studies. [16,17]The present study showed a specificity of 55%.Reasons for the poor specifi city could be many.The areas chosen for assessment by monofi lament varied in diff erent studies.The diff erent areas chosen in various studies were the dorsum of the hallux, ankle, and plantar aspects of great toe, metatarsal heads and heel.In the present study, we utilized the plantar aspect of great toe and heel.Some of the patients had thicker soles, especially the heels where the ability to feel the monofi lament was diffi cult even in the absence of neuropathy.The discrepancies in the use of Monofi lament are also with regard to the number of applications, varying from 10 to 1 site.Semmes-Weinstein fi laments are available in a number of variable diameters -1 g, 10 g and 75 g.The 10 g (5.07) monofi lament has been shown to be a useful measure of foot ulcer risk in various studies.However, the use of 1 g monofi lament in these patients increased the specifi city.There are no guidelines as to the application of monofi laments.The fi laments that are available also need to be standardized.Booth and Young identifi ed that fi laments manufactured by certain companies do not actually buckle at 10 g of force.Indeed, several fi laments buckled at Ͻ8 g. and could give erroneous results. [18]ny studies have taken VPT as a gold standard, comparing SWME, and clinical examination with VPT.Dyck and colleagues used computer-assisted QST to compare vibration thresholds with signs and symptoms of neuropathy in three large cohorts: The Rochester Diabetic Neuropathy Study, the recombinant human growth factor study, and the pancreas-renal transplant cohort. [19]In these patient groups, there was a "strong and consistent correlation" between sensory loss and other markers of diabetic neuropathy.Further, the data confirmed that vibration thresholds are especially sensitive to mild or subclinical neuropathy.Davies and co-workers also demonstrated that vibratory thresholds can detect subclinical neuropathy in children and adolescents with Type1 diabetes. [20]Nerve conduction studies subsequently confi rmed the neuropathy detected by QST in these young patients.At the other end of the severity spectrum, Boulton and colleagues documented that vibration thresholds provided a strong indication of "risk" for future ulceration across a wide range of ages and durations of diabetes. [21]n the present study, VPT remained highly sensitive (0.86) and specifi c (0.76) as compared to NCS.Nasseri K and coworkers compared the reproducibility of nerve conduction studies and VPT and concluded that both NCS and VPT are reproducible methods to assess diabetic neuropathy.Determination of VPT has the advantage of being a simple and unobtrusive method. [22]alyzing the various subtypes of neuropathy by electro diagnosis, distal sensorimotor neuropathy was found to be the commonest, followed by pure sensory neuropathy.Motor neuropathy was seen rarely, in 3 of the 71 neuropathic subjects.Cranial neuropathy was seen in two cases and asymmetrical axonal in one case.The prevalence of the types of neuropathy in this study is similar to previous data.Carpal Tunnel Syndrome was more common in this series, around 44%.

Conclusion
The DNE score is quite sensitive in diagnosing DPN.Among the three parameters tested, Vibration Perception Threshold is the most specifi c.The results of Vibration Perception Threshold are comparable to Nerve Conduction Studies in diagnosing DPN.Monofi lament examination, though highly sensitive, was less specifi c in diagnosing DPN.Duration of diabetes, and HbA1c were positively correlated with neuropathy.Our study showed a higher prevalence of neuropathy and foot involvement compared to the earlier studies.Distal Sensorimotor Neuropathy and Carpal Tunnel Syndrome were the common electrophysiological demonstrable types of neuropathy.

[
Downloaded free from http://www.ijddc.comon Saturday, October 09, 2010, IP: 59.183.146.111]duration of diabetes and history of foot ulceration were recorded.Blood glucose, serum creatinine, routine biochemical and hematological tests, and glycosylated hemoglobin were done in all the subjects.All 100 patients were subjected to: 1. Diabetic Neuropathy Symptom Score 2. Diabetic Neuropathy Examination Score 3. Semmes-Weinstein monofi lament examination 4. Vibration Perception Threshold 5. Nerve Conduction Studies The DNE scores, monofi lament test results and vibration perception thresholds were compared against the Nerve Conduction Studies which are taken as a gold standard and the data analyzed.Diabetic neuropathy symptom score All subjects were questioned regarding the presence or otherwise of symptoms, either positive or negative suggesting the presence of neuropathy.The questionnaire was the Diabetic Neuropathy Symptom DNS Score (2) adopted from the Neuropathy Symptom Score (NSS) of Dyck (3).Diabetic neuropathy symptom Score: The questions should be answered 'yes' (positive: 1 point) if a symptom occurred more times a week during the last 2 weeks or 'no' (negative: No point) if it did not.1. Symptoms of unsteadiness in walking? 2. Do you have a burning, aching pain or tenderness of your legs or feet? 3. Do you have pricking sensations at your legs and feet? 4. Do you have places of numbness on your legs or feet?Maximum score: 4 points; 0 points-PNP absent; 1-4 points -PNP present (PNP ϭ Polyneuropathy)

[
Downloaded free from http://www.ijddc.comon Saturday, October 09, 2010, IP: 59.183.146.111] less Ͼ15 voltsMeans Ϯ SD for the various characteristics were calculated.Sensitivity and specifi city for the DNE, SWME and VPT were calculated, taking NCS as gold standard.The relation of diabetic neuropathy to age of the subject, duration of diabetes and glycemic control was determined and their signifi cance was assessed by chi-square test.The Pearson correlation coeffi cient -r (95% CI) was used to measure the degree of association between the DNE and VPT.A P value Ͻ 0.05 was considered statistically signifi cant.

Figure 1 :
Figure 1: Proportion of subjects with and without neuropathy based on duration of diabetes

Figure 2 :
Figure 2: Correlation between diabetic neuropathy examination score and vibration perception threshold