**4. Verification of early detection of DPN**

**3.4. Experimental procedures for detection by diabetes mellitus subjects based on** 

Three different procedures were performed. In the first, tactile stimuli were presented to both fingers simultaneously, in a single direction starting at the fingertips (Pattern 6 in **Figure 8**). Subjects were asked if they had perceived the stimuli. This procedure is known as the tactile sensation threshold 1 direction test (TST-1) or PNV 1 direction test (PNV 1) and was used to investigate the perception of tactile stimuli in two fingers. In the second procedure, a moving stimulus was presented to one of the two fingers in a random direction, and the subject was asked to identify both the finger and the direction of movement. In this procedure, known as the tactile sensation threshold 4 direction test (TST-4) or PNV 4 direction test (PNV 4), the subject was asked to identify the tactile perception as matching one of the four patterns shown in **Figure 8**. In the third procedure, known as the tactile sensation threshold 8 direction test (TST-8) or PNV 8 direction test (PNV 8), stimuli moving in random directions were applied to one or both fingers, and the subject was asked to match the finger(s) and direction of move-

In all procedures, the examination began at a stimulus intensity of 15. Based on the accuracy

Again, based on the accuracy of the answer given, in the next round, a stimulus intensity of 26, 19, 11, or 4 was presented to the subject. The stimulus intensity was then changed until the subject gave a correct answer 66.7% or more of the time. This TST score or PNV score was defined as the tactile threshold. The value for the tactile threshold was defined as the lowest value among the 30-stage stimulus intensity in which subjects were able to correctly answer

To reduce the examination time as much as possible, we applied a protocol to stimuli levels

In our preliminary research on healthy subjects, we gradually increased the stimuli intensity from the weakest stimulus to the strongest. Inspecting patients with obvious neurological

**Figure 8.** Eight patterns of moving directions of tactile stimuli [3]. Mid = middle finger; Indx = index finger.

of the answer given, the next round started at an intensity of 22 or 7.

**tactile sensation threshold scores**

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ment with one of the same eight patterns.

more than 66.7%.

in 30 successive stages.

#### **4.1. Pilot study to confirm tactile reduction in long-term diabetic patients**

The device was first used in a pilot study of 15 diabetic patients with a long history of treatment, and a significant decrease in tactile sensation compared with healthy subjects was confirmed [1].

#### **4.2. Validation of DPN evaluation for diabetic patients**

The device was next used to validate the evaluation of DPN in diabetic patients [2]. Based on the criteria [19] for diagnosis of DPN provided by the American Diabetes Association (ADA), tactile sensation was quantified, and a comparison was made of patients with and without DPN. A significant reduction in tactile sensitivity was confirmed in the DPN group.

The goal of this part of the study was to investigate the effectiveness of the proposed method in diagnosing DPN.

A cross-sectional study was conducted of 52 type 2 diabetic outpatients. Patients were evaluated for DPN using the ADA criteria, the Michigan Neuropathy Screening Instrument (MNSI), and our proposed finger method. Patients were assigned to probable DPN or non-DPN groups, based on the ADA criteria. The finger method was used to produce a PNV score from the index and middle fingers, using the three procedures introduced above: PNV 1, PNV 4, and PNV 8. The scores ranged from 1 to 30, and comparisons were made between the two groups.

The PNV scores of the DPN group were significantly higher (P < 0.01). The PNV scores for the right fingers of the DPN and non-DPN groups were 10.2 ± 7.4 and 3.4 ± 3.3 in PNV 1, 20 ± 4.9 and 10.7 ± 5.3 in PNV 4, and 23.2 ± 4.9 and 14.6 ± 7.8 in PNV 8, respectively (**Table 2**).

Overall, the tactile threshold of the DPN group was higher than that of the non-DPN group.

The results suggested that the finger method, performed using the proposed device, can be used to evaluate DPN.


Data are presented as mean ± standard deviation or as N (%). P-values were calculated using the \* Mann-Whitney U and † χ2 tests. N = number; DPN = diabetic peripheral neuropathy; MNSI-Q = Michigan neuropathy screening instrument questionnaire; MNSI-E = Michigan neuropathy screening instrument examination; PNV = peripheral neuropathy vibration.

**4.4. Summary of the three previous studies**

**Table 3.** Scores on the tactile sensation threshold test [3].

**4.5. Statistical revalidation using propensity score**

patient's background, a propensity score was derived.

than that of healthy subjects.

direction test.

control group.

In this section, we summarize the results of the three tests performed on the quantitative tactile examination device. The instrument was demonstrated to be capable of quantitative evaluation of the reduction in tactile sensitivity (or increase in tactile threshold) of patients with DPN. The instrument was also able to distinguish between patients with DPN and non-DPN. Finally, the tactile sensitivity of asymptomatic DPN patients was shown to be lower

N = number; TST = tactile sensation threshold; TST-1 = TST 1 direction test; TST-4 = TST 4 direction test; TST-8 = TST 8

Mann-Whitney U test.

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**Test conditions Healthy controls (N = 32) Asymptomatic diabetic patients (N = 31) P-value** TST-1 for left fingers 2.7 ± 2.9 5.9 ± 6.2 0.025 TST-1 for right fingers 2.9 ± 3.5 4.7 ± 5.2 0.160 TST-4 for left fingers 8.7 ± 6.4 15.3 ± 7.0 <0.001 TST-4 for right fingers 8.4 ± 6.7 13.9 ± 7.2 0.002 TST-8 for left fingers 12.7 ± 9.1 19.3 ± 7.8 0.005 TST-8 for right fingers 12.1 ± 8.9 17.3 ± 7.9 0.009

Quantitative Tactile Examination Using Shape Memory Alloy Actuators for the Early Detection…

Data are presented as mean ± standard deviation or as N (%). P-values were calculated using \*

Although the tests involved a relatively small number of subjects, they suggested that a decrease in tactile sensitivity was present in patients with both severe and mild DPN (**Figure 9**).

To examine whether significance could be added to the TST score by adjusting to reflect the

In a cross-sectional study, the novel micro-vibration actuator with shape memory alloy wires was used to measure the tactile sensations of 68 type-2 diabetic outpatients and 89 healthy controls. Patients were again evaluated using the ADA criteria [16], the Michigan Neuropathy Screening Instrument (MNSI) [20], and the TST scores for the index and middle fingers. Patients were classified as probable DPN (n = 31) or non-DPN (n = 37) using the ADA criteria and as symptomatic (n = 26) or asymptomatic (n = 42) using the MNSI. Propensity score weighting was applied to compare the scores of each patient group with that of the

The mean time for determining the TST score was approximately 3 min/patient for all groups. The TST score of every patient group was significantly higher than that of the control group (P < 0.01). The right finger scores of the DPN, non-DPN, symptomatic, asymptomatic, and

This suggests that the device can be used to distinguish the different stages of DPN.

**Table 2.** Results of neuropathy examinations [2].

#### **4.3. Detection of a decrease in asymptomatic tactile sensation in diabetic patients**

Next, a comparison was made of the tactile sensitivity of 31 asymptomatic DPN patients and 32 healthy volunteers. The results confirmed that the asymptomatic DPN patients exhibited a significant reduction in sensitivity [3].

This part of the study focused on the asymptomatic development of decreased sensation, associated with diabetes mellitus. The goals were to investigate the use of the quantitative tactile sensation measurement device to examine diabetic patients who were unaware of abnormal or decreased sensation and to determine whether tactile sensation is reduced in asymptomatic patients. A group of healthy controls was recruited, and the finger method was used to measure the TST score of the index and middle fingers in the three procedures TST-1, TST-4, and TST-8. The TST scores ranged from 1 to 30, and a comparison was made between the two groups. The TST scores of the diabetic patients were significantly higher (P < 0.05). The TST scores for the left fingers of the diabetic patients and healthy controls were 5.9 ± 6.2 and 2.7 ± 2.9 in TST-1, 15.3 ± 7.0 and 8.7 ± 6.4 in TST-4, and 19.3 ± 7.8 and 12.7 ± 9.1 in TST-8, respectively (**Table 3**).

Overall, the tactile threshold of the fingers of asymptomatic DPN patients was shown to be higher than that of the healthy controls.

The results suggested that the quantitative tactile sensation measurement device was able to detect a decrease in tactile sensation in diabetic patients who were themselves unaware of abnormal or decreased sensitivity.

Quantitative Tactile Examination Using Shape Memory Alloy Actuators for the Early Detection… http://dx.doi.org/10.5772/intechopen.75084 121


Data are presented as mean ± standard deviation or as N (%). P-values were calculated using \* Mann-Whitney U test. N = number; TST = tactile sensation threshold; TST-1 = TST 1 direction test; TST-4 = TST 4 direction test; TST-8 = TST 8 direction test.

**Table 3.** Scores on the tactile sensation threshold test [3].

#### **4.4. Summary of the three previous studies**

**4.3. Detection of a decrease in asymptomatic tactile sensation in diabetic patients**

Data are presented as mean ± standard deviation or as N (%). P-values were calculated using the \*

Neuropathic symptoms (%) 2 (9.5%) 15 (48.4%) 0.003† MNSI-Q score 1 ± 0.8 2.1 ± 2 0.017\* MNSI-E score 1 ± 0.5 2.9 ± 1.3 <0.001\*

PNV 1 left 4.1 ± 5 9.7 ± 7.2 <0.001\* PNV 1 right 3.4 ± 3.3 10.2 ± 7.4 0.004\* PNV 4 left 12.6 ± 6.3 20.4 ± 4.8 <0.001\* PNV 4 right 10.7 ± 5.3 20 ± 4.9 <0.001\* PNV 8 left 16 ± 7.3 (n = 19) 25.1 ± 3.9 (n = 30) <0.001\* PNV 8 right 14.6 ± 7.8 (n = 19) 23.2 ± 4.9 (n = 30) <0.001\*

Abnormal MNSI score (%) 0 (0%) 20 (64.5%)

significant reduction in sensitivity [3].

**Table 2.** Results of neuropathy examinations [2].

higher than that of the healthy controls.

abnormal or decreased sensitivity.

respectively (**Table 3**).

PNV score

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χ2

vibration.

Next, a comparison was made of the tactile sensitivity of 31 asymptomatic DPN patients and 32 healthy volunteers. The results confirmed that the asymptomatic DPN patients exhibited a

Mann-Whitney U and †

 tests. N = number; DPN = diabetic peripheral neuropathy; MNSI-Q = Michigan neuropathy screening instrument questionnaire; MNSI-E = Michigan neuropathy screening instrument examination; PNV = peripheral neuropathy

**Non-DPN group (N = 21) DPN group (N = 31) P-value**

This part of the study focused on the asymptomatic development of decreased sensation, associated with diabetes mellitus. The goals were to investigate the use of the quantitative tactile sensation measurement device to examine diabetic patients who were unaware of abnormal or decreased sensation and to determine whether tactile sensation is reduced in asymptomatic patients. A group of healthy controls was recruited, and the finger method was used to measure the TST score of the index and middle fingers in the three procedures TST-1, TST-4, and TST-8. The TST scores ranged from 1 to 30, and a comparison was made between the two groups. The TST scores of the diabetic patients were significantly higher (P < 0.05). The TST scores for the left fingers of the diabetic patients and healthy controls were 5.9 ± 6.2 and 2.7 ± 2.9 in TST-1, 15.3 ± 7.0 and 8.7 ± 6.4 in TST-4, and 19.3 ± 7.8 and 12.7 ± 9.1 in TST-8,

Overall, the tactile threshold of the fingers of asymptomatic DPN patients was shown to be

The results suggested that the quantitative tactile sensation measurement device was able to detect a decrease in tactile sensation in diabetic patients who were themselves unaware of In this section, we summarize the results of the three tests performed on the quantitative tactile examination device. The instrument was demonstrated to be capable of quantitative evaluation of the reduction in tactile sensitivity (or increase in tactile threshold) of patients with DPN. The instrument was also able to distinguish between patients with DPN and non-DPN. Finally, the tactile sensitivity of asymptomatic DPN patients was shown to be lower than that of healthy subjects.

This suggests that the device can be used to distinguish the different stages of DPN.

Although the tests involved a relatively small number of subjects, they suggested that a decrease in tactile sensitivity was present in patients with both severe and mild DPN (**Figure 9**).

#### **4.5. Statistical revalidation using propensity score**

To examine whether significance could be added to the TST score by adjusting to reflect the patient's background, a propensity score was derived.

In a cross-sectional study, the novel micro-vibration actuator with shape memory alloy wires was used to measure the tactile sensations of 68 type-2 diabetic outpatients and 89 healthy controls. Patients were again evaluated using the ADA criteria [16], the Michigan Neuropathy Screening Instrument (MNSI) [20], and the TST scores for the index and middle fingers. Patients were classified as probable DPN (n = 31) or non-DPN (n = 37) using the ADA criteria and as symptomatic (n = 26) or asymptomatic (n = 42) using the MNSI. Propensity score weighting was applied to compare the scores of each patient group with that of the control group.

The mean time for determining the TST score was approximately 3 min/patient for all groups. The TST score of every patient group was significantly higher than that of the control group (P < 0.01). The right finger scores of the DPN, non-DPN, symptomatic, asymptomatic, and

**Figure 9.** Severity and classification of DPN. DPN = diabetic neuropathy.

control groups were 20.1 ± 4.9, 11.7 ± 5.1, 19.4 ± 4.5, 15.7 ± 6.9, and 6.5 ± 5.7, respectively. This gave P values of 0.00 for DPN, 0.198 for non-DPN, 0.002 for symptomatic, and 0.025 for asymptomatic.

The results confirmed that our novel device provides simple quantitative evaluation of tactile sensation in diabetic patients, facilitating the early detection of asymptomatic DPN.

**5.2. Comparison of qualitative methods and the quantitative method**

DSPN: distal symmetric polyneuropathy (used synonymously with DPN in this chapter).

and weakness.

Confirmed DSPN

that of a healthy person.

ankle reflexes

absent ankle reflexes

**Table 4.** Definitions of minimal criteria for DSPN [16].

one or more signs of neuropathy

the sensations are dulled.

short time.

The pain sensation test, made with a sharp object such as a pin, is used to test for hyperalgesia

**Diagnosis Diagnosis items Purpose**

Quantitative Tactile Examination Using Shape Memory Alloy Actuators for the Early Detection…

sensation, positive neuropathic sensory symptoms (e.g., "asleep numbness," prickling or stabbing, burning, or aching pain) mainly in the toes, feet, or legs. Signs: symmetric decrease in distal sensation or unequivocally decreased or absent

neuropathic symptoms, decreased distal sensation, or unequivocally decreased, or

The presence of a nerve conduction abnormality and one or more symptoms or

Clinical use

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Clinical use

Clinical use Clinical research

Possible DSPN The symptoms or signs of DSPN may include the following. Symptoms: decreased

Probable DSPN The combination of any or two or more of the following symptoms and signs:

In the vibration sensation test, sensitivity to vibration is investigated by applying a 128 Hz tuning fork to the ankle or the toe of the foot. The ability to sense vibration is compared with

In patients with DPN, the Achilles tendon reflex is often attenuated or absent, providing an

In the 10-g monofilament test, a thin thread of monofilament nylon is placed on the foot. It is used to investigate the function of the nerve that senses tactile and pressure. In DPN patients,

These tests are representative qualitative examination techniques that can be performed in a

In NCS, the stimulation conductivity of the peripheral nerve is measured. In patients who have developed neuropathy, the speed with which the stimulus is transmitted becomes slower. NCS is able to produce a quantitative measurement of the speed of the peripheral nerves of the human body [21, 22]. However, it requires the patient to be subjected to painful electric shocks. NCS also requires the use of expensive equipment. The examination time is lengthy, and if multiple peripheral nerves on both the left and right side are examined, the procedure

The proposed finger method is superior to NCS in some respects. First, the inspection time is short, taking a maximum of approximately 3 min. Second, the patient experiences no

may take several hours. NCS is therefore only available at large specialized hospitals.

**5.3. Comparison of NCS and quantitative tactile examination methods**

excellent test that can be performed in a short time if the examiner is proficient.
