Introduction

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that can cause significant morbidity and mortality. About 30% of hospitalized and 20% of community-dwelling diabetes patients have peripheral neuropathy; the annual incidence rate is approximately 2%. The primary risk factor is hyperglycemia. Sensomotor neuropathy is marked by pain, paresthesia, and sensory loss (Boulton, 2005; Bril, 1999).

One of the major risk factors for the development of diabetic foot complications is distal symmetric sensomotor polyneuropathy. For diagnosing DNP, no principal standard is available. The San Antonio consensus panel has recommended that at least one measurement should be performed in five different diagnostic categories (Meijer, Bosma, Lefrandt, Links et al., 2003). These are symptom scoring, physical examination scoring, quantitative sensory testing, cardiovascular autonomic function testing, and electrodiagnostic studies. Methods which are simple, but sensitive and specific, are required to evaluate sensory neuropathy.

Damage (decrease) in vibration sensitivity can already be registered at early stages of pathological process development, much more earlier than a development of againmuscular defeat of distal parts of lower limbs (Shnayder, Petrova, Kirichkova, and Kurumchina, 2009; Shnayder, Petrova, Kurumchina, and Kirichkova, 2008). A sign of peripheral polyneuropathy groups of myelinic pathologic and mixed forms (axonmyelinopathy), mainly is damage of vibration sensitivity for the account of defeat thick myelinic fibers type Аß. Definition of vibration sensitivity is the important component of early diagnostics of DPN at the same time with traditional methods of diagnostics as nerve conduction studies and needle electromyography. That allows to begin in due time treatment-and-prophylactic establishments and to lower incapacitating injuries of young, able-bodied population (Kirichkova, Shnayder, Petrova, Kurumchina, Darsavelidze, and Kiselev, 2009; Kirichkova, Ustinovich, Shnayder, Petrova, and Kurumchina, 2008).

Objective changes in nerve function must be demonstrable in DPN before the efficacy of any pharmaceutical intervention can be accepted. Failure to do so would cause the efficacy of the therapy to be questioned (Meijer et al., 2003). Any measurement of peripheral neuropathy needs to be quantitative. Different clinical scales are being developed to achieve this, with varying degrees of validity. Dyck (Duby, Campbell, Setter, White, and Rasmussen, 2004) has introduced the Neuropathy Symptom Score (NSS), Neuropathy Symptom Profile (NSP) and the Neurologic Disability Score (NDS); these scales are designed to quantify symptoms and signs in neurological disorders. These clinical measures have been shown to correlate well with electrophysiological testing in neuropathy and also with sural nerve structural changes, used as the “gold standard” for the evaluation of neuropathy. The Neurologic Impairment Score in the Lower Limbs (NIS-LL) is a new scale that has been developed to quantify clinical manifestations of the neurological deficits evident in the lower limbs of patients who have neuropathies.

However, because the scale is a generic neuropathy scale, the scale is weighted with superfluous measures which are inappropriate for the evaluation of DPN. The scale also has limited potential for the measurement of clinical improvement in short treatment intervals of 12- 24 months in DPN, a disease process which evolves over 10 years (Meijer et al., 2003)

Besides, now clinical physicians (neurologists, neurogenetics, and pediatricians) use the graduated and not graduated tuning forks with vibration frequency 128 Hz for diagnostics vibration sensitivity in the low limbs. However, the tuning research method is may be subjective for evolution of vibration sensitivity condition and inexact for diagnostics of DPN. Physicians use devices for computer esthesiometry various updating for tool diagnostics of peripheral polyneuropathies in other countries. For example: in the USA - Biothesiometer (Biomedical Instruments, Newbury, OH); in UK - Neurothesiometer (Horwell, London), in RF - Vibration Tester - MBN ВТ-02-1 (MBN, Moscow). The closest and economically accessible to equipment of an out-patient-polyclinic link of public health services of treatment-and-prophylactic establishments of the RF is the domestic device Vibration Tester - MBN ВТ-02-1 for measurement of vibration sensitivity on distal parts of the upper extremities at vibration illness which has been adapted by us in 2009 (the patent No83906 from 27.06.2009).

The purpose of our research was to define the most important criteria an early diagnosis of distal polyneuropathy in diabetic patients.

Materials and methods

Research was made in the Neurophysiology Laboratory in Department of Medical Genetics and Clinical Neurophysiology at Krasnoyarsk State Medical University during 2007-2009 years.

175 patients with diabetes mellitus (97 with diabetes mellitus type 1 and 78 with diabetes mellitus type 2) were enrolled in this study. There were 89 (50.9%) males and 86 (49.1%) females; the mean (SD) age of the patients was 42.02 (15.27) years old. Before examination, the careful selection and survey were delivered by the neurologist and the therapist for an exclusion of a current neurologic and somatic pathology which could be other reason of development of polyneuropathies in the lower limbs with decrease in indicators of vibration sensitivity.

Study participants underwent history and physical examination to evaluate exposure variables, including demographic data, general medical history, history of diabetes and diabetes-related complications. We assessed DPN using 10-g Semmes-Weinstein monofilament (Germany), Tip-therm (Germany), the Rydel-Seiffer tuning fork (Germany), computer diagnostic equipment “Vibration Tester - MBN” (Moscow, RF),Total Symptom Score (TSS), Neuropathy Symptom Score (NIS), Neuropathy Symptom Score in the Lower Limbs (NSS-LL), Neuropathy Impairment Score (NIS), Visual Analog Score (pain score). For gauge fastening of vibration sensor our original support (the patent RF No 83906 from 27.06.09) was used (Kirichkova et al., 2009; Shnayder, Kurumchina, and Lipinskiy, 2009).

Vibration sensitivity examination was performed in the distal parts of the lower extremities. During carrying out esthesiometry the investigated patients were in a prone position on a medical couch, blindly. Certain conditions were met: an ambient temperature from +20 till + 22ºС, exception (minimization) external exciters (noise, loud sounds, bright light). For gauge fastening of vibration sensor our original support (the patent RF No 83906 from 27.06.09) was used. We developed standard reference corridors of vibration sensitivity for lower extremities at young and middle age persons (rationalization proposal No2489 from 18.01.2010) for Vibration Tester - MBN ВТ-02-1 (MBN, Moscow, RF). Automatic submode of the stimulations was used, including frequencies - 8, 16, 32, 63, 125, 250 and 500 Hz. Research was began with an ascending number, in the absence of the patient’s answer. The feedback with the surveyed was carried out by pressing the registration button at the first appearance of subjective vibration sense in an investigated part of a body on each of offered frequencies. When the sense appeared the surveyed pressed the button and kept it in such condition till the moment of disappearance of vibration sense. The received indicators were entered in the research report of vibration sensitivity (computer esthesiometry) on the research termination. Computer vibration record represented graphic display of the data about sensitivity level surveyed on various vibration frequencies on lower extremities.

Processing of the received results was done with an applied package, the statistical programs Statistica v. 8.0 (StatSoft, USA). Statistical data processing was performed with use of the standard parametrical and nonparametric methods of comparison. The parametrical data represented in the form of mean values with standard deviations. Distinctions statistically significant at р ≤ 0.05. For the system analysis frequencies or table of an interlinking were used. For definition of a degree of dependence between two grouping variables were used criteria Pirson Chi-square, Contingency coefficient and Cramer’s V (Tolstova, 2000 ).

Results of the research and discussion

We identified 166 patients who had DPN during the study period, of which 15 had initial damage, 30 - mild, 85 - moderate, 34 - expressed.

The diagnosis of DPN was made using clinical criteria, included the degree of diabetic polyneuropathy, lesion topography (higher or lower limbs), type of DPN and presenting complications. Among the patients with diabetes mellitus type 1 and 2, approximately 86 (49.1%) of them had isolated lesion of lower limbs, about 80 (45.7%) of them had lesions of both higher and lower limbs. Any cases with isolated lesions of higher limbs were not detected. In each case of DPN diagnostics the full investigation was applied. To reduce the time of diagnosis it was necessary to reveal the most important criteria of DPN with high sensitivity.

To find the most sensitive diagnostic criteria of DPN we needed to perform the system analysis of data base. For variables “The Degree of diabetic polyneuropathy in the lower limbs” and “The Degree of diabetic polyneuropathy on higher-limbs”, the degrees of their dependence on other variables are shown in Tables 1 and 2.

The variables with the highest degree of dependence were identified based on criteria Pearson’s Chi-square, Contingency coefficient and Cramer’s V. The degree of dependence was different for higher or lower limbs. But computer esthesiometry had the highest significance both for higher or lower limbs. Contingency tables “The Degree of diabetic polyneuropathy in the lower-limbs” from “Computer esthesiometry”, “NIS-LL” and “Neuropathy pain” are shown in Tables 3, 4, and 5. There were a dependent variable “The Degree of diabetic polyneuropathy in the lower-limbs” and independent variables “Computer esthesiometry”, “NIS-LL” and “Neuropathy pain”.

In 71.4% of cases the “Computer esthesiometry” index 1 (normal vibration sensitivity) was corresponded to the “The Degree of diabetic polyneuropathy” index 1 (none DPN). In 97.5% of cases the “Computer esthesiometry” index 2 (initial damage of vibration sensitivity on lower-limbs) was corresponded to the presence of moderate DPN in the lower limbs. In 100% of cases the “Computer esthesiometry” index 3 (moderate decrease of vibration sensitivity in the lower-limbs) was corresponded to presence of DPN in the lower-limbs, included 96.8% of moderate or expressed DPN. In 100% of cases the “Computer esthesiometry” index 4 (expressed damage of vibration sensitivity in the lower limbs) was corresponded to the obvious presence of moderate or expressed DPN in the lower limbs, including 45.8% of expressed DPN.

99.3% of cases (156 of 157), when the value of “NIS-LL” was greater than 0 (a presence of any neuropathic disorders), corresponded to the presence of DPN on lower-limbs. Only in 55.6% of cases (10 of 18) the value of “NIS-LL” 0 was corresponded to the absence of DPN in the lower limbs. Thus, “NIS-LL” index 0 is not an indicator of the absence of DPN. In 100% of cases the “NIS-LL” index above 20 was corresponded to the presence of moderate and expressed DPN in the lower-limbs.

In 100% of cases (86 of 86) the value of “Neuropathic pain” index 2 (presents of symptoms) indicated the presence of DPN in the lower limbs. In 87.64% of cases (78 of 89) the value of “Neuropathic pain” index 1 (no symptoms) was related to the presence of DPN in the lower limbs. So, the value of “Neuropathic pain” index 1 is not an indicator of the absence DPN.

Dual-frequency contingency tables (Table 6) show degree of significance of two factors in the diagnosis of DPN. In 99.37% of cases (160 out of 161), when the value of “NIS-LL” was greater than 0 with “Computer esthesiometry” index greater than 1, DPN was present in the lower limbs. 100% of cases, when the value of “Computer esthesiometry” index 4 (expressed damage of vibration sensitivity in the lower limbs), were related to presence of the moderate and expressed DPN, including 45.8% of expressed DPN (“The Degree of diabetic polyneuropathy” index 5).

Consequently, DPN is the most common type of neuropathy in the world. Progress in the quantification of the severity of DPN has been observed in recent years. The NIS-LL (Neuropathy Impairment Score in the Lower Limbs) is a new scale which quantifies the neurological function in DPN (Bril, 1999). This scale for determining the neuropathy impairment in DPN optimizes the chances of demonstrating clinical change following pharmaceutical intervention in patients with early stage neuropathy. The use of the NISLL in clinical trials, together with computer esthesiometry tests measuring nerve function, provides the best opportunity to evaluate the efficacy of new therapeutic agents for the treatment of DPN.

Conclusion

The evaluation and measurement of DPN continues to present a significant challenge in clinical trials. The search for positive therapeutic interventions leads to expanding our knowledge about all aspects of DPN; this process will be facilitated by the use of sensitive and reliable tests and scales which measure changes in the disease (Bril, 1999). As demonstrated, the most sensitive diagnostic criteria an early diagnosis of distal polyneuropathy in the lower limbs in diabetic patients were vibration sensitivity decrease (computer esthesiometry method) and presence of neuropathy pain. The NIS-LL has been designed in an effort to maximize the measurement of potential changes in sensory neuropathies. This quantitative neurological examination evaluates changes in motor, sensory and reflex activity specifically in the lower limbs. Scores for the upper limbs and cranial nerves are omitted because they are expected to be normal in the early stages of DPN. The most sensitive diagnostic criteria an early diagnosis of distal polyneuropathy in the higher limbs in diabetic patients were vibration sensitivity decrease (computer esthesiometry method), presence diabetic polyneuropathy in the lower limbs and presence neuropathy pain. The most sensitive method an early diagnosis of distal polyneuropathy in diabetic patients was combination of computer esthesiometry method and NIS-LL.

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(c) Все права защищены. Полное или частичное копирование материала статьи разрешено только при обязательном указании автора и прямой гиперссылки. // Kurumchina O., Shnayder N., Petrova M., Lipinskiy L., Faustov A., Terenteva E., Kantimirova E., Darsavelidze O., Kiselev I., Kozulina E., Terskov D. Relation of computer esthesiometry and symptom scores in diagnostics of diabetic polyneuropathy // Medical and Health Science Journal, MHSJ. - 2010. - Vol.4 pp. 101-112