NATALIA SHNAYDER
1
ELENA GLUSHCHENKO1
ELENA KANTIMIROVA
1
DIANA DMITRENKO1
EKATERINA KOZULINA
1
VLADIMIR MAKSIMOV2
1Krasnoyarsk State Medical University,
Russian Federation
2Scientific Research Institute of
Therapy, Novosibirsk,
Russian Federation
The purpose: to define the diagnostic importance of computer
esthesiometry for use in diagnostics of hereditary neuropathy with
primary defeat of myelin sheath of peripheral nerves of the upper
extremities. Materials and methods: 47 individuals in a condition
of relative health (control group) from 21 to 50 years, comparable
group - 40 patients from 6 to 81 years, with hereditary neuropathy
Charcot-Marie-Tooth (CMT). Vibrating sensitivity was
investigated by means of computer vibrometer “Vibrotester
MBN” VТ-02-1 (MBN, RF) in a wide strip of frequencies of
vibration (8, 16, 32, 64, 125, 250, 500 Hz). Statistical data
processing of research was lead by means of programs
STATISTICA v. 7.0 (StatSoft, USA). Results and discussion: We
compared received corridors vibrating sensitivity on the upper
extremities for healthy volunteers with those at patients with
CMT. Statistically significant increase of vibration sensitivity
thresholds in a wide range of vibration frequencies on upper
extremities and at patients with CMT versus healthy volunteers is
shown. Computer esthesiometry method demonstrates high
sensitivity in diagnostics of hereditary neuropathy with primary
damage of myelin sheath of peripheral nerves of upper extremities
on an example of CMT.
Keywords: Vibration perception, computer esthesiometry, hereditary neuropathy Charcot-Marie-Tooth
(CMT).
UDC: 616-009.66
Introduction
Polyneuropathy is one of the most urgent problems of the modern neurology, occupying
special place among other diseases of nervous system. A sign of peripheral (distal)
polyneuropathy in group of myelinopathy and mixed forms (axon-myelinopathy) is
infringement of vibrating sensitivity due to damage of thick myelinated fibers of type A
(beta). Definition of vibrating sensitivity is an important component of early diagnostics
of one of the most common forms of hereditary neuropathy - Charcot-Marie-Tooth
neuropathy (1:3000 cases in the population), that allows to begin in due time treatmentand preventive measures to reduce disability in young, employable population (Benstead
and Grant, 2001; Shnayder, Kozulina, Glushenko, and Kantimirova, 2010). In the
presence of CMT the peripheral nerves of the lower and upper extremities are involved in
the pathological process.
Now clinical physicians (neurologists, neurogenetics doctors, pediatricians) use the
graduated and not graduated tuning forks with vibration frequency 128 Hz for diagnostics
of vibration sensitivity decrease caused by CMT or other neuropathies. However, the
tuning research method might be inaccurate for diagnostics of hereditary neuropathies.
Physicians use devices of computer esthesiometry in diagnostics of diabetic
polyneuropathy: e.g. physicians in the U.S. use Biothesiometer (Biomedical Instruments,
Newbury, OH); in UK - Neurothensiometer (Horwell, London). But the above-stated
devices have an inconvenient design (the device should be held in a hand that is
inconvenient both for the doctor, and for the patient). Distinction in the device of devices
and parameters, and also in the price policy is observed. Besides, data on wide use of these devices in the Russian Federation in the accessible literature poor (Kirichkova, Ustinovich,
Shnayder, Petrova, Kurumchina, 2008; Shnayder, Kirichkova, and Kozulina, 2008;
Shnayder, Gluschenko, Dmitrenko, and Kozulina, 2010), and their application is usually
adapted only for needs of a neuroendocrinology (diabetology) (Kirichkova et al., 2008).
The economically accessible equipment of out-patient-polyclinic link of public health
services in treatment-and-prophylactic establishments of the RF is the domestic device
“Vibrotester - MBN ВТ-02-1”; it provides measuring of vibration sensitivity on distal
parts of the upper extremities (distal phalanges). In view of the fact that the CMT
violation of vibration sensitivity is due to the defeat of thick myelin fibers type A (beta),
but not axon terminals located in the terminal phalanges, the ideal point of the study of
vibration sensitivity of distal parts of upper extremity is the styloid process of radial bone.
Consequently, the existing regulatory corridors of vibration sensitivity of the distal
phalanges are not comparable with those of vibration sensitivity of the radial styloid
process in patients with CMT. This prompted us to develop regulatory corridors of
vibration sensation to the styloid process of elbow bone (distal parts of the upper
extremities) for the national diagnostic equipment “Vibrotester - MBN BT-02-1” (MBN,
RF).
Several genetically heterogeneous but clinically similar forms of CMT are spread
nowadays; but the pathogenesis of most of them causes genetic damage of the myelin
sheath of peripheral nerves (myelinopathy), including the thick myelin fibers of type A
(beta) such as vibration sensitivity. Violation (decrease) in vibration sensitivity can be
detected at early stages of pathological process, far outpacing the development of
secondary muscle damage (amyotrophic syndrome), paresis, and contractures distal parts
of extremities, which is important when examining clinically asymptomatic carriers of the
mutant gene, including family members probands (patients with CMT) to develop a
personalized plan for preventive and rehabilitative measures (Auer-Grumbach, Wagner,
Strasser-Fuchs et al., 2000; Benstead and Grant, 2001; Shnayder et al., 2008, 2010).
Due to the fact that the method of computer esthesiometry by diagnostic equipment
“Vibrotestere - MBN BT-02-1”, using a wide band of vibration (from 8 to 500 Hz), has a
higher sensitivity compared to tuning forks method in the lower extremities with CMT,
we have put forward a scientific hypothesis about the potentially high sensitivity and
diagnostic value of this method of functional diagnostics in the upper limbs at CMT.
Materials and methods
Research was made during 2007-2010 years in Neurophysiology Laboratory of
Department of Medical Genetics and Clinical Neurophysiology performing in
Krasnoyarsk State Medical University named after Prof. V.F. Vojno-Jasenetsky
(Krasnoyarsk). Molecular-genetic testing of gene mutations was made in Laboratory of
Medical Genetics of Scientific Research Institute of Therapy (Novosibirsk).
Careful selection and survey by neurologist and therapist were made before analysis to
exclude current neurologic and somatic pathology which could be other reason of
development of polyneuropathies of upper extremities with decrease in indicators of
vibration sensitivity. Selection of the surveyed was carried out by a method of the
stratified randomization with criteria of inclusion and an exception, developed according
to the purpose and problems of the present research.
Criteria of inclusion in control group: men and women, age from 21 till 50 years old,
inhabitants of Krasnoyarsk and Krasnoyarsk Region, condition of relative health. Criteria
of an exception: inhabitants of other regions RF, the patients, not wishing to carry out the
research or procedure report.
Criteria of inclusion in comparable group: men and women, age from 18 till 57 years old,
inhabitants of Krasnoyarsk and Krasnoyarsk region, suffer from CMT. Criteria of an
exception: inhabitants of other RF regions, the patients, not wishing to carry out the
research or procedure report, suffer from hereditary or another genesis of
polyneuropathies (раraneoplastic, dysmetabolic, inflammatory and others), alcoholism (including the daily use more than 30 ml of alcohol within last 3 months), drug
dependence, professional intoxications.
During working out of a way of research, we typed control group (47 persons) - healthy
volunteers of young age from 21 till 50 years old, mean age - 26.96±6.32 [95% CI: 22-29]
years old, including: men - 46.7%, age - from 21 to 33 years old, mean age - 25.57±5.07
[95% CI: 21-33] years old; women - 53.3%, age - from 21 till 50 years old, mean age -
28.18±7.17 [95 % CI: 25-29] years old.
Investigated (comparable) group made 40 patients with the developed CMT clinical
pattern. The investigated group included the patients being on hospitalization in
neurological department and patients being on the dispensary account on CMT in
advisory polyclinic of Clinical Hospital No.51 FMBA (Zheleznogorsk city, RF), the
patients passing hospitalization in neurologic department of Urban Hospital No.5
(Krasnoyarsk city, RF), and also the patients actively revealed by us in the Neurologic
Centre of Epileptology, Neurogenetic and Brain Researches of University Clinic. The age
of patients varied from 6 till 81 years old, median age - 30.5 [25:47] years, including the
men - 22 years, median age - 25.5 [19:41] years, the women - 18 years, median age - 30.0
[26:51] years. Before research of vibration sensitivity on distal parts of upper extremities
(styloid process of elbow bone) by computer esthesiometry method we defined decrease
of vibration sensitivity by a tuning research method (C 128 Hz).
Vibration sensitivity examination was performed in control and comparable groups on
distal parts of the upper extremities consistently to the right and left (fig. 1). During
carrying out esthesiometry investigated were sitting on a chair, facing the medical couch
with his eyes closed. 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.
Automatic submode stimulation of “Vibrotestere - MBN BT-02-1” was used, including
frequencies - 8, 16, 32, 64, 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 appears 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 upper extremities.
Processing of the received results was done with an applied package, the statistical
programs STATISTICA v. 7.0 (StatSoft, USA). Statistical data processing was performed
with use of the standard parametrical and nonparametric methods of comparison. Data
for variation numbers with nonparametric distribution are described in the form of a
median (Me) and percentiles [P25:Р75].The parametrical data represented in the form of
mean values with standard deviations (SD) and 95% of the confidence interval (CI).
Distinctions statistically significant at р≤0.05.
Results of research
During the research we have defined the reference intervals for healthy volunteers in the
study of vibrator sensitivity in distal parts of upper extremities, which were comparable to
the results of computer esthesiometry in patients with CMT. Borders of vibration
sensitivity at healthy volunteers were much lower (p<0.01) than at patients with CMT on
all vibration frequencies of “Vibrotester - MBN ВТ-02-1” (8, 16, 32, 64, 128, 250, 500 Hz)
on 3 σ and more (1 σ = 10%) (Table 1, Figure 2).
Clinically significant violations of the vibration sensitivity of distal parts of upper
extremities (styloid process of radial bone) were identified by computer esthesiometry in
all patients with CMT (100%) on the expanded disease stage, in 66% of cases on the initial
stage of the disease, while the using classical method tuning forks method (frequency 128
Hz) of vibration sensitivity violation have been identified and deployed the initial stages of
the disease in 80% and 60% accordingly (Table 2). It should also be noted that only by
using a computer pallesthesiometry identified expressed disturbances vibration sensitivity
as on initial (53%) and on developed (15%) stages of the disease (Table 2).Discussion
The vibration sensitivity level decrease on distal parts of upper extremities correlated with
developed clinical semiology of CMT (р<0.05): presence and expressiveness of sensitive
ataxia, frustration of painful and tactile sensitivities. At the same time, decrease of
vibration sensitivity was revealed in the course of carrying out computer esthesiometry
comparison with frustration of other kinds of deep (proprioceptive) and superficial
(painful, tactile, temperature) sensitivities. Firstly, this could be explained with
ethiopathogenesis of CMT conditioning genetically determined myelin sheath damage of
peripheral nerves. Thus, vibration sensitivity suffers the first, and damage of other kinds
of sensitivity joins at later stages of pathological process development when damage of
vibration sensitivity becomes considerable. Secondly, the research found diagnostic
possibilities of computer esthesiometry method using “Vibrotestere - MBN BT-02-1” in
examination of patients with CMT at early stages of disease development, including
periods of planning preventive rehabilitation actions and carrying out diagnostic screening
of disease among members of a proband’s family. People who are clinically symptomless
or asymptomatic carriers of a mutant gene can be endured to such screening also.
Taking into account, difficult access to DNA typing in various forms of CMT for most
people living in remote regions of the Russian Federation, the computing esthesiometry
method could be the method of choice for screening diagnostic of families burdened by
CMT, and will appoint a timely methods of drug and non-pharmacological treatment in
the early stages of the disease, to slow the progression of the pathological process and the
degree of disability of patients of working age.
Conclusion
The computer esthesiometry method using the diagnostic equipment “Vibrotestere -
MBN BT-02-1” (RF) has high sensitivity in diagnostics of myelin sheath damage in
patients with CMT. It reflects first of all degree damage of the thick myelin fibers of type
А (beta) caused by pathology of myelin fibers.
The computer esthesiometry method could be widely used in clinical practice for
diagnostics of hereditary neuropathies with genetically determined pathology of myelin
sheath (myelinopathy), including CMT, hereditary neuropathy with liability to pressure
palsies, Dejerine-Sottas disease.
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(c) Все права защищены. Полное или частичное копирование материала статьи разрешено только при обязательном указании автора и прямой гиперссылки. // Natalia Shnayder,Elena Glushchenko, Elena Kantimirova, Diana Dmitrenko, Ekaterina Kozulina, Vladimir Maksimov Sensitivity of сomputer esthesiometry on distal parts of the upper extremities at patients with hereditary neuropathy Сharcot-Marie-Tooth// Medical and Health Science Journal, MHSJ. - 2011. -Vol.9 pp. 25-30
