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Khaydarova Gavkhar Saidakhmatovna, Assistant, ENT Department of Tashkent Medical Academy E-mail: haydarovadoc@mail.ru
Differential-diagnostic criteria auditory neuropathy in children
Abstract: The article presents the results of objective techniques of hearing study in 36 children with auditory neuropathy. Based on these data, a comparative analysis of auditory neuropathy, and sensorineural hearing loss. The differences in the mechanisms underlying disorders.
Keywords: auditory neuropathy, sensorineural hearing loss, otoacoustic emission.
The use of auditory evoked potential techniques such as the auditory brain stem response (ABR) and otoacoustic emission (OAE) for the assessment ofhearing in young and difficult-totest children is now well established. Auditory neuropathy (AN) — is a new type ofhearing loss, which was made possible thanks to an objective method to diagnose hearing research. Unlike sensorineural hearing loss (SNL), where the damaged outer and inner hair cells of the cochlea, while AN preserved outer hair cells.
Evidence for the existence of AN in the infant population recently has begun to appear in the literature. Deltenre et al. [2, 17-22] described the findings for three infants who had suffered major neonatal illness and who showed electrophysiologic results fitting the AN profile within the first year of life. Stein, Tremblay, Pasternak, Banerjee, Lindermann, and Kraus [5, 197-213] identified four children through a special care nursery screening program with normal GAEs and absent or abnormal ABRs in the neonatal period.
The complexity of detection AN and a variety of clinical symptoms of the disorder hinder the development of adequate rehabilitation measures. Do not clear the causes and mechanisms of this disorder. A number of publications has been suggested that the probable causes of auditory neuropathy may be a high level of bilirubin, hypoxia, low birth weight, demyelinating disease [1, 933-938; 3, 184-186; 7, 1026-1030; 4, 741-753]. There is information about the presence of genetic factors associated with the development of AN [8, 45-50; 9, 770-778].
A particular problem is the choice of tactics rehabilitation of patients with AN, as observations show that traditional in patients with sensorineural hearing loss techniques are not always effective in these patients [6, 1-5; 10, 325-333]. As a rule, all of these studies were conducted in small groups of patients, characterized by a certain inconsistency of the results obtained by different authors.
Objective: To conduct a comprehensive study of auditory function and identify the characteristics of auditory neuropathy.
Material and Methods
During the period from 2012 to 2014 yy. were surveyed 180 hearing impaired. Of these, 36 children were selected with auditory neuropathy. This was 5 % of all patients. Among the surveyed, 20 were boys (56 %), 16 — the girls (44 %).
The majority ofpatients (29 men) diagnosed with AN has been established under the age of 5 years. In 5 patients AN was identified at the age of1-3 years. One patient AN was identified as a teenager.
As the objective methods ofhearing assessment on patients using registration techniques evoked otoacoustic emission (TEOAE) and brainstem auditory evoked potentials (ABR), the acoustic impedance (AI). Some patients also recorded otoacoustic emission distortion product (PIOAE) and stationary auditory potentials in the modulated tones (ASSR).
The study was conducted using the "Neuro-Audio" company "Neuro-Soft" (Russia). For registration UAE used the probe, which houses two phones and a microphone. After one phone single tone is
continuously fed through another continuously thereto a second tone. The microphone provides a registration and monitoring OAE levels of test tones. To highlight the OAE is also necessary to minimize the level of input noise. Therefore, a survey was carried out in a quiet room, and the probe is installed tightly into the ear canal.
Incentives were broadband acoustic clicks to be met with a repetition rate of 20-50/sec. retractable microphone response signal amplified in the passband from 500 to 5000 Hz. and sent to a computer via an analog-digital converter.
The source of the sound stimuli for ABR registration were in-the-phone with a pre-chosen size ear bud. To register brain responses using pan silver chloride electrodes. The electrodes were fixed at the border area on the scalp (the reference electrode) and mastoid region right and left (active electrodes). In studies of the inter-electrode resistance does not exceed 5 ohms, which was achieved by pre-treating the skin of a patient and using special conductive gels. When carrying out various types of stimulus ABR were used — acoustic click 100 ms, frequency tones 1000, 4000, 2000 and 500 Hz.
The acoustic impedance (AI) was performed on impedancem-etry AZ- 28, Interacoustics (Denmark). In the measurement ofmiddle ear pressure was applied to the probe tone frequency of226 Hz. intensity of 85 dB. SPL. The results were evaluated according to the classification of tympanometric curves, proposed by James Jerger.
Results of the study
A characteristic feature of patients with AN was the fact that all patients in the initial evaluation TEOAE on the right and left ear was registered. An exception was one patient who was registered TEOAE only one ear. This is different in patients with AN of patients with sensorineural hearing loss, in which TEOAE not recorded during stimulation of both ears.
The acoustic reflex is not recorded in the most part (55 %) of patients with AN. In 29 % of patients with AN acoustic reflex was registered at frequencies of500-1000 Hz. Threshold reflex registration in these cases was 120 dB.
When ABR registration is revealed stability of the studied parameters. Most children are not ABR recorded in primary and re-examination. In 2 (5 %) of children were registered in the ABR acoustic stimuli level 95-103 dB. HL. Discussion
It is expected that the sensorineural hearing loss and auditory neuropathy related to violations of sound perception and vary in topic destruction of structures of the inner ear and the auditory nerve. When SHL damage the inner and outer hair cells, whereas with AN preserved outer hair cells, thus recorded TEOAE and OAEPI. The presence of TEOAE in the absence ofregistration ofABR or ABR registers only on maximum levels of stimulus is a recognized symptom specific for AN.
However, our findings suggest that some patients with AN TEOAE can fade with time. According to our data, it was observed in 22 % ofpatients. This is not the case for children with CHT who have over the entire observation period TEOAE not recorded (Table 1).
Differential-diagnostic criteria auditory neuropathy in children
Table 1. - Comparative analysis of TEOAE in patients with auditory neuropathy and sensorineural hearing loss
Patients with AN (N = 36) Patients with SHL (N =180)
Number of patients ( %) during the initial examination of TEOAE recorded: with 2 sides 92 % 0 %
one side 5 % 0 %
Number of patients ( %), in which the re-testing TEOAE recorded: with 2 sides 76 % 0 %
one side 0 % 0 %
Number of patients ( %) who have disappeared during the second TEOAE examination 22 % 0 %
The disappearance of TEOAE difficult differential diagnosis AN with SNT. In this case, the child with AN based on the results ofABR registration (not registered) and TEOAE (lack of) will be diagnosed as a child with a 4 degree SHL. Thus, the possibility of the disappearance of TEOAE in AN should be considered in its diagnosis.
Significant differences between patients with AN and sensorineural hearing loss were found when comparing the results of ABR registration. In 95 % of patients with auditory neuropathy ABR not recorded during stimulation, both right and left ear. Only 2 of the 36 patients of ABR were recorded in the sound stimulus level 95-103 dB. HL.
In contrast, in patients with SHL ABR threshold of detection ranged from 40 dB. with a small hearing loss to lack of ABR with severe hearing loss.
Of particular interest is the comparison of the data registration ABR in patients with SHL and AN during follow-up. It was found that
Table 2. - Changes in enrollment ratios
Obtained data shows that a single study in children auditory function is insufficient and requires follow-up.
Based on the foregoing, electrophysiological diagnostic criteria for hearing loss is sufficiently definite and do not allow different interpretations. At the same time, the results of instrumental studies of patients with AN is not always unambiguous, and require in-depth understanding of the whole complexity of the audio perception mechanisms.
Timely detection of features of character pathology in sound reproduction system has important clinical implications in connection with the difference between the tactics of treatment and
patients with hearing loss in 15 % of cases detected change detection thresholds ABR in repeated surveys. At the same time in 22 patients with hearing loss was an increase in ABR thresholds of visualization, in 16 patients — lowering thresholds. Unlike patients with SHL in patients with AN not detected any changes in the ABR.
These impedance, apparently, are of limited value for the differential diagnosis of AN and SHL. Of course, conducting tympanometry is necessary because only the tympanogram when characterizing normal middle ear sound-conducting system, the absence of TEOAE can be interpreted as a sign of the defeat of the outer hair cells, which is characteristic of the SHL. Registration threshold reflex was thus proportional to the degree of hearing loss.
Dynamic observation was conducted to analyze the variability registration ABR and TEOAE in children with AN and SHL. The data show that patients with SHL has positive dynamics visualization ABR thresholds. The results of this analysis are presented in Table 2. ABR and TEOAE in repeated surveys
rehabilitation of such patients. This in turn makes it possible to carry out a full rehabilitation of such patients.
Conclusions:
1. Features of the auditory function in patients with AN and SHL indicate differences in the mechanisms underlying auditory function disorders in these groups of patients. This gives grounds for their separation into separate disease entities.
2. The results showed that in children with AN, on the one hand, there are disturbances in the transmission of acoustic signals central auditory system, on the other — disturbances maturation pathways and auditory centers.
Number of children Incidence ( %)
Raising thresholds Lowering thresholds Stability thresholds
ABR ОАE ABR ОАE ABR ОАE
SHL 180 12 7 9 11 79 82
AN 36 - - - - 100 100
References:
1. Berg A., Spitzer J., Towers H., Bartosiewicz C., Diamond B. Newborn hearing 535 screening in the NICU: Profile of failed auditory brainstem response/passed otoacoustic emission//Pediatrics. - 2005. - 116(4): 933-938.
2. Deltenre P., Mansbach A., Bozet C., Clercx A., Hecox K. Auditory neuropathy: A report on three cases with early onsets and major neonatal illnesses//Electroencephalography and Clinical Neurophysiology. - 1997. - 104: 17-22.
3. Khaydarova G., Shaykhova Kh., Shukurov D. Study of the auditory analyzer in children with diseases of the central nervous system. Bulletin of the Kyrgyz State Medical Academy. - 2012. - № 3, Volume 2: 184-186.
4. Starr A., Picton W., Sininger Y. et al.//Brain. - 1996. - 119: 741-753.
5. Stein L., Tremblay K., Pasternak J., Banerjee S., Lindermann K., Kraus N. Brainstem abnormalities in neonates with normal otoacoustic emissions//Seminars in Hearing. - 1996. - 17: 197-213.
6. Avilala V. K. Y. et al. Spontaneous otoacoustic emissions in individuals with auditory neuropathy spectrum disorder//Audiological Medicine. - 2012. - 1: 5.
7. Madden C. et al. Clinical and audiological features in auditory neuropathy//Arch Otolaryngol Head Neck Surg. - 2002. - 128: 1026-1030.
8. Varga R., Kelley P. M., Keats B. J., Starr A., Leal S. M., Cohn E., Kimberling W. J. Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene//Journal of Medical Genetics. - 2003. - 40: 45-50.
9. Delmaghani S., del Castillo F. J., Michel V. et al. Mutations in the gene encoding pejvakin, a 550 newly identifies protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy//Nature Genetics. - 2006. - 38: 770-778.
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Khaydarova Mukhtabar Mannapovna, Senior staff scientist of Republican Specialized Scientific and Practical Medical Center of Pediatric, Republic of Uzbekistan
E-mail: evovision@bk.ru
Changes cytokine spectrum in children with bronchopulmonary diseases with bronchial obstruction
Abstract: In bronchopulmonary diseases with bronchial obstruction immune response develops mainly on Th-type, which suggests that in the occurrence of symptoms of bronchial obstruction, the leading role is played by the formation of the hearth of an infectious inflammation of the lung tissue. When analyzing the changes in the level of IL-4 in patients with ROB it has been found that the immune response feature is its Th-2 direction, which leads to overproduction of IgE and IgG. These processes ultimately determine the course and prognosis of the disease.
Keywords: Bronchopulmonary diseases with bronchial obstruction, cytokines, immune system.
The development of the disease with immune pathogenetic basis should be considered from the point ofview of the effector parts of the immune system, which is involved in pathological processes is largely due to a cascade of cytokines. It is believed that when BO which the considered as a systemic inflammatory reaction cascade triggered by weight of pro-inflammatory and anti-inflammatory cytokines.
It is known that antigen entry into the body activates macrophages and causes secretion of a number of mediators, including IL-1p stimulating T cell proliferation and which is the main mediator of local inflammatory reaction, in any type of inflammation [1; 2; 3]. In addition, it is proved that the physiological conditions, IL-1 is able to increase the activity of Th1 cells by stimulating the secretion of IFN-y. Normally, the dominant form of secretion in humans is IL-1p [2].
IL-4 limits the incidence and intensity of inflammation, inhibits the production of pro-inflammatory IL-1p, activates B lymphocytes, increases the synthesis of immunoglobulin's primarily immunoglobulin G, E, contributing to the production of antibodies protective properties which neutralize the action of pathogenic agents. The development of the disease with immune pathogenetic basis should be considered from the point ofview of the effectors parts of the immune system, which is involved in pathological processes is largely due to a cascade of cytokines. It is believed that when BO which considered as a systemic inflammatory reaction cascade triggered by weight of pro-inflammatory and anti-inflammatory cytokines.
In order to characterize the functional state of the T1 and T2 have surveyed our children with bronchopulmonary pathology (BLP) with bronchial obstruction (BO) studied the features of production IL-1p and IL-4 in serum Peripheral blood.
Material and methods
We observed 371 children aged from 3 months up to 7 years: 110 of them to OB, 50 children with obstruktiv recurrent bronchitis flow (OBRT), BLP 211 patients with symptoms of OB and 20 healthy children.
When the diagnosis into account medical history, the results of clinical, radiographic, functional, biochemical, immunological and psychological research methods. Verification of the diagnosis based on the classification adopted in Moscow at the Symposium (on improving the classification of non-specific lung diseases in children, 1995).
Children have been subjected to clinical examination with the standard description of the personal data, including during
pregnancy, nutrition of pregnant and breastfeeding, childbirth, the neonatal period, the application timing to the chest, child nutrition in infancy transferred somatic diseases background state.
Results and its discussion
Our studies have shown that in healthy children IL-1^ products ranged from 14-69 pg/ml and the average stood at 52.4-3.5 pg/ml. Children with BLP, hypercytokinemia marked both by pro- and anti-inflammatory cytokine with a maximum concentration of IL-1p in patients with intense inflammation and adequately reflect the severity of their course.
A comparative analysis of the level of pro-inflammatory cytokine IL-1p, depending on the presence or absence of BO showed that when ON 1.3 times at OB 1.9 times and 2 times in the BPBO was increased in patients with BO. Study of anti-inflammatory indicators cytokine IL-4 showed an increase in their standard of 1.6 times, 2 times and 1.4 times at the BW in children with OB, OP, and RB, respectively.
We have found that in children with AOB production IL-1p was significantly (P < 0.01) increased to 125.8 ± 5.7 pg/mL compared with healthy children. In patients with BPBO indicator IL-1^ production was significantly (P < 0.01) increased to 286.2 ± 10.7 pg/ml, which was 5.4 times higher than the norm. Patients with OBRT index products IL-1^ succeed to 198.5 ± 21.2 pg/ml. These data suggest the presence of IL-1p depending on the level of production on the nature of the infectious process, as evidenced by the upconsciously high level of secretion in patients with OBRT. There regulation increase in proinflammatory interleukin IL-1p in all the surveyed groups, but it is more pronounced in case of acute pneumonia with obstructive syndrome, exceeding the norm by 5.4 times. We fixed that when AOB and OBRT their level increased by 2.4 and 2.3 times, respectively, that is, the severity of the changes of this indicator was practical the same in case of bronchitis.
The study showed that the increase in IL-4 takes place in all groups with the AOB, but it is most pronounced in patients with BPBO. If patients with acute process OBRT - IL-4 levels in serum increased by 3.2 and 3.3 times, respectively, the BPBO at 4.5 times. Intensive synthesis of IL-1^ and IL-4 at OBRT displays cytokine imbalance in the system. At the same time the immune response in patients with OP BO develops pre and property by Th-1-type,
