LALITA CHAUDHARI*, O. P. TANDON,
N. VANEY AND N. AGARWAL**
Departments of Physiology and Gynae-Obstetrics**,
University College of Medical Science and G.T.B. Hospital,
Dilshad Garden, Delhi - 110 095
( Received on June 12, 2002)

 

Key words : evoked potential, gestational diabetes,auditory brainstem ,response,mid latency response, slow vertex response

 

INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

INTRODUCTION

Glucose is an essential metabolic fuel for the brain. It is therefore not surprising that perturbation in glucose regulation can cause functional or even structural impairment of the nervous system.  The changes in neural generator activity and sensory conduction in CNS could be detected by monitoring auditory evoked potentials.  Auditory evoked potential testing serves as a non-invasive clinical tool in characterizing the electrophysiological phenomena of neural excitation, conduction and transmission across auditory pathways (1).

Human auditory evoked potentials are generally divided into early Auditory brainstem responses (ABR), Mid latency responses (MLR) and late Slow vertex response (SVR).  Waves of ABR primarily represent volume conducted electrical activity generated from cochlear nerve to inferior colliculus and interpeak latencies between these waves reflect neural conduction in the corresponding segment of central auditory pathway.  MLR are the potentials derived from thalamocortical projections of auditory pathways.  SVR originate from the primary auditory cortex and temporo-parietal association areas.

Diabetes can alter the peripheral and central nervous system.  These are studies showing a decrease in amplitude and increase in latencies of various component of auditory evoked responses suggesting presence of conduction delay in nonpregnant diabetic subjects (2,3,4,5).  To our knowledge no study so far has been done to show changes in auditory evoked potentials in diabetic pregnancy.  However reports of evoked potentials even in normal pregnancy show variable responses; delayed sensory conduction in the brainstem auditory pathways (6), improvement on Pl latency of VEP (7) and delayed cognitive functions (8).  So this study was undertaken to observe changes in ABR, MLR and SVR in gestational diabetics as compared to normal pregnant women.
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METHODS

Study was conducted on 40 pregnant females reporting to Gynecology and Obstetrics department of Guru Teg Bahadur Hospital, Delhi.  Study included 20 pregnant women with single pregnancy that were diagnosed as having gestational diabetes after undergoing glucose tolerance test with 100 grams of glucose as per criteria suggested by O' Sullivan & Mahan (9). Twenty age and gestational age matched normal pregnant females were taken as control.  Age (mean ± S.D.) of the subjects in control group was 25.42 ± 7 years and in diabetic group was 26.06 ± 7.5 years.  Gestational age in control group was 31.58 ± 4 weeks and in diabetic pregnant group was 32.85 ± 4 weeks.  All the subjects having history of ear discharge, hearing loss, tinnitus, plugging of ear or other ear pathology, psychiatric disorder, or other medical condition e.g. Pre-eclampsia along with diabetes, were excluded from the study.  Clearance was obtained from college ethical committee.  All subjects were well informed about the nature and consequences of the procedure beforehand.  A written consent was taken.  During the procedure each subjects was lying down and relaxed in a sound proof air conditioned room.  Ag/AgCl disc electrodes were affixed with collodion according to 10/20 international system of' electrode placement.  The active (+) electrode was placed over the vertex at C_Z area, reference electrodes at left and right ear lobule (A_1, A₂), and the ground electrode was placed on the forehead.  All the electrodes were plugged to a junction box and skin to electrode impedance was monitored and kept below 5 K ohms.  The signals picked up by these electrodes from the scalp after a standard click were filtered, amplified, averaged, and displayed on the screen of MEB 5200 Neuropack 11... plus (Nihon Kohden, Japan) Evoked Potential Recorder.  ABRs were recorded using standardized technique (1,10).  Click stimuli having intensity 70 dB above normal hearing threshold were presented independently to each ear at the rate of 10/ s and 0.1 ms duration.  During testing of one ear the other ear was masked by a white noise of -40 dB. 2048 clicks were generated by passing 0.1 ms square pulses through shielded headphones with alternating polarity.  The signals picked up by these electrodes were displayed on the screen in form of waves after filtration (with band pass of 3000 Hz), amplification and averaging.  Peak latencies of waves I to V, inter peak latencies (IPL) of I-III, III-V, I-V and amplitudes of I & V were determined. For MLR same procedure was repeated using the same electrode placement.  Alternating rarefaction and condensation clicks were generated by an acoustic stimulator with duration of 0.1 ms. Total of 256 stimuli were given with stimulus rate of 5 Hz through shielded headphones to each ear separately and average of 256 response was recorded.  The other ear was masked with a white noise of -40dB as done for ABR recording.  Peak latencies of negative and positive waves (No, Po, Na, Pa, Nb, Pb) were recorded.  SVR was measured by giving 64 clicks of alternating polarity for 0.1ms at 0.5 Hz at the same sound intensity.

Statistical significance was assessed by using unpaired Student's t-test.
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RESULTS

The absolute peak latencies, inter peak latencies and amplitudes of different waves of ABR are shown in Table I, The ABR values obtained from our normal pregnant control group are in close agreement with data from our laboratory reported by Tandon et al (5), using similar stimulus and recording parameters.  In gestational diabetic women, a significant prolongation of absolute latencies of all the waves of ABR i.e. wave I, II, III, IV and V was observed.  Also IPLs I-III and I-V were significantly increased whereas amplitude of wave V was decreased in gestational diabetics as compared to normal pregnant women.  No significant change in latency of any component of MLR was observed between the two groups (Table II).  As shown in Table III significant prolongation of latencies of all components of SVR was observed in gestational diabetics as compared to normal pregnant women.  Representative tracings of ABR, MLR and SVR are depicted in Fig. 1, 2 and 3 respectively.

Table I click to see full view

Table I: Comparison of absolute peak latencies, interpeak latencies and amplitude of ABR in normal pregnant and gestational diabetic subjects.

 

Table II click to see full view

Table II: Comparison of latencies of components of MLR in normal pregnant and gestational diabetic subjects.

 

Table III click to see full view

Table III: Comparison of latencies of components of SVR in normal pregnant and gestational diabetic subjects.

 

Fig. 1 click to see full view

Fig. 1: Showing representative tracing of ABR in normal pregnant controls (A) and gestational diabetics (B).   Fig. 2: Showing representative tracings in MLR in normal pregnant controls (A) and gestational diabetics (B).

 

Fig. 3 click to see full view

Fig. 3: Showing representative tracings of SVR in normal pregnant controls (A) and gestational diabetics (B).

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DISCUSSION

Diabetes mellitus is a syndrome characterized by a loss of glucose homeostasis.  It is associated with high risk of various diseases e.g. angiopathy, retinopathy and neuropathy.  Many studies have compared auditory evoked responses in non-pregnant diabetic patients and normal individuals (2,3,4,5,) and have reported prolongation of latencies of various components of ABR.

Auditory evoked responses so far have not been studied in gestational diabetes.  In the present study auditory evoked responses in normal pregnancy and gestational diabetes were compared.  The ABR values obtained from normal pregnant control group were in close agreement with data from our laboratory reported by Tandon et al (5).  In gestational diabetic a significant prolongation of' absolute peak latencies of all components of ABR and inter peak latencies I – III  and I-V was observed and amplitude of wave V was found to be smaller in diabetic pregnancy as compared to control group.

Latencies of ABR reflect the neural conduction velocity in the corresponding segment of auditory pathways.  A delay of absolute lateric (AL) of wave I to wave V in pregnant diabetics suggests the central neuropathy both at the level of auditory nerve and auditory pathways in the brainstem.  In present study IPLs I-III (conduction time from 8th nerve to superior olivery complex) and I-V (conduction time from 8th nerve to inferior colliculus) were also prolonged which indicates prolongation of both peripheral transmission time (PTT) and central transmission time (CTT) in gestational diabetics.  Prolongation of PTT could be related to pathological observation of degeneration of spiral ganglion of cochlea and demyelination of 8th nerve (11).  Prolongation of AL of wave V and IPL I-V points to a primary locus in upper brainstem and midbrain structures and suggest the presence of central neuropathy in patients with diabetes.

A correlation has been observed between ABR abnormalities and the minute hypodense lesion within the brainstem on MRI scan (4), and it was postulated that the micro- and macroangiopathic changes in the brainstem could be responsible for the ABR abnormalities in diabetes.  Another explanation may be impairment of the electro-conductive properties of myelin sheath, evoked by various metabolic changes caused by diabetes (12).

In the present study no significant overall difference in latencies of any component of MLR (No, Po, Na, Pa, Nb, Pb) was observed in diabetic pregnant patients and normal pregnant controls.  ABR may be more sensitive to structural and plausibly subtle CNS changes than middle latency response (MLR).  MLRs involve diverse polysynaptic pathways of higher brain region including mesencephalic reticular formation and thalamo-cortical pathways (13, 14), which may compensate for deficiencies in lower central neural structures.  However definite significance of MLRs for the assessment of primary auditory cortex is still a matter of controversial debate.  In this study a statistically significant prolongation of latencies of all the components of slow vertex response (SVR) i.e. P1, N1, P2, N2, was observed in gestational diabetic as compared to normal pregnant females.  Since SVR represents the neural conduction at the level of cortex and association areas, the prolongation of latencies of SVR components in this study implicate cortex in the central diabetic neuropathy.  The observed delay in neural conduction process in the diabetic pregnant patients may be related to degeneration of central neural structures which has been described by many workers as an expression of widespread diabetic encephalopathy (15).  Other pathological studies in diabetic patients have shown multiple infarctions in neural tissue, cell loss, demyelination and degeneration of ganglion cells and nerve fibers in the cerebrum, brainstem and cerebellum (16).  It is accepted by many authors that the damage in the neural tissue in diabetes is induced by microangiopathy of vasa nervosum which causes demyelination of the neural trunk (12).  Others believe that diabetic neuropathy is the result of alteration in the electrophysiological properties of myelin sheath due to various metabolic disturbances induced by diabetes (17).  The pathological changes in the myelin sheath whether quantitative or qualitative or both induce the alteration in normal and synchronic neural conduction process which results in slowing of conduction velocity along with affected nerves (18).

Although the structural and functional changes in the nervous system can be deduced from our observations, it is not clear from this study if the diabetic microangiopathy or macroangiopathy or primary diabetic abnormality of the brain tissue constitute the pathogenic mechanism for disturbed CNS function in gestational diabetics, it is therefore suggested that further studies should be done in diabetic pregnancy to identify the underlying mechanism for CNS dysfunction as detected by auditory evoked responses.

REFERENCES  

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2.       Martini A, Commachio F, Fedele D, Crepaldi G, SalaO. Auditory brainstem evoked responses in the clinical evaluation and follow up of insulin dependent diabetic subjects.  Acta Oto-Laryngo 1987; 103: 620-627.

3.       Buller N, Laurian L, Shivill I, Laurian N. Delayed brainstem auditory evoked responses in diabetic patients.  J Laryngol Otol 1988; 102: 857-860.

4.       Nakamura Y, Takahashi M, Kitaguti M, et al.  Abnormal brainstem evoked potentials in diabetes mellitus : Evoked potential testing and magnetic resonance imaging.        Electromyograph Clin Neurophysiol 1991; 31: 243-249.

5.       Alexander M, Thomas SV, Mohan PK, Narendernathan M. Prolonged brainstem auditory evoked potential latencies in tropical pancreatic diabetics with normal hearing.  Electromyogr Clin Neurophysiol 1995; 35: 95-98.

6.       Tandon OP, Misra R, Tandon 1. Brainstem auditory evoked potentials in pregnant women.  Indian J Physiol Phamacol 1990; 34(l): 42-44.

7.       Tandon OP, Bhatia S. Visual evoked potential responses in pregnant women.  Indian J Physiol Pharmacol 1991; 35: 263-265.

8.       Tandon OP, Bhatia R, Goel N. P3 event related potentials in pregnancy.  Indian J Physiol Pharmacol 1996; 40(4): 345-349.

9.       O'Sullivan JB, Mahan CM.  Criteria for oral glucose tolerance test in pregnancy.  Diabetes 1964; 13: 278-285.

10.    Stockard JJ, Sharbrough FW.  Unique contribution of short latency sensory evoked potentials to neurological diagnosis.  Prog Clin Neurophysiol 1980; 7: 231-263.

11.    Makishima K, Tanaka K. Pathological changes of inner ear and central pathway in diabetics. Ann Otolaryngol 1971; 80: 218-228.

12.    Winegrad Al, Morrison AD, Greene DA.  In: Text book of Endocrinology 1979; 2: 1041-1055.

13.    Martini A, Commachio F, Magnavita V. Auditory brainstem and middle latency evoked responses in clinical evaluation of diabetes.  Diabetic Med 1991; 8: 574-577.

14.    Kraus N, Therese M, Thomas L, Trent L. Reticular formation influences on primary and non primary auditory pathways as reflected by the middle latency response.  Brain Res 1992; 587: 186-194.

15.    Reske-Nielsen E, Lundbaek K, Rafelsen OJ.  Pathological changes in central and peripheral nervous system of young long term diabetics.  Diabetic encephalopathy.  Diabetologia 1965; 1: 233-241.

16.    De Jong RN.  CNS manifestation of diabetes mellitus.  Post Grad Med 1977; 61: 101-107.

17.    Clements RS, Bell DS.  Diabetic nephropathy, peripheral and autonomic syndrome.  Post Grad Med 1982; 71: 50-67.

18.    Buller N, Laurian N, Shivill 1, Laurian L. Delayed brainstem auditory evoked responses in experimental diabetes mellitus.  J Laryngol Otol 1986;100:883-891.

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