words : evoked
potential, gestational diabetes,auditory brainstem ,response,mid
latency response, slow vertex response
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.
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 CZ area, reference electrodes at left and right
ear lobule (A1, 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.
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
| Table III
click to see full view
Table III: Comparison of latencies
of components of SVR in normal pregnant and gestational
| Fig. 1
click to see full view
Fig. 1: Showing representative tracing
of ABR in normal pregnant controls (A) and gestational
Fig. 2: Showing representative tracings
in MLR in normal pregnant controls (A) and gestational
| Fig. 3
click to see full view
Fig. 3: Showing representative tracings
of SVR in normal pregnant controls (A) and gestational
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
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
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
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.
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