Keywords
down syndrome - cervical vestibular-evoked myogenic potentials - postural balance
Introduction
Down syndrome (DS) is one of the most common chromosomal birth defects in children,[1] and it is the phenotypic consequence of trisomy 21. As consequence of nonhereditary
intellectual disability, several problems arise, such as developmental delay, respiratory
dysfunctions, vision problems, hearing problems, and balance dysfunction.[2]
[3] Control of balance requires the integration of vestibular sensory information with
somatosensory and visual information,[4] and its dysfunction may be evaluated via standardized scales and tests. Some of
those are the Pediatric Balance Scale (PBS),[4] the Romberg test,[5] the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB),[6] and the Timed Up and Go (TUG) test.[7] These tests and their uses are presented in [Table 1].
Table 1
Scales and tests used to evaluate balance dysfunction
|
Pediatric Balance Scale (PBS)
|
Functional balance in everyday life activities (Franjoine et al.,[4] 2003).
|
|
Romberg test
|
The integrity among different sensory organs and neuronal conduction pathways utilized
in the constitution of balance (Black et al.,[5] 1982).
|
|
Modified Clinical Test of Sensory Interaction on Balance (mCTSIB)
|
Sensory system dysfunction on a stable and unstable floor, with eyes open and closed.
In the tests on unstable ground with the eyes closed, the effects of visual and somatosensory
inputs are eliminated, and the effects of vestibular inputs on postural stability
are evaluated more efficiently (Shumway-Cook et al.,[6] 1986).
|
|
Timed Up and Go Test (TUG)
|
Functional mobility and balance through different variables such as walking speed,
postural control, functional mobility, and balance are evaluated (Podsiadlo et al.,7 1991).
|
The vestibular system is responsible for maintaining the sense of head orientation
and acceleration, both at rest and in motion.[8]
[9] Vestibular inputs through vestibulo-spinal connections play a major role in trunk
stabilization.[10] The activation of otolith organs evokes the vestibulocollic reflex (VCR), which
provides stabilization of the position of the head in space.[11] The cervical vestibular evoked myogenic potential (cVEMP) is a test used for neurotologic
examination both in adults and in children. It verifies the integrity of vestibular
otolith function through a muscular response evoked by a high-intensity acoustic stimulation
which activates the saccular macula and records the transient inhibition of the sternocleidomastoid
(SCM) muscle via surface electrodes.
While several studies have reported balance and gait dysfunction in DS,[12]
[13]
[14] the impact of vestibular otolith function in balance control in DS has not been
fully addressed. The principal aim of the present study was to assess vestibular otolith
function using cervical vestibular-evoked myogenic potentials (cVEMPs) in children
with DS and matched control children. In addition, the static and dynamic balance
performances were also measured through conventional balance tests and correlated
with cVEMP responses.
Methods
The present study was conducted in compliance with the Declaration of Helsinki, and
it was approved by the local Ethics in Research Committee. In total, 15 children with
DS, 7 females and 8 males, aged between 9 and 11 years (mean age: 10.25 ± 0.70 years)
were included. An age- and gender-matched control group (CG) composed of 15 participants
(7 females and 8 males) without DS was also included. The inclusion criteria for the
subjects in the DS group were: the presence of trisomy 21; the absence of any visual
or organic disorders, and independence in stance and ambulation (having no hearing
loss, no additional impairment, and no neurologic or vestibular system problem). The
participants in the control group were healthy, with no orthopedic or neurological
disorders, no impairment in somatosensory activity, hearing, vestibular or uncorrected
visual functions, and free of medications for at least three months before the beginning
of the study. Written informed consent was obtained from all parents and children.
All children (DS and control) underwent the cVEMP, the PBS, the Romberg test, the
mCTSIB and the TUG test. The CVEMPs were recorded with the Neurosoft Neuro-Audio.Net
(Neurosoft Ltd., Ivanovo, Russia) software. The electromyographic activity of the
SCM muscle was recorded while the children were sitting on a chair and were asked
to turn their head to both sides to activate their neck flexors, and the saccular
receptors were acoustically stimulated. Electromyography (EMG) biofeedback was used
to reject all traces outside the minimum/maximum root mean square (RMS) EMG limits.
Prior to the cVEMP test, the maximum contraction level is determined for each individual.
Then, the target level for all subsequent cVEMP tests is set at ∼ 70% to 80% of the
maximum contraction level. The RMS is calculated for the EMG before each stimulus
(prestimulus area) and displayed on a dial on a computer screen for the patient to
see. The subjects are instructed to keep the EMG level constant and at a predefined
target level (50 μV ± 20 μV). The acoustic stimulus was a click of 500 Hz at an intensity
of 105 dB nHL. The rate was of 4 stimuli per second, and it was presented monoaurally
through earphones. Recordings were obtained with an average of 200 stimuli response,
and 2 traces from each side were obtained to assess reproducibility. In each trace,
we determined the latency of positive-negative waves (P1 and N1), in addition to the
amplitude of the P1-N1.
Functional balance in everyday activities is measured with PBS on a 5-point scale
to obtain overall scores for each subject. In the Romberg test, children were asked
to stand upwards for 30 seconds withtheir eyes closed, and then we noted whether they
could sustain their position or not. In the mCTSIB, children were asked to preserve
their balance in 4 different conditions (eyes open, on stable ground; eyes closed,
on stable ground; eyes open, on unstable ground; and eyes closed, on unstable ground),
and the maximum time each child managed to stand in balance was recorded. In the TUG
test, the participants were seated on a chair and asked to stand up without handling
the grip, and to walk 3 m and take a seat again. The time to complete the task was
recorded. All tests were conducted in the same day, with adequate breaks between them.
The variables studied were: gender; date of birth; latency to onset of the P1 wave;
latency to onset of the N1 wave; value of the P1-N2 amplitude. Overall scores for
the scale and the time (seconds) for the other tests were recorded. Descriptive data
were expressed as means and standard deviations. In addition, the measurements of
the central tendency (median) of the continuous variables were calculated, as well
as their respective interquartile range (IQR). For the comparative analyses concerning
cVEMP responses (latencies and amplitudes) and balance tests between patient and control
groups and also in relation to gender, the Mann-Whitney U test was used. Values of
p < 0.05 indicated statistical significance.
Results
The demographics of the subjects in both groups are presented in [Table 2]. There were no significant differences regarding age and gender between the two
groups (p > 0.05). To assess saccular function and differentiate from healthy controls (30
ears of 15 children), the air-conduction cVEMP test was administered to 30 ears of
15 children with DS; in addition, the severity if the balance dysfunction was evaluated
with PBS, the Romberg test, the mCTSIB and the TUG test.
Table 2
Demographics of the study sample
|
Patient Group
|
Control Group
|
|
Males
|
Females
|
TOTAL
|
Males
|
Females
|
TOTAL
|
|
Mean
|
Standard deviation
|
Range
|
Mean
|
Standard deviation
|
Range
|
Mean
|
Standard deviation
|
Range
|
Mean
|
Standard deviation
|
Range
|
Mean
|
Standard deviation
|
Range
|
Mean
|
Standard deviation
|
Range
|
|
Age, years
|
10.25
|
.70
|
9.00–11.00
|
10.14
|
.69
|
9.00–11.00
|
10.2
|
.67
|
9.00–11.0
|
10.25
|
.70
|
9.00–11.00
|
9.00–11.00
|
10.14
|
.69
|
10.2
|
.67
|
9.00–11.0
|
Testing of the cVEMPs was performed on both sides in all DS and control subjects.
All subjects (100%) completed the cVEMP testing with data for analysis. In total,
30 (60%) subjects included for analysis had measurable bilateral responses at 105 dB
of air-conducted click stimulus. The P1 and N1 peak latencies for the DS subjects
ranged from 10.80 ms to 13.40 ms, with a median (IQR) of 12.40 ms (1.00 ms), and from
16.00 ms to 20.40 ms, with a median of 18.30 ms (1.70 ms) respectively. The P1-N1
amplitudes for the DS group ranged from 33.30 μV to 83.50 μV, with a median amplitude
(IQR) of 62.30 μV (19.75 μV). The P1 and N1 peak latencies for the control subjects
ranged from 11.40 ms to 18.50 ms, with a median (IQR) of 12.70 ms (1.10 ms), and from
17.30 ms to 26.20 ms, with a median (IQR) of 20.00 ms (2.30 ms) respectively. The
P1-N1 amplitudes for the control group ranged from 36.40 μV to 174.70 μV, with a median
(IQR) of 104.75 μV (59.05 μV). [Table 3] shows the median values (IQR) of the P1, N1 latancies and the amplitude of the P1-N1
obtained for the whole sample.
Table 3
Results of the balance tests, latencies of P1 and N1, amplitude of P1-N1 in the Down-syndrome
and control subjects and their comparison
|
Grups
|
Pediatric Balance Scale
|
Timed Up and Go Test
|
P1
|
N1
|
P1-N1
|
|
Down syndrome group
|
N
|
Valid
|
30
|
30
|
30
|
30
|
30
|
|
Missing
|
0
|
0
|
0
|
0
|
0
|
|
Median
|
30.00
|
20.00
|
12.40
|
18.30
|
62.30
|
|
Interquartile range
|
|
7.00
|
8.00
|
1.00
|
1.70
|
19.75
|
|
Control Grup
|
N
|
Valid
|
30
|
30
|
30
|
30
|
30
|
|
Missing
|
0
|
0
|
0
|
0
|
0
|
|
Median
|
56.00
|
9.00
|
12.70
|
20.00
|
104.75
|
|
Interquartile range
|
|
0.00
|
1.00
|
1.10
|
2.30
|
59.05
|
|
Mann Withney U test
|
|
|
p = 0.000
|
p = 0.000
|
p = 0.08
|
p = 0.000
|
p = 0.000
|
The statistical analysis demonstrated a significant difference between DS and control
subjects in the latencies of N1 (p = 0.000) and the amplitude of P1-N1 (p = 000). There was no significant difference among cVEMP parameters regarding the
right and the left ears of the control subjects or regarding gender (p > 0.05).
The ability of the subjects to maintain a quiet upright stance was assessed with the
mCTSIB under four conditions in which sensory inputs were systematically altered.
Balance times were recorded. All subjects in both groups were able to fully maintain
their balance for 30 seconds. The Romberg test was negative for the whole sample,
which means that all subjects could stand with their eyes closed for 30 seconds. The
median PBS score (IQR) for the DS subjects was of 30.00 s (7.00 s), which was significantly
lower than that of the control subjects (56.00 s [0.00 s]; p = 000). Task in the TUG test for DS 20.00 (8.00) which significantly longer than
control subjects 9.00 (1.00) (p = 000).
Discussion
In the present study, the results of the saccular function test showed that there
was a significant difference between children with and without DS. The DS subjects
had significantly earlier N1 latancy and lower amplitude in the cVEMPs (< 70m V) compared
with the control subjects. In addition, there was a statistically significant difference
in the static-dynamic balance ability in DS children compared with the controls.
Under everyday conditions, the vestibular system works in a complementary way with
the somatosensory and visual systems to provide balance/postural control. Balance
functions of DS has been put forth before,[12]
[13]
[14]
[15] and the cVEMPs have been extensively studied in subjects without DS,[16]
[17]
[18]
[19] as well as some other pathological conditions.[20] On the contrary, balance function and cVEMP testing have not been correlated in
DS before.
The present study was performed to compare balance and saccular functions between
DS children and typically developing children. In this regard, the static balance
and the dynamic balance were tested and correlated with the saccular function test
(cVEMP). As expected, the DS children had significant differences in all areas of
balance ability in comparison with typically developing children (p < 0.05). Typically developing children showed higher balance ability than the DS
children. This is in line with the following previous study results: the static-dynamic
balance of DS children showed more differences compared with typically developing
children and DS children lack static balance ability.[12]
[14]
[15] The reason for this is that their muscle reaction velocity is significantly slower
compared with their peers,[21] and there is much difficulty with motor control.
We used the cVEMP with air-conduction stimuli that measures saccular function. The
cVEMPs were recorded while the children were sitting on a chair and were asked to
turn their head to both sides to activate their neck flexors bilaterally. As mentioned
in the literature,[16] activation of the the SCM muscle by turning the head while sitting was sufficient
to generate the cVEMP responses without early fatigue. Reproducible, unrectified cVEMP
tracings were easily obtained with clicks at 105 dB in all DS and control children.
In other words, the response rate in the present study was of 100%. Despite the usual
muscle weakness and motor control handicap among DS children, the cVEMPs could be
easily recorded in those subjects.
Our results demonstrated that the cVEMP parameters for the control group are similar
to the normative values, as reported in the literature.[18] On the other hand, we detected that the fundamental parameters of the cVEMP test
(latency and amplitude) among DS children are significantly different than those obtained
among the controls. Differences in latencies and amplitudes should be considered as
N1 latencies were shorter and P1-N1 amplitudes were lower than those obtained among
the controls. These results suggest that cVEMPs recording, demonstrating that the
saccule, the vestibular afferent fibers and the vestibular nuclei are not similar
to tupically developing children. No statistically significant difference was detected
between the right and left sides regarding the P1 and N1 latencies and the P1-N1 amplitude.
This agrees with the studies by Picciotti et al.[17] and Gonzalez et al.,[22] who demonstrated no differences between the right and left ears.
The recording rate was of 100%. This means that the cVEMP test could be applied successfully
to diagnose saccular function among the pediatric DS population, as it can be recorded
easily in all children to make appropriate decisions about interventions and program
placement and planning, and to track the progress of children with DS.
Regarding the use of cVEMPs in the examination of the vestibular system in the pediatric
population, Tribukait et al.[23] showed that the function of the semicircular canal correlated best with the function
of the saccule, and, if the hearing was better than 90 dB, the function of the vestibular
otolith was often normal, while for hearing levels of 100 dB to 120 dB, otolith function
declined significantly. De Kegel et al.[24] found that children between 3 and 12 years of age with moderate hearing impairment
and absent cVEMP perform significantly weaker on static balance measurements in which
visual and/or somatosensory information is unreliable. This confirms that the saccule
has an important role in the development of static balance.
Conclusion
In the present study, the most remarkable result is that cVEMP responses are effected
in children with DS means that saccular function is altered in those children. This
finding may have implications to the understanding of the basis of the balance problem
that affects children with DS in their everyday lives. When assessing static and dynamic
balance dysfuction among DS children, vestibular otolith functions should be considered.
Future studies on the functions of the utricle and semicircular canal are needed for
a more complete understanding of vestibular dysfunction among DS children.
