166
Paediatrica Indonesiana
Vol. 41 No. 5-6, May-June 2001
Paediatrica Indonesiana
Paediatr Indones 2001; 41:166-170
Original article
Brainstem auditory evoked potentials features in
thalassemia major
Jimmy Passat, Bulan Ginting Munthe, Fauzi Mahfuzh, Taralan Tambunan
Department of Child Healh Faculty of Medicine University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta
ABSTRACT Patients with thalassemia major are at high risk for hearing impairment. The objective of the study is to determine
the prevalence, grade and type of hearing impairment according to brainstem auditory evoked potentials (BAEP) investigation
in thalassemia major. A descriptive cross sectional study was conducted between December 1999 until August 2000 in 72
thalassemic patients between 3 and 18 years of age. Only 65 patients were evaluated, because of time limitation. The results
showed the prevalence of hearing impairment in thalassemia major was 29.2%. Most of them were moderate to severe
unilateral sensorineural hearing impairments. Mild sensorienural hearing impairment occured in only 12.3%. Conductive
hearing impairment was only found in 1 patient. Hearing impairment was frequently found between 7 to 12 years of age
(41.5%). Conclusion: the prevalence of hearing impairment in thalassemia major according to BAEP investigation is high and
BAEP examination should be done regularly in all of thalassemic patients to investigate early detection and treatment of
hearing impairment. [Paediatr Indones 2001; 41:166-170]
Keywords: thalassemia, brainstem evoked potentials, children.
THALASSEMIA
DISEASE IS A LIFE-LONG HEMOLYTIC
disease, causing various problems for the patient.
Chronic anemia caused by hemolytic process may
affect various organ disorders either as a result of
the disease or the treatment.1,2 Hearing impairment
is one of the disorders that may occur in thalassemic
patients. 3 Hearing impairment in thalassemia is
generally correlated to chronic anemia, 4 iron
overload,4-6 extramedullary hematopoiesis,7 and the
side effect of desferoxamine chelation therapy.6,8-12
Correspondence: Jimmy Passat, M.D., Department of Child Health,
Medical School, University of Indonesia, Jalan Salemba 6, Jakarta
10430. Tel. 62-21-3907743; Fax, 62-21-3907743.
Various diagnostic tools are used to detect hearing
impairment, one of them is brainstem auditory evoked
potential (BAEP). BAEP as a neurophysiologic
diagnostic tool can detect hearing impairment
precisely and accurately. BAEP advantages are not
requiring patient’s cooperation, objective, and non
invasive.13-16
BAEP that has been performed in thalassemic
patients to detect early diagnosis and to monitor
hearing impairment during the course of the disease,17-19 are reported by Wong et al in 12% patients,17
and Konzoglou et al in 27% patients.18 Meanwhile
Zafeiriou et al demonstrated sensorineural hearing
impairment with prolonged I-V interpeak latencies
in 25% patients and I-III interpeak latencies in
10% patients.19
Passat et al.: Brainstem auditory evoked potential in thalssemia major
In Indonesia, various studies in thalassemic patients have been done, 20 while brainstem auditory
evoked potentials features in thalassemia major have
not been reported. The aim of this study was to determine brainstem auditory evoked potentials (BAEP)
features in thalassemia major patients.
167
Nineteen patients (29.2%) showed hearing impairment by BAEP. Unilateral hearing impairment was
the most frequently found in 13 (20%) patients, and
bilateral hearing impairment was found in 6 (9.2%)
patients as shown in Table 2.
TABLE 2. DISTRIBUTION OF HEARING IMPAIRMENT BY
BAEP INVESTIGATION
Methods
This descriptive cross sectional study was performed at the
Department of Child Health, Cipto Mangunkusumo
Hospital, Jakarta, from December 1, 1999 until August 31,
2000. The inclusion criterias were all of thalassemia major
patients, age of the patients ranged between 3 to 18 years,
and there was consent provided by patient or parents.
Sample size was calculated using descriptive formula for single with a = 0.05 and Z= 1.96, giving the
required subject of 72 patients. BAEP examination was
done in 72 thalassemic patients with Neuropack 4 mini
evoked potential measuring system MB-5304K. Sedation with chloralhydrate was done in patients under 6
years of age or uncooperative ones. BAEP examination
was performed twicely by staff in BAEP laboratory and
was interpreted by pediatric neurologist. Patient was
judged as having hearing impairment if his hearing
threshold was more than 30 decibels as recommended
by World Health Organization in assessing hearing status. Data were analyzed with SPSS version 9.01.
Results
Hearing threshold
n
Normal
Abnormal :
Unilateral hearing impairment
Bilateral hearing impairment
46
Total
65
Normal hearing threshold (<30 decibels) was
found in 46 (70.8%) patients, and abnormal hearing
threshold (> 30 decibels) was 19 (29.2%) patients have
abnormal hearing threshold as shown in Table 3.
TABLE 3. DISTRIBUTION OF HEARING THRESHOLD BY
AGE GROUP
Age group
(Yr)
Hearing threshold
30 dB 31-40 dB 41-60 dB > 60 dB
(normal) (mild)
(moderate) (severe)
3 - 6
7 - 12
13 - 18
Total
Subject characteristics
13
6
Total
15
18
13
3
4
1
3
5
2
0
0
1
21
27
17
46
8
10
1
65
During study period BAEP was performed in seventy
two thalasemic patients. Seven patients were
excluded. Analysis was done in 65 patients aged from
3 to 18 (mean 9.9; SD 4.5) years. Patients consisted
of 35 females and 30 males. See Table 1.
Hearing impairment was frequently found in patients between 7 to 12 years of age group. According
to the grade of hearing impairment, moderate hearing impairment was the most frequently found in 10
patients. The youngest patient with hearing impairment was 3 years of age.
TABLE 1. CHARACTERISTIC OF THALASSEMIA MAJOR
PATIENTS BY SEX AND AGE
TABLE 4. DISTRIBUTION OF HEARING THRESHOLD BY
SEX.
Age (years)
Sex
Male
Total
Female
3- 6
7 - 12
13 - 18
10
13
7
11
14
10
21
27
17
Total
30
35
65
Sex
<30 dB
(normal)
Hearing threshold
31-40 dB 41-60 dB
> 60 dB
(mild)
(moderate) (severe)
Total
Male
Female
21
25
4
4
5
5
0
1
30
35
Total
46
8
10
1
65
Paediatrica Indonesiana
168
Vol. 41 No. 5-6, May-June 2001
According to sex, as shown in Table 4 there was
no sex difference in the patients.
TABLE 5. DISTRIBUTION OF HEARING IMPAIRMENT TYPE
BY AGE GROUP
Age group
(yr)
3- 6
7 - 12
13 - 18
Total
Type of hearing impairment
Conductive Sensorineural
Total
0
1
0
6
8
4
6
9
4
1
18
19
Table 5 shows that in the 19 patients with hearing
impairment, one patient showed conductive hearing impairment, and 18 patients with sensorineural hearing impairment while mixed hearing impairment was not found.
TABLE 6. DISTRIBUTION OF HEARING IMPAIRMENT TYPE
BY GRADE OF HEARING IMPAIRMENT
Grade
Type of hearing impairment
Conductive Sensorineural Total
Mild
Moderate
Severe
0
1
0
8
9
1
8
10
1
Total
1
18
19
Table 6 shows that moderate hearing impairment was
more frequently found in sensorineural hearing impairment.
Discussion
Study limitations
The current investigation had several limitations
including incomplete BAEPs results and limitated time
to complete the sample data.
Subject characteristics
During study period, only 65 patients with thalassemia major
could be analyzed. Most of the patients are 7 to 12 years
found in 27 patients (41.5%), 3 to 6 years (32.3 %), and 13
to 18 years (26.2%), respectively. Patients consisted of 30
males (46.2%) and 35 females (53.8%), ranged between 3
to 18 years with the means age of 9.9 (SD 4.5) years.
The features of hearing impairment in
thalassemia major
Regarding the BAEP examination in 65 thalassemia major
patients, hearing impairment was found in 19 patients
(29.2%), consisted of 10 females (15.4%) and 9 males
(13.9%). This result was lower than DeVirgilis study,4 but
higher than Zafeiriou’s.19 DeVirgilis et al demonstrated 45
patients (73%) with hearing impairment in 75 thalassemia
major patients.4 Other studies reported between 2 to 47%
patients with conventional audiometry.3,6,8,9,12 BAEP study
in thalassemia major patients was first reported by Amabile
et al, who studied 24 thalassemic patients but did not
found any patient with hearing impairment.21 Other BAEP
studies reported between 12% to 36.6% patients.17-19,22 This
differrence results were probably as the result of the
difference in methods.
Argiolu et al studied 309 thalassemia major patients who received blood transfusion since age of 5
months and found the youngest age with hearing impairment was 3 years.6 Logothetis et al, investigated in
138 thalassemia major patients ranged between 2 to 28
years, demonstrated hearing impairment in 2 patients
with the youngest age of 12 years.3 DeVirgilis et al,
reported the youngest age was 3 years in 2 patients with
sensorineural hearing impairment.4 In this study, the
youngest of age can not be determine because we limited the age of patient between 3 to 18 years.
We also found unilateral hearing impairment
(20%) was more frequent compared to bilateral hearing impairment (9.23%). This result was in inverse
ratio compared with DeVirgilis study, which showed
12% patients with conductive hearing impairment
were all bilateral. From 57.33% patients with sensorineural hearing impairment, bilateral hearing impairment was found in 41.33% patients and unilateral
hearing impairment in 16% patients.4
Hearing impairment was mostly found in age group
between 7 to 12 years, nine patients (13.9%), with
means 9.9 (SD 4.5) years. Argioulu et al found hearing
impairment in 15.5% patients with mean 11.5 (SD 3)
years,6 Kontzoglou et al demonstrated mean 9.66 (SD
3.1) years,18 and Gallant demonstrated mean 12 years.8
Whereas Zafeiriou found mean 16.2 (SD 18) years, and
suggested that there were a significant correlation between the age of patients over 15 years of age with the
involvement of auditory pathways.19 Several investigators reported that hearing impairment in thalassemia
major patients as a result of chronic anemia,4,11 iron
Passat et al.: Brainstem auditory evoked potential in thalssemia major
overload,4,6,9-11,15,19,22 extramedullary hematopoiesis,4,7
desferoxamine (DFO) neurotoxicity,6,8-12,15,17-19,22 and
blood transfusion.4,19 In the current study, the causal
factor of hearing impairment was not investigated.
Grade of hearing impairment
In this study, hearing threshold (=30 decibels) was
found in 46 patients (70.8%), mild hearing impairment
(31-40 decibels) in 8 patients (12.3%), whereas moderate
to severe (>40 decibels) in 11 patients (16.9%). Gallant
et al demonstrated mild hearing impairment in 7.86%
patients and moderate hearing impairment in 16.85%
patients,8 whereas other investigator demonstrated
moderate hearing impairment in all of their patients.4
Regarding to sex proportion, males were close to females
in proportion (DeVirgilis4 and Bentur).9
Type of hearing impairment
In audiology, BAEP is used to determine hearing threshold,
type and grade of hearing impairment. Of waves occur on
the nerve nuclei along the auditory pathways, waveform
and latency that is required from the onset of sound stimulus
to reach nucleus can be determine. Any delayed on time to
reach each nerve nuclei can give clinical values on auditory
nerves condition, and around brainstem pathways. Celesia
et al, suggest that BAEP latencies value can not be
interpreted without considering the patient’s hearing status.16
Conductive/sensorineural hearing
impairment
Conductive hearing impairment in thalassemia major
patients were reported by several investigators, such
as De Virgilis et al, who performed study in
thalassemia major patients and found 16% cases of 75
patients.4 Whereas Argiolu et al, did not find any case
of conductive hearing impairment in 309 patients.6
The studies above using conventional audiometry.
Triantafyllou, et al performed BAEP investigation and
found 15% patients with conductive hearing
impairment,22 whereas other investigators did not find
it. 17-19 In the current study, conductive hearing
impairment was found in 1 patient (1.54%).
Sensorineural hearing impairment was reported
by Triantafyllou,et al. in 12 patients (36.66%) from 44
patients,22 whereas other studies reported sensorineural hearing impairment in all of patients with hearing
impairment by BAEPs examination.17-19 Previous stud-
169
ies by conventional audiometry, demonstrated sensorineural hearing impairment was higher compared to
conductive hearing impairment 4,6,8-12 Sensorineural
hearing impairment in the current study was demonstrated in 94.74% patients from all of hearing impairment as well as the previous studies. The low prevalence of conductive hearing impairment compared to
sensorineural hearing impairment in this study and other
BAEP studies, probably as the result of high transfusion regimen that was performed in patients study.
Muhidin demonstrated 60 patients with mean post
transfusion Hb level was 12.43 (SD 0.99) g/dl.23 Iskandar
suggested that with high transfusion regimen, the bone
marrow would not became hyperactive and the bone
marrow disorders would not be found.24
Conductive/sensorineural hearing
impairment according to grade of hearing
impairment
Regarding the grade of hearing impairment as shown
on Table 7, moderate sensorineural hearing
impairment is more frequent and found in 47.39% from
all hearing impairments. These results are similar with
the previous studies.4,8 Whereas conductive hearing
impairment is only found in 1 patient as moderate
conductive hearing impairment.
Regarding to the BAEP, prolonged I-III interpeak latency is demonstrated in 1 patient with moderate bilateral
sensorineural hearing impairment, whereas prolonged I-III and
I-V interpeak latencies are demonstrated in 1 (1.54%) patient, with moderate unilateral sensorineural. Prolonged I-III
interpeak latency demonstrates defect in brainstem auditory
conduction system between N.VIII close to the cochlea and
lower portion of the pons.14,25-27 Whereas prolonged I-III and
III-V interpeak latencies demonstrates diffused lesion in
brainstem auditory pathways.27 This findings are different with
Zafeiriou et al, that found prolonged I-V interpeak latency in
25% patient and prolonged I-III in 10% patient with sensorineural hearing impairment that estimated as a result of ototoxic effect of DFO.19 Prolonged I -V interpeak latency demonstrates several dysfunction of acoustic nerve or brainstem,
but the localization of the lesion could not be specified.25
To sum up the study, we have shown that the
prevalence of hearing impairment in thalassemia major was 29.2%. There is no sex difference in patient’s
hearing impairment and it is mostly found in age group
between 7 to 12 years. Moderate to severe unilateral
sensorineural hearing impairment are more frequently
170
Paediatrica Indonesiana
found. Prolonged interpeak latency is found in 2 patients, indicating dysfunction in brainstem auditory
pathways. All of the patients were without symptoms
of hearing impairment. Following this study result,
BAEP is expected to be applied every six months in
thalassemic patient without hearing problems and
more frequently in those with problems.
Acknowledgments
Sincere thanks is due to Dwi Putro Widodo,M.D., of the Department of Child Health, Medical School, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, for his assistance
in brainstem auditory evoked potential investigation.
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