Studies on Pediatric Patients with

Absent Auditory Brainstem Response (ABR)

Later Components
Makiko Kaga, MD, Toshikazu Murakami, MD, Haruko Naitoh, MD
and Kenji Nihei, MD

Eleven pediatric patients with only wave I or waves I and II of their ABR were clinically analyzed. The clinical diagnoses
of these patients were as follows: 1) anoxic encephalopathy in two cases; 2) neonatal asphyxia in one; 3) infantile
Gaucher's disease in one; 4) mitochondrial encephalomyopathy in one; 5) suspected Pelizaeus-Merzbacher disease in
three; 6) degenerative disease of unknown etiology in two (presumptive diagnoses were progressive supranuclear palsy
and dentate-rubro-pallido-Luysian atrophy); and 7) infantile spasms with congenital malformation of the brain and
bones in one. The incidence of the patients with this type of ABR abnormality was 0.67% among 1,650 of our pediatric
patients whose ABRs were examined because of audiological or neurological problems. All eleven patients showed severe
mental retardation. Nine of the eleven had convulsions and likewise, eight of eleven showed deterioration in mental and/
or motor activities. Furthermore seven of eleven had disturbed consciousness and four of these seven were in deep coma.
Other brainstem and bulbar signs and symptoms were frequently found in these patients. In our series, patients without
the later components of ABR manifested marked neurological abnormalities inside and outside the brainstem. Key
Words: Auditory brainstem response, evoked potentials, auditory, pedilltric neurological disease, anoxia, brain death,
Pelizaeus-Merzbacher disease, degenerative disease of central nervous system.
Kaga M, Murakami T, Naitoh H, Nihei K. Studies on pediatric patients with
absent auditory brainstem response (ABR) later components. Brain Dev 1990;12:380-4

Auditory brainstem response (ABR) is a stable and

reproducible examination that employs strict recording
conditions. The presence of wave I is essential for the neurological evaluation of retrocochlear abnormalities. The
absence or disappearance of the later components of ABR
are found in cases of brain death [1, 2] , Pelizaeus-Merzbacher disease (PMD) [3,4], metachromatic leukodystrophy [5], brainstem tumor, maple syrup urine disease [6]

From the National Center of Neurology and Psychiatry, National

Institute of Mental Health, Ichikawa, Chiba (MK); Department of
Pathology (Mejirodai Campus), The University of Tokyo, Tokyo
(TM); and Department of Neurology, National Children's Hospital,
Tokyo (HN, KN).
Received for pUblication: September 27,1989.
Accepted for publication: March 9, 1990.
Correspondence address: Dr. Makiko Kaga, National Institute of
Mental Health, National Center of Neurology and Psychiatry,
1-7-3, Kohnodai, Ichikawa, Chiba 272, Japan.
This paper was read at the tenth biennial meeting of the Electric
Response Audiometry Study Group held at Charlottesville,
Virginia, USA, on Aug. 1987.

and adrenoleukodystrophy [7]. In pediatric practice, this

type of ABR abnormality is relatively rare. In this paper,
the authors describe the clinical analysis of such patients.

SUBJECTS AND METHODS

Subjects were patients whose ABR showed only wave I or
waves I and II at some point in their clinical course. Highintensity click stimuli were used for the examination. The
settings of parameters has already been described in a
previous paper [8].

RESULTS
Eleven of 1,650 patients were found to have this type of
ABR abnormality among our pediatric patients whose
ABRs were examined because of audiological and/or
neurological problems. An incidence was about 0.67%
among our ABR examined popUlation. The clinical diagnoses of these patients are as follows (Figures in the
parenthesis are the numbers of patients with the same
disease whose ABRs were examined by us): 1) anoxic

encephalopathy in two cases (14); 2) neonatal asphyxia

in one (87); 3) infantile Gaucher's disease in one (1);
4) mitochondrial encephalomyopathy in one (16); 5)
suspected Pelizaeus-Merzbacher disease in three (3); 6)
degenerative disease of unknown etiology in two (presumptive diagnoses were progressive supranuclear palsy
(1) and dentate-rubro-pallido-Luysian atrophy (1)) and
7) infantile spasms with congenital malformation of the
brain and bones in one (1).
We observed anoxia-related disorders (1) and (2) in
three patients, all of whom were in deep coma after the
anoxic event.
Case 1 was a girl aged 7 months (Fig 1) who was floppy, mentally retarded and had tonic convulsions. ABR
was almost normal. She suddenly became apneic, suffered
cardiopulmonary arrest, was comatose and showed no
brainstem reflexes. The second ABR recording, done two
days after cardiopulmonary arrest, showed only wave I
in the right lead. This patient died 4 days after this
recording.
Case 2 was a boy aged eight months who was found
suffocated [9]. Energetic cardiopulmonary resuscitation
was done for more than 30 minutes, and his heart eventually began to beat again. The first ABR recording was
done one week after the anoxic event. At this time, ABR
showed only wave I and a questionable wave II. There
were no auditory middle and long latency responses or
visual evoked response. Repeated examinations every one
to three months showed the same results. He died eight
months after the accident.
Case 3 was a newborn (Fig 2) who was delivered by
cesarian section because of prolapse of the cord and premature detachment of the placenta. Her Apgar score was
only 1. Assisted ventilation has been necessary for six
months since birth. Fig 2 shows her ABR recordings at
1 and 2 months of age. Clinical symptoms were not so
different between the two recordings.
.
Case 4 had infantile Gaucher's disease [8]. His disease
progressed steadily and ABR showed deterioration. He
died when he was 1 year and 4 months of age. Autopsy
revealed well preserved myelinated structure of the brainstem. The nerve cells of the auditory pathways were
relatively well preserved.
Case 5 had mitochondrial encephalomyopathy [10].
The clinical history has already been reported.
Case 6, 7 and 8 were boys who were suspected of having had PMD (Fig 3). They showed similar clinical signs
and symptoms, namely mental retardation, trunkal hypotonia with later spasticity of the lower extremities, and
congenital pendular nystagmus. No regression was confirmed during five years of observation. Hearing acuity
was normal in all three patients by the conditioned response audiometry.
Case 9 was suspected of having progressive supranuclear palsy (Fig 4). The age of onset was 8 years. The

female

7m

9.

o.~v

1111sec

Fig 1 ABR of case 1. Mental retardation with epilepsy.

fe:sale

IICUT

J "nth

2 .onths

O.Is.y

L
I"se:

Fig 2 ABR of case 3. Severe neonatal asphyxia.

4.oDcb.

II.oIlCh.

~~

~l
2m...c

Fig 3 ABRs of cases 6, 7 and 8. Suspected Pelizaeus-Merzbacher

disease.

Kaga et al: Absence of later ABR components 381

initial symptoms were a tendency to fall and waddling

gait. His disease has been slowly progressive. Head control was lost and the patient now is bed-ridden, though his
mentality has been less affected than motor activity.
Speech is very slow and articulation is disturbed. External
strabismus, ptosis of the eyelids, gaze nystagmus, limitation of ocular movements, dysphagia, fasciculation of the
tongue and accentuated deep tendon reflexes were noted.
However, oculocephalic response was elicited.

male.

Progressive supuranlo/Clear palsy susp

RIGHT

LEFT
I

ISy 5m

16y 8m

O.2YV

lltsec

Fig 4 ABR of case 9. Suspected progressive supranuclear palsy.

.1e.

Case 10 was a 15-year-old boy suspected of having

Dentate-rubro-pallido-Luysian atrophy (Fig 5). Mild mental retardation was found when he was 3 years old. Gait
disturbance began from 4 years old. He has suffered from
intractable epilepsy since the age of 5 years. Deterioration
in mental and motor activities progressed slowly. Involuntary movements including tremor and myoclonus began
when he was 9 years old. He has a decorticate posture. He
underwent tracheostomy and on tube feeding. Photostimulation readily provokes myoclonus and clinical
seizures.
Case 11 (Fig 6) was a boy whose chief complaint was
corrective surgery for an anomaly of the tarsus. He was a
product of healthy parents. His birth weight was 4,400 g
at 40 weeks gestation. His Apgar score was 1 for 1 minute
and 5 for 5 minutes. He had congenital arthrogryposis.
Infantile spasms began when he was two months old.
ABR showed only wave I from the first recording when he
was one month old. This patient also had hypoplasia of
the cerebellar vermis and partial agenesis of the corpus
callosum.
The clinical fmdings of these patients are summarized
in Table 1. All eleven of the patients showed severe
mental retardation. Nine of eleven had convulsions and
likewise, eight of eleven showed deterioration in mental
and/or motor activities; seven of eleven had disturbed

DRPLA susp

Table 1 Clinical findings of the patients

LEFT

13y Zno

141 ,.

D.3uV

L
',,0<

Fig 5 ABR of case 10. Suspected dentaterubro-pallido-Luysian

astrophy.

male

RI

1 ma
4 ma

O.2UVL
Im.ec

Fig 6 ABR of case 11. Infantile spasms with congenital arthrogryposis and brain anomaly.

382 Brain & Development, Vol 12, No 4,1990

Major neurological fmdings

Mental retardation
Convulsions
Consciousness disturbance
(in deep coma
Deterioration
Brainstem and bulbar signs and symptoms
Light reflex absent
Corneal reflex absent
Oculocephalic response absent
Ciliar reflex absen t
Restricted ocular movements
Nystagmus
Respiratory disturbance
(on mechanical ventilation
Dysphagia
Gag reflex absent
Responses to the sound stimuli
None
Diminished
Normal
I or I and II waves only
From the first recording
Serial recordings effective

11/11
10/11
7/11
4/7)
8/11
4/11

4/11
4/11
4/11

4/11
4/11
5/11
4/5)
7/11
3/11
4/11

3/11
4/11
5/11
6/11

consciousness and four of these seven were in deep coma.

Three of the patients died four days, six months and eight
months, respectively, after they showed this type of ABR
abnormality. Light reflex, corneal reflex, oculocephalic
response, ciliar reflex, ocular movements, presence of
nystagmus, respiratory abnormality necessitating mechanical ventilation, and swallowing reflex were examined.
Many patients showed abnormalities on these examinations.
By conventional audiometry, hearing acuity was well
preserved in four patients. The hearing threshold was
elevated in another three patients, and the fmal four
patients showed no response to sound stiniuli.
Serial recordings revealed this type of ABR abnormality in six patients.
COMMENTS
In general, we cannot diagnose patients from the shape of
the ABR However, diagnosis may be possible in PMD
because of its characteristic ABR configuration (wave I or
I and II only from the early stage of the disease) and
similar clinical fmdings. The diagnosis of PMD is done by
autopsy findings. However, when compared with other
types of leukodystrophy, ABR abnormalities in PMD are
found from the early stage of the disease, and this may be
compatible with the pathological myelin dysgenesis found
in early infancy.
Case 11, showed this type of ABR abnormality at an
early stage, but the clinical findings were different from
those of suspected PMD. There is also possibility about
this type of ABR abnormality in birth asphyxia. However,
as the patient had signs of the cerebral/cerebellar dysgenesis and skeltal abnormalities, it was unlikely that his abnormal ABR derived merely from aspyixia. He has been
followed up without defmitive clinical diagnosis.
Wave I is relatively strong and tends to be present until
the critical stage of brainstem death [1]. Sohmer et al
[11-13] experimentally demonstrated the persistence of
wave I in anoxia induced by decreased cerebral perfusion
pressure accompanied by normal mean arterial pressure.
If both pressures are depressed, ABR and cochlear microphonic potential disappears at the same time. Thus, the
minor pressure difference between the cochlea and the
cerebrum is thOUght to be a major reason for the persistence of wave I. Although very rare, it is well known
that "brain death" and highly abnormal ABR in infants
[14] are possibly reversible. There is a report ofamotor
vehicle accident patient with only wave I ABR who recovered with only minor neurological abnormalities [15].
In our series, two out of 14 patients with severe anoxic
encephalopathy showed this type of ABR abnormality
and subsequently died. However, since autopsy could not
be performed, the brainstem lesions could not be confirmed pathologically.

The order of loss of ABR waves in coma is different

from disease to disease. For example, in hypothermia
[16] and hydantOin intoxication [17], waves I and V are
the last ones to disappear, but in high dose barbiturate
coma [18], the shape of ABR itself is normal, but with
prolonged latencies of all waves. The mechanism of this
difference has not been clarified. Changes in ABR and
pathological correlates mayor may not be pararell [7, 8].
Brainstem and bulbar signs and symptoms described in
our patients are not directly related to the auditory pathway. Most reflexes, such as light reflex, take place above
the level of the entrance of acoustic nerve to the brainstem. Ascending pathway merely runs near the reflex
circuit. However, because ABR is a stable response, its
loss usually indicates a severe pathological process in the
brainstem auditory pathway.
Moreover, the incidence of major neurological abnormalities such as mental retardation and convulsions were
extreamly high in such cases. These are related to cortical
but not to brainstem function.
In our series, patients without the later components of
ABR manifested marked neurological abnormalities both
inside and outside the brainstem.

REFERENCES
1. Star A. Auditory brain-stem re~ponses in brain death. Brain
1976;99:543-54.
2. Hall JW, Mackey-Hargardine JR, Kim EE. Auditory brain'stem response in determination of brain death. Arch OtolaryngoI1985;111:613-20.
3. Ocks R, Markand 0, DeMyer WE. Brainstem auditory evoked
responses in leukodystrophies. Neurology 1979; 29: 1089-93.
4. Shiomi M, Ookuni H, Sugita T. Auditory brainstem response,
CT and MR imaging in a family with classical type PelizaeusMerzbacher disease (in Japanese). No To Hattatsu (Tokyo)
1989; 19:210-15.
5. Davis SL, Aminoff MJ, Berg BO. Brainstem auditory evoked
potentials in children with brain-stem or cerebellar dysfunction. Arch Neurol 1985;42: 156-60.
6. Chen YJ, Kurokawa T, Mitsudome A, et al. Brainstem auditory evoked potentials in children with neurodegenerative
diseases. EurJ Pediatr 1986; 145:471-4.
7. Kaga K, Tokoro Y, Ushijima H. The progress of adrenoleukodystrophy as revealed by auditory brainstem evoked
responses and brainstem histology. Arch Otorhinolaryngol
1980;228:17-27.
8. Kaga M, Azuma C, Imamura T, Murakami T. Auditory brainstem response (ABR) in infantile Gaucher's disease. Neuropediatrics 1982;13:207-10.
9. Kaga M, Sugiura M, Naitoh T, Kawano T, Nihei K. Auditory
evoked potentials after anoxic-hypoxic events (in Japanese).
Shonika Shinryo (Tokyo) 1987;50:1041-45.
10. Kaga M, Naitoh H, Nihei K. Auditory brainstem response in
Leigh's syndrome. Acta Paediatr Jpn (Tokyo) 1987; 29:
254-60.
11. Sohmer H, Gafmi M, Havatselet G. Persistence of wave I of
auditory nerve brain-stem potentials in ischemia. Electroencephalogr Clin Neurophysiol 1984;58:65-72.
12. Sohmer H, Freeman S, Malachi S. Multimodality evoked

Kaga et al: Absence of later ABR components 383

potentials in hypoxemia. Electroencephalogr Qin Neurophysiol 1986;64:328-333.

13. Sohmer H, Freeman S, Gafini M, et al. The depression of the
auditory nerve-brain-stem evoked response in hypoxaemiamechanism and site of effect. Electroencephalogr Clin Neurophysiol 1986;64:334-8.
14. Dear PRF, Godfrey DJ. Neonatal auditory brainstem response cannot reliably diagnose brains tern death. Arch Dis
Child 1985;60: 17-9.
15. DeMeirleir U, Taylor MJ. Evoked potentials in comatose
children: auditory brainstem responses. Pediatr Neurol

384 Brain & Development, Vol 12, No 4,1990

1986;2:31-4.
16. Kaga K, Takiguchi T, Myoukai T, Shiode A. Effects of deep
hypothermia and circulatory arrest on the auditory brainstem responses. Arch OtorhinolaryngoI1979;225: 199-205.
17. Hirose G, Kitagawa Y, Chujo T, et al. Acute effects of
phenytoin on brains tern auditory evoked potentials: clinical
and experimental study. Neurology 1986; 36: 1521-4.
18. Sutten LN, Frewen T, Marsh R, et al. The effects of deep
barbiturate coma on multimodality evoked potentials. J
Neurosurg 1982;57: 178-85.