Pediatric applications of serial auditory brainstem and middle-latency evoked response recordings

International Journal of Pediatric Otorhinolaryngology, 9 (1985 ) 2,01- 218

201

Elsevier POR 00314

Papers

Pediatric applications of serial auditory brainstem and middle-latency evoked response recordings James W. Hall III 1, Denice P. Brown 3 and Judy R. Mackey-Hargadine 2 I Department of Otolaryngology- Head and Neck Surgery and 2 Dioision ofNeurosurgery, Unioersity of Texas Medical School Houston, TX 77030 and 3 Audiology Seroice, Hermann Hospital Houston, TX 77030 (U.S.A.) (Received December 17th, 1984) (Revised March 16th, 1985) (Accepted April 7th, 1985)

Key words: auditory brainstem response - - auditory middle-latency response - brain - evoked responses - head injury - hearing - hydrocephalus - hyperbilirubinemia - intracranial pressure, ICP intra-operative monitoring - neonate - ototoxicity - 40 Hz response

Summary

Serial auditory brainstem (ABR) and middle-latency (AMR) response recordings were made for 12 children (8 male, 4 female) ranging in age from 2 weeks to 10 years. A total of 40 ABR and 32 AMR assessments were carried out at bedside in varied hospital environments, including a pediatric intensive care unit (ICU), a neonatal ICU and an operating rooin. Clinical entities were distributed as follows: acute, severe head injury (5), hydrocephalus (2), meningomyelocele (2), hyperbilirubinemia (1), ototoxic drug overdose (1), severe developmental delay (1). Auditory evoked responses were applied in monitoring peripheral and central auditory system status, and contributed to medical, surgical and audiologic management. Abnormalities of the ABR were reversed in some children, such as those with hydrocephalus, with medical or surgical therapy. In other cases, such as a hyperbilirubinemic child, a marked ABR abnormality apparently reversed spontaneously. We present five cases to illustrate diverse applications of serial auditory evoked response measures in children.

Correspondence: J.W. Hall III, Department of Otolaryngology-Head and Neck Surgery, University of Texas Medical School, 6431 Fannin, Houston, TX 77030, U.S.A. 0165-5876/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)

202 Introduction

In the p a s t d e c a d e , a u d i t o r y e v o k e d r e s p o n s e s ( A E R s ) have b e e n a p p l i e d clinically in v a r i e d p o p u l a t i o n s of c h i l d r e n a n d adults. Besides a u d i t o r y assessment, A E R s m a y also c o n t r i b u t e to the e v a l u a t i o n of c e n t r a l n e r v o u s i n t e g r i t y in severely h e a d - i n j u r e d c o m a t o s e p a t i e n t s [2,16,17,24-29,42,44,46,54,58,65,69]. W i t h the exception of a c c o u n t s o f i n t r a o p e r a t i v e m o n i t o r i n g [10,18-20,46], the e m p h a s i s o f clinical studies has b e e n o n the d e s c r i p t i o n of a u d i t o r y status w i t h A E R s r e c o r d e d in a single test session. Recently, we r e p o r t e d o n the use o f serial A E R m e a s u r e m e n t s in m o n i t o r i n g n e u r o l o g i c status o f c o m a t o s e b r a i n - i n j u r e d a d u l t s [25,27-29,43]. In this p a p e r , we d e s c r i b e the a p p l i c a t i o n o f serial A E R m e a s u r e m e n t s in a g r o u p o f c h i l d r e n w i t h diverse a n d d y n a m i c p e r i p h e r a l a n d c e n t r a l a u d i t o r y p a t h o l o g y . H e a r i n g i m p a i r e d c h i l d r e n u n d e r g o i n g r o u t i n e f o l l o w - u p A E R e v a l u a t i o n s are e x c l u d e d f r o m the study. W e i l l u s t r a t e d i f f e r e n t a p p l i c a t i o n s of serial A E R m e a s u r e m e n t s with five case reports.

Methods

Subjects were 12 c h i l d r e n each o f w h o m u n d e r w e n t serial (two o r m o r e ) A E R a s s e s s m e n t s as a clinical service b y A u d i o l o g y Service of the H e r m a n n H o s p i t a l . TABLE I CHARACTERISTICS OF SUBJECTS UNDERGOING SERIAL ASSESSMENT OF AUDITORY BRAINSTEM RESPONSE (ABR) AND AUDITORY MIDDLE-LATENCY RESPONSE (AMR) Subject

Age *

Sex

Clinical entity hydrocephalus hyperbilirubinemia ototoxic drug overdose acute, severe head injury posterior fossa cyst developmental delay acute, severe head injury acute, severe head injury acute, severe head injury acute, severe head injury hydrocephalus myelomeningocele; hydrocephalus

Number of tests ABR

1 2 3 4

LN RH KP AF

1 month 2 weeks 2 months 2

F M F M

5 6 7

MM JR RA

4 11 months 6

M M M

8

BK

2

M

9

LP

3

F

10

KM

10

M

11 12

HB RS

3 months 6 weeks

F M

* Chronologic age in years (unless otherwise noted) at initial assessment

AMR

3 3 6 3

1 2 6 2

3 2 3

3 1 3

2

2

3

3

4

4

2 6

1 2

40

32

203 Characteristics of the subjects are summarized in Table I. There were 8 males and 4 females. Age at initial testing ranged from two weeks to 10 years. Five subjects were, severely head-injured and comatose during AER assessment. AERs were stimulated, measured and recorded with commercially-available instrumentation (Nicolet CA-1000/DC-2000 or Nicolet Pathfinder II). All AER assessments were carried out at bedside or in the operating room by the first or second author (J.W.H. or D.P.B.). Stimuli were clicks of 0.1 ms duration presented monaurally (right and left ears) at a rate of 21.1/s (ABR) or 11.1/s (AMR) with TDH-39 earphones and MX-41/AR cushions enclosed within aural domes coupled to circumaural pads. The neural signal was detected simultaneously with four electrode arrays, as described in detail in a recent publication [26], and filtered at settings of 30-3000 Hz (ABR) and 5-1500 Hz (AMR), whenever possible, or 150-3000 Hz (ABR) and 30-100 Hz (AMR) when recordings were confounded by measurement artifact. Interelectrode resistance was always less than 5000 ohms.

Results

Clinical experience ABR findings and their contribution to management of the 12 children are summarized in Table II. In each case, serial auditory evoked response data were used in clinical decision-making. With three children, AER information was most helpful in developing a plan for audiologic rehabilitation. Subject 2 (R.H.) was hyperbilirubinemic when initially assessed at bedside in the nursery at the age of two weeks. There were no AERs under any stimulus or measurement condition, even at high intensity levels with air-conduction stimulation (up to 95 dB HL, Re: adult click threshold) and with bone-conduction stimulation (up to 50 dB HL). We recommended reassessment in three months. ABR audiometry, at that time, showed evidence of a mild (30 to 35 dB) sensorineural hearing impairment on the right, and a severe impairment (55 to 60 dB). on the left (in the 1000 to 4000 Hz region). Brainstem transmission times were normal. This pattern of findings was supported by immittance audiometry, including acoustic reflex measures. Ten months later, ABRs to air-conducted stimuli were observed at prolonged absolute latency values at 35-40 dB, bilaterally, and an ABR to bone-conducted signals was present down to 15 dB HL, suggesting a mild conductive hearing loss. This impression was supported by immittance audiometry. The child was then referred for otologic management. In contrast, ABR audiometry for subject 10 (L.P. in Tables I and II) consistently showed evidence of a severe, bilateral hearing impairment following severe head trauma. Following otologic management of a middle ear abnormality, the patient continued to show ABR evidence of severe sensorineural impairment. Two weeks post-injury, behavioral audiometry in the sound field responses at 80 dB HL for broad band noise, and 75 dB HL for 250 Hz and 95 dB HL for 500 Hz pure-tone stimulation. There were no other behavioral responses to sound, and again no ABR. Upon hospital discharge, the patient was enrolled in a local school for the deaf. The patient will return for follow-up auditory assessment and otologic examination.

204 TABLE 11 SUMMARY OF FINDINGS AND CLINICAL APPLICATIONS OF SERIAL AUDITORY BRAINSTEM RESPONSE (ABR) AND MIDDLE-LATENCY RESPONSE (AMR) FOR 12 SUBJECTS Refer to Table I for subject characteristics Subject

Serialfindings

Application

1 LN*

changes in ABR related to ventricle size by ultrasonography emergence of an ABR (including Wave 1) within the first 4 weeks post-partum consistent evidence of bilaterally normal . auditory sensitivity and brainstem function by ABR, and abnormal AMR , reversal of marked ABR abnormality and emergence of AMR in deep coma transient ABR abnormality intraoperatively; normal ABR, AMR, 40 Hz response post-op no ABR by EEG lab; normal auditory sensitivity but abnormal CNS by follow-up ABR and AMR consistent evidence of brainstem integrity but developing peripheral auditory deficit by ABR in coma marked deterioration of ABR (increased interwave latencies) bilaterally in coma consistent evidence of bilateral posttraumatic, severe auditory sensitivity deficit by ABR in coma, with subsequent return of auditory function consistent evidence of brainstem integrity (ABR) but thalamic/cortical dysfunction (AMR) in coma changes in ABR related to ventricle size by ultrasonography; resolution of ABR abnormality improvement in auditory sensitivity and emergence of brainstem components of ABR within first year of life

influenced neurosurgical management

2 RH 3 KP*

4 AF 5MM* 6JR* 7RA

8BK*

9 LP

10 KM

11 HB 12 RS

altered audiologic management •altered medical management

influenced neurosurgical management influenced neurosurgical management altered audiologic management influenced neurosurgical and otologic management influenced neurosurgical management influenced neurosurgical, otologic and audiologic management

influenced neurosurgical management

influenced neurosurgical management influenced neurosurgical, otologic and audiologic management

* Case report to follow T h e role of A E R s in children with C N S p a t h o l o g y are varied. I n our p a t i e n t group, serial A E R data were applied in n e u r o s u r g i c a l m a n a g e m e n t of c h i l d r e n with severe head injury, hydrocephalus, m e n i n g o m y e l o c e l e a n d posterior fossa cyst. M e a s u r e m e n t s were m a d e in either the pediatric or n e o n a t a l I C U , the o p e r a t i n g r o o m or at bedside, especially when the p a t i e n t ' s acute medical status p r e c l u d e d t r a n s p o r t a t i o n to our audiology test facility. A E R results were always i m m e d i a t e l y analyzed, followed b y a complete written report. These two c o m p o n e n t s of test protocol - - bedside recordings a n d p r o m p t r e p o r t i n g - - were essential to the successful a p p l i c a t i o n of A E R s in this p o p u l a t i o n . T h e three most c o m m o n factors p r o m p t i n g the request for A E R s were questions c o n c e r n i n g the extent of C N S i n j u r y

205 in deeply comatose patients, an abrupt deterioration in neurologic status a n d / o r CT-ultrasonography evidence of brainstem compression. A secondary concern in each case was information on auditory status. The use of AERs in neurosurgical management is illustrated by case reports 1, 3 and 4 which follow. Case reports Case 1: hydrocephalus The patient was a 1-month-old (1-month-premature) black female. She was discharged at two days and was reportedly thriving at home until 1 month postpartum. At that time, the patient had symptoms of an upper respiratory infection and loss of appetite for 24 h and the mother brought her to the emergency room. Upon arrival, the infant was found to be malnourished, in full respiratory arrest, cyanotic and bradycardic. She was intubated and ventilated manually, and transferred via Life Flight helicopter to the Hermann Hospital. Medical impression, following physical examination and laboratory studies, was respiratory failure and apnea secondary to hydrocephalus with elevated intracranial pressure (ICP), and probable sepsis. Computerized tomography (CT) showed marked dilation of the lateral, third and fourth ventricles, evidence of periventricular leukoencephalomalacia and a small calcific area in the subependymal region in the left lateral ventricle. Hydrocephalus with a fourth ventricle outlet disruption was considered likely. Initial AER assessment was carried out on the third day after admission. An ABR was reliably recorded at intensity levels down to 15 dB bilaterally. There was, however, an excessive prolongation of brainstem transmission times (wave I-V latency intervals were 6.96 ms on the right and 6.84 ms on the left) in comparison to age-matched normative values (+ 2.5 standard deviations is 5.00 ms) (see Fig. 1). On the first test day (11/14), the patient was lethargic, but pupils were bilaterally equal and reactive to light and there was purposeful movement to painful stimulation. CT •continued to show marked dilation of the ventricles. A ventricular line was found to be draining inadequately. Follow-up AER assessment was carried out three days later (see Fig. 1) after the ventricular drainage site was changed and additional CSF was removed. Neurologic examination showed that the patient was alert and responsive. Brainstem transmission times (wave I-V intervals) were improved bilaterally, especially with left ear stimulation (a decrease of over 1.0 ms from the initial recording). In contrast, latency of the wave I component consistently decreased across the three assessments. At the time of the final testing (see Fig. 1), the patient was alert and responsive, but she was increasingly irritable. The ventricular drainage system was in place and functioning well (85 cm3 of CSF removed in the preceding 24 h). Ultrasonography, however, showed intracerebral fluid collections, perhaps secondary to CSF leaking from the ventricular tap. Brainstem transmission time (wave I to V interval) had increased. Subsequent surgical therapy, included a ventriculo-peritoneal shunt procedure. Six weeks after hospital admission, the patient was discharged to her home. She was eating well and gaining weight. Developmental evaluation indicated normal mental development for age, but spastic quadriparesis.

206 0

Right ear

•

Left ear

1.801.60o

E

0

O ~ ~ e

~.40-

t-

g. N 6.50

_J

g~.~

o~

°

6.005.50-

o

~-._= ~ >.~o

Q. LL

.~ ~ ~

o=

0

~ '-

o~

0

o3

8°~=o "--

1>:5 > E

~ ~m o '

>~'~

~'O

o

.Sc~ E o3.E r~

I

I

I

1 (11/14)

2 (11/17)

3 (11/23)

Test session

Fig. 1. Serial auditory brainstem response latency data for 2-month-old female with marked hydrocephalus (Case 1). Note decrease in brainstem transmission time (wave I-V latency interval) associated with drainage of cerebrospinal fluid.

Comment. Evoked potential abnormalities have been associated with hydrocephalus [11,22,37,45,61,70]. Preliminary evidence suggests that serial measurement (rather than a single recording) in younger children and infants will be of most value clinically in documenting the functional effect of hydrocephalus on the CNS and in contributing to management of hydrocephalus. This presumption, however, is mainly based on studies of visual evoked potentials, which are of cortical origin. In agreement with recent investigators of the ABR in hydrocephalus [37,45], we have observed that brainstem abnormalities, such as prolongations in the wave I-V interval, may be reversible. The pathophysiologic mechanism is not known, although compression of the auditory fiber tracts in the brain stem with increased CSF pressure has been suggested [45]. Nonetheless, multiple assessments are clinically warranted, and useful in monitoring CNS status and evaluating the effectiveness of therapy. It is particularly important to rule out significant peripheral auditory deficits in hydrocephalic infants and children, as sensorineural hearing loss appears to be more common in this population [37].

207

Case 2: ototoxicity The patient was a six-week-old Latin-American female with end-stage renal disease secondary to acute tubular necrosis related to birth asphyxia. AER assessment was initially carried out in the evening of the 45th day after birth, within 6 hours of an inadvertant administration of 10-times the prescribed dosage of an ototoxic drug (Vancomycin), which was treatment for gram positive cocci found in blood samples. Within 12 hours of the overdose, an exchange transfusion was started. Vancomycin blood level was 67.4/~g/ml one hour later and 4.9/~g/ml 11 h later. At the initial test session, and a series of five subsequent assessments (4 within the first 72 h after the overdose), we consistently recorded a well-formed ABR bilaterally at intensity levels down to 25 dB. Brainstem transmission times were within the age-matched normal range. AMR and 40 Hz responses were also measured at each test session. There was an apparent AMR when a neural filter setting of 30 to 100 Hz was employed. However, at our customary less-restricted filter setting of 5-1500 Hz, no AMR Pa component was observed. A distinct Na component was recorded at both filter settings. Amplitude of the 40 Hz response (stimulus rate of 39.7/s) was comparable to the voltage difference between ABR wave V and AMR Na (0.53/~V). Comment. Vancomycin (vancomycin hydrochloride) is a glycopeptide antibiotic. It has known ototoxicity. Impairment of renal function can lead to delayed excretion and high blood levels which are associated with increased drug toxicity. Based on experience with other antibiotics, it is likely that drug-related hearing loss may progress after cessation of treatment. With Case 2, AER assessment was requested immediately following an inadvertant overdose of the drug. Immediate definition of auditory sensitivity by AERs was important for several reasons. First, early symptoms of ototoxicity could not be assessed by traditional methods. Second, valid information on normal auditory sensitivity status contributed to the decision regarding an exchange transfusion. Follow-up documentation of normal auditory sensitivity status contributed to decisions regarding further medical treatment, and audiologic management. The absence of an AMR bilaterally suggested serious higher-level auditory CNS dysfunction, even through there appeared to be peripheral and brainstem auditory integrity. This finding was consistent with CT evidence of bila;-eral temporal lobe damage. Experimental and clinical evidence supports the applit:ation of ABR in the assessment of auditory function during medical therapy with ototoxic drugs [5-7,21,48]. Case 3: intraoperative monitoring The patient was a 4-month-old male who was admitted for evaluation of macrocephaly. At 6 weeks of age the child had undergone surgery for removal of an occipital meningoencephalocele. The mother had noted that recently the child had been sleeping more and showed a downward deviation of his eyes. He had not complained of vomiting, decreased appetite or other signs of increased ICP. Physical examination revealed evidence of significant macrocephaly. Cranial nerve function was intact by clinical examination. His tone was somewhat decreased, reflexes in the lower extremities were increased and plantar responses were extensor

208

bilaterally. CT scan showed a large posterior fossa cystic lesion extending into the quadrigeminal cistern area. There was evidence of marked dilation of the lateral third ventricle. The fourth ventricle was not significantly enlarged. According to a report of the EEG laboratory (Neurology Service), the auditory brainstem evoked response was "abnormally prolonged through the pontine region bilaterally as well as disruption in the rostral pons, more so on the right". The clinical impression was significant hydrocephalus suggestive of an extra-axial or arachnoid stenosis. Medical plan included a ventriculostomy with Metrizamide injection to assess communication of the fourth ventricle and the cyst. Within the week, the patient underwent a posterior fossa craniectomy with removal of a subarachnoid cyst. Recovery was complicated by aseptic meningitis and CSF leak from the wound. He was discharged one month postoperative in good condition. Intraoperative ABR recordings are illustrated in Fig. 2. Measurements were made continuously before, during and after the three hour procedure (a total of 110 averages of 1000 stimuli each) for monaural stimulation (left ear). A well-formed and reliably-recorded ABR was consistently observed. Temperature was 98°F ( + / 0.5 °) throughout surgery. Preoperative (baseline) and initial intraoperative recordings showed an abnormal prolongation of rostral (wave III-V) brainstem transmission time. At 30 min after the opening (10 : 15), marked prolongation of both wave I-III and III-V brainstem transmission times was noted, and associated with transiently reduced arterial blood pressure (systolic 78 mmHg vs greater than 90 mmHg before and after). This abnormality subsequently reversed and for the remainder of the surgery, and post-operatively, ABR interwave latency values were within age-matched normal limits. Comment. Monitoring auditory and neurologic status intraoperatively with evoked responses has been recently described with increasing regularity [1,10, 18-20,30,31,39,41,47,56,57,68]. This clinical experience is predominantly with adult patients undergoing intracranial surgery, usually for acoustic tumors. In these cases, the ABR is typically used as an intraoperative indicator of auditory function in an attempt to reduce avoidable surgically-induced damage to the eighth nerve a n d / o r brainstem auditory structures. Based on large-scale studies, clinical feasibility and utility of intraoperative monitoring in general appears to be greater for the auditory evoked responses, than for visual or somatosensory evoked responses [18,56], although the applicability varies depending on the type and anatomic region of the surgery. Intraoperative alterations in the AERs have been associated with mechanical compression (such as retraction) of the eighth nerve, brainstem or cerebellum or, conversely, decompression of these structures, and also blood gas levels (e.g. PaO2) [10,18,20,56,57] and, the introduction of air into CSF spaces [68]. These studies, and our clinical experiences, provide ample evidence that AER abnormalities can be reversed. Intraoperatively, the reversal of ABR latency prolongations, or even the reappearance of an ABR, has been attributed to repositioning of retractors, changing the surgical dissection approach and reinstating cochlear/eighth nerve or brainstem vascular sufficiency, by either direct techniques such as microvascular decompression or systemic manipulations, such as raising arterial blood pressure. Thus, AERs

209 I

III Time

ABR I-ill

Latencies(msec) III-V

Comments

9:26

1.92

2.52

Baseline

9:44

2.10

2.82

Opening

10:02

2.16

2.82

End CSF Drain

10:15

2.58

3.21

10:32

2.07

2.40

10:44

2.04

2.46

10:58

1.92

2.46

11:25

1.98

2.28 (#1) 3.96 (#2)

11:58

1.98

2.43

12:23

1.92

2.40

Cyst Opened

Closing

Stimulus

Fig. 2. Auditory brainstem response recordings for a 4-month-old male during surgical removal of a large posterior fossa cystic lesion (Case 3). Note transient increase in caudal (I-III) and rostral (III-V) brainstem transmission times at 10 : 15 in the procedure.

offer a feasible means of continuously and non-invasively assessing auditory/neurologic function in patients under general anesthesia, and thereby influencing intraoperative strategy and postoperative outcome. As we demonstrated with Case 3, this concept can be applied with success in children, as well as adults. Case 4: acute, severe head injury

A two-year-old male sustained a closed head injury (CHI) when he fell from the

210

back of a chair. Four days earlier, he reportedly fell out of a wagon, striking his head on concrete with loss of consciousness and complaint of headaches, but a physical examination three days later by his pediatrician was neurologically unremarkable. Immediately after the second accident, he was alert and crying, but then he became limp and unconscious. He was taken to a medical clinic, where GCS was 6 and pupils were fixed and dilated. He was never hypotensive. Within 30 minutes, he was transferred via Life Flight helicopter to the Hermann Hospital. Upon arrival, GCS was still 6 and pupils remained fixed and dilated. Corneal reflexes and gag reflex were intact. There was decorticate posturing to deep painful stimulation. Tympanic membranes were clear. With emergency therapy, including intubation, Mannitol and hyperventilation, his neurologic status improved. Pupils were 3 mm and equally reactive and his movements became purposeful. CT showed brain swelling and compression of the perimesencephahc cistern. Posterior fossa was normal. 12 h post injury, neurologic status was improved with all brainstem signs observed. The initial AER assessment showed a well-formed ABR, with all wave components present. Brainstem transmission times were well within our normal limits bilaterally. An AMR, however, was not observed. Follow-up CT scanning and ultrasonography on the test day revealed no structural changes, and the patient's neurologic status continued to improve slowly. On the next day (post-injury day two) nuclear radiography indicated symmetric cerebral perfusion. Then, during the following three days ICP became elevated (25 mmHg) and difficult to manage with Mannitol and hyperventilation. An ICP monitor (Richmond bolt) was inserted. Repeat CT showed obliteration of the white/gray matter interface, suggesting altered autoregulation of cerebral circulation, and probable early infarction in the distribution of the left posterior cerebral artery. Still, there was no midline shift or mass effect, and the perimesencephalic cistern was well visualized. A second ABR assessment on the 5th post-injury day showed marked prolongation of the wave I to V latency intervals bilaterally, and apparent absence of an AMR. Barbiturate (pentobarbital) therapy and chemical paralysis (Pavulon) for management of elevated ICP compromised the neurologic examination, and the barbiturates confounded interpretation of the A M R findings [27,28]. The abnormal ABRs were considered evidence of probable brain ischemia, and very poor prognosis. The parents were counseled about the child's grave conditions. On the next day, there was no detectable cerebral blood flow by nuclear radiography. Life support was discontinued. Comment. AER applications in adult head-injured patients are well-documented, and varied. They include confirmation of site of lesion and level of structural coma [35,42,46,65,66,69], prognosis of neurologic outcome [2,17,46,54], monitoring neurologic status in acute, severe head injury [25,27-29,42,43,54] and determination of brain death [15,29,64]. There are, in comparison, few reports of AER findings in head-injured children [14,41,43]. Generalization of the information obtained from the adult AER studies to children is probably ill-advised, as there is significantly lower morbidity and mortality among head-injured children [4,9,38], even though patient age alone is probably not the main factor [4,13,38]. Our experience with over 250 severely head-injured adult patients [27-29,43], and data

211

reported by many others [2,17,41,52,57,59], clearly suggest that markedly abnormal ABR findings are strongly associated with poor neurologic outcome, and usually death, whereas a normal ABR on initial assessment has little prognostic value. In fact, over one-half of our series of adult patients yielding normal ABR findings within 24 h following the injury subsequently die within 30 days [27,28]. This latter relationship may not be confirmed in pediatric populations [14]. However, the principles of monitoring neurologic status with AERs are probably equally valid for severely head-injured, comatose children vs adults. When AER assessments are carried out within 48 h following severe head injury, the ABR is bilaterally normal in approximately three-fourths (73%) of our adult patients [25-29,43]. A finding consistent with brainstem integrity soon after the injury is not unexpected, as primary brainstem lesions are rare [32]. Serial AER recordings thereafter appear to offer a reliable and sensitive neurophysiologic indicator of secondary brainstem insults. Experimental investigations have recently begun to define the relationship among ICP, CPP, mean arterial blood pressure (MAP) and the ABR [45,49-51,62,63]. The pathophysiologic basis for ABR changes with increased ICP and transtentorial herniation appears to be brain ischemia associated with reduced MAP and CBF, with resultant inadequate CPP [52,62,63], rather than ICP alone. Electrophysiologic alterations in brain ischemia are closely linked to neuronal metabolic changes [3,55,67]. Clinical reports confirm this relationship, and provide further evidence that increased ICP, without reduced CPP, does not necessarily compromise brainstem function [27-29,36,42,43,51,59]. In contrast to this vulnerability to ischemic insult, the ABR may be resistant to the effects of hypoxia [62,63]. As illustrated by Case 4, presumably ischemia-related deterioration of the ABR may be the primary clinical indication of markedly-worsened CNS status, and therefore influence patient management. We emphasis that monitoring neurologic status with the ABR is most useful when initial assessments are carried out as soon as possible after the ,injury, and when there is consistent evidence of peripheral auditory integrity (presence of wave I). Case 5: severe developmental delay The patient was an ll-month-old male admitted to the Pediatric Neurology Service for evaluation of developmental delay. The term pregnancy, and labor and delivery, were unremarkable. The child was considered to have normal development until age 9 months, when the mother became concerned, Physical examination revealed marked hypotonia and microcephaly. There were no reflexes beyond a grading of 2 months of age. The patient had a mental age of 1.3 months and a motor age of 0.8 months on the Bayley Scale of Development. An ophthalmology examination showed borderline optic nerve hypoplasia, a cateract in the left eye, and suggested possible cortical blindness. CT revealed diffuse cerebral atrophy (see Fig. 3). Neurophysiologic tests were carried out by the EEG laboratory. The EEG showed multi-focal spike activity. Visual and somatosensory cortical evoked responses were not observed bilaterally. The report stated that ABRs 'are absent bilaterally'.

212

Fig. 3. Computerized tomography for an 11-month-old boy with severe developmental delay (Case 5). Note diffuse cerebral atrophy. In view of this ABR finding, the patient was referred to the Audiology Service for hearing evaluation. Behavioral audiometry in the sound field showed an eye-opening response to a noise stimulus at 80 dB, and eye-opening and head-turning responses to pure-tone stimuli of 500, 1000 and 2000 Hz at 100 dB H L but no startle response. Acoustic reflexes, measured ipsilaterally, were observed for each ear at intensity levels of 80 to 95 dB HL. Sensitivity prediction by the acoustic reflex (SPAR) [23] suggested normal pure hearing threshold levels in each ear. In combination, the results of the initial ABR, behavioral audiometry and immittance measures were discrepant. AER assessment was done at bedside. The patient received sedation, but testing was begun while the child was still active, before sleep. As illustrated in Fig. 4, the initial recordings for each ear at high intensity levels (95 and 85 dB) and restricted neural filter settings (300-3000 Hz, right; 150-3000 Hz, left) showed no apparent response, except for a possible wave I component on the right. The restricted filter settings were used to minimize the deleterious influence of the excessive measurement artifact associated with the child's movement. As he fell asleep, filter settings were expanded and recordings made at descending intensity levels. There was a reliable wave I component bilaterally for intensities down to 45 dB H L (Re: adult click threshold). A poorly-formed and grossly-delayed apparent wave V component was also observed, especially at higher stimulus intensity levels. Brainstem transmis-

213 J.R.: 11 month-old male (4/1/83) AUDITORYBRAINSTEMRESPONSE Right Ear

Left Ear 85dB (150-3000HZ)

•

I

A

65d9

I

15 ms

?

•~

"/.86 ms

I

.

8518

~ ]

65dO

45dB

15 ms

)

t Stimulus

SUmulus

Fig. 4. Auditory brainstem response recordings for Case 5. Note apparent effects of filter settings on the response morphology.

sign times (wave I to V interval) exceeded 7.00 ms. A M R recordings are illustrated in Fig. 5. An Na component was seen bilaterally, but a repeatable Pa component was only apparent with left ear stimulation. In summary, the ABR findings (wave I 80dB

80dB

(17.5 ms)

Fig. 5. Auditory middle-latency response recordings for Case 5. Note absence of repeatable Pa component with fight ear stimulation.

214 pattern) were in agreement with the ipsilateral acoustic reflex results, and ruled-out a serious peripheral auditory deficit. The ABR and AMR showed definite evidence of abnormal auditory CNS functioning. CNS dysfunction probably contributed to the elevated behavioral auditory thresholds and absent startle response. Comment. This case illustrates two main points about pediatric applications of the ABR. First, it highlights the importance of the "cross-check principle" in pediatric audiometry [33]. Definition of auditory sensitivity is particularly challenging in children with severe neurologic dysfunction. Initial ABR data obtained by the EEG laboratory were lent apparent confirmation by behavioral audiometry. Absence of a startle response [34] and limited behavioral response to sound, however, may have been secondary to brainstem dysfunction, rather than a sensorineural hearing impairment. Therefore, following our routine protocol and in an effort to gain further ear-specific information on peripheral auditory status, we also made immittance measurements. The bilateral presence of acoustic reflexes and a normal SPAR raised doubts about the validity of the initial ABR outcome, and prompted a follow-up assessment. Evaluation of auditory sensitivity with ABR wave V was invalidated by the marked brainstem abnormality. In this unfortunate patient with severe developmental delay and probable severe visual deficits, the finding of reasonably good hearing sensitivity (at least in the 1000 to 4000 Hz region) was especially important. Although the AMR abnormalities presumably reflected primary cortical deficits, [39] the evidence of a channel for auditory sensory stimulation led to a more positive outlook and aggressive approach for the rehabilitation team and parents. Second, the discrepancy between the initial and follow-up ABR evaluations point out the potential influence of measurement parameters, such as neural filter settings, and subject state (e.g. awake and active vs asleep and inactive) on ABR outcome. It appeared that lowering the high-pass filter limit from 300 and 150 Hz to 30 Hz enhanced the identification of waves I and V. Perhaps, the wider filter settings encompassed more spectral information of the ABR, including wave I [8,12]. In any event, the use of a 30 to 3000 Hz setting seemed to contribute to meaningful interpretation of the ABR.

Conclusions

Among 293 children age 10 years and younger that were referred to the Audiology Service of Hermann Hospital for AER assessment in a 22 month period, 12 underwent serial measurements for reasons other than routine follow-up of auditory status. Our experiences with this series of 12 children prompt the following general conclusions: (1) serial AER recordings at bedside in a pediatric population, including neonates, are feasible. Indeed, the capability for bedside testing in a variety of hospital environments is essential for the application of AERs with children whose acute medical status precludes transportation to an audiology test facility; (2) AER findings can contribute to acute-care medical management and long-term audiologic management of children. Information from AER measurements was instrumental in

215

decisions to institute medical therapy ranging from an exchange transfusion (see case report 2) to CSF drainage (see case report 1). Also, largely on the basis of AER outcome, children have been evaluated for amplification and enrolled in a timely fashion in programs for the heating impaired. Conversely, serious hearing sensitivity impairment has been ruled out by AER in children at risk for auditory abnormality; (3) AER abnormalities may be reversible with medical or surgical therapy (see Case 1) or spontaneously; (4) the evolution of marked AER abnormalities, in patients with CNS damage, may reflect serious brainstem pathophysiology and the need for aggressive management. Persistent abnormalities imply a poor neurologic prognosis.

Acknowledgements Wende Yellin, M.S., audiologist, Hermann Hospital, assisted in data collection. Robert A. Jahrsdoerfer, M.D., Professor and Chairman, Department of Otolaryngology-Head and Neck Surgery, University of Texas Medical School, Stephen Fletcher, D.O., and Michael E. Miner, M.D., Ph.D., Chief, Division of Neurosurgery, University of Texas Medical School contributed to patient selection.

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