Journal of

J Neurol (1982) 227:219-228

Neurology ~) Springer-Verlag 1982

Brainstem Auditory Evoked Potentials in Syndromes of Decerebration, the Bulbar Syndrome and in Central Death* N. Klug Department of Neurosurgery (Head: Prof. Dr. Dr. b.c.H.W. Pia), University of Giessen, Klinikstr. 29, D-6300 Giessen, Federal Republic of Germany

Summary. The results are reported of serial brainstem auditory evoked potentials recordings in 51 patients with decerebration and bulbar syndrome. In contrast to the stability of latencies of single components of the potential in healthy subjects, patients with decerebration syndromes show considerable instability and an increase in the latency of all the components of the potential. In 34 decerebrate patients the P-I latency and the interpeak latencies for the medullo-pontine and ponto-mesencephalic segments as well as the central conduction time were significantly increased. There was marked reduction of the amplitude of P-V and P-III and deformation of the single components of the potential with widening and smoothing. The amplitude ratios A-V to A-I and A-III to A-I were significantly decreased. The findings are interpreted as due to mesencephalic and pontine functional disturbance during decerebration. The brainstem auditory evoked potential can be used to estimate the time of brain death. Possible causes of misinterpretation are discussed. Key words: Brainstem auditory evoked potentials- Decerebration syndrome Central death - Intracranial pressure

Zusammenfassung.Anhand des Verlaufes von 51 Patienten wird das Verhalten des frtihen akustisch evozierten Potentials (BAEP) im Decerebrations- und Bulb~irhirnsyndrom sowie im Stadium des zentralen Todes beschrieben. Entgegen der ausgesprochenen intra- und interindividuellen Latenzstabilit~it der einzelnen Potentialkomponenten beim Gesunden besteht bei der Decerebration eine Latenzinstabilit~it und eine ausgepr~igte Latenzvergr6f~erung aller Potentialkomponenten. Die Interpeak-Latenzen ftir die medullopontinen und die ponto-mesencephalen Abschnitte sowie die zentrale Oberleitungszeit liegen auf~erhalb des 2-Sigma-Bereiches eines gesunden Kontrollkollektivs. Auffallend ist eine Amplitudenreduktion von P V und P I I I und eine Deformierung der einzelnen Potentialkomponenten im Sinne einer Verplumpung und Verbreiterung der Potentiale. Die beschriebenen Ver~inderungen werden als Ausdruck sowohl einer mesencephalen als auch einer pontinen funktionellen Sch~idigung im Decerebrationsstadium angesehen. * This study was supported by Deutsche Forschungsgemeinschaft, SFB 32

0340-5354/82/0227/0219/$02.00

220

N. Klug U n t e r B e a c h t u n g m ö g l i c h e r F e h l i n t e r p r e t a t i o n e n k a n n das frühe akustisch evozierte P o t e n t i a l ( B A E P ) im F i n a l s t a d i u m den eingetretenen H i r n t o d beweisen u n d im Einzelfall den T o d e s z e i t p u n k t festlegen.

R e c o r d i n g o f b r a i n s t e m a u d i t o r y e v o k e d p o t e n t i a l s ( B A E P s ) has g r a d u a l l y been i n t r o d u c e d into the r o u t i n e clinical diagnosis o f localized b r a i n s t e m lesions, systemic diseases a n d lesions o f the p o s t e r i o r fossa or cerebello-pontine angle [2, 3, 6, 9, 10, 13, 15-19, 20]. Little i n f o r m a t i o n is available a b o u t the B A E P in patients with diffuse or transverse lesions o f the b r a i n s t e m [1, 4, 5, 12]. The p r o g n o s t i c value o f B A E P in patients with c r a n i o - c e r e b r a l injuries has rarely been studied [4, 5]. B A E P s have also been used for e v a l u a t i o n o f b r a i n d e a t h [2, 14]. So far little is k n o w n a b o u t serial B A E P studies in patients with the d e c e r e b r a t i o n s y n d r o m e which is d e t e r i o r a t i n g into the b u l b a r s y n d r o m e a n d in the final stages o f b r a i n death. O u r p u r p o s e was to study whether B A E P changes in such patients c o r r e l a t e d with localized areas in the b r a i n s t e m . D e c e r e b r a t i o n can be defined as a functional s e p a r a t i o n o f the b r a i n s t e m f r o m the rostral structures, p a r t i c u l a r l y the cortex a n d the b a s a l ganglia. T h e m a i n clinical signs are c o m a a n d d i s t u r b a n c e o f vegetative regulation. T h e so-called u p p e r d e c e r e b r a t i o n [7, 8, 11] is associated with a n increase o f flexor tone o f the u p p e r a n d extensor t o n e o f the lower extremities. ' L o w d e c e r e b r a t i o n ' [7, 8, 11] is associated with increased extensor tone in all the extremities. Progressive d e c e r e b r a t i o n leads to the a p p e a r a n c e o f p a t h o l o g i c a l b r a i n s t e m reflexes. The b u l b a r s y n d r o m e follows with decrease o f muscle tone, r e s p i r a t o r y arrest a n d c i r c u l a t o r y collapse preceding b r a i n death ( c o m a dépassé).

Patients and Methods Control data were obtained from 35 healthy subjects (age 20-30 years) with normal auditory function. A total of 51 patients were studied in 161 sessions (Fig. 1). The cause ofdecerebration was brain injury in 16 cases, intracerebral haemorrhage in 10 cases, subarachnoid bleeding in 4 cases, extensive ischaemic brain infarction in 2 cases and brain tumour in 2 cases. BAEP was elicited by monaural stimulation using a click of 200 las with a frequency of 10/s. The intensity of the stimulus in the control group was 50, 60 and 70 dB in relation to the individual sensation level (50, 60, 70 dB SL) and 70-80 dB above the normal hearing level in the patients (70-80dB HL). The contralateral ear was masked with 60dB (shielded headphones Bayer DT-48). Bipolar recording was performed with surface electrodes on the ipsilateral mastoid process. The EEG signal was amplified 100,000 times and filtered with 1 kHz using a time constant of 20ms. Each side was recorded twice, averaging 2,048 signals. For recording we used the

n (Pahents)

Recordings

Decerebration - S

15

63

D e c e r . / B u l b a r - S.

19

75

Bulbar-S/Central Death

17

23

51

161

Fig. 1. Summary of 161 BAEP recordings in 51 patients

Brainstem Auditory Evoked Potentials

221

Table 1. Interpeak latencies in 35 healthy control subjects (70 auditory pathways tested). T III-T I: Extra-axial and medullo-pontine segments. TV-T I: Central conduction time (Tz). T V-T III: Ponto-mesencephalic segments dB SL

T[u-Ti (ms}

Tv-TI ( Tz ) (ms)

50

2.11±0.18

3,92 ± 0.12

1.81±0,10

60

2,12±0.17

3,91± 0.18

1.79±0,18

70

2,13 ± 0,15

3,93 ± 0.19

1.79 ± 0,12

Tv -TIII

(ms)

Table 2. Interpeak latencies in 35 adult healthy subjects and in 34 patients with decerebration 70 dB

Tm-T] (ms)

Tv-Tt (Tz) {ms)

5L

2.13_+0.15

3,93_+0.19

4L

2,51 -+ O.L,2**

4.53 -+ O.Z.7* «' 2.05-+ 0,35 *~

Tv-TIII

(ms) 1.79 + 0,12

o= 35 Healthy Adutts 70Äuditory Pathwoys (Control Grouo) n= 34 Decerebrated

Potients

{58Auditory Pothways)

myograph DA II, Tönnies Company. The latency of the single peak was calculated from the time interval between the onset of the signal and the upward directed maximum amplitude. In all the figures the dick appears 0.2 ms after the start of registration.

Results In the control group the latency for the cochlear response (P-I) at 70 dB SL was 1.88 ms (+0.15). In 34 patients with decerebration the latency of the cochlear potential was significantly increased (P < 0.01) to 2.13 ms (+ 0.34) at 70-80 dB HL. Table 1 shows that interpeak latencies are independent of different intensities of the click stimulus in the control group. Table 2 shows the results in 34 patients with decerebration. Latencies for the extra-axial and medullo-pontine segments were increased. The increase of latency was also found at the ponto-mesencephalic level and for the central conduction time (Tz). All interpeak latencies proved to be significantly increased (P < 0.01). The medullo-pontine latency was outside the 2 SD limits (considered as normal range) in 20 patients, the ponto-mesencephalic latency outside 2 SD limits in 17 patients and the central conduction time in 26 patients. Eight patients had increased interpeak latencies above the normal range in all segments. The interpretation of the amplitude of potentials is known to be difficult. We therefore used (for the evaluation of pathological changes) the amplitude relation A-III to A-I, A-V to A-I, and A-V to A-III. In accordance with the findings of other authors, the A-V to A-I ratio was markedly larger than 1; in our control group the value was 1.6.

222

N. Klug

Table 3. Amplitude relations A-III to A-I, A-V to A-I and A-V to A-III in 35 healthy subjects and 34 »atients with decerebration 70 dB

Am/Al

Av/AI

Av/Am

SL

0.91 ± 0./,4

1.60 ± 0.51

1.93 ± 0.63

n = 35 Heolthy Adu[ts (70 Auditory Pathways )

HL

0.64 t 0.35 * *

0.97 +_0.49 *~

1.97 t 1.24

n= 34 Decerebrated Patients (58 Auditory t%thways)

~!

Œ

Fig. 2. R.L. serial BAEPs in a patient with acute mesencephalic herniation. Recovery within 7 months The amplitude ratio A-V to A-I proved to be reduced to 0.97 in the patients with decerebration. The ratio A-III to A-I was also reduced (P < 0.01, Table 3). Apart from the reduction of the amplitude the majority of the potentials showed more or less pronounced deformation of the single components with widening and smoothing of single peaks. These deformations were more pronounced with the progression of the decerebration. The deformation of the peak eventually made the estimation of the latency of a single peak impossible. In the following examples serial BAEPs are illustrated in patients with transient and reversible decerebration syndrome, as weil as in patients with irreversible decerebration and the bulbar syndrome. Figure 2 shows the BAEP o f a 40-year-old patient with a tumour of the midline. The first record was obtained at the stage of mesencephalic herniation with

Brainstem Auditory Evoked Potentials

223

Fig. 3 a. CT in a patient with a traumatic (lower) decerebration syndrome and secondary pontine and mesencephalic bleeding. Bulbar syndrome and central death after 6 days

Left

8

Right

8

f 6 ~

T

~T5

5 T4

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T3

E

~

T

3

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C

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2 ~

~T1

J

0

0 0 I 2 3 4 5 6Days 0 1 2 3 /ù 5 6Days Fig.3b. Serial BAEPs in lower decerebration syndrome with secondary pontine and mesencephalic haemorrhage (some patient as in Fig. 3 a)

beginning decerebration. There was marked reduction of the amplitude o f P - I I I and P-V, while P-IV cannot be recognized. The central c o n d u c t i o n time was considerably increased, mainly in the medullo-pontine segment. P-V shows an instability of latency. After treatment with h y p e r o s m o l a r agents 2 days later, there was a tendency t o w a r d i m p r o v e m e n t but not to normalisation o f the single peak latencies. There was still an instability o f latency for P-V and to a lesser degree for P-III.

224

N. Klug ]11

q/,."X

, j'X,.,4..-, -\,8.o2/,~.oo

Io~5~v

%

~ ' ~'k, 19.02 / 8.35

-"~,

8.40

ù'-'T'~ ù'-"&,

8.48

f

~/"

\

ù.~ f

_--,-.--~ AEP 03

"J~

8.57

~'~,

9.00

~'~

9.08

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Fig.4. Serial BAEPs in the transient phase between the decerebration and bulbar syndrome. Note: The last potential in this recording is a reference signal

Seven months later, after operative treatment and clinical improvement, there was a further tendency to recovery and the latencies for single components were stable. In contrast to the first recordings we could now isolate P-IV in the patient. The instability of the single-peak latencies was seen in nearly all decerebrated patients and was particularly well demonstrated in a 20-year-old patient with a secondary haemorrhage in the pons and tegmentum after severe head injury (Fig. 3 a). For several days he had a lower decerebration syndrome and then deteriorated rapidly, developing the bulbar syndrome and the signs of central death. The clinical course correlates well with a final latency increase and loss of P-V, latency delay for P-III, followed by disappearance of P-III and finally also of P-I (Fig. 3 b). Figure 4 shows serial BAEPs of a 48-year-old patient with a spontaneous cerebellar haemorrhage with hypertension that perforated into the ventricular system. Serial BAEPs demonstrated a latency increase of P-III and P-Il and then a sequential loss of the single peaks. All patients with the bulbar syndrome in whom the study of BAEPs revealed the presence of the first component of the potential only, or sometimes with P-II, always had an isoelectric EEG and showed loss ofstructure of the brainstem on CT scan. In order to analyse the time sequence of BAEP changes at different stages of decerebration and the bulbar syndrome BAEPs were studied in cats under conditions of progressive increase of intracranial pressure (ICP). A part of an original record is shown in Fig. 5 a: a progressive increase of ICP produced by expansion of a supratentorial balloon resulted in mesencephalic herniation. The corresponding BAEP showed disproportionate increase of latency of the singte components of the potentials in the rostro-caudal direction. P-V was lost first and

Brainstem Auditory Evoked Potentials

Time

225

B \ I~~LI i [CP Pupils [ra:Hg]

11.02

11.22

l~ß, I 40 Slightlydilated

,~i~o,,~rl~,Xdd~'~~°t:~

11.54 12.04

/-~q

8

re. I,.

A I

12.23

il i~o:::::

12.24

i I J

12.26

Apnoe

~~ 1 50 Centra[Death lOm: II I 0.125~uV

I

K15 Fig. 5 a. Serial BAEPs in relation to intracranial pressure (ICP) in the cat. (Part of the original recording)

~'°°t~ ~ ~ ~ / 8~

iT5 ~ T,-,

6 ~~.-

J

J C _.J

~

"

T2

, ..iT1

2¸

O, 11.00 K15

T3

11.30

"l'ime

12100

12.30

Fig. 5 b. Graphic demonstration of the complete recording of the same cat. Relationship between BAEP and intracranial pressure

226

N. Klug

did not recover after the release of pressure. Repeated increase of ICP resulted in the abolishing of the third component of the potential, which recovered however upon the return of ICP to normal levels. After the critical tolerance level had been reached, at the time of respiratory arrest, only the cochlear response was still present. Release of the balloon at that stage did not produce recovery of the BAEP. The time sequence of changes of single potential components of one experimental animal is shown in Fig. 5 b.

Discussion

In contrast to the known marked stability and uniformity of latencies of the single BAEP components in control subjects, patients with decerebration show considerable instability of latencies of the single peaks, particularly of pontine- and mesencephalic-generated components. The instability of tatencies is particularly marked in the acute stage, i.e. during the first days after the brain injury or intracerebral haemorrhage. During the development of the bulbar syndrome the latency of single peaks increases rapidly. We interpret the instability of latency in the first days of decerebration syndrome as a sign ofirritation of the brainstem. On the other hand the changing latencies may reflect spontaneous regulatory mechanisms (hyperventilation) and therapeutic measures (controlled ventilation, antioedema treatment, improvement of microcirculation). The instability may reflect the changing functional activity within the brainstem, which may be influenced by such factors as oedema, contusion or circulatory disturbances. In our patients with decerebration we were unable to lateralize lesions in the way that has been reported in circumscribed brainstem lesions [10]. It appears, therefore, that the neural function disturbance involves the whole brainstem. Increased latencies, which were found both for the medullo-pontine and ponto-mesencephalic segments as well as increased central conduction time, suggest a global functional disturbance of the brainstem in decerebrate patients. In spite of the known difficulties in interpreting amplitudes of single peaks, A-V to A-I and A-III to A-I proved to be significantly reduced in the decerebrate patients. However, the amplitude ratio can be used as a criterion of the severity of brainstem disturbance in decerebration. Some authors also consider A-V to A-I to be significantly abnormal when the value is below 1 [2]. It is interesting to note that the amplitude ratio A-V to A-III was not lower in our patients with decerebration, compared to those of normal subjects. Again this finding suggests a global functional brainstem disturbance in decerebration. The significant decrease of the amplitude ratio A-III to A-I suggests functional pontine irritation. Apart from the reduction of the amplitude in the majority of recordings considerable changes of the 'morphological structure' of the single peaks were found. This was particularly evident for the P-V and P-III components. Even after the resolution of decerebration and the recovery of the patient the disturbance which occurred at the brainstem could still be detected for several months. The morphological structure of single peaks could recover, and single peaks lost at the stage of decerebration could reappear. A recovery of BAEP occurred considerably later than clinical recovery from decerebration.

Brainstem Auditory Evoked Potentials

227

B A E P s have a c q u i r e d c o n s i d e r a b l e value in the diagnosis o f b r a i n death. A l l p a t i e n t s in w h o m the p r e v i o u s r e c o r d i n g s revealed m e d u l l a r y , p o n t i n e or m e s e n c e p h a l i c p o t e n t i a l s a n d in w h o m n o p e a k s b e y o n d P - I l were registered d u r i n g r e p e a t e d studies h a d a silent E E G trace a n d clinical signs o f b r a i n death. W e have never o b s e r v e d the r e c o v e r y o f B A E P after d i s a p p e a r a n c e o f P-II. T h e findings were c o n f i r m e d in e x p e r i m e n t a l studies in cats. Once P - I l d i s a p p e a r e d no recovery o f B A E P o c c u r r e d even when the pressure was i m m e d i a t e l y released. T h e r e is a l i m i t a t i o n in the i n t e r p r e t a t i o n o f the lack o f B A E P as a sign o f b r a i n d e a t h , p a r t i c u l a r l y in p a t i e n t s after severe b r a i n injuries, n a m e l y the u n c e r t a i n t y a b o u t the p r e m o r b i d a u d i t o r y f u n c t i o n a n d the p o s s i b i l i t y o f a c c o m p a n y i n g lesions such as p y r a m i d a l fractures, h a e m a t o t y m p a n u m o r m e a t a l injury. W e d i d n o t o b t a i n B A E P s in a 38-year-old p a t i e n t with acute occlusion o f the b a s i l a r a r t e r y w h o h a d a n o r m a l a u d i t o r y f u n c t i o n before the stroke. Isoelectric B A E P ( ' O B A E P ' ) in this p a t i e n t resulted f r o m the acute i n t e r r u p t i o n o f c i r c u l a t i o n in b o t h o f the i n t e r n a l a u d i t o r y arteries. B A E P is o f value in the diagnosis o f central d e a t h a n d e v a l u a t i o n o f the time o f b r a i n death. H o w e v e r , it is essential for this diagnosis that B A E P has to be r e c o r d e d in a r e p r o d u c i b l e w a y in each case p r e c e d i n g the ' O - B A E P ' .

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15. Starr A, Achor LJ (1975) Auditory brain stem responses in neurological disease. Arch Neurol 32:761-768 16. Starr A, Hamilton AE (1976) Correlation between confirmed sites of neurological lesions and abnormalities of far-field auditory brainstem responses. Electroenceph Clin Neurophysiol 41 : 595-608 17. Stockard J J, Rossiter VS, Wiederholt WC, Kobayashi PM (1976) Brain stem auditoryevoked responses in suspected central pontine myelinolysis. Arch Neurol 33:726-729 18. Stockard J J, Rossiter VS (1977) Clinical and pathologic correlates of brain stem auditory response abnormalities. Neurology 27 : 316-325 19. Stockard J J, Stockard JE, Sharbrough FW (1977) Detection and localization of occult lesions with brain-stem. Auditory responses. Mayo Clin Proc 52:761-769 20. Terkildsen K, Huis in't Veld F, Osterhammel P (1977) Auditory brain stem responses in the diagnosis of cerebellopontine angle tumours. Scand Audiol 6:43-47

Received March 3, 1982