ACTA

Acta Neurochirurgica 68, 85--92 (1983) NEUROCHIRURGICA

9 by Springer-Verlag 1983

Department of Neurosurgery, University of Giessen, Federal Republic of Germany

Effect of Increased Intracranial Pressure

o n the B l i n k R e f l e x i n C a t s *

By

G. Cs6csei, N. K l u g , and Z. M. Rap

With 5 Figures

Summary
During an acute increase in ICP produced by balloon inflation three different
phases could be observed. In the first phase (ICP 40-50 mmHg) the latencies
of R 1 and R 2 showed an initial decrease followed by increase in latency. In the
second phase (ICP 50-70 mm Hg) R 2 disappeared, whereas R 1 showed marked
alterations, prolongation of the latency and duration, and a decreasing amplitude.
In the third phase no response could be evoked. The pathophysiological observa-
tions correlated with the morphological alterations. Two ischaemic zones with
BBB damage which ,,transsected" the mesodiencephalic and pontomesencephalic
border were found. The results suggest that the disappearance of R 2 depends on
rostral damage, whereas alteration of R 1 is caused by a pontomesencephalic
lesion.

In the last ten years a few reports have been published about
alterations in the blink reflex (BR) in comatose patients. Most of
them concerned phenomenological changes of the reflex responses and
their relationship to other electrophysiological parameters as well
as to the clinical symptoms 1, 2, 6, 7, 10 There are still no data avail-
able regarding the influence of intracranial hypertension ( I H ) on the
BR recorded in comatose patients, although it is k n o w n to be an
i m p o r t a n t factor in the physiological activity of the central nervous
system (CNS), and in particular of the brain stem. In order to
explain some unusual findings obtained in decerebrated patients with
increased intracranial pressure (ICP), we carried out an experimental
study in which the effect of I H on the BR was evaluated.

* This study was supported by Deutsche Forschungsgemeinschaft, SFB 32.

0001-6268/83/0068/0085/$ 01.60
86 G. Cs6csei et al.:

Method
The experiments were performed on 10 anaesthetized cats weighing 2.2-3.1 kg
under spontaneous respiration. The animals were tracheotomized and the femoral
artery and vein were cannulated. A small silastic balloon was placed epidurally
over the right frontal area and a Statbam SP 50 transducer for recording intra-
cranial pressure on the opposite side. The balloon was inflated slowly with
0.1 ml/minute. I H was recorded twice, first until BR disappeared and the balloon
was deflated and then again after 20 minutes, when the balloon was reinflated.
The second recording was continued until respiratory and cardiac arrest occurred.
ICP, respiration rate (RR), heart rate (HR), systemic blood pressure (SBP),
central venous pressure (CVP) and ECG were continuously monitored. The
temperature of the animals was kept at a constant level of between 36.5-37.5 ~
A two per cent Evans blue solution (2 ml/kg) was injected i.v. before the first
increase in ICP in order to detect blood-brain barrier (BBB) damage. The BR
was elicited by stimulating the nictitating membrane with two small wire electrodes
placed 5 mm apart. BR responses were recorded from the orbicularis oculi muscles
with small concentric needle electrodes. Before producing IH, stimulation was
performed by gradually increasing the voltage in order to determine threshold
values and to find the optimal evoked responses. After finishing the experiments
the cats were perfused with 10 per cent neutralized Formalin solution. All the
brains were fixed in Formalin and sections were examined under fluorescence
microscopy (Leitz-Orthoplan with combined filters M 2-513421).

Results
Pathophysiological Observations
The changes in ICP could be divided into three periods ac-
companied by marked changes in vegetative and electrophysiological
parameters. In the first period ICP increased continuously with the
amount of fluid infused into the balloon. In the second phase ICP
showed a fluctuating plateau. In the third phase ICP decreased in
spite of further inflation of the balloon (Fig. 1).
In the first phase SBP, CVP, and RR remained nearly unchanged.
In some cases the rate of respiration showed a mild decrease at the
end of this first phase. At the beginning of the second phase, when
ICP decreased, most of the animals showed a more or less pronounced
hyperventilation. Later on, in the second phase, all animals showed
a periodic respiration, and the H R decreased while SBP and CVP
increased. Pupillary dilatation developed ipsilateral to the balloon.
In the third phase, after ICP had reached values about 80 to
100 mm Hg, respiratory arrest occurred and the HR, SBP, and CVP
fell parallel to ICP. The pupils were maximally dilated and the
cats died after a short time.
Changes in Reflex Responses
Electrical stimulation of the trigeminal afferent nerves elicited
double responses, namely an ipsilateral early R 1 and bilateral late
 Effect of Increased Intracranial Pressure 87

".,minf 1 I
ICP [mmHgl

[msecl mVl
30- -3

20 2 Duration [ msecl
Latency [msec]

10-

Amplitude [mV]

] I I i
~'o 20 3o ~o s~o 6'o ?o 80 90 t [mini
Fig, 1. Alterations in the R 1 response concerning latency, duration and amplitude
during repeated IH. ~" onset of inflation, ~ deflation of the balloon

oom. i: 1mY<
5rns

oom.L -~'/~---~" 200B/ k

5ms
Fig. 2. Normal blink reflex of the cat. Stimulation on the right side. Recording
from right (oorn. r.) and left (oorn. I.) orbicularis oculi muscles

R 2, similar to the human BR (Fig. 2). Depending on the increase

of the stimulus intensity, responses showed a shorter latency (Fig. 3)
whereas duration and amplitude increased. The threshold for R 2
was higher than that for R 1. R 2 contralateral to the stimulation
always had a longer latency than that ipsilaterally.
BR behaved differently during the first and the second period
of inflation. Both R 1 and R 2 showed an initial decrease in latency-
in response to an ICP increase of between 30 and 40 mm Hg, after
 88 G. Cs6csei e t al.: Effect of Increased Intracraniai Pressure

which the latencies began to increase (see Fig. 1). At the end of the
first phase R 2 disappeared and did not recover again (Fig. 4 a).
In the second period of IH the latency and duration of R 1 became
prolonged, the amplitude decreased and finally R 1 disappeared.
During the time between the two inflation periods, R 1 recovered
qui&ly but the latency remained longer than before the increase in
the ICP.
During the second IH, R 1 showed more marked changes, prob-
ably because of secondary brain stem damage caused by the previous
I H (Fig. 4 b). After initial shortening, the latency showed a gradual

Latency
[msec]
30_ {

20

10_

i I J I
10 20 30 40 Stirn.ln[ [V]

Fig. 3. Latency-dependency of R 1 and R 2 responses with increasing stlmulus

intensity (vertical bars • SD)

increase which was particularly extended immediately before R 1

disappeared. The duration of R 1 increased rapidly, becoming 200 to
300 per cent longer in the second period of IH. At the same time
the amplitude increased and finally decreased rapidly. In the third
period of IH, R 1 disappeared shortly before respiration arrested and
blood pressure fell (see Fig. 1).
One of the cats was artificially ventilated after respiratory and
cardiac arrest immediately after deflating the balloon. Some minutes
later spontaneous respiration recovered and blood pressure returned
to nearly normal. R 1 and R 2 on the other hand did not recover
again.
Pathornorphological Findings
All the brains were cut by sagittal section into two symmetrical
parts. The localization of the ischaemic lesions in the nervous s t r u c -
 a b

ICP [ram Hg] ICP [ram Hg]

12

20 s ~"V'--

30

20
44
32 ~,
53
/*2 ~ ~ / ~ ~
60
50 ~ ~ - V ' q / ' ~
56

62 56 ~ ~ ~

65 ~-~'V'-V 60 ~--

.~ 70 70 -~'-- .-

1mY[_,
5ms
Fig. 4. Alteration of blink responses during repeated IH insults, a) first inflation,
b) second inflation. 1" onset of inflation, "1" deflation of the balloon

Fig. 5. Median sagittal section of the cat's brain after repeated inflation of an
epidural balloon. Note the zones of BBB damage
90 G. Cs&sei et al.:

tures were shown by extravasation of Evans blue. Macroscopically,

two primary ischaemic zones with BBB damage, sometimes with
secondary bleeding, were found (Fig. 5): the first was localized in
front of the tentorium and the second behind. The first ischaemic
lesion extended from the cingulate gyrus and splenium of the corpus
callosum through the massa intermedia of the thalamus to the mamil-
lary bodies. The second zone began in the superior and inferior
colliculi "cutting" the mesencephalon at the pontine border. Some-
times extravasation of Evans blue was also observed in the occipital
lobe and in the cerebellum, particularly in the cerebellar tonsils.
Fluorescence microscopic examination revealed a diffuse spread of
Evans blue-albumen complex in the primary ischaemic areas, whereas
in the pons and medulla oblongata it was concentrated mostly in
nervous fibres, nerve cells and glia ceils. Details of the morphological
observations by light and electronmicroscopy from these experi-
ments are presented elsewhere 9

Discussion

An increase in ICP alters the brain stem reflexes, amongst others,

the blink reflex. R 2 is very sensitive to I H and disappears very
early. On the other hand, respiratory disturbances and anisocoric
pupils accompanying the disappearance of R 2 indicate the beginning
of mesencephalic herniation. R 1, being an oligosynaptic pontine
reflex 5, showed marked alterations only at higher ICP levels and
the disappearance of R 1 coincided with the breakdown of vegetative
regulation expressing in each case a severe functional disturbance of
the lower brain stem. The more obvious changes of R 1 and la&
of R 2 during repeated I H indicate previous damage of the brain
stem structures. Initial shortening of the latencies during an increase
of ICP could be explained by a transient increase in neuronal
activity. A similar phenomenon was observed by George (1980) in
mesodiencephalic, mesencephalic and ponto-bulbar nuclei. An increase
in ICP resulted in an increase of multi-unit activity, followed by a
rostro-caudal deterioration. The initial shortening of the latency
could also be related to a humoral response involving activation of
the hypothalamo-hypophyseal-adrenal axis. Release of A C T H gluco-
corticoids, and first of all, catecholamines into the blood and CSF
(Rap et al. 1975) during IH may have an influence on reflex
activity.
The prolonged latency and decreased amplitude at higher ICP
levels suggests direct damage of the reflex arc, which is clearly
manifested by the increase in R 1 duration. This phenomenon can be
 Effect of Increased Intracranial Pressure 91

explained by a desynchronization of the neuronal and synaptic

activity of the brain stem, depending on the disturbance of facili-
tatory and inhibitory impulses from more rostral structures 8. In the
later phase of decerebration, when the latency is also increased, the
slow-down of neural conduction and increase of synaptic trans-
mission time could also play a role in the prolongation of R 1. The
pathomorphological examination showed BBB damage in the meso-
diencephalic and pontomesencephalic structures parallel to the bony
tentorium. These observations support the findings of Tokunaga
et al. (1958) and Hiraoka et al. (1977) who made transsections of
the brain stem at different levels. After mesodiencephalic trans-
section they found a complete loss of R 2, whereas R 1 disappeared
after midpontine hemitranssection. Accordingly, in our experiments
the loss of R 2 with increasing ICP occurs earlier than the loss of R 1
and the inference is clear that rostral damage occurs earlier than
caudal damage.

References

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Author's address: OA Dr. N. Klug, Neurochirurgische Universit~itsklinik,

D-6300 Giessen, Federal Republic of Germany.