- Email: [email protected]
Long-lasting EEG reactions in comatose patients after repetitive stimulation
402
Electroencephalograph)' and clinical Neurophysiologv, 1986, 6 4 : 4 0 2 - 4 1 0 Elsevier Scientific Publishers Ireland, Ltd.
L O N G - L A S T I N G E E G R E A C T I O N S IN C O M A T O S E P A T I E N T S AFTER R E P E T I T I V E S T I M U L A T I O N t G. P F U R T S C H E L L E R *, G. S C H W A R Z ** and W. LIST ** * Department of Computing, Institute of Biomedical Engineering, Technical University of Graz, A-8010 Graz, and ** Institute of A naesthesiology, University of Graz, A-8036 Graz (Austria) (Accepted for publication: April 9, 1986)
Summary
Twenty patients with severe head injury and a Glasgow Coma Scale of 4 - 6 were subjects of a multimodality EP study. After EEG recording during rest (control 1) 60 mechanical vibration stimuli and 60 visual stimuli (interstimulus interval 10 sec) were applied. Thereafter a second EEG (control 2) was measured. To quantify a long-lasting stimulated EEG alteration, control 2 was compared with control 1 on the basis of the spectral t h e t a / b e t a ratio calculated from central derivations. In 50% of the patients the t h e t a / b e t a ratio was changed in control 2 and therefore a long lasting stimulation effect can be assumed. Stimulus-induced cardiac alterations were also found.
Keywords: EEG reactions - coma - repetitive stimulation
The E E G reactivity studies during and after various forms of sensory stimulation play an important part in the evaluation of c o m a t o s e patients. In 1946, Fischgold and Bones suggested that the EEG changes could be regarded as signs of cortical reactions to sensory input. This EEG reactivity can occur immediately after a single stimulus or with delay; it can be short lasting in the form of bursts or spindles (Rumpl et al. 1983), long lasting for minutes (Arfel 1975), or result in a new EEG pattern (Chatrian et al. 1963). In light coma the application of a single stimulus will produce widespread reactions immediately; in deep coma, however, the immediate reaction of cerebral activity is very often abolished, but there may still be a delayed and long-lasting EEG alteration (Arfel 1975). In a retrospective study long-lasting EEG reactions after repetitive stimulation were analysed in comatose patients. When stimulus-induced E E G alterations are found it could be speculated that an arousal or lightening of coma has occurred.
1 Supported by the ' F o n d s zur Foerderung der wissenschaftlichen Forschung,' Project 5393, the Styrian Research Fonds, and the 'Oesterr. Nationalbank,' Project 1915.
This would mean that repetitive stimulation of a special modality and quality is not only a diagnostic tool alone but could be used for therapeutic purposes as well. Whether or not the stimulus-induced alterations in brain activity are desirable or should be avoided principally in comatose patients is not in the scope of this paper. The material includes quantitative EEGs recorded before and after repetitive mechanical vibration and visual stimulation in groups of normals and comatose patients. This stimulation is part of a multimodality evoked potential evaluation.
Patients and Methods
Studies were performed in the intensive care unit of the Institute of Anaesthesiology, University of Graz, where comatose patients with severe head injury are under medical treatment. Combined quantitative EEG and multimodality evoked potentials were used for assessment of cerebral dysfunction (Pfurtscheller et al. 1983, 1985a). Twenty patients with severe head injury (12 of them with polytrauma) and a Glasgow C o m a Scale (GCS) of 4 - 6 (Teasdale and Jennett
0013-4649/86/$03.50 ~ 1986 Elsevier Scientific Publishers Ireland, Ltd.
EEG REACTIONS IN COMATOSE PATIENTS
1976) are included in this study. The outcome was classified according to the Glasgow Outcome Scale (Jennett and Bond 1975). Using this classification, 7 patients showed 'good recovery,' 4 'moderate disability' and 1 'severe disability,' 1 was classified as 'vegetative state' and 7 died. The ages ranged from 18 to 64, mean 31 + 16 years. To be able to compare the effect of cerebral stimulation in comatose patients and conscious subjects and to set up thresholds, 2 control groups were formed, one consisting of 8 comatose patients after good clinical recovery, aged between 17 and 22 (mean 20_+ 1 year), and the other composed of 14 volunteers between 19 and 47 years (mean 26 + 7 years). The test programme used for multifunctional measurements in comatose patients and controls consisted of the following sequences: EEG recording during rest (control 1); slow, repetitive mechanical vibration; slow, repetitive light stimulation; E E G recording during rest (control 2); further EEG recordings (control 3, control 4, etc.) in some patients. EEGs were recorded from Cz-C3, Cz-C4, CzA2, and approximately F3-F4 and O1-O2; but only the two central records were used for statistical analysis in this study. During each control session maximally sixty 6 sec trials with intervals of 6.5 or 8 sec were sampled by a PDP 11/23 computer and used for calculation of power spectra. The E E G spectra were divided into 4 frequency bands (0-4, 4-7.5, 6.5-13.5, 14.5-24 Hz); the absolute and relative band powers and the t h e t a / b e t a power ratios were calculated. Sixty 1 sec mechanical vibration stimuli of 100 Hz were applied via a plastic ring to the last digit of the index finger of the right hand. After a break of about 15 min, used for changing the stimulator and starting the computer programme, 60 light stimuli of 1 sec duration each were applied to both eyes. The stimulus interval was 10 sec for each modality (Pfurtscheller et al. 1985a). This experimental paradigm has been used in our ICU as standard since 1980 and does not include randomization of the stimulation procedures. In this retrospective study therefore vibration has always been given before light stimulation. Depending on the stimulation sequences and
403
also on occasional therapeutic interventions, control 2 was started about 60 min after the end of control 1. Further successive controls were performed in some patients at intervals of about 30 min. Special attention has been given to the medication. Clinical data, medication, GCS and clinical outcome are summarized in Table I.
Results
Spectral ratios of the types d e l t a / b e t a (Steadman and Morgan 1974), (delta + theta)/(alpha + beta) (Gotman et al. 1975) and t h e t a / b e t a (K6pruner et al. 1984) have the benefit of normalization, are especially suitable for follow-up studies and are used very often in quantitative EEG. In studies where movement artefacts can occur, as in our intensive care patient for example (sucking, measurement of blood pressure, obtaining of blood samples, etc.), the delta power should be avoided as parameter. Therefore we decided to use the t h e t a / b e t a ratio, particularly as this parameter has been successfully used in follow-up studies in
20
/--\ •
Bin. 17 ( 13 weeks)
15
10
/
4,., .
/
'
/ //
~
" 12di
",7~
~ ' ~
"
6"
"
'9
And, 20 (8days)
\ N
X
"
-'~'7" .........
Id '3
I. " - - . ,
'
'12"
'
sve,t9
~ ~
(19 weeks)
GCS 15
G.R.
Fig. 1. Time course of the theta/beta ratio evaluated in 4 comatose patients with good clinical recovery during control 1 before stimulation. Note the inverse U-shaped form. Two patients (BIN, 17 and H•L, 20), both with severe head injury, were not in the study because the latter had no control 2 and the former a GCS > 6 at the first examination. The length of the follow-up (in days) and interval from the injury are marked.
404
G. P F U R T S C H E L L E R
stroke patients (KiSpruner et al. 1984) and a large data pool is available. To give an impression of the magnitude of the theta/beta ratio during, control 1, the mean values and standard deviations of each of the 3 groups were calculated: comatose patients recovered patients after severe head injury volunteers
4.1+3.4
(N=20)
4.0+2.9 1.4 + 0.7
(N=8) (N = 14)
The mean of 1.4 _+ 0.7 is characteristic for a normal brain function during wakefulness. Increased theta/beta ratios have been found in the comatose state but also after emergence from coma. High t h e t a / b e t a ratios are characteristic for slow
ET AL.
monorhythmic activity; low t h e t a / b e t a ratios have been found in the awake state and with polymorphic sleep activity as well. The t h e t a / b e t a ratio measured before stimulation (control 1) can be used for long-term EEG monitoring of comatose patients. The data of the patients displayed in Fig. 1 show inverse U-shaped curves with initially increasing t h e t a / b e t a ratios and later, usually when awake, with decreasing t h e t a / b e t a ratios. In very deep coma an increased t h e t a / b e t a ratio can also be found. From the t h e t a / b e t a ratios obtained in both central derivations during control 1 and control 2 the percentage increase or decrease (referred to control 1) was calculated. Two arbitrary thresholds have been established: + 50% and - 25%. Subjects
TABLE I S u m m a r i z e d patient data: clinical status, G l a s g o w C o m a Scale (GCS) at the time of testing, medication~ respiration, clinical o u t c o m e (GR, good recovery; SD, severe disability; MD, mild disability; VS, vegetative state; D, death), t h e t a / b e t a ratios before s t i m u l a t i o n m e a s u r e d in b o t h hemispheres, percentage change of the t h e t a / b e t a ratio (control 2 referred to control 1), classification into 2 s u b g r o u p s and percentage c h a n g e of heart rate (HR). Patient no. 13 with the a s y m m e t r i c response had a right hemisphere lesion. Patient G C S Age Polyno,
Medication*
Respiration
Outcome
trauma
1 2 3 4 5 6
4 4 5 4 4 5
29 20 64 16 20 19
+ +
7 8 9 10 11
5 6 6 6 5
49 24 45 20 18
12 13 14 15 16 17
6 5 4 5 6 5
18
19 20
T h e t a / b e t a C1
%
Left
Right
Left
Right
Class.
HR
~-83 ~186 0 +2
C C -
+9 +17 - 3 4
+63
+ 50
C
- 4
+10
+15
-
0
14.0 1.2 4.2 2.1 2.8
51 -23 +9 -20 +5
6O 25 0 -29 18
C C
10.8 1.7 4.8 5.2 1.8 7.0 5.4 3.0 3.8
+8 +54 -21 +57 +43 16 + 14 + 5 47
+ 19 12 15 +40 i-67 0 9 + 20 24
C C C
Spont/int Artificial D r o p e r i d o l + fentanyl 2 ml Artificial PS 250 mg Spont/trach Spont/int D r o p e r i d o l + fentanyl 5 ml Artificial F c n t a n y l 0.1 mg
Death G o o d recov. Death Veg. state G o o d recov. G o o d recov.
2.2 2.3 1.6 5.8 1.1 4.0
3.5 2.3 1.4 4.8
+18 + 148 + 13 -16
1,0
3.4
+ + -
PS 250 mg PS 250 mg
Spont/int Spont/int Spont/int Spont/int Spont/int
Mod. disab. 16.9 Mod. disab. 1.3 Severe disab. 2.1 G o o d recov. 1,5 G o o d recov. 2.2
19 22 56 38 19 59
+ + + + +
F e n t a n y l 0.1 mg D i a z e p a m 20 mg -
4
25
-
6 4
39 18
+ +
Artificial Spont/int Spont Spont/int Spont/int Artificial Spont/int Spont/int Spont/trach
Mod. disab. G o o d recov. Death Death Mod. disab. Death Death G o o d recov. Death
+
M e l p e r o n 10 mg M P C 50 m g
Piracetam 400 mg M H 1 mg
9.3 1.3 3.9 4.2 1,4 5.7 2,9 3.8 4.5
* I n t r a v e n o u s m e d i c a t i o n within 6 h before E E G study, last a p p l i c a t i o n 2 h before. PS = p h e n y t o i n - s o d i u m ; M P C = m e t h y l p e r o n c h l o r i d e (i.m.): M H = m o r p h i u m h y d r o c h l o r (i.m.); spontaneous: trach = tracheotomised; + = p a t i e n t s with p o l y t r a u m a ; C = classified as ' c h a n g e d . '
C -
C
int = i n t u b a t e d ;
- 7 + 10 5 -7 -21
0 3 +3 +1 -9 + 2 0 + 3 7
spont =
EEG REACTIONS IN COMATOSE PATIENTS
2-r~
THETA BETA
AND, 20
+63% -21
,
.
0
8
,, . . . . .
16
24
405 THETA BETA
Kai, 18a
15-
10 -53d
32 Hz
. [--~---~ibr. =
HR
LSP O-
150- min !
+10%
-1
pre
~
02 ~
stimulation
post 5
~
C4 I 65
95 rain
11d
125
-2
'
v
v
8
w
v
w
16
l
l
24
3~Hz
100
~
53d ~
°
~ ~
6 .
4 ~
d 60d
75
1,
LOP 04
-1.
,C2 ,
-=
0
-47 %
Ci X('-.\ i6 44 g2Hz
Fig. 2. Example of logarithmic spectra belonging to the "changed' subgroups (upper and lower panels) and the 'unchanged' subgroups (middle panel). Full line spectra calculated before stimulation (control 1), stippled line spectra calculated after stimulation (control 2). Data from patients no. 5, 6 and 20 (from top to bottom) are displayed.
with a t h e t a / b e t a ratio increase (from control 1 to control 2) > 50%, or a t h e t a / b e t a ratio decrease < 25% in one or both of the central channels were classified as 'changed,' all others as 'unchanged.' Using this classification, 10 out of 20 of the comatose patients demonstrated a change in control 2 EEG, whereby the t h e t a / b e t a ratio showed an increase in 6 patients and a decrease in 4 (Table I).
Fig. 3. Time course of the theta/beta ratio (upper panel) and the heart rate (lower panel) in patient no. 20 measured on different days (d) after head injury. The GCS improved in this time from 4 to 9.
In the control groups of recovered patients and normal volunteers 8 out of 22 (41%) showed a stimulus-induced E E G alteration; in 6 the t h e t a / beta ratio was increased and in 2 it was decreased. The heart rate (HR) was also measured. The percentage changes of the H R during control 2 compared with control 1 are summarized in Table I, last column. H R changes > 5% (arbitrary threshold) were classified as significant. Eight patients showed an altered HR, 3 patients an acceleration and 5 a slowing. In 7 patients stimulus-induced E E G and cardiac alterations were found in parallel; 9 patients demonstrated neither E E G nor cardiac alterations. Examples of logarithmic spectra of 3 subjects belonging to the subgroups classified as ' u n changed' and 'changed' are displayed in Fig. 2.
406
G. P F U R T S C H E L L E R
A
A
J
O
8
16
24
32
O
8
8
16
16
24
24
:11O ~8
82
32
O
8
16
24
32
1/ J
~
,T,,ERS..
I,$T
-~' ~'
~ONTROL~
UNIVeRSitY
16
8
post
24
0~
ORR,
8
16
24
32
12:40
8
16
24
0
tO Z4
$2
% FO848N
KRI. 8.H.T. 4TH
0
HERS.,
CONTROL
2
'
. . . . . .
/
A
4PL. I IL! -
~2
INST RNRESTHESIOLOGY INST BIOHEDICRL ENG UNIVERSITY OF GRAZ
MRNFREO. 1 8 R
O
i2
0
8
16
24
32
7
8
t6 24 32
-2,.
~ ½..~4.
i2
I
post 95min
65rain
I -JUL-82
. . . . . . . . 0
/CNT4 0
0
-2
11:40
CONT3
I
,'~'i','~
1-JUL-82
RNR~STHE~IO~O~Y
]
32
-t
FOB4,N
I~R
24
%
post 5min
H~N~RE~.
16
2
pre i-JUL-S2
\ SPEC
CONT2
SPEC x""1
"/CONT 1
0
E T AL.
~i
KRI MRNFRED,18R 5.H.T. 4TH HERS., COhlTROL 3
Foo,oN INST RNRESTHESIOLOGY INST BIOMEDICAL ENG UNIVERSITY OF GRRZ
1-JUL-82
1~:10 KRI MRNFREO,18FI 5.M.T. CTH HERS., CONTROL ¢
INST RNAESTHESIOLOGY INST BIOMEDICAL ENG UNIVERSITY OF GRRZ
Fig. 4. Topographical display of power spectra before (control 1) and after stimulation (controls 2, 3 and 4). Data from patient no. 20 (GCS = 9), 60 days after injury. Note the similarity of the spectra measured before (control 1) and 95 rain after stimulation (control 4).
EEG REACTIONS IN COMATOSE PATIENTS The deviations between the spectra are visible although the scale is logarithmic. Stimulus-induced EEG and H R alterations are extremely variable and depend on the level of coma, the neurological status, the medication and other things; t h e t a / b e t a increase or decrease and cardiac slowing or acceleration can be found in the same patient. To demonstrate this, data from patient no. 20 are displayed in Fig. 3, recorded on different days during clinical improvement (the data of the 11 day measurement are used in Table I). From the last 2 measurements (60 and 64 days after injury) further controls after stimulation are available. Examples of the topographical display of the power spectra in the 60 day measurement are displayed in Fig. 4. The peaks at 12 Hz (marked by arrows in Fig. 4) in the frontal and central derivations indicate 12 Hz spindle activity. These spindles, together with a decreased heart rate (see Fig. 3, lower panel), are characteristic of a 'sleep' state (Gibbs and Gibbs 1950).
Discussion
Half of our comatose patients showed an increase or decrease of the t h e t a / b e t a ratio, indicating a stimulus-induced prolonged EEG alteration. Most of these patients showed heart rate changes additionally. This raises some questions, which are worth discussion: (1) which stimulus modality, vibration or light, is responsible for the long-lasting effect on the EEG? (2) the t h e t a / b e t a ratio shows an increase in some patients and a decrease in others; how can this be interpreted? (3) is there any correlation between the clinical outcome and the subgroups classified as 'changed' and ' unchanged,' respectively? (1) Referring to stimulus-induced EEG alteration two possibilities have to be taken into consideration, (i) a direct modality-specific and (ii) an indirect modality-unspecific activation or modulation of EEG generating structures in superficial cortical layers. In one case the primary sensory pathway and in the other the ascending reticular activating system in the brain-stem probably plays
407 a role. Evidence for modality-specific EEG alterations is given by Pfurtscheller et al. 1985b; in two patients with a flat EEG repetitive mechanical vibration of the index finger provoked an EEG activity for about 30 min, strictly localized to the sensorimotor region. Stimulus-induced EEG alterations have already been observed during vibration but are reinforced during light stimulation and reach the largest extent during control 2 (see Fig. 5). This observation and the close linkage of EEG and cardiac changes refer more to a contribution of modality-unspecific reticular structures in the brain-stem than to a modality-specific activation. At this time no clear answer can be given to the question of whether vibration or light stimulation or a modality-unspecific activation of reticular structures is primarily responsible for long-latency EEG alterations. (2) Follow-up measurements of the t h e t a / b e t a ratio in some comatose patients with good clinical recovery demonstrate a characteristic pattern. In states with low GCS values (deep and moderate coma) the t h e t a / b e t a ratio increased. Before reaching GCS = 15 and afterwards, the t h e t a / b e t a ratio decreased; some initial numbers of the t h e t a / b e t a ratio obtained during deep coma (GCS 3-4) were high and decreased afterwards. These data indicate that in the course of emergence from 250- %
200-
5 15 16
150
100 . . . . . .
5¢ Control 1 I
Vibr.
I
Light
l Control 2
Fig. 5. Changes of the theta/beta ratio (control 1 = 100%) in some patients during stimulation and control 2.
408 coma the t h e t a / b e t a ratio increases and after reaching an altered state of consciousness the t h e t a / b e t a ratio decreases in parallel with the involution of cerebral dysfunction. A slowly declining t h e t a / b e t a ratio is also typical and characteristic in alert patients with cerebrovascular insufficiency during clinical recovery. A decrease of the t h e t a / b e t a ratio during wakefulness characterizes an improvement of cortical functions. This inverse U-shaped time course of the t h e t a / b e t a ratio (first increase, then decrease during recovery) could indicate that stimulation can produce either a decrease or increase of the t h e t a / beta ratio, which depends on the amount of t h e t a / b e t a at the time when the stimulus is applied. When the t h e t a / b e t a ratio in coma was low in our study, repetitive stimulation resulted mainly in a t h e t a / b e t a ratio increase; when the ratio was high, vibration resulted mainly in a t h e t a / b e t a ratio decrease. Therefore both types of change can be interpreted as a positive stimulation effect in the direction of emergence from coma. (3) Patients with an unfavourable outcome (death, vegetative state, severe disability) have to be divided into those with a clinical outcome directly related to the head injury (e.g., brain death) and those unrelated to it, e.g., patients with polytrauma. Some of them showed clinical improvement in the ICU (e.g., patient no. 2 0 ) b u t died later, e.g., following septic complications. Therefore only data of patients with a favourable outcome (good recovery, moderate disability) were analysed with regard to the prolonged EEG alterations. All except one of this subgroup, receiving no droperidol, fentanyl or morphia (patients no. 2, 5, 7, 8, 10, 13, 16), had prolonged EEG alterations. The only patient with brain death (no. 18) demonstrated no EEG and H R alteration. Some correlation between a favourable outcome and stimulusinduced EEG alteration is therefore evident. On the other side this confirms the results of Rumpl et al. (1983) that an unfavourable outcome is indicated by the loss of reactivity to external stimuli. Coma can be best defined as a state of impaired consciousness that may be either stable or unstable. In stable coma stimulation produces no behavioural response and no EEG or heart rate
G. PFURTSCHELLERET AL. alteration. Examples of this type belong to the subgroup classified as 'unchanged' (patients no. 3, 4, 6, 9, 12, 14, 17, 18 and 19). From this group a subgroup can be formed (patients no. 3, 6, 12 and 19), in which the absence of stimulus-induced EEG and heart rate alterations is probably the result of a brain 'protection.' These patients received droperidol and fentanyl or morphia. A typical unstable coma is the light coma which marks a limit between unconscioussness and wakefulness. In light coma the patient can be aroused by external stimulation and the EEG demonstrates a marked change after stimulation (Fischer 1969). A change in coma level can be either spontaneous or stimulated. The former can be quantified by measuring the t h e t a / b e t a ratio from control EEGs recorded on different days, the latter by calculation of the t h e t a / b e t a ratio before and after repetitive stimulation. With lightening of the coma the t h e t a / b e t a ratio increases first (up to 10 or more) and then decreases. After emergence from coma and recovering full consciousness the t h e t a / b e t a ratio can still be higher and then decrease slowly to a normal level of 1.4 + 0.7. Sometimes this normal level may be reached only weeks after regaining full consciousness. A high t h e t a / b e t a ratio during control 1 is therefore not only characteristic of a state of unconsciousness but can also be observed in waking patients with brain dysfunction. A typical example of this is the control group of recovered patients with a t h e t a / beta ratio of 4.0 +_ 2.9; in the course of clinical recovery the t h e t a / b e t a ratio can decrease to the normal values of 1.4 _+ 0.7 of healthy subjects. Spontaneous changes of the t h e t a / b e t a ratio in a comatose patient can be interpreted partly as a shift in the state of unconsciousness and partly as being due to involution of cerebral dysfunction. Variations of the EEG pattern and the t h e t a / b e t a ratio, respectively, can also be due to the appearance of typical or atypical sleep potentials and changes between the 'alert' state and the 'sleep' state (Chatrian et al. 1963; Silverman 1963; Kubicki and Freund 1979; Rumpl et al. 1983). Such spontaneous EEG variations are more frequent in mild than in deep coma (Bricolo et al. 1978). Stimulated EEG alterations can be quantified
LEG REACTIONS IN COMATOSE PATIENTS
by the t h e t a / b e t a ratio measured before and after repetitive stimulation and were found in half of our comatose patients. This form of LEG reactivity to various types of sensory input has already been reported by Fischgold and Bones (1946), Fischgold et al. (1955), Chatrian et al. (1963) and others. In contrast to spontaneous LEG changes, the stimulated alterations cannot be the result of involution of cerebral dysfunction (e.g., recovery from haemorrhage) and therefore have to be interpreted as changes in the state of unconsciousness or level of coma. The stimulated t h e t a / b e t a changes in awake subjects could be explained by changes of vigilance and the state of attention; subjects became either drowsy because of the monotonous repetitive stimulation ( t h e t a / b e t a increase) or more alert ( t h e t a / b e t a decrease). Stimulus-induced LEG and cardiac alterations after repetitive vibration and light stimulation could be interpreted as lightening of coma, even though the patient may not remain in this state very long. Whether or not the stimulation technique is of clinical benefit needs further research work.
R~sum~ Rbactions EEG h long terme chez des patients en comas aprbs stimulation rbpbtitive Vingt patients avec traumatisme crfinien grave et dont le comas se situait entre 4 et 6 sur l'6chelle de Glasgow ont 6t6 soumis g une &ude multimodale de potentiels 6voqurs. Apr+s un enregistrement LEG pendant le repos (t~moin 1), des stimulus composrs de 60 vibrations mrcaniques et des stimulus visuels (intervalle interstimulus 10 sec) ont ~t6 appliques. Un second LEG fut alors effectu6 (trmoin 2). Afin de quantifier les altrrations ~t long terme de I'EEG apr+s stimulation, les trmoins 2 ont 6t6 comparrs aux trmoins 1 sur la base du taux spectral th~ta/b~ta calcul6 pour les ddrivations centrales. Pour 50% des patients, le taux th~ta/b~ta a 6t~ trouv6 modifi6 chez les trmoins 2, traduisant un effet durable de la stimulation. Des altrrations cardiaques induites par la stimulation ont ~galement 6t6 trouvres.
409
References Arfel, G. Introduction to clinical and LEG studies in coma. In: R. Harner and R. Naquet (Eds.), Clinical LEG. II. Handbook of Electroencephalography and Clin. Neurophysiol., Vol. 12. Elsevier, Amsterdam, 1975: 5-19. Bricolo, A., Turazzi, S., Faccioli, F., Odorizzi, F., Sciarretta, G. and Erculiani, P. Clinical application of compressed spectral array in long-term LEG monitoring of comatose patients. Electroenceph. clin. Neurophysiol., 1978, 45: 211-225. Chatrian, G.E., White, Jr., L.E. and Daly, D. Electroencephalographic patterns resembling those of sleep in certain comatose states after injuries to the head. Electroenceph. clin. Neurophysiol., 1963, 15: 272-280. Fischer, C.M. The neurological examination of the comatose patient. Acta neurol, scand., 1969, 45 (Suppl. 36): 56. Fischgold, H. et Bones, (3-. Exploration 61ectroencrphalographique des ~tats comateux. Sem. H~p. Paris, 1946, 22: 1245-1247. Fischgold, H., Torrubia, H., Mathis, P. et Arfel-Capdevielle, G. Rraction LEG d'rveil (arousal) dans le coma. Correlations cortico-cardio-respiratoires. Presse mrd., 1955, 61: 1231-1233. Gibbs, E.L. and Gibbs, F.A. Atlas of Electroencephalography, Vol. 1. Addison-Wesley, Cambridge, MA, 1950. Gotman, J., Gloor, P. and Ray, W.F. A quantitative comparison of traditional reading of the LEG and interpretation of computer-extracted features in patients with supratentorial brain lesions. Electroenceph. clin. Neurophysiol., 1975, 38: 623-639. Jennett, B. and Bond, M. Assessment of outcome after severe brain damage. Lancet, 1975, 1: 480-481. KiSpruner, V., Pfurtscheller, G. and Auer, L.M. Quantitative LEG in normals and in patients with cerebral ischemia. In: G. Pfurtscheller, E.J. Jonkman and F.H. Lopes da Silva (Eds.), Progress in Brain Research, Vol. 62. Elsevier, Amsterdam, 1984: 29-50. Kubicki, St. and Freund, G. Residual polymorphic sleep activity in moderate coma. In: E.J. Speckmann and H. Caspers (Eds.), Origin of Cerebral Field Potentials. Georg Thieme, Stuttgart, 1979:115 121. Pfurtscheller, G., Schwarz, G., Pfurtscheller, B. und List, W. Computeruntersti~tzte Analyse von LEG, evozierten Potentialen, EEG-Reaktivitgt und Herzfrequenzvariabilit~it an komat~Ssen Patienten. Z. EEG-EMG, 1983, 14: 66-73. Pfurtscheller, G., Schwarz, G. and Gravenstein, N. Clinical relevance of long-latency SEPs and VEPs during coma and emergence from coma. Electroenceph. clin. Neurophysiol., 1985a, 62: 88-98. Pfurtscheller, G., Schwarz, G. and List, W. Brain death and bioelectrical activity. Intens. Care Med., 1985b, 11: 149-153. Rumpl, E., Prugger, M., Bauer, G., Gerstenbrand, F., Hackl, J.M. and Pallua, A. Incidence and prognostic value of spindles in post-traumatic coma. Electroenceph. clin. Neurophysiol., 1983, 56: 420-429.
410 Silverman, D. Retrospective study of the EEG in coma. Electroenceph, clin. Neurophysiol., 1963, 15: 486-503. Steadman, J.W. and Morgan, R.J. Use of a spectral ratio in lateralization of CNS lesions. Electroenceph. clin. Neurophysiol., 1974, 37: 399-402.
G. PFURTSCHELLER ET AL. Teasdale, G. and Jennett, B. Assessment and prognosis of coma after head injury. Acta neurochir. (Wien), 1976, 34: 45-55.
Electroencephalograph)' and clinical Neurophysiologv, 1986, 6 4 : 4 0 2 - 4 1 0 Elsevier Scientific Publishers Ireland, Ltd.
L O N G - L A S T I N G E E G R E A C T I O N S IN C O M A T O S E P A T I E N T S AFTER R E P E T I T I V E S T I M U L A T I O N t G. P F U R T S C H E L L E R *, G. S C H W A R Z ** and W. LIST ** * Department of Computing, Institute of Biomedical Engineering, Technical University of Graz, A-8010 Graz, and ** Institute of A naesthesiology, University of Graz, A-8036 Graz (Austria) (Accepted for publication: April 9, 1986)
Summary
Twenty patients with severe head injury and a Glasgow Coma Scale of 4 - 6 were subjects of a multimodality EP study. After EEG recording during rest (control 1) 60 mechanical vibration stimuli and 60 visual stimuli (interstimulus interval 10 sec) were applied. Thereafter a second EEG (control 2) was measured. To quantify a long-lasting stimulated EEG alteration, control 2 was compared with control 1 on the basis of the spectral t h e t a / b e t a ratio calculated from central derivations. In 50% of the patients the t h e t a / b e t a ratio was changed in control 2 and therefore a long lasting stimulation effect can be assumed. Stimulus-induced cardiac alterations were also found.
Keywords: EEG reactions - coma - repetitive stimulation
The E E G reactivity studies during and after various forms of sensory stimulation play an important part in the evaluation of c o m a t o s e patients. In 1946, Fischgold and Bones suggested that the EEG changes could be regarded as signs of cortical reactions to sensory input. This EEG reactivity can occur immediately after a single stimulus or with delay; it can be short lasting in the form of bursts or spindles (Rumpl et al. 1983), long lasting for minutes (Arfel 1975), or result in a new EEG pattern (Chatrian et al. 1963). In light coma the application of a single stimulus will produce widespread reactions immediately; in deep coma, however, the immediate reaction of cerebral activity is very often abolished, but there may still be a delayed and long-lasting EEG alteration (Arfel 1975). In a retrospective study long-lasting EEG reactions after repetitive stimulation were analysed in comatose patients. When stimulus-induced E E G alterations are found it could be speculated that an arousal or lightening of coma has occurred.
1 Supported by the ' F o n d s zur Foerderung der wissenschaftlichen Forschung,' Project 5393, the Styrian Research Fonds, and the 'Oesterr. Nationalbank,' Project 1915.
This would mean that repetitive stimulation of a special modality and quality is not only a diagnostic tool alone but could be used for therapeutic purposes as well. Whether or not the stimulus-induced alterations in brain activity are desirable or should be avoided principally in comatose patients is not in the scope of this paper. The material includes quantitative EEGs recorded before and after repetitive mechanical vibration and visual stimulation in groups of normals and comatose patients. This stimulation is part of a multimodality evoked potential evaluation.
Patients and Methods
Studies were performed in the intensive care unit of the Institute of Anaesthesiology, University of Graz, where comatose patients with severe head injury are under medical treatment. Combined quantitative EEG and multimodality evoked potentials were used for assessment of cerebral dysfunction (Pfurtscheller et al. 1983, 1985a). Twenty patients with severe head injury (12 of them with polytrauma) and a Glasgow C o m a Scale (GCS) of 4 - 6 (Teasdale and Jennett
0013-4649/86/$03.50 ~ 1986 Elsevier Scientific Publishers Ireland, Ltd.
EEG REACTIONS IN COMATOSE PATIENTS
1976) are included in this study. The outcome was classified according to the Glasgow Outcome Scale (Jennett and Bond 1975). Using this classification, 7 patients showed 'good recovery,' 4 'moderate disability' and 1 'severe disability,' 1 was classified as 'vegetative state' and 7 died. The ages ranged from 18 to 64, mean 31 + 16 years. To be able to compare the effect of cerebral stimulation in comatose patients and conscious subjects and to set up thresholds, 2 control groups were formed, one consisting of 8 comatose patients after good clinical recovery, aged between 17 and 22 (mean 20_+ 1 year), and the other composed of 14 volunteers between 19 and 47 years (mean 26 + 7 years). The test programme used for multifunctional measurements in comatose patients and controls consisted of the following sequences: EEG recording during rest (control 1); slow, repetitive mechanical vibration; slow, repetitive light stimulation; E E G recording during rest (control 2); further EEG recordings (control 3, control 4, etc.) in some patients. EEGs were recorded from Cz-C3, Cz-C4, CzA2, and approximately F3-F4 and O1-O2; but only the two central records were used for statistical analysis in this study. During each control session maximally sixty 6 sec trials with intervals of 6.5 or 8 sec were sampled by a PDP 11/23 computer and used for calculation of power spectra. The E E G spectra were divided into 4 frequency bands (0-4, 4-7.5, 6.5-13.5, 14.5-24 Hz); the absolute and relative band powers and the t h e t a / b e t a power ratios were calculated. Sixty 1 sec mechanical vibration stimuli of 100 Hz were applied via a plastic ring to the last digit of the index finger of the right hand. After a break of about 15 min, used for changing the stimulator and starting the computer programme, 60 light stimuli of 1 sec duration each were applied to both eyes. The stimulus interval was 10 sec for each modality (Pfurtscheller et al. 1985a). This experimental paradigm has been used in our ICU as standard since 1980 and does not include randomization of the stimulation procedures. In this retrospective study therefore vibration has always been given before light stimulation. Depending on the stimulation sequences and
403
also on occasional therapeutic interventions, control 2 was started about 60 min after the end of control 1. Further successive controls were performed in some patients at intervals of about 30 min. Special attention has been given to the medication. Clinical data, medication, GCS and clinical outcome are summarized in Table I.
Results
Spectral ratios of the types d e l t a / b e t a (Steadman and Morgan 1974), (delta + theta)/(alpha + beta) (Gotman et al. 1975) and t h e t a / b e t a (K6pruner et al. 1984) have the benefit of normalization, are especially suitable for follow-up studies and are used very often in quantitative EEG. In studies where movement artefacts can occur, as in our intensive care patient for example (sucking, measurement of blood pressure, obtaining of blood samples, etc.), the delta power should be avoided as parameter. Therefore we decided to use the t h e t a / b e t a ratio, particularly as this parameter has been successfully used in follow-up studies in
20
/--\ •
Bin. 17 ( 13 weeks)
15
10
/
4,., .
/
'
/ //
~
" 12di
",7~
~ ' ~
"
6"
"
'9
And, 20 (8days)
\ N
X
"
-'~'7" .........
Id '3
I. " - - . ,
'
'12"
'
sve,t9
~ ~
(19 weeks)
GCS 15
G.R.
Fig. 1. Time course of the theta/beta ratio evaluated in 4 comatose patients with good clinical recovery during control 1 before stimulation. Note the inverse U-shaped form. Two patients (BIN, 17 and H•L, 20), both with severe head injury, were not in the study because the latter had no control 2 and the former a GCS > 6 at the first examination. The length of the follow-up (in days) and interval from the injury are marked.
404
G. P F U R T S C H E L L E R
stroke patients (KiSpruner et al. 1984) and a large data pool is available. To give an impression of the magnitude of the theta/beta ratio during, control 1, the mean values and standard deviations of each of the 3 groups were calculated: comatose patients recovered patients after severe head injury volunteers
4.1+3.4
(N=20)
4.0+2.9 1.4 + 0.7
(N=8) (N = 14)
The mean of 1.4 _+ 0.7 is characteristic for a normal brain function during wakefulness. Increased theta/beta ratios have been found in the comatose state but also after emergence from coma. High t h e t a / b e t a ratios are characteristic for slow
ET AL.
monorhythmic activity; low t h e t a / b e t a ratios have been found in the awake state and with polymorphic sleep activity as well. The t h e t a / b e t a ratio measured before stimulation (control 1) can be used for long-term EEG monitoring of comatose patients. The data of the patients displayed in Fig. 1 show inverse U-shaped curves with initially increasing t h e t a / b e t a ratios and later, usually when awake, with decreasing t h e t a / b e t a ratios. In very deep coma an increased t h e t a / b e t a ratio can also be found. From the t h e t a / b e t a ratios obtained in both central derivations during control 1 and control 2 the percentage increase or decrease (referred to control 1) was calculated. Two arbitrary thresholds have been established: + 50% and - 25%. Subjects
TABLE I S u m m a r i z e d patient data: clinical status, G l a s g o w C o m a Scale (GCS) at the time of testing, medication~ respiration, clinical o u t c o m e (GR, good recovery; SD, severe disability; MD, mild disability; VS, vegetative state; D, death), t h e t a / b e t a ratios before s t i m u l a t i o n m e a s u r e d in b o t h hemispheres, percentage change of the t h e t a / b e t a ratio (control 2 referred to control 1), classification into 2 s u b g r o u p s and percentage c h a n g e of heart rate (HR). Patient no. 13 with the a s y m m e t r i c response had a right hemisphere lesion. Patient G C S Age Polyno,
Medication*
Respiration
Outcome
trauma
1 2 3 4 5 6
4 4 5 4 4 5
29 20 64 16 20 19
+ +
7 8 9 10 11
5 6 6 6 5
49 24 45 20 18
12 13 14 15 16 17
6 5 4 5 6 5
18
19 20
T h e t a / b e t a C1
%
Left
Right
Left
Right
Class.
HR
~-83 ~186 0 +2
C C -
+9 +17 - 3 4
+63
+ 50
C
- 4
+10
+15
-
0
14.0 1.2 4.2 2.1 2.8
51 -23 +9 -20 +5
6O 25 0 -29 18
C C
10.8 1.7 4.8 5.2 1.8 7.0 5.4 3.0 3.8
+8 +54 -21 +57 +43 16 + 14 + 5 47
+ 19 12 15 +40 i-67 0 9 + 20 24
C C C
Spont/int Artificial D r o p e r i d o l + fentanyl 2 ml Artificial PS 250 mg Spont/trach Spont/int D r o p e r i d o l + fentanyl 5 ml Artificial F c n t a n y l 0.1 mg
Death G o o d recov. Death Veg. state G o o d recov. G o o d recov.
2.2 2.3 1.6 5.8 1.1 4.0
3.5 2.3 1.4 4.8
+18 + 148 + 13 -16
1,0
3.4
+ + -
PS 250 mg PS 250 mg
Spont/int Spont/int Spont/int Spont/int Spont/int
Mod. disab. 16.9 Mod. disab. 1.3 Severe disab. 2.1 G o o d recov. 1,5 G o o d recov. 2.2
19 22 56 38 19 59
+ + + + +
F e n t a n y l 0.1 mg D i a z e p a m 20 mg -
4
25
-
6 4
39 18
+ +
Artificial Spont/int Spont Spont/int Spont/int Artificial Spont/int Spont/int Spont/trach
Mod. disab. G o o d recov. Death Death Mod. disab. Death Death G o o d recov. Death
+
M e l p e r o n 10 mg M P C 50 m g
Piracetam 400 mg M H 1 mg
9.3 1.3 3.9 4.2 1,4 5.7 2,9 3.8 4.5
* I n t r a v e n o u s m e d i c a t i o n within 6 h before E E G study, last a p p l i c a t i o n 2 h before. PS = p h e n y t o i n - s o d i u m ; M P C = m e t h y l p e r o n c h l o r i d e (i.m.): M H = m o r p h i u m h y d r o c h l o r (i.m.); spontaneous: trach = tracheotomised; + = p a t i e n t s with p o l y t r a u m a ; C = classified as ' c h a n g e d . '
C -
C
int = i n t u b a t e d ;
- 7 + 10 5 -7 -21
0 3 +3 +1 -9 + 2 0 + 3 7
spont =
EEG REACTIONS IN COMATOSE PATIENTS
2-r~
THETA BETA
AND, 20
+63% -21
,
.
0
8
,, . . . . .
16
24
405 THETA BETA
Kai, 18a
15-
10 -53d
32 Hz
. [--~---~ibr. =
HR
LSP O-
150- min !
+10%
-1
pre
~
02 ~
stimulation
post 5
~
C4 I 65
95 rain
11d
125
-2
'
v
v
8
w
v
w
16
l
l
24
3~Hz
100
~
53d ~
°
~ ~
6 .
4 ~
d 60d
75
1,
LOP 04
-1.
,C2 ,
-=
0
-47 %
Ci X('-.\ i6 44 g2Hz
Fig. 2. Example of logarithmic spectra belonging to the "changed' subgroups (upper and lower panels) and the 'unchanged' subgroups (middle panel). Full line spectra calculated before stimulation (control 1), stippled line spectra calculated after stimulation (control 2). Data from patients no. 5, 6 and 20 (from top to bottom) are displayed.
with a t h e t a / b e t a ratio increase (from control 1 to control 2) > 50%, or a t h e t a / b e t a ratio decrease < 25% in one or both of the central channels were classified as 'changed,' all others as 'unchanged.' Using this classification, 10 out of 20 of the comatose patients demonstrated a change in control 2 EEG, whereby the t h e t a / b e t a ratio showed an increase in 6 patients and a decrease in 4 (Table I).
Fig. 3. Time course of the theta/beta ratio (upper panel) and the heart rate (lower panel) in patient no. 20 measured on different days (d) after head injury. The GCS improved in this time from 4 to 9.
In the control groups of recovered patients and normal volunteers 8 out of 22 (41%) showed a stimulus-induced E E G alteration; in 6 the t h e t a / beta ratio was increased and in 2 it was decreased. The heart rate (HR) was also measured. The percentage changes of the H R during control 2 compared with control 1 are summarized in Table I, last column. H R changes > 5% (arbitrary threshold) were classified as significant. Eight patients showed an altered HR, 3 patients an acceleration and 5 a slowing. In 7 patients stimulus-induced E E G and cardiac alterations were found in parallel; 9 patients demonstrated neither E E G nor cardiac alterations. Examples of logarithmic spectra of 3 subjects belonging to the subgroups classified as ' u n changed' and 'changed' are displayed in Fig. 2.
406
G. P F U R T S C H E L L E R
A
A
J
O
8
16
24
32
O
8
8
16
16
24
24
:11O ~8
82
32
O
8
16
24
32
1/ J
~
,T,,ERS..
I,$T
-~' ~'
~ONTROL~
UNIVeRSitY
16
8
post
24
0~
ORR,
8
16
24
32
12:40
8
16
24
0
tO Z4
$2
% FO848N
KRI. 8.H.T. 4TH
0
HERS.,
CONTROL
2
'
. . . . . .
/
A
4PL. I IL! -
~2
INST RNRESTHESIOLOGY INST BIOHEDICRL ENG UNIVERSITY OF GRAZ
MRNFREO. 1 8 R
O
i2
0
8
16
24
32
7
8
t6 24 32
-2,.
~ ½..~4.
i2
I
post 95min
65rain
I -JUL-82
. . . . . . . . 0
/CNT4 0
0
-2
11:40
CONT3
I
,'~'i','~
1-JUL-82
RNR~STHE~IO~O~Y
]
32
-t
FOB4,N
I~R
24
%
post 5min
H~N~RE~.
16
2
pre i-JUL-S2
\ SPEC
CONT2
SPEC x""1
"/CONT 1
0
E T AL.
~i
KRI MRNFRED,18R 5.H.T. 4TH HERS., COhlTROL 3
Foo,oN INST RNRESTHESIOLOGY INST BIOMEDICAL ENG UNIVERSITY OF GRRZ
1-JUL-82
1~:10 KRI MRNFREO,18FI 5.M.T. CTH HERS., CONTROL ¢
INST RNAESTHESIOLOGY INST BIOMEDICAL ENG UNIVERSITY OF GRRZ
Fig. 4. Topographical display of power spectra before (control 1) and after stimulation (controls 2, 3 and 4). Data from patient no. 20 (GCS = 9), 60 days after injury. Note the similarity of the spectra measured before (control 1) and 95 rain after stimulation (control 4).
EEG REACTIONS IN COMATOSE PATIENTS The deviations between the spectra are visible although the scale is logarithmic. Stimulus-induced EEG and H R alterations are extremely variable and depend on the level of coma, the neurological status, the medication and other things; t h e t a / b e t a increase or decrease and cardiac slowing or acceleration can be found in the same patient. To demonstrate this, data from patient no. 20 are displayed in Fig. 3, recorded on different days during clinical improvement (the data of the 11 day measurement are used in Table I). From the last 2 measurements (60 and 64 days after injury) further controls after stimulation are available. Examples of the topographical display of the power spectra in the 60 day measurement are displayed in Fig. 4. The peaks at 12 Hz (marked by arrows in Fig. 4) in the frontal and central derivations indicate 12 Hz spindle activity. These spindles, together with a decreased heart rate (see Fig. 3, lower panel), are characteristic of a 'sleep' state (Gibbs and Gibbs 1950).
Discussion
Half of our comatose patients showed an increase or decrease of the t h e t a / b e t a ratio, indicating a stimulus-induced prolonged EEG alteration. Most of these patients showed heart rate changes additionally. This raises some questions, which are worth discussion: (1) which stimulus modality, vibration or light, is responsible for the long-lasting effect on the EEG? (2) the t h e t a / b e t a ratio shows an increase in some patients and a decrease in others; how can this be interpreted? (3) is there any correlation between the clinical outcome and the subgroups classified as 'changed' and ' unchanged,' respectively? (1) Referring to stimulus-induced EEG alteration two possibilities have to be taken into consideration, (i) a direct modality-specific and (ii) an indirect modality-unspecific activation or modulation of EEG generating structures in superficial cortical layers. In one case the primary sensory pathway and in the other the ascending reticular activating system in the brain-stem probably plays
407 a role. Evidence for modality-specific EEG alterations is given by Pfurtscheller et al. 1985b; in two patients with a flat EEG repetitive mechanical vibration of the index finger provoked an EEG activity for about 30 min, strictly localized to the sensorimotor region. Stimulus-induced EEG alterations have already been observed during vibration but are reinforced during light stimulation and reach the largest extent during control 2 (see Fig. 5). This observation and the close linkage of EEG and cardiac changes refer more to a contribution of modality-unspecific reticular structures in the brain-stem than to a modality-specific activation. At this time no clear answer can be given to the question of whether vibration or light stimulation or a modality-unspecific activation of reticular structures is primarily responsible for long-latency EEG alterations. (2) Follow-up measurements of the t h e t a / b e t a ratio in some comatose patients with good clinical recovery demonstrate a characteristic pattern. In states with low GCS values (deep and moderate coma) the t h e t a / b e t a ratio increased. Before reaching GCS = 15 and afterwards, the t h e t a / b e t a ratio decreased; some initial numbers of the t h e t a / b e t a ratio obtained during deep coma (GCS 3-4) were high and decreased afterwards. These data indicate that in the course of emergence from 250- %
200-
5 15 16
150
100 . . . . . .
5¢ Control 1 I
Vibr.
I
Light
l Control 2
Fig. 5. Changes of the theta/beta ratio (control 1 = 100%) in some patients during stimulation and control 2.
408 coma the t h e t a / b e t a ratio increases and after reaching an altered state of consciousness the t h e t a / b e t a ratio decreases in parallel with the involution of cerebral dysfunction. A slowly declining t h e t a / b e t a ratio is also typical and characteristic in alert patients with cerebrovascular insufficiency during clinical recovery. A decrease of the t h e t a / b e t a ratio during wakefulness characterizes an improvement of cortical functions. This inverse U-shaped time course of the t h e t a / b e t a ratio (first increase, then decrease during recovery) could indicate that stimulation can produce either a decrease or increase of the t h e t a / beta ratio, which depends on the amount of t h e t a / b e t a at the time when the stimulus is applied. When the t h e t a / b e t a ratio in coma was low in our study, repetitive stimulation resulted mainly in a t h e t a / b e t a ratio increase; when the ratio was high, vibration resulted mainly in a t h e t a / b e t a ratio decrease. Therefore both types of change can be interpreted as a positive stimulation effect in the direction of emergence from coma. (3) Patients with an unfavourable outcome (death, vegetative state, severe disability) have to be divided into those with a clinical outcome directly related to the head injury (e.g., brain death) and those unrelated to it, e.g., patients with polytrauma. Some of them showed clinical improvement in the ICU (e.g., patient no. 2 0 ) b u t died later, e.g., following septic complications. Therefore only data of patients with a favourable outcome (good recovery, moderate disability) were analysed with regard to the prolonged EEG alterations. All except one of this subgroup, receiving no droperidol, fentanyl or morphia (patients no. 2, 5, 7, 8, 10, 13, 16), had prolonged EEG alterations. The only patient with brain death (no. 18) demonstrated no EEG and H R alteration. Some correlation between a favourable outcome and stimulusinduced EEG alteration is therefore evident. On the other side this confirms the results of Rumpl et al. (1983) that an unfavourable outcome is indicated by the loss of reactivity to external stimuli. Coma can be best defined as a state of impaired consciousness that may be either stable or unstable. In stable coma stimulation produces no behavioural response and no EEG or heart rate
G. PFURTSCHELLERET AL. alteration. Examples of this type belong to the subgroup classified as 'unchanged' (patients no. 3, 4, 6, 9, 12, 14, 17, 18 and 19). From this group a subgroup can be formed (patients no. 3, 6, 12 and 19), in which the absence of stimulus-induced EEG and heart rate alterations is probably the result of a brain 'protection.' These patients received droperidol and fentanyl or morphia. A typical unstable coma is the light coma which marks a limit between unconscioussness and wakefulness. In light coma the patient can be aroused by external stimulation and the EEG demonstrates a marked change after stimulation (Fischer 1969). A change in coma level can be either spontaneous or stimulated. The former can be quantified by measuring the t h e t a / b e t a ratio from control EEGs recorded on different days, the latter by calculation of the t h e t a / b e t a ratio before and after repetitive stimulation. With lightening of the coma the t h e t a / b e t a ratio increases first (up to 10 or more) and then decreases. After emergence from coma and recovering full consciousness the t h e t a / b e t a ratio can still be higher and then decrease slowly to a normal level of 1.4 + 0.7. Sometimes this normal level may be reached only weeks after regaining full consciousness. A high t h e t a / b e t a ratio during control 1 is therefore not only characteristic of a state of unconsciousness but can also be observed in waking patients with brain dysfunction. A typical example of this is the control group of recovered patients with a t h e t a / beta ratio of 4.0 +_ 2.9; in the course of clinical recovery the t h e t a / b e t a ratio can decrease to the normal values of 1.4 _+ 0.7 of healthy subjects. Spontaneous changes of the t h e t a / b e t a ratio in a comatose patient can be interpreted partly as a shift in the state of unconsciousness and partly as being due to involution of cerebral dysfunction. Variations of the EEG pattern and the t h e t a / b e t a ratio, respectively, can also be due to the appearance of typical or atypical sleep potentials and changes between the 'alert' state and the 'sleep' state (Chatrian et al. 1963; Silverman 1963; Kubicki and Freund 1979; Rumpl et al. 1983). Such spontaneous EEG variations are more frequent in mild than in deep coma (Bricolo et al. 1978). Stimulated EEG alterations can be quantified
LEG REACTIONS IN COMATOSE PATIENTS
by the t h e t a / b e t a ratio measured before and after repetitive stimulation and were found in half of our comatose patients. This form of LEG reactivity to various types of sensory input has already been reported by Fischgold and Bones (1946), Fischgold et al. (1955), Chatrian et al. (1963) and others. In contrast to spontaneous LEG changes, the stimulated alterations cannot be the result of involution of cerebral dysfunction (e.g., recovery from haemorrhage) and therefore have to be interpreted as changes in the state of unconsciousness or level of coma. The stimulated t h e t a / b e t a changes in awake subjects could be explained by changes of vigilance and the state of attention; subjects became either drowsy because of the monotonous repetitive stimulation ( t h e t a / b e t a increase) or more alert ( t h e t a / b e t a decrease). Stimulus-induced LEG and cardiac alterations after repetitive vibration and light stimulation could be interpreted as lightening of coma, even though the patient may not remain in this state very long. Whether or not the stimulation technique is of clinical benefit needs further research work.
R~sum~ Rbactions EEG h long terme chez des patients en comas aprbs stimulation rbpbtitive Vingt patients avec traumatisme crfinien grave et dont le comas se situait entre 4 et 6 sur l'6chelle de Glasgow ont 6t6 soumis g une &ude multimodale de potentiels 6voqurs. Apr+s un enregistrement LEG pendant le repos (t~moin 1), des stimulus composrs de 60 vibrations mrcaniques et des stimulus visuels (intervalle interstimulus 10 sec) ont ~t6 appliques. Un second LEG fut alors effectu6 (trmoin 2). Afin de quantifier les altrrations ~t long terme de I'EEG apr+s stimulation, les trmoins 2 ont 6t6 comparrs aux trmoins 1 sur la base du taux spectral th~ta/b~ta calcul6 pour les ddrivations centrales. Pour 50% des patients, le taux th~ta/b~ta a 6t~ trouv6 modifi6 chez les trmoins 2, traduisant un effet durable de la stimulation. Des altrrations cardiaques induites par la stimulation ont ~galement 6t6 trouvres.
409
References Arfel, G. Introduction to clinical and LEG studies in coma. In: R. Harner and R. Naquet (Eds.), Clinical LEG. II. Handbook of Electroencephalography and Clin. Neurophysiol., Vol. 12. Elsevier, Amsterdam, 1975: 5-19. Bricolo, A., Turazzi, S., Faccioli, F., Odorizzi, F., Sciarretta, G. and Erculiani, P. Clinical application of compressed spectral array in long-term LEG monitoring of comatose patients. Electroenceph. clin. Neurophysiol., 1978, 45: 211-225. Chatrian, G.E., White, Jr., L.E. and Daly, D. Electroencephalographic patterns resembling those of sleep in certain comatose states after injuries to the head. Electroenceph. clin. Neurophysiol., 1963, 15: 272-280. Fischer, C.M. The neurological examination of the comatose patient. Acta neurol, scand., 1969, 45 (Suppl. 36): 56. Fischgold, H. et Bones, (3-. Exploration 61ectroencrphalographique des ~tats comateux. Sem. H~p. Paris, 1946, 22: 1245-1247. Fischgold, H., Torrubia, H., Mathis, P. et Arfel-Capdevielle, G. Rraction LEG d'rveil (arousal) dans le coma. Correlations cortico-cardio-respiratoires. Presse mrd., 1955, 61: 1231-1233. Gibbs, E.L. and Gibbs, F.A. Atlas of Electroencephalography, Vol. 1. Addison-Wesley, Cambridge, MA, 1950. Gotman, J., Gloor, P. and Ray, W.F. A quantitative comparison of traditional reading of the LEG and interpretation of computer-extracted features in patients with supratentorial brain lesions. Electroenceph. clin. Neurophysiol., 1975, 38: 623-639. Jennett, B. and Bond, M. Assessment of outcome after severe brain damage. Lancet, 1975, 1: 480-481. KiSpruner, V., Pfurtscheller, G. and Auer, L.M. Quantitative LEG in normals and in patients with cerebral ischemia. In: G. Pfurtscheller, E.J. Jonkman and F.H. Lopes da Silva (Eds.), Progress in Brain Research, Vol. 62. Elsevier, Amsterdam, 1984: 29-50. Kubicki, St. and Freund, G. Residual polymorphic sleep activity in moderate coma. In: E.J. Speckmann and H. Caspers (Eds.), Origin of Cerebral Field Potentials. Georg Thieme, Stuttgart, 1979:115 121. Pfurtscheller, G., Schwarz, G., Pfurtscheller, B. und List, W. Computeruntersti~tzte Analyse von LEG, evozierten Potentialen, EEG-Reaktivitgt und Herzfrequenzvariabilit~it an komat~Ssen Patienten. Z. EEG-EMG, 1983, 14: 66-73. Pfurtscheller, G., Schwarz, G. and Gravenstein, N. Clinical relevance of long-latency SEPs and VEPs during coma and emergence from coma. Electroenceph. clin. Neurophysiol., 1985a, 62: 88-98. Pfurtscheller, G., Schwarz, G. and List, W. Brain death and bioelectrical activity. Intens. Care Med., 1985b, 11: 149-153. Rumpl, E., Prugger, M., Bauer, G., Gerstenbrand, F., Hackl, J.M. and Pallua, A. Incidence and prognostic value of spindles in post-traumatic coma. Electroenceph. clin. Neurophysiol., 1983, 56: 420-429.
410 Silverman, D. Retrospective study of the EEG in coma. Electroenceph, clin. Neurophysiol., 1963, 15: 486-503. Steadman, J.W. and Morgan, R.J. Use of a spectral ratio in lateralization of CNS lesions. Electroenceph. clin. Neurophysiol., 1974, 37: 399-402.
G. PFURTSCHELLER ET AL. Teasdale, G. and Jennett, B. Assessment and prognosis of coma after head injury. Acta neurochir. (Wien), 1976, 34: 45-55.