Journal of Neurology, Neurosurgery, and Psychiatry, 1976, 39, 392-402

Patterns of arousal in comatose patientsB. M. EVANS

From the Regional Department of Clinical Neurophysiology,Brook General Hospital, London

SYNOPSIS The EEG changes, with associated cardiorespiratory phenomena and, where possible,postmortem findings, are described in six patients in coma, with some reference to other similarcases. Spontaneously occurring periodic changes were observed at varying intervals between 20 s

and 4 min but most commonly at 4-2 min. These involved simultaneous cardiorespiratory, EEG,and somatic motor phenomena related to changes in the level of arousal. It is suggested that a

physiological periodicity of the arousal mechanisms exists which may be of importance in the under-standing of the pathophysiology of comatose states.

Changes in the EEGs of comatose patients withassociated changes in the pulse and respirationrates, related to arousal stimuli, were describedby Fischgold and Mathis (1959) but have re-

ceived little attention since. Periodicities of thesame systems have also been observed in theearly stages of sleep (Bulow, 1963, Lugaresi etal., 1972) and in subacute spongiform encephalo-pathy (Evans, 1975).

Changes of similar timing have been widelystudied in the cerebrospinal fluid pressure whichare also associated with cardiorespiratory,blood pressure, and EEG changes (Lundberg,1960; lngvar and Lundberg, 1961; Kjallquist etal., 1964; Cooper and Hulme, 1966; Symon etal., 1972).

This study presents some of the results ob-tained from monitoring a large number ofpatients in coma. Those patients in whom thechanges were most prominent or instructivehave been described in detail. It is suggested thatall the different periodicities mentioned have a

common origin in the inherent periodicity of thearousal mechanisms, the system in which thechanges are most apparent being determined bythe particular pathological or physiologicalcircumstances.

METHODS

All the patients studied were admissions to theemergency or neurosurgical services of the Brook(Accepted 16 December 1975.)

392

General Hospital, London. The records were madewith SLE encephalographs, E18/16 or E8b, usingsilver disc or needle electrodes placed according tothe modified Maudsley system (Pampiglione, 1956).The electrocardiogram (ECG) was recorded fromthe left and right shoulder, giving a modified standardlead 1. The respiration was recorded with a thermo-couple transducer over the nose or mouth.The respiratory and pulse rates were calculated

from the paper speed by measuring each breath froma suitable stable feature on the trace and betweenevery other R wave on the ECG. Line graphs werethen drawn to show the changes of rate at 2 sintervals. In each of the Figures these graphs havebeen shown under a representative section of theEEG, the location of which has been indicated on thegraphs by broad arrows. If the machine was stopped,the base line of the graph has been broken. If EEGchanges could be seen clearly, their duration hasbeen shown by a solid line above the graphs; in eachcase the respiration graph has been shown above thepulse rate graph but the time scale is the same forboth and they were plotted concurrently. Othernotations are described individually and, where pos-sible, the neuropathology is illustrated on theFigures.

CASE HISTORIES AND EEG FINDINGS

CASE 1

(N28438MB) A woman aged 53 years whose pre-vious health was good, apart from menstrualirregularities which had been treated with oestrogensfor three years, collapsed unconscious in the street.Admitted to her local hospital, she was found to be

Patterns of arousal in comatosepatients39

A,V~~~ ~ ~ ~ ~ ~ ~~- -v4-~~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ M~~~~~~~~~t~~~~~~tt/4t~~~~~~~~~~~~~~~~~%~0

!rGk

Ar isA

Fl j4Jiv.xk. lilA I

FIG. 1 Case 1. Woman, 53 years, subarachnoid haemorrhage. Above: LEG at 1.5 cm/s. Bursts of 1-7 Hz12activity alternatinig with lower voltage 7-12 Hz activity. Pulse and respiratory rate change in relation to LEGpattern. Below: graphs of breath to breath respiratory rate and beat to beat pukse rate at 2 s intervals. Solidblack linie indicates periods of LEG change. Events occurring at one to two minute intervals, event at C precipi-tated by clap. Prolonged episode of raised pukse and respiration after electrode change (E.C.).

deeply unconscious with a right hemiplegia and ablood pressure of 210/130 mmHg. The CSF wasuniformly blood stained. During the following threedays her level of consciousness improved and she wastransferred to the neurosurgical unit. On admission,she was drowsy and dysphasic with a dense righthemiplegia sparing the face. She had subhyaloidhaemorrhages in both eyes and her blood pressurewas 150/90 mmHg. Left carotid angiography showedno aneurysm but displacement of the pericallosalartery and the deep veins to the right suggested asmall intracerebral clot. Three days after admissionher level of consciousness deteriorated and she diedafter an illness of eight days. Postmortem examina-tion was refused.The EEG (Fig. 1) was recorded four days before her

death; she was very drowsy but occasionally obeyed

simple commands; her pupils were equal and reactedto light. The record showed frequent prolonged burstsof high voltage activity at frequencies between 1 and7 Hz alternating with periods of low voltage activityat frequencies between 7 and 12 Hz. Each episode ofslow activity was associated with an increase in thepulse and respiration rate. The end of each episodeof slow activity showed marked 'swinging' of thefrontal channels probably due to rolling eye move-ments (Fig. 1). The pulse and respiratory rate graphbelow the EEG record showed that the bursts of slowactivity were occurring at one to two minute inter-vals, most commonly at about one minute and thatsome of them were associated with movements of thelimbs or head, or by swallowing, chewing or sighing.Any minor stimulus, pinch, clap, or even a loudnoise on the ward occurring when the EEG was of

h hi

-.U.L. !.A.: a;i iL..

393

-, f"... f - :. :7 ,

. t . - A ,.. ;. -. h .,_I

I ..:

1;

B. M. Evans

FIG. 2 Case 2. Woman, 66 years, subarachnoid haemorrhage. Anterior communicating artery aneurysm.Above: EEG at 1.5 cm/s, low voltage 7-10 Hz and slower waves followed by suppression and then highervoltage slow waves with muscle artefact. Increase in pulse and respiratory rates start with suppression. Below:events occurring at about four minute intervals. Last event precipitated by pinch (P) andfurther peak by secondpinch. Indication offaster 20 s interval on descending pulse rate graph at 12th and 16th minutes. EKG = electro-cardiogram.

low voltage would precipitate slow wave activitywhich was identical with that occurring spon-taneously. This effect is indicated at C on the graphin Fig. 1.At one point an electrode was changed (E.C. on

Fig. 1) and this was followed by a period of theEEG slow activity with raised pulse and respirationrates which lasted for nearly five minutes before sub-siding spontaneously. During this period the patientremained motionless.

Changes similar to those described have beenobserved in many other patients with subarachnoidhaemorrhage, although not always so well marked.

CASE 2

(N28559B) A woman of 66 years with angina

pectoris suddenly developed severe occipital head-ache and lost consciousness briefly. Headache per-sisted and her CSF was bloodstained with xantho-chromic supernatant fluid. She was transferred to theneurosurgical unit and found to be alert with a slightright facial weakness and a blood pressure of 130/70mmHg. Bilateral angiography revealed an aneurysmof the anterior communicating artery which wasjudged to be inoperable. Thirteen days after theinitial haemorrhage she became unconscious with aright hemiplegia; she died after an illness of fiveweeks. At postmortem examination the heartshowed marked ventricular hypertrophy and fibrosis.The aneurysm of the anterior communicating arterywas associated with a left intracranial haemorrhageextending from the frontal pole to the anterior endof the corpus striatum; microscopy of the haemor-

394

Patterns of arousal in comatose patients

f&2.....

P~~~~~~~.......~fetxt£rs0r,-Z21.2.vP r -#*8

'A / I

FIG. 3 Case 3. Woman, 42 years, left middle cerebral artery embolus. Above: EEG at 0.75 cm/s. Chann2els 1,2, anid 3 right hemisphere 2-3 Hz wares of higher voltage (A) alternate with 6 Hz theta (B and C), C periodsassociated with slower pulse anid respirationi, B periods associated with movement and high pulse and respirationlrates. Chamiiiels 4, 5, anid 6 left hemisphere. Contin1uous very slow waves duiring A and B periods of lower voltagedurilg C periods. EKG= electrocardiogranm. Below: events at about one miniute initervals. Some irregularitywhenl spoken to (T).

rhage showed it to have been present for more than72 hours. It involved the anterior part of the caudatenucleus and the anterior limb of the corpus callo-sum; there was also some herniation of the cingulategyrus (Fig. 2). Blood was present in the left ventriclebut there was no fresh subarachnoid harmorrhage.The EEG was taken three days after her final

deterioration. She was responding to painful stimuliwith quasipurposeful movements in her right limbsonly; her pupils were equal and reacted to light. Herblood pressure was 190/90 mmHg. The recordshowed spontaneous periodic changes; low voltage7-10 Hz activity mixed with some slower waves atabout 1 Hz was interrupted by a suppression withloss of the faster frequencies followed by highervoltage slow waves. During the latter period, the

patient shivered slightly and muscle artefact ap-peared on the trace (Fig. 2). At the time of the sup-pression there was an increase of pulse and respira-tion rates which persisted for 1-2 min.

The graphs in Fig. 2 showed that the events wereoccurring at about four minute intervals and thatthey were sensitive to stimulation. The last event, at20 minutes on the graph, was precipitated by apinch and a further pinch given when the EEGchange had subsided produced a secondary peak.The pulse rate graph showed some evidence of ashorter interval at about 20 s. This is best seen at the12th and 16th minutes on the graph, during the fallof the pulse rate after the initial rise.

Very similar changes were seen in this patient in a

395

B. M. Evans

_~ A 1tZ -5:.

.:., . ......

l . ........ ..... ...

^.JW_ Fi ;.:., a:_S s .o :' .... ;'* . O f ::: <. :~~~~~~

FIG. 4 Case 4. Man, 49 years. Left intracerebral haemorrhage and old infarct. Above: EEG at 1.5 cm/s.Slowest activity and loss offaster frequencies over left hemisphere. Minimal EEG change at time ofpulse rateincrease and double breath (X). Below: events at about two minute intervals. Short gaps on respiration graphindicate double breaths. EKG= electrocardiogram.

record taken two days earlier, they were absent froma third record two days before death.

CASE 3

(227122) A woman aged 42 years had been noticedto have a cardiac murmur 19 years previously andhad been breathless for three years. She was ad-mitted to hospital with a history of sudden onset ofinability to move her right arm and leg or to speak,coupled with severe dyspnoea. On admission, shewas unconscious with a profound right hemiplegiainvolving the face, and acute pulmonary oedema.She was treated with diuretics, aminophylline,diamorphine, and cedilanid. An hour later she had arespiratory arrest lasting for eight minutes whichrecovered spontaneously; her heart rate remainedsteady at 80/min.

A diagnosis was made of mitral stenosis with acerebral embolus; blood cultures were negative. Thefollowing day she was conscious but drowsy, lookingaround and making purposeful movements with herright arm; she did not speak or obey commandsbecause of her dysphasia. She had a dense righthemiplegia involving the face and both plantarresponses were extensor. She remained in about thesame condition with a regular pulse between 80 and100 per min until she died during the night after anillness of six days.Postmortem examination showed a massive left

hemisphere infarct involving the territory of themiddle cerebral artery. It extended from the frontalpole to the parietal regions and involved the tip ofthe temporal lobe. It involved the head of the caudatenucleus buit spared the thalamus. There were noother lesions in the brain. The heart showed mitral

396

Patterns of arousal in comatose patienits

stenosis with fusion of the cusps; there was noevidence of bacterial endocarditis.The EEG in Fig. 3 was taken 36 hours before

death. The top three channels from the righthemisphere showed varied activity. Periods of lowvoltage, 6 Hz activity (labelled B and C) alternatedwith higher voltage waves at 21-3 Hz (labelled A).There was periodicity of the respiration. The slowerrespiratory rates were associated with the lowervoltage C periods, during which the patient waslying still with her eyes closed, whereas the highestrates were associated with the B periods when thepatient often made a purposeful movement oropened her eyes. The traces from the left hemisphere(channels 4, 5, and 6) showed continuous slow waveswhich were of lower voltage during the C periodsthan at other times. The graphs showed the eventsoccurring at about one minute intervals, when thepatient was indisturbed; talking to her producedsome irregularity. From the EEG alone it wouldhave been difficult to distinguish between the Bperiods and the C periods, although they clearlyrepresented different clinical situations.

CASE 4

(28780B) A man of 49 years developed dysphasiaand right-sided weakness two weeks before transferto the neurosurgical unit. He had had a thoracotomyone year before to remove a tumour from his rightlung which proved to be a secondary melanoma. Onadmission, he was alert but dysphasic with a righthemiparesis. His condition deteriorated rapidly.Carotid angiography showed a large avascular massin the right parietal region. A biopsy of the area pro-duced pigmented cells thought to be a secondarycarcinoma.At postmortem examination a melanomatous

deposit was found in the head of the pancreas, but inthe brain there was no evidence of tumour eithermacroscopically or microscopically. A large intra-cerebral haemorrhage occupied the left fronto-parietal region extending into the corpus callosumbut not involving the basal nuclei. There was an oldcystic infarct of the internal capsule on the left side.The EEG in Fig. 4 was taken the day before

death. He was responding by quasipurposeful move-ment with his left limbs to painful stimuli. He hadequal pupils reactive to light and a blood pressure of130/80 mmHg. The traces showed low voltage 1.0 Hzactivity over both sides most marked on the left withloss of faster frequencies on the left. Spontaneousarousals occurred, with swallowing, coughing, andchewing, which were associated with slightly highervoltage activity over the right hemisphere and with amarked increase in the pulse rate. Marked fluctua-

tions of the pulse rate were also seen which were notassociated with clinical arousals. The pulse rategraph showed a stereotyped pattern, sharp peaks atabout two minute intervals were followed by aplateau and then by a dip before the next peak.The respiration showed little periodicity but a

double breath marked X on Fig. 4 was seen with eachclinical arousal or increase in pulse rate. This breathhas not been charted on the respiratory graph andappears as a gap which can be seen to coincide withthe pulse rate peaks, whether or not these wereassociated with a clinical arousal (see third andfourth minutes of graph on Fig. 4).

CASE 5

(28486N) This 57 year old woman was admittedwith a four week history of gradually increasingweakness and sensory disturbance of the rightlimbs, with headache. On admission, she was con-scious and orientated with a left hemiparesis andsensory loss of cortical type. Her level of conscious-ness rapidly deteriorated until she was respondingonly to painful stimuli. A right carotid angiogramshowed a large avascular mass in the right frontaland anterior parietal regions. Burr hole biopsyrevealed a necrotic, malignant glioma. She died afteran illness of four weeks. At postmortem examinationthere was a large glioma of the right frontoparietal-occipital region measuring 7 cm by 5 cm, extendingfrom the head of the caudate nucleus to the level ofthe splenium. There was marked cingulate hernia-tion, uncal grooving and compression of the midbrain with no reactionary haemorrhage.The EEG in Fig. 5 was taken the day before the

patient died. She was very drowsy but respondedpurposefully to painful stimuli. Her pupils wereequal and reacted to light. She made frequent,spontaneous flexion movements mainly with herright limbs. Her blood pressure was 140/80 mmHg.The record showed little evidence of the under-

lying tumour; the principal feature was high voltageslow waves at 1-3 Hz, maximal anteriorly. There waslittle periodicity of the respiration but the pulse rateshowed marked fluctuations often associated withspontaneous movement. At periods of slower pulserate there was some lowering of the EEG voltage.The pulse rate graph showed that the principal eventswere occurring at 4-1 I minute intervals but thatthese peaks were associated with subsidiary changesat shorter 20 s intervals (see events between one andtwo minutes and again between 17 and 18 minutes ongraph Fig. 5). The period between the 11th and 16thminutes was taken up by a prolonged episode ofraised pulse rate with the shorter 20 s interval super-imposed throughout.

397

B. M. Evans

;t S o f ||8EW j 2* . A

4V I -. I...--. - .

j* ,YV jf.~A;sF e 0 ' X s *;tZ W- s 'tX w-s~ ~

l{ iI

i ,AV

FIG. 5 Case 5. Woman, 57 years. Grade 11 astrocytoma. Above: EEG at 1.5 cm/s. Continuous high voltageslow activity maximal frontally. Some variation in pulse rate little respiratory change. Below: pulse rategraph shows major peaks at I -1I minutes with evidence ofsecondary peaks at 20 s best seen on events betweenfirst and second minutes and 17th and 18th minutes. Also during episode of raised pulse rate between 11th and16th minutes. EKG= electrocardiogram.

CASE 6

(N29016MB) This 36 year old man was admittedto hospital after a road traffic accident without lossof consciousness. He was alert, with fractures of theshaft of the left femur, the left ischiopubic ramus,and the sixth and seventh ribs. The following day hebecame semiconscious with a blood pressure of100/50 mmHg and pulse rate of 130/min. He wasgiven 540 ml blood and 540 ml plasma and brieflyimproved. His level of consciousness again deterior-ated, with dyspnoea and hyperventilation; a lefthaemothorax was drained before transferring him tothe neurosurgical unit. On admission he was re-sponding to stimulation with decerebrate move-ments. It was concluded that he was severely hypoxicdue to blood loss and whole blood was thereforegiven as quickly as possible, with considerable

general improvement. During the next five days heshowed frequent, violent, spontaneous, decerebratespasms. These gradually lessened with steadily im-proving level of consciousness. He eventually madean excellent recovery and returned to work fourmonths after the accident.

The EEG shown in Fig. 6 was taken 36 hours afteradmission. At this time the patient was having fre-quent spasms both spontaneously and on minimalstimulation, a light touch or loud noise beingsufficient to precipitate one. Each spasm consisted ofextension of the back and neck with extension andinternal rotation of the arms and legs and wasassociated with sweating and dilatation of the pupils.He showed no awareness of his surroundings. Therewere no focal signs in the nervous system. With eachspasm the EEG showed high voltage activity at 1.0

398

Patterns of arousal in comatose patients

_ DAfb'" A _I s _ - C.N,r A-} ~~~~~~~-s ;-.iS s_w@F

^ % 2 _, _-, . a, -C '% .s-: -. -i

'A1..

~ ~ ~ ~

__________~ :.rAk.:

tXty.,:NI;

*: ;... .\ . ... . :.:. . . .*i \

.R X --flf; a;, iL

* 7 ^F .; t^,

.11 , A A1 I I

., ,_

i _....*

"

;' 4..

I 1.

FIG. 6 Case 6. Man, 36 years. Decerebrate spasms. ?Aetiology. Above: EEG at 1.5 cm/s. A. EEG shows slowwaves without spasm but some pulse and respiration change. B. Slow wave burst with spasm and marked pulseand respiration increase. C. Taken between two spasms, EEG remains slow but pulse and respiratory ratedecrease. Below: respiration peaks at approximately 20 s intervals, see histogram and curve. Periods of relativefreedom from spasms (S) at second, eighth, and 20th minutes alternate with frequent spasms and continuousEEG slow activity. P shows effects ofpinch.

Hz or less and there was a marked increase in thepulse and respiration rates. Between the spasms theEEG activity was at 8-10 Hz of low voltage (Fig.6B). The spasms tended to occur in groups withperiods of relative freedom between. During themore quiescent times the EEG showed bursts of slowwaves, with some increase in pulse and respirationrates, which were not accompanied by spasms (Fig.6A). During the times when the spasms were fre-quent the EEG continued to show high voltage slowwaves between the spasms, even when the pulse andrespiration rates had dropped (Fig. 6C; takenbetween spasms). The pulse and respiration graphsshowed that the spasms were occurring at about 20 s

intervals and that respiratory and pulse rate peakswere seen at the same intervals during the periods

without spasms (see second, eighth, and 20th minutesof graph). The histogram in Fig. 6 demonstrates thepreferred 20 s interval; it shows the results ofmeasurements between all the respiratory peaksduring one hour of record. The curve above showsthe number of intervals in any 4 s period. A series ofpinches (P, Fig. 6) were given when the EEG showed8-10 Hz activity and the patient was still. The firstpair of pinches produced only EEG change; thesecond pair isolated spasms and the third pair aseries of spasms.

There is some doubt about the exact aetiology ofthe cerebral disturbance in this patient; however, theclinical picture of frequent, highly reactive decere-brate spasms is commonly seen in children with headinjuries. Similar data have been collected from a

1.:

399

|

B. M. Evans

seven year old child in whom the spasms were alsooccurring at 20 s intervals.

DISCUSSION

The events observed in these patients consist ofsimultaneous changes in the EEG, pulse rate,respiration rate, and somatic musculaturewhich occur spontaneously but can be precipi-tated by minor stimuli. The clinical behaviour ofthe patient at the time of the event is that ofarousal and the stimuli produce arousal re-sponses in the EEG which are identical with thechanges occurring spontaneously, although dif-fering in appearance from patient to patient. It istherefore concluded that the changes representspontaneously occurring changes in the level ofarousal, which confirms the observations ofFischgold and Mathis (1959).The increase in arousal was not necessarily

correlated with greater awareness, a point illus-trated by cases 2 and 6 who were equally un-aware in periods of high and low arousal. In onepatient (case 3) a further EEG change was seenbriefly at the height of each arousal at whichtime she was aware of her surroundings.The interval between the spontaneous events

varies considerably from case to case, the mostcommon interval being between I and twominutes. In some patients the intervals weremuch longer (case 2) and in some shorter atabout 20 s (case 6). Cases 2 and 5 suggest thatthe shorter interval may be present at the sametime as the longer one.

It is probable that the triggering effect ofarousal stimuli is mediated by the same mechan-isms as those responsible for the orienting,startle, and defensive reflexes originally describedby Pavlov in 1927, Strauss in 1929, and Sokolovin 1960. These reflexes arise in response to anynovel stimulus and involve the same systems asthose described here (EEG, heart rate, respira-tion rate, and somatic musculature), as well asthe skin resistance and pupil size. They habituaterapidly in the alert state but fail to do so duringsleep (Sokolov and Paramanova, 1961; Johnsonand Lubin, 1967). In fact, there may be someaugmentation of the heart rate response insleep (Johnson and Lubin, 1967).

OTHER PERIODICITIES RELATED TO CENTRAL NER-

VOUS SYSTEM Periodic respiration has been

recognized in the early stages of sleep for a longtime (Magnussen, 1944; Robin et al., 1957;Bulow, 1963). Bulow (1963) showed that itoccurred in 10% of normal individuals; he alsocommented on the extremely close relationshipbetween the breathing pattern and the state ofarousal of the EEG. Coccagna et al. (1971) andLugaresi et al. (1972) have shown respiratoryperiodicity in sleep which is related to corre-sponding changes of the skin resistance andblood pressure and also to limb jerking inpatients with nocturnal myoclonus. The physio-logical expression of the arousal cycle wouldtherefore seem to be the early stages of sleep(stage 1 and 2 of Dement and Kleitman, 1957).North and Jennett (1974) studied periodicrespiration in acute brain damage and found itto be present in 55 of their 227 cases. Poole(1960) has shown a correlation between theperiodic slow wave discharge in the EEG recordsof patients with subacute sclerosing panencephal-itis and the phase of the respiratory cycle.

Lundberg (1960) studied the cerebrospinalfluid pressure by continuous monitoring. Hedescribed several types of short-term variation inpressure which show a very close resemblance tothe periodicities of this series. He recognizedthree different phenomena which he called theA, B, and C waves. The B waves occurred atintervals of to two minutes, were seen at bothhigh and normal pressures but were present onlyin sleep or coma and not when the patient wasalert. They were always accompanied by periodicrespiration and sometimes by movements of thepatient, more rarely they were associated withmyoclonus. Kjallquist et al. (1964) and Cooperand Hulme (1966) have shown that these wavesare associated with changes in the blood pres-sure and pulse rate. These B waves bear a strikingresemblance to the l- to two minute waves of thepresent series.The A waves of Lundberg, also known as

plateau waves, are more prolonged episodes ofraised pressure lasting several minutes, whichusually occur spontaneously but are sometimesprecipitated by minor arousal stimuli. They areseen both in alert and comatose states but arealways associated with raised intracranial pres-sure. These waves are probably the samephenomenon as the prolonged periods of raisedpulse and respiration rates shown by cases 1 and

400

Patterns of arousal in comatose patients

5. The latter patient certainly had raised pressureand the former probably had. Ingvar andLundberg (1961) performed EEGs on thosepatients in their series who had myoclonic jerksand found no paroxysmal activity but only slightbut definite increase in arousal.

The C waves of Lundberg are a shorterphenomenon seen four to six times a minute andare often seen superimposed on the A waves inmuch the same way that the shorter 20 s intervalwas seen during the period of raised pulse rate incase 5.

Cooper and Hulme (1966) studied the CSFpressure continuously with a cortical pressure

transducer and observed the same fluctuationsparticularly during stage 1 and 2 of sleep butabsent from deeper levels of sleep as well as

from the alert state.

Another system in which periodicities havebeen observed is the systemic blood pressure.Waves known as the Traub-Herring-Meyerwaves were originally described in 1865. Theyoccur about four to six times a minute and were

believed by Coccagna et al. (1971) and Lugaresiet al. (1972) to be related to the periodic eventsthey recorded in sleep and by Lundberg (1960)to be related to the C waves in the CSF pressure.The present study suggests that they may also berelated to the timing of events in some patientswith decerebrate spasms, a hypothesis that re-

ceives some support from the observation ofBarnes and Burnham (1969) that each Mayerwave is preceded by an increase in excitability ofthe monosynaptic lumbar reflex.

ORIGIN OF THE CHANGES Although arousal isclearly a neural phenomenon associated with thereticular system, it is not necessarily the case thatthe primary mechanism is neural in origin. It ispossible that changes in cerebral blood flow,blood pressure, pH or CO2, about which no

information is available in this study, are givingrise to secondary changes in the reticular system.A reciprocal relationship between the systemicblood pressure and the reticular system has beendemonstrated experimentally by Baust et al.(1963) and by Kakolewski and Takeo (1967) anda direct effect on cerebral blood flow by thereticular activating system has been shown

experimentally by Meyer et al. (1969) andclinically by Ingvar et al. (1964).

It is probably fruitless to attempt an exhaust-ive discussion in the face of inadequate data,however this series lends some support to thehypothesis that central nervous system periodici-ties may be due to an inherent brain-stem rhythm.This possibility was suggested by Kjallquist et al.(1973) to explain the periodic CSF pressurechanges and by Lugaresi et al. (1972) to explainthe periodicities of sleep.

Whatever may be the theoretical basis of thesephenomena, their practical implications may bemore relevant. For instance, it is difficult toimagine a situation more likely to lead to troubleafter a subarachnoid haemorrhage from ananeurysm than a cardiovascular system whichbehaves as though the patient were performing a50 yard dash every time he stirs in bed.Mechanisms which are related to changes in so

many areas, both within the cranium and else-where, must be of importance in comatose statesand also possibly in many other conditions.

REFERENCES

Barnes, C. D., and Burnham, E. (1969). The reflection ofthird order blood pressure waves in the lumbar mono-synaptic reflex. Brain Research, 13, 183-186.

Baust, W., Niemczyk, H., and Vieth, J. (1963). The action ofblood pressure on the ascending reticular activating systemwith special reference to adrenaline-induced EEGarousal. Electroencephalographyv and Clinical Neutro-physiology, 15, 63-72.

Bulow, K. (1963). Respiration and wakefulness in man. ActaPhysiologica Scandinavica, 59, suppl. 209.

Coccagna, G., Mantovani, M., Brignani, F., Manzini, A.,and Lugaresi, E. (1971). Arterial pressure changes duringspontaneous sleep in man. Electroencephalography andClinical Neurophysiology, 31, 277-281.

Cooper, R., and Hulme, H. (1966). Intracranial pressure andrelated phenomena during sleep. Journal of Neurology,Neurosuirgery, and Psychiatry, 29, 564-570.

Dement, W. C., and Kleitman, N. (1957). Cyclic variationsin EEG during sleep and their relation to eye movements,body motility and dreaming. Electroencephalography andClinical Neurophysiology, 9, 673-690.

Evans, B. M. (1975). Cyclic EEG changes in subacute spongi-form and anoxic encephalopathy. Electroencephalographyand Clinical Neurophysiology, 39, 587-598.

Fischgold, F., and Mathis, H. (1959). Obnubilations, comaset stupeurs. Electroencephalography and Clinical Neuro-phvsiology, 11, suppl.

Ingvar, D., Haggendal, E., Nilsson, N. J., Sowrander, P.,Wicklsom, I., and Lessan, N. A. (1964). Cerebral circula-tion and metabolism in a comatose patient. Archives ofNeurology, 11, 13-21.

Ingvar, D. H., and Lundberg, N. (1961). Paroxysmal symp-toms in intracranial hypertension studied with ventricularfluid pressure recording and EEG. Brain, 84, 446-459.

401

B. M. Evans

Johnson, L. C., and Lubin, A. (1967). The orienting reflexduring waking and sleeping. Electroencephalography andClinical Neurophysiology, 22, 11-21.

Kakolewski, J. W., and Takeo, Y. (1967). Relationshipsbetween EEG patterns and arterial pressure changes.Electroencephalography and Clinical Neurophysiology, 22,239-244.

Kjaliquist, A., Lundberg, N., and Ponten, U. (1964). Cardio-vascular changes during rapid spontaneous variations ofventricular fluid pressure in patients with intracranialhypertension. Acta Neurologica Scandinavica, 40, 291-317.

Lugaresi, E., Coccagna, J., Mantovani, M., and Lebrun, R.(1972). Some periodic phenomena arising during drowsi-ness and sleep. Electroencephalography and ClinicalNeurophysiology, 32, 701-705.

Lundberg, N. (1960). Continuous recording and control ofventricular pressure in neurosurgical practice. ActaPsychiatrica Scandinavica, suppl. 149, 36.

Magnussen, G. (1944). Studies on the Respiration DuringSleep. A Contribution to the Physiology of Sleep Function.Lewis: London.

Meyer, J. S., Normura, F., Sakamoto, K., and Kondo, A.(1969). Effect of stimulation of the brain-stem reticularformation on cerebral blood flow and oxygen consump-tion. Electroencephalography and Clinical Neurophysiology,26, 125-132.

North, J. B., and Jennett, S. (1974). Abnormal breathingpatterns associated with acute brain damage. Archives ofNeurology, 31, 338-344.

Pampiglione, G. (1956). Some anatomical considerationsupon electrode placement in routine EEG. Proceedings ofElectrophysiological Technologists' Association, 7, 20-30.

Pavlov, J. (1927). Conditioned Reflexes, an Investigation ofthe Physiological Activity of the Cerebral Cortex. OxfordUniversity Press: London.

Poole, E. W. (1960). Periodic EEG discharges in subacuteencephalitis with reference to respiratory and cardiaccycles. Electroencephalography and Clinical Neuro-physiology, 12, 759.

Robin, E. D., Whaley, R. D., Crump, C. H., and Travis,D. M. (1957). Alveolar gas concentrations and respiratorycenter sensitivity to CO2 during natural sleep. FederationProceedings, 16, 107-108.

Sokolov, E. N. (1960). Neuronal models and the orientingreflex. In The Central Nervous System and Behavior, pp.187-276. Edited by M. A. B. Brazier. Josiah Macy JrFoundation: New York.

Sokolov, E. N., and Paramonova, N. P. (1961). Progressivechanges in the orienting reflex in man during the develop-ment of sleep inhibition. Pavlov, J. Journal of Highe-Nervous Activity, 11, 217-226.

Strauss, H. (1929). Das Zuzammenschrechen. Jolurlna7l lfiirPsychologie und Neurologie, 39, 111-321.

Symon, L., Dorsch, N. W. C., and Stephens, R. T. (1972).Pressure waves in so-called low pressure hydrocephalus.Lancet, 2, 1291.

402