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The effect of sleep upon the electroencephalogram in patients with brain tumors
Electroencephalography and Clinical Neurophysiology Elsevier Publishing Company, Amsterdam - Printed in The Netherlands
521
T H E E F F E C T OF SLEEP U P O N T H E E L E C T R O E N C E P H A L O G R A M IN PATIENTS W I T H B R A I N T U M O R S 1 DAVID D. DALY, M.D.
Department of Neurology, The Unioersity of Texas, Southwestern Medical School at Dallas, Dallas, Texas 75235 (U.S.A.) (Accepted for publication: April 25, 1968)
INTRODUCTION
Alterations in the EEGs of patients with brain tumors have long preoccupied electroencephalographers. From their studies, a consensus has emerged regarding the nature of these changes. Tumors are electrically silent and manifest themselves only through disorganization of normal neuronal activity (Walter 1936). In the areas of maximal cortical disturbance, certain local signs appear, with polymorphic delta activity having the greatest significance. Such activity consists of small amplitude, irregular nonrhythmic discharges which occur continuously without the superimposition of normal rhythms. Adjacent to this may be a region containing what Arfel and Fischgold (1961) have termed "marginal slow waves". Such a region contains not only polymorphic delta activity but also intermixed rhythmic bursts of varying frequencies. Tumors may also evoke abnormal discharges at remote sites. The term "distant rhythms" has been applied to these abnormalities. Among the "distant rhythms" are paroxysmal rhythmic slow waves in the delta range, so-called "monorhythmic delta" (Cordeau 1959). These rhythms have a highly fixed rate of repetition, a form which may be either sinusoidal or sawtoothed due to a rapidly ascending limb, and a tendency to occur in paroxysmal bursts of varying duration. Such rhythms commonly occur in association with deeply seated tumors, particularly those in the posterior fossa. The processes generating these abnormal rhythms remain 1 Based upon the Presidential Address, 20th Annual Meeting, American EEG Society, Denver, Colorado, October 3--4, 1966.
obscure. As a result, various authors hold divergent views concerning the significance of these rhythms. Some investigators (Daly et al. 1953; Dow 1956) have regarded increased pressure within the third ventricle as a major, although not the sole, responsible factor. On the other hand, DykeD et al. (1964) have suggested that occurrence of paroxysmal bursts depends upon the presence of lesions in "an area immediately lateral to the dentate nucleus...although an associated distention of the third ventricle favored their appearance". Similarly, Bagehi et al. (1961) have stressed the occurrence of abnormality on the surface of the head contralateral to cerebellar tumors attributing this to "alteration of neural activity in crossed pathways". Electroencephalographers have remained curiously silent about the effect of sleep upon these various abnormal rhythms. Some years ago, Silverman and Groff (1957) had concluded that a slow wave focus which persisted into sleep with "suppression of sleep potentials" occurred with the most superficially located tumors. In contrast, disappearance of the slow rhythms and relatively little distortion of sleep patterns indicated that the tumor was situated at least 3 cm from the surface of the cortex. Gibbs and Gibbs (1964) have since challenged this viewpoint concluding: "our material shows no clear relationship between the depth of the tumor and changes in delta foci with sleep". They noted that some foci decreased with drowsiness while others became more evident. In some cases, the frequency of the abnormal rhythms changed during sleep. In other cases, epileptiform activity developed. They have summarized their position by saying, "We have not been able to find anything consistent about Electroenceph. din. NeurophysioL, 1968, 25:521-529
522
D.D. DALY TABLE I Location and types of tumors Location
Histological types Astrocytoma Grade 1 Grade 2 Grade 3 Grade 4 Ependymoma Sarcoma Medulloblastoma Meningioma Neurinoma Metastatic Miscellaneous Aqueduct stenosis Unverified Total
Supratentorial
Infratentorial
5 2 6 6 3 3 4 9 8 4
3 3 2 6 3 3 2 3 2
50
28
1
such changes, nor are we able to explain the inconsistencies". Because of this paucity o f information, I thought it might prove rewarding to review the problem. METHOD This study rests on a series o f seventy-eight patients who underwent a total of 93 E E G recordings. In twenty-eight of these patients, tumors were present in the posterior fossa (Table I). Fifty patients had supratentorial tumors, but further categorization poses problems. I have classified sixteen as " d e e p " tumors: five involved the thalamus, five were suprasellar in location, two were located in the region of the pineal body, two were within the third ventricle and two lay along the wall of the lateral ventricle constituting what pathologists describe as a subependymal glioma. The remaining thirty-four tumors were termed "hemispheric" but were not classified as superficial or deep principally because m a n y of them were infiltrating, malignant gliomas o f extensive size and without simply definable margins. Four extracerebral meningiomas formed too small a g r o u p to consider separately. In analyzing the E E G data, I have necessarily resorted to a degree o f oversimplification in view of the relatively small size o f the series. Extensive
E E G classification would have yielded categories with too few cases to permit meaningful conclusions; hence, I have used three descriptive categories: polymorphic delta, rhythmic slow, and normal. " P o l y m o r p h i c delta" refers to wave forms lasting more than 250 msec which have localized origin and persist virtually continuously. Morphologically, these waves have an irregular and unpredictable form which is rarely repeated. I have used this criterion as the crucial one and disregarded the presence or absence o f "marginal slow waves" and the more diffuse rhythmic slow waves. By "rhythmic slow" I am referring to m o n o r h y t h m i c delta or theta rhythms occurring in brief bursts or long trains. These rhythms may appear bisynchronously or occasionally be restricted to one hemisphere. RESULTS The data in Table lI confirm numerous previous studies which have shown that polymorphic delta activity appears in association with hemispheric lesions. In the three patients with hemispheric tumors who fell in the "rhythmic slow" category, rhythmic slow activity occurred maximally on the same side as the t u m o r but without a focus of polymorphic delta activity. In contrast, TABLE 1I Relationship between depth of tumor and type of abnormality Location Hemispheric Deep Infratentorial
Polymorphic " delta
Rhythmic slow
Normal
28 5 0
3 9 20
3 2 8
TABLE III Relation of deep hemispheric tumors to type of abnormality Location Thalamus Periventricular Third ventricle Suprase!lar Pineal body
Polymorphic delta
Rhythmic slow
Normal
3 2 0 0 0
2 0 2 4 1
0 0 0 1 1
Electroenceph. clin. Neurophysiol., 1968, 25:521-529
SLEEP EEG IN BRAIN TUMORS none of the infratentorial tumors exhibited foci of polymorphic delta activity but showed either rhythmic disturbances " a t a distance" or a normal recording. In Table I I I the deep supratentorial tumors are further subdivided. The data are consistent with observations made on the two larger supratentorial and infratentorial categories and indicate that tumors involving the parenchyma of the hemisphere, even those located at great depth, generally produce polymorphic delta activity. On the other hand, tumors obstructing the third ventricle seem to produce rhythmic slow abnormalities. It is interesting that in one patient in whom the E E G showed only rhythmic slow activity, autopsy disclosed a glioma of the thalamus intruding into the posterior portion of the third ventricle and obstructing the aqueduct. Smith et al. (1939) have suggested that occipital monorhythmic delta activity results from
523
compression of the occipital lobe by a distorted tentorium. A more likely explanation relates it to maturational changes in the brain. The data in Table IV indicate that in adults monorhythmic delta activity occurs predominantly in the f r o n t a l regions, whereas in children it appears chiefly over the posterior head regions (Fig. 1). These TABLE IV Effects of maturation on monorhythmic delta activity Age (years) <10 10-14 15-19 20-29 30+
Frontal intermittent rhythmic delta activity
Occipital intermittent rhythmic delta activity
1
9
0 5 * 10
2 1 * 0
* Occurred together in same patient.
F3-C 3
C3-P3 P3-oi Fp2F4
F4-C4 C4-P4
e -02 t
i
3405 2-21-64
i
150 ,~V 1 sec
A
5956 1-19-65
T.C.0.12 sec
B Fig. 1
Maturational changes in spatial distribution of rhythmic delta activity. A: A 7-year-old boy with ependymoma in the fourth ventricle. The EEG shows bursts of left occipital monorhythmic delta activity. B: A 17-year-old girl with a pincaloma. The EEG shows bursts of bisynchronous monorhythmic frontal delta activity (FIRDA). In this and subsequent figures, electrodes are placed in accordance with the "10-20 system" except for At1 and At2 which are 2 cm inferior to F7 and F8 respectively. Electroenceph. clin. Neurophysiol., 1968, 25:521-529
524
D.D. DALY TABLE V Stage I sleep
Awake
Stages II-IV sleep
Number of patients
A. Effect of sleep on rhythmic slow activity
+
+
f
1
[
7 .
.
.
.
!--
3
B. Effect of sleep on polymorphic delta activity 4k +
+ +
' .
2l
-.
.
5 2
.
= Slow activity present. = Absent.
findings parallel the maturational changes in spatial distribution of rhythmic slow activity induced by hyperventilation in normal persons. Turning to the effects of sleep upon these abnormal rhythms, let us consider first the rhythmic slow discharges. Previous studies have shown that
these distant rhythms react more than polymorphic slow wave activity and may, for example, be inhibited by eye opening or mental activity (Cobb 1945; Daly et al. 1953). Table V, A documents the effects of sleep on rhythmic slow activity. With few exceptions, the abnormal rhythms disappeared in the deeper levels of sleep (Fig. 2). None of the patients showed changes in normal sleep rhythms. Spindle rhythms seemed symmetrical. Spontaneous arousal occurred as well as K complexes in response to environmental stimuli. Curiously, in three patients the abnormality appeared during drowsiness and persisted into sleep, but there was no apparent explanation for these exceptions. In some patients, the slow rhythms appeared accentuated during drowsiness. Relatively minor abnormalities in the waking record often became more prominent as the patient drifted in and out of Stage 1 sleep (Fig. 3). Consideration of the reactivity of polymorphic delta activity discloses a different story. The reactivity of polymorphic delta activity in the thirty-four patients with hemispheric tumors is
FPcF 3
Fpl-T 3
FPl-A 1 - . . ~ / ~ _
F 3- C 3
Fp2--T 4
FpTA 2 _ ~ / ~ r . ~ - - .
C3- P3
FP C F 3
T 3- A 1 .~. J ~ . - . ~ .
P3- O1 . j - ~ ~ . ,
FP 2 F4
T 4 - A 2 ........
FP2-'F 4
c3-Pa
C 3- A 1 ~ - ~ - ~ .
F4 - C 4 ~ ~ J " ~ / ~
C4- P4
C 4- A 2
c,-P 4
~-~.p
01- A 1
P4-O2
P4-02
0 2- A 2
p. 191
p. 338
p. 520
Awake
Drowsy
Asleep
I.C. 0.12 sec
[ 50~tv
7464 7-3-65
1 sec
Fig. 2 A 15-year-old girl with headaches and papilledema was found to have a colloid cyst in the third ventricle. Waking record shows bursts of monorhythmic frontal delta activity (FIRDA) which disappears in Stage I sleep.
Electroenceph. clin. NeurophysioL, 1968, 25:521-529
SLEEP EEG IN BRAIN TUMORS
525
Fp?T3 Fp~-T,
FpFF Fp;-F, C3-P 3
c,-P, P -O, P,-o2 ~ J
5 0 ,uV
T.C. 0.12 sec
1 sec
8591 1-3-65
Fig. 3 A 19-year-old boy with headaches, ataxia and papilledema. Operation revealed an astrocytoma in the right cerebellar hemisphere. The waking record shows low voltage theta activity in the fronto-temporal regions. Arousal from Stage I sleep is followed by a burst of diffuse high voltage rhythmic theta activity.
FPl-At
1
Atl-T 3 T3-C 3 C3-O I Fp~-At 2 At~-T 4
T,-C, C4-O 2 Awake
Drowsy T.C. 0.12 sec
1 sec
15o~,v
Asleep 6663
4-5-65
Fig. 4 A four-year-old girl with papilledema, left hemiparesis and hemianesthesia. Autopsy revealed astrocytoma involving the right thalamus and hypothalamus. The recording in the waking state shows polymorphic delta activity intermixed with theta rhythms in the right Rolandic region. During drowsiness and sleep, theta activity disappears, but polymorphic theta activity persists.
Eleclroenceph. din. NeurophysioL, 1968, 25:521-529
526
D.D. DALY
shown in Table V, B. In general, polymorphic delta activity persisted into the deeper levels of sleep although in a few instances it remained only in the drifting stage of Stage 1 sleep. In contrast with rhythmic slow activity, in no instance did polymorphic delta activity appear only during sleep. In patients with deeply seated tumors, polymorphic delta activity occurred in five instances and in each case persisted into deeper levels of sleep (Fig. 4). Rhythmic slow activity occurred in eighteen of thirty-four patients with hemispheric tumors usually in association with polymorphic delta activity. In those in whom both monorhythmic and polymorphic delta activity occurred; the reactivity paralleled observations on patients with infratentorial tumors; namely, although occasionally persisting into the earliest levels of Phase I sleep, rhythmic slow discharges disappeared in deeper levels of sleep. Again, in one patient activation of rhythmic slow activity occurred in the drifting phase. Consideration of the characteristics of sleep
spindles disclosed another difference between the patients with hemispheric and infratentorial tumors. In the latter group, none of the EEGs showed asymmetrical sleep spindles; however, in those with hemispheric tumors, asymmetry of spindles occurred with relative frequency. Of twenty-four patients whose records disclosed polymorphic delta activity, thirteen had spindle asymmetry. In only one instance did spindle asymmetry occur in the absence of polymorphic delta activity. In all but two patients, the asymmetry consisted of reduction in voltage and frequency of occurrence of spindle bmsts or even of complete absence of spindles in the hemisphere involved by the tumor. In the two exceptions, augmentation of spindle voltage occurred in the involved hemisphere paralleling the observations of Arfel and Fischgold (1961) on augmentation of alpha activity. In the group of patients with deeply seated tumors, spindle asymmetry appeared in three patients with tumors involving the thalamus and in one with a tumor along the wall of the lateral
C3"-P3
FpI"At I At -T3
POOl
T3- P3
F3- C 3
P3- O1 F4-C 4
Fp;At 2 At2-T,
c -P. P4-o2 At;T 4
Awake 1 sec
150pV
T,-P, P,-O T.C. 0.12 s e c
Asleep 559. 12-20-62
Fig. 5 A 3-year-old girl with papilledema and right hemiparesis. Left parietal craniotomy revealed a subependymal ependymoma involvingthe lateral wall of the left lateral ventricle. The recording in the waking state shows symmetricalalpha rhythms and no polymorphic delta activity. A lengthy sleep recording shows persistent absence of spindle rhythms over the left hemisphere. Electroenceph. clin. Neurophysiol., 1968, 25:521-529
527
SLEEP EEG IN BRAIN TUMORS
FprAt3 At I -T 3 T3-P 3 P3-Om
FP -At2I Ate-T4 T4-P 4
~
v
vvw.,.,,,~
P4-O2 Asleep
Awake
5117
15o #V 1 sec
T.C. 0.12 sec
!0-6-64
Fig. 6 A 78-year-old woman suffered focal motor seizures and recurrent right hemiplegia. Craniotomy disclosed a meningioma overlyingthe left temporal lobe. Recording in the waking state shows polymorphic delta activityin the left temporal regions. This persists during sleep. ventricle (Fig. 5). In the latter patient, complete absence of spindles from one hemisphere was, in fact, the first electrographic abnormality observed. There was no evidence of spindle asymmetry in any of the remaining patients in this group in whom the EEG showed rhythmic slow activity. In agreement with the observations of Gibbs and Gibbs (1964), these data fail to confirm the criteria of Silverman and Groff for differentiating between superficial and deep hemispheric tumors (Fig. 4 and 6); but they do indicate that both spindle asymmetry and polymorphic delta activity signify involvement of the parenchyma of the cerebral hemisphere. DISCUSSION
This brief study suggests some general conclusions while at the same time raising certain questions. Previous studies have shown that "distant rhythms" exhibit marked reactivity to changes in the physiologic state of the patient: opening the eyes abolishes rhythmic slow discharges in 62 ~o of patients while hyperventilation
increases them in 60~o (Daly et al. 1953). This study demonstrates that sleep exerts a comparable effect, tending in general to eliminate the abnormal rhythms. In this regard, a rather striking parallelism exists with 3/sec generalized spikewave discharges. These latter abnormal rhythms are regularly provoked by overb~eathing. They tend to disappear in deeper levels of sleep (Delange et al. 1962) and to disappear with eyeopening. Tasks requiring the attention and concentration of patients will often abolish either "distant rhythms" or spike-wave discharges. If these similarities are more than fortuitous, they suggest that both these abnormal rhythms utilize similar anatomical systems and depend for their genesis upon derangements of thalamo-cortical mechanisms as Cordeau (1959) has suggested with respect to monorhythmic frontal delta activity (FIRDA). Further, van der Drift and Magnus (1961) have postulated that FIRDA depends on "irritative" lesions of the dorsomedial nucleus of the thalamus and noted its absence after destruction of this nucleus. In contrast, polymorphic delta activity shows Electroenceph. clin. NeurophysioL, 1968, 25:521-529
528
D.D. DALY
virtually no reactivity. Opening the eyes does not abolish it and hyperventilation exerts only inconstant and minor effects. It persists essentially unchanged throughout all levels of sleep even though its presence may be largely obscured by the general slow activity in Stages III and IV. The genesis of polymorphic delta activity poses many unanswered questions although it is usually attributed to interference with local cortical synchronizing mechanisms. Yet, polymorphic delta activity may appear in cortical areas uninvolved by tumor as attested by three patients in this study who had thalamic tumors. Skeptics may invoke arguments based upon the existence of cerebral edema or the lack of anatomically defined lesions. However, van der Drift and Magnus have also shown that tumors restricted to the thalamus can produce polymorphic delta activity in overlying regions of the cortex while Hess (1961) has reported the appearance of polymorphic delta activity following the creation of discrete, stereotactically placed subcortical lesions. Perhaps, then, polymorphic delta activity may result either from localized intracortical derangement through direct invasion by the tumor or from disruption of input into the cortex through neoplastic extension into white and gray matter in the hemispherical depths. The enduring nature of the defect may account for the loss of reactivity. By the same token, disruption of normal sleep activity; e.g., spindle rhythms, would depend upon similar mechanisms and explain their lack of reliability as indicators of the proximity of the tumor to the cortex. All these observations apply only to so-called "slow wave" or NREM sleep and give no clues as to what may occur in the rapid eye movement (REM) phase. The complexities of prolonged recording necessary to attain this phase of sleep account for this lamentable lack and, no doubt, explain the similar absence of information in other published reports. One may suspect that polymorphic delta activity will continue to show a resistance to alteration even in REM sleep. On the other hand, it is less clear what influence of REM sleep might exert on rhythmic slow activity, particularly intermittent or paroxysmal rhythmic delta bursts. A larger series of patients would permit more thorough study of the correlations between the
deranged reactivity of normal waking rhythms and distorted sleep rhythms. The present study contains too few patients to answer such crucial questions. Thus, at the moment, it appears that the clinical electroencephalographer will piofit little from extending his examination to include sleep. However, I hazard the opinion that systematic prospective studies which combine precise anatomical localization with meticulous observations of both reactivity and the abnormal waking and sleeping rhythms will disclose unexpected vistas. From this, the electroencephalographer may evolve skills which will permit localization not in the crude anatomical terms of "lobe involved" but by the more subtle physiological description of "system involved". SUMMARY
I. Electroencephalograms were recorded during the waking and sleeping states in seventyeight patients, fifty with supratentorial and twenty-eight with infratentorial tumors. 2. Tumors involving the parenchyma of the hemisphere produced focal polymorphic delta activity; tumors of the posterior fossa or those obstructing the third ventricle produced rhythmic slow activity (distant rhythms). 3. Distant rhythms show marked reactivity and generally disappear in deeper levels of sleep although sometimes being "activated" during drowsiness. 4. Polymorphic delta activity shows little reactivity and persists in deeper levels of sleep. Distortion of sleep rhythms, usually in the form of reduced spindle (sigma) rhythms, often occurs in association with polymorphic delta activity and signifies involvement of the cerebral hemisphere. Neither proved to be reliable indicators of whether the tumor was cortical or subcortical in location. These studies were carried out at the Barrow Neurological Institute; I wish to express my appreciation to Mrs. James Brittenham, chief technologist, for her assistance. REFERENCES
ARFEL, G. AND FISCHGOLD, H. EEG-signs in tumours of the brain. Electroenceph. din. Neurophysiol., 1961, Suppl. 19: 36-50.
Electroenceph. clin. Neurophysiol., 1968, 25:521-529
SLEEP EEG IN BRAIN TUMORS BAGCm, B. K., Koox, K.A., SELVING,B.T. and CALHOUN, H. D. Subtentorial tumors and other lesions: an electrocncelahalographic study of 121 cases. Electroenceph. clin. Neurophysiol., 1961, 13: 180-192. COBB, W. A. Rhythmic slow discharges in the electroencephalogram. J. Neurol. Neurosurg. Psychiat., 1945, 8: 65-78. CORDEAU,J. P. Monorhythmic frontal delta in the human electroencephalogram: a study of 100 cases. Electroenceph. clin. Neurophysiol., 1959, 11 : 733-746. DALY,D., WHELAN,J. L., BICKFORD,R. G. and MACCARTY, C. S. The electroencephalogram in cases of tumors of the posterior fossa and third ventricle. Electroenceph, clin. Neurophysiol., 1953, 5: 203-216. DELANGE,M., CASTAN,P., CADILHAC,J. and PASSOUANT, P. Study of night sleep during centrencephalic and temporal epilepsies. Electroenceph. clin. Neurophysiol., 1962, 14: 777. Dow, R. S. Electroencephalographic findings in cerebellar tumors. A review of current and old concepts. Electroenceph. clin. Neurophysiol., 1956, 8: 165.
529
DRIFT, J. H. A. VANDER and MAGNUS,O. Primary thalamic lesions. Electroenceph. din. Neurophysiol., 1961, Suppl. 19: 125-137. DYKEN, P., MANNING, H. L. and WHITE, P. Electroencephalographic changes associated with cerebellar hemisphere tumours. J. Neurol. Neurosurg. Psychiat., 1964, 27: 340-344. GIBES, F. A. and Gmes, E. L. Atlas ofelectroencephalo-
graphy. Vol. 3, Neurological and psychiatric disorders. Addison-Wesley, Reading, Mass., 1964, 538 p. HESs, R. The influence of stereotactic lesions on the EEG. Electroenceph. clin. Neurophysiol., 1961, Suppl. 19: 166-171. SILVERMAN, D. and GROFF, R. A. Brain tumor depth determination by electrographic recordings during sleep. Arch. Neurol. Psychiat. (Chic.), 1957, 78: 15-28. SMITH, J. R., WALTER, C. W. P., LAIDLAW,R. W. and CASAMAJOR,L. Posterior fossa neoplasms in children: an electroencephalographic study. Trans. Amer. neurol. Ass., 1939: 149-152. WALTER, W. G. The location of cerebral tumors by electroencephalography. Lancet, 1936, 2: 305-308.
Reference: DALY,D, D. The effect of sleep upon the electroencephalogram in patients with brain tumors. Electroenceph. clin. Neurophysiol., 1968, 25: 521-529.
521
T H E E F F E C T OF SLEEP U P O N T H E E L E C T R O E N C E P H A L O G R A M IN PATIENTS W I T H B R A I N T U M O R S 1 DAVID D. DALY, M.D.
Department of Neurology, The Unioersity of Texas, Southwestern Medical School at Dallas, Dallas, Texas 75235 (U.S.A.) (Accepted for publication: April 25, 1968)
INTRODUCTION
Alterations in the EEGs of patients with brain tumors have long preoccupied electroencephalographers. From their studies, a consensus has emerged regarding the nature of these changes. Tumors are electrically silent and manifest themselves only through disorganization of normal neuronal activity (Walter 1936). In the areas of maximal cortical disturbance, certain local signs appear, with polymorphic delta activity having the greatest significance. Such activity consists of small amplitude, irregular nonrhythmic discharges which occur continuously without the superimposition of normal rhythms. Adjacent to this may be a region containing what Arfel and Fischgold (1961) have termed "marginal slow waves". Such a region contains not only polymorphic delta activity but also intermixed rhythmic bursts of varying frequencies. Tumors may also evoke abnormal discharges at remote sites. The term "distant rhythms" has been applied to these abnormalities. Among the "distant rhythms" are paroxysmal rhythmic slow waves in the delta range, so-called "monorhythmic delta" (Cordeau 1959). These rhythms have a highly fixed rate of repetition, a form which may be either sinusoidal or sawtoothed due to a rapidly ascending limb, and a tendency to occur in paroxysmal bursts of varying duration. Such rhythms commonly occur in association with deeply seated tumors, particularly those in the posterior fossa. The processes generating these abnormal rhythms remain 1 Based upon the Presidential Address, 20th Annual Meeting, American EEG Society, Denver, Colorado, October 3--4, 1966.
obscure. As a result, various authors hold divergent views concerning the significance of these rhythms. Some investigators (Daly et al. 1953; Dow 1956) have regarded increased pressure within the third ventricle as a major, although not the sole, responsible factor. On the other hand, DykeD et al. (1964) have suggested that occurrence of paroxysmal bursts depends upon the presence of lesions in "an area immediately lateral to the dentate nucleus...although an associated distention of the third ventricle favored their appearance". Similarly, Bagehi et al. (1961) have stressed the occurrence of abnormality on the surface of the head contralateral to cerebellar tumors attributing this to "alteration of neural activity in crossed pathways". Electroencephalographers have remained curiously silent about the effect of sleep upon these various abnormal rhythms. Some years ago, Silverman and Groff (1957) had concluded that a slow wave focus which persisted into sleep with "suppression of sleep potentials" occurred with the most superficially located tumors. In contrast, disappearance of the slow rhythms and relatively little distortion of sleep patterns indicated that the tumor was situated at least 3 cm from the surface of the cortex. Gibbs and Gibbs (1964) have since challenged this viewpoint concluding: "our material shows no clear relationship between the depth of the tumor and changes in delta foci with sleep". They noted that some foci decreased with drowsiness while others became more evident. In some cases, the frequency of the abnormal rhythms changed during sleep. In other cases, epileptiform activity developed. They have summarized their position by saying, "We have not been able to find anything consistent about Electroenceph. din. NeurophysioL, 1968, 25:521-529
522
D.D. DALY TABLE I Location and types of tumors Location
Histological types Astrocytoma Grade 1 Grade 2 Grade 3 Grade 4 Ependymoma Sarcoma Medulloblastoma Meningioma Neurinoma Metastatic Miscellaneous Aqueduct stenosis Unverified Total
Supratentorial
Infratentorial
5 2 6 6 3 3 4 9 8 4
3 3 2 6 3 3 2 3 2
50
28
1
such changes, nor are we able to explain the inconsistencies". Because of this paucity o f information, I thought it might prove rewarding to review the problem. METHOD This study rests on a series o f seventy-eight patients who underwent a total of 93 E E G recordings. In twenty-eight of these patients, tumors were present in the posterior fossa (Table I). Fifty patients had supratentorial tumors, but further categorization poses problems. I have classified sixteen as " d e e p " tumors: five involved the thalamus, five were suprasellar in location, two were located in the region of the pineal body, two were within the third ventricle and two lay along the wall of the lateral ventricle constituting what pathologists describe as a subependymal glioma. The remaining thirty-four tumors were termed "hemispheric" but were not classified as superficial or deep principally because m a n y of them were infiltrating, malignant gliomas o f extensive size and without simply definable margins. Four extracerebral meningiomas formed too small a g r o u p to consider separately. In analyzing the E E G data, I have necessarily resorted to a degree o f oversimplification in view of the relatively small size o f the series. Extensive
E E G classification would have yielded categories with too few cases to permit meaningful conclusions; hence, I have used three descriptive categories: polymorphic delta, rhythmic slow, and normal. " P o l y m o r p h i c delta" refers to wave forms lasting more than 250 msec which have localized origin and persist virtually continuously. Morphologically, these waves have an irregular and unpredictable form which is rarely repeated. I have used this criterion as the crucial one and disregarded the presence or absence o f "marginal slow waves" and the more diffuse rhythmic slow waves. By "rhythmic slow" I am referring to m o n o r h y t h m i c delta or theta rhythms occurring in brief bursts or long trains. These rhythms may appear bisynchronously or occasionally be restricted to one hemisphere. RESULTS The data in Table lI confirm numerous previous studies which have shown that polymorphic delta activity appears in association with hemispheric lesions. In the three patients with hemispheric tumors who fell in the "rhythmic slow" category, rhythmic slow activity occurred maximally on the same side as the t u m o r but without a focus of polymorphic delta activity. In contrast, TABLE 1I Relationship between depth of tumor and type of abnormality Location Hemispheric Deep Infratentorial
Polymorphic " delta
Rhythmic slow
Normal
28 5 0
3 9 20
3 2 8
TABLE III Relation of deep hemispheric tumors to type of abnormality Location Thalamus Periventricular Third ventricle Suprase!lar Pineal body
Polymorphic delta
Rhythmic slow
Normal
3 2 0 0 0
2 0 2 4 1
0 0 0 1 1
Electroenceph. clin. Neurophysiol., 1968, 25:521-529
SLEEP EEG IN BRAIN TUMORS none of the infratentorial tumors exhibited foci of polymorphic delta activity but showed either rhythmic disturbances " a t a distance" or a normal recording. In Table I I I the deep supratentorial tumors are further subdivided. The data are consistent with observations made on the two larger supratentorial and infratentorial categories and indicate that tumors involving the parenchyma of the hemisphere, even those located at great depth, generally produce polymorphic delta activity. On the other hand, tumors obstructing the third ventricle seem to produce rhythmic slow abnormalities. It is interesting that in one patient in whom the E E G showed only rhythmic slow activity, autopsy disclosed a glioma of the thalamus intruding into the posterior portion of the third ventricle and obstructing the aqueduct. Smith et al. (1939) have suggested that occipital monorhythmic delta activity results from
523
compression of the occipital lobe by a distorted tentorium. A more likely explanation relates it to maturational changes in the brain. The data in Table IV indicate that in adults monorhythmic delta activity occurs predominantly in the f r o n t a l regions, whereas in children it appears chiefly over the posterior head regions (Fig. 1). These TABLE IV Effects of maturation on monorhythmic delta activity Age (years) <10 10-14 15-19 20-29 30+
Frontal intermittent rhythmic delta activity
Occipital intermittent rhythmic delta activity
1
9
0 5 * 10
2 1 * 0
* Occurred together in same patient.
F3-C 3
C3-P3 P3-oi Fp2F4
F4-C4 C4-P4
e -02 t
i
3405 2-21-64
i
150 ,~V 1 sec
A
5956 1-19-65
T.C.0.12 sec
B Fig. 1
Maturational changes in spatial distribution of rhythmic delta activity. A: A 7-year-old boy with ependymoma in the fourth ventricle. The EEG shows bursts of left occipital monorhythmic delta activity. B: A 17-year-old girl with a pincaloma. The EEG shows bursts of bisynchronous monorhythmic frontal delta activity (FIRDA). In this and subsequent figures, electrodes are placed in accordance with the "10-20 system" except for At1 and At2 which are 2 cm inferior to F7 and F8 respectively. Electroenceph. clin. Neurophysiol., 1968, 25:521-529
524
D.D. DALY TABLE V Stage I sleep
Awake
Stages II-IV sleep
Number of patients
A. Effect of sleep on rhythmic slow activity
+
+
f
1
[
7 .
.
.
.
!--
3
B. Effect of sleep on polymorphic delta activity 4k +
+ +
' .
2l
-.
.
5 2
.
= Slow activity present. = Absent.
findings parallel the maturational changes in spatial distribution of rhythmic slow activity induced by hyperventilation in normal persons. Turning to the effects of sleep upon these abnormal rhythms, let us consider first the rhythmic slow discharges. Previous studies have shown that
these distant rhythms react more than polymorphic slow wave activity and may, for example, be inhibited by eye opening or mental activity (Cobb 1945; Daly et al. 1953). Table V, A documents the effects of sleep on rhythmic slow activity. With few exceptions, the abnormal rhythms disappeared in the deeper levels of sleep (Fig. 2). None of the patients showed changes in normal sleep rhythms. Spindle rhythms seemed symmetrical. Spontaneous arousal occurred as well as K complexes in response to environmental stimuli. Curiously, in three patients the abnormality appeared during drowsiness and persisted into sleep, but there was no apparent explanation for these exceptions. In some patients, the slow rhythms appeared accentuated during drowsiness. Relatively minor abnormalities in the waking record often became more prominent as the patient drifted in and out of Stage 1 sleep (Fig. 3). Consideration of the reactivity of polymorphic delta activity discloses a different story. The reactivity of polymorphic delta activity in the thirty-four patients with hemispheric tumors is
FPcF 3
Fpl-T 3
FPl-A 1 - . . ~ / ~ _
F 3- C 3
Fp2--T 4
FpTA 2 _ ~ / ~ r . ~ - - .
C3- P3
FP C F 3
T 3- A 1 .~. J ~ . - . ~ .
P3- O1 . j - ~ ~ . ,
FP 2 F4
T 4 - A 2 ........
FP2-'F 4
c3-Pa
C 3- A 1 ~ - ~ - ~ .
F4 - C 4 ~ ~ J " ~ / ~
C4- P4
C 4- A 2
c,-P 4
~-~.p
01- A 1
P4-O2
P4-02
0 2- A 2
p. 191
p. 338
p. 520
Awake
Drowsy
Asleep
I.C. 0.12 sec
[ 50~tv
7464 7-3-65
1 sec
Fig. 2 A 15-year-old girl with headaches and papilledema was found to have a colloid cyst in the third ventricle. Waking record shows bursts of monorhythmic frontal delta activity (FIRDA) which disappears in Stage I sleep.
Electroenceph. clin. NeurophysioL, 1968, 25:521-529
SLEEP EEG IN BRAIN TUMORS
525
Fp?T3 Fp~-T,
FpFF Fp;-F, C3-P 3
c,-P, P -O, P,-o2 ~ J
5 0 ,uV
T.C. 0.12 sec
1 sec
8591 1-3-65
Fig. 3 A 19-year-old boy with headaches, ataxia and papilledema. Operation revealed an astrocytoma in the right cerebellar hemisphere. The waking record shows low voltage theta activity in the fronto-temporal regions. Arousal from Stage I sleep is followed by a burst of diffuse high voltage rhythmic theta activity.
FPl-At
1
Atl-T 3 T3-C 3 C3-O I Fp~-At 2 At~-T 4
T,-C, C4-O 2 Awake
Drowsy T.C. 0.12 sec
1 sec
15o~,v
Asleep 6663
4-5-65
Fig. 4 A four-year-old girl with papilledema, left hemiparesis and hemianesthesia. Autopsy revealed astrocytoma involving the right thalamus and hypothalamus. The recording in the waking state shows polymorphic delta activity intermixed with theta rhythms in the right Rolandic region. During drowsiness and sleep, theta activity disappears, but polymorphic theta activity persists.
Eleclroenceph. din. NeurophysioL, 1968, 25:521-529
526
D.D. DALY
shown in Table V, B. In general, polymorphic delta activity persisted into the deeper levels of sleep although in a few instances it remained only in the drifting stage of Stage 1 sleep. In contrast with rhythmic slow activity, in no instance did polymorphic delta activity appear only during sleep. In patients with deeply seated tumors, polymorphic delta activity occurred in five instances and in each case persisted into deeper levels of sleep (Fig. 4). Rhythmic slow activity occurred in eighteen of thirty-four patients with hemispheric tumors usually in association with polymorphic delta activity. In those in whom both monorhythmic and polymorphic delta activity occurred; the reactivity paralleled observations on patients with infratentorial tumors; namely, although occasionally persisting into the earliest levels of Phase I sleep, rhythmic slow discharges disappeared in deeper levels of sleep. Again, in one patient activation of rhythmic slow activity occurred in the drifting phase. Consideration of the characteristics of sleep
spindles disclosed another difference between the patients with hemispheric and infratentorial tumors. In the latter group, none of the EEGs showed asymmetrical sleep spindles; however, in those with hemispheric tumors, asymmetry of spindles occurred with relative frequency. Of twenty-four patients whose records disclosed polymorphic delta activity, thirteen had spindle asymmetry. In only one instance did spindle asymmetry occur in the absence of polymorphic delta activity. In all but two patients, the asymmetry consisted of reduction in voltage and frequency of occurrence of spindle bmsts or even of complete absence of spindles in the hemisphere involved by the tumor. In the two exceptions, augmentation of spindle voltage occurred in the involved hemisphere paralleling the observations of Arfel and Fischgold (1961) on augmentation of alpha activity. In the group of patients with deeply seated tumors, spindle asymmetry appeared in three patients with tumors involving the thalamus and in one with a tumor along the wall of the lateral
C3"-P3
FpI"At I At -T3
POOl
T3- P3
F3- C 3
P3- O1 F4-C 4
Fp;At 2 At2-T,
c -P. P4-o2 At;T 4
Awake 1 sec
150pV
T,-P, P,-O T.C. 0.12 s e c
Asleep 559. 12-20-62
Fig. 5 A 3-year-old girl with papilledema and right hemiparesis. Left parietal craniotomy revealed a subependymal ependymoma involvingthe lateral wall of the left lateral ventricle. The recording in the waking state shows symmetricalalpha rhythms and no polymorphic delta activity. A lengthy sleep recording shows persistent absence of spindle rhythms over the left hemisphere. Electroenceph. clin. Neurophysiol., 1968, 25:521-529
527
SLEEP EEG IN BRAIN TUMORS
FprAt3 At I -T 3 T3-P 3 P3-Om
FP -At2I Ate-T4 T4-P 4
~
v
vvw.,.,,,~
P4-O2 Asleep
Awake
5117
15o #V 1 sec
T.C. 0.12 sec
!0-6-64
Fig. 6 A 78-year-old woman suffered focal motor seizures and recurrent right hemiplegia. Craniotomy disclosed a meningioma overlyingthe left temporal lobe. Recording in the waking state shows polymorphic delta activityin the left temporal regions. This persists during sleep. ventricle (Fig. 5). In the latter patient, complete absence of spindles from one hemisphere was, in fact, the first electrographic abnormality observed. There was no evidence of spindle asymmetry in any of the remaining patients in this group in whom the EEG showed rhythmic slow activity. In agreement with the observations of Gibbs and Gibbs (1964), these data fail to confirm the criteria of Silverman and Groff for differentiating between superficial and deep hemispheric tumors (Fig. 4 and 6); but they do indicate that both spindle asymmetry and polymorphic delta activity signify involvement of the parenchyma of the cerebral hemisphere. DISCUSSION
This brief study suggests some general conclusions while at the same time raising certain questions. Previous studies have shown that "distant rhythms" exhibit marked reactivity to changes in the physiologic state of the patient: opening the eyes abolishes rhythmic slow discharges in 62 ~o of patients while hyperventilation
increases them in 60~o (Daly et al. 1953). This study demonstrates that sleep exerts a comparable effect, tending in general to eliminate the abnormal rhythms. In this regard, a rather striking parallelism exists with 3/sec generalized spikewave discharges. These latter abnormal rhythms are regularly provoked by overb~eathing. They tend to disappear in deeper levels of sleep (Delange et al. 1962) and to disappear with eyeopening. Tasks requiring the attention and concentration of patients will often abolish either "distant rhythms" or spike-wave discharges. If these similarities are more than fortuitous, they suggest that both these abnormal rhythms utilize similar anatomical systems and depend for their genesis upon derangements of thalamo-cortical mechanisms as Cordeau (1959) has suggested with respect to monorhythmic frontal delta activity (FIRDA). Further, van der Drift and Magnus (1961) have postulated that FIRDA depends on "irritative" lesions of the dorsomedial nucleus of the thalamus and noted its absence after destruction of this nucleus. In contrast, polymorphic delta activity shows Electroenceph. clin. NeurophysioL, 1968, 25:521-529
528
D.D. DALY
virtually no reactivity. Opening the eyes does not abolish it and hyperventilation exerts only inconstant and minor effects. It persists essentially unchanged throughout all levels of sleep even though its presence may be largely obscured by the general slow activity in Stages III and IV. The genesis of polymorphic delta activity poses many unanswered questions although it is usually attributed to interference with local cortical synchronizing mechanisms. Yet, polymorphic delta activity may appear in cortical areas uninvolved by tumor as attested by three patients in this study who had thalamic tumors. Skeptics may invoke arguments based upon the existence of cerebral edema or the lack of anatomically defined lesions. However, van der Drift and Magnus have also shown that tumors restricted to the thalamus can produce polymorphic delta activity in overlying regions of the cortex while Hess (1961) has reported the appearance of polymorphic delta activity following the creation of discrete, stereotactically placed subcortical lesions. Perhaps, then, polymorphic delta activity may result either from localized intracortical derangement through direct invasion by the tumor or from disruption of input into the cortex through neoplastic extension into white and gray matter in the hemispherical depths. The enduring nature of the defect may account for the loss of reactivity. By the same token, disruption of normal sleep activity; e.g., spindle rhythms, would depend upon similar mechanisms and explain their lack of reliability as indicators of the proximity of the tumor to the cortex. All these observations apply only to so-called "slow wave" or NREM sleep and give no clues as to what may occur in the rapid eye movement (REM) phase. The complexities of prolonged recording necessary to attain this phase of sleep account for this lamentable lack and, no doubt, explain the similar absence of information in other published reports. One may suspect that polymorphic delta activity will continue to show a resistance to alteration even in REM sleep. On the other hand, it is less clear what influence of REM sleep might exert on rhythmic slow activity, particularly intermittent or paroxysmal rhythmic delta bursts. A larger series of patients would permit more thorough study of the correlations between the
deranged reactivity of normal waking rhythms and distorted sleep rhythms. The present study contains too few patients to answer such crucial questions. Thus, at the moment, it appears that the clinical electroencephalographer will piofit little from extending his examination to include sleep. However, I hazard the opinion that systematic prospective studies which combine precise anatomical localization with meticulous observations of both reactivity and the abnormal waking and sleeping rhythms will disclose unexpected vistas. From this, the electroencephalographer may evolve skills which will permit localization not in the crude anatomical terms of "lobe involved" but by the more subtle physiological description of "system involved". SUMMARY
I. Electroencephalograms were recorded during the waking and sleeping states in seventyeight patients, fifty with supratentorial and twenty-eight with infratentorial tumors. 2. Tumors involving the parenchyma of the hemisphere produced focal polymorphic delta activity; tumors of the posterior fossa or those obstructing the third ventricle produced rhythmic slow activity (distant rhythms). 3. Distant rhythms show marked reactivity and generally disappear in deeper levels of sleep although sometimes being "activated" during drowsiness. 4. Polymorphic delta activity shows little reactivity and persists in deeper levels of sleep. Distortion of sleep rhythms, usually in the form of reduced spindle (sigma) rhythms, often occurs in association with polymorphic delta activity and signifies involvement of the cerebral hemisphere. Neither proved to be reliable indicators of whether the tumor was cortical or subcortical in location. These studies were carried out at the Barrow Neurological Institute; I wish to express my appreciation to Mrs. James Brittenham, chief technologist, for her assistance. REFERENCES
ARFEL, G. AND FISCHGOLD, H. EEG-signs in tumours of the brain. Electroenceph. din. Neurophysiol., 1961, Suppl. 19: 36-50.
Electroenceph. clin. Neurophysiol., 1968, 25:521-529
SLEEP EEG IN BRAIN TUMORS BAGCm, B. K., Koox, K.A., SELVING,B.T. and CALHOUN, H. D. Subtentorial tumors and other lesions: an electrocncelahalographic study of 121 cases. Electroenceph. clin. Neurophysiol., 1961, 13: 180-192. COBB, W. A. Rhythmic slow discharges in the electroencephalogram. J. Neurol. Neurosurg. Psychiat., 1945, 8: 65-78. CORDEAU,J. P. Monorhythmic frontal delta in the human electroencephalogram: a study of 100 cases. Electroenceph. clin. Neurophysiol., 1959, 11 : 733-746. DALY,D., WHELAN,J. L., BICKFORD,R. G. and MACCARTY, C. S. The electroencephalogram in cases of tumors of the posterior fossa and third ventricle. Electroenceph, clin. Neurophysiol., 1953, 5: 203-216. DELANGE,M., CASTAN,P., CADILHAC,J. and PASSOUANT, P. Study of night sleep during centrencephalic and temporal epilepsies. Electroenceph. clin. Neurophysiol., 1962, 14: 777. Dow, R. S. Electroencephalographic findings in cerebellar tumors. A review of current and old concepts. Electroenceph. clin. Neurophysiol., 1956, 8: 165.
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DRIFT, J. H. A. VANDER and MAGNUS,O. Primary thalamic lesions. Electroenceph. din. Neurophysiol., 1961, Suppl. 19: 125-137. DYKEN, P., MANNING, H. L. and WHITE, P. Electroencephalographic changes associated with cerebellar hemisphere tumours. J. Neurol. Neurosurg. Psychiat., 1964, 27: 340-344. GIBES, F. A. and Gmes, E. L. Atlas ofelectroencephalo-
graphy. Vol. 3, Neurological and psychiatric disorders. Addison-Wesley, Reading, Mass., 1964, 538 p. HESs, R. The influence of stereotactic lesions on the EEG. Electroenceph. clin. Neurophysiol., 1961, Suppl. 19: 166-171. SILVERMAN, D. and GROFF, R. A. Brain tumor depth determination by electrographic recordings during sleep. Arch. Neurol. Psychiat. (Chic.), 1957, 78: 15-28. SMITH, J. R., WALTER, C. W. P., LAIDLAW,R. W. and CASAMAJOR,L. Posterior fossa neoplasms in children: an electroencephalographic study. Trans. Amer. neurol. Ass., 1939: 149-152. WALTER, W. G. The location of cerebral tumors by electroencephalography. Lancet, 1936, 2: 305-308.
Reference: DALY,D, D. The effect of sleep upon the electroencephalogram in patients with brain tumors. Electroenceph. clin. Neurophysiol., 1968, 25: 521-529.