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Folia Psychiatrica et Neurologica Japonica, Vol. 23, No. 1, 1969

An Electroencephalographic Study of Nocturnal Sleep in Temporal Lobe Epilepsy

Sadao KIKUCHI, M.D.

Department of Neuropsychiatry, Faculty of Medicine, University of Tokyo, Tokyo

INTRODUCTION

The neurophysiological study of sleep has made a great progress since the electroen- cephalography (EEG) was introduced. EEG is generally believed to be the best indicator of the activity level of the brain, for the sleep EEG pattern shows characteristic changes during sleep. This fact prompted many in- vestigators to study electroencephalographically the sleep of both normal and pathologi- .cal subjects.

It has been our common knowledge that some epileptic attacks are prone to occur during nocturnal sleep. It seems to suggest a close functional relationship between the neuronal mechanism underlying sleep and that of triggering epileptic seizures, and sleep seems to predispose to actual epileptic patients. Previously Gibbs and Gibbs*) reported that epileptic patients showed paroxysmal discharges on EEG during sleep more than twice as much as during waking state and the greatest amount of paroxysms such as spikes or spike and wave complex appeared in the light sleep stage. Light sleep may enhance electrical spike activity in the EEGs of the patients with abnormal brain function. Thereafter sleep is being employed at the present time as one of the most effec- tive and convenient routine activating methods for the exact disagnosis of epilepsy in the clinical EEG. Furthermore Dement and Kleitmans) made an important observation on the EEG patterns during nocturnal sleep.

Received for publication Mar. 4, 1969.

They observed cyclic appearance of low voltage irregular pattern, which had been thought to be a characteristic EEG pattern of drowsy state, accompanied with rapid eye ball movements during nocturnal sleep and called this sleep stage “activated sleep stage”. Thereafter the interests are developed from a new point of view in the EEG study of all night sleep on the patients with various conditions.

Many authors (Batini et al.l), Delange et al.4), Passouant et al.14), Schwartz et a1.16) and Christianz)) already studied on the characteristics of nocturnal sleep EEG of epileptic patients compared with those of normal subjects and also on the mode of incidence of seizure discharges during all- night sleep. Their results, do not seem as yet to give sufficient information on the nocturnal sleep of epileptics because their studies were performed on a few patients with varied types of seizures. The author and his colleagues have been studying systemati- cally the EEG of nocturnal sleep of epileptics since several years. The results obtained on both centrencephalic epilepsy and focal cortical epilepsy were already published by the co-workers (Kazamatsurilz), Fujimori‘)). The author attempted in this paper to clarify the characteristic features of nocturnal sleep of temporal lobe epileptics by all-night polygraphic recording.

SUBJECTS AND METHODS 1 ) Subjects examined

Twenty patients of temporal lobe epilepsy

60 S. Kikuchi

and fourteen normal control subjects were selected for this study. All the patients had electrographic spike focus at anterior- or mid-temporal region while awake or/and during sleep. The patients were 13 males and 7 females between 8 and 31 years of age. They were divided into two groups by age. Group A consisted of 6 younger patients ranging in age from 8 to 11 years old and group B, fourteen older patients from 15 to 3 1 years old. Characteristic clinical features of the patients examined, i.e., type of seizures, past history, main ictal symptoms and frequency of seizures are briefly illustrated in Table 1. They have been suffering from their seizures during past 1-18 years and they were ambulant patients of Tokyo University Hospital with the exception of a few in-patients. From an etiological point of view, fourteen out of twenty cases were suspected to be symptomatic and the others idiopathic or cryptogenic. The majority (thirteen out of twenty) of their seizure type were automatism. Besides, as illustrated in Table 1, other various seizure types such as generalized convulsion, focal convulsion, ictal autonomic symptom, brief loss of consciousness and psychic phenomena with or without aura were observed. Twelve patients had automatism only and the other eight patients had combined seizures of various kinds. They have been treated with anti- epileptic drugs for a long period. Some of them were proved, by psychiatric and psychological examinations, to have “epileptoid” character disorders such as egocentri- city, pedantry or dullness.

As for control sampling, the author examined fourteen healthy male volunteers ranging in age from 1 9 to 26 years old. These control subjects were also divided into two groups by age, that is, group A’ consisted of younger subjects from 19 to 21 years old and group B’ from 25 to 26 years old.

2) Methods for recordings

An all-night polygraphic recording of EEG, heart rate, respiratory rate, and horizontal eye movement was performed on each subject in a sound-proof, electrically shielded room without any external stimuli as a rule. Exceptionally the repeated auditory stimuli of lOOOc/s pure tone were given to two patients in order to know auditory threshold during sleep. The room temperature was adjusted sufficiently as to enable patients to have comfortable sleep near 20°C. EEG was obtained from bilateral frontal, anterior- temporal, mid-temporal, central (or parietal) and occipital regions through monopolar lead with reference electrode to ipsilateral ear on a 13 channel inkwriting electroen- cephalograph with a time constant of 0 .1 or 0 .3 second. The electrodes were placed by standardized ten-twenty system and attached to skin with celloidin. Horizontal eye movement was recorded with the electrodes on both outer canthi with a time constant of 1.5 second. Pulse rate was taken from right arm and respiratory rate from the abdominal part. The details of the polygraphic recording methods have been described by the author’s colleagues in other papers7J2). Anti- epileptic medications were withdrawn for 2- 3 days before recording.

3 ) Methods of arranging the recordings The grading of the depth of sleep was

scored at electroencephalographic level every one minute. Furthermore, pulse rate and respiratory rate per minute were actually counted and also presence or absence of rapid eye movements was noted. The depth of sleep was divided into the following five stages.

wakefulness, alpha waves are dominant,

drowsiness and light sleep, low voltage theta waves are dominant and parietal humps appear.

moderately deep sleep, spindle waves are dominant.

very deep sleep, high voltage

A stage:

B stage:

C stage:

D stage:

An EEG study of Nocturnal Sleep in Temporal Lobe Epilepsy 61

Table 1 Clinical characteristics of the patients examined.

Group No. Case Sex Age

1 M.M m 8

2 T.0 m 8

3 Y.Y f 10

A 4 M.1 m 11

5 T.S f 8

6 M.M f 9

7 S.K m 15

Age of

Onset of

Seizure 7

8

9

11

8

9

15

Type

Seizure History of

Frequency EEG of Ictal

Symptoms Seizures* focus

Asthma GM-tPsM bronchiale

febrile PsM convulsion forceps Focal delivery neonatal GM+PsM asphyxia neonatal PsM asphyxia head PsM injury encephali- GM,PsM tis?

loss of consci- 5/y LaT ousness rs. hemiconvulsion twilight state indefinite L,RaT

twitching of 2/y RmT facial muscles automatism 1-2/m LmT

loss of con- 2/y RmT siousness psychic seizure l /m L,R.

F,mT loss of consci- l/m RaT ousness, grand ma1

8 M.T m 16

9 K.N m 19

10 M.S m 20 11 T.K m 30

12 M.C m 31

B 13 C.A f 24 14 Y.K f 24

15 Y.M f 17

16 K.F f 25 17 S.S m 30

18 Y.T m 23

19 K.1 m 30

20 K.T m 24

11

16

16 12

31

24 21

15

19 14

18

25

18

neonatal PsM automatism 2/w LaT,mT intracranial autonomic aura hemorrhage febrile PsM automatism indefinite RaT convulsion

- PsM automatism 1-2/m LaT nephritis PsM automatism 2/m RaT

forceps Focal focal convulsion 2/y RaT delivery PsM automatism scarlatina PsM automatism S/day RaT,mT head PsM automatism 4/m LaT injury encepha- PsM arrest of motion l/m LaT litis automatism

neonatal GM+PsM automatism 2/y RmT asphyxia forceps GM+PsM loss of 5/day LaT,mT delivery consciousness

head PsM automatism 1-2/m LaT,mT injury

- GM+PsM loss of 1 4 / m RaT,mT consciousness

autonomic aura

- PsM automatism 4/m LaT,mT

dCjh vu

GM: grand ma1 PsM: psychomotor seizure Focal: focal convulsion GM,PsM: grand ma1 accompanied with psychomotor seizures GM-tPsM: psychomotor seizure transformed from grand ma1 aT: anterior-temporal m T mid-temporal

* Frequency of seizures is the average during one year before recording.

delta waves are dominant. paradoxical sleep, low voltage

irregular theta waves are seen accompanied by rapid eye movements.

The classification of sleep stage was sometimes rather diflicult on some patients because of irregularities of basic patterns, so the author adopted relatively simple classifi-

P stage:

62 S. Kikuchi

cation of stages of sleep compared with those of other authors’. Thus the polygraphic sleep diagrams of all the patients were drawn as shown in Figs. 2, 3 and 4 on each patient.

The numbers of spike discharges were actually counted, then enumerated every stage of sleep. The mean values of number of spikes per minute as well as the rate of incidence of spike discharges every sleep stage were also calculated.

RESULTS

1) Characteristic features of the course of nocturnal sleep

All the patients slept for 4-10 hours. The mean sleeping time of twenty patients was 465 minutes. By analyzing the whole course of sleep throughout a night, the author excluded three cases because their recordings

were inappropriate. Namely, a male patient, M.T. (No. 8) was awaking for a long time during midnight, from 12 p.m. to 7 a.m., so his sleep EEG record could not be considered as his usual nocturnal sleep. Further- more, for another two cases the external stimuli of phonic stimulation of 1000 c/s pure tone were frequently given during sleep, so the author also excluded their sleep recordings for the evaluation of nocturnal sleep cycles.

Fig. 1 illustrates the sleep diagrams of all the patients examined except for one (No. 16). Out of all the remaining seventeen patients, three patients, S.K. (No. 7) K.I. (No. 19) and T.O. (No. 2) showed almost normal course of sleep. Cyclic fluctuations of the depth of sleep as well as regular and periodical appearance of P stage were ob-

Table 2 Actual time in each sleep stage on normal control subjects. Its ratio to all the sleeping time is given in parentheses. SD: standard deviation.

sleep stage (min) Total

A B C D P time Group No. Age sleeping

1 20 2 19 3 20 4 21 5 20

A’ 6 22 7 22 8 20 Subtotal

SD M

0 (0) 0 (0) 4.1(0.9) 0 (0) 0 (0) 6.0(1.1) 6.0(1.2) 4.0 (0.8)

20.1(0.5) 2.60

5

6.2(1.4) 6.1(1.2) 9.q2.1) 5.0(1.1) 8.6(1.9)

30.5(5.4) 13.9 (2.8) 20.0 (4.0) 99.8 (2.6) 2.64

13

177.6(40.1) 238.6(46.6) 194.9 (43.4) 297.0 (65.7) 315.1(69.4) 254.6(46.8) 23 1.1 (46.4) 274.0 (54.9)

1982.9 (5 1.5) 55.48 248

129.8 (29.3) 160.8(31.4) 145.8 (32.4) 76.4( 16.9) 63.6 ( 14.0) 79.4 (14.6)

142.9 (28.7) 85.3( 17.1)

884.0(22.9) 35.64

111

128.9(29.1) 106.0 (20.7) 95.9(21.3) 73.7 (16.3) 66.7 (14.7)

173.0 (32 .O) 104.1 (20.9) 115.q23.2) 864.1 (22.4) 31.17 108

442.5 511.5 450.2 452.1 454.0 543.5 498.0 499.1

3850.9 34.37 48 1

9 26 10 26 11 25 12 25

B’ 13 25 14 26 Subtotal

SD M

3.1 (1.3) 0.9 (0.2) 0 (0) 0 (0) 0 (0)

16.6(3.4) 20.6(0.8) 5.99 3.4

14.4(6.0) 26.7 (6.3) 35.7(7.7) 9.7 (2.3)

17.7 (4.7) 46.8 (9.6)

151.0(6.2) 28.23 50.3

136.8 (56.5) 257.0 (60.6) 291.9 (63.0) 232.7 (55.1) 198.7 (52.9) 221.6(45.7)

1338.7 (55.5) 48.34

223.1

11.8( 4.9) 21.6( 5.1) 28.8 ( 6.2) 47 .O( 1 1.1) 80.7(21.2)

108.6(22.4) 298.5 (12.4) 34.39 49.8

75.9(31.4) 117.9(27.8) 106.7 (23.0) 132.8(31.5) 78.8(21.0) 91.6(18.9)

603.6(25.6) 20.49

100.6

242.0 424.1 463.1 422.2 375.9 485.2

2412.5

402.1 83.13

A‘ Total 40.7(0.6) 250.8(4.0) 3321.6(53.0) 1182.5(18.9) 1467.8(23.4) 6263.4 SD 4.43 11.85 51.7 46.4 27.4 70.1 M 2.9 17.9 237.3 84.5 104.8 447.4 +

B’ +2SD f 8 . 8 6 3~23.70 k103.4 f92.8 f54.8 f140.2

SD: standard deviation M: mean value

An EEG study of Nocturnal Sleep in Temporal Lobe Epilepsy

I . X .

16. ..

19, m.

M I.

20..1.

C A. '1 $ I II n-mIu- 249.1.

Y.X.

24.. I . n n 1 R I n

10, m.

x I .

I t. 1.111.

Y . Y .

9 , I.

63

No. I

NO. a

No. 9

No. IC

No. 1 1

No. 12

No. 13

No. 14

No. 15

No. 17

NO. i s

No. 29

No. 20

No. 1

No. 2

No. 3

No. A

No. 5

No. 6

Fig. 1. Sleep course of all the patients except for one (No. 16). The abscissa represents the chronological time and the ordinate of each histogram represents the depth of sleep from A to D. The shaded parts indicate P stage of sleep. White arrows are clinical attacks and black arrows are repeated phonic stimulation performed during sleep. Note the shortening or rare appearance of D stage, prolongation and frequent appearance of C stage and irregular appearance of P stage. (see text)

served. The ratio of each sleep stage during a whole night was approximately similar to that of normal control subjects. In another fourteen patients, disorganizations of sleep cycles were observed in a greater or lesser degree. Their sleep courses were characterized by rare incidence or shortening of D stage, extreme prolongation of a single C

stage, increased ratio of C stage to all the sleeping time and irregular appearance of P stage. Table 3 shows the actual time of each sleep stage, its mean value and standard deviation on all the patients. The mean ratio of D stage to all the sleeping time was 18.9% on normal subjects, whereas 15.3% in temporal lobe epileptics. Exceptionally, a

64 S. Kikuchi

female patient, Y.M., (No. 15) showed extremely long-lasting D stage during a night. If this patient was excluded, the mean ratio of D stage on the patients was 13.2% and the large difference of D stage ratio between temporal lobe epileptics and normal subjects became more obvious. All the normal subjects had D stage of sleep, ranging from 4.9% to 39.4%, during a whole night. In the patients’ group, three patients did not show any D stages throughout a whole night and in another six patients the ratio of D stage to all the sleeping time were below 10%. The younger patients belonging to

group A, however, generally slept deeply and the mean percentage of D stage was 18.9%, ranging from 7.4% to 23.2%. C stage occupied relatively long time in the total sleeping time of the patients as well as the normal subjects. On the other hand, the ratio of B stage and P stage was variable individually in the patients, above all in the adult patients.

2) Characteristics of background sleep

Some characteristic features of EEG EEG patterns

waves were observed as follows.

Table 3 Actual time in each sleep stage on the patients with temporal lobe epilepsy. Its ratio to all the sleeping time is given in parentheses. SD: standard deviation.

Total Group No. A B C D P sleeping

time 1 32(6.5) 19( 3.9) 223(45.6) llO(22.5) 105(21.5) 489 2 0 (0) 7( 1.4) 3 44(7.9) 72(12.9) 4 39(8.1) 3( 0.6)

6 0 (0) 3( 0.7)

M 19.2 (3.8) 17.3 (3.4) SD 16.72 25-20

k2SD f33.44 f50.40

A 5 0 (0) 0 (0)

Subtotal 115 104

7 6( 1.8) 0 (0) 8 382(65.1) 23( 3.9) 9 15( 2.4) 117(18.7)

10 32( 8.0) 7( 1.8) I 1 25( 4.4) 32( 6.3)

13 22( 4.3) 25( 4.9) 14 10( 4.0) 0 (0)

B 15 11( 2.1) 7( 1.3) 16 35( 5.7) llO(18.0) 17 20( 4.4) 68(14.8) 18 19( 6.1) 163(52.1) 19 0 (0) 1( 0.3) 20 19( 6.1) 33(10.5)

M 44.9 ( 10.0) 44.2 (9.9) SD 99.0 49.33

f2SD f188.0 f98.66

I2 33( 7.3) 33( 7.3)

Subtotal 629 619

225 (44.6) 215 (38.6) 171 (35.4) 3 17 (57.4) 192 (4 1 .9)

223.8 (44.1) 46.79

f93.58

1343

115 (22.5) 101 (18.1) 112(23.2) 41( 7.4) 98(21.4)

96.2 ( 18.9) 25.38

f50.76

577

157(31.2) 125 (22.4) 158 (32.7) 194(35.1) 165 (36.0) 904 150.7 (29.7) 28.64

f57.28

504 557 483 552 458 3043 507.2 36.14

f72.28 180 (53.4) 33( 5.6) 334 (53.4) 160 (40.4) 261(55.4) 149(33.1) 390 (76.2) 175 (69.7) 85 (1 6.3) 287 (46.9) 304(66.4) 64 (20.4) 137 (34.5) 232 (74.1)

194.4 (44.6) 2791

87.41 f174.82

57 (170) 13 1 (22.3) 0 (0) 90(22.5) 31 ( 6.1) 44( 9.8) 22( 4.3) 0 (0)

268 (5 1.4) 33( 5.4) 0 (0) M(12.8) 129(32.5) 9( 2.9)

854 61 .O (13.6) 71.23

f142.46

92 (27.5) 18( 3.1) 159 (254. ) 11 l(27.8) 138 (27.2) 191 (42.4)

5 3 ( 10.4) 66 (26.3) 150(28.8) 147 (24.0) 66 (14.4) 27( 8.6) 130 (32.7) 20( 6.4)

97.7 (21.8) 55.14

f110.28

1368

335 5 87 625 400 507 450 512 25 1 52 1 612 458 313 397 313 626 1 447.2 97.04

f 194.08 Total 744 723 4134 143 1 2272 8304 (%I (8.0) (7 * 8) (44.4) (15.4) (24.4) SD: standard deviation M: mean value


The mean voltage of background activities was considerably lower than that of normal subjects. It was markedly so in the delta waves seen during the deepest stage of sleep. They did not usually exceed approximately 100 microvolts. Therefore the EEG pattern of D stage of the patients looked more flat than that of normal subjects. The appearance of distinct humps during the light sleep stage was relatively poor. Some of the patients often showed irregular basic EEG patterns intermingled with sporadic low voltage theta waves in the waking state, so the author sometimes could not distinguish between awaking and light sleep pattern elec-

trographically when the patient was falling asleep.

Spindle-formed rhythmic waves which had the longer duration and slower frequencies than normal spindle waves, were frequently observed in the sleep EEG of adult temporal lobe epileptics. These spindle-formed rhythmic waves had the frequencies ranging from 11 to 16 c/s, often used to appear inde- pendently and sometimes accompanied with normal spindle waves centering around 14 c/s. The predominant site of appearance of these spindle-formed waves were front- central areas in general but sometimes were parietal or occipital area. These waves were

Table 4 Incidence of temporal spikes during different stages of nocturnal sleep on seven patients. (see text)

(1) actual numbers of spikes

Case No. Spike focus A B C D P Total

67 228 3939 1961 1124 7319 aT 1 k 75 326 5578 2078 540 6597

97 348 5225 2616 1333 9619 99 367 5185 2747 1073 9471

2 LaT 392 3722 2477 1832 8423 5 RmT 7536 2711 1354 11601

595 5626 9 RaT 34 604 4389 11 RaT 4 72 919 115 56 1166

268 55 1 4438 212 384 5853 mT { k 3 248 2655 129 217 3288

13

15 LaT 1 1 8 97 2 109

1 [ m T [ k

* * *

**

(2) Rate of incidence of spikes per minute during each stage of sleep ~~ ~

Case No. Spike focus A B C D P

L 2 12 18 18 11

3 18 23 24 13 3 19 23 25 10

2 LaT 56 12 22 12 5 RmT 24 66 7

4 9 RaT 2 5 13 ** 11 RaT (0.3) 2 3 4 (0.4)

12 22 11 10 7

aT [ R 2 17 16 19 5 1 I m T ( k

* * *

mT I k (0.1) 11 7 6 4 13

I5 LaT (0.1) (0.1) (0.1) (0.4) (0.0)

**: no D stage appeared * : data not available

66 S. Kikuchi

not observed in the sleep EEG of the normal subjects. The author regarded these waves as the varied forms of normal spindle waves because of common co-existence of these waves with normal spindles. There- fore the author identified the sleep stage in which these varied spindle waves appeared as C stage of sleep.

3 ) The mode of incidence of temporal

Table 4 illustrates total numbers of temporal spikes appeared during each stage of sleep throughout a whole night as well as the rate of incidence of spikes per minute on the selected seven patients. Out of these seven cases, three belonged to group A, and the other four to group B.

On a female patient, Y.M. (No. 15), the actual numbers of spike discharges were too few to deal with the rate of incidence of spikes, so the author excluded this patient and analyzed the data with the remaining six patients. On the three patients out of them, (No. 1, No. 11 and No. 13) temporal spikes appeared most frequently during C stage as well as D stage. On the other two patients (No. 2 and No. 5 ) , the rate of incidence of temporal spikes during D stage was higher than during C stage. On a patient (No. 13) which mid-temporal mirror foci were observed in right hemispheres, the rate of incidence of spikes differed between right and left hemisphere, namely, in the left side, spikes appeared twice as that in the right side. The mode of incidence of temporal spikes in each stage of sleep, however, was almost equal on both hemispheres. Another patient (No. 1) also showed anterior- and mid-temporal mirror foci. In this case, the rate of incidence of spikes during each stage of sleep was also almost equal between both hemispheres. The most frequent incidence of spikes during B stage was observed on the two patients (No. 2 and No. 13). A male patient, K.N. (No. 9) did not show any D -stage during a whole night. The most fre-

spikes during all night sleep

quent incidence of spikes was observed during C stage on this patient.

The rate of incidence of spikes during P stage was generally larger than during A stage, but relatively less than during C stage or D stage. During this sleep stage, the slight suppression of temporal spikes were generally observed. During A stage, the rate of incidence of temporal spikes was generally the lowest. Namely, in two patients out of seven, A stage could not be recorded in a whole night and in the remaining five patients, four showed the lowest value and another one showed approximately same as that of P stage.

In the younger patients belonging to group A, the actual numbers of spike discharges were more numerous than in the adult patients belonging to group B. Thousands of temporal spikes occasionally appeared during a whole night. The mode of incidence of spikes, however, was similar to that of adult patients.

The correlation between the mode of the incidence of spikes and the clinical factors of the patients was examined but no distinct relationship between them could be found.

As to the mode of incidence of spikes during an all-night sleep, it is concluded that the temporal spikes appeared most frequently during C stage and were suppressed during P stage as well as A stage in general. Some exceptional cases, however, were observed.

4 ) Clinical seizures observed during nocturnal sleep

Nine clinical seizures during nocturnal sleep recordings were observed in seven patients. These seizures, five automatisms and two abortive convulsive seizures, all re- sembled to their habitual ones. Seven patients which showed clinical seizures during recordings all belonged to group B, the older patients. The younger patients did not show any clinical seizures during sleep. From an etiological viewpoint, five patients out of seven were suspected to be symptomatic or


Table 5 Clinical features of the seizures observed during nocturnal sleep recordings.

Sleep

Ictal Spike EEG of sleep Time Stage

No. Case Sex Age of when Seizure Seizure Symptoms focus pattern seizure stage

occurs

EEG Ictal Duration* Postictal

7 S.K m 15 3:lO D abortive RaT rhythmic 4 (min) C generalized theta waves convulsion

theta waves

theta waves

sion theta waves

9 K.N m 19 12:12 C automatism RaT rhythmic 1 C

11 T.K m 30 4:06 P automatism RaT rhythmic 6 C

12 M.C m 31 10:40 D focal convul- RaT rhythmic 4 B

13 C.A f 24 10:23 D automatism RaT,mT irregular 4 B

11:OO B A 14 Y.K f 24 1256 P automatism LaT rhythmic 1-4 A

6:02 P theta wave A 17 S . S m 30 3:37 C automatism RmT rhythmic 6 P

spike and wave

theta wave

* The author took all the time from the onset of seizure to the complete recovery of EEG pattern for the duration of seizure.

residual epilepsy. Table 5 illustrates the time of the onset of seizures, the depth of sleep which seizures were provoked, EEG spike focus, ictal EEG pattern, the duration of each seizure and the postictal EEG changes respectively.

The nocturnal seizures had not always the tendency to occur in a definite stage of sleep. That is, two seizures occurred during C stage, three during D stage, three during P stage and one during B stage. Three out of seven seizures took place in the first half of a night, two at midnight and another four in the latter half of a night. A female patient, Y.K., (No. 14) showed three fits during one same night. First seizure of automatism was provoked during B stage and the other two during P stage respectively. The incidence of clinical attacks did not show any paral- lelisms with the incidence of spike discharges during sleep and a definite relationship between the type of seizures and the sleep stage which clinical seizures took place was not confirmed in this study.

Although the ictal EEG patterns could not be always recorded completely throughout a

seizure because of mingling of EMG due to body movements, the most frequently observed EEG patterns during a seizure were the generalized rhythmical theta wave burst. These ictal slow waves usually started at the site of the spike focus initially and were relatively low voltage. They spread to all the regions gradually, transformed into a higher voltage with a slowing of frequency. Occa- sionally these theta waves appeared domi- nantly at the hemisphere where the spike focus was seen. At the end of the seizure diffuse high voltage delta waves frequently appeared. A female patient, C.A. (No. 13), exceptionally showed irregular spike and wave complex at the onset of the seizure. She looked around as if she was searching something, turned her head to the left and stretched her extremities.

The duration of the seven seizures ranged between 1 and 6 minutes. After the seizures, the majority of the patients did not awake and did not remember their nocturnal attacks. EEG pattern used to return to pre- ictal sleep stage and the depth of sleep did not usually alter afterwards. Only one fe-

68 S. Kikuchi

male patient, however, which three seizures were provoked during one night awoke on each occasion and could remember the seizures. But other patients used to declare in the next morning that they had been aware of neither type of seizures during night and they were innocent as to their nocturnal seizures.

ILLUSTRATIONS OF SLEEP COURSE ON 4 TYPICAL CASES

In the previous chapter the author described generally some characteristic features of the patients’ nocturnal sleep course and the mode of incidence of spike discharges during each stage of sleep. In this chapter the various courses of sleep during a whole night are presented on four typical patients

of the temporal lobe epilepsy. Figs. 2, 3, 4 and 5 illustrate the sleep

diagrams of these patients. The upper part of this figure shows the depth of sleep and the bottom part shows the histographical illustration of actual numbers of the spike discharges per minute.

A) Male patient of 19 years old. He was suf-

fering from frequent attacks of automatism since 16 years old in spite of continuous medications of various anti-epileptic drugs. In early infancy he had had some febrile convulsions of grand ma1 type. Frequency of the seizures were not always constant. Routine EEG examinations revealed spike focus at the right anterior-temporal region.

Case K. N. (No. 3 )

Fig. 2. Diagrammatic representation of the incidence of temporal spikes in all-night sleep recording on case 9 (m. 19 y.). The upper part is a whole night sleep diagram and the abscissa represents the chronological time. The ordinate on the top of the figure represents the depth of sleep. The shaded area is P stage of sleep. The lower part of the figure shows the actual numbers of right anterior temporal spikes per minute. REM: rapid eye movement. Note the suppression of spikes during P stage.

An EEG study of Nocturnal Sleep in Temporal Lobe Epilepsy

7.K.m. 3 0 ~ . 9 10 I1 12 I 2 3 4 5 6

Sleepstage A

B-

C- 1

Pi1 I se Rate . . . . .. .

69

I . .

Fig. 3. Sleep diagram on case 11 (m. 30. y.). Note the suppression of right anterior-temporal spikes during P stage.

Fig. 2 is the schematic diagram of his whole night sleep.

In this case D stage of sleep did not appear throughout one whole night, whereas C stage of sleep appeared frequently and repetitively, and lasted for a long time. P stage of sleep appeared between two C stages and the mode of its appearance was considerably regular but its duration was shorter than that of C stage. His sleep course seemed to be relatively stable, rather flat or monotonous in other words, although he once awoke at mid-night. A clinical seizure occurred at 12" 10' during recording, but this seizure scarcely exerted any influences upon his sleep course. During the seizure he showed transient tonic movements of muscles of extremities with oral automatism and looked as if he was anxious and suprising. His ictal EEG pattern during sleep began with low voltage, rhythmical theta-waves, in-

creased amplitude gradually and then trans- fered into high voltage delta wave burst. After the seizure, EEG pattern returned again to C stage as before without awakening.

Right anterior-temporal spikes were frequently observed on this patient during nocturnal sleep. The maximum numbers of spikes reached to about 50 per minute. The spike discharges did not always appear constantly during the whole course of sleep. They sometimes appeared sporadically and sometimes in the form of spike burst lasting for several seconds accompanied by suppression afterwards. So the histogram of spikes during a whole night is irregular as illustrated in Fig. 2. Spikes appeared more numerously during C stage than during P stage in general and the suppression of spike discharges during P stage was observed. If all the sleeping time were divided into three periods con-

B-

C -

D-

R E M

I

- -

I =I I m - B M Y Movement

L Number Of F-C Spikes R

I, I 11 . I, . L R

L R

L R

Fig. 4. Sleep diagram on case 15 (f. 17 y.). Note that numbers of spikes led from bilateral

aT-C . II I I1 . I, I

mT-C

c- 0 1 r l r i m . I, I

hemispheres shows almost similar fluctuations according to the changes of depth of sleep.

111 11 11 IIIIIII in1 I I I I I I ~ ~ I I B I B I ~ ~ I I I I I IIIIIIIIII IIII I ti111 i n 11 I

,rlOlY(L ,, ,a, I YL %

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veniently, spike discharges were most frequently observed in the second period of night although a great portion of each period was occupied by same C stage.

B) Male patient of 30 years old. He had

renal disease in his past history. Automatism with an aura of nausea and uncomfortable sensations began at 12 years old. These fits were observed once or twice per month in spite of continuous medications of anticon- vulsants. Fig. 3 demonstrates his sleep diagram, the changes of the depth of sleep and also the mode of incidence of spike discharges during a whole night His sleep course was rather irregular in comparison with that of the previous case, K. N. Name- ly, he awoke immediately after falling asleep early in the evening, slept again and soon long and monotonous C stage appeared. Thereafter P stage and C stage were alter-

Case T. K. (No. 11)

L R F-aT

nately observed during a night. P stage was initially short in its duration and gradually became longer, while C stage decreased its duration in the latter half of a night. At the end of the third P stage, a clinical seizure was provoked. Nevertheless, his sleep persisted without any changes of the depth of sleep afterwards. Before awakening in the morning, P stage and C stage were observed by turns. D stage was never observed in the whole course of his sleep. The mode of appearance and the duration of P stage seemed to be rather irregular. As to the mode of incidence of spike discharges during his nocturnal sleep, the most characteristic findings were the frequent appearance of spike discharges during C stage and their suppression during P stage. The appearance of spikes was observed most frequently in the midnight. The rate of incidence of spikes was not always constant during a single C stage of sleep. This fact seems to indicate that the

I YL m A I


Fig. 5. Sleep diagram on case 5 (f. 8 y.).

mode of appearance of spikes is determined not merely by the depth of sleep, but by other various etiological and clinical factors.

C) Female patient of 17 years old. She had

experienced several attacks of febrile convulsions in her early infancy. The onset of her psychomotor seizures, such as arrest of motion and oral automatism with salivation, was at 15 years old. These seizures occurred approximately once a month at the time of nocturnal EEG recording. Since 17 years old, she had been treated continuously with anti-convulsants and thereafter the frequency of seizures remarkably reduced. She showed some marked character disorders of “epileptoid”, namely dullness of thought and behavior, importunity and irritability. She had been complaining frequent enuresis noc- turna and sometimes insomnia. Routine sleep EEG revealed left anterior-temporal

Case Y. M. (No. 15)

spike focus. Her sleep course was rather exceptional, differed from those of two patients mentioned above and did not show any characteristic features which were generally observed in the majority of adult temporal lobe epileptics. As illustrated in Fig. 4, C stage of her sleep was shortened and scarcely observed in the second half period of sleep. On the other hand, long lasting, regularly repeated D stages and considerably long con- tinued P stages appeared alternately. Among them poor-developed short C stages were observed. Her sleep course seems to be more monotonous in comparison with those of normal subjects due to extremely long lasting D stage. Temporal spikes were observed most numerously during D stage and nearly disappeared during P stage. The rate of incidence of spikes, however, differed among different D stages and during a same single D stage.

72 S. Kikuchi

D) Female patient of 8 years old. She had

experienced neonatal asphyxia by difficult delivery. Frequent attacks of automatism had began a few months before this nocturnal EEG recording. EEG proved right temporal spike focus which frequently and constantly appeared during a whole night sleep. Such frequent appearance of spikes were commonly observed in the most cases of younger patients in this series. Immedi- ately after falling asleep, P stage with duration of half an hour was observed and thereafter C stage and D stage appeared and her sleep deepened gradually. In the first half of her nocturnal sleep, C stage and D stage appeared alternately and in the latter half D stage were never observed. D stage occupied only 7.4% of all the sleeping time, while the appearance rate of C stage was 57.4%. Her C stage lasted long and appeared repeti tively. P stage occupied 35.1% of all the sleeping time. She did not awake during a whole night, so her sleep seemed to be stable. As to the rate of incidence of spikes, temporal spikes were observed more frequently during C stage as well as D stage and their appearance were suppressed during P stage. Spike discharges often appeared in the form of burst and the numbers of spikes fluctuated during the same stage of sleep. In younger patients, the numbers of spikes observed were generally more numerous than those of adult patients.

DISCUSSION The present study shows some character-

istic features of sleep course as well as the mode of incidence of spike discharges during natural nocturnal sleep on temporal lobe epileptics. In the discussion, the author in- tends to compare the findings observed in this study with the results previously reported by other authors on the patients with various types of epilepsy and also to recon- sider the neurophysiological mechanisms

Case T. S. (No. 5 ) underlying electrographic manifestations of epileptic disorders in the light of modern knowledge regarding sleep.

1 ) Course of nocturnal sleep observed on patients

Before the discussion on the characteristic features of course of nocturnal sleep of the patients, the classification of EEG depth of sleep which the author adopted in this study should be reconsidered.

The author classified the depth of sleep into five stages, namely, A, By C, D and P stage. This classification was rather rough compared with the other authors’ ones of various kinds. The background EEG patterns frequently observed on the patients with temporal lobe seizures were sometimes so disorganized and irregular that the author often could not classified the depth of sleep precisely. The main purpose of this paper consisted in the study on the mode of incidence of paroxysmal discharges during a nocturnal sleep, the author prefered to adopt this classification on the depth of sleep in this study.

The most remarkable and characteristic features observed on the sleep course of temporal lobe epileptics were rare incidence or shortening of D stage, extreme prolongation of a single C stage, increased ratio of C stage to all the sleeping time and irregular appearance of P stage. The disorganizations of sleep cycles were observed more or less in the majority of the patients. It should be considered that the unusual experimental conditions might modify the course of the natural nocturnal sleep of the patients. Although the experimental conditions them- selves were common to both patients and normal subjects, it could be considered that the patients were more sensitively affected by such external conditions, whereas normal control subjects were rather indifferent and often disregarded the experimental conditions. For example, a hypochondriac male patient, Y.T. (No. 18), was complaining the


uncomfortableness of electrode attachment during a whole night and therefore he could not get nocturnal sleep sufficiently. Thus his sleep course was characterized by long lasting B stage over half a night and did not show any D stage. The majority of the patients, however, slept well as usual and the modifications of course of sleep mentioned above seemed to be common findings to the greater parts of temporal lobe epileptics examined.

Christian2) studied on the nocturnal sleep of the patients of two different types, i.e., epilepsy on awaking (“Aufwachepilepsie” by Janz) and the sleep epilepsy (“Schlafepi- lepsie” by Janz) and found that each had characteristic course of sleep. He adopted Janz’s classification of epilepsy which seemed remarkably unique because of the new, ex- cellent conception that there was a definite correlation between the occurrence of epileptic attacks and human biological circadian rhythms, i.e., sleeping and waking peri- odicity. According to Christian’s remarks, the patients of sleep epilepsy fell into sleep promptly and reached easily to the deepest stage of sleep. The sleep course of sleep epileptics was generally stable, that is, dream, body movements and changes of postures during sleep were rare and their sleep was not interrupted by awaking, and they usually awoke refreshingly in the morning. On the contrary, the sleep course of the epileptics on awaking was entirely different from that of the sleep epileptics. Their sleep was often easily interrupted by external stimuli and sleep course was rather superficial and unstable. They slept deeply at first in the morning. Thus he found the different mode of the sleep course between these two group of epileptic patients, and he stated that this difference was based on the biological constitution which was underlying the pathophysiological genesis of two types of idiopathic epilepsy. It should be noticed, however, that his classification was mainly made on the idiopathic grand ma1 epileptics.

According to his classification, the temporal lobe epilepsy accompanied by grand ma1 seizures belonged to sleep epilepsy. The author’s results obtained in this study indicates that sleep course of the adult patients with temporal lobe epilepsy was not always sim7- lar to those of sleep epilepsy. For, the temporal lobe epileptics showed relatively long duration of a single stage of sleep, especially of C stage, so the course of sleep was rather stable and they slept fairly well apparently. On the other hand, the temporal lobe epileptics did not reach to the deepest stage of sleep easily. Although Christian’s work was done before the introduction of the conception of “paradoxical phase of sleep” into study of sleep, it is interesting that the results obtained by both Christian and the author were almost similar in some respects regarding to the course of sleep. By compar- ing both findings, however, the difference of the materials examined should be considered.

The colleagues of the author also have been studying on the nocturnal sleep of various epileptic patients. Kazamatsuri12) studied on twenty-one cases with petit ma1 absences which showed electroencephalographically 3 c/s spike and wave complex only during a clinical seizure and found that the nocturnal sleep cycles of these patients were almost normal. The majority of his cases were idiopathic ones, and they showed almost normal background EEG on interseizure recordings while awake except for a few cases. Fuji- mori’) also studied on the nocturnal sleep of fourteen epileptics with focal spikes. He reported that ten out of total fourteen patients had almost normal course of nocturnal sleep and another four cases showed considerable disorganizations of sleep cycles. From an etiological or clinical point of view, the Iat- ter cases were suspected to have some organic lesions of brain. If one compared their findings with the results obtained in this study, it is interesting that most of the temporal lobe epileptics showed a disorganized course of sleep. As stated previously in this

74 S. Kikuchi

paper, the most remarkable characteristics on the nocturnal sleep course of patients with temporal lobe seizures were shortening of D stage, prolongation of C stage and irregular appearance of P stage. Temporal spikes were considered to originate in the deeper structure of temporal lobe. These patients which showed the characteristics mentioned above were suspected to have a certain organic lesions in limbic structures of the brain, especially in hippocampus. So the modifications of sleep course observed in the temporal lobe epileptics were suspected partly due to the dysfunctions of limbic structures. The irregular appearance and the unstable duration of P stage were commonly observed on the patients, and these facts were also found on the patients with brain diseases. Jouvet’s worklo) seems to be sug- gestive in this respect. He intended to identi- fy the neuronal structure responsible to the appearance of paradoxical phase of sleep in cat. In order to make clear of localizations of this structure, he destroyed various parts of brain-stem and found that the destruction of nucleus reticularis pontis caudalis suppressed the appearance of paradoxical phase of sleep or “rhombencephalic phase of sleep” as well as hippocampal rhythmical theta waves without any suppressions of cortical arousal. He also proved that even if the ascending pathway was destroyed, rhombencephalic phase of sleep could persist as far as the mid-brain reticular formation and the ventral part of brain-stem remained intact. The modifications of sleep course observed on temporal lobe epileptics seemed partly due to the dysfunctions of the limbic system, and partly due to the participations of the functional disturbances of the brain-stem structures regarding to the regulations of sleeping-waking cycle.

In this study, the author observed some characteristics of EEG waves appeared during sleep of the patients. One of them was “slow spindles” with frequencies ranging from 8 to 12 c/s. These spindle-formed

rhythmic waves, observed frequently during the nocturnal sleep of the patients, lasted for a few seconds and appeared intermittently as well as normal spindles. These waves sometimes appeared accompanied by normal spindles at the same stage of sleep. So the author took the stage where these slow spindles appeared for C stage and considered them as one of the varied types of normal spindles. Spindles were defined by Davis et al.3) as characteristic brief trains of 14 c,/s waves which appeared during sleep with the amplitude over approximately 50 microvolts. Gibbs and Gibbs reported that they could record 10-12 c/s slow spindle waves appeared predominantly at the fronto-parietal regions during sleep of normal subjects. It has been well known that the spindle-formed waves might appear during various stages of nocturnal sleep. Hoffman et also stated that 14-16 c/s spindle waves sometimes appeared during light sleep, 13-1 6 c/s spindle waves during moderately deep sleep and 9- 12 c/s slow spindle waves during deep sleep. So the appearance of spindle-formed waves does not always characterize C stage of sleep, In the sleep EEG records of the patients, the long lasting, irregular and monotonous background patterns, characterized by slow spindles of 8-10 c/s, were frequently observed and large delta waves did not appear during this stage. This pattern, i.e., slow spindles, seems to be a characteristic finding on the sleep pattern of the temporal lobe epileptics. Spindle waves are considered to originate in the thalamic nuclei because of their bilaterally synchronous appearance and to have a close relationship to the non-specific thalamo- cortical ascending pathways. Although the genesis of these slow spindles is not clearly confirmed, these waves are suspected to have the same genesis if one considered its constant and bilaterally synchronous appearance on both hemispheres. The appearance of these slow spindles observed in the temporal lobe epileptics was suspected to be an


expression of the disturbance of some neuronal mechanisms regarding the formation of normal spindle waves. In addition to the appearance of the slow spindles, it was also observed that humps during the light sleep stage appeared very poorly and the delta waves during the deepest sleep stage showed rather low voltage. It has been well known that these findings mentioned above are also commonly recognized on the sleep of the patients with the obvious organic lesions of brain such as presenile psychosis or CO-intoxication. So these findings suggest the latent lesions of the brain on the temporal lobe epileptics.

2) The incidence of spike discharges during nocturnal sleep of temporal lobe epileptics

Gibbss) and Fuster6) already stated that natural or drug-induced sleep EEG was very useful to make an exact diagnosis of epilepsy because spikes appeared more frequently during sleep than in arousal state. Their studies, however, were done in short- time diurnal sleep from a clinical diagnostic viewpoint and it seems insufficient to know the mode of incidence of spike discharges during each stage of nocturnal sleep. More- over, after the introduction of a new con- cept, “paradoxical phase of sleep”, by Dement and Kleitman6) into the study of sleep, the reconsideration upon the sleep of epileptics as well as the mode of incidence of spikes during sleep seems to be necessary. Natural nocturnal sleep was the best condi- tion to know about the correlations between course of sleep and various sorts of epileptic manifestations. In this chapter, the author would like to take account of the correlations between the mode of incidence of spike discharges and the electroencephalographic depth of sleep during a whole night.

Out of seven cases which numbers of temporal spikes were calculated during a whole course of an all-night sleep in this study, five patients showed the most frequent incidence

of spikes during C stage as well D stage. In the remaining two cases, spike discharges appeared most frequently during B stage of sleep. The frequent incidence of spike discharges on EEG recordings seems to mean in general the elevated excitability of neu- rones during a certain stage of sleep. There- fore it has been hitherto explained that the increase of incidence of epileptic discharges is due to enhanced hypersynchronization during the middle depth of sleep where spindle burst appeared. The mode of incidence of spikes during B stage was not confirmed in this study, because the rate of appearance of B stage occupied in whole total time of nocturnal sleep was relatively few. Some patients showed fairly frequent incidence of spikes in B stage. It could be said generally that spikes appeared more frequently during B stage than during A stage. These facts were consistent with the observations of Schwartz and his colleagues15) who reported on the all-night EEG tracings on three patients and remarked the different modes of incidence of single or multiple spikes during each stage of sleep throughout a night. In their paper, five types of paroxysmal discharges, observed on three patients with various types of seizure, were examined in order to analyze precisely the mode of incidence of spikes during a whole night. For example, on their first case with temporal lobe seizures, which showed right anterior-temporal spikes in EEG, single spikes appeared most frequently during deep sleep stage, next during very deep sleep stage and least frequently during waking as well as REM sleep stage. In their second case with frequent Jacksonian seizures, multiple spikes and wave burst appeared most frequently during drowsy stage, next during light sleep stage and most rarely during deep sleep stage. From their observations on the sleep EEGs of three patients, they suggested that paroxysmal seizure activities with similar morphology, appeared in different patients, might show the different

76 S. Kikuchi

mode of incidence during each stage of sleep. They concluded that these facts could be partly due to some unknown personal characteristics of the patients and partly due to the different etiology or topographical dis- tributions of spikes in each case.

Passouant et al.13) stated that psychomotor epileptics in childhood often showed unstable localizations of spike focus and differed from these of adults patients with regard to their mode of incidence of spikes. Kazamatsuri12) also investigated the correlations between the depth of sleep and the modifications of centrencephalic paroxysms during a whole night sleep on the twenty- one cases of petit mal absences with 3c/s spike and wave complex. He found that centrencephalic spike and wave complex transformed itself as the sleep deepened. He classified the paroxysms appeared during various stage of sleep into six types according to EEG morphology such as wave forms, duration of burst, rhythmicity and topography. His studies revealed some correlations between the depth of sleep and the modifications of EEG paroxysms, namely, 3 c/s classical spike and wave complex burst appeared only during A stage, irregular spike and wave complex with short or long dura- tions mainly during B stage, and diffuse spikes or isolated spike and wave complex during C stage as well as during D stage. As to the incidence of paroxysms, centrencephalic spike and wave bursts were observed most frequently during B stage as well as C stage, while during A stage as well as P stage there could not be observed any paroxysms other than 3 c/s regular spike and wave burst. His findings were almost identical to those of Schwartz et al. that the paroxysmal burst of bilateral multiple spikes, subclinical seizures, appeared most frequently during C stage as well as D stage and never appeared during A stage as well as P stage. Fujimori7) also studied the changes of discharge rate of various focal spikes during each stage of nocturnal sleep throughout a night. He clas-

sified tentatively the mode of changes of discharge rate into three types during each stage of sleep. His classification was as follows: Type I; the discharge rate was very low during A stage, increased slightly during B stage, showed marked increase during C stage and decreased again during D stage as well as P stage. This type could be divided into two subgroups furthermore. Type 11; the discharge rate was considerably high even during A stage and increased gradually as the sleep deepened into B, C and D stage. Spike discharges were observed during P stage almost equally as during A stage without any suppressions. Type 111; the discharge rate was highest during A stage, decreased gradually as the sleep deepened and increased again during P stage where spikes appeared approximately equally as during B stage. These three types, classified according to the mode of incidence of focal spikes, had some characteristics in morphology, duration and topography of the spike discharges respectively during nocturnal sleep. He could not find, however, any definite correlations between these three types and clinical or electrographic factors such as type of seizures or localizations of spikes. Compared with his results, the mode of changes of discharge rate by temporal lobe epilepsy was similar to that of his type I. Namely, the rate of incidence of temporal spikes was relatively low in arousal state, became gradually higher as the sleep deepened and the suppression of spikes was observed during P stage. According to Fujimori’s comments in his paper, the mode of incidence of spikes belonged to type I1 or 111 when the localization of their spike focus was suspected to exist near the surface of cerebral cortex, whereas it belonged to type I when the localization of spike focus was suspected in the deeper structures of the brain. The localization of spike focus of temporal lobe epilepsy is suspected to exist in the deeper structure of temporal lobe, so the author’s results seemed to correspond to those of


Fujimori’s and also to prove his suppositions mentioned above.

Kajtor and his coworkersll) also reported induced sleep EEG tracings by a small dosis of Evipan-Natrium in seven temporal lobe epileptics of whom Ammon’s horn sclerosis was confirmed by autopsy. They mentioned that the spikes led from the surface of the temporal cortex appeared most frequently during middle and deep stage of sleep, while spikes led from mesobasial part of temporal lobe and suspected to originate from hippocampal gyri appeared most predominantly during light stage of sleep. They suggested that the different modes of incidence of spikes during each stage of sleep were due to the different localization of electrogenesis of spikes. The observed three adults patients with anterior-temporal foci showed the most frequent incidence of spikes during B stage as well as C stage of sleep in this study. All these patients were suspected to have exoge- nous organic lesions from an etiological or clinical point of view, and their epileptogenic lesions were suspected to exist around mesobasial deeper parts of temporal lobe. So these findings coincided with those of Kajtor and his coworkers’. On the contrary, in a female patient Y.M., (No. 15) with left anterior-temporal spike foci, who had suf- fered from encephalitis of unknown etiology in her early infancy, spikes appeared most frequently during D stage of sleep. Her ictal symptoms were considerably complex, i.e., arrest of motions, oral automatism and paroxysmal autonomic dysfunctions. So the localization of lesions was suspected in the neocortex of temporal lobe.

It has been our common knowledge that the seizure types of temporal lobe epileptics are further divided clinically into two subgroups, namely, automatism and psychic seizure. The patients with automatism have generally their spike foci at mesobasial parts of temporal lobe such as hippocampal gyri, whereas the patients with psychic seizures have their spike foci at the superficial neo-

cortex of temporal lobe. From the results otained from this study, the author concluded that the spike discharges originating in neocortex of temporal lobe generally appeared most frequently during the deeper stage of sleep, while the spikes originating in the mesobasial parts of temporal lobe or such as hippocampal gyri, which was a part of limbic system of brain, appeared most frequently during the light stage of sleep.

3 ) Clinical seizures during nocturnal sleep The author observed nine clinical seizures

in seven patients during all night sleep recording and thereby ictal EEG patterns were simultaneously recorded. Although the anti- epileptic medicaments were withdrawn before recording for several days, the fact that clinical seizures occurred in seven out of total twenty patients proved an important role of sleep to provoke temporal lobe seizures. It also corresponds to our common knowledge that some forms of epileptic seizures are apt to develop frequently during natural nocturnal sleep. From neurophysiological and clinical points of view, the time and the depth of sleep which the seizures were observed in this study are mainly discussed here.

All the seven patients which showed clinical seizures during nocturnal sleep belonged to group B, i.e., the older patients. The younger patients belonging to group A, did not show any clinical seizures during sleep recordings, All night sleep recordings were performed upon only one night on each patient, so it could not be said that these patients which seizures were observed showed nocturnal clinical seizures every night. From the facts mentioned above, however, it would be possible to say that the older patients with temporal lobe seizures were apt to have nocturnal seizures than the younger ones.

The time and the depth of sleep where clinical seizures occurred were very important to make clear the background condi-

78 S. Kikuchi

tions for provoking epileptic seizures during nocturnal sleep. As to the time of attacks, these clinical seizures, however, occurred indefinitely, i.e., immediately after falling asleep in three patients (No. 12, 13, 14-l), at the midnight in two patients (No. 9, 14-2) and early in the morning in four patients (No. 7, 11, 14-3, 17). Although several authors found before the introduction of EEG into the study of sleep that some of the nocturnal epileptic attacks had their predilected hours, the author could not find any predilected hours for norturnal seizures from these results.

In this study, there could not be found any definite depth of sleep where nocturnal seizures were prefered to occur. Three patients showed their clinical seizures during D stage, two patients during C stage and one during P stage. A remaining female patient of 24 years old, Y. K. (No. 14) provoked exceptionally automatisms three times during a night. Two of them were observed during P stage and one during B stage. From these findings it could be concluded that nocturnal seizures might occur in any stage of sleep. Delange and his coworkers4) also reported clinical seizures observed during all night sleep. They observed clinical seizures on two patients out of ten epileptics consisted of six patients with centrencephalic form of epilepsy as well as four patients with temporal lobe epilepsy. Their first case, whose clinical seizure was right-sided hemiconvulsion, provoked a clinical seizure during light stage of sleep (sommeil leger) . Their second case, whose clinical seizure was adversive seizure with acceleration of respiration, elicited six clinical seizures during a night and these seizures took place during the drowsy stage of sleep. The postictal sleep stage of the latter patient shifted to P stage and sleep persisted without awakening. Delange et al. stated that these seizures, resembling pavor nocturnus, were followed by paradoxical phase of sleep and thus they suggested the possible correlations between clinical seizures and the para-

doxical phase of sleep which was considered as period of dreaming by Kleitman. Fuji- mori7) also observed in his study two clinical seizures out of twelve patients with various types of focal seizures. One of them occurred during C stage and the other during P stage of sleep. Their results seem to correspond to the author’s observations in regard that clinical seizures do not necessarily take place during a definite stage of slecp and they may occur during different stages in a same patient, even during paradoxical phase of sleep.

The correlation between the incidence of spike discharges and the occurrence of clinical seizures seems to be another important problem. It has been generally considered that the frequent incidence of spike discharges on EEG represents the enhanced excitability of pathological neuronal activity in focal region. In order to examine the correlation between them, the depth of sleep in which spike discharges appeared most frequently were compared with the depth of sleep which clinical seizures occurred in two patients. In a male patient, K. N., (No. 3) clinical seizure was provoked during C stage and spike discharges also appeared most frequently during the same C stage. On the other hand, in another male patient, T. K., (No. 11 ) seizure occurred during P stage, while spikes appeared most frequently during D stage of sleep. These findings seems to indicate that clinical seizures do not necessarily occur during the stage of sleep which spike discharges are most frequently observed. There may be discordance to a certain degree.

In this study, the author could record ictal EEG patterns during nocturnal spontaneous seizures. These EEG paterns during seizures were, except for one case, rhythmical theta wave burst which usually started in the region of spike focus. These findings were already described by many authors hitherto- fore. Exceptionally only one female patient, C. S., (No. 13) with bilateral temporal foci


predominantly appeared in left side on interseizure EEG, showed an asymmetrical spike and wave complex at the onset of clinical seizure. In general, these paroxysmal theta waves used to increase gradually their amplitude and the frequencies of them became slower. During the seizures, the artifacts due to body movements always mingled into EEG records and the complete recordings of EEG often could not be done. In other male patient, T. K., (No. 11 ) transient alpha waves were observed predominantly in bilateral occipital region before the onset of seizure, and then the clinical seizure began. After the seizure, these occipital alpha waves still lasted for a while. High voltage delta waves were observed consistently in the other regions of hemisphere, so it did not mean at all that he awoke for some time after the seizure. The author supposes, however, that this alpha-like waves represent the enhanced activity level of the brain, which does not reach to fully awaking state, persisted for a while after clinical seizure. The further detailed examinations of EEG, however, revealed that in some patients the postictal depth of sleep was rather just a lit- tle more superficial than the pre-ictal depth of sleep without any shifts of sleep stage.

Judging from the author’s observations on nocturnal seizures of the patients with temporal lobe epilepsy, the patients did not generally awake after the seizures during sleep and therefore could not remember their nocturnal fits in the next morning. After seizures they used to continue sleeping without any shifts of the depth of sleep, so they usually declared that they had never experienced any seizures during sleep. From a clinical point of view, it seems very important that the patients could not remember the nocturnal seizures, especially automatisms or abortive convulsive seizures. Therefore it is considered that these nocturnal seizures were often apt to be over- looked by the patients clinically.

SUMMARY A whole night EEG study was car-

ried out on twenty temporal lobe epileptics and fourteen normal subjects. ECG, respiratory curve, GSR and horizontal eye movements were also simultaneously recorded polygraphically. Primary attention was de- voted to the changes of temporal spikes in different stages of nocturnal sleep and also to the characteristics of sleep course of the patients.

2) The electrographic depth of sleep was divided into the following five stages; A (wakefulness), B (drowsiness and light sleep), C (moderately deep sleep), D (deep sleep) and P (paradoxical phase of sleep or REM sleep). The sleep diagrams were drawn on all the patients and the rate of incidence of spike discharges throughout a whole night was demonstrated in each stage of sleep on seven patients.

As to the pattern of sleep cycles during a whole night, the majority of twenty patients with temporal lobe epilepsy showed some disorganizations of the pattern of sleep cycles to more or less degree. Although there were great individual differences, the most characteristic features observed on the sleep course of the patients were prolongation and frequent appearance of C stage, shortening or poor appearance of D stage and irregular appearance of P stage. These changes were observed more remarkably in younger patients. The disorganizations of sleep cycles observed on temporal lobe epileptics seemed partly due to the dysfunctions or lesions of limbic system of the brain.

Spindle-formed rhythmical waves with frequencies ranging from 8 to 12 c/s were found during C stage of the patients. The lower voltage of delta waves during the deepest stage of sleep and the poor appearance of humps during light stage of sleep were also observed.

The most frequent incidence of temporal spikes was observed during C stage on

1)

3 )

4)

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most of the patients. Only a few patients showed the most frequent incidence of spikes during B stage. No clear correlation was found between the types of the incidence of spike discharges and etiological or clinical factors. During P stage, spike discharges were generally suppressed as well as during A stage in most of the patients. On the patients with bilateral multifoci, the mode of incidence of spikes during sleep almost the same in both hemispheres.

5 ) Nine clinical seizures were observed on seven patients during nocturnal recordings. Two seizures occurred during C stage, three during D stage, three during P stage and one during B stage, On a female patient, three seizures were provoked during B stage and P stage in one night. So the predilected depth of sleep for nocturnal seizures was never found in this study. After clinical seizures, the depth of sleep did not alter, the patients did not generally awake and could not remember their nocturnal fits next morning. Ictal EEG patterns were rhythmic slow waves started at the region of the EEG spike focus with a exception of a case which showed irregular spike and wave complex.

6) The neuronal mechanisms underlying the modifications of incidence of spike discharges during sleep were discussed in terms of interrelation between the activity level of the brain and the mechanism producing seizure discharges.

ACKNOWLEDGEMENT This work was carried out with the earnest

co-operations of Dr. Yoshihito Tokuda, Dr. Hajime Kazamatsuri and Dr. Masamoto Fujimori under the guidance of former Prof. Haruo Akimoto and former assistant Prof. Shuji Taen. The author wishes to express his sincere gratitude to these collaborators and also to thank Prof. Hiroshi Utena for his critical reading of the manuscript.

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