Interrelationships between rapid eye and body movements during sleep: polysomnographic examinations of infants including premature neonates

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Eh,ctroencephalography and clinical Neurophysiology , 79 (1991) 277-280 © 1991 Elsevier Scientific Publishers Ireland, Ltd. 0013-4649/91/$03.50 ADONIS 001346499100145Y

EEG 90093

Interrelationships between rapid eye and body movements during sleep: polysomnographic examinations of infants including premature neonates Jun Kohyama and Yoshihide Iwakawa a Department of Pediatrics, Tsuchiura Kyoudou Hospital, Tsuchiura, and ~'Department of Pediatrics, Faculty of Medicine, Tokyo Medical and Dental Unit ersiO,, Tokyo (Japan) (Accepted for publication: 18 February 1991)

Summary Myoclonic twitching and rapid eye movements (REMs) are believed to occur in close association in animals; but, there have been few studies on their interrelations in humans. Polysomnograms were made from 33 normal infants of 34-84 conceptional weeks of age in order to observe the developmental aspect of the relation between twitching and REMs. We examined the small body movements (BMs), which appeared to be equivalent to twitches in animals and calculated the percentage of BMs that occurred together with the REM bursts in comparison to the total number that occurred during active REM sleep (% BMs in REM bursts). Polysomnograms were also obtained from 5 infant patients whose pathophysiologies were considered to be due to brain-stem immaturity. Whereas the values showed abrupt decreases during early infancy, nearly reaching 0, for the normal infants, they were high in some of the patients' records. These results suggest that few BMs occur during REMs in humans as opposed to animals. The maturation of inhibitory mechanisms, which are located in the brain-stem and act during REMs, may account for the rapid decrease of % BMs in REM bursts during early infancy. Increases of this index may reflect delayed brain-stem maturation. Key words: Sleep; Development; Rapid eye movement burst; Body movement

Myoclonic twitching, a representative phasic sleep component during active R E M sleep (AS) of animals (the executive systems of which are known to be in the brain-stem (Vertes 1984)), is closely correlated with bursts of rapid eye movement (REMs) (Gassel et al. 1964; Glenn and Dement 1981; Vertes 1984). Segawa and Nomura (1990), however, have reported that in children few twitches occur during bursts of REMs. To determine whether this is so, we made polysomnograms of normal infants, and examined the development of the relation between REMs and small body movements (BMs) which are considered equivalent to the muscle twitches of animals. For this purpose we used a newly developed index (the % BMs in REM bursts (Hakamada et al. 1985; Segawa and Nomura 1990)). We also applied this index to the polysomnograms of 5 infant patients whose pathophysiologies were considered to be due to brain-stem immaturity in order to ascertain whether this index adequately reflects brain-stem dysfunction.

Correspondence to: Jun Kohyama, MD, Department of Physiology If, Asahikawa Medical College, Nishikagura 4-5-3-11, Asahikawa 078 (Japan). Tel.: 0166-65-2111 (2332); Fax: 0166-65-7563.

Subjects Thirty-three normal infants of 34-84 weeks conceptional age (CA) were studied after obtaining the informed consent of their parents. The infants were divided into 4 groups ( I - I V ) based on their recorded CAs; group I included preterm neonates and group II consisted of term neonates. As the incidence of phasic sleep components differs markedly before and after CA 52 weeks (Kohyama and Iwakawa 1990), we selected this age as the critical one which distinguished the infants in group III (younger infants) from those in group IV (older infants). All the infants in groups I I - I V had had uneventful term deliveries. Polysomnograms were also obtained from 5 infant patients: one was subsequently the victim of sudden infant death syndrome (SIDS), and the other four had experienced apparent life-threatening events (ALTE) (Consensus statement 1987) (ALTE 1-41. Details of their cases have been presented elsewhere (Kohyama and Iwakawa 1989; Kohyama et al. 1991). The gestational ages of all the subjects were assessed by the criteria of Dubowitz et al. (1970). No medication was administered during the study.

Recording procedures Polygrams were obtained at least 3 days after birth in order to eliminate the influence of delivery. The

278

J. KOHYAMA, Y. IWAKAWA

record for the infant with SIDS was obtained 5 weeks prior to his death, and the first ones for the A L T E infants were obtained within 2 weeks of the events. Three subsequent records were made for A L T E 1 and one for each of the other 3 patients. Recording was done while the subject lay supine in the crib, except in the cases of some preterm neonates who were in incubators. We secured a minimum of 3 h total sleep time that consisted of at least 2 A S - q u i e t sleep cycles. Most records were obtained in the evening, but those for groups III and IV. and for the patients, were made overnight. Each polygram consisted of E E G , bipolar horizontal electro-oculogram, respiratory monitoring and surface EMGs, including those of mental muscle. The recording speed was 1.5 c m / s e c .

Data analysis The sleep state was classified according to Anders et al. (1971). The standards of Rechtschaffen and Kales (1968) were applied to group IV (we considered AS in LC- LP

~..~..,..~,,~.~.z.~,,.,

~r,./-

RC-RP __)

T.C. 2.0 T.C. 0.03

EOG EMG

r

meat.

~

__)

Fig. I. Localized movement (L) of mental muscle independent of a REM burst (underlined) in a normal infant 37 weeks CA. LC-LP (RC-RP): EEG obtained between the left (right) central and left (right) parietal portions; EOG: electro-oculogram; T.C.: time constant: EMG: electromyogram; ment.: mental muscle.

LC-LP

-"---~-~._,~.-,~-~.....

RC - RP

-"~,~.,~,~,~.,-'J~"~~"~

T.C. 2.0 ~ T.C. 0.03

EOG

~

~

EMG merit.

"~ T

__J

Fig. 3. Twitch movement (T) in a REM burst (underlined) in a normal infant 42 weeks CA. This REM burst consists of 3 REMs. Abbreviations as for Fig. 1.

the former criteria as having the same meaning as stage R E M in the latter). REMs (time constant, 2.0; calibration, 50 # V / m m ) during AS were defined as having a 75 #V, or more, amplitude with a 50 °, or greater, angle of rise. A R E M burst was defined according to Glenn and D e m e n t (1985) as more than 2 consecutive REMs at intervals of less than 0.5 sec (Figs. 1-3). Of the various BMs, we studied localized muscular discharges of mental muscle, which reached twice the level of the surrounding muscle tone (calibration, 50 p.V/5 ram) (Kohyama and Iwakawa 1990). These BMs were divided into 2 categories based on duration: localized movements (LMs) lasting more than 0.5 sec (Figs. 1 and 2) and twitch movements (TMs) lasting 0.5 sec or less (Fig. 3) (Kobyama and lwakawa 1990). The percentages of TMs and LMs that occurred with the R E M bursts (Figs. 2 and 3) to the total number of BMs during AS (% TMs (LMs) in R E M bursts) were calculated. Spearman's correlation coefficient (r) was calculated to show the relationship of age to % TMs (LMs) in the R E M bursts. Significance was assessed by the t test. Results

Normal infants (Table I)

LC-LP

Both the % TMs and % LMs in the R E M bursts decreased significantly with age (% TMs: r = -0.55,

RC-RP

TABLE I % TMs and LMs in REM bursts in normal infants.

EOG

T.C. 2.0 T.C. 0.03

EMG

m nt.

;

Fig. 2. Localized movement (L) associated with a REM burst in a normal infant 37 weeks CA. Two REM bursts (underlined) are present. Abbreviations as for Fig. 1.

Group

Conceptional weeks

~4 TMs in REM bursts (mean_+ S.D.)

% LMs in REM bursts (mean_+ S.D.)

l. Pretermneonates (n = 7) II. Term neonates (n = 9 ) lII. Younger infants (n = 10) IV. Older infants (n = 7)

34-36

9.2_+6.1

14.0±7.1

37-42

8.1 +_6.4

11.7.+4.9

43-52

3.9±3.3

5.4.+3.1

53-84

2. I + 1.3

5.5 .+ 1.7

INTERRELATION

279

BETWEEN PHASIC SLEEP EVENTS

T A B L E 11 c/~ T M s and LMs in R E M bursts in p a t i e n t s with A L T E and S1DS.

SIDS ALTE I

AL.TE 2 ALTE 3 A[TE 4

Conceptional w e e k s at recording

C/c T M s in R E M bursts

% LMs in R E M bursts

43 39 42 511 76 46 t~8 44 52 42 52

17.9 13.3 11.5 14.9 8.5 9.8 3.8 14.1 5.O 6.{) 2.4

6.4 15.0 9.5 12.5 * 6.4 4.6 3.3 7.8 5.() 9.9 2.9

*

* * * *

* I)eviation of more than + 1.5 S.D. from the m e a n for the controls.

P<0.001; % reaching zero.

LMs:

r=-0.69,

P<0.00Á),

nearly

Patients with A L T E and SIDS (Table II) Of the 11 records obtained, % TMs in the R E M bursts were greater than + 1.5 S.D. of the control value in 5 records, while the % gMs in the R E M bursts was more than + 1.5 S.D. of the value in 1 record. The other values, both for the % TMs and LMs in the R E M bursts, were all within _+ 1.5 S.D. of the control value.

Discussion In human adults, REMs and muscle twitches increase across successive R E M periods during the night, but they are free from the first night effects (Geisler et al. 1987). Moreover, individual variations in the sleep of neonates is thought to be due to maturation of the central nervous system rather than to environmental factors (Anders 1975). We therefore studied at least 2 A S - q u i e t sleep cycles for the neonates of CA 42 weeks or less and obtained overnight records for infants of CA 43 weeks or more. We could extract 2 findings from the present study on normal infants. One was the relatively low incidences of small BMs occurring with R E M bursts, and the other was the rapid decrease of the % BMs in R E M bursts during early infancy. As for the first point, taken together with the report by Segawa and Nomura (1990), % BMs in R E M bursts must be low in humans. On the second point, the incidences of both TMs (Kohyama and Iwakawa 1990) and R E M bursts (Petre-Quadens 1974; Ktonas et al. 1990) increase during early infancy, which means that our second finding is noteworthy.

Mechanisms underlying the simultaneous occurrence of twitches during REMs have been studied in feline motoneurons. Excitatory potentials during AS override postsynaptic phasic inhibition during REMs, and generate action potentials leading to muscular twitches (Chase and Morales 1982). Neurons that correlate with twitching during AS are localized in the rostral medullary-caudal pontine reticular formation, from which there are direct projections to trigeminal motoneurons (Vertes 1984). Medullary reticular neurons are believed to inhibit trigeminal motoneurons mono- and post-synaptically during R E M periods (Chase et al. 1984). These suggest that our first finding (low % BM in R E M bursts in man) may reflect stronger inhibition, or weaker motor excitation, functioning at the motoneuron level during REMs in humans as opposed to animals. As the incidence of TMs increases during early infancy (Kohyama and lwakawa 1990), it seems unlikely that the case of weaker motor excitation is acceptable. Then, our second finding (the rapid decrease of the ~, BMs in R E M bursts during early infancy) suggests that the above mentioned inhibitory systems, which are located in the brain-stem and act during REMs, mature rapidly during early infancy to prevail over excitatory information. Namely, central inhibitory mechanisms originating in the brain-stem seem to conquer excitatory drives at motoneuron level in combination with phylogenetic evolution as well as ontogenetic development. As for the chronological changes in the % BMs in REM bursts, mechanisms other than the maturation of central inhibitory systems must be taken into consideration; that is, the increase in the size of motoneurons with age, the distal shift of synapses resulting from dendritic development, and postnatal elimination of synapses on motoneurons ( H a k a m a d a et al. 1988). The pathogenesis of SIDS and A L T E has been thought to be brain-stem immaturity (Quattrochi et al. 1985; Denoroy et al. 1987; Hunt and Brouillette 1987). We have shown that there was no significant difference in the total R E M densities for the controls and our patients, and reported lower incidences of TMs in infant patients (Kohyama et al. 1991). This implies that high % TMs in REM bursts in some of our patients have pathological meaning. Elevations of indexes equivalent to ours have been reported for neonates with central apnea ( H a k a m a d a et al. 1985). Although more definitive studies are needed the increase in the % BMs in R E M bursts suggests the possibility of delayed brain-stem maturatkm, especially that of the cholinoceptive inhibitory system (Steriade and McCarley 199(I).

W e t h a n k Dr. M a s a y a Segawa for his critical r e a d i n g of our manuscript.

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