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Ontogenesis of paradoxical sleep in the human newborn
SHORT REPORTS
153
at present, and its effects are usually attributed to antiphlogistic properties. This study is unable to furnish any evidence for the hypothesis that the action o f A C T H might be mediated by modification o f platelet stickiness.
SUMMARY The administration o f an A C T H infusion in a small series o f patients with multiple sclerosis has not influenced platelet adhesiveness.
ACKNOWLEDGEMENTS The author wishes to t h a n k Dr. E. J. Field for help and encouragement and also Professor H e n r y Miller, whose patients were studied. Medical Research Council Demyelinating Research Unit, and Department of Neurology, Royal Victoria Infirmary and University, Newcastle upon Tyne (Great Britain)
P. MILLAC
REFERENCES CASPARY,E. A., J. PRINEAS,H. MILLERANDE. J. FIELD(1965) Lancet, ii: 1108. FIELD,E. J. ANDE. A. CASPARY(1964)Lancet, ii: 876. HELLEM,A. J. (1960 Scand. J. Clin. Lab. Invest., Suppl. 57: 12. MILLER,H. (1964)Practitioner, 192: 62. MITCHELL,J. R. A. ANDA. A. SHARP(1964) Brit. J. Haematol., 10: 78. NATHANSON,M. ANDJ. P. SAVITSKY(1954) Bull. N.Y. Acad. Med., 28 : 462. THOMPSON,R. H. S. (1964) Proc. roy. Soc. Med., 59: 269. WRIGHT,H. P. (1941) J. Path. Bact., 53 : 255. WRIGHT,H. P., R. H. S. THOMPSONANDK. J. ZILKHA(1965) Lancet, ii: 1109. (Received 23 July, 1966) J. neuroLSci. (1967) 4:151-153
Ontogenesis of paradoxical sleep in the human newborn INTRODUCTION I n 1957, two years after the discovery by ASERINSKY AND KLEITMAN (1955) o f a period o f multiple eye-movements during sleep, DEMENT AND KLEITMAN drew attention to the fast cortical activity in the L E G which characterizes this period o f sleep and showed that in men it is closely related to dreaming. The localisation in the reticular nuclei o f the pons of the structures responsible for This study was supported by the Scientific Medical Research Foundation of Belgium, by the 'Fondation Reine Elisabeth de Belgique', and the grant USAF (EOAR) 61(052)-949. J. neurol. Sci. (1967) 4:153-157
154
SHORT REPORTS
paradoxical sleep (PS) (JOUVET 1962) rapidly led DANI~LE JOUVET to examine the problem of its ontogenesis in the kitten (1961). In the human newborn, DELANGEet al. (1961) and ROFFWARGet al. (1964) described a phase of sleep in all respects similar to PS in adults. But whereas the PS of an adult occupies about 20 % of the night, it appears that the PS of the newborn occupies about half the duration of sleep. Earlier, we have been able to establish the individuality of PS in the mature newborn and to distinguish it from another state of active sleep called 'drowsiness' or stage a (PETRE-QUADENS 1966). Using the same criteria, an attempt has been made to establish in the premature the ontogenesis of PS and the simultaneous disappearance of EMG activity in the levator menti. MATERIAL AND METHOD
Simultaneous recordings of the EEG, EMG, eye-movements, cardiac and respiratory rate, have been made on 14 premature infants whose gestational age varied from 28 to 37 weeks. Gestational age is calculated from the probable date of conception, term being defined as 268 days or 38 weeks. The duration of recordings is 3 hours. RESULTS
Disappearance of the EMG activity Paradoxical sleep (PS) defined by the electroencephalographic activation, the presence of rapid eye-movements and the increase in respiratory rate, is found to be °/o EMG 0 in PS
o0oD
100
coo
o
®
•
•
•
•
O
90 80 O
0
0
70 0
60-
o o
50
0
0
0 o
8 8
40 30 20 10
. . . . . . . . . . . . . . . . . . . 0 28 30 32 34 36 381 2
AGE
I
weeks gestational
age
~
I
4
weeks
•. . - . . ;..--¢/--4,¢--¢/ . . . 6 i 2 3 7 10 141 2 3 4
i months p a s t term
(term=268days
i years '
+_. 5 d a y s )
Fig. 1. Evolution of the relative proportions of E MG abolition during paradoxical sleep, according to age. O: Night-sleep recordings; o : day-sleep recordings; [] represents 15 new-borns, day-sleep recordings. J. neurol. Sei. (1967) 4:153-157
SHORT REPORTS
155
present from the 28th week of foetal life. But whereas in the mature newborn at term, the period of electrocortical activation with rapid eye-movements is most often accompanied by abolition of electromyographic activity, the disappearance of muscle action potentials is found to be inconstant in the premature (Fig. 1). At 28-30 weeks, the EMG is characterized by low voltage activity which does not vary during the course of the recording. At the age of 33 weeks, this activity is replaced by an adult EMG pattern. This ceases in a few per cent during PS. The degree of abolition of EMG activity during PS increases as the foeta lage approaches 37 weeks. Smiling which appears in the newborn at term during PS (PETRE-QUADENS AND LAROCHE1966) most frequently associated with abolition of EMG activity - - can be seen in the premature not only during PS when EMG activity is absent, but also when it is preserved. Up to the age of 7 months, the abolition of EMG activity is not an absolute criterion of PS and it is only the character of the ocular movements which distinguishes it. Eye-movements are discrete and infrequent during stage a and occur in bursts during PS. In the premature and the mature newborn, the figures refer to recordings made during the day. The night recordings (between 7 p.m. and 3 a.m.) in the newborn reveal a greater dissociation between the phase of rapid eye-movements and the simultaneous disappearance of muscle tone, than the day sleep recordings. PS is frequently followed by a brief period of awakening. Up to the age of 7 months, periods of PS may be seen interrupting stage a. This phenomenon ceases by the age of 10 months at the same time as stage a vanishes. -
-
%PS 50, o
40.
30"
0
0
Z "e" . . . . .
~''t
20
10
J 0 28 AGE"
. . . . 30
' ' ' 32 34 weeks
' ' 36
gestationa[ age
' ' 3BJ I
' 2
L , , 4 weeks
, / / , //._~/._//._// , , , 6 2 3 7 10 141 2 3 4 m o n t h s : years past t e r m ( t e r m = 2 6 8 d a y s "4" 5 d a y s )
Fig. 2. Evolution of the percentage of paradoxical sleep per sleep-cycle, according to age. o : Paradoxical-sleep day-sleep recordings; 0 : % paradoxical sleep night-sleep recordings; D: average of ~o paradoxical sleep in 21 new-borns, day-sleep recordings; • : average of % paradoxical sleep in 5 new-borns, night-sleep recordings. J. neurol. Sci. (1967) 4:153-157
156
SHORT REPORTS
Maturation o f P S
We realize that in the course of maturation the periods of rapid eye-movements tend to coincide with the disappearance of E M G activity and achieve maximum duration at term (Fig. 2). Fig. 2 clearly indicates that PS increases before the 38th week. After full term, the duration of PS rapidly decreases. At the age of one month, PS occupies 21-22 ~ of the sleep cycle and this proportion remains constant. It should be understood that these percentages of PS have reference to a complete sleep cycle and not to a period of 24 hours. In the older child and in the adult, the proportion of PS per cycle and per 24 hours is the same. It must also be pointed out that daily recordings in children between the age of one and two months show a lower percentage of PS than the nocturnal recordings taken at about the same age. It is difficult not to attempt to compare this observation with the results of nocturnal recordings in the newborn where the inverse relationship may be recorded. At 38 weeks nocturnal recordings show the lowest percentage of PS. It is just possible that during the first weeks of life there is an inversion of the sleep cycle. After two months of age, periods of sleep occurring during the day become shorter and no longer encompass all the stages of sleep. For this reason, after this particular age, only nocturnal recordings have been studied. Also at two months, 'saw tooth' waves appear over the vertex in the E E G during PS. By 10 months, sleep has the same characteristics as those seen in the adult.
DISCUSSION
It is impossible to know to what extent the stages of sleep seen in the adult develop from the sleep stages of the newborn. On the one hand it would appear that stage a or 'undifferentiated sleep' (PARMELEE et al. 1964) belongs to an ontogenetically primitive state of vigilance which disappears during the first months of life at the time when the duration of awakening tends to increase. On the other hand the provocation of smiling during awakening by the maternal image about the age of one month, coincides with the reduction of PS. These findings also indicate that the mechanisms which determine the homeostasis of PS are acquired very early in life, at about the age of one or two months. O. PETRE-QUADENS Department of Developmental Neurology, Born-Bunge Foundation (Dr. L. van Bogaert), Berchem-Antwerp; and Department of Gynecology and Obstetrics, University St. Pierre Hospital (Prof. Hubinont), Brussels (Belgium)
REFERENCES
ASERINSKY,E. ANDN. KLEITMAN(1955) A motility cycle in sleeping infants as manifested by ocular and gross bodily activity, J. appl. Physiol., 8 : 11-18. DELANGE,M., PH. CASTAN,J. CADILHACANDP. PASSOUANT(1962) Les divers stades du sommeil chez le nouveau-n6 et le nourrisson, Rev. neurol., 107: 271-276. DEMENT,W. C. AND N. KLEITMAN(1957) The relations of eye movements during sleep to dream activity: an objective method for the study of dreaming, J. exp. Psychol., 53 : 339-346. neurol. Sci. (1967) 4:153-157
SHORT REPORTS
157
JOUVET, D., J. L. VALATXAND M. JOUVET(1961) l~tude polygraphique du sommeil du chaton, C.R. Soc. Biol., 155: 1660-1664. JOUVET, M. (1962) Recherches sur les structures nerveuses et les m6canismes responsables des diff6rentes phases du sommeil physiologique, Arch. ital. Biol., 100: 125-206. PARMELEE,A. H., W. H. WENNER, Y. AKIYAMAAND J. FLESCHER(1964) EEG and brain maturation, CIOMS Symposium on Regional Maturation of the Nervous System in Early Life, Paris, December 1964, to be published by Blaekwell, Oxford. PETRE-QUADENS,O. (1966) On the different phases of the sleep of the newborn and particularly of the activated phase or phase d, J. neurol. Sci., 3 : 152-162. PETRE-QUADENS,O. AND J. L. LAROCHE(1966) Sommeil du nouveau-n6, phases paradoxales spontan6es et provoqu6es, J. Psychol. norm.path., 1 : 19-27. ROFFWARG, H., W. C. DEMENTAND C. FISCHER(1964) Preliminary observations of the sleep-dream pattern in neonates, infants, children and adults. In: E. HARMS(Ed.), Problems of Sleep and Dream in Children, Vol. 2 (Intern. Series of Monographs on Child Psychiatry), Pergamon Press, Oxford, New York, p. 60-72. (Received 24 June, 1966)
J. neurol. Sci. (1967) 4:153-157
153
at present, and its effects are usually attributed to antiphlogistic properties. This study is unable to furnish any evidence for the hypothesis that the action o f A C T H might be mediated by modification o f platelet stickiness.
SUMMARY The administration o f an A C T H infusion in a small series o f patients with multiple sclerosis has not influenced platelet adhesiveness.
ACKNOWLEDGEMENTS The author wishes to t h a n k Dr. E. J. Field for help and encouragement and also Professor H e n r y Miller, whose patients were studied. Medical Research Council Demyelinating Research Unit, and Department of Neurology, Royal Victoria Infirmary and University, Newcastle upon Tyne (Great Britain)
P. MILLAC
REFERENCES CASPARY,E. A., J. PRINEAS,H. MILLERANDE. J. FIELD(1965) Lancet, ii: 1108. FIELD,E. J. ANDE. A. CASPARY(1964)Lancet, ii: 876. HELLEM,A. J. (1960 Scand. J. Clin. Lab. Invest., Suppl. 57: 12. MILLER,H. (1964)Practitioner, 192: 62. MITCHELL,J. R. A. ANDA. A. SHARP(1964) Brit. J. Haematol., 10: 78. NATHANSON,M. ANDJ. P. SAVITSKY(1954) Bull. N.Y. Acad. Med., 28 : 462. THOMPSON,R. H. S. (1964) Proc. roy. Soc. Med., 59: 269. WRIGHT,H. P. (1941) J. Path. Bact., 53 : 255. WRIGHT,H. P., R. H. S. THOMPSONANDK. J. ZILKHA(1965) Lancet, ii: 1109. (Received 23 July, 1966) J. neuroLSci. (1967) 4:151-153
Ontogenesis of paradoxical sleep in the human newborn INTRODUCTION I n 1957, two years after the discovery by ASERINSKY AND KLEITMAN (1955) o f a period o f multiple eye-movements during sleep, DEMENT AND KLEITMAN drew attention to the fast cortical activity in the L E G which characterizes this period o f sleep and showed that in men it is closely related to dreaming. The localisation in the reticular nuclei o f the pons of the structures responsible for This study was supported by the Scientific Medical Research Foundation of Belgium, by the 'Fondation Reine Elisabeth de Belgique', and the grant USAF (EOAR) 61(052)-949. J. neurol. Sci. (1967) 4:153-157
154
SHORT REPORTS
paradoxical sleep (PS) (JOUVET 1962) rapidly led DANI~LE JOUVET to examine the problem of its ontogenesis in the kitten (1961). In the human newborn, DELANGEet al. (1961) and ROFFWARGet al. (1964) described a phase of sleep in all respects similar to PS in adults. But whereas the PS of an adult occupies about 20 % of the night, it appears that the PS of the newborn occupies about half the duration of sleep. Earlier, we have been able to establish the individuality of PS in the mature newborn and to distinguish it from another state of active sleep called 'drowsiness' or stage a (PETRE-QUADENS 1966). Using the same criteria, an attempt has been made to establish in the premature the ontogenesis of PS and the simultaneous disappearance of EMG activity in the levator menti. MATERIAL AND METHOD
Simultaneous recordings of the EEG, EMG, eye-movements, cardiac and respiratory rate, have been made on 14 premature infants whose gestational age varied from 28 to 37 weeks. Gestational age is calculated from the probable date of conception, term being defined as 268 days or 38 weeks. The duration of recordings is 3 hours. RESULTS
Disappearance of the EMG activity Paradoxical sleep (PS) defined by the electroencephalographic activation, the presence of rapid eye-movements and the increase in respiratory rate, is found to be °/o EMG 0 in PS
o0oD
100
coo
o
®
•
•
•
•
O
90 80 O
0
0
70 0
60-
o o
50
0
0
0 o
8 8
40 30 20 10
. . . . . . . . . . . . . . . . . . . 0 28 30 32 34 36 381 2
AGE
I
weeks gestational
age
~
I
4
weeks
•. . - . . ;..--¢/--4,¢--¢/ . . . 6 i 2 3 7 10 141 2 3 4
i months p a s t term
(term=268days
i years '
+_. 5 d a y s )
Fig. 1. Evolution of the relative proportions of E MG abolition during paradoxical sleep, according to age. O: Night-sleep recordings; o : day-sleep recordings; [] represents 15 new-borns, day-sleep recordings. J. neurol. Sei. (1967) 4:153-157
SHORT REPORTS
155
present from the 28th week of foetal life. But whereas in the mature newborn at term, the period of electrocortical activation with rapid eye-movements is most often accompanied by abolition of electromyographic activity, the disappearance of muscle action potentials is found to be inconstant in the premature (Fig. 1). At 28-30 weeks, the EMG is characterized by low voltage activity which does not vary during the course of the recording. At the age of 33 weeks, this activity is replaced by an adult EMG pattern. This ceases in a few per cent during PS. The degree of abolition of EMG activity during PS increases as the foeta lage approaches 37 weeks. Smiling which appears in the newborn at term during PS (PETRE-QUADENS AND LAROCHE1966) most frequently associated with abolition of EMG activity - - can be seen in the premature not only during PS when EMG activity is absent, but also when it is preserved. Up to the age of 7 months, the abolition of EMG activity is not an absolute criterion of PS and it is only the character of the ocular movements which distinguishes it. Eye-movements are discrete and infrequent during stage a and occur in bursts during PS. In the premature and the mature newborn, the figures refer to recordings made during the day. The night recordings (between 7 p.m. and 3 a.m.) in the newborn reveal a greater dissociation between the phase of rapid eye-movements and the simultaneous disappearance of muscle tone, than the day sleep recordings. PS is frequently followed by a brief period of awakening. Up to the age of 7 months, periods of PS may be seen interrupting stage a. This phenomenon ceases by the age of 10 months at the same time as stage a vanishes. -
-
%PS 50, o
40.
30"
0
0
Z "e" . . . . .
~''t
20
10
J 0 28 AGE"
. . . . 30
' ' ' 32 34 weeks
' ' 36
gestationa[ age
' ' 3BJ I
' 2
L , , 4 weeks
, / / , //._~/._//._// , , , 6 2 3 7 10 141 2 3 4 m o n t h s : years past t e r m ( t e r m = 2 6 8 d a y s "4" 5 d a y s )
Fig. 2. Evolution of the percentage of paradoxical sleep per sleep-cycle, according to age. o : Paradoxical-sleep day-sleep recordings; 0 : % paradoxical sleep night-sleep recordings; D: average of ~o paradoxical sleep in 21 new-borns, day-sleep recordings; • : average of % paradoxical sleep in 5 new-borns, night-sleep recordings. J. neurol. Sci. (1967) 4:153-157
156
SHORT REPORTS
Maturation o f P S
We realize that in the course of maturation the periods of rapid eye-movements tend to coincide with the disappearance of E M G activity and achieve maximum duration at term (Fig. 2). Fig. 2 clearly indicates that PS increases before the 38th week. After full term, the duration of PS rapidly decreases. At the age of one month, PS occupies 21-22 ~ of the sleep cycle and this proportion remains constant. It should be understood that these percentages of PS have reference to a complete sleep cycle and not to a period of 24 hours. In the older child and in the adult, the proportion of PS per cycle and per 24 hours is the same. It must also be pointed out that daily recordings in children between the age of one and two months show a lower percentage of PS than the nocturnal recordings taken at about the same age. It is difficult not to attempt to compare this observation with the results of nocturnal recordings in the newborn where the inverse relationship may be recorded. At 38 weeks nocturnal recordings show the lowest percentage of PS. It is just possible that during the first weeks of life there is an inversion of the sleep cycle. After two months of age, periods of sleep occurring during the day become shorter and no longer encompass all the stages of sleep. For this reason, after this particular age, only nocturnal recordings have been studied. Also at two months, 'saw tooth' waves appear over the vertex in the E E G during PS. By 10 months, sleep has the same characteristics as those seen in the adult.
DISCUSSION
It is impossible to know to what extent the stages of sleep seen in the adult develop from the sleep stages of the newborn. On the one hand it would appear that stage a or 'undifferentiated sleep' (PARMELEE et al. 1964) belongs to an ontogenetically primitive state of vigilance which disappears during the first months of life at the time when the duration of awakening tends to increase. On the other hand the provocation of smiling during awakening by the maternal image about the age of one month, coincides with the reduction of PS. These findings also indicate that the mechanisms which determine the homeostasis of PS are acquired very early in life, at about the age of one or two months. O. PETRE-QUADENS Department of Developmental Neurology, Born-Bunge Foundation (Dr. L. van Bogaert), Berchem-Antwerp; and Department of Gynecology and Obstetrics, University St. Pierre Hospital (Prof. Hubinont), Brussels (Belgium)
REFERENCES
ASERINSKY,E. ANDN. KLEITMAN(1955) A motility cycle in sleeping infants as manifested by ocular and gross bodily activity, J. appl. Physiol., 8 : 11-18. DELANGE,M., PH. CASTAN,J. CADILHACANDP. PASSOUANT(1962) Les divers stades du sommeil chez le nouveau-n6 et le nourrisson, Rev. neurol., 107: 271-276. DEMENT,W. C. AND N. KLEITMAN(1957) The relations of eye movements during sleep to dream activity: an objective method for the study of dreaming, J. exp. Psychol., 53 : 339-346. neurol. Sci. (1967) 4:153-157
SHORT REPORTS
157
JOUVET, D., J. L. VALATXAND M. JOUVET(1961) l~tude polygraphique du sommeil du chaton, C.R. Soc. Biol., 155: 1660-1664. JOUVET, M. (1962) Recherches sur les structures nerveuses et les m6canismes responsables des diff6rentes phases du sommeil physiologique, Arch. ital. Biol., 100: 125-206. PARMELEE,A. H., W. H. WENNER, Y. AKIYAMAAND J. FLESCHER(1964) EEG and brain maturation, CIOMS Symposium on Regional Maturation of the Nervous System in Early Life, Paris, December 1964, to be published by Blaekwell, Oxford. PETRE-QUADENS,O. (1966) On the different phases of the sleep of the newborn and particularly of the activated phase or phase d, J. neurol. Sci., 3 : 152-162. PETRE-QUADENS,O. AND J. L. LAROCHE(1966) Sommeil du nouveau-n6, phases paradoxales spontan6es et provoqu6es, J. Psychol. norm.path., 1 : 19-27. ROFFWARG, H., W. C. DEMENTAND C. FISCHER(1964) Preliminary observations of the sleep-dream pattern in neonates, infants, children and adults. In: E. HARMS(Ed.), Problems of Sleep and Dream in Children, Vol. 2 (Intern. Series of Monographs on Child Psychiatry), Pergamon Press, Oxford, New York, p. 60-72. (Received 24 June, 1966)
J. neurol. Sci. (1967) 4:153-157