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Periodic nocturnal myoclonus in a patient with hyperexplexia (startle disease)
Journal of the Neurological Sciences, 1978, 38 : 207-213 © Elsevier/North-Holland Biomedical Press
207
PERIODIC NOCTURNAL MYOCLONUS IN A PATIENT WITH HYPERE X P L E X I A ( S T A R T L E DISEASE)
J. H. M. de GROEN and H. A. C. KAMPHUISEN Leiden University Medical Center, Leiden (The Netherlands)
(Received 7 March, 1978) (Accepted 3 May, 1978)
SUMMARY The periodic nocturnal myoclonus of a patient with hyperexplexia has been studied. Evidence has been given that the jerks are spontaneous arousal reactions. The temporal characteristics of the jerks have been analysed. The jerks appear to be correlated with the respiratory rhythm and the data suggest a correlation of the jerks with circulatory and respiratory higher order waves. The results are discussed with relation to the literature concerning spontaneous sleep jerks.
INTRODUCTION Hyperexplexia or startle disease is a hereditary (Suhren, Bruyn and Tuynman 1966; Gastaut and Villeneuve 1967) disease, characterized by an abnormal exaggerated startle reaction. An unexpected stimulus causes a short-lasting generalized muscular stiffness, associated with loss of voluntary muscle control. There is no disturbance of consciousness. The symptom probably is caused by hyperexcitability of the brain-stem arousal system. During sleep, patients with hyperexplexia sometimes show spontaneous sleep jerks, identical to those observed in normal subjects but more intense and frequent (Gastaut and Villeneuve 1967). This article reports the spontaneous sleep jerks of a child with hyperexplexia. Case history Our patient, K.W., is a girl, 2½years old, out of the family with hereditary hyperexplexia, studied by Suhren et al. (1966). After a normal pregnancy, birth was one week before term, but uneventful. The birth weight was 2380 g, the Apgar score 8 after 1 min. Soon after birth, the mentally retarded child presented the characteristic symptomsofhyperexplexia: hypertonia, hypokinesia and an abnormal startle reaction. She differs from the other afflicted members of her family, because of the severity of the symptoms and of the occurrence of periodic nocturnal myoclonus. Treatment with anti-epileptics and sedatives was unsatisfactory.
208
Neurologicalexamination: normalfindings.Therewereno abnormalitiesin the repeated EEG's, apart from a slight underdevelopmentof the physiologicalsleep activitiesduring N-REM sleep. Once, whenthechildwasabout2yearsold, leftRolandicspikes,not correlatingwith the nocturnalmyoclonus, occurred during N-REM sleep. In myoclonicepilepsythe Somato-SensoryEvoked Responseis augmented(Halliday1975). In our patientthe SSER was normaland amountedto 5 ltV. Photostimulation did not provoke irritative activity. Method of polygraphic sleep registration and data analysis Several periods of day-time sleep and the sleep of one whole night were registered polygraphically on a 20 channels Van Gogh EEG apparatus and in part on a tape recorder. There were 9 EEG-leads, 7 EMG-leads (surface electrodes submentally and on 6 extremity muscles), EOG, respiratory movement (strain gauge), ECG and PGR. The sleep stages of the night sleep record were scored manually, per minute, in agreement with international criteria. An unselected part of non-interrupted SW-sleep has been used for the calculation of the correlation between respiration and jerks. The interval histograms of the jerks have been plotted by means of a Data Retrieval Computer. RESULTS
(a) Hypnogram of the night sleep record (Fig. 1) The night sleep consists mainly of SW-sleep stages I, II and III, interrupted by short awakenings; 5 irregular sleep cycles may be discerned, only the 4th with a period of REM-sleep (A in Fig. 1). During relaxed waking and SW-sleep, the frequency of the jerks (B in Fig. 1) is about 5 min and fairly constant. During REM-sleep and during periods of alertness the jerks disappear (C in Fig. l).
(b) Analysis of the jerks The jerks consist of short-lasting bursts of activity, synchronous in all muscles. The EEG shows often an activation pattern: irritative EEG-phenomena are lacking. Each SW-sleep stage has a different EEG activation pattern during the jerk (Fig. 2). During relaxed waking (A in Fig. 2) the jerk is accompanied by a desynchronisation of the EEG-activity and opening of the eyes; during dozing (B in Fig. 2) the jerk is accompanied by a paradoxical a-0 pattern; during light sleep (C in Fig. 2) by 0-bursts and during deep sleep (D in Fig. 2) by primitive K-complexes. The EEG activation pattern coincides with the jerk or precedes it. The data concerning the H-reflex (F in Fig. 2) and the tendon reflex (G in Fig. 2) of the triceps muscle are obtained during a day-time sleep registration. The equal increase of both H-reflex and tendon reflex during the jerk suggests that the jerk mainly is caused by an excitability increase of a-motoneurones. The accompanying signs of EEG activation suggest that the jerks arise from sudden repeatedly occurring increase of muscle tone, as a part of spontaneous arousal reactions.
.<
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o
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~.
l::le ~
~'~
0
,.Q
&
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r,
0
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o~oo
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ol~
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r
no remllrlt llon
o~,oo
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- -
E
Fig. 1. Hypnogram of a whole night sleep registration. The black bars on the time axis represent periods of continuous muscle activity. At A the child woke up spontaneously and as usual at midnight, diapers were changed. Between A and B, and C and D, the registration has been interrupted, the child being behaviourly awake and very alert; at E the night sleep ends. This night sleep pattern does not differ essentially from the sleep pattern of other nights.
c
B
c
B
A
O
210 A_~ awake
~e~ closure
eye open~g
eye movements
,
~hRmiz~t~n MQui~
R
,
_
~.-
..... ~ _
•
~
~
,
,
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8 ~ drowsy
M Quld~ R ~
cJsws~ Co-~ch,n actwllion
thole
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.
~
O2-)C delta activation M Quad¢R . . . . . . . . . . . . . . . . . . . . . .
~J
~
......................
_
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zca/e o f a . c . d ~ 4 0 0 , ' u v
.
,
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el P,.r#lexa~ringSWS • M Tric suqae,
/
~
% Tamdon.~k= during SWS ¢M Tric.surm,
/ 1
12o~ 5m~c
during lhe wk
Fig. 2. A - D : the EEG activation-pattern accompanying a jerk; F-G: H-reflex and tendon jerk of the m. triceps surac before, during and after the jerk.
of all the jerks during the night sleep registration. Two peaks are to be seen, a smaller one, at 3 sec (equalling the duration of the respiratory cycle) and a larger one, at 1l sec. The 3rd interval histogram presents the interval distribution of another sleep registration, a week later.
211
IMit~lil~lalmm !
l~tB O
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•
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eo
li
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:
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m
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3 ol Nw~:
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Ikl~
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/f
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/,,.
Fig. 3. Interval histogramsof the spontaneoussleepjerks. At that time the child had a fever of 39 °C, caused by acute otitis media; she then jerked less frequently. This histogram illustrates the increase of the number of long intervals and is also remarkable because of the occurrence of a subharmonic, at a peak at 22 see. This may be expected if the jerk-generating system is coupled with or is part of another system, ready to oscillate with its own frequency or its (sub)harmonics. The correlation between the jerks and the respiration has been calculated as follows. From 25 consecutive jerks during an unselected period of non-interrupted SW-sleep the interval between each jerk and the preceding inspiration has been measured. The cumulative frequency diagram of the quotients of these 25 intervals divided by the length of the whole preceding respiratory cycle has been made. ! n this diagram the cumulative frequency line for the 25 quotients is significantly different (with P < 1 ~) from the line expected under H0, when there would be no correlation. This indicates that the jerks are significantly correlated with the respiration. The peaks at 11 and 22 sec in the interval histograms suggest a correlation of the jerks with the so-called higher order waves, slow oscillations of cardiovascular and respiratory variables. The generation of the higher order waves is related with the control of these variables by the cardiovascular and respiratory control systems of the lower brain stem. However, the suggestion of such a correlation must remain unproved,
212 because assessment of higher order waves was not possible. Blood pressure has not been recorded because of technical difficulties. The respiratory pattern is too often interrupted by sudden contractions of the respiratory muscles, accompanying the jerks. DISCUSSION It is a common experience, that sudden arousal out of the sleep, caused by a strong sensory stimulus, is often accompanied by a jerk. Spontaneous jerks, not provoked by exogenous stimuli, also may occur sporadically during normal sleep and they do not have any known pathological significance. Oswald (1959) studied spontaneous sleep jerks polygraphically. He observed the accompanying EEG activation pattern and pointed to the resemblance to arousal reactions on stimuli from outside. In patients afflicted by hyperexolexia, the incidence and the intensity of the spontaneous sleep jerks are increased. This increase has been attributed to hyperexcitability of the brain-stem arousal system (Suhren et al. 1966; Gastaut and Villeneuve 1967). This stresses the possible role of the reticular structures of the brain stem in the generation of the jerks. Lugaresi, Coccagna, Mantovani and Lebrun (1972) studied the spontaneous sleep jerks in patients with restless legs syndrome and nocturnal myoclonus. The jerks were accompanied with an EEG activation pattern, occurred often periodically and appeared to be related to higher order waves of respiration and blood pressure. The authors explain the relationship of the jerks with the higher order waves by suggesting that the mesencephalo-pontine reticular structures, important for the control of muscle tone and cortical excitability, might be influenced in an abnormally strong way by cardiovascular and respiratory variables. Our patient with nocturnal myoclonus is afflicted by hyperexplexia; her night sleep is interrupted by a large number of very intense jerks. Analysis of the jerks obtained the following results: The jerks are spontaneous arousal reactions, occurring periodically with preferred intervals of about 3, 11 and 22 see. The jerks appear to be correlated with the respiratory rhythm. The data suggest also a correlation with higher order waves, but this could not be proved. So in our patient both factors which enhance spontaneous sleep jerks, are present: hyperexcitability of the brain-stem arousal system, and an abnormally strong influence of respiratory and possibly also circulatory variables on reticular excitability. ACKNOWLEDGEMENTS We are greatly indebted to Dr. A. C. B. Peters for referring the patient for this study, to P. A. Volker, H. M. Th. Van Oosten, M. C. Ph. Beckman Lapr6, J. E. M. Van Diemen, J. M. Franzen and C. G. S. Kramer for their technical assistance, to G. Kroon and W. Goddijn for their photographical assistance and to T, Tjalkens for typing the manuscript. Statistical assistance has been given by Dr. J. Thijsse, Dept. of Medical Statistics, University of Leiden.
213 REFERENCES Gastaut, H. and A. Villeneuve (1967) The startle disease or hyperekplexia - - Pathological surprise reaction, J. neurol. Sci., 5 : 523-542. Halliday, A. M. (1975) The neurophysiology of myoclonic jerking, a reappraisal. In M. A. Charlton (Ed.), Myoclonic Seizures, Excerpta Medica, Amsterdam, pp. 1-29. Lugaresi, E., G. Coccagna, M. Mantovani and R. Lebrun (1972) Some periodic phenomena arising during drowsiness and sleep in man, Electroenceph. clin. Neurophysiol., 32: 701-705. Oswald, I. (1959) Sudden bodily jerks on falling asleep, Brain, 82: 92-103. Siegel, S. (1956) Nonparametric Statistics, McGraw-Hill, New York, London, pp. 47-51. Suhren, O., G. W. Bruyn and J. A. Tuynman (1966) Hyperexplexia, a hereditary startle syndrome, J. neurol. Sci. , 3 : 577-605.
207
PERIODIC NOCTURNAL MYOCLONUS IN A PATIENT WITH HYPERE X P L E X I A ( S T A R T L E DISEASE)
J. H. M. de GROEN and H. A. C. KAMPHUISEN Leiden University Medical Center, Leiden (The Netherlands)
(Received 7 March, 1978) (Accepted 3 May, 1978)
SUMMARY The periodic nocturnal myoclonus of a patient with hyperexplexia has been studied. Evidence has been given that the jerks are spontaneous arousal reactions. The temporal characteristics of the jerks have been analysed. The jerks appear to be correlated with the respiratory rhythm and the data suggest a correlation of the jerks with circulatory and respiratory higher order waves. The results are discussed with relation to the literature concerning spontaneous sleep jerks.
INTRODUCTION Hyperexplexia or startle disease is a hereditary (Suhren, Bruyn and Tuynman 1966; Gastaut and Villeneuve 1967) disease, characterized by an abnormal exaggerated startle reaction. An unexpected stimulus causes a short-lasting generalized muscular stiffness, associated with loss of voluntary muscle control. There is no disturbance of consciousness. The symptom probably is caused by hyperexcitability of the brain-stem arousal system. During sleep, patients with hyperexplexia sometimes show spontaneous sleep jerks, identical to those observed in normal subjects but more intense and frequent (Gastaut and Villeneuve 1967). This article reports the spontaneous sleep jerks of a child with hyperexplexia. Case history Our patient, K.W., is a girl, 2½years old, out of the family with hereditary hyperexplexia, studied by Suhren et al. (1966). After a normal pregnancy, birth was one week before term, but uneventful. The birth weight was 2380 g, the Apgar score 8 after 1 min. Soon after birth, the mentally retarded child presented the characteristic symptomsofhyperexplexia: hypertonia, hypokinesia and an abnormal startle reaction. She differs from the other afflicted members of her family, because of the severity of the symptoms and of the occurrence of periodic nocturnal myoclonus. Treatment with anti-epileptics and sedatives was unsatisfactory.
208
Neurologicalexamination: normalfindings.Therewereno abnormalitiesin the repeated EEG's, apart from a slight underdevelopmentof the physiologicalsleep activitiesduring N-REM sleep. Once, whenthechildwasabout2yearsold, leftRolandicspikes,not correlatingwith the nocturnalmyoclonus, occurred during N-REM sleep. In myoclonicepilepsythe Somato-SensoryEvoked Responseis augmented(Halliday1975). In our patientthe SSER was normaland amountedto 5 ltV. Photostimulation did not provoke irritative activity. Method of polygraphic sleep registration and data analysis Several periods of day-time sleep and the sleep of one whole night were registered polygraphically on a 20 channels Van Gogh EEG apparatus and in part on a tape recorder. There were 9 EEG-leads, 7 EMG-leads (surface electrodes submentally and on 6 extremity muscles), EOG, respiratory movement (strain gauge), ECG and PGR. The sleep stages of the night sleep record were scored manually, per minute, in agreement with international criteria. An unselected part of non-interrupted SW-sleep has been used for the calculation of the correlation between respiration and jerks. The interval histograms of the jerks have been plotted by means of a Data Retrieval Computer. RESULTS
(a) Hypnogram of the night sleep record (Fig. 1) The night sleep consists mainly of SW-sleep stages I, II and III, interrupted by short awakenings; 5 irregular sleep cycles may be discerned, only the 4th with a period of REM-sleep (A in Fig. 1). During relaxed waking and SW-sleep, the frequency of the jerks (B in Fig. 1) is about 5 min and fairly constant. During REM-sleep and during periods of alertness the jerks disappear (C in Fig. l).
(b) Analysis of the jerks The jerks consist of short-lasting bursts of activity, synchronous in all muscles. The EEG shows often an activation pattern: irritative EEG-phenomena are lacking. Each SW-sleep stage has a different EEG activation pattern during the jerk (Fig. 2). During relaxed waking (A in Fig. 2) the jerk is accompanied by a desynchronisation of the EEG-activity and opening of the eyes; during dozing (B in Fig. 2) the jerk is accompanied by a paradoxical a-0 pattern; during light sleep (C in Fig. 2) by 0-bursts and during deep sleep (D in Fig. 2) by primitive K-complexes. The EEG activation pattern coincides with the jerk or precedes it. The data concerning the H-reflex (F in Fig. 2) and the tendon reflex (G in Fig. 2) of the triceps muscle are obtained during a day-time sleep registration. The equal increase of both H-reflex and tendon reflex during the jerk suggests that the jerk mainly is caused by an excitability increase of a-motoneurones. The accompanying signs of EEG activation suggest that the jerks arise from sudden repeatedly occurring increase of muscle tone, as a part of spontaneous arousal reactions.
.<
N
o
g-
~.
l::le ~
~'~
0
,.Q
&
0
r,
0
~l"oo
REM-!
W
~21h~
111
SWS I
REMSf
W
22"00
oi~oo
2t"oo
o~oo
~m
n
21~o
ol~
L
r
no remllrlt llon
o~,oo
O~hOo
- -
E
Fig. 1. Hypnogram of a whole night sleep registration. The black bars on the time axis represent periods of continuous muscle activity. At A the child woke up spontaneously and as usual at midnight, diapers were changed. Between A and B, and C and D, the registration has been interrupted, the child being behaviourly awake and very alert; at E the night sleep ends. This night sleep pattern does not differ essentially from the sleep pattern of other nights.
c
B
c
B
A
O
210 A_~ awake
~e~ closure
eye open~g
eye movements
,
~hRmiz~t~n MQui~
R
,
_
~.-
..... ~ _
•
~
~
,
,
~
8 ~ drowsy
M Quld~ R ~
cJsws~ Co-~ch,n actwllion
thole
M Ouad¢R
.
~
O2-)C delta activation M Quad¢R . . . . . . . . . . . . . . . . . . . . . .
~J
~
......................
_
T.
zca/e o f a . c . d ~ 4 0 0 , ' u v
.
,
~
~
ll-1.-~c ---d ...I
el P,.r#lexa~ringSWS • M Tric suqae,
/
~
% Tamdon.~k= during SWS ¢M Tric.surm,
/ 1
12o~ 5m~c
during lhe wk
Fig. 2. A - D : the EEG activation-pattern accompanying a jerk; F-G: H-reflex and tendon jerk of the m. triceps surac before, during and after the jerk.
of all the jerks during the night sleep registration. Two peaks are to be seen, a smaller one, at 3 sec (equalling the duration of the respiratory cycle) and a larger one, at 1l sec. The 3rd interval histogram presents the interval distribution of another sleep registration, a week later.
211
IMit~lil~lalmm !
l~tB O
•
•
¢ a~pai~:
eo
li
iqlr~
:
I n l w W lbl~ ~ n
aaa~lm
i
m
e4~
3 ol Nw~:
g7
Ikl~
[l Iq .I-1 I-2 -"
/f
J /f/
/,,.
Fig. 3. Interval histogramsof the spontaneoussleepjerks. At that time the child had a fever of 39 °C, caused by acute otitis media; she then jerked less frequently. This histogram illustrates the increase of the number of long intervals and is also remarkable because of the occurrence of a subharmonic, at a peak at 22 see. This may be expected if the jerk-generating system is coupled with or is part of another system, ready to oscillate with its own frequency or its (sub)harmonics. The correlation between the jerks and the respiration has been calculated as follows. From 25 consecutive jerks during an unselected period of non-interrupted SW-sleep the interval between each jerk and the preceding inspiration has been measured. The cumulative frequency diagram of the quotients of these 25 intervals divided by the length of the whole preceding respiratory cycle has been made. ! n this diagram the cumulative frequency line for the 25 quotients is significantly different (with P < 1 ~) from the line expected under H0, when there would be no correlation. This indicates that the jerks are significantly correlated with the respiration. The peaks at 11 and 22 sec in the interval histograms suggest a correlation of the jerks with the so-called higher order waves, slow oscillations of cardiovascular and respiratory variables. The generation of the higher order waves is related with the control of these variables by the cardiovascular and respiratory control systems of the lower brain stem. However, the suggestion of such a correlation must remain unproved,
212 because assessment of higher order waves was not possible. Blood pressure has not been recorded because of technical difficulties. The respiratory pattern is too often interrupted by sudden contractions of the respiratory muscles, accompanying the jerks. DISCUSSION It is a common experience, that sudden arousal out of the sleep, caused by a strong sensory stimulus, is often accompanied by a jerk. Spontaneous jerks, not provoked by exogenous stimuli, also may occur sporadically during normal sleep and they do not have any known pathological significance. Oswald (1959) studied spontaneous sleep jerks polygraphically. He observed the accompanying EEG activation pattern and pointed to the resemblance to arousal reactions on stimuli from outside. In patients afflicted by hyperexolexia, the incidence and the intensity of the spontaneous sleep jerks are increased. This increase has been attributed to hyperexcitability of the brain-stem arousal system (Suhren et al. 1966; Gastaut and Villeneuve 1967). This stresses the possible role of the reticular structures of the brain stem in the generation of the jerks. Lugaresi, Coccagna, Mantovani and Lebrun (1972) studied the spontaneous sleep jerks in patients with restless legs syndrome and nocturnal myoclonus. The jerks were accompanied with an EEG activation pattern, occurred often periodically and appeared to be related to higher order waves of respiration and blood pressure. The authors explain the relationship of the jerks with the higher order waves by suggesting that the mesencephalo-pontine reticular structures, important for the control of muscle tone and cortical excitability, might be influenced in an abnormally strong way by cardiovascular and respiratory variables. Our patient with nocturnal myoclonus is afflicted by hyperexplexia; her night sleep is interrupted by a large number of very intense jerks. Analysis of the jerks obtained the following results: The jerks are spontaneous arousal reactions, occurring periodically with preferred intervals of about 3, 11 and 22 see. The jerks appear to be correlated with the respiratory rhythm. The data suggest also a correlation with higher order waves, but this could not be proved. So in our patient both factors which enhance spontaneous sleep jerks, are present: hyperexcitability of the brain-stem arousal system, and an abnormally strong influence of respiratory and possibly also circulatory variables on reticular excitability. ACKNOWLEDGEMENTS We are greatly indebted to Dr. A. C. B. Peters for referring the patient for this study, to P. A. Volker, H. M. Th. Van Oosten, M. C. Ph. Beckman Lapr6, J. E. M. Van Diemen, J. M. Franzen and C. G. S. Kramer for their technical assistance, to G. Kroon and W. Goddijn for their photographical assistance and to T, Tjalkens for typing the manuscript. Statistical assistance has been given by Dr. J. Thijsse, Dept. of Medical Statistics, University of Leiden.
213 REFERENCES Gastaut, H. and A. Villeneuve (1967) The startle disease or hyperekplexia - - Pathological surprise reaction, J. neurol. Sci., 5 : 523-542. Halliday, A. M. (1975) The neurophysiology of myoclonic jerking, a reappraisal. In M. A. Charlton (Ed.), Myoclonic Seizures, Excerpta Medica, Amsterdam, pp. 1-29. Lugaresi, E., G. Coccagna, M. Mantovani and R. Lebrun (1972) Some periodic phenomena arising during drowsiness and sleep in man, Electroenceph. clin. Neurophysiol., 32: 701-705. Oswald, I. (1959) Sudden bodily jerks on falling asleep, Brain, 82: 92-103. Siegel, S. (1956) Nonparametric Statistics, McGraw-Hill, New York, London, pp. 47-51. Suhren, O., G. W. Bruyn and J. A. Tuynman (1966) Hyperexplexia, a hereditary startle syndrome, J. neurol. Sci. , 3 : 577-605.