- Email: [email protected]
Paroxysmal periodic motor attacks during sleep: clinical and polygraphic features
Electroencephalography and clinical Neurophysiology , 86 (1993) 161-166 © 1993 Elsevier Scientific Publishers Ireland, Ltd. 0013-4649/93/$06.00
161
EEG91719
Paroxysmal periodic motor attacks during sleep: clinical and polygraphic features E. Sforza, P. Montagna, R. Rinaldi, P. Tinuper, A. Cerullo, F. Cirignotta and E. Lugaresi Institute of Neurology, University of Bologna, Bologna (Italy) (Accepted for publication: 29 September 1992)
Summary Three patients complained of paroxysmal motor attacks during sleep. Videopolygraphic recordings showed that motor activity could be divided into events of increasing behavioural complexity. Simpler motor events often represented the initial fragment of more complex attacks. Clinical features suggested the attacks represented frontal lobe epileptic seizures. The attacks recurred during NREM sleep with a periodic repetition every 20-60 sec. This periodicity could be related to the analogous physiological oscillation during light sleep and the periodicity of K complexes, exerting a facilitating influence upon epileptic mechanisms. Key words: Nocturnal attacks; Periodicity; Frontal epilepsy; Motor seizures
Nocturnal complex m o t o r attacks are unusual clinical events that occur in patients without definite E E G abnormalities in scalp records. The term nocturnal paroxysmal dystonia (NPD) has been introduced to define these events, which are characterized by different semeiology and duration (Lugaresi and Cirignotta 1981; Lugaresi 1990). A comparison of the clinical manifestations of frontal lobe epilepsy and the attacks of N P D has recently revealed several common features. Moreover, we reported patients showing clear-cut epileptic activity during short-lasting N P D attacks that represented cases of frontal lobe epilepsy from deepseated loci (Tinuper et al. 1990). In these patients, and in several other cases with nocturnal attacks, we observed that the same patient could display episodes of widely different duration and intensity. More detailed scrutiny, however, demonstrated that the attacks could be arranged into a few distinct types, each with highly stereotyped clinical features, but of increasing complexity. Simpler events could occur in isolation or represent the beginning of a m o r e complex episode. Moreover, the motor attacks seemed to recur at periodic intervals of about 20-60 sec for long stretches during sleep. The periodicity of the attacks thus resembled other sleep p h e n o m e n a such as the physiological varia-
Correspondence to: Emilia Sforza, M.D., Clinica Neurologica, Via U. Foscolo 7, 40123 Bologna (Italy). Tel.: + +39/51/6442183; Fax: 6442165.
tions of heart rate, blood pressure, respiratory amplitude (Lugaresi et al. 1972) and the periodicity of sleep apneas and nocturnal myoclonus (Coleman et al. 1980). In 3 patients, selected for the high frequency of attacks during sleep, we performed a detailed videopolygraphic study trying to better define the clinical features and sleep evolution and origin of the nocturnal attacks.
Methods Video-polygraphic recording was performed with a 19-channel polygraph (Grass Instrument, Model 78E) and a closed split-screen audiovisual circuit. Scalp electrodes were placed according to the 10-20 international system; bilateral sphenoidal and superficial supraorbital electrodes were added. Polygraphic channels included E M G of tibialis anterior muscles, E C G and thoracic respirogram. Video-polygraphic recording started at 9.00 p.m. and ended at 7.00 a.m. the following morning. In 2 patients (cases 1 and 2) sleep recording was repeated on 2 different nights. During light sleep a series of K complexes was purposefully and randomly evoked by acoustic stimuli. Video-records were analysed by two examiners (ES, R R ) and the attacks were divided into minimal, minor and major according to duration, intensity and complexity of motor behaviour. "Minimal" attacks were simple motor events involving one or more body segments (such as
E. SFORZA ET AL.
162
body touching, repetitive flexion and extension of feet or legs, chewing, scratching) without purposeful or intentional behaviour and with a short duration. "Minor" events were defined by the involvement of more body segments associated with prolonged purposeful or semipurposeful behaviour (such as hyperextension of limbs in a dystonic posture, vocalization, eye opening). During "major" attacks generalized dystonic postures were associated with forced extension and disorganized movements involving all limbs. The latter were typical NPD attacks as identified in our previous studies (Lugaresi and Cirignotta 1981; LugareSi 1990). The clinical features of each attack, its frequency (index: number of events/h), and mean duration as well as the mean interval between the attacks were studied. Events separated by less than 5 sec were considered a single event. A periodic occurrence was defined by a series of at least 3 consecutive events with an interval between 5 and 180 sec. The awake state was excluded from the analysis because of the absence of attacks in this state. Since the frequency of the attacks changed during the transition into slow and REM sleep, 5 min of recording before and after slow and REM sleep were arbitrarily excluded when computing the mean interval between attacks. For the purpose of computation of time intervals between attacks, no distinction was made between minimal, minor or major attacks. Standard criteria (Rechtschaffen and Kales 1968) were used for sleep scoring. Polygraphic examination included the analysis of EEG changes, the correlation between EEG findings and motor attacks and the examination of sleep figures before the onset of attacks. The duration of the nocturnal events was calculated on the polygraphic records and defined by the length of muscular artifacts and autonomic changes. The numbers of events during light, slow and REM sleep were then computed. In order to disclose long-term trends during the night, the number, duration and interval between events were also estimated for each third of the night and for each 1 h period between 23.00 and 06.30.
Results
The clinical and polygraphic features of the nocturnal attacks are detailed for each patient (Table I). Case 1 A 41-year-old man, without relevant family history, developed at age 35 nocturnal attacks consisting of brief and sudden movements of limbs and trunk followed by screaming and vocalization. Despite phenobarbital, phenytoin and sodium valproate the attacks persisted at an average rate of 7/night.
TABLE I Clinical and polygraphic findings of nocturnal motor events.
Index of events ( N / h ) Mean duration of minimal attacks (sec) Mean duration of minor attacks (sec) Mean duration of major attacks (sec) Mean polygraphic duration of minimal attacks(sec) Mean polygraphic duration of minor attacks(sec) Mean polygraphic duration of major attacks (sec) Mean clinical interval between the attacks (sec)
Case 1
Case 2
Case 3
42.6
42.8
18.3
4.5-+ 3.9
4.9-+ 3.7
8.0 5:6.9
11.95:4.7
13.0_+ 8.3
13.1+ 6.7
39.3 _+10.3
82.5 _+19.8
74.0 _+ 2.8
8.1_+ 4.8
8.6_+ 4.3
11.0_+ 6.4
14.7_+ 4.7
14.8_+ 7.1
17.6_+ 5.4
70.0 _+15.0
89.5 _+17.3
80.5 _+ 4.9
28.0 _+14.3
41.8 _+27.5
66.0_+47.7
During video-polygraphic recording the minimal events consisted of brief (4.5 sec) plantar flexion and adduction of feet and legs, chewing and touching of genitalia. In minor attacks these minimal events progressed to eye opening, elevation of shoulders, clapping, grunting, vocalization and semipurposeful gesticulation. During major attacks the initial plantar flexion and adduction of legs or vocalization and gesticulation were followed by left head turning, tonic limb hyperextension and disorganized movements with rocking of the trunk. After the attacks, the patient awakened amnesic for the episode. The index of nocturnal events was 43 with a mean duration of the minimal and minor events of 7 sec. The interval between events was 10-40 sec with a mean of 28.0 5:14 sec. During the second night the mean duration of minimal and minor attacks was 6 sec with a mean interval between attacks of 35 sec. Case 2 The patient, a 36-year-old woman, at the age of 9 began to have nocturnal attacks of sudden awakening. The attacks consisted in screaming and sitting up in bed sometimes followed by tonic extension and abduction and violent disorganized movements of all limbs. Phenytoin partially reduced the frequency of attacks. On polysomnography, the minimal events consisted of jerks of the limbs, repeated elevation of shoulders, torsion of the trunk and inappropriate gestures, i.e., scratching or rubbing her nose and head, touching of genitalia and grunts. In the minor events this was followed by sitting up with pelvic thrusting, vocalization of simple words, gesticulating with hyperextension of the fingers. During 3 major events that could be
163
P E R I O D I C ATTACKS D U R I N G SLEEP case 2 ~
o ~)
36yrs
'"'t
j-t_u_
1-2 3-4
REM
,.J
TIIITf TTT TTTTTTITTTT,TT I ITT TTT TTTTIT TTTTT ITINTTT 8,,', Z
i
23.50
i
i
0.00
TM,N,MALEVENT
i
0.30
T MINOR EVENT
T i
1.00
1.30
i
2.00
T SE,ZURE
Fig. 1. Sleep histogram in case 2. Bars over the histogram represent times of periodic motor activity present during light sleep and disappearing during slow and R E M sleep. Stars represent major attacks during stages 3-4. During the first part of the night periodic repetition of minimal and minor events in light sleep with a mean interval between attacks of 44 sec.
recorded the patient sat up and then presented forced hyperextension of the limbs with vocalization and rotation to the left of head and trunk and, on one occasion, generalized clonus. The index of events during sleep was 43 with a mean clinical duration of minimal and minor events of 8 sec. The interval between attacks was 10-50 sec with a mean interval of 42 sec during the first night and 45 sec during the second night (Fig. 1).
lateral torsion of the head and fanning of the fingers, followed during minor events by hyperextension of the arms and arching of the trunk. Major attacks were followed by a tonic attack with forced extension and adduction of arms and, sometimes, clonus of the arms and eyelids. These major seizures were associated with a diffuse sharp wave followed by diffuse spikes (Fig. 2). The index of attacks was 18 with a mean interval between events of 66 sec and a mean duration of minimal and minor events of 9 sec.
Case 3 This 24-year-old man began having nocturnal attacks at the age of 15 characterized by a sudden arousal with swallowing and chewing, screaming and tonic extension and adduction of arms. The attacks did not respond to phenobarbital and phenytoin treatment. During nocturnal study the patient presented minimal events characterized by chewing and swallowing,
Polygraphic findings The onset of the minimal and minor events coincided with a K complex followed by brief flattening of background activities and EMG artifacts. Autonomic records showed a uniform response consisting of brief tachycardia, deep inspiration and tachypnea, more marked during minor events. K complexes were not
P,F.r,-
Fz -
,,
T.or Resp.
.
.
.
.
. so
.
pl~sec.
case 3 oi 15 yrs
Fig. 2. Case 3. E E G during a major attack. The onset of attack was associated with diffuse shaTp waves With a left frontal region predominance.
164
E. SFORZA ET AL.
so2 -F~__ ~
~
.
~
F ~ " F4 - - - ~ . _ ~ . , ~ _ . ~ _ F8 - T
T4
4
0
SpH~ s
~
2
o
.....
~
~
~
s ~ 2 - Fs,~_.~. " S 01
I ~1 .....
Fm - F 7 ~ _ _ ~ , _ , _ ~ . ~ _ ~
T3 - 01~~.~_~.~.~
S~H,- s o ~ ~ _ _
S.H~ - F
T
~__
~
~z " C z - - - - ~ - ~ - ~ - - - - - -
EMG
R. L. Tib. ant.
1..._ J . L . ir-,.r- W
ECG Thor. Resp. ~
~
'
~
ACOUSTIC STIMULUS
C.G.R.
o,v 1see.
t
MINIMAL EVENT
~. 36yrs
Fig. 3. Sample of ictal recording during a minimal attack in case 1 showing the sudden onset of the motor event (arrow) coinciding with a K complex followed by brief EEG desynchronization (to the right). Similar EEG changes were evoked by acoustic stimuli (to the left).
associated with spindle-like activity or paroxysmal activity. K complexes purposely evoked by acoustic stimuli during light sleep were morphologically similar to those occurring during the attacks (Fig. 3). During major attacks polygraphic study showed only EMG artifacts with marked and prolonged tachycardia and tachypnea without EEG abnormalities in cases 1 and 2. In case 3 an epileptic diffuse spike activity was recorded only during major attacks. While minimal and minor events were most frequent during light sleep, major attacks typically tended to appear during slow sleep. Events occurred mainly in the first third (mean index: 38.1 + 16.7) without differences during the middle (mean index: 24.3 + 12.9) and last (mean index: 22.2 + 9.4) part of the night. The index of events decreased during the night in all patients between 01.00 and 02.00, 03.00 and 04.00 and 05.00 and 06.00 with
the greatest amount of REM sleep. Attacks occurred during stage 1 (mean % of attacks: 5.98 + 1.2) and especially stage 2 (mean % of attacks: 88.8 + 4.7) whereas they decreased during stages 3-4 (mean %: 3.84 + 3.5) and particularly stage REM (mean %: 1.3 + 0.6). There were no significant differences in duration of attacks or interval between events during the first (mean interval: 42.7 + 13.8 sec), second (mean interval: 47.5 + 25.0 sec) and third part (mean interval: 49.3 + 28.8 sec) of the night except for case 3 who had a reduced interval in the first third of the night. In all patients the most frequent interval between attacks was between 20 and 40 sec (Fig. 4). Sleep structure was disrupted by frequent arousals associated with the motor events. Slow sleep (% mean: 10.1 + 7.1) and REM sleep (% mean: 16.3 + 3.8) were reduced and light sleep (stage 1: % mean: 12.9 + 4.0;
PERIODIC ATFACKS DURING SLEEP
165
30-
I-
o~
I-
2O
10
.N 5-10
10-20
INTERVAL
20-30
30-40
BETWEEN
40-50
ATTACKS
50-60
> S0
(sec.)
Fig. 4. Histogram of distribution of time intervals between motor attacks. The most frequent intervals in all patients were 10-40 sec.
stage 2: % mean: 60.7 + 2.6) increased without alterations in sleep continuity (mean sleep efficiency: 90.7% + 1.5).
Discussion
A bewildering variety of paroxysmal motor activities could be seen during sleep in our patients. On closer analysis, however, the motor attacks, fairly stereotyped for each patient, could be broken down to 3 main types, ranging from simple motor behaviour, to more complex and semipurposeful motor activity and finally to fully developed attacks. Moreover, each type of motor event, highly stereotyped in itself, represented the initial fragment of the subsequent complex attacks. "Minor" attacks seemed to develop into "minimal" and "major" into "minor" attacks, according to a pattern which remained stereotyped throughout each night and successive nights. The hypothesis that the complexity of attacks regularly increases during the night accounts for the abundant and apparently disordered motor activity of our patients during sleep. The stereotyped features, the high frequency of the motor events, especially minimal and minor, and their arising upon a background of undisturbed sleep also weighed against their being merely coincidental or physiological motor activity during sleep. The second striking feature in our cases was the periodic occurrence of the motor events during NREM sleep. This was not merely coincidental as indicated by the fact that periodicity and duration of each type of attack remained much the same for each patient during successive nights of recording. This periodicity resembled the physiological oscillations of cortical, motor and autonomic functions typical of light sleep (Lugaresi et al. 1972) and the periodicity of K complexes related to nocturnal myoclonus (Coleman et al. 1980). Recently, Terzano et al. (1985) found that during NREM sleep, EEG activity is organized into periodic sequences of 40 sec cycles (cyclic alternating pattern) composed of two stereotyped patterns. A phase of activation composed by K complex, reactive slow wave
and transitional desynchronization of the EEG is followed by a second phase consisting of the reappearance of the EEG background activity specific to NREM sleep. These two patterns correspond respectively to levels of greater and lesser arousal. These periodic fluctuations in cortico-subcortical excitability may exert a modulating effect on the motor attacks. Moreover, such periodic oscillations are typical of light sleep and in our cases this could explain the relationship of the motor attacks to sleep stages and their decrease during slow and especially REM sleep, phases characterized by greater stability of the arousal system (Terzano et al. 1985). The causative mechanism of the motor attacks remains speculative. Clear-cut epileptic EEG activity was, however, recorded during major attacks in our case 3. Varied simple or complex paroxysmal motor activity, isolated and in clusters, is a feature of frontal lobe epilepsy, ranging from semipurposeful bilateral arm movements to sexual automatism, postural adjustments, axial tonic or torsional movements (Tharp 1972; Geier et al. 1977; Waterman et al. 1987; Morris et al. 1988; Wada 1988). The scalp EEG is often normal in these patients (Wada 1988). Frontal lobe epilepsy was demonstrated for some of our patients with paroxysmal awakenings during sleep (Montagna et al. 1990) or short-lasting NPD (Tinuper et al. 1990). In these cases which display motor attacks quite similar to our cases we found paroxysmal EEG discharges, indicating a n epileptic, probably deep frontal, origin of the attacks (Tinuper et al. 1990). On the other hand, frontal lobe seizures are known to show a tendency for nocturnal quasiperiodic repetition (Tharp 1972; Wada and Purves 1984) and the oscillatory phases of cyclic alternating pattern are frequently associated with the periodic activation of an epileptic focus (Terzano et al. 1989). Periodic arousals during sleep could thus modulate the reactivity of the cortico-subcortical circuits responsible for triggering paroxysmal attacks in our patients (Lugaresi 1990). Notably, the motor events in our cases were often correlated with a K complex, which is considered an arousal response favoring the activation of an epileptic focus (Niedermeyer 1987). Stereotyped progression of the attacks from minimal to more complex activity has not, to our knowledge, been noticed before. In this regard, it may be relevant that a stereotyped progression of motor events has been observed upon stimulation of the cingulate gyrus. In conscious man stimulation of the cingulate gyrus evoked contralateral and less often bilateral responses characterized by stereotyped simple movements of fingers, hand and lips. These simple events could be part of a complex behavioural pattern as an expression of a progressive propagation along the precentral motor cortex (Talairach et al. 1973). Thus "minimal" events in our patients could represent the paroxysmal activa-
166
tion of a "minimal" nervous epileptogenic area which more rarely would progress to wider cortical structures and give rise to a "major" attack. Even though the evidence is indirect, we suggest that our patients represent cases of frontal lobe seizures not showing a clear-cut scalp E E G epileptic activity. Current routine electrophysiological methods cannot clarify the exact mechanism of either ,the increasing complexity or the activating influence of periodic arousals. Mr. Carlo Grassi, Ms Laura Solieri and Ms Marzia Tosi assured technical assistance.
References Coleman, R.M., Pollak, C.P. and Weitzman, E.D. Periodic movements in sleep (nocturnal myoclonus): relation to sleep disorders. Ann. Neurol., 1980, 8: 416-421. Geier, S., BanCaud, J., Talairach, J., Bonis, A., Szikla, G. and Enjelvin, M. The seizure of frontal lobe epilepsy. Neurology, 1977, 27: 951-958. Lugaresi, E. Nocturnal paroxysmal dystonia. In: M.J. Thorphy (Ed.), Handbook of Sleep Disorders. Marcel Dekker, New York, 1990: 551-565. Lugaresi, E. and Cirignotta, F. Hypnogenic paroxysmal dystonia: epileptic seizure or a new syndrome? Sleep, 1981, 4: 129-138. Lugaresi, E., Coccagna, G., Mantovani, M. and Lebrun, R. Some periodic phenomena arising during drowsiness and sleep in man. Electroenceph. clin. Neurophysiol., 1972, 32: 701-705. Montagna, P., Sforza, E., Tinuper, P., Cirignotta, F, and Lugaresi, E.
E. SFORZA ET AL. Paroxysmal arousals during sleep. Neurology, 1990, 40: 10631066. Morris, H.H., Dinner, D.S., Liiders, H., Wyllie, E. and Kramer, R. Supplementary motor seizures: clinical and electroencephalographic findings. Neurology, 1988, 38: 1075-1082. Niedermeyer, E. Phasic events and epileptic phenomena in sleep. Clin. Neurol. Neurosurg., 1987, 89: 174-178. Reehtschaffen, A. and Kales, A. A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Brain Information Service, Brain Research Institute, Los Angeles, CA, 1968. Talairaeh, J., Bancaud, J., Geier, S. et al. The cingulate gyrus and human behaviour. Electroenceph. clin. Neurophysiol., 1973, 34: 45 -52. Terzano, M.G., Mancia, D., Salati, M.R., Costani, G., Decembrino, A. and Parrino, L. The cyclic alternating pattern as a physiologic component of normal NREM sleep. Sleep, 1985, 8: 137-145. Terzano, M.G., Parrino, L., Anelli, S. and Hal~sz, P. Modulating of generalized spike and wave discharges during sleep by cyclic alternating pattern. Epilepsia, 1989, 30: 772-781. Tharp, B.R. Orbital frontal seizure. A unique electroencephalographic and clinical syndrome. Epilepsia, 1972, 13: 627-642. Tinuper, P., Cerullo, A., Cirignotta, F., Cortelli, P., Lugaresi E. and Montagna, P. Nocturnal paroxysmal dystonia with short-lasting attacks: three cases with evidence for an epileptic frontal lobe origin of the seizures. Epilepsia, 1990, 31: 549-556. Wada, J.A. Nocturnal recurrence of brief, intensely affective vocal and facial expression with powerful bimanual, bipedal, axial and pelvic activity with rapid recovery as manifestations of mesial frontal lobe seizure. Epilepsia, 1988, 29: 209. Wada, J.A. and Purves, S.J. Oral and bimanual-bipedal activity as ictal manifestations of frontal lobe epilepsy. Epilepsia, 1984, 25: 668. Waterman, K., Purves, S.J., Kosaka, B., Strauss, E. and Wada, J.A. An epileptic syndrome caused by mesial frontal lobe seizure loci. Neurology, 1987, 37: 577-582.
161
EEG91719
Paroxysmal periodic motor attacks during sleep: clinical and polygraphic features E. Sforza, P. Montagna, R. Rinaldi, P. Tinuper, A. Cerullo, F. Cirignotta and E. Lugaresi Institute of Neurology, University of Bologna, Bologna (Italy) (Accepted for publication: 29 September 1992)
Summary Three patients complained of paroxysmal motor attacks during sleep. Videopolygraphic recordings showed that motor activity could be divided into events of increasing behavioural complexity. Simpler motor events often represented the initial fragment of more complex attacks. Clinical features suggested the attacks represented frontal lobe epileptic seizures. The attacks recurred during NREM sleep with a periodic repetition every 20-60 sec. This periodicity could be related to the analogous physiological oscillation during light sleep and the periodicity of K complexes, exerting a facilitating influence upon epileptic mechanisms. Key words: Nocturnal attacks; Periodicity; Frontal epilepsy; Motor seizures
Nocturnal complex m o t o r attacks are unusual clinical events that occur in patients without definite E E G abnormalities in scalp records. The term nocturnal paroxysmal dystonia (NPD) has been introduced to define these events, which are characterized by different semeiology and duration (Lugaresi and Cirignotta 1981; Lugaresi 1990). A comparison of the clinical manifestations of frontal lobe epilepsy and the attacks of N P D has recently revealed several common features. Moreover, we reported patients showing clear-cut epileptic activity during short-lasting N P D attacks that represented cases of frontal lobe epilepsy from deepseated loci (Tinuper et al. 1990). In these patients, and in several other cases with nocturnal attacks, we observed that the same patient could display episodes of widely different duration and intensity. More detailed scrutiny, however, demonstrated that the attacks could be arranged into a few distinct types, each with highly stereotyped clinical features, but of increasing complexity. Simpler events could occur in isolation or represent the beginning of a m o r e complex episode. Moreover, the motor attacks seemed to recur at periodic intervals of about 20-60 sec for long stretches during sleep. The periodicity of the attacks thus resembled other sleep p h e n o m e n a such as the physiological varia-
Correspondence to: Emilia Sforza, M.D., Clinica Neurologica, Via U. Foscolo 7, 40123 Bologna (Italy). Tel.: + +39/51/6442183; Fax: 6442165.
tions of heart rate, blood pressure, respiratory amplitude (Lugaresi et al. 1972) and the periodicity of sleep apneas and nocturnal myoclonus (Coleman et al. 1980). In 3 patients, selected for the high frequency of attacks during sleep, we performed a detailed videopolygraphic study trying to better define the clinical features and sleep evolution and origin of the nocturnal attacks.
Methods Video-polygraphic recording was performed with a 19-channel polygraph (Grass Instrument, Model 78E) and a closed split-screen audiovisual circuit. Scalp electrodes were placed according to the 10-20 international system; bilateral sphenoidal and superficial supraorbital electrodes were added. Polygraphic channels included E M G of tibialis anterior muscles, E C G and thoracic respirogram. Video-polygraphic recording started at 9.00 p.m. and ended at 7.00 a.m. the following morning. In 2 patients (cases 1 and 2) sleep recording was repeated on 2 different nights. During light sleep a series of K complexes was purposefully and randomly evoked by acoustic stimuli. Video-records were analysed by two examiners (ES, R R ) and the attacks were divided into minimal, minor and major according to duration, intensity and complexity of motor behaviour. "Minimal" attacks were simple motor events involving one or more body segments (such as
E. SFORZA ET AL.
162
body touching, repetitive flexion and extension of feet or legs, chewing, scratching) without purposeful or intentional behaviour and with a short duration. "Minor" events were defined by the involvement of more body segments associated with prolonged purposeful or semipurposeful behaviour (such as hyperextension of limbs in a dystonic posture, vocalization, eye opening). During "major" attacks generalized dystonic postures were associated with forced extension and disorganized movements involving all limbs. The latter were typical NPD attacks as identified in our previous studies (Lugaresi and Cirignotta 1981; LugareSi 1990). The clinical features of each attack, its frequency (index: number of events/h), and mean duration as well as the mean interval between the attacks were studied. Events separated by less than 5 sec were considered a single event. A periodic occurrence was defined by a series of at least 3 consecutive events with an interval between 5 and 180 sec. The awake state was excluded from the analysis because of the absence of attacks in this state. Since the frequency of the attacks changed during the transition into slow and REM sleep, 5 min of recording before and after slow and REM sleep were arbitrarily excluded when computing the mean interval between attacks. For the purpose of computation of time intervals between attacks, no distinction was made between minimal, minor or major attacks. Standard criteria (Rechtschaffen and Kales 1968) were used for sleep scoring. Polygraphic examination included the analysis of EEG changes, the correlation between EEG findings and motor attacks and the examination of sleep figures before the onset of attacks. The duration of the nocturnal events was calculated on the polygraphic records and defined by the length of muscular artifacts and autonomic changes. The numbers of events during light, slow and REM sleep were then computed. In order to disclose long-term trends during the night, the number, duration and interval between events were also estimated for each third of the night and for each 1 h period between 23.00 and 06.30.
Results
The clinical and polygraphic features of the nocturnal attacks are detailed for each patient (Table I). Case 1 A 41-year-old man, without relevant family history, developed at age 35 nocturnal attacks consisting of brief and sudden movements of limbs and trunk followed by screaming and vocalization. Despite phenobarbital, phenytoin and sodium valproate the attacks persisted at an average rate of 7/night.
TABLE I Clinical and polygraphic findings of nocturnal motor events.
Index of events ( N / h ) Mean duration of minimal attacks (sec) Mean duration of minor attacks (sec) Mean duration of major attacks (sec) Mean polygraphic duration of minimal attacks(sec) Mean polygraphic duration of minor attacks(sec) Mean polygraphic duration of major attacks (sec) Mean clinical interval between the attacks (sec)
Case 1
Case 2
Case 3
42.6
42.8
18.3
4.5-+ 3.9
4.9-+ 3.7
8.0 5:6.9
11.95:4.7
13.0_+ 8.3
13.1+ 6.7
39.3 _+10.3
82.5 _+19.8
74.0 _+ 2.8
8.1_+ 4.8
8.6_+ 4.3
11.0_+ 6.4
14.7_+ 4.7
14.8_+ 7.1
17.6_+ 5.4
70.0 _+15.0
89.5 _+17.3
80.5 _+ 4.9
28.0 _+14.3
41.8 _+27.5
66.0_+47.7
During video-polygraphic recording the minimal events consisted of brief (4.5 sec) plantar flexion and adduction of feet and legs, chewing and touching of genitalia. In minor attacks these minimal events progressed to eye opening, elevation of shoulders, clapping, grunting, vocalization and semipurposeful gesticulation. During major attacks the initial plantar flexion and adduction of legs or vocalization and gesticulation were followed by left head turning, tonic limb hyperextension and disorganized movements with rocking of the trunk. After the attacks, the patient awakened amnesic for the episode. The index of nocturnal events was 43 with a mean duration of the minimal and minor events of 7 sec. The interval between events was 10-40 sec with a mean of 28.0 5:14 sec. During the second night the mean duration of minimal and minor attacks was 6 sec with a mean interval between attacks of 35 sec. Case 2 The patient, a 36-year-old woman, at the age of 9 began to have nocturnal attacks of sudden awakening. The attacks consisted in screaming and sitting up in bed sometimes followed by tonic extension and abduction and violent disorganized movements of all limbs. Phenytoin partially reduced the frequency of attacks. On polysomnography, the minimal events consisted of jerks of the limbs, repeated elevation of shoulders, torsion of the trunk and inappropriate gestures, i.e., scratching or rubbing her nose and head, touching of genitalia and grunts. In the minor events this was followed by sitting up with pelvic thrusting, vocalization of simple words, gesticulating with hyperextension of the fingers. During 3 major events that could be
163
P E R I O D I C ATTACKS D U R I N G SLEEP case 2 ~
o ~)
36yrs
'"'t
j-t_u_
1-2 3-4
REM
,.J
TIIITf TTT TTTTTTITTTT,TT I ITT TTT TTTTIT TTTTT ITINTTT 8,,', Z
i
23.50
i
i
0.00
TM,N,MALEVENT
i
0.30
T MINOR EVENT
T i
1.00
1.30
i
2.00
T SE,ZURE
Fig. 1. Sleep histogram in case 2. Bars over the histogram represent times of periodic motor activity present during light sleep and disappearing during slow and R E M sleep. Stars represent major attacks during stages 3-4. During the first part of the night periodic repetition of minimal and minor events in light sleep with a mean interval between attacks of 44 sec.
recorded the patient sat up and then presented forced hyperextension of the limbs with vocalization and rotation to the left of head and trunk and, on one occasion, generalized clonus. The index of events during sleep was 43 with a mean clinical duration of minimal and minor events of 8 sec. The interval between attacks was 10-50 sec with a mean interval of 42 sec during the first night and 45 sec during the second night (Fig. 1).
lateral torsion of the head and fanning of the fingers, followed during minor events by hyperextension of the arms and arching of the trunk. Major attacks were followed by a tonic attack with forced extension and adduction of arms and, sometimes, clonus of the arms and eyelids. These major seizures were associated with a diffuse sharp wave followed by diffuse spikes (Fig. 2). The index of attacks was 18 with a mean interval between events of 66 sec and a mean duration of minimal and minor events of 9 sec.
Case 3 This 24-year-old man began having nocturnal attacks at the age of 15 characterized by a sudden arousal with swallowing and chewing, screaming and tonic extension and adduction of arms. The attacks did not respond to phenobarbital and phenytoin treatment. During nocturnal study the patient presented minimal events characterized by chewing and swallowing,
Polygraphic findings The onset of the minimal and minor events coincided with a K complex followed by brief flattening of background activities and EMG artifacts. Autonomic records showed a uniform response consisting of brief tachycardia, deep inspiration and tachypnea, more marked during minor events. K complexes were not
P,F.r,-
Fz -
,,
T.or Resp.
.
.
.
.
. so
.
pl~sec.
case 3 oi 15 yrs
Fig. 2. Case 3. E E G during a major attack. The onset of attack was associated with diffuse shaTp waves With a left frontal region predominance.
164
E. SFORZA ET AL.
so2 -F~__ ~
~
.
~
F ~ " F4 - - - ~ . _ ~ . , ~ _ . ~ _ F8 - T
T4
4
0
SpH~ s
~
2
o
.....
~
~
~
s ~ 2 - Fs,~_.~. " S 01
I ~1 .....
Fm - F 7 ~ _ _ ~ , _ , _ ~ . ~ _ ~
T3 - 01~~.~_~.~.~
S~H,- s o ~ ~ _ _
S.H~ - F
T
~__
~
~z " C z - - - - ~ - ~ - ~ - - - - - -
EMG
R. L. Tib. ant.
1..._ J . L . ir-,.r- W
ECG Thor. Resp. ~
~
'
~
ACOUSTIC STIMULUS
C.G.R.
o,v 1see.
t
MINIMAL EVENT
~. 36yrs
Fig. 3. Sample of ictal recording during a minimal attack in case 1 showing the sudden onset of the motor event (arrow) coinciding with a K complex followed by brief EEG desynchronization (to the right). Similar EEG changes were evoked by acoustic stimuli (to the left).
associated with spindle-like activity or paroxysmal activity. K complexes purposely evoked by acoustic stimuli during light sleep were morphologically similar to those occurring during the attacks (Fig. 3). During major attacks polygraphic study showed only EMG artifacts with marked and prolonged tachycardia and tachypnea without EEG abnormalities in cases 1 and 2. In case 3 an epileptic diffuse spike activity was recorded only during major attacks. While minimal and minor events were most frequent during light sleep, major attacks typically tended to appear during slow sleep. Events occurred mainly in the first third (mean index: 38.1 + 16.7) without differences during the middle (mean index: 24.3 + 12.9) and last (mean index: 22.2 + 9.4) part of the night. The index of events decreased during the night in all patients between 01.00 and 02.00, 03.00 and 04.00 and 05.00 and 06.00 with
the greatest amount of REM sleep. Attacks occurred during stage 1 (mean % of attacks: 5.98 + 1.2) and especially stage 2 (mean % of attacks: 88.8 + 4.7) whereas they decreased during stages 3-4 (mean %: 3.84 + 3.5) and particularly stage REM (mean %: 1.3 + 0.6). There were no significant differences in duration of attacks or interval between events during the first (mean interval: 42.7 + 13.8 sec), second (mean interval: 47.5 + 25.0 sec) and third part (mean interval: 49.3 + 28.8 sec) of the night except for case 3 who had a reduced interval in the first third of the night. In all patients the most frequent interval between attacks was between 20 and 40 sec (Fig. 4). Sleep structure was disrupted by frequent arousals associated with the motor events. Slow sleep (% mean: 10.1 + 7.1) and REM sleep (% mean: 16.3 + 3.8) were reduced and light sleep (stage 1: % mean: 12.9 + 4.0;
PERIODIC ATFACKS DURING SLEEP
165
30-
I-
o~
I-
2O
10
.N 5-10
10-20
INTERVAL
20-30
30-40
BETWEEN
40-50
ATTACKS
50-60
> S0
(sec.)
Fig. 4. Histogram of distribution of time intervals between motor attacks. The most frequent intervals in all patients were 10-40 sec.
stage 2: % mean: 60.7 + 2.6) increased without alterations in sleep continuity (mean sleep efficiency: 90.7% + 1.5).
Discussion
A bewildering variety of paroxysmal motor activities could be seen during sleep in our patients. On closer analysis, however, the motor attacks, fairly stereotyped for each patient, could be broken down to 3 main types, ranging from simple motor behaviour, to more complex and semipurposeful motor activity and finally to fully developed attacks. Moreover, each type of motor event, highly stereotyped in itself, represented the initial fragment of the subsequent complex attacks. "Minor" attacks seemed to develop into "minimal" and "major" into "minor" attacks, according to a pattern which remained stereotyped throughout each night and successive nights. The hypothesis that the complexity of attacks regularly increases during the night accounts for the abundant and apparently disordered motor activity of our patients during sleep. The stereotyped features, the high frequency of the motor events, especially minimal and minor, and their arising upon a background of undisturbed sleep also weighed against their being merely coincidental or physiological motor activity during sleep. The second striking feature in our cases was the periodic occurrence of the motor events during NREM sleep. This was not merely coincidental as indicated by the fact that periodicity and duration of each type of attack remained much the same for each patient during successive nights of recording. This periodicity resembled the physiological oscillations of cortical, motor and autonomic functions typical of light sleep (Lugaresi et al. 1972) and the periodicity of K complexes related to nocturnal myoclonus (Coleman et al. 1980). Recently, Terzano et al. (1985) found that during NREM sleep, EEG activity is organized into periodic sequences of 40 sec cycles (cyclic alternating pattern) composed of two stereotyped patterns. A phase of activation composed by K complex, reactive slow wave
and transitional desynchronization of the EEG is followed by a second phase consisting of the reappearance of the EEG background activity specific to NREM sleep. These two patterns correspond respectively to levels of greater and lesser arousal. These periodic fluctuations in cortico-subcortical excitability may exert a modulating effect on the motor attacks. Moreover, such periodic oscillations are typical of light sleep and in our cases this could explain the relationship of the motor attacks to sleep stages and their decrease during slow and especially REM sleep, phases characterized by greater stability of the arousal system (Terzano et al. 1985). The causative mechanism of the motor attacks remains speculative. Clear-cut epileptic EEG activity was, however, recorded during major attacks in our case 3. Varied simple or complex paroxysmal motor activity, isolated and in clusters, is a feature of frontal lobe epilepsy, ranging from semipurposeful bilateral arm movements to sexual automatism, postural adjustments, axial tonic or torsional movements (Tharp 1972; Geier et al. 1977; Waterman et al. 1987; Morris et al. 1988; Wada 1988). The scalp EEG is often normal in these patients (Wada 1988). Frontal lobe epilepsy was demonstrated for some of our patients with paroxysmal awakenings during sleep (Montagna et al. 1990) or short-lasting NPD (Tinuper et al. 1990). In these cases which display motor attacks quite similar to our cases we found paroxysmal EEG discharges, indicating a n epileptic, probably deep frontal, origin of the attacks (Tinuper et al. 1990). On the other hand, frontal lobe seizures are known to show a tendency for nocturnal quasiperiodic repetition (Tharp 1972; Wada and Purves 1984) and the oscillatory phases of cyclic alternating pattern are frequently associated with the periodic activation of an epileptic focus (Terzano et al. 1989). Periodic arousals during sleep could thus modulate the reactivity of the cortico-subcortical circuits responsible for triggering paroxysmal attacks in our patients (Lugaresi 1990). Notably, the motor events in our cases were often correlated with a K complex, which is considered an arousal response favoring the activation of an epileptic focus (Niedermeyer 1987). Stereotyped progression of the attacks from minimal to more complex activity has not, to our knowledge, been noticed before. In this regard, it may be relevant that a stereotyped progression of motor events has been observed upon stimulation of the cingulate gyrus. In conscious man stimulation of the cingulate gyrus evoked contralateral and less often bilateral responses characterized by stereotyped simple movements of fingers, hand and lips. These simple events could be part of a complex behavioural pattern as an expression of a progressive propagation along the precentral motor cortex (Talairach et al. 1973). Thus "minimal" events in our patients could represent the paroxysmal activa-
166
tion of a "minimal" nervous epileptogenic area which more rarely would progress to wider cortical structures and give rise to a "major" attack. Even though the evidence is indirect, we suggest that our patients represent cases of frontal lobe seizures not showing a clear-cut scalp E E G epileptic activity. Current routine electrophysiological methods cannot clarify the exact mechanism of either ,the increasing complexity or the activating influence of periodic arousals. Mr. Carlo Grassi, Ms Laura Solieri and Ms Marzia Tosi assured technical assistance.
References Coleman, R.M., Pollak, C.P. and Weitzman, E.D. Periodic movements in sleep (nocturnal myoclonus): relation to sleep disorders. Ann. Neurol., 1980, 8: 416-421. Geier, S., BanCaud, J., Talairach, J., Bonis, A., Szikla, G. and Enjelvin, M. The seizure of frontal lobe epilepsy. Neurology, 1977, 27: 951-958. Lugaresi, E. Nocturnal paroxysmal dystonia. In: M.J. Thorphy (Ed.), Handbook of Sleep Disorders. Marcel Dekker, New York, 1990: 551-565. Lugaresi, E. and Cirignotta, F. Hypnogenic paroxysmal dystonia: epileptic seizure or a new syndrome? Sleep, 1981, 4: 129-138. Lugaresi, E., Coccagna, G., Mantovani, M. and Lebrun, R. Some periodic phenomena arising during drowsiness and sleep in man. Electroenceph. clin. Neurophysiol., 1972, 32: 701-705. Montagna, P., Sforza, E., Tinuper, P., Cirignotta, F, and Lugaresi, E.
E. SFORZA ET AL. Paroxysmal arousals during sleep. Neurology, 1990, 40: 10631066. Morris, H.H., Dinner, D.S., Liiders, H., Wyllie, E. and Kramer, R. Supplementary motor seizures: clinical and electroencephalographic findings. Neurology, 1988, 38: 1075-1082. Niedermeyer, E. Phasic events and epileptic phenomena in sleep. Clin. Neurol. Neurosurg., 1987, 89: 174-178. Reehtschaffen, A. and Kales, A. A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Brain Information Service, Brain Research Institute, Los Angeles, CA, 1968. Talairaeh, J., Bancaud, J., Geier, S. et al. The cingulate gyrus and human behaviour. Electroenceph. clin. Neurophysiol., 1973, 34: 45 -52. Terzano, M.G., Mancia, D., Salati, M.R., Costani, G., Decembrino, A. and Parrino, L. The cyclic alternating pattern as a physiologic component of normal NREM sleep. Sleep, 1985, 8: 137-145. Terzano, M.G., Parrino, L., Anelli, S. and Hal~sz, P. Modulating of generalized spike and wave discharges during sleep by cyclic alternating pattern. Epilepsia, 1989, 30: 772-781. Tharp, B.R. Orbital frontal seizure. A unique electroencephalographic and clinical syndrome. Epilepsia, 1972, 13: 627-642. Tinuper, P., Cerullo, A., Cirignotta, F., Cortelli, P., Lugaresi E. and Montagna, P. Nocturnal paroxysmal dystonia with short-lasting attacks: three cases with evidence for an epileptic frontal lobe origin of the seizures. Epilepsia, 1990, 31: 549-556. Wada, J.A. Nocturnal recurrence of brief, intensely affective vocal and facial expression with powerful bimanual, bipedal, axial and pelvic activity with rapid recovery as manifestations of mesial frontal lobe seizure. Epilepsia, 1988, 29: 209. Wada, J.A. and Purves, S.J. Oral and bimanual-bipedal activity as ictal manifestations of frontal lobe epilepsy. Epilepsia, 1984, 25: 668. Waterman, K., Purves, S.J., Kosaka, B., Strauss, E. and Wada, J.A. An epileptic syndrome caused by mesial frontal lobe seizure loci. Neurology, 1987, 37: 577-582.