Polysomnography in locked-in syndrome

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Electroeneephalographv and chnica/ Neurophysiology, 1991.78:314 317 v) 1991 Elsevier Scientific Publishers Ireland, Ltd. 0013-4649/91/$03.50 A D O N I S 001346499100086A

EEG 90604

Short communication

Polysomnography in locked-in syndrome 1 Arie Oksenberg a, N a c h u m Soroker b, Pablo Solzi b and Irith Reider-Groswasser ~ " Sleep Disorders Unit, and h Department for Stroke Rehabilitation. Loewenstein Rehabilitation ("enter. Raanana (lsrael). and c Department of Radiolo~', Tel-A viv Medical Center, Tel-A ~'it' (Israel) (Accepted for publication: 22 November 1990)

Summary Sleep patterns were evaluated in a case of 'locked-in" syndrome. This patient had an ischemic infarction involving the ventral portion of the upper half of the pons bilaterally, with a posteromedial extension into the tegmentum. Reticular structures, notably the median raphe nuclei, supposed to play a major regulatory role in sleep, were most probably involved. Unexpectedly. repeated polysomnographic studies revealed sleep patterns with only minor abnormalities. Key words: Locked-in syndrome; H u m a n sleep; Ventral pons, Median raphe

The term 'locked-in' syndrome (L1S) denotes a clinical condition of quadriplegia and anarthria with preserved consciousness. This entity is usually, but not exclusively, the result of a ventral pontine infarction following basillary artery occlusion (Plum and Posner 1%6). Sleep studies in LIS are scarce, in spite of the fact that cell populations thought to play a crucial role in sleep regulation are located near the area usually involved in this syndrome (Hobson et al. 1986). These studies in general agree that sleep is disturbed and that R E M sleep in particular is markedly reduced or completely abolished (Feldman 1971; Freemon et aL 1974; Markand and Dyken 1976; Cummings and Greenberg 1977). We provide polysomnographic evidence of only minor sleep abnormalities in a patient with very severe and persistent LIS. Moreover, magnetic resonance imaging (MRI) and computed tomography (CT) demonstrate an involvement of the pontine tegmentum, including most probably the m e d i a n raphe nuclei, for which an important role in sleep regulation has been postulated (Jouvet 1969).

Ca~ report This '35-year-old mildly diabetic man experienced an intense acute headache and collapsed onto the °ground while playing with his children. Soon afterwards he became c o m a t o s e . Cerebrospinal fluid examination and CT scanning of the brain revealed no abnormalities. He regained consciousness after several days but has remained 'locked in' since then. During the early period after onset, the patient suffered from recurrent respiratory and urinary infections. No reliable information is available concerning his sleep behavior at that time. After 5 weeks, he was admitted to the Loewenstein Rehabilitation Hospital (LRH) for continuous treatment. The patient's neurological condition since

1 An abbreviated description of this case was presented at the 12th International Congress of Electroencephalography and Clinical Neurophysiology, Rio de Janeiro, Brazil, January 1990. Correspondence to: Dr. A. Oksenberg, Sleep Disorders Unit, Loewenstein Rehabilitation Center, Raanana 43100 (Israel).

his admission to the LRH i~, as follows: there is spastic tetraplegia with some residual voluntary movements in the left hand. All types of somatic and facial sensation are bilaterally preserved. The patient is alert and oriented. Articulation and voluntary voice production are impossible and communication is accomplished by y e s / n o responses with either eye/lid movements or left t h u m b adduction, and through computerized word processing using a special adapter for keyboard operation. There is a persistent right-sided abducence palsy. In the beginning, eye movements were restricted to the vertical plane only. Later, paralysis of right horizontal gaze persisted, while horizontal gaze to the left became possible. Mandibular movements are severely impaired. Restricted movements of the facial musculature are observed during the expression of strong emotions, but cannot be produced voluntarily. Pure-tone audiometry, taste sensibility and the gag reflex are normal. The patient is able to produce very slow and restricted tongue and neck movements. Brain imaging CT scans of the brain during the acute stage revealed no clear abnormality. However, in follow-up CT, a bilateral ventral upper pontine hypodense area compatible with infarction was observed. MR study using a 2T magnet was performed several months post onset. Spin echo Tl-weighted sagittal (A) and axial (B, C) cuts of the brain-stem are shown in Fig. 1. Polysomnographic ~'tudv No major sleep disturbances were detected by the medical staff during the hospitalization period at the LRH, although the patient complained of back pain from time to time, both in the daytime and at night. No psychotropic, sedative or hypnotic medication was given before or during the polysomnographic evaluations. Mild analgesic treatment and routine anti-aggregant therapy were provided. The following recording channels were used: 6 electro-oculograms (EOG, vertical and horizontal), 2 submental electromyograms (EMG), 8 electroencephalograms (EEG), 2 bipolar anterior tibialis EMGs (1 for each leg), 1 electrocardiogram (ECG), and 2 respiratory channels. Two m o n t h s after onset, a continuous 12 h polysomnographic recording was carried out (Fig. 2~. In this first recording session the patient had a total sleep time (TST) of 462 min, which gives a sleep efficiency (SE) of 64.1% for the entire 12 h and 80.8% for the first 8 h. Sleep latency was 4.0 rain and

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Fig. 1. A: mid-sagittal MRI cut demonstrating a wedge-shaped area of low intensity signal in the ventral upper pons. B: axial mid-pontine MRI cut. The low intensity area measures 1.5-2 cm in diameter. It involves the ventral portion of the pons bilaterally. C: axial MRI cut through the upper pons, demonstrating involvement of the basis pontis and a posteromedial extension of the lesion through the tegmentum. The lesion communicates with the fourth ventricle.

In order to corroborate these findings, 2 additional polysomnographic recordings were performed at several months' interval. Except for a decrease in REM sleep (17.1% of 402 min TST, and 21.7% of 336 min TST) and an increase in stage '2' (53.9%, 43.5%), no major differences were observed in sleep architecture or in the polygraphic features of REM and N R E M sleep compared to the first recording session.

the rapid eye movement (REM) latency was 87.5 min. The percentages of the various sleep stages out of TST were as follows: stage '1' - 7.8%; stage '2' - 36.1%; stage '3' - 7.8%; stage '4' - 13.8% (giving a total slow wave sleep (SWS) of 21.6%); and REM sleep 34.4%. Wakefulness after sleep onset (WASO) for the 12 h recording was 252 min (this includes 2 long waking periods of 94.0 min and 93.5 min after the 2 last R E M periods respectively). For the first 8 h the WASO was 88 min. These WASO values are higher than those usually obtained in normal subjects, although it should be noted that this first recording session was undertaken without a previous adaptation night. The average length of the 6 REM sleep periods was 26.6 + 8.8 min, and the average length of the 6 non-REM ( N R E M ) / R E M cycles was 84.7 ± 19.2 min. During REM sleep, all the polysonmographic features which normally characterize this stage were present. However, in every REM period, the frequency of vertical rapid eye movements was consistently higher than that of the horizontal ones, paralleling the situation during wakefulness (Fig. 3). No breathing abnormalities were found. Some periodic leg movements (PLM) were observed in REM and N R E M sleep. Movement index (MI), i.e., the average number of PLMs per hour of sleep, was 4.2.

Discussion

The sleep d a t a obtained in our patient contrast with the sleep abnormalities usually reported in LIS patients. In Feldman's (1971) patient, REM sleep occupied only 3-4% of a short TST and there were only small amounts of stage '4.' In the Markand and Dyken (1976) series, 5 out of 7 LIS patients showed complete absence of REM sleep while N R E M sleep was either absent, reduced or altered. One of Cummings and Greenberg's (1977) LIS patients had 3 REM periods (16% Of TST) and a reduced amount of SWS, while the other

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LOCKED-IN SYNDROME

Fig. 3. Sample of a polysonmographic recording during REM sleep. Note that except for an unusually high frequency of vertical eye movements (also observed in all other REM periods), the polygraphic features characterizing normal REM sleep are present. See text for description of the -~ recording channels.

patient had markedly reduced N R E M sleep and no REM activity at all. In contradistinction to these reports, in our patient, the 4.0 min sleep latency, the typical gradual progression from s t a g ~ ' l ' to stage '4,' the 48.5 min duration of the first SWS period, the REM latency of 87.5 min, and the average length of the N R E M / R E M cycle of 84.7 min, are all essentially normal polysomnographic features. The decrease in REM sleep percentages in the second and third recording sessions (17.1% and 21.7% respectively), as compared with the high amount of REM sleep in the first sleep evaluation (34.4%), possibly reflects less pain-related sleep disturbance with the passage of time. Musculoskeletal pains during the early hospitalization period were not uncommon and could result in some sleep deprivation with a concomitant rebound increment in the amount of REM sleep. As no psychotropic or hypnotic medication was given, this is the most probable explanation for the increased amount of REM sleep observed in the first recording session. How could the relative paucity of sleep abnormalities in our patient, as compared tO most other LIS patients described, be explained? The most probable explanation for this discrepancy may be found in differences in the location and extent of the causative lesions. In the present case, neuroimaging shows a massive lesion of the basis pontis, extending posteriorly across the midline of the upper pontine tegmentum. The presence of horizontal gaze disturbances suggests some involvement also of the adjacent paramedian pontine reticular structures. The limited nature of the tegmental involvement, evidenced by the intactness of sensory afferentation through the medial

lemniscus, possibly explains why this patient, although he suffered from a very severe and persistent form of LIS, had only minor sleep disturbances. The location of tegmental involvement in the present case is of special interest, as it most probably includes structures belonging to the serotoninergic system of the median raphe, at the upper pons level. The raphe system has been studied extensively in its relation to sleep in the cat, and as a result, a major role has been postulated for that system in the regulation of SWS and in the priming of REM sleep. In this species, destruction of the nuclei raphes dorsalis and centralis superior is followed by an almost complete suppression of SWS while REM sleep may persist, appearing even directly following the waking state. Destruction of the nt/clei raphes pontis and raphes magnus is followed by a selective decrease of REM sleep and by only a slight decrease of SWS (Jouvet 1969). Sleep data in humans with lesions to the median raphe are scarce. Lavie et al. (1984) described an almost complete absence of REM sleep in a patient with a traumatic pontine lesion. It is hard to conclude from the CT findings in that case whether the raphe system was involved. Guilleminault's (1973) patient with unspecified brainstem lesion and a low CSF level of 5-HIAA, had hyposornnia but no specific REM sleep abnormalities. Freemon et al. (1974) described a LIS patient with a massive infarction of the basis pontis and the ponto-mesencephalic tegmentum, including the raphe nuclei. In this patieot, TST was only 57 min out of almost 11 h of recording. During that very short sleep period N R E M and REM sleep percentages were normal, although no stage '4' was observed. Recently, Autret et al. (1985) reported a reduction in REM and N R E M sleep in 4 patients

POLYSOMNOGRAPHY IN LIS with brain-stem lesions sharing a common involvement of the medial pontine tegmentum. In fact, the most significant disturbance in these cases, as in Freemon et al.'s (1974) LIS patient, was the extremely short TST rather than R E M / N R E M alterations. In all the cases cited above, tegmental involvement seems to be greater and less specific than in the present case. The results of this case study indicate that, contrary to the impression arising from the literature, LIS patients, even those with very severe and persistent neurological deficits, may present no major sleep abnormalities. Moreover, our patient's sleep data raise the question of whether the median raphe system, or at least the portion located in the upper half of the pons, plays a significant role in sleep regulation in man. Doubts as to the critical role of the raphe system in sleep also arise from research done in rats (Mouret and Coindet 1980). In humans, further studies providing correlated polysomnographic and lesion data are necessary before we can answer this question. Such studies, in patients with circumscribed brain-stem lesions, are expected to enrich our understanding and knowledge of the neuroanatomy of sleep.

References

Autret, A., Laffont, F., De Toffol, B. and Cathala, H.P. A syndrome of REM and non-REM sleep reduction and lateral gaze paresis after medial tegmental pontine stroke. Arch. Neurol., 1988, 45: 1236-1242.

317 Cummings, J.L. and Greenberg, R. Sleep patterns in the 'locked-in' syndrome. Electroenceph. clin. Neurophysiol., 1977, 43: 270-271. Feldman, M.H. Physiological observations in a chronic case of 'locked-in' syndrome. Neurology, 1971, 21: 459-478. Freemon, F.R., Salinas-Garcia, R.F. and Ward, J.W. Sleep patterns in a patient with a brain stem infarction involving the raphe nucleus. Electroenceph. clin. Neurophysiol., 1974, 36: 657-660. Guillerninault, C., Cathala, J.P. and Castaigne, P. Effects of 5-hydroxytryptophan on sleep of a patient with a brain-stem lesion. Electroenceph. clin. Neurophysiol., 1973, 34: 177-184. Hobson, J.A., Lydic, R. and Baghdoyan, H.A. Evolving concepts of sleep cycle generation: from brain centers to neuronal populations. Behav. Brain Sci., 1986, 9: 371-448. Jouvet, M. Biogenic amines and the states of sleep. Science, 1969, 163: 32-41. Lavie, P., Pratt, H., Scharf, B., Peled, R. and Brown, J. Localized pontine lesion: nearly total absence of REM sleep. Neurology, 1984, 34: 118-120. Markand, O.N. and Dyken, M.L. Sleep abnormalities in patients with brain stem lesions. Neurology, 1976, 26: 769-776. Mouret, J. and Coindet, J. Polygraphic evidence against a critical role of the raphe nuclei in sleep in the rat. Brain Res., 1980, 186: 273-287. Plum, F. and Posner, J.B. The Diagnosis of Stupor and Coma. Davis, Philadelphia, PA, 1966:197 pp.