mise à jour du
29 septembre 2005
J Neuol Neurosur Psychiat
Pathological yawning as a presenting symptom
of brainstem ischemia in two patients
L Cattaneo, L Cucurachi, E Chierici, G Pavesi
Sezione di Neurologia, Dipartimento di Neuroscienze, Università di Parma
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Yawning and stroke
We report two cases of brainstem stroke involving the upper pons and the ponto-mesencephalic junction, presenting with transient excessive pathological yawning, associated with gait ataxia and in one subject by upper limb and facial hemiparesis. In these patients we hypothesise a causal relationship between the brainstem lesion and pathological yawning, possibly related to denervation hypersensitivity of a putative brainstem centre of yawn. Excessive yawning can be a heralding sign of brainstem ischemia.
Yawning is a very common and phylogenetically old behavioural event that occurs in vertebrates under different conditions. A yawn consists of a stereotyped behavioural pattern that begins with an inspiration associated with marked dilatation of the pharynx. At the peak of inspiration there are associated facial movements and the final part of yawning is passive rapid expiration. During yawning a coordinated sequence of events takes place, involving facial, oropharingeal, tongue, and respiratory muscles, associated with activity in the axial extensor and limb extensor muscles and with autonomic changes characterized by an increased parasympathetic outflow.[1] The physiological stimuli that give rise to the yawning response and its functional significance are not clear. It has been shown that yawning frequency is not modified by hypercapnia or by pure oxygen breathing, it does not seem therefore to have a straightforward respiratory function.[2] Yawning occurs preferentially in conditions of low vigilance and causes transient increases in arousal as indicated by EEG desynchronisation though an active role in the maintenance of arousal has not been demonstrated. The social importance of yawning is particularly evident in mammals, where it seems to have a communicative role in conditions of decreased vigilance.[2] The neural structures that control yawning are presumably located in the brainstem near or within other respiratory and vasomotor centres, especially those that control facial mimics, mastication, throat and respiration and possibly stretching.[3] Excessive or pathological yawning, is defined as a compulsive, repetitive action that is not triggered by appropriate stimuli such as fatigue or boredom. We describe here two cases of excessive yawning behaviour associated with ischemic lesions in the brainstem.
Patient 1: A 74 years old male was admitted to our clinic complaining of unsteadiness of stance and gait lasting for 12 hours. The patient referred the acute onset of excessive repetitive, compulsive yawning that he was unable to control; the yawns were repeated at a frequency of about 3 per minute. Forty minutes later the patient noticed also gait ataxia and inability to stand without assistance. When admitted to the hospital, the neurological examination showed a slight intention tremor of the left arm and slight dysmetria in the finger-to-nose manoeuvre; no limb weakness was present and tendon reflexes were normal. The patient was able to stand and walk but the gait was possible only with enlarged base, irregular steps and leftward veering. Cranial nerves were unaffected and nystagmus was not present. The state of vigilance was constantly normal. The patient reported abnormally frequent yawning for three days following the acute onset with progressively longer intervals between one yawning act and the other. Three days later the neurological examination was normal and all symptoms had disappeared. An MRI scan, executed 3 days after the onset of the neurological deficit, showed a small hyperintense lesion in the left paramedian region of the middle pons on fluid attenuated inversion recovery (FLAIR) images (Figure 1). The lesion was also evident as an area of hyperintense signal in T2-weighted images. At a three months follow-up the patient was free of all symptoms.
Patient 2: A 66 years old woman presented with acute-onset unbalance of stance and gait, followed two hours later by a single episode of vomiting and by weakness of the left upper limb. She reported that the symptoms were preceded 20 to 30 minutes before by unjustified excessive yawning, at a frequency of approximately one event every 2 minutes. On admission to hospital the clinical examination disclosed in the cranial district a slight left lower facial paresis, a horizontal nystagmus beating leftwards and a right-sided internuclear ophtalmoplegia. A pronator drift in antigravitary posture and clumsiness in distal finger movements were observed in the left upper limb. Slight proximal weakness was present also in the left lower limb. Tendon reflexes were normally elicitable in the four limbs. An extensor plantar response was present on the left side. Finger to nose and reaching manoeuvres showed slight dysmetria on the right and could not be evaluated on the left due to the motor deficit. No sensory deficit could be observed both in the trigeminal and somatic territory. The patient showed wide-base gait and a marked left lateropulsion on stance. Vigilance was normal. An MRI scan obtained at 5 days from the onset of symptoms showed a right pontine ischemia (Figure 1) and MRI-angiography disclosed a pseudoocclusive stenosis of the basilar artery. The frequency of yawning gradually decreased and returned to normal within 36 hours. The motor deficit on the left side and the gait ataxia was still present, though moderately improved, at three weeks from onset.
We describe here for the first time two patients with brainstem ischemic stroke presenting with excessive yawning. The possible causal relationship between the brainstem lesion and the excessive yawning behaviour could provide useful information on the anatomical location of the neural systems controlling yawning in humans.
The central anatomical pathways subserving yawning have not been clearly defined.[4] The evidence in literature indicates the presence in mammals of a sub-cortical circuit mediating the yawning phenomenon, involving the hypothalamus, the midbrain and the reticular formation of the pons and medulla.[2][3][4] In the rat experimentally induced excessive yawning behaviour can be produced by direct or indirect activation of the oxytocinergic neurones in the paraventricular hypothalamic nucleus, which is thought to play a primary role in initiating the yawning phenomenon. The activity of hypothalamic yawning related neurons undergoes a complex pharmacological control, being enhanced by dopamine D2 and possibly D3 agonists, nytric oxide, acetylcoline and ACTH Ð MSH peptides, orexins and serotonin and downregulated by opioids.[5] Similar pharmacological mechanisms may act in humans, where D2 agonists, SSRI agents and withdrawal from morphine exert a facilitatory effect on the yawning behaviour. Also Valproate overdose, Imipramine and oestrogen substitution may cause pathological excessive yawning.[5]
The existence also in humans of a putative yawning centre in the lower brainstem is suggested by lesional data. Three reports[6][7][8] have described patients with locked-in syndrome, with preserved yawning movements and complete volitional paralysis of the bulbar musculature. Also, it has been observed that yawning movements persist in anencephalic infants.[2] Up to now the existence of a cortical representation of yawning has not been clearly demonstrated, though a recent brain-imaging work demonstrated the presence of an area in the posterior cingulated cortex that is activated by observation of yawning and is supposed to be involved in the well-known phenomenon of contagious yawning.[9] In both our cases, we observed excessive yawning behaviour associated with a brainstem infarction. The lesion was located in the paramedian region in the ponto-mesencephalic junction in both patients, though the lesion in patient 2 was much more extended caudally, involving also the upper half of the pons (Figure 1). The clinical picture was characterised by gait ataxia in both patients which is known to occur extremely frequently in paramedian mesencephalic and pontine infarction.[10] [11] Only in patient 2, due to the anterior extension of the lesion also a motor deficit was present. Focal brainstem lesions have already been reported to cause pathological yawning.
Jurko et al.[12] reported excessive yawning during hyperventilation in patients who had previously undergone thalamotomy or with recent head trauma and concluded that excessive yawning can be a sign of brainstem damage. None of our patients did report a facilitatory effect of hyperventilation.
Arai et al.[13] reported excessive yawning in a patient with tumour of the floor of the fourth ventricle and Postert reported excessive yawning as a symptom of brainstem localization of multiple sclerosis.[14] Additionally, excessive yawning has been observed in progressive supranuclear palsy, intracranial hypertension and in temporal lobe epilepsy, though it was not given a specific value in the localization of the epileptic focus.[15] [16] The exact mechanism of excessive yawning following focal brain lesions is not fully understood. Possibly the pathological behaviour is the expression of the liberation from the control of more cranial structures of a putative yawning centre, caudal to the lesion, analogously to the hypothesis postulated for hiccups caused by medullary lesions[17] or for the symptom of excessive yawning behaviour in patients with ALS.[18] Also in our two patients we hypothesise that the pathogenesis of the excessive yawning could be related to a denervation hypersensitivity mechanism. To our knowledge, this is the first report of excessive yawning after brainstem stroke and, more importantly, in both patients yawning appeared as the earliest symptom reported of the ischemic insult. We conclude that excessive yawning can be a presenting symptom of an acute brainstem lesion and should not be overlooked.
Figure 1: Fluid attenuated inversion recovery (FLAIR) brain images of the two patients. A) Patient 1. Axial section
showing a small hyperintense left paramedian area at the ponto-mesencephalic border. The scan was acquired at 3 days
from onset of the symptoms B) Patient 2. Coronal section, showing the ischemic area in the right paramedian pons and
ponto-mesencephalic border. The scan was acquired at 5 days from onset of the symptoms
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Response (O. Walusinski)
Yawning : a behavior testifying arousal reinforcement during brainstem stroke.
 PDF de cette réponse
The two case reports by Cataneo et al. have the great interest to complete the knowledge about yawning. Our purpose is to give another view of the meaning of excessive yawning observed during brainstem stroke. Among mammals, there are three types of morphologically identical yawns occurring in three distinct situations: situations relative to circadian rest-activity rhythms, situations relative to feeding, situations relative to sexuality or social interactions (1). Until now, no specific cerebral structure has been identified as a yawning centre.
A good number of clinical and pharmacological arguments indicate that yawning involves the hypothalamus (particularly the paraventricular nucleus), the bulbus and pontic regions, with frontal region connections in primates and to the cervical medulla (2). During the few hours of life of anencephalous babies, it has been noted that they yawn and stretch, a sign of the mammalian syndrome of awakening activity or « Rekel Syndrom » (3). Patients afflicted with the locked-in syndrome, still yawn, despite being paralysed (4,5,6,7). This shows that yawning originates in the brain's archaic structures common to all vertebrates. The central nervous system is based on a common overall organisational plan and reveals, from the most ancient to the most recent vertebrates, a gradual increase in complexity corresponding to life levels that are increasingly independent and functionally developed. Yawning helps understand the phylogenesis of the encephalon by inferring a functional organisational pattern of the nervous system similar to that advanced by Paul MacLean (8) with the superposition of: (a) an ancestral "reptilian" brain (brain stem and diencephalon), where yawning originates; (b) a "paleomammalian" brain (limbic system) common to all mammifers, functioning as a synaptic and humoral interface, in fact the seat of the monkeys' emotivity yawn; (c) a "neomammalian" brain characterised by human's cortical development, particularly the frontal lobes, seat of the "contagious" yawn.
The phylogenetic appearance of sleep proposes that the nocturnal rest of poikilotherms most probably becomes in mammals a form of the rapid eye movement sleep (REM sleep) or paradoxical sleep which is caracterized by peripheral muscular atonia originating in the dorsal part of the brainstem, rostral to the pons (9). The ultrasound investigation specifies is ontogenesis precociousness between 12 and 15 weeks of gestation. Based on numerous studies of fetuses and infants in a variety of mammalian species, it is widely believed that the earliest form of sleep is properly characterized as active sleep, that is an immature form of REM sleep and preponderant at birth. Accordingly, it is thought that quiet sleep, an immature form of slow-wave sleep (SWS), emerges as REM sleep's predominance diminishes during ontogeny. Behavioral pattern continuity from prenatal to postnatal life shows a strict parallelism between the ontogeny of REM sleep and yawning. Basically, REM sleep in the human declines from 50% of total sleep time (8 h) and a frequency of 30 to 50 yawns per day, in the fetus and newborn, to 15% of total sleep time (1 h) and less than 20 yawns per day, in the adult. This decrease takes place mainly between birth and the end of puberty. As a flip-flop switch, the reciprocal interactions between sleep and wake promoting brain regions allow the emergence of distinct states of arousal. By its ontogenical links with REM sleep, yawning appears as a behavior which procures an arousal reinforcement through the powerful stretch and the neuromuscular rewiring induced. The powerful muscular contraction caused by yawning releases arousal by activation of the reticular-formation (locus coeruleus) to which the cranial nerves send retro-projections. At becoming aware, the yawning and stretching reverse the muscular atonia which characterize REM-sleep (10).
Face-scratching, nose-face rubbing movements, yawning, sighs have been reported as automatisms before or after typical absence seizures or minimal epileptic seizures arising from sleep and they evoke temporal lobe seizures (11). These behaviors are also seen as a characteristic behavioral pattern of the arousal from sleep in healthy subjects. Velocity and repetition of the movements change in a different physiological (sleep arousal) or pathological (epileptic seizure, brainstem stroke) context. These behaviours can be related to the activation of brainstem and diencephalic circuitries, where the 'central pattern generators' of these behaviours are located, when cortex appears as deconnected by the epileptic discharge or stroke. The networks controlling awaking must be tonically reinforced and yawning apparears as a behaviour testifying arousal reinforcement.
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