Pathological yawning can be a clinical sign
in disorders affecting the brain stem. Here we
describe seven patients with pathological
yawning due to acute middle cerebral artery
(MCA)-stroke, indicating that pathological
yawning does also occur in supratentorial
stroke. We hypothesize that excessive yawning is
a consequence of lesions in cortical or
subcortical areas, which physiologically control
diencephalic yawning centers.
Introduction
Pathological yawning has been described in
various neurological disorders, including
migraine, epilepsy, basal ganglia disorders,
multiple sclerosis or brain tumors.(1) In
patients with focal brain lesions,
infratentorial lesions dominated and
pathological yawning has been linked to a
disturbance of the ascendant activatory
reticular system (MRS). While various
neurotransmitters (dopamine, acetylcholine,
serotonin, GARA) or hormones (oxytocine, ACTH)
as well as nitric oxide have been proven to
modulate yawning, the exact anatomical
structures involved in yawning are still not
well characterized. However, there is
experimental evidence that the hypothalamus
(especially the paraventricular nucleus, PVN)
plays a pivotal role n the elicitation of
yawning. A current hypothesis claims, that
activation of oxytocinergic neurons of the PVN
projecting to extrahypothalamic regions
including the hippocampus, pans and the medulla
oblongata elicits yawning. (2, 3) Lately, the
involvement of anatomical structures of the
lower brain stem in human yawning has been
emphasized by a case report of two patients
presenting with pathological yawning due to
acute brain stem ischaemia. (4) The authors
speculated that the brain lesions, located at
the pontomesencephalic junction, liberated the
control of a putative yawning center caudal to
the described lesions. However, little is known
about the involvement of cortical-subcortical
brain areas in the control of yawning. We
hypothesized that if neocortical structures are
involved in the control of spontaneous yawning,
it is likely to find pathological yawning also
in acute supratentorial stroke.
Methods
During an observation period of 6 months
patients referred to our neurological department
with the clinical suspicion of acute middle
cerebral artery (MCA) stroke (symptom onset
<12h) were observed immediately after arrival
(i.e. during taking the patient's history or
shortly thereafter) for an abnormal yawning
frequency. This was arbitrarily defined as more
than 3 yawns during 15 minutes. Healthy
individuals yawn about 20 times per day,
although the frequency differs substantially
according to age, circadian rhythms and between
individuals (range O-28 per day). (5, 6)
However, more than 3 yawns per 15 minutes
appears to be a reasonable cut-off between
physiological and excesslve" yawning. The
restriction to patients with a defined symptom
onset shorter than 12 h prior to admission was
chosen to minimize secondary reasons for an
increased yawning frequency as tiredness
associated with the sudden disturbance of the
daily routine or space-occupying cerebral edema
compromising blood flow in other vascular
territories than the primarily affected. Basic
clinical data, the time-point of examination, as
well as the National Institutes of Health Stroke
Scale (NIHSS) scores at admission and modified
Rankin Scale (MRS) scores at discharge were
assessed. All patients received computed
tomography immediately after arrival. Values are
given as mean±SD unless otherwise
stated.
Results
During the observation period, we registered
seven acute stroke patients (three males, mean
age 73*12 years, time interval between symptom
onset and examination 5h±3.6h) with an
abnormal high yawning frequency (mean
7.3±5.3 in 15 mm). Five patients arrived at
the hospital during daytime (between 9.40 am.
and 5.00 p.m.), while two patients were examined
during evening hours (7.00 p.m. and 9.20 p.m.).
Six patients experienced ischaemic and one
patient a haemorrhagtc stroke. Five patients had
left hemispheric and two patients right
hemispheric strokes. Average NIHSS-score at
admission was 17*4 (mean±SD). 4 patients
had a mild disturbance of consciousness at
arrival (patients being not alert but arousable
by minimal stimulation, scored I on the LOC item
of the NIHSS). There was no association between
the level of consciousness and the yawning
frequency. All patients presented with signs of
cortical dysfunction (aphasia n=5, neglect n=3,
gaze palsy n=6). Outcome at hospital discharge
was unfavourable in 6 of 7 patients (MRS
5or6).
Computed tomography revealed in 5 of 6
patients signs of cerebral infarction of more
than 1/3 of the MCA territory. No patient had CT
signs of additional infarctions in other than
the MCA-territory. Only one patient (No 2) had
CT-morphological evidence of relevant space
occupying cerebral edema at presentation.
Discussion
The observation of pathological yawning in
seven patients with acute anterior circulation
stroke provides strong evidence that excessive
yawning can be a sign of supratentorial lesions
affecting the middle cerebral artery (MCA)
territory.
The interpretation of this finding in the
light of the known neuroanatomy of yawning is
not straightforward. Both the hypothalamus and
the brain stem, which include regions critical
for yawning, are not supplied by the MCA.
Currently, in particular the paraventricular
nucleus (PVN) is believed to be the dominant
diencephalic relay station, which sends
oxytocinergic neurons to brain stem structures
involved in yawning. One possible explanation
for our finding of pathological yawning in
supratentorial stroke could be that the lesions
release the PVN from (presumably existing)
neocortical control mechanisms, leading to an
increase in the activity of the PVN. Whether
this phenomenon is due to a sudden reduction of
an inhibitory input from cortical structures
resulting in a disinhibition of the PVN or due
to an increase of excitatory input i.e. via
anoxic depolarization of penumbral tissue
remains speculative.
Due to the small sample size and often large
lesions of our patients we did not attempt an
exact topographic lesion analysis. However,
there is little doubt that circumscribed
neocortical dysfunctions can lead to excessive
yawning, as several case reports on yawning
after epileptic seizures (predominantly temporal
lobe seizures) confirm. (7, 8) Of further
interest is a case report of a woman
experiencing excessive (spontaneous) yawning
months prior to the development of a
bulbar/pseudobulbar palsy due to amyotrophic
lateral sclerosis. (9) The author speculated,
that her pathological yawning was due to a
dysfunction of the upper motor neurones loosing
their inhibitory influence on the brain stem and
lower motor neurones.
There is evidence from functional MRI
studies, that neocortical areas are involved in
the well known phenomenon of contagious
(visually mediated) yawning: Platek et al. (10)
describe substantial activations in the
posterior cingulate cortex (Brodman area (BA)
31) and precuneus (BA 23) bilaterally as well as
in the thalamus and parahippocampal gyrus (BA
30) of both hemispheres. In addition,
Schürmann et al. (11) found significant
bilateral activation of the anterior part of the
superior temporal sulcus (STS) and in the
posterior part of the right STS being involved
in the visual processing of observed yawning.
More importantly, they found a negative
association between the subjective yawning
susceptibility and the BOLD response in the left
periamygdalar region, an area mostly supplied
from the anterior choroidal artery. (12) Given
the known tight hippocampal-hypothalamic
neuroanatomical connections, and the fact that
five of our patients had left hemispheric
strokes partially involving temporal structures,
case reports on yawning after temproal lobe
seizures, it is tempting to speculate, that a
dysfunction of hippocampal/periamygdalar
structures may be linked with excessive yawning.
However, the fMRI data refer to the specific
phenomenon of visually mediated contagious
yawning; thus, their relevance for spontaneous
yawning remains speculative.
Our pilot study has several shortcomings:
First, the cut-off for excessive yawning
(3/15mm) is somewhat arbitrary, since healthy
individuals may also yawn in clusters of similar
frequency. However, we believe that frequent
yawning in the setting of hospital admission and
physical examination is inappropriate,
especially since the majority of the patients
arrived during daytime hours. Second, we did not
keep a screening log, making estimates about the
incidence of excessive yawning in acute stroke
impossible. Finally, we did not attempt a
qualitative or phenonienologic description of
the yawns, i.e. if appearing solitary or in
sequences.
We conclude that pathological yawning can
occur in supratentorial stroke. Our observations
suggest that neocortical brain areas have a
regulatory effect on diencephalic and brain stem
yawning centers. Further imaging studies will
need to clarify the exact neuroanatomical
structures involved in the higher control of
(excessive) spontaneous yawning.
Argiolas
A, Melis MR. The neuropharmacology of
yawning. Eur J Pharmacol1998;343(1):1-16.
Cattaneo L,
Cucurachi L, Chierici E, Pavesi G.
Pathological yawning as a presenting symptom of
brain stem ischaemia in two patients. J Neurol
Neurosurg Psychiatry 2006;77(1):98-100.
Walusinski
O. Yawning: unsuspected avenue for a better
understanding of arousal and interoception. Med
Hypotheses 2006;67(1):6-14.
Since
the 19th century, cases of pathological
yawning have occasionally been published in
medical journals. In this issue of JNNP, O
Singer et al present the first study to focus
specifically on yawning during acute stroke
affecting the middle cerebral artery (MCA)
territory.
None of the seven patients suffering from
abnormal repetitive yawning had diencephalic
lesions. Classically, yawning is thought to
originate in archaic brain structures common to
all vertebrates. It appears to be a powerful
muscular stretch which recruits specific control
systems, particularly the paraventricular
nucleus of the hypothalamus (PVN), the locus
coeruleus, and the reticular activating system;
these structures explain its ability to increase
arousal. A persistent vestige of the past,
yawning has survived evolution with little
variation (1). O Singer et al suggest that
neocortical brain areas have an inhibitory
effect on the PVN, and that in certain MCA
strokes, this region is liberated, provoking
repetitive yawning. This hypothesis merits
discussion.
According to J Lapresle (2), palatal
myoclonus is the human homologue of a primitive
respiratory reflex in gill-breathing
vertebrates, submerged but not lost, reappearing
when the inhibitory system is damaged by lesions
to the dentato-olivary pathway.
We coined the term "parakinesia
brachialis oscitans" (3) to describe cases
of hemiplegia where the onset of yawning
coincides with involuntary raising of the
paralysed arm. We argued that a lesion in the
internal capsule affecting an inhibitory pathway
liberates certain subcortical structures that
coordinate the massive inspiration of yawning
and the motor control associated with
quadrupedal locomotion.
In these examples, the loss of cortical
inhibition following stroke releases a hidden
function, phylogenetically more primitive. O
Singer et al do not provide evidence of such an
event.
Face-scratching,
nose-face rubbing, yawning, and sighs are
automatisms frequently reported after epileptic
seizures. These behaviours are also considered a
characteristic pattern in healthy subjects upon
waking. Movement speed and repetition are the
factors that vary, based on whether the context
is physiological (sleep, arousal) or
pathological (epileptic seizure, stroke). These
behaviours are related to the brainstem and
diencephalic activation that occurs when the
cortex is disconnected from these areas (where
the "central pattern generators" are located) by
an epileptic discharge or a stroke.(4)
Adaptive behaviours depend on interactions
between neural networks at various levels,
requiring continuous mutual feedback. Yawning is
an exterior manifestation of the tonic
stimulation of the cortex by subcortical
structures, particularly when the brainstem does
not receive appropriate feedback from the
cortex.
I agree with the conclusion reached by O
Singer et al: further studies are necessary to
determine the exact neuroanatomical structures
involved in repetitive yawning during stroke and
the pathophysiological role of this
behaviour.
References
Walusinski
O, Deputte BL. Le bâillement :
phylogenèse, éthologie,
nosogénie. Rev Neurol (Paris).
2004;160(11):1011-21.
Lapresle
J. Palatal myoclonus. Adv Neurol.
1986;43:265-73.
Différentes
localisations d'AVC peuvent-elles aider à
concevoir la neuro-anatomie d'un comportement
comme le bâillement ?
Depuis
le XIX° siècle, quelques
observations de bâillements pathologiques
sont publiées dans la littérature
médicale. Dans ce numéro du JNNP,
O. Singer et al. proposent, pour la
première fois, un travail dont le but
assigné est l'étude des
bâillements au cours d' AVC affectant
l'artère sylvienne.
Aucun des sept patients souffrant de
bâillements anormalement fréquents
et répétés n'a de
lésion diencéphalique.
Classiquement, l'origine du bâillement est
située au niveau du noyau
paraventriculaire de l'hypothalamus (PVN)
avec des projections vers le Locus Coeruleus et
la réticulée ascendante du tronc
cérébral. C'est par l'implication
de ces structures qu'est expliqué son
effet physiologique de stimulation de
l'éveil. Le bâillement
apparaît comme un comportement aux allures
de vestige ubiquitaire et ancestral, persistant
sans variation évolutive notable, O.
Singer et al. suggèrent que des aires
néocorticales auraient une fonction
inhibitrice sur le PVN, levées par
certains AVC, et permettant alors
l'extériorisation de bâillements
répétés. Cette proposition
mérite d'être discutée.
J.
Lapresle explique que la myoclonie du voile
du palais est l'homologue humain d'un
réflexe branchiale des
vertébrés aquatiques, enfoui mais
non disparu au cours de l'évolution, et
réapparaissant lors d'un lésion de
la voie dentatoolivaire.
Nous avons nommé «
parakinésie brachiale oscitante
» l'apparition , au cours d'une
hémiplégie, d'un mouvement portant
le bras paralysé vers la bouche,
simultanément à un
bâillement. Nous avons proposé de
l'expliquer par l'effet d'une lésion, au
niveau de la capsule interne, d'une voie
inhibitrice libérant une structure
sous-corticale, coordonnant l'inspiration ample
et la motricité du membre
supérieur, lors de la course chez les
quadrupèdes.
Dans ces exemples, la perte de l'effet
inhibiteur d'origine corticale, secondaire
à l'AVC libère une fonction
cachée, constamment inhibée et
phylogénétiquement plus ancienne.
O. Singer et al. ne proposent pas d'explication
comparable, extériorisant une fonction
archaïque normalement inhibée.
Se
gratter le visage, se frotter le nez,
bâiller, soupirer sont des gestes
d'allure automatique fréquemment
notés après des crises
d'épilepsie, par exemple. Ces
comportements se voient également
aussitôt après l'éveil, chez
des sujets sains. C'est la rapidité et la
répétition de ces gestes, suivant
qu'ils apparaissent de façon
physiologique (sommeil, éveil) ou
pathologiques (épilepsie, AVC) qui se
modifient. Ils peuvent être
rapportés à l'activation de
centres de mouvements coordonnés,
automatiques, situés au niveau du tronc
cérébral, quand la crise
épileptique ou l'AVC déconnecte le
tronc cérébral du cortex.
Les comportements adaptés
dépendent d'une interaction harmonieuse
entre différents circuits neuronaux
cortico sous-corticaux engageant une dialogue
bidirectionnel continu. L'apparition de ces
comportements répétitifs
extériorisent l'activité
stimulante des structures sous-corticales quand
elles ne reçoivent pas de feed-back
adapté des aires corticales.
Nous nous associons à la conclusion
de O. Singer et al.: d'autres études
seront nécessaires pour clarifier les
structures neuroanatomiques mises en jeu lors
des bâillements
répétés survenant lors des
AVC et pour en expliquer le rôle
physiopathologique.
