The Big
Yawning: Pathological Yawning as a Symptom of
Neuromyelitis Optica Spectrum
Disorders
Veronika Spahlinger, Annette Niessen,
Sebastian Rauer, Stefan Krämer, and
Matthias Reinhard
Department of Neurology and
Clinical Neurophysiology, Medical Center
Esslingen, Academic Teaching Hospital of the
University of Tübingen, Germany
Abstract
Pathological yawning is rarely observed in
cerebral or spinal diseases. A 67-year-old woman
was admitted with a seven-day progressive
hemisyndrome with left-sided limb ataxia and
hypesthesia. The patient yawned with a high
frequency, partially in salve-like episodes. MRI
showed a cervical myelitis over more than three
vertebral segments up to the lower medulla and
Aquaporin-4-antibodies were positive (diagnostic
criteria for a Neuromyelitis optica spectrum
disorder were fulfilled). Under treatment with
methylprednisolone, followed by plasmapheresis
and immunoadsorption, clinical symptoms were
regressive and the frequency of yawning
completely normalized. When observing
pathological yawning, even in the absence of
other cerebral or brainstem symptoms, one should
be aware of NMOSD as a possible cause.
1. Introduction
Yawning is an everyday phenomenon.
Pathological yawning is defined by a yawning
rate higher than commonly accepted without
triggers like fatigue or boredom. Various
anatomical structures such as the insula,
thalamus, hypothalamus, and brainstem reticular
formation as well as the locus coeruleus are
involved in the initiation and procedure of
yawning [1]. As a symptom, pathological
yawning can occur as part of epileptic seizures,
premigraine, and strokes or as side effects of
medications [2].
2. Case Presentation
A 67-year-old woman was admitted to our
hospital with a seven-day progressive
hemisyndrome with left-sided limb ataxia and
hypesthesia. On admission, the patient yawned
with a high frequency (>3/minute) and
partially in salve-like episodes (>8 yawns).
There was no increased level of fatigue or
boredom. Yawning was accompanied by nausea and
vomiting. There were no cranial nerve deficits.
The cranial MRI showed moderate leukoaraiosis
not suggestive of inflammation and a signal
enhancement of the coregistered myelon up to the
lower medulla. The cervical MRI then revealed
the full extent of the cervical myelitis over
more than three vertebral segments (see Figures
1(a) and 1(b)). The cerebrospinal fluid (CSF)
showed a slight pleocytosis with lymphocytes (7
cells) without elevation of CSF protein.
CSF-restricted oligoclonal IgG bands were
present. The visual evoked potentials were
normal on both sides. The diagnostic criteria
for a NMOSD were fulfilled: positive test for
AQP4-IgG and acute myelitis [3]. There
was no evidence for alternative diagnoses such
as other systemic autoimmune, infective,
vascular, neoplastic, or paraneoplastic disease.
The patient had a history of autoimmune
hepatitis with increased ANA titer, which was
inactive under long-term treatment with low-dose
azathioprine. Under initial high-dose treatment
with methylprednisolone, followed by
plasmapheresis and immunoadsorption, clinical
symptoms of ataxia and hypesthesia and the
spinal cord enhancement on MRI were regressive
within 10 days (see Figures 1(c) and 1(d)).
Consequently, the frequency of yawning
normalized and no more salves of yawning were
observed. Treatment with rituximab was
initiated.
Distinct oedema of the cervical spinal cord
on T2-weighted sequences with spinal cord
swelling and expansion into the brainstem.
Distinct gadolinium enhancement of the
cervical spinal cord on T1-weighted sequences
with cord swelling
3. Discussion
This case shows pathological yawning as a
symptom of NMOSD. So far, one series of 9 NMOSD
patients with pathological yawning lasting over
a period of at least two weeks was described
[4]. Our case supports this previous
notion of excessive yawning with NMOSD. The
phenomenon of pathological yawning in NMOSD may
be underrecognized by both patients and
physicians because yawning is a regular
physiological phenomenon. Only 2 of the
previously reported 9 cases did not show other
brainstem symptoms; one of them, however,
exhibited hypothalamic symptoms. All these
patients had abnormal brain MRI with
inflammatory lesions in the hypothalamus and/or
brainstem. In the present case, yawning existed
only for a few days and dissolved rapidly after
immune therapy. Interestingly, in our patient,
no other brainstem or hypothalamic symptoms were
observed apart from nausea and vomiting. MRI
only showed involvement of the lower medulla
including the area postrema but no other
inflammatory brainstem or hypothalamic lesion.
This might be due to treatment initiation prior
to radiologically visible extension of the
disease to more rostral structures.
Differential diagnoses for pathological
yawning include ischemic stroke (in the upper
brainstem, insula, or caudate nucleus [1, 5,
6], autonomic epileptic seizures
[7], parkinsonism, intracranial
hypertension due to infections or brain tumors,
and side effects of medications (e.g., serotonin
reuptake inhibitors and apomorphine)
[2]. We could not find such factors in
the present case as an alternative
explanation.
Pathological yawning is not frequently
observed in other chronic inflammatory central
nervous system diseases apart from a single case
report in multiple sclerosis [8]. It
thus seems to be a rather characteristic
clinical sign of NMOSD, which could be explained
by the fact that brain regions with high
aquaporin-4 expression are also those being
involved in the mechanism or control of yawning.
Assuming an increased local temperature with
extensive NMOSD inflammation in the myelon and
lower brainstem, an additional factor to the
increased yawning frequency could be the
thermoregulatory function of yawning via
suggested brain cooling effects [9]. The
fact that yawning subsided following
administration of methylprednisolone, which
decreases temperature of inflammatory tissue,
supports this hypothesis.
In conclusion, when observing
pathological yawning, even in the absence of
other cerebral or brainstem symptoms, one should
be aware of NMOSD as a possible cause.
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