- Lana-Peixoto MA,
Callegaro D, Talim N, Talim LE, Pereira SA,
Campos GB, et al. Pathologic yawning in
neuromyelitis optica spectrum disorders. Mult
Scler Relat Disord 2014;3:527-32.
-
- Spahlinger
V, Niessen A, Rauer S, Krämer S, Reinhard
M. The big yawning: Pathological yawning as a
symptom of neuromyelitis optica spectrum
disorders. Case Rep Neurol Med
2019;2019:9691863.
-
- Gutierrez
C, Rodrigues S, Trillo M, Vasquez A,
Aguirre-Quispe W. Neuromyelitis optica
spectrum disorder after BIBP COVID-19 vaccine: A
case report. Neuroimmunol Rep
2023;3:100174.
-
- Saroja
AO, Naik KR. Persistent Pathological Yawning
due to Neuromyelitis Optica Spectrum Disorder.
Ann Indian Acad Neurol. 2026 Jan 8.
-
-
- Neuromyelitis optica spectrum disorders
(NMSOD) are inflammatory disorders of the
central nervous system and have circulating
immunoglobulin (IgG) antibodies against
aquaporin-4. NMSOD has a relapsing course with
diverse clinical manifestations resulting from
involvement of the optic nerves, spinal cord,
diencephalon, brainstem, area postrema, and
cerebrum. Clinical presentations include visual
impairment, paraparesis, quadriparesis,
sphincter disturbance, intractable hiccups,
vomiting, itching, tonic spasms, narcolepsy,
etc.Pathological yawning has been described in a
few NMSOD patients.
-
- The authors report a young lady who had
persistent yawning for more than 3 years as a
disabling residual manifestation of seropositive
NMSOD.
-
- Les troubles du spectre de la
neuromyélite optique (NMSOD) sont des
troubles inflammatoires du système
nerveux central caractérisés par
la présence d'anticorps immunoglobulines
(IgG) circulants dirigés contre
l'aquaporine-4.
- Les NMSOD ont une évolution
récidivante avec diverses manifestations
cliniques résultant de l'atteinte des
nerfs ophtalmiques, de la moelle
épinière, du diencéphale,
du tronc cérébral, de l'area
postrema et du cerveau. Les manifestations
cliniques comprennent une perte visuelle, une
paraparésie, une
tétraparésie, des troubles
sphinctériens, des hoquets
réfractaires, des vomissements, des
démangeaisons, des spasmes toniques, une
narcolepsie, etc. Des bâillements
pathologiques ont été
décrits chez quelques patients atteints
de NMSOD.
-
- Les auteurs rapportent le cas d'une jeune
femme qui présentait des
bâillements persistants depuis plus de
3 ans, manifestation résiduelle
invalidante d'une NMSOD séropositive.
- A 17-year girl presented in 2017 with acute
onset of paraparesis and difficulty in walking
without sensory, sphincter, or cranial symptoms,
progressing to a bedbound state within 2 days.
She was seen at another hospital 2 months
earlier for left hemiparesis, which had improved
with steroids. She had intact cognitive and
cranial nerve function with mild weakness of the
distal upper limbs, spastic paraparesis, and
exaggerated muscle stretch reflexes. Magnetic
resonance imaging (MRI) of the spine revealed
longitudinally extensive myelitis (LETM) of the
cervical spinal cord. Her serum was positive for
aquaporin-4 antibodies by cell-based assay.
Other laboratory parameters, including
cerebrospinal fluid analysis, were normal.
Pulse-dose methylprednisolone resulted in good
improvement, and subsequently, she was given two
doses of rituximab, after which she was lost to
follow-up.
-
- In 2022, she was admitted to another
hospital due to hypersomnolence, with cranial
MRI revealing bilateral asymmetric thalamic and
internal capsular hyperintensities.
Hypersomnolence improved after pulse-dose
methylprednisolone therapy. However, she had
been having persistent pruritus, yawning,
repetitive vocalization, hemifacial spasm, and
hypersomnolence since then, which was not
associated with headache.
-
- In July 2024, she developed acute onset
asymmetric spastic paraparesis. Spine MRI
revealed LETM from the D10 to D12 level. Cranial
MRI revealed right medial thalamic and
hypothalamic gliosis [Figure 1],
periaqueductal T2 hyperintensity, and
enlargement of the aqueduct [Figure 2].
She received pulse-dose methylprednisolone
therapy followed by rituximab, after which
paraparesis recovered and she could
independently perform all activities of daily
living. She received pregabalin from July 2024
for 3 months for the troublesome tract pains,
which was stopped due to lack of efficacy.
Rituximab infusion was continued (1 g every 6
months).
-
- She came back for follow-up in April 2025
with pruritus and persistent yawning associated
with involuntary repetitive stereotyped
utterance. In addition, she has persistent
hypersomnolence with burning pain over the
scalp, along with recent onset of anger
outbursts due to yawning. Persistent yawning
throughout the awake period interfered with her
social life and interactions, causing reactive
depression and anger outbursts. Escitalopram was
started for depression and had to be stopped due
to an increase in yawning. She was given
modafinil for hypersomnolence and oxcarbazepine
for tract pain without definite benefit.
-
- Persistent yawning has been described in
patients with NMSOD, unrelated to sleep
deprivation and fatigue. Nine women with
pathological yawning were reported from an
neuromyelitis optica (NMO) seropositive cohort.
Yawning occurred at presentation in five
patients and occurred before optic
neuritis/myelitis in three patients. These
patients had nausea, hiccups, brainstem and
hypothalamic involvement on MRI. 31
Short-lasting yawning was described in an
elderly lady with aquaporin-4 IgG antibodies and
left-sided ataxia, hypoesthesia secondary to
long-segment cervical demyelination, along with
leuoaraiosis and enhancement in the medulla
oblongata.4] Pathological yawning was also
reported after NMSOD, which occurred after
Beijing Institute of Biological Products-COVID
19 (BIBP COVID-19) vaccination.]
- The average number of yawns is nine per day,
and more than 15 per day is considered
excessive. Excessive yawning occurs due to sleep
deprivation, hypersomnolence, obstructive sleep
apnea, opioid withdrawal, and drugs like
selective serotonin reuptake inhibitors (SSRIs),
naloxone, and apomorphine. Yawning is seen in
neurological disorders including amyotrophic
lateral sclerosis, epilepsy, head injury,
migraine, multiple sclerosis, stroke,
parkinsonism, intracranial hypertension, and
brain tumors. It is thought that yawning
switches the default mode network.(?,8]
Yawning is probably related to the involvement
of the insula, hypothalamus, brainstem reticular
formation, and locus coeruleus.? Neural pathways
involved in yawning are thought to be due to (1)
oxytocinergic neurons from the hypothalamic
paraventricular nucleus, hippocampus, pons,
medulla oblongata, and spinal cord; and (2)
adrenocorticotrophic neurons and
melanocyte-stimulating neurons from the
paraventricular nucleus to the hippocampus. The
neurotransmitters implicated are acetylcholine,
serotonin, gamma-aminobutyric acid, glutamate,
dopamine, nitric acid, adrenocorticotrophic
hormone (ACTH)-related peptide,
melanocyte-stimulating hormone, and oxytocin.
Dopamine and oxytocin transmission are thought
to be essential to yawning. Another proposed
mechanism is the communication hypothesis, as in
empathy, with involvement of mirror neurons. The
insula has been proposed to be the region for
serotonin-mediated yawning. The hypothalamus,
especially the paraventricular nucleus and its
connection with the reticular formation, has a
role in the generation of yawning. 6,71
Pathological yawning as a persistent sequela of
NMSOD is rare, and in our patient, it was likely
to have resulted from bilateral thalamic,
hypothalamic, and periaqueductal grey matter
involvement. Treatment of pathological yawning
in our patient was challenging, as therapeutic
interventions were unsuccessful.
-
-
- References
- 1. Wingerchuk DM, Banwell B, Bennett JL,
Cabre P, Carroll W, Chitnis T, et al.
International consensus diagnostic criteria for
neuromyelitis optica spectrum disorders.
Neurology 2015;85:177-89.
- 2. Jarius S, Aktas O, Ayzenberg I,
Bellmann-Strobl J, Berthele A, Giglhuber K, et
al. Update on the diagnosis and treatment of
neuromyelits optica spectrum disorders
(NMOSD)-revised recommendations of the
Neuromyelitis Optica Study Group (NEMOS). Part
I: Diagnosis and differential diagnosis. J
Neurol 2023;270:3341-68.
- 3. Lana-Peixoto
MA, Callegaro D, Talim N, Talim LE, Pereira SA,
Campos GB, et al. Pathologic yawning in
neuromyelitis optica spectrum disorders. Mult
Scler Relat Disord 2014;3:527-32.
- 4. Spahlinger
V, Niessen A, Rauer S, Krämer S, Reinhard
M. The big yawning: Pathological yawning as a
symptom of neuromyelitis optica spectrum
disorders. Case Rep Neurol Med
2019;2019:9691863.
- 5. Gutierrez
C, Rodrigues S, Trillo M, Vasquez A,
Aguirre-Quispe W. Neuromyelitis optica
spectrum disorder after BIBP COVID-19 vaccine: A
case report. Neuroimmunol Rep
2023;3:100174.
- 6. Krestel
H, Bassetti CL, Walusinski O. Yawning-Its
anatomy, chemistry, role, and pathological
considerations. Prog Neurobiol 2018;161:61-78.
7. Walusinski O. Pathological yawning, laughing
and crying. Front Neurol Neurosci
2018;41:40-9.
- 8. Teive
HAG, Munhoz RP, Camargo CHF, Walusinski O.
Yawning in neurology: A review. Arq
Neuropsiquiatr 2018;76:473-80.
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