Compulsive
yawning as migraine premonitory
symptom
DE Jacome
Franklin Medical
Center, department of medecine, Greenfield,
Massachusetts and Darthmouth-Hitchcock Medical
Center, Division of neurology, Lebanon, New
Hampsire, USA
Blau
JN Migraine postdromes: symptoms after
attacks
Introduction : For the purpose
of discussion in this paper, an artificial
distinction is made between the stereotypic
symptoms taking place within a few minutes of a
migraine headache, or typical aura, and the
symptoms of less abrupt developpment preceding
the headache by 20 or more minutes, or
premonitory symptom. These symptoms may be
understood as a precephalgic aura, in contrast
to the immediate symptoms surrounding the onset
of heaclaches, or pericephalgic (typical) aura.
Yawning is a normal motor phenomenon of
brainstem origin, that signifies drowsiness,
fatigue, hunger or boredom (1). Yawning is
listed as a migraine symptom that may precede or
follow the headache phase, sometimes for hours
(2, 3). Drowsiness or the urge to sleep, may be
part of migraine episodes. Three patients with
sustained, isolated yawning in the absence of
drowsiness, prior to the initiation of their
headaches, are reported. None had intracranial
lesions and all had normal neurological
examinations. The mother of one of the patients
had similar symptoms, giving basis to the
speculation that in certain cases inheritance
may play a role in the appearance of this
phenomenon. Because premonitory symptoms are
precephalgic rather than pericephalgic, as
defined above, yawning
may go unrecognized by physicians as an early
sign of migraine. Case reports
Case 1 : A 47-year-old female was seen
in a neurological consultation because of
protracted headache. She described global
throbbing headaches associated with nausea and
sometimes diarrhoea for the last 30 years. She
had three headaches a week. For the last 20
years she had experienced repetitive yawning
without feeling tired or drowsy, anteceding her
headaches for heurs. If she began yawning in the
evening she would wake up with a headache the
following morning. Her mother had similar
symptoms before the onset of her headaches for
many years. She had past history of
perimenopausal oestrogen deficient urethritis
and restless legs syndrome. She had developed
symptoms of depression after a recent divorce.
Her complete blood count, sedimentation rate,
chemistries and thyroid function tests were
normal. She had no cardiolipin, antinuclear or
neutrophil cytoplasrnatic antibodies. Brain MRI
vvas normal. Her general physical and
neurological examinations were normal. After a
trial different medications, her headaches
becaine less frequent and less intense while
taking Riboflavin 200 mg twice a day. During 3
years follow-up she reported no new symptoms or
changes in the characteristics of her yawning or
headaches.
Case 2 : A 50-year-old female had
right frontal and retroauricular throbbing
headaches associated with stabbing pains and
nausea for 10 years but more frequent recently.
Her headaches were preceded 30 min earlier by
sustained yawning in the absence of drowsiness
or fatigue. Headaches lasted 24 hours and
occurred once a week on average. She has a
history of temporomandibular joint dysfunction,
carpal tunnel syndrome, Raynaud's phenomenon and
perimenopausal depression. Her general physical
examination was normal. Her neurological
examination was unremarkable except for left
carpal Tinel sign. CBC was normal. She had mild
hypercholesterolaemia but the remaining of her
chemistries were normal. CT of the head and EEG
were normal. Her depression responded to the
administration of sertraline at the usual doses
but she was unable to tolerate nifedipine
prescribed for headaches. Eventually she
reported improvement in her headache after
attending a stress-reduction clinic. She had no
new symptoms or intercurrent illness to report
at a 2-year follow-up visit.
Case 3 : A 54-year-old female reported
headaches for 42 vears that became more frequent
and intense after the onset of her menopause.
She describes daily global pressure-like
headaches with superimposed occasional stabbing
pains on top of her head, beginning recently.
She had headaches of greater intensity once a
month along with nausea, photophobia and
malaise. When younger she had photopsia over her
right eye immediately preceding her headaches.
She experienced sustained yawning 30 min prior
to the onset of her headaches. Precephalgic
yawning disappeared with menopause. Her mother
and two cousins had migraine. She had
osteoarthritis. Her general physical and
neurological examinations were normal. She had a
normal CT of the head and EEG. Headaches were
relieved by butalbital. She chose not to take
prophylactic agents for the treatment of
headaches.
Discussion : Experimental studies have
demonstrated that dopamine, serotonin and nitric
oxide mediate yawning (4, 5). Yawning and penile
erection in rodents is induced by dopaminergic
drugs and oxytocin and can also be precipitated
experimentally in rats by cortical spreading
depression (6). This phenomenon is accompanied
by increased nitric oxide synthesis in the
paraventricular nucleus of the hypothalamus, and
tachykinin receptor activation of serotonergic
midbrain neurones (7, 8). Recurrent yawning is a
sign of anaemia in fetuses and rarely a sign of
the 'on response' to levodopa in patients with
Parkinson's disease (9, 10). In contrast,
pathological yawning and periodic leg movements
of sleep may be relieved by levodopa (11).
Compulsive yawning is a rare side-effect of
tricyclic antidepressants and a manifestation of
opiate withdrawal (12, 13). D'Mello et al. (14)
reported a patient with persistent yawning
following the administration of
electroconvulsive therapy and neuroleptic
withdrawal. Finally, yawning may be a
manifestation of epileptic seizures in rodents
and humans (15, 16). Current knowledge strongly
supports the role of dopamine in the
pathogenesis of migraine (17). An association
between dopamine D-2 receptor genes and migraine
without aura has been found in a subgroup of
'dopaminergic migraineurs' of Sardinian families
exhibiting precephalgic yawning (18).
Pharmacologically induced yawning may be
employed to uncover latent dopaminergic receptor
hypersensitivity in subjects with migraine. Del
Bene et al. (19) administered sublingual
apomorphine, a dopamine agonist drug, to a group
of 14 migraineurs. A great amount of yawning was
induced in the patients when compared with the
control group given placebo. Hence, patients
with migraine and dopaminergic dysfunction
rnanifested by early yawning are suitable to be
treated with dopamine blocking agents. Because
apomorphine-induced yawning in rodents can also
be suppressed by the administration of opiates,
calcium channel blockers and oestrogens, the
administration of any of these agents may be
appropriate in these patients (20-22). Oestrogen
replacement, in particular, may be a viable
therapeutic option for perimenopausal women with
dopaminergic hyperresponsiveness and migraine.
Although two of the patients herein described
experienced menopausal symptoms al the time of
their neurological evaluation, their premonitory
yawning had anteceded the menopause for many
years. On the third patient, yawning disappeared
during her rnenopause. Of additional interest in
the first patient, was the presence of restless
leg syndrome, a movement disorder secondary to
central dopaminergic dysfunction (23).
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