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mise à jour du
22 septembre 2001
Jun 2001, 21, 623-625
cas cliniques
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
Extracephalic yawning pain
Jacome D Cephalalgia2004; 24; 5; 411-413
Primary yawning headache
Jacome D Cephalalgia 2001; 21; 6; 697-699
Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing syndrome treated with microvascular decompression of the trigeminal nerve A Lagares


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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