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mise à jour du 13 mars 2002
 Intern. J. Neuroscience 1999; 97; 1-2; 139-145
cas cliniques
Yawning and stretching induced by transcranial application of AC pulsed electromagnetic fields in parkinson's disease
Reuven Sandyk
Department of Neuroscience at the Institute fr Biomedical Engineeringand Rehabilitation Services of Touro College, Dix Hills, NY, 11746, U.S.A
The biological significance of Yawning elicited by application of electromagnetic fields in multiple sclerosis.Sandyk R


Yawning is a poorly understood phenomenon which is observed in humans and a wide variety of species (Lehmann, 1979). The occurrence of yawning, often associated with stretching, prior to falling asleep and upon awakening and the observation that yawning is associated with increased cortical EEG activity indicate that it is a reliable predictor of a change in arousal levels (Concu et al.. 1974, Serra et al., 1986; Baenninger et al., 1996). Experimental lesion studies indicate that the striatum is critically involved in the yawning process (Zarrindast et al., 1995a). Apomorphine and other dopamine (DA) receptor agonists administered to rats systemically or directly into the caudate nucleus induce yawning responses indicating that a central dopaminergic system is involved in yawning behavior (Mogilinicka and Klimek, 1977, Zarrindast et al., 1995a, b). Pharmacologie studies indicate that yawning is associated with increased DA release coupled with activation of postsynaptic DA-D2 receptors (Rollinson et al., 1979; Serra et al., 1986, 1987). The DA-D2 receptors mediating yawning appear to be functionally linked to Dl receptors in such a way that endogenous DA by stimulating Dl receptors plays a permissive role for the expression of yawning induced by postsynaptic DA-D2 agonists (Longoni et al., 1987). The relationship between yawning and the dopaminergic system is of particular interest for Parkinson's disease (PD) since PD is associated with decreased striatal dopaminergic activity and also because the disease is treated with levodopa or DA receptor agonists which stimulate DA-D, receptors and enhance striatal dopaminergic activity. Little is known about the occurrence of yawning in medicated PD patients although Goren and Friedman (1998) recently reported a patient treated with levodopa in whom yawning, often associated with stretching, preceded the onset of "on" periods. I recently encountered a patient with juvenile onset PD in whom yawning and stretching were observed during treatment with AC pulsed electromagnetic fields (EMFs) of picotesla flux density applied transcranially.

The patient was a 49 year old right handed woman who was diagnosed with PD at the age of 38 after she developed micrographia and stiffness of the right arm. She has been treated with carbidopa-levodopa since the age of 40 and was functioning well until about a year ago when she began to experience worsening of her symptoms with increasing tremor and stiffness of the right arm and hand, increasing bradykinesia, stiffness of the neck, debilitating fatigue, and increasing depression and anxiety. At the time of presentation in July of 1998 she was treated with a sustained release carbidopa-levodopa (Sinement CR, 25/100, 6 tabs/d), carbidopa-levodopa (Sinement 25/'100, 3 tabs/d), sertraline hydrochloride (Zoloft 100mg/d) and ergoloid mesylaies (H\yergine 3mg/d). On examination she exhibited masking of facial expression, hypophonia, resting tremor and rigidity in the right arni and hand, generalized bradykinesia with shuffling gait, and difficulties with balance and postural stability. She also exhibited -on-off- fluctuations in motor performance. "Off - periods were associated with increasing immobility and worsening of the tremor while "on" periods, each lasting up to 2 hours were associated with improved mobility and the emergence of dystonic dyskinesias of the neck and trunk. Due to a rather rapid deterioration of her Parkinsonisin in the past several months she elecied to undergo treatment with EMFs.

After obtaining an informed consent the patient received daily (mid-morning), for 5 consecutive days, two successive treatments with EMFs using the Sandyk Electromagnetic Stimulator in a quiet and artificially illurninated room that was magnetically unshielded. The Electromagnetic Stimulator produced on AC pulsed EMF of 7.5 picotesla flux density whichwas applied transcranially via a set of 24 coils placed over the patient's head. A 5 Hz sinusoidal wave was used in the first treatment of 15 minutes duration and following an interval of 15 minutes during which time the device was turned off, a second pulse of 7 Hz sinusoidal wave was administered for 20 minutes. The patient's eyes were shielded during the applications of EMFs. Treatment with EMFs was initiated each time during an -on" period about 20 - 30 minutes after the patient was medicated with carbidopa-levodopa. Characteristically, during the administration of the first treatment this patient reported feeling relaxed and towards the end of the treatment she felt slightly drowsy. Usually within several minutes after initiation of treatment she began to yawn at a rate of about 1 - 2 yawns per minute. The patient noted that the onset of yawning coincided with a complete cessation of the tremor and resolution of the rigidity in the right arm and neck muscles. Episodes of yawning continued throughout the duration of the first treatment and also during the interval when the magnetic stimulator was turned off. During the second treatment she felt more awake and alert, yawned more frequently (2 - 3 yawns/minute) and also exhibited stretching movements of the arms and trunk some of which were identical to those observed at night prior to falling asleep or upon awakening from physiological sleep. After the termination of the second treatment she continued to yawn, albeit less frequently, for about 10- 15 minutes. The patient could not recall yawning or stretching in association with the use of dopaminergic medications.

Yawning is considered an evolutionary vestige of a behavior associated with changes in activity and arousal levels (Anias et al., 1984: Baenninger et al., 1996). The yawning reflex is mediated through subcortical pathways which reach no higlier than the basal ganglia. Frequent yawning may occur with cerebral disease. It may be an epileptiform phenomenon or could occur as a sequela of encephalitis. Paroxysms of' yawning may also be caused by cerebral tumors, especially those located in the posterior fossa, opiate withdrawal hypothalamic disease, and as a complication of electroconvulsive therapy and concurrent neuroleptic withdrawal (Boshes, 1969; DeJong, 1979; D'Mello et al., 1988). Recurrent episodes of yawning have also been observed in patients with Tourette's syndrome and multiple sclerosis during transcranial administration of AC pulsed EMFs (Sandyk, l995 Sandyk, 1997).

Yawning is a DA mediated phenomenon although it is regulated also by other neurotransmitters and neuropeptides such as acetylcholine, serotonin, adrenocorticotropic hormone (ACTH) and melanocyte stimulating hormone (MSH), opioid peptides, oxytocin, and luteinizing hormone releasing hormone (LHRH) (Mogilnicka and Kliniek, 1977; Rollinson et al., 1979, Yamada and Furukawa, 1980, Bertolini and Gessa, l98l Mora and Diaz-Veliz, 1989; Argiolas and Melis, 1998). For instance, serotonergic mechanisms may have a facilitatory effect with respect to DA receptor agonist induced yawning (Urba Holnigren et al., 1979) and ACTH/MSH peptides may act in concert with DA receptors to induce yawning (Bertolini and Gessa, 1981). Sex steroids, in particular estrogens, also exert a permissive effect on DA receptor agonist induced yawning (Argiolas et al., 1998). Since in experimental animals and humans yawning is induced by L-dopa as well as by DA receptor agonists (i.e., apomorphine) (Mogilnicka and Klimek, 1977; Serra et al., 1986; Szechtman et al., 1988), one would expect it to occur frequently in Parkinsonian patients treated with levodopa or DA receptor agonists. It remains unclear why in Parkinsonian patients this phenomenon has not been mentioned more often in the literature (Goren and Friedman, 1998). Nevertheless, the occurrence of yawning and stretching in this patient during treatment with AC pulsed EMFs may further the understanding of the mechanisms of action of magnetic fields on the dopaininergic system in medicated PD patients.

It has been suggested that yawning is associated with activation of presynaptic DA autoreceptors stimulation of which results in inhibition of DA synthesis and release (Yamada and Furukawa, 1980; Cooper et al., 1989). In addition, since anticholinergic drugs block apomorphine induced yawning, Yamada and Furukawa (1980) proposed that yawning is mediated by cholinergie activation secondary to inhibition of DA transmission. However, some data argue against this hypothesis (Argiolas and Melis, 199S). Inhibition of DA transmission by other means such as administration of reserpine or neuroleptic agents or degeneration of DA neurons (Mogilnicka and Kliniek, l977 Dourish and Cooper, 1985) is not associated with yawnirig. Furthermore, the autoreceptor activation hypothesis of yawing, has been questioned since administration of' selective DA-D2 autoreceptor agonists failed to induce yawing, (Stahle and Ungerstedt, 1984). Current concepts follow the investigations of Serra et al. ( 1986, 1987) who demonstrated that yawning is caused by activation of postsynaptic DA-D2, receptors rather than inhibition of DA transmission by autoreceptor stimulation. In addition. the study of' Serra et al. (1986) suggested for the first time, that increased DA release is also required to elicit a yawning response. If this hypothesis is correct then yawning induced by transcranial administration of picotesla flux density E-MFs is caused by increased presynaptic DA release associated with stimulation of postsynaptic DA-D2 receptors.

Levodopa is thought to produce its antiParkinsonian effect through its decarboxylation and conversion to DA in presynaptic neurons thus increasing the synaptic availability of this transmitter in doparninergic neurons of the nigrostriatal pathways. DA-D2 receptors, which are located postsynaptically on striatal neurons (Reynolds and Riederer, 1990) are also the principal site of' action of DA agonist drugs in PD (Kebabian and Calne. 1979: Schachter et al., 1981, Gershanik et al., 1983). Yet, the use of levodopa alone or in combination with DA receptor agonists has not been associated yawning and stretching behavior in this or other PD patients. Moreover. yawning and stretching have not been observed in unmedicated PD patients during application of AC pulsed EMFs. Since in this patient AC pulsed EMF-s were administered in conjunction with levodopa, it is concelvable that yawning and stretching responses resulted from a synergistic interaction between EMFs and levodopa with EMFs possibly facilitating the release of DA derived from levodopa supplementation and simultaneously causing activation of postsynaptic DA-D2 receptors. Moreover, since stimulation of DA receptors increases the release of ACTH and MSH peptides from the pituitary or from peptidergic neurons in the brain (Bertolini and Gessa, 1981) and these peptides induced yawning and stretching behaviors in experimental animals and humans (Ferrari. l958 Ferrari et al, 1963 Floris, 1963 Gessa et al, l967) it is possible that a surge in the release of these peptides reinforced this yawning, and stretching behavior beyond the duration of EMFs exposure