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mise à jour du 13 mars 2002
 Intern. J. Neuroscience 1997; 89; 1; 53-60
cas cliniques
The biological significance of yawning elicited by application of electromagnetic fields in mutiple sclerosis Reuven Sandyk
Department of Neuroscience at the Institute fr Biomedical Engineeringand Rehabilitation Services of Touro College, Dix Hills, NY, 11746, U.S.A
Yawning and stretching induced by transcranial application electromagnetic in Parkinson's disease.Sandyk R


Brief extracerebral applications of AC pulsed electromagnetic fields (ENIFs) in the picotesla range intensity have been reported beneficial in the symptornatic treatment of patients with multiple sclerosis (NIS) with either a relapsing-remitting or a chronic progressive course (Sandyk, 1992, 1994 a, b, 1995 a; Sandyk & Derpapas, 1993 a, b. Sandyk & lacono, 1993, 1994 a, b; Sandyk & Dann, 1994, 1995). This treatment modality is effective also in the symptomatic management of acute exacerbation of symptoms and has also been shown to stabilize the course of the disease (Sandyk & Derpapas, 1993 b; Sandyk & Dann, 1995; Sandyk, in press). The mechanisms by which administration of these EMFs improves symptoms of MS remain elusive. Application of DC EMFs of higher intensities has been shown to alter synaptic conductivity by modifying the release of neurotransmitters through an effect involving changes in transmembrane calcium flux (Bawin & Adey 1976; Jaffe et al., 1980; Blackman, 1988~ Rusovan & Kanje, 1992). In addition, exposure to EMFs has been shown to alter the circadian release of pineal melatonin (Welker et al., 1983; Semm, 1992) which, in turn, influences synaptic neurotransmission and immune mechanisms (Erlich & Apuzzo, 1985; Maestroni et al., 1987: Macstroni, 1993). Cerebral serotonin (5-HT) neurotransmission is diminislied in MS patients (Sonninen et aL, 197-3. Claveria et al., 1974; Davidson et al.. 1977) and since 5-HT is involved in motor, affective. autonomie and cognitive functions (Barasi & Roberts, 1973; Baumgarten & Lacherunayer, 1985; Jacobs, 1991, 1994: Jacobs & Fornal, 1993), its has been proposed that increased synaptic availability of 5-HT is related to the therapeutic efficacy of picotesla EMFs in MS (Saudyk 1993). Behavioral changes, which are observed in MS patients during the application of picotesla EMFs, provide additional insights concerning the biological effects of these magnetic fields in patients with MS.

CASE REPORT : This 48 car old right-handed woman developed in 1985 right-sided optic neuritis. One year later she experienced numbness in the her legs and was diagnosed with MS after a brain MRI scan showed numerous areas of demyelinating plaques in the subcortical white matter and periventricularly. In 1988 she began to experience increasing fatigue, difficulties with balance and bladder control with urinary frequency, constant pain in the lower back, intolerance to heat and progressive weakness with spasticity of her legs. In 1993 she began using, a walker for ambulation. In August of 1994 the patient began experimental treatment with EMFs. These fields were applied extracerebrally in a magnetically unshielded room using the Sandyk- Elcctroniagnetic Stimulator which emits an alternating current (AC) pulsed EMF of an amplitude of 7,5 picotesla. Since then she received two treatment sessions per week whereby a session was comprised of two successive applications each of 30 minutes duration separated by a 15 minute break. The frequency of stimulation was 2 Hz for the first treatment and 3 Hz for the second treatment using a sinusoidal wave in both treatments. On this regimen the patient experienced improvement in her balance vision, bladder control and fatigue with complete resolution ofthe pain in the lower back. In addition, she experienced, over the following two years, stabilization in the course of the disease.

Up until July of 1996 the patient experienced no behavioral changes during the application of EMFs with the exception of mild intermittent itching sensations in the face and scalp. In July of 1996 she had a major seizure related to an accidental overdose of 4-aminopyridine and vvas placed subsequently on phenytoin (200 mg/d). Her EMF treatment protocol was modified so that a treatment session included two successive applications each of 20 minutes duration separated hy an interval of 10 minutes employing, a 3Hz sinusoidal wave in the first treatment and a 4 Hz trapezoidal wave in the second treatment. Since that time her response to the application of EMFs has changed and for the first time she began to exhibit, during the treatment, frequent recurrent episodes of prolonged yawning. Careful observation revealed that these episodes of yawning always developed during fisrt second treatment following a period of at least 30 minutes from the onset of the treatment. At the beginning of the second treatment she exhibited brief and infrequent (1-2 yawns/minute) episodes of yawning, but with progression of the treatment yawning became increasingly more frequent (3-5 yawns/min) and prolonged with occasional yawns lasting up to 5 seconds. Yawning was associated with nuld itching sensations in the face and scalp and also with an urge to stretch the limbs and trunk. After the conclusion of treaunent with EMFs she continued to yawn, albeit less frequently, for an additional hour two hours. It is of interest that the patient reported that even though she was yawning frequently during the second treatment she felt mentally alert during and after termination of the treatment.

DISCUSSION : The physiological significance of yawning and the neuronal mechanisins triggering and coordinating its various components remain unclear (Urba-Holingren, 1977). It is thought that yawning and stretching reflect an evolutionary vestige of a behavior subserving arousal when attention is decreasing in the presence of danger (Serra et al., 1986). Frequent yawning has been mentioned as a symptom of CNS diseases. particularly in cases of frontal tumors, hypothalamic disease and encephalitis (Boshes, 1969; DeJong, 1979). ln rats yawning occurs shortly after the administration of smail doses dopamine receptor agonists such as apomorphine (Mogilnicka & Klimek, J977; Rollison et al., 1979; Yaniada & Furukawa, 1980; Mogilnicka et al., 1984; Serra et al., 1986; Szechtinan et al., 1988, Cooper et al., 1989) or following administration of physostigmine, a short-acting reversible, centrally active cholinesterase inhibitor which increases central choliner-gc activity (Urba-Holiiigren et al., 1977). There is also pharmacological evidence for serotonercic modulation of yawning (Urba-Holnigren et al., 1979) which is commonly associated with the state of drowsiness preceding sleep.

Yawning and stretching may also be elicited in experimental aninials and humans by intracranial or intrathecal injection of nanogram or microgram doses of the neuropeptides ACTH and alpha-MSH which exert direct effect ou the brain independent of their known endocrine effects (Ferrari, l958~ Ferrari et al., 1963; Gessa et al., 1967; Wood et al., l978; Bertolini & Gessa, 1981; O'Donohue & Dorsa, 1982). While yawning induced by doparninergic drugs emerges shortly after their administration, a lag of 25-30 minutes is always observed in experimental animals after intraventricular administration of ACTH/MSH peptides (O'Donohue & Dorsa, 1982; Argiolas & Gessa, 1987). Moreover, yawning induced by these peptides may persist for 1-2 hours (Ferrari, 1958; Gessa et al., 1967). It is thought that ACTH/MSH peptides induced yawning involves activation of cholinergic neurons since it is inhibited by atropine (Ferrari et al., 1963; Tonnaer et al., 1986). Others have suggested that oxytocin mediates the effects of ACTH/MSH peptides on yawning (Argiolas & Gessa, 1987).

A subset ofMS patients, usually women, exhibit episodes of recurrent yawning durin- application of picotesla EMFs. If is of note that recurrent episodes of yawnin- bas been observed in patients with Tourette's syndrome administered these EMFs (Sandyk, 1995 b) but is not seen in patients with other diagnostic categories treated with these EMFs such as Parkinson's disease, Alzheimer's disease, epilepsy, motor neuron disease, depression, and pain syndromes. In the majority of MS patients yawning appears with a time lag ranging from 30-40 minutes and may persist for over an hour after cessation of EMFs treatment. This patient characteristically began te, exhibit recurrent uncontrollable yawning behavior starting about 30 minutes after the initiation of treatment with EMFs. These episodes of' yawning, which were associated with a mental arousal. became more frequent and Ion-er with continued application of EMFs and persisted for about an hour after discontinuation of this treatment. This pattern of yawning behavior, which bas been observed in experimental animals and humans following intracerebral application of ACTH/MSH peptides, suggests that in MS patients application of'these EMFs may trigger the release of ACTH/MSH peptides \vhich have been identified throu,-hout the human brain with specific predilection to the hypothalamus. striatum, mesencephalic gray matter, amygdala and thalamus (Abrains et al., 1980: Kleber et al., 1980; Arai et aL, 1986). If validated by direct CSF measurements of these peptides prior to and after treatinent with EMFs. these findings are of'-reat importance as they may explain some of the biological mechanisms associated with the therapeutic benefits of these EMFs in patients with MS.

According to Gispen et al. (1986) ACTH/MSH peptides possess profound neurotrophic effects on peripheral and central nervous structures one example of which includes their beneficial effects in recovery froin peripheral nerve damage (Bijlsma et al., 1983). In addition, ACTH/MSH peptides enhance cerebral oxygen consumption and glucose utilization, stimulate RNA and protein synthesis, and increase acetylcholine turnover in the hippocampus (Gispen et al., 1986~ Wood et al., 1979; Botticelli & Wurtman, 1981). Their administration in experirriental animals and humans has been shown also to increase the arousal state in midhrainlimbic structures, enhance vigilance specifically to visual information, improve Icarning and memory functions particularly visual memory and participate in behavioral adaptation to stress (Miller et al., 1978; Bertolini & Gessa. 198 1 ~ O'Donohue & Dorsa, 1982: Gilad et al., 1985: Anderson, 1986). Other relevant biological effects of these peptides iiiclude facilitation ofsynaptic transmission in the spinal cord, modulation of brainsteni postural reflexes and increased endurance of the neuromuscular systein (Strand & Cayer, l975~ O'Donohue & Dorsa, l982~ Jacquet & Abranis, 1982; Strand et al., l973~ Strand & Cayer, 1975). Clinically, MSH peptides have been implicated in derrientia as CSF coucentrations of alpha-MSH are significantly decreased in patients with Alzheinier's disease as compared with aged-niatched controls (Facchinetti et al., 1984; Raincro et al., 1988: Anderson, 1986). Moreover, a significant coi-relation has been found between CSF concentrations of alpha-MSH and performance ou nonverbal-visual tasks in these patients (Berardi et ai., 1988). MS is associated with coniplex cognitive deficits and dernentia, which is characterized by predoininant impairirient of attention, incidental meniory, and psychoinotor function (Caine et al., 1986; Filley et al., 1989). The complex biological effects of' ACTH/MSH peptides and their widespread distribution in flic brain su-gests that these peptides contribute to the symptornatology of the disease. Application of picotesla EMFs may enhance the cerebral relcase of' these peptides which, throu,,h their neurotrophic effects, proinote recovery of symptoms of the disease.