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.
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