Initial Exploration of Pulsing Electromagnetic
Fields
(Diapulse) for Treatment of Migraine
|
| Richard A. Sherman,
PhD; Linda Robson, BA; Linda A. Marden, MD
From HEADACHE Journal, Volume 38, Number 3, March, 1998 |
Two studies were conducted during which 23
patients with chronic migraine were exposed to pulsing electromagnetic
fields over the inner thigh. In an open study, 11 subjects kept
a 2-week headache log before and after 2 to 3 weeks of exposure
to pulsing electromagnetic fields for i hour per day, 5 days
per week. The number of headaches per week decreased from 4.03
during the baseline period to 0.43 during the initial 2-week
follow-up period and to 0.14 during the extended follow-up,
which averaged 8.1 months. In a double-blind study, 9 subjects
kept a 3-week log of headache activity and were randomly assigned
to receive 2 weeks of real or placebo pulsing electromagnetic
field exposures as described above. They were subsequently switched
to 2 weeks of the other mode, after which they kept a final
3-week log. Three additional subjects in the blind study inadvertently
received half-power pulsing electromagnetic field exposures.
The 6 subjects exposed to the actual device first showed a change
in headache activity from 3.32 per week to 0.58 per week. The
3 subjects exposed to only half the dose showed no change in
headache activity. Large controlled studies should be performed
to determine whether this intervention is actually effective.
Key words: migraine headache, pulsed electromagnetic
fields, treatment
Abbreviation: PEMFs pulsing electromagnetic fields
(Headache 1998;38:208-213)
From the Services of Orthopedic Surgery (Dr. Sherman and
Ms. Robson) and Neurology (Dr. Marden), Madigan Army
Medical Center, Tacoma, Wash.
Presented in part at the Eighth World Congress on Pain (International
Association for the Study of Pain) in Vancouver, Canada, August,
1996.
The opinions and assertions contained in this manuscript are
the private views of the authors and are not to be construed
as official or as reflecting the views of the United States
Departments of Army or Defense.
Address all correspondence to LTC Richard A. Sherman, PhD, Department
of Clinical Investigation, Madigan Army Medical Center, Tacoma,
WA 98431.
Accepted for publication August 21, 1997.
Most adults in the United States have at least occasional headaches.
Headache is now the leading medical cause of lost days of work
and costs billions of dollars per year to treat. The Nuprin
Pain Report found that 157 million workdays per year were lost
due to this problem alone. Numerous surveys of the general population
have indicated that about 65% of males and 78% of females reported
having had at least one headache within the past year (1). About
half of men and 65% of women report having at least one headache
per month. About 30% of males and 44% of females reported that
these were severe, with about 15% having headaches severe enough
to affect daily activities. Among young adults, severe headaches
lasted about 6 hours for men and 8 hours for women with 8% of
men and 14% of women losing a day or more of work per month
due to headaches.2 About 6% of people attending civilian general
medical practices request treatment for headaches as their primary
reason for coming. About 7% of males and 17% of females reporting
headaches requested treatment within the previous year.3 A survey
of over 20 000 typical Americans (with a response rate of over
60%) showed that about 17% of women and 6% of men had at least
one headache per year which met the International Headache Society’s
criteria for migraine (eg, vomiting, unilateral or pulsatile
pain with photophobia or phonophobia, visual or sensory aura
before the headache). About 59% of females and 50% of males
reported at least one headache per month. These headaches caused
moderate to severe disability in about 47% of the females and
43% of the males.4
Pulsing electromagnetic fields (PEMFs) have been in use as therapeutic
modalities for at least 40 years. One of the well-recognized,
standard uses of PEME generators is in enhancing the rate of
healing of un-united fractures.5 The investigators were treating
a patient for such a knee condition when she mentioned a long
history of weekly migraine headaches with auras (classic migraines)
which had stopped shortly after PEMF treatment began. She reported
that the visual auras had continued to occur as usual, but the
subsequent headache did not follow. Her headaches did not return
for months following treatment. This effect led us to wonder
how exposure to PEMFs at the upper leg could have an effect
on headaches presumably centered in the head.
The PEMF units used in our clinic (Diapulse model D103; Diapulse,
lnc, New York, USA) are set to produce pulsed, high-frequency,
high peak power, electromagnetic energy at a frequency of 27.12
MHz in 65-microsecond bursts occurring in 600-pulse-per-second
sequences at 975 watts peak. This is sufficient power to light
a 60-waif bulb placed in the field. The field extends about
12 cm from the unit’s head in a conical pattern. The head
of the unit is placed just above the area to be exposed and
turned on for a set amount of time. Units from other manufacturers
differ slightly in a variety of ways such as the exact shape
of the wave, rise and fall times, and power. The device looks
like a floor-mounted hair drier from the 1950s, has a relatively
loud fan, a ticking timer, and sufficient knobs, lights, and
a meter, etc to be quite impressive. This impression has to
be considered when attempting to differentiate actual from placebo
effects.
Exposure to PEMFs of the type described above appears to result
in at least a temporary increase in peripheral blood flow. For
example, Erdman6 recorded peripheral blood flow from 20 normal
subjects using both a temperature probe and volumetric measurements
while they were being exposed to pulsing electromagnetic-generated
fields. He found a high correlation between the amount of energy
produced by the device and peripheral blood flow, with increases
beginning within about 8 minutes and plateauing by 35 minutes.
Pulse rate and rectal temperature did not change.
This relationship has been confirmed in basic studies of blood
flow in rabbit ears.7 Ross8 recently reviewed the basic science
and animal studies, as well as some of the clinical studies,
showing the effectiveness of PEMF generators in increasing blood
flow and wound healing. Cameron9 demonstrated increased rates
of healing in experimentally induced wounds in dogs. Goldin
et al10 found similar results among humans in a double-blind
study using changes in fibroblast concentration, fibrin fibers,
and collagen in the wound sites and in swelling. The increased
rate of wound healing was ascribed to increased blood flow.
Thus, it is very likely that exposure to this device does result
in increased peripheral blood flow, at least while exposure
is in progress.
Freedman has reviewed the effect of temperature biofeedback
on peripheral blood flow. Numerous double-blind studies with
5- to 15-year follow-up have demonstrated that training patients
with migraine to increase peripheral blood flow, through such
techniques as temperature biofeedback from the finger, results
in sustained decreases in all aspects of headache activity among
a large percentage of people who successfully learn the techniques.
Thus, whatever other mechanisms come into play, a technique,
which is aimed solely at increasing peripheral blood flow, frequently
results in decreased headache activity.
Synthesis of this background material led us to believe it was
possible that application of a PEME directed only to the thigh,
with its significant vascular supply, could produce sufficient
increases in peripheral blood flow to affect headache activity
for as long as the effect on blood flow continued. The following
explorations were attempts to begin testing that hypothesis. |
| METHODS |
Twenty-three patients (19 women, 4 men; mean
age 46.4 ±14.9 years, range 20 to 73 years) having multiyear
histories of headaches (mean 17.9 ± 9.9 years, range
2 to 40 years) were recruited from among the patients at a large
military medical center. All of the subjects met the normally
accepted criteria for migraine set out by the International
Headache Society.’ Several of the subjects had mixed headaches
because they reported headaches meeting both the criteria for
migraine and those for tension headache. After listening to
an explanation of the study, each was given a consent form approved
by the institutional review board of the center to read and
sign. Two different pilot studies, one open and one double blind,
placebo-controlled were performed. Demographic and diagnostic
data for the participants in the open study are presented in
Table 1, while those for participants in the controlled study
are presented in Table 2.
Open Study - Each of the 11 patients kept a 2-week diary of
headache activity before and after being exposed to PEMFs. Several
studies reviewed by Blanchard et al13 indicate that 2 weeks
should be sufficient time to determine the actual baseline level
of activity in this population. The structure of the open study
was essentially an "ABA" design with nonexposure periods
surrounding a single exposure period. Prophylactic medications
were stopped abruptly during the weekend between the end of
the 2-week initial log and the start of the treatment period.
Thus, any rebound effect should have developed by the end of
the treatment period and have been observed during the last
week of treatment or the 2 initial posttreatment weeks. During
the exposure period, patients were exposed to between 2 and
3 weeks of PEMF treatments for i hour per day, 5 days per week
at a power of 975 watts with 600 pulses per second. The PEMF
was applied to the medial thigh. Headache activity during treatment
was reported to the therapist every day. The PEMF unit utilized
in the study was described in the introduction. Additional follow-up
data beyond the 2-week "posttreatment" log period
were collected telephonically for all of the subjects,
Double-Blind Placebo-Controlled Study
Twelve subjects kept a 3-week log of headache activity and two
kept a 6-week log. They were then randomly assigned to receive
2 weeks of real or placebo PEMF exposures as described above.
The log was extended from 2 to either 3 or 6 weeks to insure
an adequate representation of baseline stability. Randomization
was performed by picking a sealed envelope from a basket. The
letter "A" or "B" was on a folded card inside
the envelope. This determined which device they were exposed
to for the first 2 weeks. The placebo machine was identical
to the functioning machine both in looks (lights, dials, etc)
and sounds (fan, timer noise, etc). The only difference was
that several crucial tubes had been removed so it produced no
field. As subjects could not sense the field, there was no way
for them to know which machine was actually functioning. The
machines were randomized by the senior author, who was not involved
in working with the subjects, so the therapist working with
the subjects was also unaware of which machine was which. At
the end of 2 weeks, the subjects were switched to 2 weeks of
the other device after which they kept a final 3-week log. Additional
follow-up data beyond the 3-week "post-treatment"
log period were collected telephonically and by a mail response
survey for all of the subjects. At the end of each 2-week exposure
period, each subject rated how likely they felt they had just
been in the real exposure period on a scale of 0 to 10 110 being
certain they received the real exposure).
During 7 weeks of this study, the machine, which was to provide
the actual exposure partially failed, so three subjects inadvertently
received half-power PEMF exposures for their 2 weeks of "actual"
exposure. This happened because the senior author, who was supposed
to calibrate the device twice per week, went on two trips and
forgot to calibrate the device for several weeks. As "Murphy’s
law" dictates, it was during this period that the device
partially failed and the signal strength was reduced by half.
The data were analyzed using repeated measures analyses of variance
to determine whether there was an overall difference in headache
activity between pretreatment, posttreatment, and follow-up
periods. Paired t tests were used to determine whether there
were differences between any two periods when the analysis of
variance was significant. The data met the entrance criteria
for the tests. Because very few people agreed to cross over
from actual to placebo exposure, we used a pretreatment-to-posttreatment
analysis rather than a cross-over analysis. |
RESULTS |
Open Study - The results for each individual
are presented in Table 1. The average number of headaches per
week decreased from 4.03 (± 2.02) during the 2-week pretreatment
baseline period to 0.43 (± 0.36) during the 2-week postexposure
period (statistically different at P=0.001; paired t=5.998 with
10 df). Follow-up ranged from 1 week to 14 months with a mean
of 8.1 months and a standard deviation of 3.09 months. The average
number of headaches continued to decrease during the long-term
follow-up period to an average of 0.14 (± 0.08) per week
(statistically different at P=0.001; paired t=5.77 with 9 df).
A one-way, repeated measures analysis of variance indicates
that there was an overall difference between the periods (P=0.0001,
F=31.21).
Before exposure, all 11 subjects took medications virtually
every time headaches occurred. They used an average of 3.1 medications
including Midrin®, Fiorinal®, Advil®, Toradol®,
Tylenol®, Imitrex®, Cafergot®, and propranolol.
After exposure, 8 had stopped using any medications at all,
1 had one visit to the emergency department where she was given
Toradol, 1 took Midrin several times, and i said she used Premarin®
several times.
Double-Blind Study
The results for each individual are presented in Table 2. For
the 6 patients who received actual exposure to PEMF first, the
average number of headaches per week decreased from 3.32 (±
1.40) during the 3-week pretreatment baseline period to 0.67
(± 0.26) during the exposure period (statistically different
at P=0.003; paired t=5.56 with 5 df). Follow-up ranged from
2 to 6 months with a mean of 2.94 months (± 1.29 months).
The average number of headaches during the long-term follow-up
period averaged 0.58 (± 0.80) per week (statistically
different at P=O.O01; paired t=7.81 with 5 df). A one-way, repeated
measures analysis of variance indicates that there was an overall
difference between the periods (P=0.0001, F=35.67).
Table 1.- Open Study: Patient Characteristics and Results
Migraine With Nonvisual Precursors or Auras
2-Week Log of No. of
Headaches per Week
Duration of
follow-up, mo, #
Age, Y
Headache
Headaches
Patient
Sex
History, Y
Pretreatment
Posttreatment per Week
The subjects receiving actual exposure for the first 2-week
period rated their certainty that they received the real treatment
as an average of 8.6 with 10 being certain of having had actual
exposure (three 8’s, two 9’s, and one 10). Only
one of them agreed to cross over to the placebo exposure period.
This person showed a decrease from 4.6 headaches per week during
the baseline to one per week during actual exposure, and then
an increase to two per week during placebo exposure, which was
sustained during follow-up. The three who received the placebo
for the first 2 weeks rated their certainty that they had been
exposed to actual PEMF as 0 (sure they did not receive actual
exposure). After being crossed over to the actual exposure,
these three subjects rated their certainty as 1, 5, and 7. The
three patients who were inadvertently exposed to half power
rated their certainty that they were receiving actual exposure
as 1 or 0 after both periods.
There were no statistically significant differences in headache
rates for the few subjects who did cross over from placebo to
actual exposure. They were 4, 3, and 3 during placebo exposure
and 5, 1, and 1.5 during the subsequent actual exposure (t=0.64
with 4 df P=0.557). The baseline to follow-up period (6, 4,
and 2.8 versus 6, 2, and 0) is also not significantly different
(t=0.63 with 4 df, P=0.561).
There was no significant difference between the baseline headache
rates of those who got actual exposure first and those who got
placebo exposure first (3.5, 2, 4.6, 5.3, 2, and 2.5 versus
6, 4, and 2.8 (t=.92 with 7 df; P=0.389). However, the headache
incidence rates during initial exposure were different for the
actual exposure first group (0.5, 0.5, 1, 1, and 5.5) than for
the placebo exposure first group (4, 3, and 3) (t= -9.88 with
7 df; P=0.00 1).
Table 2 - Double-Blind, Placebo-Controlled, Cross-Over Study:
Patient Characteristics & Results
Migraine With Nonvisual Precursor Symptoms
Age, Y Headache 3-Week
3-Week Long-term
follow-up, mo
Patient Sex
History, Y Baseline
Actual Placebo
Placebo Actual Follow-up
# of headaches/ week
1
63 F
20
06
-
-
4
5
6.5
3 – 6
2
33 F
08
03.5
0.5
Declined*
-
-
0.5
2.5 – 0.25
3
42 F
20
02
0.5
Declined
-
-
0
2.5 – 0.10
4
59 F
10
04.6
i
2
-
-
2
3 - 2
Migraine With Visual Aura Preceding Headache
Age, Y Headache 3-Week
3-Week Long-term follow-up,
mo
Patient Sex
History, Y Baseline Actual
Placebo Placebo
Actual Follow-up
# of headaches/ week
1
59 F
20
5.3
1
Declined
-
-
1
2.5 – 0.25
2
50 F
16
2
0.5
Declined
-
-
0
2 – 0.25
3
51 M
12
2.5
0.5
Declined
-
-
0
6 – 0.5
Modified Design With 6-Week Baseline
Age, Y Headache 3-Week
3-Week Long-term follow-up,
mo
Patient Sex
History, Y Baseline Actual
Placebo Placebo Actual
Follow-up # of headaches/ week
1
63 F
33
4
-
-
3
1
2
5 - 2
2
40 F
20
2.8
-
-
3
1.5
2
None
Half-Power Treatment With No Visual Aura Preceding Headache
Age, Y Headache 3-Week
3-Week Long-term follow-up, mo
Patient Sex
History, Y Baseline Actual
Placebo Placebo
Actual Follow-up # of headaches/
week
1
49 F
35
2.5
2.5
2.5
-
-
2.4
2 - 2.5
2
42 F
30
4
-
-
4
4
5
1 – 4.3
Half-Power Treatment With Visual Aura Preceding Headache
Age, Y Headache 3-Week
3-Week Long-term follow-up,
mo Patient Sex
History, Y Baseline Actual
Placebo Placebo Actual
Follow-up # of headaches/ week
1
48M
16
5
-
-
4
4
4.3
2 - 4.3
* = Declined to cross over. All values given as number of headaches
per week.
COMMENTSMost of the patients with a long history of vascular
migraine headache, not initiated by other problems, who were
exposed to adequate PEMFs showed a dramatic decrease in headache
activity during the weeks of exposure and for months afterwards.
It is possible that exposure to PEMFs did cause sufficient increase
in peripheral blood flow to affect headache activity. This increase
would have initiated some chain of psychophysiological events,
which actually caused the improvement. Of course, it is quite
possible that exposure to the fields induced a currently unrecognized
physiological effect, having nothing to do with blood flow,
which somehow resulted in decreased headache activity. Interestingly,
none of the patients who had aura preceding onset of their headaches
reported a change in aura activity. The usual headache simply
did not follow the aura.
The literature reviewed in the introduction shows considerable
evidence that the particular PEMF generator used in this study
has some ability to increase peripheral blood flow. The same
body of evidence does not seem to exist for the weaker, battery-powered
magnetic field generators, which do not pulse, nor for the permanent
magnets that people strap to themselves for a variety of reasons.
If the working hypothesis (that increased peripheral blood flow
has resulted in decreased headache activity) is correct, then
devices incapable of increasing peripheral blood flow to a similar
extent may not be effective. This is supported by the three
patients who received half the normal exposure not showing any
change in headache activity. Conversely, any device, which can
safely increase peripheral blood flow sufficiently, should be
equally efficacious. Pulsing electromagnetic field units may
produce increases in blood flow simply by heating the underlying
tissues14 rather than through any esoteric effects of their
fields, so it is possible that diathermy units could also produce
these effects.
It should be noted that the average number of headaches per
week among our participants is higher than that usually reported
by people with migraine. About half of our subjects had more
than four headaches per week while most surveys report far lower
rates.24’3 Thus, we may have been working with a more
complex population than usually encountered.
In spite of the impressive nature of the PEMF generator, the
investigators do not feel that the major effects were due to
placebo responses because (1) subjects in the placebo arm of
the study did not show decreases in headache activity, (2) the
participants each had multiyear histories of unsuccessful treatments
with numerous highly touted therapeutic approaches, (3) the
change in headache activity was much greater than would be anticipated
due to a placebo response, (4) the decrease in headache activity
has been maintained longer than the 6 months or so anticipated
for a placebo effect, and (5) the rebound effect from stopping
the prophylactic medicines should have hit sometime near the
end of "treatment" and would have overwhelmed any
placebo effect.
One of the staff who was responsible for exposing the subjects
to PEMFs was also responsible for gathering the postexposure
logs. As the results show that by the end of 2 weeks of exposure
subjects had little difficulty differentiating between the real
and placebo machines, it is possible that this staff person
also realized which was the placebo device. Strong support for
the study’s "double-blind" integrity having
been maintained, and thus avoiding a potential therapist expectation
effect, is provided by the lack of improvement shown by all
three patients who were accidentally exposed to half the normal
dose due to partial machine failure. The therapist had no way
to know that the "actual" machine had failed.
When we began these exploratory studies we had no idea that
the headaches would not return shortly after exposures stopped,
therefore, we used a cross-over design to help determine differences
between responses to an actual and a placebo device. During
the course of these studies, it became apparent that the headaches
did not return within a short enough time for a crossover design
to be effective because there was no opportunity for any effects
of the treatment to "wash-out" between the end of
exposure to one device and start of exposure to the other. Further
studies of this technique will require a parallel design.
Because of the powerful effects demonstrated in this trial,
it is worth performing a large paralel-group controlled study
to determine whether this intervention is actually effective
and longitudinal studies to determine whether inexpensive, wearable
pulsing magnetic field devices or other means of increasing
peripheral blood flow can be used to keep the headaches from
returning.
Acknowledgment:This study was entirely supported by the Clinical
Investigation activity within the US Army’s Medical Command.
However, the opinions and assertions contained in this manuscript
are the private views of the authors and are not to be construed
as official or as reflecting the views of the United States
Departments of Army or Defense. |
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