PEMF RESEARCH

Magnetic field deficiency syndrome.

Research of K. Nakagawa.
After evaluating more than 11,000 human subjects Japanese researcher K. Nakagawa concluded that a large part of Western civilization is suffering from a lack of magnetic field—an epidemic of magnetic field deficiency—caused by the natural weakening of the Earth’s magnetic field. (Nakagawa K. Japan Med J 1976; 2745, December 4.) It manifests itself as chronic tiredness, insomnia, back pain and headaches as well as a lack of energy.

Is it possible that fibromyalgia, chronic fatigue syndrome and other disease processes involving pain and fatigue are, in reality, magnetic field deficiency syndromes? Is it possible that “new illnesses” associated with modern society are due to a deficiency of exposure to the Earth’s magnetic field rather than some chemical or hormonal imbalance, deficit or overload? Do magnetic field deficiency syndromes exist?

Nakagawa has identified the fact that the human body requires sufficient levels of magnetic energy for optimal health. Our lifestyles, living quarters, modes of transportation and work environments are not conducive to receiving adequate exposure to the Earth’s field.


More research on PEMF:
http://onlinelibrary.wiley.com/enhanced/doi/10.1002/bem.21848/

Microsecond pulsed magnetic field improves efficacy of antifungal agents on pathogenic microorganisms Abstract

Control and treatment of the emerging filamentous and yeast fungal
diseases are of high priority in the biomedical field. This study
investigated the influence of the pulsed magnetic field combined with
common antifungal agents on the viability of various pathogenic fungi
such as Aspergillus fumigatus, Candida albicans, and Trychophyton
rubrum. Repetitive microsecond pulsed magnetic fields up to 6.1 T were
applied in the study. The synergistic effect of co-applying drugs and
magnetic treatment to different fungi species causing various human
mycoses showed the potential for more effective and less toxic therapy.
Bioelectromagnetics. 35:347–353, 2014. © 2014 Wiley Periodicals, Inc.

http://onlinelibrary.wiley.com/enhanced/doi/10.1002/bem.21832/
Pulsed electromagnetic fields (PEMF) promote early wound healing and
myofibroblast proliferation in diabetic rats

http://onlinelibrary.wiley.com/enhanced/doi/10.1002/bem.21822/
Extremely low frequncy non-invasive electromagnetic fields have shown
beneficial influence for cartilage regeneration

http://onlinelibrary.wiley.com/doi/10.1002/bem.21770/abstract
Pulsed electromagnetic fields on postmenopausal osteoporosis in
southwest China: A randomized, active-controlled clinical trial
Alendronate-

Indications and Usage

Treatment of osteoporosis in postmenopausal women; prevention of
osteoporosis in postmenopausal women at risk of developing osteoporosis;
increase bone mass in men; treatment of glucocorticoid-induced
osteoporosis in men and women; treatment of Paget disease of the bone


This study examined the effects of constant magnetic fields in patients
with fractures. Results showed that magnetic exposure reduced pain and
the onset of edema shortly after trauma.

G.B. Gromak & G.A. Lacis, “Evaluations of the Efficacy of Using a
Constant Magnetic Field in Treatment of Patients with Traumas,” in I.
Detlav, (ed.), Electromagnetic Therapy of Injuries and Diseases of the
Support- Motor Apparatus. International Collection of Papers, Riga,
Latvia: Riga Medical Institute, 1987, . 88-95 – See more at:
http://www.wellnessdevices.net/pemf-and-fractures.html#sthash.0Q458NAe.dpuf

This review article notes that the use of pulsed electromagnetic fields
began in 1974, and that 250,000 nonunion patients have received the
treatment since. The author argues that success rates are comparable to
those of bone grafting, and that PEMF treatment is more cost-effective
and free of side effects. The FDA approved PEMF use in 1982, although it
remains widely unused due to physician misunderstanding and lack of
knowledge concerning the treatment.

A. Bassett, “Therapeutic Uses of Electric and Magnetic Fields in
Orthopedics,& quot; in D.O. Carpenter & S. Ayrapetyan, (eds.),
Biological Effects of Electric and Magnetic Fields. Volume II:
beneficial and Harmful Effects, San Diego: Academic Press, 1994, .
13-48.
– See more at:
http://www.wellnessdevices.net/pemf-and-fractures.html#sthash.0Q458NAe.dpuf

http://en.wikipedia.org/wiki/Pulsed_Electromagnetic_Field_Therapy
http://en.wikipedia.org/wiki/Membrane_potential

Tumours

F: Daudert, physician in Bad Aibiling at Rosenheim: Second International Congress for Energy Medicine in Seefeld 1998. People with the following criteria were used for this study: advanced cancer, people who had exhausted the usual resources of traditional medicine and people with greatly reduced immune competent cells (less than 50%). More than 300 patients with epithelial tumors were divided into two groups and treated one of the two groups additionally with PEMF. The treatment was otherwise identical for both groups (vitamin and mineral infusions, immune stimulation, oxygen flooding therapy). The treatment was administered for a period of two weeks with a repetition after three months. Blood tests, which were analysed by an independent clinical laboratory, yielded comparable values between the two groups. It was found that the buildup of the immune system could be significantly accelerated with PEMF.

Biological effects of PEMF (pulsing electromagnetic field): an attempt to modify cell resistance to anticancer agents.
Pulsing Electromagnetic Field (PEMF) effects lead to a modification of the multidrug resistance (MDR) of cells in vitro and in vivo.

The murine leukemic doxorubicin-resistant cell line, P388/Dx, subjected to PEMF irradiation in vitro, showed a significant difference in thymidine incorporation when the concentration of doxorubicin reached a level of 1 microgram/mL, which corresponds to the inhibition dose 50 (ID50). The human lymphoblastic leukemia vinblastine-resistant cell line, CEM/VLB100, also showed a significant modification under the same experimental conditions at the in vitro ID50 corresponding to a vinblastine concentration of 100 ng/mL.

BDF1 mice transplanted with P388/Dx cells also had an increase in their life span when doxorubicin was injected intraperitoneally in fractionated doses, while being subjected to PEMF irradiation.

Pasquinelli, P., J Environ Pathol Toxicol Oncol 1993 Oct-Dec;12(4):193-7

Input – 220VAC 50/60 Hz 1 Kw Fuse 6 amps
Output – Complex (0.3-250 MHz) pulse train
Average field power – 60 watts
Pulse width – <1 microsecond Pulse repetition rate - 2-5 pulses per second Applicator (probe) - 15 cm diameter indiction coil Average induced voltage - 18 volts within 8 cm Body Penetration - 15cm at ful power Attenuation - 1 /D3(D = distance) Overall dimensions - 44.5"h, 21.5"w, 20"d Net weight - Approx. 150 lb (68 Kilo) Mounting - Four 3" castor wheels Treatment timer - 5 minutes max Ventilation - Chassis fan Interference suppression EMI shielded NOTE: Ozone produced in plasma chamber must be vented to outside with - 2" dia. flexible hose. USAGE Simplicity of usage is a major feature of the IMI, as magnetic pulses pass through all matter except certain metals. The applicator probe is held flat against the clothing or skin of the area to be treated, and the start button pressed. The device will begin emitting several popping noises per second (from the arc in the plasma chamber that initiates each pulse) until the 5-minute treatment timer turns it off. if desired, or if the probe is moved to another location, the start button will initiate another 5minute operation for up to four cycles, depending on the treatment protocol for a particular clinical condition. It is noted that in over 100,000 IMI treatments for a variety of medical problems, no adverse effects or incidents have been reported in patients or in technicians exposed to IMI pulses for many hundreds of hours a year. THEORY OF OPERATION Normal Cells All of the many types of living cells that make up the tissues and organs of the body are tiny electrochemical units. They are powered by a "battery* that is continually recharged by the cells' metabolic chemistry in a closed loop of biological energy. We are concerned here with that battery, which consists of the membrane that surrounds the cell. The electrical charge, or voltage across the membrane of a normal, healthy cell varies from about 70 to 100 millivolts; this is called the Transmembrane Potential, or TIVIP. When a cell is poisoned, damaged, deprived of nutrients or infected, energy is lost in fighting the problem and the TIVIP falls to a level where the cell loses its vitality and either struggles to heal itself or dies. Medical literature over the past few decades offers ample proof that the induction of tiny currents of electricity is remarkably effective in healing, regenerating and revitalizing cells damaged by trauma. Many of the earlier techniques developed from this research involved implanting fine electrodes at the boundaries of the injured tissue, and causing a tiny current to flow through the affected area from low-voltage batteries. Subsequently, it was found that these healing currents could also be induced by relatively weak magnetic devices placed close to the trauma and kept there for days or weeks. Return to:| Top Thus the healing effects of microcurrents generated or induced in the conductive pathways of the body have been well established and this application is an accepted clinical procedure. There remained for Professor Pappas to discover that a weak pulsed magnetic field, hundreds of times faster than had ever been used, applied for a millionth of a second at a time within a frequency spectrum never before used in medical devices, could accomplish much more within a few minutes what other stronger magnetic induction devices required days or weeks to affect--and to do so with much more efficient and far-reaching therapeutic results. In short, the IMI is capable of raising the TMP of sick or damaged cells into a normal range, thus restoring their bioenergy, facilitating the exchange of potassium and sodium ions (the Na/K pump) and restoring their normal rate of production of ATP which fuels the entire process. Normal healthy cells are not adversely affected by IMI because, as in recharging any battery, the membrane-batteries of living cells in particularly will not accept an overcharge. Let us consider the action of the IMI in electrical terms. The massive surge of current circulating in the applicator loop, which acts as an antenna, generates a field of complex radiofrequency energy energy that is "broadcast" outward in all directions normal to the direction of current flow in the loop. The quickly expanding and collapsing pulse of magnetic energy easily penetrates biological tissues. When a changing magnetic field intersects a conductor in a closed circuit, it generates a current in the conductor; this is the basic principle on which all rotary electric generators and alternators operate. The expanding and contracting magnetic component of the pulse causes current to flow in the many conductive paths of the body, including nerve fibers, blood vessels (blood serum is electrically conductive) and the fluid bathing the cells. As the magnetic field expands through the living tissue, it induces electron flow, or current in one direction; as it collapses, the direction is reversed. Electrons always flow from negative (cathode) to positive (anode) potential. The membrane itself is a dielectric that could be compared to a capacitor. Its electrical charge is positive on the outer surface, negative on the inner surface. Therefore such induced current polarized to push ions toward the positive outside of the cell membrane are blocked just as no current will flow when the positive terminals of two batteries are connected together. Conversely, current flowing away from the membrane will pull electrons away from it, and cause more electrons or negative ions to pile up on its interior surface, thus incrementally increasing the charge, or potential across the membrane and driving the TMP up towards a normal, healthy value for that cell. This is one reason why the IMI is so quick and effective in helping damaged cells heal. Also, although it produces no heat in the tissue, for reasons that cannot yet be presented here it appears to increase the blood circulation around damaged tissue. This is important, as increasing the supplies of nutrients is also an effective aid to cell repair; this is particularly true in trauma where circulation has been impaired by crushed or severed blood vessels or the inflarnation and swelling that compress capillaries, blocking flow to both the injured and uninjured cells. Put in terms of physical chemistry, rather than biological terms, another parallel phenomenon appears to occur: the acceleration of adencisine triphosphate (ATP) synthesis and other aspects of the cell's biochemical anabolism. The electrons drawn to the inner membrane by elevating the TMP increase the ionic charge in the interior. This raises the internal degrees of freedom at a molecular level, catalyzing dormant biochemical reactions that would not otherwise proceed as quickly due to lack of available energy. Entropy is reduced and the cell's metabolic rate increased, enabling the cell to heal itself and attain an optimum functional level. Return to:| Top Cancer Cells Cancer cells grow faster, divide and multiply much more rapidly than normal cells. As with all living cells, once their TMP falls into a critical low value, mitosis is triggered and the cell divides into two identical copies. When the magnetic induction action of the IMI prevents a drop in the TMP to that critical mitosis-trigger level, the fastgrowing cancer cell cannot divide and continues to grow larger until death occcurs. It is clear that as a cancer cell grows at an uncontrolled rate without dividing, the membrane is stretched thinner and thinner. When the ratio of volume to surface area becomes too large, the membrane is unable to absorb enough nutrients to support the bulk of the cell and starvation will result in cell death. There are several theories about what happens to bring about cell death under these conditions; some or all of these may apply to different types of cancer cells. Soft, harmless, electromagnetic treatment of cancer is quite new to medical science, and there are still new facts to be discovered. But research continues as new tools are developed to explore phenomena at the microscopic levels of the molecule and the cell. Bjorn Nordenstrom, a predminent Swedish scientist has found that cells of cancers he has successfully treated with electrotherapy appear to become dehydrated and die. He used an invasive surgical procedure, implanting electrodes in the tumor to generate the microcurrents that the IMI appears to create non-invasively by magnetic induction. His basic techniques were adopted in China where, from 1988 to 1993 over 4,000 cases of advanced malignancy were treated. Of 2516 carcinoma cases in patients over 50 years old, a 78% favorable response rate was reported. Dr. C.K. Chou, an American cancer researcher and his colleagues have found that these same microcurrents alter the pH of the cancer cell and alter its DNA so that it cannot reproduce. In the special cases of HIV and hepatitis infections, repeated experiments have shown that when the infected blood is treated in vitro with 50 to 100 microamperes of current, it appears to be virtually free of these viruses. This is an exciting discovery as it suggests that the same phenomenon may occur in the body ana raises the possibility that when an IMI device can be designed large and powerful enough to scan or cover tne whole body in a single treatment, these and perhaps other viral infections could be successfully conquered. Another important aspect of the thinning membrane of a growing cancer cell is that it becomes more porous. This appears to have two significant results. Anticancer antibodies of the immune system can more easily penetrate the membrane to attack the cell. Also, when electromagnetic fields are applied to the cancer, a phenomenon known as Electroporosis develops; this permits certain pharmaceuticals that have proven effective in chemotherapy to penetrate the membrane more quickly and easily--allowing a significant reduction in the dosage of chemicals that may have harmful side effects. Bjorn Nordenstrom, a predminent Swedish scientist has found that cells of cancers he has successfully treated with electrotherapy appear to become dehydrated and die. He used an invasive surgical procedure, implanting electrodes in the tumor to generate the microcurrents that the IMI appears to create non-invasively by magnetic induction. His basic techniques were adopted in China where, from 1988 to 1993 over 4,000 cases of advanced malignancy were treated. Of 2516 carcinoma cases in patients over 50 years old, a 78% favorable response rate was reported. Dr. C.K. Chou, an American cancer researcher and his colleagues have found that these same microcurrents alter the pH of the cancer cell and alter its DNA so that it cannot reproduce. Cancer & Chemotherapy Effect of magnetic fields on human and rodent cancer cell survival Use of artificial magnetic field for rehabilitation of children with malignant tumors Antitumor effect: local hyperthermia using dextran magnetite complex in hamster tongue carcinoma Clinical study of static magnetic field combined with anti-neoplastic chemotherapy in treatment of human malignancy Targeting therapy of magnetic doxorubicin liposome in nude mice bearing colon cancer Heat shock protein gene therapy combined with hyperthermia using magnetic nanoparticles Investigation on Tc tuned nano particles of magnetic oxides for hyperthermia applications Antitumor effects of combined therapy of recombinant heat shock protein 70 and hyperthermia using magnetic nanoparticles Significant differences in the effects of magnetic field exposure on mammary carcinogenesis in rats Regional Therapy with a Magnetic Targeted Carrier Bound to Doxorubicin Principles of magnetodynamic chemotherapy Systemic chemotherapy with magnetic liposomal doxorubicin and a dipole external electromagnet -------------------------------------------------------------------------------- Effect of magnetic fields on human and rodent cancer cell survival. Tata, D., Vanhoutten, N., Brook, C., &TrItton T. In a laboratory study, several rodent and human cancer cell types were exposed to permanent magnetic fields for one hour to determine what percent of the cells would survive compared to unexposed cells. The permanent magnetic field was extremely strong (11.6 Tesla = 116,000 gauss) and was generated by sophisticated equipment. Some of the surviving cell fractions included 25% for human breast carcinoma, 40% for human ovarian carcinoma, and 4% for human mouth carcinoma. Non-Invasive permanent magnetic field modality induces lethal effects on several rodent and human cancers. In Vitro. Proceedings of the American Association for Cancer Research, 1994; 35, 386. Go to top -------------------------------------------------------------------------------- Use of artificial magnetic field for rehabilitation of children with malignant tumors. Kiselev AV, Grushina TI. N.N. Blokhin Center for Oncology Research, Russian Academy of Medical Sciences, Moscow. Local complications of standard intravenous injections for chemotherapy and due to error of administration were compared in 400 patients (200 of them children) and general wound pathologies described. Treatment for wounds included two modalities: standard medication and alternating or pulsating magnetic field. Magnetic therapy proved highly effective: wound healing was 3-3.5 times faster while duration of treatment--2-3 times shorter than in standard procedure. Clinically-verified partial adhesion-related intestinal obstruction was eliminated by magnetic procedure in 18 children after combined treatment for lymphosarcoma involving the ileum. Vopr Onkol. 2000;46(4):469-72. Go to top -------------------------------------------------------------------------------- Antitumor effect of new local hyperthermia using dextran magnetite complex in hamster tongue carcinoma. Wada S, Tazawa K, Furuta I, Nagae H. Department oqf Dentistry and Oral Surgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan. swada-tym@umin.ac.jp OBJECTIVE: This study was performed to clarify the usefulness of Dextran magnetite (DM) for the oral cancer hyperthermia. METHODS: Tumors were induced in golden hamster tongue by 9,10-dimethyl 1-1,2-benzanthracene (DMBA) application. DM suspension was locally injected into the tumor-bearing tongue and tongues were heated up to 43.0-45.0 degrees C, by AC magnetic field of 500 kHz. RESULTS: The average time taken for the temperature to rise to 43.0 degrees C or above was 162 s (n = 17) at the margin of the tumor and 420 s (n = 17) at the center of the tumor. According to the tumor volume, the time required for an increase in the central temperature of tumor to 43.0 degrees C tended to be prolonged. Both temperatures could be maintained at approximately 43.0-45.0 degrees C for 30 min. The inhibition of the growth of tongue carcinoma in the four-time heating group was significantly greater than in the control group (P < 0.01). Moreover, the survival rate was significantly higher in the heated groups than in the control group (P < 0.01). Histological examination revealed a brown uniform DM accumulation at the stroma in the margin of the tumors. Many of tumor cells disappeared at the site adjacent to this accumulation. CONCLUSION: These results strongly suggest the usefulness of this local hyperthermic system in the oral region that is accessible to this treatment. Oral Dis. 2003 Jul;9(4):218-23. Go to top -------------------------------------------------------------------------------- Phase I clinical study of a static magnetic field combined with anti-neoplastic chemotherapy in the treatment of human malignancy: initial safety and toxicity data. Salvatore JR, Harrington J, Kummet T. Division of Hematology-Oncology, Carl T Hayden VA Medical Center, Phoenix, Arizona 85012, USA. joseph.salvatore@med.va.gov We have completed the lowest level of exposure in a Phase I study, designed to establish the safety and toxicity of the combination of a static magnetic field (SMF) and antineoplastic chemotherapy in patients with advanced malignancy. The SMF application is carefully controlled by applying the magnet to the patient only in our clinic during chemotherapy administration. No increase in the severity of chemotherapy toxicity as measured by white blood cell count and platelet count was seen in the participants exposed to SMF compared to the historical control subjects. These data have permitted the next group of subjects to be treated at the next dose level. Published 2003 Wiley-Liss, Inc. Bioelectromagnetics. 2003 Oct;24(7):524-7. Go to top -------------------------------------------------------------------------------- Targeting therapy of magnetic doxorubicin liposome in nude mice bearing colon cancer. Zhou PH, Yao LQ, Qin XY, Shen XZ, Liu YS, Lu WY, Yao M. Zhongshan Hospital, Fudan University, Shanghai 200032, China. OBJECTIVE: To investigate the effect of magnetic doxorubicin liposome (MDL) in the targeting treatment of nude mice bearing colon cancer. METHODS: Human colon cancer line LoVo cells were implanted hypodermically into nude mouse. Two weeks after the mouse was killed and the tumor was taken out and cut into small pieces to be retransplanted into nude mice so as to establish an experimental model. MDL was prepared by reverse-phase evaporation method. The particle size and structure of MDL were evaluated. Eighteen nude mice with colon cancer were divided into 3 groups of 3 mice: free DOX group, MDL (-) group (no magnetic field was added to the tumor surface), and MDL (+) group (magnetic field with the strength of 4 500 G was added). DOX of the dosage of 5 mg/kg was injected through the caudal vein in these 3 groups. Then the mice were killed 30 minutes after. Fluorescence spectrophotometry was used to examine the concentrations of DOX in the tissues and plasma. Another 36 nude mice with colon cancer were divided into 6 groups of 6 mice: normal saline group (as controls), DOX group, blank liposome group, magnetic liposome group, MDL (-) group (non-magnetic alloy was implanted into the tumor), and MDL (+) group (rare earth magnet was implanted into the tumor). The body weight, longest diameter of tumor, and short diameter vertical to the longest diameter were calculated regularly. The mice were killed 11 days after. The tumors were taken out to undergo staining and light microscopy. Flow cytometry was used to examine the apoptosis of tumor cells. RESULTS: The particle size of MDL was 230 nm and the magnetic particles (Fe(3)O(4)) were evenly distributed within the liposome. The DOX concentration in tumor tissue of the MDL (+) group was remarkably higher than those of the DOX and MDL (-) groups (both P < 0.05). The DOX concentration in heart and kidney of the DOX group were higher than those of the other 2 groups, and the plasma DOX concentrations of the DOX group was significantly lower than those of the other groups (all P < 0.05). The growth speed of tumor in the MDL (+) group was significantly lower, and the tumor weight was significantly less than in other groups. CONCLUSION: Magnetic doxorubicin liposome, as a carrier of anticancer drug, has a good targeting function toward the magnetite and has a significant anticancer effect. Zhonghua Yi Xue Za Zhi. 2003 Dec;83(23):2073-6. Go to top -------------------------------------------------------------------------------- Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles. Ito A, Matsuoka F, Honda H, Kobayashi T. Department of Biotechnology, School of Engineering, Nagoya University, Nagoya 464-8603, Japan. Heat shock proteins (HSPs) are recognized as significant participants in immune reactions. We previously reported that expression of HSP70 in response to hyperthermia, produced using our original magnetite cationic liposomes (MCLs), induces antitumor immunity. In the present study, we examine whether the antitumor immunity induced by hyperthermia is enhanced by hsp70 gene transfer. A human hsp70 gene mediated by cationic liposomes was injected into a B16 melanoma nodule in C57BL/6 mice in situ. At 24 hours after the injection of the hsp70 gene, MCLs were injected into melanoma nodules in C57BL/6 mice, which were subjected to an alternating magnetic field for 30 minutes. The temperature at the tumor reached 43 degrees C and was maintained by controlling the magnetic field intensity. The combined treatment strongly arrested tumor growth over a 30-day period, and complete regression of tumors was observed in 30% (3/10) of mice. Systemic antitumor immunity was induced in the cured mice. This study demonstrates that this novel therapeutic strategy combining the use of hsp70 gene therapy and hyperthermia using MCLs may be applicable to patients with advanced malignancies. Cancer Gene Ther. 2003 Dec; 10(12): 918-25. Go to top -------------------------------------------------------------------------------- Investigation on T_c tuned nano particles of magnetic oxides for hyperthermia applications. Giri J, Ray A, Dasgupta S, Datta D, Bahadur D. Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology, Powai, Mumbai-400076, India. Superparamagnetic as well as fine ferrimagnetic particles such as Fe_{3}O_{4}, have been extensively used in magnetic field induced localized hyperthermia for the treatment of cancer. The magnetic materials with Curie temperature (T_c) between 42 and 50 degrees C, with sufficient biocompatibility are the best candidates for effective treatment such that during therapy it acts as in vivo temperature control switch and thus over heating could be avoided. Ultrafine particles of substituted ferrite Co_{1-a}Zn_{a}Fe_{2}O_{4} and substituted yttrium-iron garnet Y_{3}Fe_{5-x}Al_{x}O_{12} have been prepared through microwave refluxing and citrate-gel route respectively. Single-phase compounds were obtained with particle size below 100 nm. In order to make these magnetic nano particles biocompatible, we have attempted to coat these above said composition by alumina. The coating of alumina was done by hydrolysis method. The coating of hydrous aluminium oxide has been done over the magnetic particles by aging the preformed solid particles in the solution of aluminium sulfate and formamide at elevated temperatures. In vitro study is carried out to verify the innocuousness of coated materials towards cells. In vitro biocompatibility study has been carried out by cell culture method for a period of three days using human WBC cell lines. Study of cell counts and SEM images indicates the cells viability/growth. The in vitro experiments show that the coated materials are biocompatible. Biomed Mater Eng. 2003;13(4):387-399. Go to top -------------------------------------------------------------------------------- Antitumor effects of combined therapy of recombinant heat shock protein 70 and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma. Ito A, Matsuoka F, Honda H, Kobayashi T. Department of Biotechnology, School of Engineering, Nagoya University, Nagoya 464-8603, Japan. Heat shock proteins (HSPs) are recognized as significant participants in cancer immunity. We previously reported that HSP70 expression following hyperthermia using magnetic nanoparticles induces antitumor immunity. In the present study, we examine whether the antitumor immunity induced by hyperthermia is enhanced by administration of recombinant HSP70 protein into the tumor in situ. Hyperthermia was conducted using our original magnetite cationic liposomes (MCLs), which have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis loss. MCLs and recombinant mouse HSP70 (rmHSP70) were injected into melanoma nodules in C57BL/6 mice, which were subjected to AMF for 30 min. Temperature within the tumor reached 43 degrees C and was maintained by controlling the magnetic field intensity. The combined treatment strongly inhibited tumor growth over a 30-day period and complete regression of tumors was observed in 20% (2/10) of mice. It was also found that systemic antitumor immunity was induced in the cured mice. This study suggests that novel combined therapy using exogenous HSP70 and hyperthermia has great potential in cancer treatment. Cancer Immunol Immunother. 2004 Jan;53(1):26-32. Epub 2003 Oct 09. Go to top -------------------------------------------------------------------------------- Significant differences in the effects of magnetic field exposure on 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in two substrains of Sprague-Dawley rats. Fedrowitz M, Kamino K, Loscher W. Department of Pharmacology, Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany. We have shown previously (S. Thun-Battersby et al., Cancer Res., 59: 3627-3633, 1999) that power-line frequency (50-Hz) magnetic fields (MFs) at micro T-flux densities enhance mammary gland tumor development and growth in the 7,12-dimethylbenz(a)anthracene (DMBA) model of breast cancer in female Sprague-Dawley (SD) rats. We also demonstrated that MF exposure results in an enhanced proliferative activity of the mammary epithelium of SD rats (M. Fedrowitz et al., Cancer Res., 62: 1356-1363, 2002), which is a likely explanation for the cocarcinogenic or tumor-promoting effects of MF exposure in the DMBA model. However, in contrast with our data, in a similar study conducted by Battelle in the United States, no evidence for a cocarcinogenic or tumor-promoting effect of MF exposure was found in the DMBA model in SD rats (L. E. Anderson et al., Carcinogenesis, 20: 1615-1620, 1999). Probably the most important difference between our and the Battelle studies was the use of different substrains of SD rats; the United States rats were much more susceptible to DMBA than the rats used in our studies. This prompted us to compare different substrains of SD outbred rats in our laboratory in respect to MF effects on cell proliferation in the mammary gland, susceptibility to DMBA-induced mammary cancer, and MF effects on mammary tumor development and growth in the DMBA model. The SD substrain (termed "SD1") used in all of our previous studies was considered MF-sensitive and used for comparison with another substrain ("SD2") obtained from the same breeder. In contrast with SD1 rats, no enhanced cell proliferation was determined after MF exposure in SD2 rats. MF exposure significantly increased mammary tumor development and growth in SD1 but not SD2 rats. These data indicate that the genetic background plays a pivotal role in effects of MF exposure. Different strains or substrains of rats may serve to evaluate the genetic factors underlying sensitivity to cocarcinogenic or tumor-promoting effects of MF exposure. Cancer Res. 2004 Jan 1;64(1):243-51. Go to top -------------------------------------------------------------------------------- Hepatocellular Carcinoma: Regional Therapy with a Magnetic Targeted Carrier Bound to Doxorubicin in a Dual MR Imaging / Conventional Angiography Suite--Initial Experience with Four Patients. Wilson MW, Kerlan RK Jr, Fidelman NA, Venook AP, LaBerge JM, Koda J, Gordon RL. Departments of Radiology and Medicine, University of California, San Francisco, 505 Parnassus Avenue, Room M-361, San Francisco, CA 94143. Four patients with inoperable hepatocellular carcinoma were treated with a magnetic targeted carrier bound to doxorubicin (MTC-DOX) by using a joint magnetic resonance (MR) imaging/conventional angiography system consisting of a 1.5-T short-bore magnet connected to a C-arm angiography unit by a sliding tabletop. Selective transcatheter delivery of the MTC-DOX to the hepatic artery was monitored by using intraprocedural MR imaging, and interim catheter manipulation was performed with fluoroscopic guidance to optimize agent delivery to the tumor and minimize delivery to normal tissue. The final fraction of treated tumor volume ranged from 0.64 to 0.91. The fraction of affected normal liver volume ranged from 0.07 to 0.30. The dual MR imaging/conventional angiography system shows promise for directing magnetically targeted tumor therapies. Copyright RSNA, 2004 Radiology. 2004 Jan;230(1):287-93. Go to top -------------------------------------------------------------------------------- Principles of magnetodynamic chemotherapy. Babincova M, Leszczynska D, Sourivong P, Babinec P, Leszczynski J. Department of Biophysics and Chemical Physics, Comenius University, Mlynska dolina F1, Bratislava 842 48, Slovakia. Basic principles of a novel method of cancer treatment are explained. Method is based on the thermal activation of an inactive prodrug encapsulated in magnetoliposomes via Neel and Brown effects of inductive heating of subdomain superparamagnetic particles to sufficiently high temperatures. This principle may be combined with targeted drug delivery (using constant magnetic field) and controlled release (using high-frequency magnetic field) of an activated drug entrapped in magnetoliposomes. Using this method drug may be applied very selectively in the particular site of organism and this procedure may be repeated several times using e.g. stealth magnetoliposomes which are circulating in a blood-stream for several days. Moreover the magnetoliposomes concentrated by external constant magnetic field in tumor vasculature may lead to embolic lesions and necrosis of a tumor body and further the heat produced for thermal activation of a drug enhances the effect of chemotherapy by local hyperthermic treatment of neoplastic cells. Med Hypotheses. 2004 Mar;62(3):375-7. Go to top -------------------------------------------------------------------------------- Evaluation of systemic chemotherapy with magnetic liposomal doxorubicin and a dipole external electromagnet. Nobuto H, Sugita T, Kubo T, Shimose S, Yasunaga Y, Murakami T, Ochi M. Department of Orthopedic Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. The development of an active drug delivery system is an attractive approach to increase the targetability of anticancer agents. In the present study, we examined the efficiency of systemic chemotherapy with small magnetic liposomes containing doxorubicin (magnetic DOX liposomes) and an externally applied electromagnetic force in osteosarcoma-bearing hamsters. Syrian male hamsters inoculated with osteosarcoma, OS515, in the limb were studied 7 days after inoculation. The efficiency of this system was evaluated by measuring the tissue distribution and tumor-suppressing effects of DOX on primary tumor growth and lung metastases. A DC dipole electromagnet was used, and the hamster's tumor-bearing limb was placed between 2 poles after the i.v. administration of liposomes. The dose of DOX and the magnetic field strength were fixed at 5 mg/kg and 0.4 T, respectively. Administration of magnetic DOX liposomes followed by 60 min application of magnetic field produced a 3- to 4-fold higher maximum DOX concentration in the tumor. This newly designed systemic chemotherapy significantly suppressed primary tumor growth for at least 2 weeks, though other DOX treatments also suppressed compared to control. Histologic examination confirmed a greater antitumor effect of this systemic chemotherapy compared to standard methods. In addition, this approach significantly suppressed lung metastases measured at 3 weeks posttreatment. These results suggest that this systemic chemotherapy can effectively reduce primary tumor growth and suppress lung metastasis due to increased targeting of DOX. Such targeted drug delivery for anticancer agents would provide clinical advantages compared to current methods. Copyright 2004 Wiley-Liss, Inc. Int J Cancer. 2004 Apr 20;109(4):627-35. - *Source: http://altered-states.net/barry/newsletter203/pemfcancer.htm

Magnetic Therapy and Parkinson’s Disease; a pulsed magnetic therapy research bibliography.
Peer reviewed pulsed magnetic therapy research studying effects of non-invasive pulsed electromagnetic stimulation in Parkinson’s disease is presented.

These studies prove many non-invasive, pulsed electromagnetic field therapies provide beneficial effects while significantly reducing some symptoms of Parkinson’s disease. Unlike electroconvolsive therapy (ECT), these types of therapy lack detrimental side effects, expected or unexpected adverse reactions.

Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson’s disease.

Ikeguchi M, Touge T, Nishiyama Y, Takeuchi H, Kuriyama S, Ohkawa M.

Third Department of Internal Medicine, Kagawa Medical University, 1750-1, Ikenobe, Miki-cho Kita-gun, Kagawa, 761-0793, Japan. mag@kms.ac.jp

We studied the effects of 0.2 Hz repetitive transcranial magnetic stimulation (rTMS) successively performed 6 times for 2 weeks in 12 patients with idiopathic Parkinson’s disease (PD). Ten patients received rTMS to the bilateral frontal cortex (frontal rTMS) and six patients received rTMS to the bilateral occipital cortex (occipital rTMS). Before and after rTMS, we evaluated regional cerebral blood flow (rCBF) using 99m-Tc-ECD single photon emission computed tomography (SPECT) and clinical tests.In an analysis with statistic parametric mapping, both frontal and occipital rTMS reduced rCBF in the cortical areas around the stimulated site. The activities of daily living (ADL) and motor scores of Unified Parkinson’s Disease Rating Scale (UPDRS), pronation-supination movements, and buttoning up significantly improved after frontal rTMS than before it, while occipital rTMS had no significant effects in clinical tests.The findings of the present study suggest that successive 0.2 Hz rTMS has outlasting inhibitory effects on neuronal activity around the stimulated cortical areas. Because there were no significant relations between improved clinical tests and reduced rCBF, we speculate that the indirect effects of 0.2 Hz rTMS on subcortical structures are related to improved parkinsonian symptoms. Further studies recruiting large numbers of subjects are required to confirm the efficacy of 0.2 Hz rTMS on PD.

Publication Types:
Clinical Trial

Int J Neurosci. 1992 Oct;66(3-4):209-35. Related Articles, Links

Magnetic fields in the therapy of parkinsonism.

Sandyk R.

NeuroCommunication Research Laboratories, Danbury, CT 06811.

In a recent Editorial published in this Journal, I presented a new and revolutionary method for the treatment of Parkinson’s disease (PD). I reported that extracranial treatment with picoTesla magnetic fields (MF) is a highly effective, safe, and revolutionary modality in the symptomatic management of PD. My conclusion was based on experience gained following the successful treatment of over 20 Parkinsonian patients, two of whom had levodopa-induced dyskinesias. None of the patients developed side effects during a several month period of follow-up. In the present communication, I present two reports. The first concerns four Parkinsonian patients in whom picoTesla MF produced a remarkable and sustained improvement in disability. Three of the patients had idiopathic PD and the fourth patient developed a Parkinsonian syndrome following an anoxic episode. In all patients, treatment with MF was applied as an adjunct to antiParkinsonian medication. The improvement noted in these patients attests to the efficacy of picoTesla MF as an additional, noninvasive modality in the therapy of the disease. The second report concerns two demented Parkinsonian patients in whom treatment with picoTesla MF rapidly reversed visuospatial impairment as demonstrated by the Clock Drawing Test. These findings demonstrate, for the first time, the efficacy of these MF in the amelioration of cognitive deficits in Parkinson’s disease. Since Alzheimer’s pathology frequently coexists with the dementia of Parkinsonism, these observations underscore the potential efficacy of picoTesla MF in the treatment of dementias of various etiologies.

Publication Types:
Case Reports
Review
Review, Tutorial

Int J Neurosci. 1992 Mar;63(1-2):141-50. Related Articles, Links

Magnetic fields in the treatment of Parkinson’s disease.

Sandyk R, Anninos PA, Tsagas N, Derpapas K.

Democrition University of Thrace, Department of Medical Physics and Polytechnic School, Alexandroupolis and Xanthi, Greece.

Levodopa-induced dyskinesias are a common complication of chronic dopaminergic therapy in patients with Parkinson’s disease (PD). The overall prevalence of levodopa-induced dyskinesias ranges from 40%-90% and is related to the underlying disease process, pharmacologic factors, and to the duration of high dose levodopa therapy. The mechanisms underlying the emergence of levodopa-induced dyskinesias are unknown, although most investigators favor the theory that striatal dopamine receptor supersensitivity is directly responsible for the development of these abnormal movements. In laboratory animals, the pineal hormone melatonin has been shown to regulate striatal dopaminergic activity and block levodopa-induced dyskinesias (Cotzias et al., 1971). Since the pineal gland is known to be a magnetosensitive organ and as application of external magnetic fields has been shown to alter melatonin secretion, we studied the effects of application of external artificial weak magnetic fields in a Parkinsonian patient with severe levodopa-induced dyskinesias (“on-off”). Application of weak magnetic fields with a frequency of 2 Hz and intensity of 7.5 picotesla (pT) for a 6 minute period resulted in a rapid and dramatic attenuation of Parkinsonian disability and an almost complete resolution of the dyskinesias. This effect persisted for about 72 hours after which the patient regressed to his pretreatment state. To ascertain if the responses elicited in the laboratory were reproducible, the patient was instructed to apply magnetic fields of the same characteristics daily at home. These subsequent treatments paralleled the initial response with a sustained improvement being maintained during an observation period lasting at least one month. This case demonstrates the efficacy of weak magnetic fields in the treatment of Parkinsonism and motor complications of chronic levodopa therapy.

Publication Types:
Case Reports

Int J Neurosci. 1995 Jun;82(3-4):255-68. Related Articles, Links

Reversal of visuospatial deficit on the Clock Drawing Test in Parkinson’s disease by treatment with weak electromagnetic fields.

Sandyk R.

NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.

Visuospatial deficits are among the most frequently encountered abnormalities in neuropsychological testing of patients with Parkinson’s disease, being present in up to 90% of cases. Clinically, impairment of visuospatial functions may not be noted by Parkinsonian patients but may contribute to various functional disabilities including frequent falls, difficulties operating a vehicle, ambulating, and dressing. I have reported recently that treatment with external electromagnetic fields (EMFs) in the picotesla (pT) range intensity is an effective nonpharmacological modality in the management of the motor and various cognitive deficits of Parkinsonism including visuoperceptive and visuospatial functions. The present communication concerns four fully medicated Parkinsonian patients who, in response to treatment with EMFs, exhibited reversal of visuospatial impairments as demonstrated on the Clock Drawing Test. Specifically, prior to treatment with EMFs these patients demonstrated a visuospatial deficit which was evident by the placement of the numbers on the clock distant from the periphery. Following a series of treatments with EMFs this visuospatial deficit was corrected. The report supports prior observations demonstrating that externally applied pT range intensity EMFs may bring about reversal of visuospatial deficits in Parkinsonian patients which usually are not improved by treatment with dopaminergic or anticholinergic drugs.

Publication Types:
Case Reports

PMID: 12686400 [PubMed – indexed for MEDLINE]

Transcranial magnetic stimulation

[Article in Portuguese]

Conforto AB, Marie SK, Cohen LG, Scaff M.

Divisao de Clinica Neurologica, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil. abcong@yahoo.com

Transcranial magnetic stimulation (TMS) allows non-invasive study and modulation of cortical excitability in humans. Changes in cortical excitability in physiological and pathological conditions can be tracked by measurements such as motor threshold, motor evoked potentials, recruitment curves, intracortical facilitation and inhibition. The central motor conduction time can estimate neural transmission in central motor pathways. Changes in areas of representation in sensorimotor cortex can be studied with cortical mapping. Modulation of cortical processing can be used to evaluate different brain functions. Therapeutic use in depression, Parkinson’s disease and epilepsy has raised great interest over the past decade. Non-invasive cortical mapping may be achieved by combining TMS to other neurophysiological/ neuroimaging techniques. TMS has great potential both as an investigational and as a therapeutical tool in Neurology and Psychiatry.

Publication Types:
Review
Review, Tutorial

PMID: 12715042 [PubMed – indexed for MEDLINE]

Further observations on the efficacy of picoTesla range magnetic fields in Parkinson’s disease Treatment of Parkinson’s disease with magnetic fields reduces the requirement for medications A drug naive parkinsonian patient successfully treated with weak electromagnetic fields Effect of electromagnetic fields on amplitude of pattern reversal VEP response in Parkinson’s disease Reversal of an acute parkinsonian syndrome associated with multiple sclerosis Treatment with weak electromagnetic fields restores dream recall in a parkinsonian patient Reversal of a body image disorder (macrosomatognosia) in Parkinson’s disease by treatment with pulsed electromagnetic fields

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Further observations on the unique efficacy of picoTesla range magnetic fields in Parkinson’s disease.

Sandyk R, Derpapas K.

NeuroCommunication Research Laboratories, Danbury, CT 06811.

External application of picoTesla range magnetic fields (MF) has been reported recently to be efficacious in the treatment of patients with Parkinson’s disease (PD) including those who manifest levodopa-related dyskinesias. In the present communication, we present four additional Parkinsonian patients who showed, within a brief period of time, marked improvement in motor symptoms after therapy with MF. Three of the patients had been maintained on antiParkinsonian medication during treatment with MF while the fourth patient had never received pharmacotherapy. Improvement with magnetic therapy was noted not only in the motor sphere (resting tremor, gait apraxia, postural instability), but also in nonmotor aspects of the disease including mood, sleep, pain, anorexia, autonomic, and cognitive functions attesting to the unique efficacy of external picoTesla range MF in the treatment of Parkinsonism. Poverty of facial expression (hypomimia, “masked facies”), which correlates with the degree of striatal dopaminergic deficiency, is one of the clinical hallmarks of PD reflecting the severity of hypokinesia and rigidity in the orofacial musculature. In this report, we emphasize the effects of MF on the hypomimia of PD and provide visual documentation illustrating the changes in the patients’ facial expression which follow treatment with MF.

Int J Neurosci. 1993 Mar-Apr;69(1-4):167-83.

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Treatment of Parkinson’s disease with magnetic fields reduces the requirement for antiparkinsonian medications.

Sandyk R.

NeuroCommunication Research Laboratories, Danbury, CT 06811.

Recently, I reported that extracranial treatment with picoTesla range magnetic fields (MF) is an effective, safe, and revolutionary modality in the management of Parkinsonism including those patients manifesting levodopa-induced motor complications. This treatment, which has emerged as a potentially more advantageous modality than pharmacologic therapy, also produces improvements in nonmotor aspects of the disease including mood, cognitive functions, sleep, pain, appetite, autonomic functions, and sexual behavior, which are usually minimally, if at all, ameliorated by long term therapy with levodopa or anticholinergic agents. The present communication concerns a 69 year old Parkinsonian patient who, following a series of two treatments with extracranial picoTesla range MF on two separate days, improved to the point where he was able to discontinue most of his antiparkinsonian medications for a period of two weeks without experiencing deterioration in symptoms. On the third week he began to develop recurrence of symptoms and resumed taking his regular medications. At the end of the fourth week the patient received a series of four magnetic treatments on four successive days after he completely discontinued his antiparkinsonian medications. During this period he experienced a remarkable improvement in motor disability as well as in cognitive functions (i.e., visuospatial performance), mood, sleep, appetite, bowel functions and resolution of pain in the lower extremity. This report attests to the antiparkinsonian efficacy of picoTesla range MF and suggests that this treatment, when applied on a regular basis, may reduce the requirement for antiparkinsonian medications. This observation, when confirmed in a larger cohort of patients, may carry important implications for the therapy of Parkinsonism as it may offer an alternative treatment for patients who develop levodopa failure or experience intolerable side effects from dopaminergic medication. The observation that magnetic treatment improved the patient’s symptoms while being off dopaminergic therapy supports the role of nondopaminergic mechanisms in the pathophysiology of Parkinsonism.

Int J Neurosci. 1994 Jan-Feb;74(1-4):191-201.

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A drug naive parkinsonian patient successfully treated with weak electromagnetic fields.

Sandyk R.

NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.

Brief cerebral application of picotesla (pT) electromagnetic fields (EMF) has been demonstrated an efficacious, revolutionary treatment modality for the therapy of Parkinson’s disease (PD) with clinical benefits being evident in all motor aspects of the disease as well as in nonmotor symptoms such as mood, sleep, pain, sexual dysfunction, autonomic regulation and cognitive functions. Since treatment with pT EMF has involved PD patients who were treated with dopaminergic agents at the time they received EMF there may have been a synergistic interaction between dopaminergic drugs and EMF. The present communication concerns a 49-year-old male Parkinsonian patient with stage 3 disability on the Hoehn and Yahr scale (1967) who, in response to brief extracranial applications of pT EMF, demonstrated a marked improvement in motor, depressive symptomatology and cognitive functions and was classified as stage 1 several weeks later. This case is remarkable in that the patient did not receive treatment with dopaminergic drugs prior to or during the course of EMF therapy. It suggests that (a) pT range EMF may be efficacious as a monotherapy for PD and should be considered also as a treatment modality for de novo diagnosed patients, and (b) application of these EMF improves Parkinsonism by a mechanism which involves, among others, augmentation of dopaminergic and serotonergic neurotransmission.

Int J Neurosci. 1994 Nov;79(1-2):99-110.

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Effect of weak electromagnetic fields on the amplitude of the pattern reversal VEP response in Parkinson’s disease.

Sandyk R.

NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.

Visual evoked potential (VEP) studies are widely used for the diagnosis of multiple sclerosis (MS) and are also useful in monitoring the effects of various therapeutic modalities in the disease. Prolongation of the VEP latencies has been demonstrated in patients with MS and in other neurodegenerative disorders including Parkinson’s disease (PD), a disorder characterized by deficient cerebral dopamine (DA) functions. Pharmacological and biochemical studies have demonstrated a positive correlation between the amplitude of the VEP response and cerebral DA levels. Since brief, extracerebral applications of picotesla (pT) range flux intensity electromagnetic fields (EMFs) of low frequency have been shown to produce rapid improvement in motor and cognitive symptoms in PD, it is expected that application these EMFs would lead also to an increase in the amplitude of VEP response. This report documents three randomly selected PD patients who, following two successive brief extracerebral applications of pT range EMFs, showed an almost 3-fold increase of the mean pretreatment amplitude of the pattern reversal VEP in response to monocular stimulation. One patient underwent also a placebo EMF treatment which did not result in a significant change in the posttreatment amplitude. The study demonstrates that in Parkinsonian patients extracerebral application of these EMFs rapidly increases in amplitude of the VEP response and, by inference, cerebral DA levels presumably by increasing DA release.

Int J Neurosci. 1996 Feb;84(1-4):165-75.

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Reversal of an acute parkinsonian syndrome associated with multiple sclerosis by application of weak electromagnetic fields.

Sandyk R.

NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.

The occurrence of movement disorders and particularly Parkinsonian symptoms is uncommon in patients with multiple sclerosis (MS) despite the rather frequent presence of demyelinating plaques in the basal ganglia. This disparity between the occurrence of clinical symptoms in MS and the distribution of demyelinating plaques suggests that impairment of neurotransmitter functions rather than demyelination may be critical to the clinical manifestations of the disease. A 48 year old woman with remitting-progressive MS developed a bilateral Parkinsonian syndrome in association with acute emotional stress which resolved after she received two brief successive extracerebral applications of low frequency picotesla flux density electromagnetic fields (EMFs). It is believed that in this patient Parkinsonism may have existed in a subclinical form and that acute stress, which previously has been shown to precipitate symptoms of Parkinson’s disease, triggered the onset of Parkinsonism by further reducing dopaminergic and serotonergic neurotransmission in the basal ganglia. The rapid reversal of the Parkinsonian syndrome by EMFs was related to a presumed augmentation of dopaminergic and serotonergic neurotransmission which, on the basis of CSF studies, is reduced in chronic MS patients. The efficacy of EMFs in the treatment of Parkinson’s disease had been documented previously but this report demonstrates that this treatment modality is beneficial also for the treatment of Parkinsonism developing in the setting of other neurodegenerative disorders.

Int J Neurosci. 1996 Jul;86(1-2):33-45.

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Treatment with weak electromagnetic fields restores dream recall in a parkinsonian patient.

Sandyk R.

Department of Neuroscience, Institute for Biomedical Engineering and Rehabilitation Services, Touro College, Dix Hills, NY 11746, USA.

Absent or markedly reduced REM sleep with cessation of dream recall has been documented in numerous neurological disorders associated with subcortical dementia including Parkinson’s disease, progressive supranuclear palsy and Huntington’s chorea. This report concerns a 69 year old Parkinsonian patient who experienced complete cessation of dreaming since the onset of motor disability 13 years ago. Long term treatment with levodopa and dopamine (DA) receptor agonists (bromocriptine and pergolide mesylate) did not affect dream recall. However, dreaming was restored after the patient received three treatment sessions with AC pulsed picotesla range electromagnetic fields (EMFs) applied extracranially over three successive days. Six months later, during which time the patient received 3 additional treatment sessions with EMFs, he reported dreaming vividly with intense colored visual imagery almost every night with some of the dreams having sexual content. In addition, he began to experience hypnagogic imagery prior to the onset of sleep. Cessation of dream recall has been associated with right hemispheric dysfunction and its restoration by treatment with EMFs points to right hemispheric activation, which is supported by improvement in this patient’s visual memory known to be subserved by the right temporal lobe. Moreover, since DA neurons activate REM sleep mechanisms and facilitate dream recall, it appears that application of EMFs enhanced DA activity in the mesolimbic system which has been implicated in dream recall. Also, since administration of pineal melatonin has been reported to induce vivid dreams with intense colored visual imagery in normal subjects and narcoleptic patients, it is suggested that enhanced nocturnal melatonin secretion was associated with restoration of dream recall in this patient. These findings demonstrate that unlike chronic levodopa therapy, intermittent pulsed applications of AC picotesla EMFs may induce in Parkinsonism reactivation of reticular-limbic-pineal systems involved in the generation of dreaming.

Int J Neurosci. 1997 Jun;90(1-2):75-86.

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Reversal of a body image disorder (macrosomatognosia) in Parkinson’s disease by treatment with AC pulsed electromagnetic fields.

Sandyk R.

Department of Neuroscience, Institute for Biomedical Engineering and Rehabilitation Services of Touro College, Dix Hills, NY 11746, USA.

Macrosomatognosia refers to a disorder of the body image in which the patient perceives a part or parts of his body as disproportionately large. Macrosomatognosia has been associated with lesions in the parietal lobe, particularly the right parietal lobe, which integrates perceptual-sensorimotor functions concerned with the body image. It has been observed most commonly in patients with paroxysmal cerebral disorders such as epilepsy and migraine. The Draw-a-Person-Test has been employed in neuropsychological testing to identify disorders of the body image. Three fully medicated elderly Parkinsonian patients who exhibited, on the Draw-a-Person Test, macrosomatognosia involving the upper limbs are presented. In these patients spontaneous drawing of the figure of a man demonstrated disproportionately large arms. Furthermore, it was observed that the arm affected by tremor or, in the case of bilateral tremor, the arm showing the most severe tremor showed the greatest abnormality. This association implies that dopaminergic mechanisms influence neuronal systems in the nondominant right parietal lobe which construct the body image. After receiving a course of treatments with AC pulsed electromagnetic fields (EMFs) in the picotesla flux density applied transcranially, these patients’ drawings showed reversal of the macrosomatognosia. These findings demonstrate that transcranial applications of AC pulsed EMFs affect the neuronal systems involved in the construction of the human body image and additionally reverse disorders of the body image in Parkinsonism which are related to right parietal lobe dysfunction.

Int J Neurosci. 1998 Feb;93(1-2):43-54.

Parkinson’s Disease

A 73-year-old male Parkinson’s patient suffering from disabling resting and postural tremors in the right hand, as well as other symptoms. Two successive 20-minute treatments with AC pulsed electromagnetic fields of 7.5-picotesla intensity and 5-Hz frequency sinusoidal wave led to improvements in visuospatial performance and a legible signature. Significant improvements in Parkinsonian motor symptoms were also seen following additional treatments. The case of a medicated 61-year-old Parkinson’s patient who experienced rapid reversal of symptoms following a single external application of picotesla-range magnetic fields.

The application of ELF magnetic fields via a plastic helmet device housing a set of coils (generating fields of 8 Hz and 7.5 pT) produced beneficial clinical effects after 30 minutes in patients suffering Parkinson’s disease and multiple sclerosis.

R. Sandyk, Brief Communication: Electromagnetic Fields Improve Visuospatial Performance and Reverse Agraphia in a Parkinsonian Patient, International Journal of Neurosci, 87(3-4), and Reversal of Visual Neglect in Parkinson’s Disease Treatment with picoTesla Range Magnetic Fields J. Bardasano, Extracranial Device for Noninvasive Neurological Treatments with Pulsating ELF Magnetic Fields.

Parkinson’s Disease

Bardasano et al.: ‘Extracranial Device for Noninvasive Neurological Treatments with PEMF, ‘Second World Congress for Electricity and Magnetism in Biology and Medicine, 1997, Bologna, Italy. -This study shows that the use of pulsed electromagnetic fields in the Pikotesla range yielded a definite clinical improvement in patients suffering from Parkinson’s disease and multiple sclerosis.
R. Sandyk: ‘Parkinsonian Micrographia Reversed by Treatment low intensity Electromagnetic Fields,’ International Journal of Neurosci, 81 (1-2), March 1995, pp. 83-93. – Two Parkinsonian patients experienced a definite improvement in their symptoms in the area of movement after using extremely low frequency and low-intensity pulsed electromagnetic fields.
R. Sandyk: ‘Low intensity Magnetic Fields in the Treatment of Parkinson’s Disease with the ‘On-Off Phenomenon’, ‘International Journal of Neurosci, 66 (1-2), September 1992, pp. 97-106. – This article reports on the case of an 87 year old man who suffered from Parkinson’s disease and so-called ‘on-off phenomenon’. PEMF brought a definite relief from symptoms.
R. Sandyk: ‘Brief Communication: Electromagnetic Fields Improve Visuo-spatial Performance and Rivers Agraphia in a Parkinsonian patient,’ International Journal of Neurosci, 87 (3-4), Nov. 1996. – In this case a 73-year-old man suffering tremors and other Parkinsonian symptoms was treated successfully with pulsating electromagnetic fields in the picotesla range (!).
M.S. George et al.: ‘Trans-cranial Magnetic Stimulation: A neuro-psychiatric Tool for the 21st Century,’ Journal of Neuropsychiatry Clin neurosci, 8 (4), Fall 1996, pp. 373-382. -Trans-crainal magnetic stimulation leads to definite improvements in symptoms of Parkinsonian patients, especially depression.

Applications of transcranial magnetic stimulation in movement disorders.

Cantello R.

Department of Medical Sciences, Section of Neurology, School of Medicine, Amedeo Avogadro University, Novara, Italy. cantello@med.unipmn.it

The author reviews the applications of transcranial magnetic stimulation (TMS) in a series of movement disorders–namely, Parkinson’s disease, corticobasal degeneration, multiple system atrophy, progressive supranuclear palsy, essential tremor, dystonia, Huntington’s chorea, myoclonus, the ataxias, Tourette’s syndrome, restless legs syndrome, Wilson’s disease, Rett syndrome, and stiff-person syndrome. Single- and paired-pulse TMS studies have been done mainly for pathophysiologic purposes. Repetitive TMS has been used largely for therapy. Many TMS abnormalities are seen in the different diseases. They concur to show that motor cortical areas and their projections are the main target of the basal ganglia dysfunction typical of movement disorders. Interpretation has not always been clear, and sometimes there were discrepancies and contradictions. Largely, this may be the result of the extreme heterogeneity of the methods used and of the patients studied. It is premature to give repetitive TMS a role in treatment. Overall, however, TMS gives rise to a new, outstanding enthusiasm in the neurophysiology of movement disorders. There is reason to predict that TMS, with its continuous technical refinement, will prove even more helpful in the near future. Then, research achievements are reasonably expected to spill over into clinical practice.

Publication Types:
Review
Review, Tutorial

PMID: 12436085 [PubMed – indexed for MEDLINE]

Improved executive functioning following repetitive transcranial magnetic stimulation.

Moser DJ, Jorge RE, Manes F, Paradiso S, Benjamin ML, Robinson RG.

Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA 52240, USA. David.Moser@uiowa.edu

The cognitive effects of active and sham repetitive transcranial magnetic stimulation (rTMS) were examined in 19 middle-aged and elderly patients with refractory depression. Patients received either active (n = 9) or sham (n = 10) rTMS targeted at the anterior portion of the left middle frontal gyrus. Patients in the active rTMS group improved significantly on a test of cognitive flexibility and conceptual tracking (Trail Making Test-B).

Publication Types:
Clinical Trial
Randomized Controlled Trial

Transcranial magnetic stimulation of the cerebellum in essential tremor: a controlled study.

Gironell A, Kulisevsky J, Lorenzo J, Barbanoj M, Pascual-Sedano B, Otermin P.

Servei de Neurologia, Hospital de Sant Pau, Av Sant Antoni Ma Claret 167, 08025 Barcelona, Catalonia, Spain. agironell@cataloniamail.com

BACKGROUND: Growing evidence implicates an overactivity of the cerebellum in the pathophysiology of essential tremor. In a small series of patients, we explored the acute effects and therapeutic possibilities of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellum in patients with essential tremor in a double-blind, crossover, placebo-controlled design. METHODS: Ten patients with essential tremor underwent an active and a sham rTMS session, at a 1-week interval. The rTMS was performed with a focal double 70-mm butterfly coil (maximum peak field of 2.2 T) applied 2 cm below the inion. Each session consisted of 30 trains of 10-second duration separated by 30-second pauses, at 100% of the maximum output intensity and at 1-Hz frequency. Major evaluation outcomes were the score on the Tremor Clinical Rating Scale and accelerometric recordings obtained before (-5 minutes), immediately after (+5 minutes), and 1 hour after (+60 minutes) each rTMS session. Both clinical and accelerometric measurements were obtained by a blinded neurologist. RESULTS: On the +5-minute assessment, active rTMS produced a notable tremor improvement compared with sham rTMS, as evidenced by a significant reduction in scores on the clinical rating scale and accelerometric values. At +60 minutes, no clinical or accelerometric benefit was evidenced. No adverse effects of rTMS were observed. CONCLUSIONS: This exploratory study of the potential therapeutic properties of rTMS on essential tremor showed an acute antitremor effect. Further investigation in search of a more lasting benefit is warranted.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11890845 [PubMed – indexed for MEDLINE]

Contralateral and ipsilateral repetitive transcranial magnetic stimulation in Parkinson patients]

[Article in German]

de Groot M, Hermann W, Steffen J, Wagner A, Grahmann F.

Klinik und Poliklinik fur Neurologie, Universitatsklinikum Leipzig, Liebigstrasse 22a, 04103 Leipzig.

In seven women and two men with Parkinson’s disease, Hoehn and Yahr stage 1 or 2, the effect of repetitive transcranial magnetic stimulation (rTMS) was evaluated. Primary endpoint outcome measure was the changing of the motor items of the Unified Parkinson’s Disease Rating Scale (subscale III of UP-DRS) 24 h after stimulation. Kinesiologic tests and writing samples were secondary outcome measures. After discontinuing all medication, stimulation was performed with 5 Hz at 90% of the motor threshold over the primary motor cortex of the more affected. There were 2250 stimuli applied, divided into 15 trains at intervals of 10 s. The identical treatment of the opposite side served as control treatment. Only treatment of the more affected side resulted in a significant improvement of the clinical symptoms of 46% as assessed by the UPDRS (p < 0.02). This effectiveness differed significantly from the control treatment (21%, p < 0.02). The kinesiological testing did not show any significant speeding of movements (p > 0.05). Some patients showed a normalisation of the previously disturbed handwriting specimen. These data confirm the previous observation that rTMS of primary motor regions leads to at least temporary clinical improvement of symptoms in patients with Parkinson’s disease.

PMID: 11789438 [PubMed – indexed for MEDLINE]

Therapeutic effect and mechanism of repetitive transcranial magnetic stimulation in Parkinson’s disease.

Shimamoto H, Takasaki K, Shigemori M, Imaizumi T, Ayabe M, Shoji H.

Shimamoto Neurosurgical Clinic, Kurume University School of Medicine, Ohnojo-city, Fukuoka, Japan.

The therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) on clinical performance was assessed by a double-blind study in 9 patients with Parkinson’s disease (PD). Nine other patients underwent sham stimulation as controls. The modified Hoehn and Yahr (H&Y) staging scale, the Schwab and England Activities of Daily Living (ADL) scale, and the Unified Parkinson’s disease rating scale (UPDRS) were used to assess changes of clinical performance. Patients were assessed prior to and following 2 months of rTMS. In addition, the mechanism of rTMS was investigated by dopamine and homovanillic acid (HVA) in the lumbar cerebrospinal fluid (CSF) of 17 patients before and after therapeutic rTMS for three or four months. rTMS was applied manually to the frontal areas 60 times per session, i. e., 30 times per side using a large circular coil, a pulse intensity of 700 V, and a frequency of 0.2 Hz. Sessions were continued once a week for 2 months. The 9 control patients showed no changes of symptoms between the initial evaluation and that after 2 months of sham rTMS. In contrast, all 9 patients receiving rTMS showed a significant decrease of the modified H&Y and UPDRS scores after 2 months, while the Schwab and England ADL Scale scores increased significantly. In the second CSF sample from patients receiving rTMS, HVA showed a significant decrease These results suggest that rTMS is beneficial for the symptoms of Parkinson’s disease and that it may act via inhibition of dopaminergic systems.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11697688

Brain Topogr. 2000 Winter;13(2):135-44. Related Articles, Links

Nonlinear analysis of brain activity in magnetic influenced Parkinson patients.

Anninos PA, Adamopoulos AV, Kotini A, Tsagas N.

Dept. of Medicine, Demokrition University of Thrace, Alexandroupolis, Greece. anninos@med.duth.gr

Magnetoencephalogram (MEG) recordings were obtained from the brain of patients suffering from Parkinson’s disease (PD) using the Superconductive Quantum Interference Device (SQUID). For each patient the magnetic activity was recorded from a total of 64 points of the skull (32 points from each temporal lobe) as defined by a recording reference system, which is based on the 10-20 Electrode Placement System. Some of the recorded points were observed to exhibit abnormal rhythmic activity, characterized by high amplitudes and low frequencies. External magnetic stimulation (EMS) with intensity 1-7.5pT, and frequency the alpha-rhythm of the patient (8-13 Hz) was applied in the left-right temporal, frontal-occipital and vertex (2 minutes over each of the above regions) and the brain magnetic activity was recorded again. The application of the EMS resulted in rapid attenuation of the MEG activity of PD patients. Furthermore, chaotic dynamic methods were used, in order to estimate the correlation dimension D of the reconstructed phase spaces. The estimated values of D, in conjunction with the results derived from the other data analysis methods, strongly support the existence of low dimension chaotic structures in the dynamics of cortical activity of PD patients. In addition, the increased values of D of the MEG after the application of EMS when compared with the corresponding ones obtained from the MEGs prior to the EMS, suggest that the neural dynamics are strongly influenced by the application of EMS.

Nippon Rinsho. 2000 Oct;58(10):2120-4.
Parkinson’s disease and depression
[Article in Japanese]Kurokawa K, Yuasa T.
Department of Neurology, Kohnodai Hospital.
Up to 40% of cases of Parkinson’s disease are associated with the occurrence of depression. The symptoms of the patients’ depressive state may be factors such as significant weight change, insomnia or hypersomnia, psychomotor retardation, fatigue or loss of energy, feelings of worthlessness or inappropriate guilt, decreased concentration and indecisiveness, and recurrent thoughts of death or suicidal ideation. Given these conditions, drugs prove ineffective in many cases. Electroconvulsive therapy (ECT) has been reported to be beneficial in cases of drug-resistant depression. ECT has also been applied to Parkinsonian patients with depression and found to be effective with both depression and the Parkinsonian symptom. Transcranial magnetic stimulation(TMS) has recently been investigated for application in cases of depression and has become known as a valuable tool for depression therapy. TMS is easily implemented even in outpatient therapy. TMS will make a great contribution to the therapy of depression with Parkinson’s disease.

Int J Neurosci. 1998 Sep;95(3-4):255-69. Related Articles, Links

Reversal of the bicycle drawing direction in Parkinson’s disease by AC pulsed electromagnetic fields.

Sandyk R.

Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.

The Draw-a-Bicycle Test is employed in neuropsychological testing of cognitive skills since the bicycle design is widely known and also because of its complex structure. The Draw-a-Bicycle Test has been administered routinely to patients with Parkinson’s disease (PD) and other neurodegenerative disorders to evaluate the effect of transcranial applications of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density on visuoconstructional skills. A seminal observation is reported in 5 medicated PD patients who demonstrated reversal of spontaneous drawing direction of the bicycle after they received a series of transcranial treatments with AC pulsed EMFs. In 3 patients reversal of the bicycle drawing direction was observed shortly after the administration of pulsed EMFs while in 2 patients these changes were observed within a time lag ranging from several weeks to months. All patients also demonstrated a dramatic clinical response to the administration of EMFs. These findings are intriguing because changes in drawing direction do not occur spontaneously in normal individuals as a result of relateralization of cognitive functions. This report suggests that administration of AC pulsed EMFs may induce in some PD patients changes in hemispheric dominance during processing of a visuoconstructional task and that these changes may be predictive of a particularly favourable response to AC pulsed EMFs therapy.

Publication Types:
Case Reports

Int J Neurosci. 1997 Nov;92(1-2):63-72. Related Articles, Links

Speech impairment in Parkinson’s disease is improved by transcranial application of electromagnetic fields.

Sandyk R.

Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.

A 52 year old fully medicated physician with juvenile onset Parkinsonism experienced 4 years ago severe “on-off” fluctuations in motor disability and debilitating speech impairment with severe stuttering which occurred predominantly during “on-off” periods. His speech impairment improved 20%-30% when sertraline (75 mg/day), a serotonin reuptake inhibitor, was added to his dopaminergic medications which included levodopa, amantadine, selegiline and pergolide mesylate. A more dramatic and consistent improvement in his speech occurred over the past 4 years during which time the patient received, on a fairly regular basis, weekly transcranial treatments with AC pulsed electromagnetic fields (EMFs) of picotesla flux density. Recurrence of speech impairment was observed on several occasions when regular treatments with EMFs were temporarily discontinued. These findings demonstrate that AC pulsed applications of picotesla flux density EMFs may offer a nonpharmacologic approach to the management of speech disturbances in Parkinsonism. Furthermore, this case implicates cerebral serotonergic deficiency in the pathogenesis of Parkinsonian speech impairment which affects more than 50% of patients. It is believed that pulsed applications of EMFs improved this patient’s speech impairment through the facilitation of serotonergic transmission which may have occurred in part through a synergistic interaction with sertraline.

Publication Types:
Case Reports

Int J Neurosci. 1997 Oct;91(3-4):189-97. Related Articles, Links

Treatment with AC pulsed electromagnetic fields improves the response to levodopa in Parkinson’s disease.

Sandyk R.

Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.

A 52 year old fully medicated Parkinsonian patient with severe disability (stage 4 on the Hoehn & Yahr disability scale) became asymptomatic 10 weeks after he received twice weekly transcranial treatments with AC pulsed electromagnetic fields (EMFs) of picotesla flux density. Prior to treatment with EMFs, his medication (Sinemet CR) was about 50% effective and he experienced end-of-dose deterioration and diurnal-related decline in the drug’s efficacy. For instance, while his morning medication was 90% effective, his afternoon medication was only 50% effective and his evening dose was only 30% effective. Ten weeks after introduction of treatment with EMFs, there was 40% improvement in his response to standard Sinemet medication with minimal change in its efficacy during the course of the day or evening. These findings demonstrate that intermittent, AC pulsed applications of picotesla flux density EMFs improve Parkinsonian symptoms in part by enhancing the patient’s response to levodopa. This effect may be related to an increase in the capacity of striatal DA neurons to synthesize, store and release DA derived from exogenously supplied levodopa as well as to increased serotonin (5-HT) transmission which has been shown to enhance the response of PD patients to levodopa. Since decline in the response to levodopa is a phenomenon associated with progression of the disease, this case suggests that intermittent applications of AC pulsed EMFs of picotesla flux density reverse the course of chronic progressive PD.

Publication Types:
Case Reports

PMID: 9394226

Int J Neurosci. 1997 Sep;91(1-2):57-68. Related Articles, Links

Reversal of cognitive impairment in an elderly parkinsonian patient by transcranial application of picotesla electromagnetic fields.

Sandyk R.

Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.

A 74 year old retired building inspector with a 15 year history of Parkinson’s disease (PD) presented with severe resting tremor in the right hand, generalized bradykinesia, difficulties with the initiation of gait with freezing, mental depression and generalized cognitive impairment despite being fully medicated. Testing of constructional abilities employing various drawing tasks demonstrated drawing impairment compatible with severe left hemispheric dysfunction. After receiving two successive transcranial applications, each of 20 minutes duration, with AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla flux density and frequencies of 5Hz and 7Hz respectively, his tremor remitted and there was dramatic improvement in his drawing performance. Additional striking improvements in his drawing performance occurred over the following two days after he continued to receive daily treatments with EMFs. The patient’s drawings were subjected to a Reliability Test in which 10 raters reported 100% correct assessment of pre- and post drawings with all possible comparisons (mean 2 = 5.0; p < .05). This case demonstrates in PD rapid reversal of drawing impairment related to left hemispheric dysfunction by brief transcranial applications of AC pulsed picotesla flux density EMFs and suggests that cognitive deficits associated with Parkinsonism, which usually are progressive and unaffected by dopamine replacement therapy, may be partly reversed by administration of these EMFs. Treatment with picotesla EMFs reflects a "cutting edge" approach to the management of cognitive impairment in Parkinsonism. Publication Types: Case Reports Int J Neurosci. 1996 Mar;85(1-2):111-24. Related Articles, Links Freezing of gait in Parkinson's disease is improved by treatment with weak electromagnetic fields. Sandyk R. NeuroCommunication Research Laboratories, Danbury, CT 06811, USA. Freezing, a symptom characterized by difficulty in the initiation and smooth pursuit of repetitive movements, is a unique and well known clinical feature of Parkinson's disease (PD). It usually occurs in patients with long duration and advanced stage of the disease and is a major cause of disability often resulting in falling. In PD patients freezing manifests most commonly as a sudden attack of immobility usually experienced during walking, attempts to turn while walking, or while approaching a destination. Less commonly it is expressed as arrest of speech or handwriting. The pathophysiology of Parkinsonian freezing, which is considered a distinct clinical feature independent of akinesia, is poorly understood and is believed to involve abnormalities in dopamine and norepinephrine neurotransmission in critical motor control areas including the frontal lobe, basal ganglia, locus coeruleus and spinal cord. In general, freezing is resistant to pharmacological therapy although in some patients reduction or increase in levodopa dose may improve this symptom. Three medicated PD patients exhibiting disabling episodes of freezing of gait are presented in whom brief, extracerebral applications of pulsed electromagnetic fields (EMFs) in the picotesla range improved freezing. Two patients had freezing both during "on" and "off" periods while the third patient experienced random episodes of freezing throughout the course of the day. The effect of each EMFs treatment lasted several days after which time freezing gradually reappeared, initially in association with "off" periods. These findings suggest that the neurochemical mechanisms underlying the development of freezing are sensitive to the effects of EMFs, which are believed to improve freezing primarily through the facilitation of serotonin (5-HT) neurotransmission at both junctional (synaptic) and nonjunctional neuronal target sites. Publication Types: Case Reports Int J Neurosci. 1995 Mar;81(1-2):67-82. Related Articles, Links Improvement in short-term visual memory by weak electromagnetic fields in Parkinson's disease. Sandyk R. NeuroCommunication Research Laboratories, Danbury, CT 06811, USA. Neuropsychological studies have demonstrated that Parkinson's disease (PD) is associated with various cognitive deficits ultimately leading in about 30% of patients to the development of dementia. These studies have demonstrated also a greater decrement of right hemispheric functions with visuospatial deficits occurring in up to 90% of PD patients. The Rey-Osterrieth Complex Figure (ROCF) Test has been employed in the assessment of right hemispheric functions and particularly for the evaluation of visuoconstructive abilities and short-term visual memory. I have demonstrated recently that external application of electromagnetic fields (EMFs) in the picotesla (pT) range intensity is an effective nonpharmacological modality in the management of the motor and cognitive deficits of Parkinsonism. In the present communication I present 3 fully medicated nondemented PD patients (mean age: 68 +/- 8.1 yrs; mean duration of illness: 9.0 +/- 4.0 yrs; mean disability on the Hoehn and Yahr scale: 3) who were tested on the ROCF Test before and after a series of treatments with EMFs. In response to the administration of EMFs the group demonstrated a mean of 23.1 +/- 13.6% improved performance on copy of the ROCF and a 39.3 +/- 13.4% improvement of short-term recall of the ROCF. These findings demonstrate that treatment with pT EMFs improves deficits in visuospatial functions and visual memory in Parkinsonism which usually remain unaffected during standard treatment with dopaminergic pharmacotherapy. Publication Types: Case Reports Int J Neurosci. 1995 Mar;81(1-2):47-65. Related Articles, Links Weak electromagnetic fields reverse visuospatial hemi-inattention in Parkinson's disease. Sandyk R. NeuroCommunication Research Laboratories, Danbury, CT 06811, USA. Drawing tasks, both free and copied, have achieved a central position in neuropsychological testing of patients with unilateral cerebral dysfunction by virtue of their sensitivity to different kinds of organic brain disorders and their ability to provide information on lateralized brain damage. In the drawings of patients with right hemispheric damage, visuospatial neglect is revealed by the omission of details on the side of the drawing contralateral to the hemispheric lesion. Patients with unilateral cerebral damage, particularly those with left hemispheric damage, also demonstrate a tendency to place their drawings on the side of the page ipsilateral to the cerebral lesion, a phenomenon which has been termed visuospatial hemi-inattention. It has been reported previously that brief external application of alternating pulsed electromagnetic fields (EMFs) in the picotesla (pT) range intensity improved visuoperceptive and visuospatial functions and reversed neglect in Parkinsonian patients. The present communication concerns four fully medicated elderly nondemented Parkinsonian patients (mean age: 74.7 +/- 4.6 yrs; mean duration of illness: 7.7 +/- 5.2 yrs) in whom application of these EMFs produced reversal of visuospatial hemi-inattention related to left hemispheric dysfunction. These findings support prior observations demonstrating that pT EMFs may bring about reversal of certain cognitive deficits in Parkinsonian patients. Publication Types: Case Reports Review Review, Tutorial Int J Neurosci. 1994 Jul;77(1-2):23-46. Related Articles, Links Improvement in word-fluency performance in Parkinson's disease by administration of electromagnetic fields. Sandyk R. Neuro Communication Research Laboratories, Danbury, CT 06811. The association between degeneration of the nigrostriatal dopamine (DA) system and the motor manifestations of Parkinson's disease (PD) provided the impetus for the development of DA replacement therapy. However, clinical experience has demonstrated that DA-ergic drugs, while attenuating the motor symptoms of PD, have little or no consistent effect on the mental and cognitive symptoms of the disease which are thought to be related partly to degeneration of the meso-cortico-limbic DA system. Thus, failure of DA-ergic drugs to improve the mental and cognitive deficits of PD indicates that these agents cannot fully restore DA functions in the meso-cortico-limbic circuits. The present communication concerns five fully medicated Parkinsonian patients in whom application of a series of treatments with electromagnetic fields (EMF) of extremely low intensity (in the picotesla range) and frequency (5-8Hz) produced a dramatic improvement in performance on Thurstone's World-Fluency Test, a sensitive marker of frontal lobe functions. These findings suggest that in contrast to DA replacement therapy application of low intensity EMF may improve frontal lobe functions in patients with PD presumably by augmenting DA activity in the mesocortical system. As deficiency of the frontal DA system has been implicated also in the development of akinesia and freezing in PD these observations may explain the beneficial effects of EMF on the motor manifestations of the disease. Publication Types: Case Reports Review Review, Tutorial Int J Neurosci. 1993 May;70(1-2):85-96. Related Articles, Links The effects of external picoTesla range magnetic fields on the EEG in Parkinson's disease. Sandyk R, Derpapas K. NeuroCommunication Research Laboratories, Danbury, CT 06811. We report a 68 year old man with a 7 year history of Parkinson's disease (PD) who obtained little benefit from treatment by dopaminergic and anticholinergic agents. During the six months prior to presentation, he experienced more rapid deterioration in symptoms including memory functions, increasing depression, and dystonia of the foot. External application of picoTesla range magnetic fields (MF) resulted in rapid attenuation of tremor and foot dystonia with improvements in gait, postural reflexes, mood, anxiety, cognitive, and autonomic functions. Plasma prolactin and luteinizing hormone (LH) levels rose three days after initiation of treatment. In addition, distinct electroencephalographic (EEG) changes were recorded nine days after two treatments with MF and included enhancement of alpha and beta activities as well as resolution of the theta activity. These findings demonstrate, for the first time, objective EEG changes in response to picoTesla range MF in PD. Since the pineal gland is a magnetosensor and as some of the clinical effects produced by MF such as relaxation, sleepiness, mood elevation, increased dreaming, and enhancement of alpha and beta activities in the EEG have also been noted in healthy subjects administered melatonin, we propose that the clinical effects as well as the EEG changes noted after treatment with MF were mediated by the pineal gland which previously has been implicated in the pathophysiology of PD. - *source: http://altered-states.net/barry/newsletter203/pemfparkinsons.htm

Transcranial pulsed electromagnetic fields for multiple chemical sensitivity: study protocol for a randomized, double-blind, placebo-controlled trial

Marie Thi Dao Tran,corresponding author1 Sine Skovbjerg,1 Lars Arendt-Nielsen,2 Karl Bang Christensen,3 and Jesper Elberling1

corresponding author

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Abstract.

Background

Multiple chemical sensitivity (MCS) is a chronic condition of unknown etiology. MCS is characterized by recurrent nonspecific symptoms from multiple organ systems in response to chemical exposures in concentrations that are normally tolerated by the majority of the population. The symptoms may have severe impact on patients’ lives, but an evidence-based treatment for the condition is nonexisting. The pathophysiology is unclarified, but several indicators point towards abnormal processing of sensory signals in the central nervous system. Pulsed electromagnetic fields (PEMF) offer a promising new treatment for refractory depression and can be targeted at the brain, thereby activating biochemical cell processes.

Methods/Design

In a parallel, randomized, double-blind, placebo-controlled trial conducted at the Danish Research Centre for Chemical Sensitivities, the effects of PEMF in MCS patients will be assessed using the Re5 Independent System. Based on sample size estimation, 40 participants will be randomized to either PEMF therapy or placebo. The allocation sequence will be generated by computer. All involved parties (that is, participants, investigators, the research nurse, and the statistician) will be blinded to group allocation. The participants will receive PEMF therapy or placebo applied transcranially 30 minutes twice a day for 7 days a week over 6 consecutive weeks. Outcomes will be measured at baseline, once weekly during treatment, post treatment, and at 2.5-month and 4.5-month follow-up according to a predefined timetable. The primary outcome will be a measurement of the impact of MCS on everyday life. The secondary outcomes will be measurements of MCS symptoms, psychological distress (stress, anxiety or depressive symptoms), capsaicin-induced secondary punctate hyperalgesia, immunological markers in serum, and quality of life.

Discussion

This trial will assess the effects of PEMF therapy for MCS. Currently, there is no treatment with a documented effect on MCS, and in terms of healthcare there is very little to offer these patients. There is thus a great need for well-conducted randomized trials aimed at assessing possible treatment effects. A positive outcome will pave the way for improved healthcare and understanding of this very disabling and overlooked condition.

Trial registration

ClinicalTrials.gov, NCT01834781

Keywords: Multiple chemical sensitivity, Pulsed electromagnetic fields, Re5 therapy, Re5 independent system, Randomized controlled trial

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Background.

Multiple chemical sensitivity (MCS) is a chronic condition of unknown etiology [1-3]. MCS symptoms are triggered by exposure to common odors and other airborne chemicals in low concentrations; for example, perfume, freshly printed newspapers or magazines, cooking fumes or new electronic equipment. Symptoms related to the central nervous system (CNS; for example, headache, exhaustion, and concentration difficulties) are commonly reported, but other organ systems such as the airways, muscles, and joints are also often involved in symptom reports [4]. In severe cases, MCS can lead to loss of employment and social isolation [2,5,6]. Other labels have been ascribed to the symptoms (for example, chemical intolerance and idiopathic environmental intolerance) but MCS is widely used in the scientific literature and will be used here without reference to any assumptions about etiology. The etiology and pathophysiology of MCS remain largely unclarified. However, current findings suggest that both biological and psychological mechanisms are involved [4,7-10]. Within the biological spectrum, the theory of an abnormal response in the CNS termed central sensitization is receiving increasing scientific attention [7-9,11], partly because this hypothesis is compatible with the polysymptomatic manifestations from multiple organ systems and with the often reported association with symptoms of negative affectivity and stress [12-17]. The theory of central sensitization is further supported by recent findings. During odor provocations, brain imaging studies have demonstrated a significantly reduced activity in the cerebral areas that process olfactory stimuli in MCS patients compared with healthy controls [18,19]. Suggestions have been made that the observed reduction in cerebral activity reflects reduced activity in the inhibitory brain circuits, thus resulting in an increased response to normal sensory input [19]; that is, central sensitization. In controlled experimental pain studies, the presence of central sensitization in MCS has also been supported by findings of enlarged areas of capsaicin-induced secondary mechanical hyperalgesia [20,21]. Capsaicin (the active component in chili peppers) injections in the skin induce secondary mechanical hyperalgesia, which is an increased sensitivity to mechanical stimuli in the skin surrounding the injection site and is considered to be a CNS response.

The development of MCS has been described in two or three stages [22]: an initiating chemical exposure induces sensory irritation, and is followed by an elicitation phase in which symptoms are elicited by chemicals in nontoxic concentrations. As a possible explanation, it has been hypothesized that the initial chemical exposure triggers plastic changes in the CNS, which result in a changed response to a specific chemosensory input – analogous to the development of a persisting pain condition following an acute pain incident [8]. A third, generalization phase has been described in which symptom-eliciting odors and chemicals begin to involve other and unrelated chemical exposures [2]. This phase is also compatible with the localization of MCS in the CNS. Whether the immune system plays a part is unknown, but increased levels of immunological markers have been demonstrated among MCS patients [23].

Very few intervention studies aimed at MCS have been published [24,25] and, apart from these, there have only been a few published case reports. Hence, it is not currently possible to make evidence-based therapeutic recommendations for MCS [26]. In accordance with the CNS hypothesis, a transient but yet pronounced effect of electroconvulsive therapy has been reported in a few MCS patients [27]. As electroconvulsive therapy involves general anesthesia and muscle relaxants in advance of cerebral electrostimulation and also potential transient amnesia, it is a less attractive theraputic option for MCS. Transcranial magnetic stimulation and pulsed electromagnetic fields (PEMF) are more modern technologies to achieve electrostimulation of the brain without employing anesthesia or muscle relaxants. Both technologies involve the generation of a time-varying magnetic field, which consists of magnetic flux lines. A change in the magnetic field produces an electrical current in conductive materials (for example, tissue). PEMF differ from transcranial magnetic stimulation in mainly two aspects: PEMF are based on weak magnetic fields and are therefore completely unable to induce action potentials in excitable cells; and the field change alternates rapidly between minimum and maximum [28]. The electrical currents generated by PEMF are thus weak and lead to activation of the biochemical processes in the cells, especially the growth-related responses.

In 1977 the first therapeutic use of PEMF took place and was used to treat pseudoarthrosis and nonunions [29]. Animal studies since then have shown that PEMF can be used to enhance peripheral nerve regeneration [30-33], activate neural tissue [34], promote wound healing [35], enhance the proliferation of chondrocytes [36], and promote angiogenesis [37] and vasodilation [33,38]. Currently, PEMF are still mostly used for the promotion of bone growth and have been approved by the US Food and Drug Administration to promote the healing of certain fractures [39]. However, the scope of application in humans is expanding, because PEMF have also been shown to have beneficial effects on osteoarthritis [40,41] as well as antidepressive effects when applied to refractory depressions [42]. The substantial individual and societal costs of MCS and the lack of evidence-based therapeutic options call for well-conducted randomized trials evaluating the effect of a possible therapeutic option such as PEMF. In the forthcoming study, PEMF will be applied transcranially to treat MCS in a randomized, double-blind, placebo-controlled trial.

Objectives

The main purpose of the forthcoming study is to investigate whether PEMF application using the Re5 Independent System (Re5 Aps, Frederiksberg, Denmark) can reduce the impact of MCS on everyday life, such as the ability to perform domestic chores, take part in social activities, attend work, and so forth. The secondary purposes are to investigate whether the intervention can decrease MCS symptoms, psychological distress (stress, anxiety or depressive symptoms), capsaicin-induced secondary punctate hyperalgesia, immunological markers in serum and increase quality of life.

Hypotheses

The primary hypothesis is that PEMF therapy can significantly reduce the impact of MCS on everyday life in the intervention group compared with the control group. The secondary hypotheses are that PEMF therapy can significantly decrease: general symptoms (that is, symptoms that are commonly experienced by MCS patients); exposure-related symptoms (that is, symptoms that are elicited by exposure to common odors and chemicals); stress, anxiety or depressive symptoms if present; and the area of capsaicin-induced secondary punctate hyperalgesia; the serum concentration of immunological markers (that is, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-21, IL-22, IL-23, TNFα, IFNγ); and can significantly improve quality of life.

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Methods/Design.

The study will be conducted as a parallel, randomized, double-blind, placebo-controlled trial with follow-up after 2.5 and 4.5 months.

Participants

Participants will be recruited among MCS patients who are registered at the Danish Research Centre for Chemical Sensitivities and have agreed to be contacted for research purposes, or MCS patients who have had recent contact with the Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Denmark.

Forty participants will be included in the period from 1 April 2013 to 26 July 2013. In the event that fewer participants are included during this period, the inclusion period will be extended to 1 November 2013, to make it possible to obtain the full number of participants.

Inclusion criteria

All participants must be between 18 and 75 years of age and meet the extended consensus criteria for MCS [43], which will be put into practice as follows: symptom duration of at least 6 months; symptoms in response to at least two of 11 categories of chemical exposure; at least one CNS symptom and one symptom from another organ system; symptoms causing lifestyle or functional impairments that score ≥35 on the Quick Environmental Exposure and Sensitivity Inventory (QEESI) Life Impact Scale; symptoms occurring when exposed, and improving or resolving when triggering exposures are removed; and symptoms being triggered by exposure levels that do not induce symptoms in other individuals exposed to the same levels. Lastly, all participants must also provide written informed consent.

Exclusion criteria

Participants will be excluded if they report: previous PEMF therapy; psychosis or a comparable disorder; epilepsy; cerebral tumors; leukemia or malignancies in the head or neck region; having a pacemaker or other active implants; pregnancy or nursing; unreliable contraception; drug or alcohol abuse; a pending application or intention to apply for early retirement; initiation of pharmacological treatment that has not stabilized; or participation in another research study.

Withdrawal

Participants will be withdrawn from the study treatment if this is their wish, if they for some reason cannot complete the required PEMF treatments, or if they experience adverse effects at an unacceptable level. Withdrawn participants will be asked to fill in the weekly questionnaires until follow-up has been completed.

Randomization

Participants will be randomly allocated with a 1:1 ratio and in block sizes of 10 to either the intervention group or the control group. The manufacturer of the Re5 device (Re5 Aps) will be responsible for the generation of the allocation sequence by computer for sequential participant numbers. Participants will be numbered sequentially according to their entry into the study. From the allocation sequence, sequentially numbered smartcards will be loaded with the allocated treatment. The allocation sequence will be kept locked up in two copies, one of which the investigators will have access to if a serious adverse event occurs.

Blinding

Re5 devices will be identical for both study groups and will be operated using a smartcard, upon which the type and duration of treatment is loaded. Two types of smartcards will be produced: smartcards that are loaded with active treatments, and smartcards that are loaded with inactive (placebo) treatments. As the appearances of the smartcards will be identical, both participants and investigators will be blinded to treatment allocation. Due to a limited time frame, the allocation sequence will be unmasked for the investigators when the last participant has completed PEMF therapy to be able to conduct the statistical analyses on the post treatment data. The unmasking of the sequence for the participants will take place when all participants have completed the last follow-up. Since the outcome measures at follow-up are self-rated by the participants and there will be no communication of any kind between the investigators and the participants, we do not expect that the premature unmasking of the allocation sequence for the investigators will have any influence on the follow-up data. A research nurse will remain fully masked and will ensure that follow-up data are collected.

Intervention

PEMF will be applied using the Re5 Independent System, which consists of the Re5 Independent (pulse generator), the Re5 Applicator Head (seven coils), and the Re5 Smartcard. Participants will receive PEMF therapy or placebo applied transcranially for 7 days a week over 6 consecutive weeks. The duration of treatment will be 30 minutes twice a day; that is, morning (06:00 to 09:00 hours) and evening (17:00 to 20:00 hours). Participants will receive instructions from the investigators on how to operate the Re5 device and the treatment will take place in the participants’ homes. PEMF therapy is painless and participants will be able to read or do whatever comes naturally to them while wearing the Re5 device.

Participants who receive pharmacological therapy for MCS or another condition will continue their treatment unchanged during the study. All medication use will be registered.

Control visits/calls

During treatment, control visits will be arranged for all participants at weeks 1, 2, and 4 after initiation of treatment. At these visits, the smartcards – which contain electronic information on if and when the participants have received the scheduled treatments – will be monitored in order to check compliance. The monitoring will be performed without disclosing the concealed treatment allocation. Furthermore, the control visits will serve to monitor the outcome measurements (filling in the questionnaires) and to register adverse effects. At weeks 3 and 5 an email reminder will be sent in advance to ensure that questionnaires are completed. At this point, the participants will also be contacted by telephone to keep compliance up and if necessary once more to remind them to fill in the questionnaires. A research nurse, who is also blinded to group allocation, will be assigned to perform the control visits/calls.

Baseline characteristics and outcome measurements

To characterize participants at baseline the following parameters will be registered: age, gender, smoking, comorbidities, medications, asthma, and neuroticism as assessed using the NEO Personality Inventory. Asthma will be assessed using questions adopted from the Stage 1 questionnaire of the European Community Respiratory Health Study [44]. Asthma will be defined in accordance with criteria employed by the European Community Respiratory Health Study as an affirmative answer to at least one of the following questions: Have you been woken by an attack of shortness of breath at any time in the last 12 months? Have you had an attack of asthma in the last 12 months? Are you currently taking any medicine (including inhalers, aerosols or tablets) for asthma?

Outcomes will be measured at baseline (week 0), once weekly during treatment (weeks 1 to 5), post treatment (week 6), and at 2.5-month and 4.5-month follow-ups as shown in Table 1. The self-administered questionnaires will be completed using an online questionnaire tool.

Table 1

Table 1

Timetable for outcome measurements

Primary outcome

Quick environmental exposure and sensitivity inventory
The QEESI was developed as a screening questionnaire for MCS to facilitate the recording of patient anamneses [45]. In this study, three of five original scales will be used by means of an evaluated Danish translation [46]: Symptom Severity Scale, Chemical Intolerance Scale, and Life Impact Scale. Each scale contains 10 items that produce a score ranging from 0 to 100. The QEESI Life Impact Scale is the primary outcome measure in this trial.

Secondary outcomes

Quick environmental exposure and sensitivity inventory
The QEESI Symptom Severity and Chemical Intolerance Scales will be used to measure the severity of general symptoms and of exposure-related symptoms, respectively.

Sheehan disability scale
The Sheehan Disability Scale is widely used in psychiatry, but has also been applied to many other chronic illnesses. This scale uses visuospatial, numeric and descriptive anchors to measure impaired functioning in three domains: work, social life and family life [47]. The scale generates four disability scores, one for each domain and a total score by adding up the three individual domain scores.

Individual self-selected tasks
In addition to the Life Impact Scale used as the primary outcome measure, the participants will be asked to select three tasks in the areas of work, social life and family life, which are impaired by MCS at baseline. The degree of impairment associated with each task is scored on a scale from 0 to 10 with visuospatial, numeric, and descriptive anchors similar to the Sheehan Disability Scale.

Noise sensitivity
To measure the participants’ sensitivity to noise, they will be asked to grade their responses to 10 different noises (for example, drone of a machine, stroke of a hammer, rustling of paper) on a 5-point Likert scale.

Symptom Check List-92
The Symptom Check List-92 subscales for depression, anxiety and somatization will be included. These subscales comprise 35 items on which responses are rated on a 5-point Likert scale ranging from ‘not at all’ to ‘very much’. The Symptom Check List-92 has been validated in a general Danish population and normative data have been established [48,49].

The 6-Item Hamilton Depression Rating Scale
The 6-item Hamilton Depression Rating Scale is a short self-administered measure of depression. The scale has been shown to be as sensitive as the more widely used 17-item Hamilton Depression Rating Scale to measure antidepressive treatment effects [50].

Perceived Stress Scale
The short version of the Perceived Stress Scale consists of 10 questions and measures self-perception of stress by grading how different life situations are perceived. The Perceived Stress Scale-10 has been shown to be a valid and reliable measure of perceived stress [51].

World Health Organization Quality of Life
The brief version of the World Health Organization Quality of Life is a short multidimensional questionnaire, which measures health-related quality of life. The scale consists of four domains: physical health, psychological well-being, social relationships and environment [52].

Capsaicin-induced secondary punctate hyperalgesia
Eight linear vectors will be outlined, arranged radiating at 45° angles on the volar side of the right forearm halfway between the cubital fossa and the wrist. Participants will then receive an intradermal injection of 0.1 ml capsaicin in a concentration of 3.3 μM (1 μg/ml, 0.01% solution) at the meeting point of the eight vectors using a 29-gauge disposable needle producing a circular blister with a radius of 0.5 cm. A handheld mechanical probe (diameter 0.6 mm, weight 50.1 g; Centre for Sensory-Motor Interaction, Aalborg University, Aalborg, Denmark) with a blunt tip, which exerts the same force at each application, will be used to determine the area of secondary punctate hyperalgesia at 10 and 30 minutes post injection. During the procedure, participants will be blindfolded and the probe will be applied to the skin for 1 second with an interstimulus interval of 2 seconds, starting from a point well outside the injection site and then sequentially reapplied to the skin moving along a vector towards the injection site in steps of 0.5 cm. The participants will be instructed to report when the pricking sensation changes in intensity or character to become more intense, painful, burning or otherwise different. When the participant reports a change in sensation at two successive points, the first point will be marked. This procedure will be repeated along all eight vectors (V1 to V8). The eight marks will be connected to form an area of secondary punctuate hyperalgesia. The area will be calculated using trigonometry by the rule of the area of a triangle, adding up and subtracting the area of the capsaicin blister:

Area=0.5⋅sin(45°)⋅(V1⋅V2+V2⋅V3+…+V7⋅V8)(+V8⋅V1)–(π⋅0.52)

An area will be calculated only when there are at least two neighboring marks. A double assessment at 10 and 30 minutes post injection will be used to derive a mean area of secondary punctate hyperalgesia. In addition, capsaicin-induced pain will be measured by means of a visual analog scale with a low anchor point (no pain) and a high anchor point (worst pain imaginable). The visual analog scale measurement will be transformed into a numerical value using a ruler.

Immunological markers in serum
Blood samples will be collected from all participants twice during the study: one sample at baseline and one sample post treatment. Plasma will be separated by centrifuge within 30 minutes, frozen at −80°C and stored until analyses in batches. The serum concentration of the following regulating inflammatory cytokines will be assessed: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-21, IL-22, IL-23, TNFα, IFNγ.

Sample size

The sample size calculation for the primary outcome measure, the QEESI Life Impact Scale, is based on a two-sample t test. A recent study among Danish MCS patients found a mean value of 61.5 with a standard deviation of 24.3 on the Life Impact Scale [46]. In this study, the intervention is expected to induce a 40% decrease on this scale. We thus expect the mean QEESI score in the intervention group to decrease to 36.9 and the mean QEESI score in the control group to remain unchanged. Since we do not know the standard deviation of the change score we base our sample size calculation on the assumption that the standard deviation of the change score is 24.3. Under these assumptions and with a two-sided significance level set at 0.05, the study will require 17 participants in each group to be able to reject the null hypothesis with a power of 0.80. Expected dropouts are estimated at three participants in each group, which means that the total number of participants needed is 40.

Statistical analyses

Statistical analyses will be conducted using SPSS (SPSS Inc, Chicago, IL, USA) and SAS (SAS Institute Inc, NC, USA). Data will be anonymized and analyzed by a statistician blinded to the participants’ group affiliation; that is, intervention group or control group. The statistician will remain fully masked during planning and conduction of the statistical analyses. Descriptive statistics for the two groups will be generated. Intention-to-treat analyses with a two-sided significance level at 0.05 will be conducted using the mixed-model repeated-measures method for continuous measures. This model ensures that data values which are missing at random will not create bias. Sensitivity analyses will be used to assess the possible impact of nonrandomly missing values. Prevention of missing values will be attempted by reminding (email and/or telephone) the participants to fill in the questionnaires. Since PEMF therapy is a new approach to treating MCS, per-protocol analyses will be carried out additionally to evaluate a possible treatment effect, if Re5 therapy is applied as specified; that is, compliance ≥80%. The final analyses will be adjusted for baseline levels to improve power. According to the sample size calculation, the two-sample t test will have sufficient power to detect a treatment effect, but a mixed model, which utilizes all available data, is likely to be more powerful. The criteria of success in the study are significantly positive changes in the intervention group compared with the control group regarding the primary and secondary outcomes.

Ethical considerations

The study has obtained approval from the regional ethics committee (registration number: H-1-2013-006) and the Danish Health and Medicines Authority (EUDAMED CIV-ID number 13-01-009621) and is registered with the Danish Data Protection Agency.

In previous studies, only few and mild adverse effects related to transcranial PEMF therapy have been reported. These include mild transient nausea and headache. If serious adverse events should occur, an evaluation will be carefully conducted in order to establish whether the event is related to PEMF therapy or other parts of the study. If an association between the serious adverse event and PEMF therapy is suspected, the allocation sequence for the participant concerned will be unmasked. Any adverse effect or event reported during the study will be registered and reported to the relevant authorities and in future publications.

The study will be conducted in accordance with Good Clinical Practice guidelines and will be monitored by the GCP Unit at Copenhagen University Hospital.

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Discussion.

MCS is a condition that may have substantial individual and social consequences. In spite of this, an effective treatment for MCS has not yet been documented. This trial will test whether PEMF therapy can effectively ameliorate the negative effects of MCS in a randomized controlled design. The main strength of the study is that this is the first randomized, double-blind, placebo-controlled trial assessing a possible treatment for MCS. The results will show whether PEMF therapy is beneficial for MCS patients in terms of impact on patients’ lives, symptoms, psychological distress, life quality and whether an associated capsaicin-related CNS response and immunological markers are influenced by the intervention.

Some limitations of the study must be considered. Although the case criteria used in this study are generally accepted, there is no officially approved case definition for MCS and the case criteria are based on self-report because no objective clinical tests are available to confirm the condition.

Furthermore, the study will include MCS patients who experience severe functional impairments because of MCS, which means that the outcomes of the study may not be applicable to all MCS cases. However, in light of the absence of objective clinical tests, functional impairment is a clinically relevant parameter in the assessment of a possible treatment effect. Apart from the fact that a treatment with well-documented effects on MCS is absent, there is very little else to offer these patients in terms of healthcare in general. There is thus a great need for well-conducted randomized trials aimed at assessing possible treatment effects. PEMF therapy is a promising treatment, which can be targeted at the CNS, and a positive outcome of this trial will pave the way for improved healthcare and understanding of this very disabling and overlooked condition.

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Trial status.

Participants are being recruited for the study.

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Abbreviations.

CNS: Central nervous system; IFN: Interferon; IL: Interleukin; MCS: Multiple chemical sensitivity; PEMF: Pulsed electromagnetic fields; QEESI: Quick Environmental Exposure and Sensitivity Inventory; TNF: Tumor necrosis factor.

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Competing interests.

The authors declare that they have no competing interests.

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Authors’ contributions.

All authors contributed to the study design. MTDT drafted the manuscript and SS, LA-N, KBC and JE reviewed and revised the manuscript. All authors read and approved the final version.

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Acknowledgements.

The authors thank Lisbeth Møller Christensen for contributing to the study design on behalf of Re5 Aps. The study is funded by the Danish Ministry of the Environment and has received a research grant from Aage Bang’s Foundation.

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References.

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*Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765111/