Answers and Questions: Forty Years in Bioelectromagnetics.

The work began in 1972 when three young assistant professors used a slime mold to see if electromagnetic fields would affect it. The fields did, though the effects were small and hard to tease out of the noise. The cell cycle was lengthened and there were changes in respiration. So, the next question was "how and why?" Further changes were seen using these and then other bacterial and eukaryotic cells in respiration, in ATP, in the protein replication chain, and so forth. Changes occurred even in cell extracts that lacked an intact plasma membrane. Nerve cells showed changes in leakage of neurotransmitters and in neurite outgrowth from excised ganglia. Based on some experiments with nerve cells, I also did some computer calculations, modeling the internal electric and magnetic fields and current densities in simplified representations of bone fractures and also of spinal cords in vertebrae. More recently, I have collaborated on some theoretical models of what fields might be doing at the cellular and molecular level, particularly with reference to the radical model. With each piece of research, my collaborators and I generally found a small piece of information about fields and biological systems; and each answer raised another set of questions, which is the way of science. Though bioelectromagnetic scientists have learned much and can say much at greater depth about what happens when an organism is exposed to a field, the fundamental question still remains: What exactly is going on here? © 2021 Bioelectromagnetics Society.

Extremely Low-Frequency Magnetic Fields and the Risk of Childhood B-Lineage Acute Lymphoblastic Leukemia in a City With High Incidence of Leukemia and Elevated Exposure to ELF Magnetic Fields.

It is important to study the relationship between extremely low-frequency magnetic fields (ELF-MFs) and childhood leukemia, particularly in locations with a high incidence of this neoplasm in children and an elevated exposure to ELF-MF, such as Mexico City. The aim was to investigate the association between ELF-MF exposure and the risk of B-lineage acute lymphoblastic leukemia (B-ALL). A case-control study was conducted in Mexico City during the period from 2010 to 2011. Residential 24-h ELF-MF measurements were obtained for 290 incident B-ALL patients and 407 controls, aged less than 16 years. Controls were frequency-matched by sex, age (±18 months), and health institution. The adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated. ELF-MF exposure at <0.2 µT was used to define the reference group. ELF-MF exposure at ≥0.3 µT was observed in 11.3% of the controls. Different ELF-MF intensity cutoff values were used to define the highest exposure category; the highest exposure category for each cutoff value was associated with an increased risk of B-ALL compared with the corresponding lower exposure categories. The aORs were as follows: ≥0.2 µT = 1.26 (95% CI: 0.84-1.89); ≥0.3 µT = 1.53 (95% CI: 0.95-2.48); ≥0.4 µT = 1.87 (95% CI: 1.04-3.35); ≥0.5 µT = 1.80 (95% CI 0.95-3.44); ≥0.6 µT = 2.32 (95% CI: 1.10-4.93). ELF-MF exposure as a continuous variable (per 0.2 µT intervals) was associated with B-ALL risk (aOR = 1.06; 95% CI: 1.01-1.12). In the present study, the proportion of children exposed to ≥0.3 µT is among the highest reported worldwide. Additionally, an ELF-MF exposure ≥0.4 µT may be associated with the risk of B-ALL. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

The effect of vitamin E and C on comet assay indices and apoptosis in power plant workers: A double blind randomized controlled clinical trial.

Extremely low frequency electromagnetic fields have been classified as a possible human carcinogen by the International Agency for Research on Cancer and this has raised some concern about its health effects on employees extensively exposed to these fields at thermal power plants. In this study, the effect of using vitamin E and C supplements have been examined on employees working at a thermal power plant. In this randomized controlled, double-blind clinical trial, 81 employees from different parts of the thermal power plant were enrolled between July and November 2017, and divided into four groups: Group 1 received vitamin E (400 units/day), Group 2: vitamin C (1000 mg/day), Group 3: vitamin E + C and Group 4: no intervention. DNA damage was measured in peripheral blood lymphocytes using comet assay and apoptosis, using flow cytometry. Based on the results, tail intensity and tail length in the vitamin E group, and all comet assay indices in the vitamin E + C and vitamin C groups (except DNA damage index) significantly decreased after the intervention, while the comet assay indices did not change significantly in the control group. None of the flow cytometry indices including early apoptosis, late apoptosis and necrosis changed after intervention in either group. The use of antioxidant vitamins such as E and C, can increase the activity of the non-enzymatic antioxidant defense system, and protect DNA from damage caused by exposure to extremely low frequency magnetic fields. But, taking these vitamins has no effect on apoptosis. It seems that consumption of vitamin E affected all investigated comet assay indices and can be probably considered as the best intervention.

Chromosome aberration in typical biological systems under exposure to low- and high-intensity magnetic fields.

The aim of this study was to investigate the response of chromosomes in typical human and plant cells under applied low-frequency magnetic fields at low and high intensities. Neuronal-like cells and roots of Allium sativum and Vicia faba were used to investigate chromosome's response to a static and 50 Hz magnetic fields at intensities ranging from 1 mT to 0.8 T, generated by two Helmholtz coils driven by direct current or alternate current voltage. Vertex spectrometer and Olympus microscope with camera were used. A significant decrease in intensity of the phosphate bands in the DNA infrared region was observed by FTIR spectroscopy analysis after exposure of neuronal-like cells to static and 50 Hz magnetic field at low intensity of 1 mT, which can be explained assuming that uncoiling and unpackaging of chromatin constituents occurred after exposure. This effect was directly observed by microscope in roots of Allium sativum and Vicia faba under exposure to a static magnetic field at high intensity of 0.8 T. These findings can be explained assuming that exposure to both low- and high-intensity magnetic fields of chromosomes in typical human and plant cells induces uncoiling and unpackaging of chromatin constituents, followed by chromosome alignment towards the direction of applied magnetic field, providing further demonstration that magnetic fields can induce the orientation of organic macromolecules even at low-intensity values.

Impact of magnetic fields generated by AC/DC submarine power cables on the behavior of juvenile European lobster (Homarus gammarus).

The number of submarine power cables using either direct or alternating current is expected to increase drastically in coming decades. Data concerning the impact of magnetic fields generated by these cables on marine invertebrates are scarce. In this context, the aim of this study was to explore the potential impact of anthropogenic static and time-varying magnetic fields on the behavior of recently settled juvenile European lobsters (Homarus gammarus) using two different behavioral assays. Day-light conditions were used to stimulate the sheltering behavior and facilitate the video tracking. We showed that juvenile lobsters did not exhibit any change of behavior when submitted to an artificial magnetic field gradient (maximum intensity of 200 µT) compared to non-exposed lobsters in the ambient magnetic field. Additionally, no influence was noted on either the lobsters' ability to find shelter or modified their exploratory behavior after one week of exposure to anthropogenic magnetic fields (225 ±â€¯5 µT) which remained similar to those observed in control individuals. It appears that static and time-varying anthropogenic magnetic fields, at these intensities, do not significantly impact the behavior of juvenile European lobsters in daylight conditions. Nevertheless, to form a complete picture for this biological model, further studies are needed on the other life stages as they may respond differently.

In Vitro Evaluation of the Effect of Stimulation with Magnetic Fields on Chondrocytes.

Magnetic fields (MFs) have been used as an external stimulus to increase cell proliferation in chondrocytes and extracellular matrix (ECM) synthesis of articular cartilage. However, previously published studies have not shown that MFs are homogeneous through cell culture systems. In addition, variables such as stimulation times and MF intensities have not been standardized to obtain the best cellular proliferative rate or an increase in molecular synthesis of ECM. In this work, a stimulation device, which produces homogeneous MFs to stimulate cell culture surfaces was designed and manufactured using a computational model. Furthermore, an in vitro culture of primary rat chondrocytes was established and stimulated with two MF schemes to measure both proliferation and ECM synthesis. The best proliferation rate was obtained with an MF of 2 mT applied for 3 h, every 6 h for 8 days. In addition, the increase in the synthesis of glycosaminoglycans was statistically significant when cells were stimulated with an MF of 2 mT applied for 5 h, every 6 h for 8 days. These findings suggest that a stimulation with MFs is a promising tool that could be used to improve in vitro treatments such as autologous chondrocyte implantation, either to increase cell proliferation or stimulate molecular synthesis. Bioelectromagnetics. 2020;41:41-51 © 2019 Bioelectromagnetics Society.

Moderate Intensity Static Magnetic Fields Prevent Thrombus Formation in Rats and Mice.

We established three types of thrombosis models to explore the effects of the static magnetic field (SMF) on thrombosis in rats and mice with three different MF intensities. In the carrageenan-induced thrombosis model in rats, the SMF treatments reduced the black tail length of rats, extracorporeal thrombus, and the mass of wet and dry thrombus, and improved the coagulation index value. In FeCl3 -induced arterial thrombosis model in rats, the SMF treatment showed some anti-thrombotic effects. More specifically, the SMF treatment affected rodent blood pressure, plasma plasminogen activator inhibitor, tissue-type plasminogen activator, thrombus mass, and thrombus protein content. In the adrenaline-induced thrombosis model in mice, the SMF treatment had certain effects on the diameter and blood flow velocity of mouse auricle microcirculation in fine veins and arteries. Overall, the highest MF intensities we tested, 20-150 mT, showed a trend of anti-thrombotic effect, indicating that the moderate-intensity SMF might serve as a potential treatment for clot-related diseases in the future. Bioelectromagnetics. 2020;41:52-62 © 2019 Bioelectromagnetics Society.

An Extremely Low Frequency Magnetic Field and Global Cerebral Ischemia Affect Pituitary ACTH and TSH Cells in Gerbils.

The neuroendocrine system can be modulated by a magnetic field and cerebral ischemia as external and internal stressors, respectively. This study deals with the separate or combined effects of an extremely low frequency (ELF) magnetic field (50 Hz, average magnetic field of 0.5 mT) for 7 days and global cerebral ischemia for 10 min on the morpho-functional features of pituitary adrenocorticotrophic (ACTH) and thyrotrophic (TSH) cells in 3-month-old gerbils. To determine the immediate and delayed effects of the applied stressors, measurements were made on the 7th and 14th days after the onset of the experiment. The ELF magnetic field and 10-min global cerebral ischemia, separately and particularly in combination, decreased (P < 0.05) the volume density of ACTH cells, while only in combination were intracellular ACTH content and plasma ACTH concentration increased (P < 0.05) on day 7. The ELF magnetic field elevated serum TSH concentration on day 7 and intracellular TSHß content on day 14 (P < 0.05). Also, 10-min global cerebral ischemia alone increased serum TSH concentration (P < 0.05), while in combination with the ELF magnetic field it elevated (P < 0.05) intracellular TSHß content on day 14. In conclusion, an ELF magnetic field and/or 10-min global cerebral ischemia can induce immediate and delayed stimulation of ACTH and TSH synthesis and secretion. Bioelectromagnetics. 2020;41:91-103. © 2019 Bioelectromagnetics Society.

Registry of Buildings With Transformer Stations as a Basis for Epidemiological Studies on Health Effects of Extremely Low-Frequency Magnetic Fields.

Buildings with indoor transformer stations may serve as a basis for improved epidemiological studies on the health effects of extremely low-frequency magnetic fields (ELF MFs). Previous studies have shown that ELF MF exposure can be adequately assessed based on the fact that MF levels are high in apartments directly above transformers. In this paper, we describe the creation of a registry of Finnish residential buildings with built-in transformer stations and discuss its usability in epidemiological studies. Information obtained from electric utilities and building blueprints were used to identify 677 buildings in which an apartment was located above or adjacent to a transformer station. All apartments in these buildings were classified into exposure categories based on their location in relation to the transformer. Residential histories of these buildings were obtained from the Population Register Centre. Out of the 287,668 individuals who have resided in the buildings, 9,126 of them have resided in an apartment located directly above a transformer station. All information was collected without contacting residents, thus avoiding selection bias. The registry can be linked with data from high-quality nationwide registries to confirm or challenge the reported associations of ELF MF exposure and diseases such as cancer, miscarriage, and Alzheimer's disease. Bioelectromagnetics. 2020;41:34-40 © 2019 Bioelectromagnetics Society.

Characterization of Levels of Extremely Low Frequency Magnetic Fields Emitted From Portable Hand-Held Fans.

This study aims to assess the levels of extremely low frequency magnetic fields (ELF-MF) emitted from portable hand-held fans (HHFs) and their principal frequency and to identify factors influencing these levels. We collected a total of eleven models of HHF and monitored the ELF-MF as a function of fan speed and distance from the fan. EMDEX II was used to monitor the ELF-MF. An SMP2 EMF-meter equipped with a P400 field probe was used to determine the levels of ELF-MF and the frequency spectrum. Ten of the fans, excluding only one bladeless-fan model, emitted a high level of ELF-MF near the source of the HHF direct-current motor. The maximum measured level of ELF-MF ranged from 14.07 to 218.7 µT. All measurements of the ELF-MF taken within 10 cm from the HHFs showed values higher than 1.0 µT. ELF-MF levels were found to decrease markedly with distance, regardless of the HHF product. The level of ELF-MF rose noticeably with increased fan speed. The speed of and distance from the HHF significantly influenced the level of ELF-MF. All principal frequencies ranged from 1 to 300 Hz, which falls in the typical range of ELF. Bioelectromagnetics. 2019;40:569-577. © 2019 Bioelectromagnetics Society.

Magnetic Resonance Examinations of Patients With Implanted Active Devices. A Low-Cost Approach in Slew Rate Evaluation.

Time-varying magnetic field gradients involved in magnetic resonance examinations can damage implanted electronic systems. The quantity related to this side effect is the gradient slew rate, which is usually not directly available on magnetic resonance console. The present study proposes a low-cost approach in slew rate assessment, which is useful in risks versus benefits evaluation as well as in sequences optimization. The experimental method is based on an analog circuit, which senses the output voltage of the scanner waveform generator. This allows taking easy and reliable slew rate measurements, even during clinical examinations on patients. Whereas previous studies required managing a considerable amount of data, the present work addresses only the maximal slew rate of any clinical sequence. Experimental results show that the smooth gradient mode, selectable on the two scanners examined, is very effective in patient safety improvement. In particular, it reduces slew rate values in the range from 52.4 up to 132.4 T m-1 s-1 , i.e. far below the interval 216-346 T m-1 s-1 , indicated as slew rate tolerance limit of modern implanted electronic devices. Bioelectromagnetics. 2019;40:512-521. © 2019 Bioelectromagnetics Society.

Effects of 50 Hz magnetic fields on circadian rhythm control in mice.

Artificial light and power frequency magnetic fields are ubiquitous in the built environment. Light is a potent zeitgeber but it is unclear whether power frequency magnetic fields can influence circadian rhythm control. To study this possibility, 8-12-week-old male C57BL/6J mice were exposed for 30 min starting at zeitgeber time 14 (ZT14, 2 h into the dark period of the day) to 50 Hz magnetic fields at 580 µT using a pair of Helmholtz coils and/or a blue LED light at 700 lux or neither. Our experiments revealed an acute adrenal response to blue light, in terms of increased adrenal per1 gene expression, increased serum corticosterone levels, increased time spent sleeping, and decreased locomotor activity (in all cases, P < 0.0001) compared to an unexposed control group. There appeared to be no modulating effect of the magnetic fields on the response to light, and there was also no effect of the magnetic fields alone (in both cases, P > 0.05) except for a decrease in locomotor activity (P < 0.03). Gene expression of the cryptochromes cry1 and cry2 in the adrenals, liver, and hippocampus was also not affected by exposures (in all cases, P > 0.05). In conclusion, these results suggest that 50 Hz magnetic fields do not significantly affect the acute light response to a degree that can be detected in the adrenal response. Bioelectromagnetics. 2019;9999:XX-XX. © 2019 Bioelectromagnetics Society.

Carcinogenicity of intermediate frequency magnetic field in Tg.rasH2 mice.

Although the likelihood of exposure to leaking intermediate frequency magnetic fields (MFs) from electronic devices, such as induction-heating and wireless power transfer systems, has increased, biological data assessing the health risks associated with human exposure remain insufficient. We examined the carcinogenicity of a 20 kHz MF, a typical frequency produced by induction-heating cookers, using a transgenic rasH2 mouse model. Twenty-five male and female CByB6F1-Tg(HRAS)2Jic mice were exposed to a 0.20 mT, 20 kHz MF (22 h/day) or sham-exposed for 26 weeks. As a positive control, 10 male and female rasH2 mice from the same batch were administered a single intraperitoneal injection of 75 mg/kg N-methyl-N-nitrosourea. A blinded histopathological evaluation was performed, and the same experiments were conducted twice, independently, to confirm the reproducibility of the results. Histopathological examination revealed that spontaneous neoplastic lesions, such as splenic hemangiosarcomas and gastric squamous cell papillomas, were less (1-3 per group) in the MF- and sham-exposed groups. The frequency of the neoplastic lesions was not significantly different between the groups. Eight to ten mice in each positive-control group exhibited malignant lymphoma. The outcomes were consistent between duplicated experiments, which indicates lack of carcinogenicity of 20 kHz MF in the rasH2 mouse model. Bioelectromagnetics. © 2019 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.

3D space-dependent models for stochastic dosimetry applied to exposure to low frequency magnetic fields.

In this study, an innovative approach that combines Principal Component Analysis (PCA) and Gaussian process regression (Kriging method), never used before in the assessment of human exposure to electromagnetic fields (EMF), was applied to build space-dependent surrogate models of the 3D spatial distribution of the electric field induced in central nervous system (CNS) of children of different ages exposed to uniform magnetic field at 50 Hz of 200 µT of amplitude with uncertain orientation. The 3D surrogate models showed very low normalized percentage mean square error (MSE) values, always lower than 0.16%, confirming the feasibility and accuracy of the approach in estimating the 3D spatial distribution of E with a low number of components. Results showed that the electric field values induced in CNS tissues of children were within the ICNIRP basic restrictions for general public, with 99th percentiles of the E values obtained for each orientation showing median values in the range 1.9-2.1 mV/m. Similar 3D spatial distributions of the electric fields were found to be induced in CNS tissues of children of different ages. Bioelectromagnetics. 9999:1-10, 2018. © 2019 Bioelectromagnetics Society.

Hypomagnetic fields cause anxiety in adult male mice.

Hypomagnetic fields (HMF), that is, the elimination of the geomagnetic field (GMF), are a risk factor to the health of astronauts in outer space. It has been established that continuous HMF exposure affects cytoskeleton assembly, cell proliferation, embryonic development, and even learning and memory. In addition, although there were some previous studies that focused on the effects of long-term HMF-exposure, so far very limited investigations have been conducted to examine the short-term HMF effect in animals. In this study, we exposed adult male C57BL/6 mice to a 3-axis Helmholtz-coil HMF-simulation system for 72 h and found that short-term HMF-exposure induced a significant increase in anxiety-related behaviors. And our findings provide important information for both psychological intervention and the health care of astronauts. Bioelectromagnetics. 40:27-32, 2019. © 2018 Wiley Periodicals, Inc.

50-Hz MF does not affect global DNA methylation of SH-SY5Y cells treated with the neurotoxin MPP.

Exposure to extremely low frequency magnetic fields (ELF-MFs) has been associated with an increased risk of neurodegenerative disorders. The underlying mechanisms, however, are still debated. Since epigenetics play a key role in the neurodegenerative process, we investigated whether exposure to ELF-MF (50 Hz, 1 mT) might affect global DNA methylation of SH-SY5Y dopaminergic-like neuroblastoma cells. We assessed the percentage of 5-methylcytosine (5-mC) of three repetitive interspersed sequences (ALU, LINE-1, or SATα), through pyrosequencing analysis. We demonstrated that ELF exposure (up to 72 h) does not induce any change in the methylation pattern of ALU, LINE-1, and SATα in both proliferating and differentiated SH-SY5Y cells. Furthermore, when administered in combination with 1-methyl-4-phenylpyridinium (MPP+ ), a neurotoxin mimicking the Parkinson's Disease (PD) phenotype, ELF-MF exposure does not trigger any modulation in the percentage of 5-mC of the repetitive elements. Our findings demonstrate that exposure to 50-Hz MF does not affect global DNA methylation in proliferating and dopaminergic differentiated SH-SY5Y cells, either under basal culture conditions or under neurotoxic stress. Bioelectromagnetics. 40:33-41, 2019. © 2018 Bioelectromagnetics Society.

The effect of 20-week continuous 60 Hz magnetic field exposure on testicular function in sprague-dawley rats.

Accumulating evidence does not yet confirm the effect of power line frequency magnetic field (MF) on human health and fertility. We recently reported that, at continuous 60 Hz MF exposure in mice, the dose given as magnetic flux density (tesla; T) and duration of exposure was related to induce testicular germ cell apoptosis. We aimed to characterize the effect of a 20-week continuous exposure to 60 Hz MF on the motility, morphology, and number of sperm as well as the apoptosis of testicular germ cell in rats. Sprague-Dawley rats were exposed for 20 weeks to 60 Hz MF of 2, 20, or 200 µT for 24 h/day with rats exposed to sham conditions, serving as the control. The exposure to 60 Hz MF of 2 and 20 µT had no effects on testicular in this study. The exposure to 60 Hz MF of 200 µT for 20 weeks induced increases of the apoptotic cells (P < 0.001) in germ cells and decreases of sperm numbers (P < 0.05). However, the MF did not significantly affect the body or testis mass, seminiferous tubule diameter, or the motility or morphology of sperm. This study concluded that exposure to 60 Hz MF of 200 µT can increase testicular germ cell apoptosis, especially spermatogonia, and reduce sperm count. Also compared to previous mice studies, rats are less sensitive than mice to exposure to 60 Hz MF. Bioelectromagnetics. 39:539-546, 2018. © 2018 Wiley Periodicals, Inc.

Calibration and non-orthogonality correction of three-axis Hall sensors for the monitoring of MRI workers' exposure to static magnetic fields.

A Magnetic Resonance Imaging (MRI) scanner uses three different electromagnetic fields (EMF) to produce body images: a static permanent magnetic field (MF), several pulsed magnetic gradients, and a radiofrequency pulse. As a result, any occupation that includes an MRI exposes workers to a strong MF. The World Health Organization has now given the monitoring of occupational EMF exposure a high priority. One design for a low-cost, compact MF exposure monitor (« MR exposimeter ¼) uses a set of three orthogonally assembled Hall sensors. However, at such a strong EMF exposure intensity, the non-linearity and non-orthogonality (misalignment between the three Hall sensors) have an impact on the accuracy of EMF measurement. Therefore, a sensor characterization was performed in order to link Hall-effect output voltage to MF intensity. The sensor was then calibrated using an orthogonalization matrix and an offset vector. For each sensor configuration, the matrix and vector parameters were optimized with a calibration set generated by the movement of a three-axis sensor inside homogeneous MF areas. Once calibrated, the sensor was tested at different MF intensities and returned accuracy improvements. This calibration procedure was tested on synthetic data and performed on experimental data. The calibration parameters can be easily reused by the user, and their stability could be used as a quality control sensor. Finally, real-time monitoring test for static MF exposure was completed and validated on an MRI worker during a typical working day. Bioelectromagnetics. 39:108-119, 2018. © 2018 Wiley Periodicals, Inc.

Occupational exposure to extremely low-frequency magnetic fields and the risk of ALS: A systematic review and meta-analysis.

We performed a meta-analysis to examine associations of occupational exposure to extremely-low frequency magnetic fields (ELF-MF) with amyotrophic lateral sclerosis (ALS). Epidemiologic studies were identified in EMBASE and MEDLINE, in reference lists and a specialist database. We included studies that reported risk estimates of ALS in association with occupational ELF-MF exposure. Summary relative risks (RR) or odds ratios (OR) were obtained with random effect meta-analysis, and analyses were stratified by type of exposure assessment. This was done to evaluate whether observed heterogeneity between studies could be explained with differences in the way the exposure had been determined. We included 20 studies in our meta-analysis. Overall, studies reported a slightly increased risk of ALS in those exposed to higher levels of ELF-MF compared to lower levels with a summary RR (sRR) of 1.14 (95% Confidence Interval [CI] 1.00-1.30) and for workers in electrical occupations (sRR 1.41, CI 1.05-1.92), but with large heterogeneity between studies (I2 > 70%). Self-reported exposure or occupations determined from death certificates did not show increased risks. Highest-longest types of exposure translated into increased risks of ALS if the studies had evaluated the whole occupational history, in contrast to evaluating only few points in time (e.g., from census records); sRR were 1.89 (CI 1.31-2.73, I2 0%) and 1.06 (CI 0.75-1.57, I2 76%), respectively. In this meta-analysis, we observed an increased risk of ALS in workers occupationally exposed to ELF-MF. Results of studies depended on the quality of the exposure assessment. Bioelectromagnetics. 39:156-163, 2018. © 2018 Wiley Periodicals, Inc.

An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke.

Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-MF in patients with acute ischemic stroke. Within 48 hours from the stroke onset, patients started ELF-MF treatment, daily for 5 consecutive days. Clinical follow-up lasted 12 months. Brain MRI was performed before and 1 month after the treatment. The distribution of ELF-MF in the ischemic lesion was estimated by dosimetry. Six patients were stimulated, three for 45 min/day and three for 120 min/day. None of them reported adverse events. Clinical conditions improved in all the patients. Lesion size was reduced in one patient stimulated for 45 minutes and in all the patients stimulated for 120 minutes. Magnetic field intensity within the ischemic lesion was above 1 mT, the minimum value able to trigger a biological effect in preclinical studies. Our pilot study demonstrates that ELF-MF are safe and tolerable in acute stroke patients. A prospective, randomized, placebo-controlled, double-blind study will clarify whether ELF-MFs could represent a potential therapeutic approach.