Oxid Med Cell Longev. 2017; 2017: 2181942. Published online 2017 Sep 12. doi:  10.1155/2017/2181942 PMCID: PMC5613626

Benign Effect of Extremely Low-Frequency Electromagnetic Field on Brain Plasticity Assessed by Nitric Oxide Metabolism during Poststroke Rehabilitation

Natalia Cicho,

 ¹ Piotr Czarny, ² Micha? Bijak, ¹ El?bieta Miller, ^{3 , 4} Tomasz liwiski, ⁵ Janusz Szemraj, ² and Joanna Saluk-Bijak ¹¹Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, Lodz, Poland ²Department of Medical Biochemistry, Medical University of Lodz, Mazowiecka 6/8, Lodz, Poland ³Department of Physical Medicine, Medical University of Lodz, Pl. Hallera 1, Lodz, Poland ⁴Neurorehabilitation Ward, III General Hospital in Lodz, Milionowa 14, Lodz, Poland ⁵Department of Molecular Genetics, Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Pomorska 141/143, Lodz, Poland

Corresponding author. Natalia Cicho: lp.zdol.inu.loib@nohcic.ailatan Academic Editor: Tanea T. Reed Author information Article notes Copyright and License information Received 2017 May 12; Revised 2017 Jul 2; Accepted 2017 Aug 14. Copyright © 2017 Natalia Cicho et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Nitric oxide (NO) is one of the most important signal molecules, involved in both physiological and pathological processes. As a neurotransmitter in the central nervous system, NO regulates cerebral blood flow, neurogenesis, and synaptic plasticity. The aim of our study was to investigate the effect of the extremely low-frequency electromagnetic field (ELF-EMF) on generation and metabolism of NO, as a neurotransmitter, in the rehabilitation of poststroke patients. Forty-eight patients were divided into two groups: ELF-EMF and non-ELF-EMF. Both groups underwent the same 4-week rehabilitation program. Additionally, the ELF-EMF group was exposed to an extremely low-frequency electromagnetic field of 40Hz, 7mT, for 15min/day. Levels of 3-nitrotyrosine, nitrate/nitrite, and TNF? in plasma samples were measured, and NOS2 expression was determined in whole blood samples. Functional status was evaluated before and after a series of treatments, using the Activity Daily Living, Geriatric Depression Scale, and Mini-Mental State Examination. We observed that application of ELF-EMF significantly increased 3-nitrotyrosine and nitrate/nitrite levels, while expression of NOS2 was insignificantly decreased in both groups. The results also show that ELF-EMF treatments improved functional and mental status. We conclude that ELF-EMF therapy is capable of promoting recovery in poststroke patients.

1. Introduction

Cardiovascular diseases, including ischemic stroke (IS), are a serious problem of the modern age, killing 4 million people each year in Europe [1]. Stroke is caused by ischemia of brain tissue. Brain structure damage occurring during ischemia/reperfusion is due to the generation of significant amounts of reactive oxygen species and inflammatory mediators [2]. Damage to brain tissue as a result of a stroke cannot be undone. However, the most important part of poststroke therapy is immediate and long-term rehabilitation, considering the enormous plasticity of the brain [3]. Although extremely low-frequency electromagnetic field (ELF-EMF) therapy is not a standard treatment in the poststroke rehabilitation, some authors suggest its increased positive effect on patients [4]. ELF-EMF treatment is based on regeneration, osteogenesis, analgesics, and anti-inflammatory action. Its biological effect is related to processes of ion transport, cell proliferation, apoptosis, protein synthesis, and changes in the transmission of cellular signals [5]. The regenerative and cytoprotective effect of ELF-EMF is based on mechanism associated with nitric oxide induction, collateral blood flow, opioids, and heat shock proteins [6].

Nitric oxide (NO) is an unstable, colourless, water-soluble gas with a short half-life (3–6?sec). The compound has one unpaired electron, which makes it a highly reactive free radical. It is characterized by the multiplicity of action in the body, in both physiological and pathological conditions [7]. Synthesis of NO in the organism is catalysed by nitric oxide synthase (NOS), occurring in three isoforms: neuronal (nNOS), inducible (iNOS), and endothelial (eNOS), encoded by different genes whose expression is subject to varying regulation. The constituent isoforms of NOS are eNOS and nNOS, whose activity is associated with concentration of calcium ions and the level of calmodulin in a cell, as well as with hypoxia, physical activity, and the level of certain hormones, that is, oestrogens [8]. In contrast, because it is closely related with the calmodulin, iNOS does not require a high concentration of calcium ions but is regulated by various endogenous and exogenous proinflammatory factors [9].

The two-stage synthesis of NO consists of the oxidation of L-arginine to N-hydroxy-L-arginine and, under the influence of NOS and oxygen, formation of L-citrulline and release of NO. All isoforms of NOS require the same cofactors: nicotinamide adenine dinucleotide phosphate (NADPH), flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), tetrahydrobiopterin (BH4), iron protoporphyrin IX (heme), and O₂[7].

Nitric oxide is one of the most important signal molecules, involved in both physiological and pathological processes. One of the major functions of NO is as a potent vasodilation, increasing the blood flow and regulation of blood pressure, which has been used in clinical practice for many years. Deficiency of this compound is observed in various disorders of many systems: cardiovascular, gastrointestinal, respiratory, and genitourinary [10]. The beneficial effects of NO lie in its platelet inhibition, macrophage cytotoxicity (antibacterial, antiviral, and antiparasitic), and protection of the mucosal lining of the digestive system. On the other hand, excessive expression of iNOS can be disadvantageous, for example, during sepsis. The adverse action of NO is associated with the production of superoxide anions and subsequent generation of peroxynitrite and hydroxyl radicals, which are highly toxic [11].

In the central nervous system, NO as a neurotransmitter regulates cerebral blood flow, as well as neurogenesis and synaptic plasticity. Furthermore, neuronal death is caused by high concentrations of NO by caspase-dependent apoptosis process and promotion of inflammation. Elevated levels of nitric oxide promote necrosis by energy depletion. On the basis of these mechanisms, NO is involved in the etiology of many neurological diseases, such as major depression, schizophrenia, epilepsy, anxiety, and drug addiction [12].

Our study was designed to investigate the effect of ELF-EMF on the metabolism of NO, as a signal molecule in the central nervous system, in the rehabilitation of acute poststroke patients.

2. Materials and Methods

2.1. Blood Sample Collection

Blood samples were collected into CPDA₁-containing tubes (Sarstedt, Nümbrecht, Germany). Immediately upon doing so, a portion of the sample was frozen at ?80°C and the rest of the samples centrifuged to isolate the plasma (15?min, 1500g) at 25°C. Blood samples were collected twice, at an interval of 14 days before and after a standard 10 sessions of therapy. For additional analysis of 3-nitrotyrosine levels, the blood samples were collected three times, at an interval of 28 days: before treatment, after 10 treatments, and after 20 treatments. All blood samples were taken in the morning (between 7am and 9am) under patient fasting condition and stored using the same protocol.

2.2. Subject Presentation

Forty-eight poststroke patients were enrolled in the study. Participants were randomly divided into two groups: ELF-EMF (n = 25) and non-ELF-EMF (n = 23). Patients with metal and/or electronic implants (pacemakers, etc.) were excluded from the ELF-EMF group, for safety reasons. The ELF-EMF group had already undergone ELF-EMF therapy with specific parameters (40Hz frequency, magnetic induction of 5mT (B), rectangular and bipolar waveforms) (Figure 1), which was conducted using a Magnetronic MF10 generator (EiE Elektronika i Elektromedycyna, Otwock, Poland). The parameters were selected on the basis of the fact that low-intensity stimuli improve the vital functions of the body. In addition, rectangular pulses are more intense than sinusoidal and trapezoid, while bipolar pulses show more range of changes than unipolar pulses [13]. The ELF-EMF and non-ELF-EMF groups were treated for the same amount of time (15minutes). The non-ELF-EMF subjects were given only sham exposure. The pelvic girdle of the patients was exposed to the electromagnetic field, because exposure of the head to ELF-EMF can affect the activation of the epilepsy focus in the brain. The same therapeutic program was used for both subject groups. This consisted of aerobic exercise (30min), neurophysiological routines (60?min), and psychological therapy (15?min). Poststroke patients with moderate stroke severity according to NIHSS scores of 4.9 ±3.1 in the ELF-EMF group (aged 48.8 ±7.7) and 5.4 ±2.9 (aged 44.8 ±8.0) in the non-ELF-EMF group were enrolled in the study. Table 1 shows the clinical and demographic characteristics. Participants with haemorrhagic stroke, dementia, chronic or significant acute inflammatory factors, decreased consciousness, and/or neurological illness other than stroke in their medical prestroke history were excluded. The subjects had undergone neurorehabilitation for 4 weeks in Neurorehabilitation Ward III of the General Hospital in Lodz, Poland, as well as internal and neurological examinations. The Bioethics Committee of the Faculty of Biology and Environmental Protection of The University of Lodz, Poland, approved the protocol with resolution numbers 28/KBBN-U/II/2015 and 13/KBBN-U/II/2016. All participants provided written informed consent prior to participation. Depression was screened in both groups using the Geriatric Depression Scale (GDS). Cognitive status was estimated in a Mini-Mental State Examination (MMSE), and functional status using the Barthel Index of Activities of Daily Living (ADL). The GDS, ADL, and MMSE were administered either on the same day as the blood sampling or on the afternoon before.

Figure 1 ELF-EMF description. B=5mT; T = 1.3sec.

Table 1 Clinical demographic characteristics.

2.3. Magnetronic MF10 Devices

ELF-EMF therapy was performed by a Magnetronic MF10 generator as per accepted guidelines. This device is able to produce pulses in rectangular, trapezoid, and sinusoidal shapes. The pulses were applied using an AS-550 applicator (EiE, Otwock, Poland), which has the following properties: 550 mm in diameter, 270mm in length, and 5 layers of 187 turns of 1.45mm twin-parallel wires. Magnetic induction was set at 5mT. The electromagnetic field intensity was not uniformed; its distribution is vertical, while the induction coils are set horizontally. Induction of the electromagnetic field of 5mT is present at the geometric center of the applicator, and the value increases in the proximity to the surface about 7mT. Other factors that could affect EMF were eliminated (electronic measuring instruments occurring in rehabilitation room and other electronic equipment).

2.4. Immunodetection of 3-Nitrotyrosine by c-ELISA

Levels of 3-NT-containing proteins in plasma were determined using a modified c-ELISA method, as described by Khan et al. [14]. 96-well microtiter plates were coated with nitro-fibrinogen (nitro-Fg) (1mg/mL) and kept overnight at 4°C. Concentrations of nitrated proteins inhibiting the binding of anti-nitrotyrosine antibodies were assessed from the standard curve (10–100nM nitro-Fg equivalents) and expressed as nitro-Fg equivalents [15].

2.5. Nitrate/Nitrite Estimation

Plasma samples were diluted twice before the measurement of nitrate/nitrite concentration using a Nitrate/Nitrite Colorimetric Assay Kit (Cayman Chemical Company, USA), based on the two-step Griess method. In the first step, the nitrate is converted to nitrite with nitrate reductase, while in the second step, after addition of the Griess reagent, the nitrite is converted to a deep purple azo compound. The absorbance measurement was performed at 540nm in a 96-well microplate reader (SPECTROstarNano, BMG Labtech, Ortenberg, Germany) [16].

2.6. Determination of NOS2 Expression in Whole Blood Samples

RNA was isolated from the frozen whole blood samples (?80°C), in accordance with the manufacturer’s protocol using TRI Reagent® (Sigma-Aldrich, USA). The aqueous phase was purified in accordance with the manufacturer’s protocol using an InviTrap Spin Universal RNA Mini Kit (Stratec Biomedical Systems, Germany). The purity and quantity of isolated RNA were assessed using a Synergy HTX Multi-Mode Microplate Reader equipped with a Take3 Micro-Volume Plate and connected to a PC running Gen5 Software (BioTek Instruments Inc., Winooski, VT, USA). Isolated RNA (20ng/L) was transcribed onto cDNA with a High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems™, Waltham, MA, USA). Quantitative assays were executed using a TaqMan Hs01075529_m1 probe for human NOS2 genes and an Hs02786624_g1 for endogenous control, which was GAPDH (Life Technologies). Reactions were carried out using a TaqMan Universal Master Mix II, without UNG (Life Technologies) in a BioRad CFX96 real-time PCR system (BioRad Laboratories, Hercules, CA, USA), all in accordance with the manufacturers’ protocols. Relative expression of NOS2 was obtained using the equation 2^Ct, where Ct is the threshold cycle (Ct) value for the target gene minus Ct values obtained for the housekeeping gene GAPDH [17].

2.7. Determination of TNF?

Measurements of human tumour necrosis factor alpha (TNF?) in plasma samples were made with a Human TNF? ELISA development kit (MABTECH, Cincinnati, OH, USA), in accordance with the manufacturer’s protocol. The combination of two coating antibodies (TNF3 and TNF4) were used for the analysis. The absorbance was measured at 450nm, and TNF? concentration was expressed as pg/mL [18].

2.8. Data Analysis

Biochemical and clinical data were expressed as mean ±SD. All measurements were executed in duplicate. Output value (100%) was determined for each measured parameter of each patient before treatment. Data from tests performed on the same study subjects after therapy constituted a percentage of the output value. Percentage values were presented as mean ± SD. Statistical analyses were performed using the Statistica 12 statistical software (StaftSoft Inc.). A Shapiro-Wilk test was used to analyse for normality. A paired Student t-test was used to the calculate differences between the values obtained for subjects before and after therapy, whereas unpaired Student t-test or Mann–Whitney U tests were used to determine differences between the ELF-EMF and non-ELF-EMF groups. p values of 0.05 were accepted as statistically significant for all analyses.

3. Results

Our comparative analysis demonstrated an increased level of 3-nitrotyrosine (3-NT) (p< 0.05) (Figure 2) and an elevated nitrate/nitrite concentration (p < 0.01) (Figure 3) in the plasma of patients from the ELF-EMF group. The gain in the 3-NT level was significantly higher with an increased amount of sessions (Figure 2). In the non-ELF-EMF group, we saw that the effect of rehabilitation on nitrative stress was largely weaker and not statistically significant (p > 0.05) (Figures (Figures22 and and3).3). The 3-NT level increased more in the ELF-EMF group than in the non-ELF-EMF after 10 treatments (68% versus 17%, p < 0.05) (Figure 2). The level of nitrate/nitrite in the non-ELF-EMF group even decreased after 10 treatments (although not statistically significantly) (Figure 3).

Figure 2 The comparison of 3-NT levels in plasma proteins obtained from the ELF-EMF group versus those from the non-ELF-EMF group. Statistical significance between the ELF-EMF and non-ELF-EMF groups: B versus D (p < 0.05).

Figure 3 The comparison of nitrate/nitrite levels in plasma proteins obtained from the ELF-EMF group versus those from the non-ELF-EMF group. Statistical significance between ELF-EMF and non-ELF-EMF groups: B versus D (p < 0.05).

In the next set of experiments, we determined the effect of magnetotherapy on gene expression in the whole blood samples of NOS2 mRNA. Its expression was unmeasurable in 35% of subjects from both the ELF-EMF and non-ELF-EMF groups. We observed a statistically insignificant decrease in the level of NOS2 mRNA expression after treatment in both the ELF-EMF and non-ELF-EMF groups (Figure 4).

Figure 4 The comparison of NOS2 mRNA expression obtained from the ELF-EMF group versus that from the non-ELF-EMF group.

Subsequently, we determined the concentration of proinflammatory cytokine TNF?. We found that the concentration of TNF? was comparable before treatment in both the ELF-EMF and non-ELF-EMF-groups. The cytokine level did not change in either groups after rehabilitation (Figure 5).

Figure 5 The comparison of TNF? levels in plasma proteins obtained from the ELF-EMF group versus those from the non-ELF-EMF group.

The ADL, MMSE, and GDS were used to evaluate the functional and mental status of poststroke patients undergoing rehabilitation. We demonstrated that treatment using ELF-EMF improves their clinical parameters, particularly in cognitive and psychosomatic functions.

Motor abilities estimated by ADL score changed at similar levels in both groups, with the observed improvement being statistically significant in all rehabilitated patients (p < 0.001) (Table 2).

Table 2 Clinical parameters: ADL, MMSE, and GDS measured in the ELF-EMF and non-ELF-EMF groups. Data presented as the delta of a clinimetric scale before and after the standard series of treatments ADL=the increase of ADL; MMSE= the …

The baseline MMSE values before treatment in both groups were comparable, but statistically different (p < 0.05) after rehabilitation. After 2 weeks of rehabilitation, MMSE parameters improved markedly in the ELF-EMF group (p = 0.002), while a small increase in the non-ELF-EMF group was not statistically significant (p = 0.2) (Table 2).

Depression syndrome expressed by GDS improved significantly in both groups after rehabilitation. However, the GDS value reached about a 60% lower result in the ELF-EMF group than in the non-ELF-EMF group (p = 0.018), starting from a similar base level in both groups (p > 0.05) (Table 2).

4. Discussion

In this study, we provide the evidence that application of extremely low-frequency electromagnetic field increases nitric oxide generation and its metabolism, as well as improving the effectiveness of poststroke ischemic patients’ treatments.

Ischemic stroke is one of the major causes of morbidity and mortality in the world’s population and is one of the main causes of long-term disability. The mechanisms of neurological function recovery after brain injury associated with neuroplasticity (cortical reorganization) are still insufficiently understood. Poststroke neurorehabilitation is designed to provide external stimuli, improving the effectiveness of compensatory plasticity [19].

In the central nervous system, NO is both a pre- and postsynaptic signal molecule. The activity of NO is associated with a cGMP-mediated signalling cascade. The presynaptic excitatory action of NO is related to the phosphorylation of synaptophysin by the cGMP-dependent protein kinase G (PKG) pathway and the subsequent potentates of glutamatergic neurotransmission [20]. On the other hand, NO causes a neurotransmission inhibition through gamma-aminobutyric acid- (GABA-) ergic synaptic communication. It is associated with ion exchange and regulation of membrane excitation [21, 22]. Moreover, NO as an important vasodilation factor mediates neurovascular coupling. The enlargement of vessel diameter is caused by increasing metabolic consumption as a result of neuronal activity. Neurovascular coupling maintains functional and structural brain integrity [23].

This study was designed to investigate the impact of ELF-EMF on the metabolism of nitric oxide in the rehabilitation of acute poststroke patients.

In our study, we demonstrate that poststroke rehabilitation increases the level of 3-NT and nitrate/nitrite concentrations. Due to its vasodilating and proangiogenic effects, NO serves as a protective function during cerebral ischemia. Su et al. investigated the role of simvastatin-regulated TRPV1 receptors (transient receptor potential vanilloid type 1) in NO bioavailability, activation of eNOS, and angiogenesis in mice. They demonstrated that simvastatin causes an influx of calcium ions through the TRPV1-TRPA1 (transient receptor potential ankyrin 1) pathway, which then causes activation of CaMKII (Ca²⁺/calmodulin-dependent protein kinase II). This then enhances the formation of the TRPV1-eNOS complex, which also includes CaMKII, AMPK (5AMP-activated protein kinase), and Akt (protein kinase B), which leads to activation of eNOS, production of NO, and thus the promotion of endothelial angiogenesis [24]. There have been numerous reports of the protective effects of NO against inflammation and oxidative stress [25]. Transgenic eNOS-deficient mice demonstrated a more extensive infarct of the middle cerebral artery (MCA), compared to controls [26]. NO effects on the regulation of endothelial integrity, anti-inflammatory and anti-apoptotic effects, as well as maintenance of cerebral blood flow, inhibition of platelet aggregation, and reduction of leukocyte adhesion [25, 27]. Khan et al. studied structurally different NO donors as agents of cerebrovascular protection in experimentally induced stroke in rats. They showed that NO donors promote cerebral blood flow through S-nitrosylation and may be an effective drug for acute stroke [28, 29].

Furthermore, Greco et al. proved the protective effect of nitroglycerin (donors of NO) on cerebral damage induced by MCA occlusion in Wistar rats. They observed a significant reduction in stroke volume in preinjected rats compared to their control group, which confirms the protective effect of nitroglycerin in vivo. They speculated that the mechanism of action is associated with the generation of a complex chain of phenomena, triggering activation of apoptosis and subsequent activation of antiapoptotic responses [30].

The biological action of ELF-EMF is still being investigated. It is suggested that ELF-EMF has an impact on the physicochemical properties of water, the liquid crystal structure generated by cholesterol, and its derivatives [31, 32]. Changes in ion balance caused by ELF-EMF appeal to the structure of tissue with piezoelectric and magnetostrictive properties, free radicals, diamagnetic molecules, and uncompensated magnetic spins of paramagnetic elements [33]. Therefore, ELF-EMF causes depolarization of cells having the ability to spontaneously depolarize, predominantly through Ca²⁺ influx [34]. In our previous study, we investigated the effect of ELF-EMF on oxidative stress in patients after ischemic stroke. We demonstrated that ELF-EMF causes activation of antioxidant enzymes [35], which leads to reduction of the oxidative modification of plasma protein (this is detailed in an article published in Advances in Clinical and Experimental Medicine). As a highly reactive molecule, NO can also regulate the level of oxidative stress. Through the covalent interaction, NO influences the activity of various enzymes. Mechanisms of this modulation can be varied: NO reacts with coenzymes and active centers containing metal ions and interacts with cysteine residues of proteins [36].

In the current study, we observed that in the ELF-EMF group, the level of plasma 3-NT was increased (Figure 2). The formation of 3-NT in protein molecules occurs in vivo by the action of nitrating agents on the polypeptide chain. The formation of 3-NT is mainly attributed to NO and superoxide anions (O₂^??), which react rapidly to form peroxynitrite (ONOO^?). This is one of the major oxidizing and nitrating agents produced in vivo in acute and chronic inflammation, as well as in ischemia/reperfusion. Endothelial cells, macrophages, and neutrophils release large amounts of NO and O₂^?. Thus, increased amounts of NO contribute to the creation of 3-NT [37].

To investigate the effect of ELF-EMF on NO metabolism, we determined nitrate/nitrite concentrations in plasma. We showed that in the ELF-EMF group, the level of nitrate/nitrite compounds in plasma increased after treatment (Figure 3), and these results correspond with the data presented by Chung et al. [38]. The authors investigated the effects of ELF-EMF (60Hz, 2mT) on the level of NO, biogenic amines, and amino acid neurotransmitters in the hippocampus, cortex, thalamus, cerebellum, and striatum in rats. They found a significant increase in NO concentration in the hippocampus, thalamus, and striatum. Moreover, ELF-EMF also caused a change in the level of biogenic amines and amino acid neurotransmitters in the brain. However, the observed effect and range were different, depending on the brain area. Balind et al. determined the effect of ELF-EMF (50Hz, 0.5mT) on oxidative stress in gerbils with induced cerebral ischemia. They measured the level of NO using the Griess reagent and showed an increased level of NO, provoked by electromagnetic fields. Moreover, ELF-EMF reduces oxidative stress generated during cerebral ischemia, thus leading to a decrease in the damaged brain tissue [39].

NO is produced from L-arginine with the involvement of nitric oxide synthase. Three NOS isoforms are expressed in different tissues. Although, in the blood, only NOS2 is expressed, in 35% of the subjects in both the ELF-EMF and non-ELF-EMF groups, mRNA expression of NOS2 was under detection. In the remaining patients, the expression of NOS2 had not significantly changed after treatment. The NOS2 gene in fact encodes for iNOS, which is primarily activated during inflammation. In order to exclude deeper inflammation, we measured the concentration of TNF?, one of the main proinflammatory cytokines. TNF? is a pleiotropic cytokine that is involved in nearly all phenomena of inflammatory responses: initiating chemokine synthesis, promoting the expression of adhesion molecules, promoting the maturation of dendritic cells, and inducing the production of inflammatory mediators and other proinflammatory cytokines [40]. TNF? stimulates collagenase synthesis in synovial fibroblasts and synovial cartilage chondrocytes and activates osteoclasts, leading to joint cartilage damage, hypertrophy, bone resorption and erosion, and angiogenesis. It also activates monocytes and macrophages, enhancing their cytotoxicity and stimulating cytokine production. Chemokines and growth factors are responsible for T cell proliferation, proliferation and differentiation of B lymphocytes, and the release of inflammatory cytokines by the lymphocytes. Moreover, in the hypothalamus, TNF? stimulates prostaglandin E and IL-1 synthesis [41]. Pena-Philippides et al. investigated the effect of pulsed electromagnetic fields on injury size and neuroinflammation in mice after middle cerebral artery occlusion (MCAO). They found, using magnetic resonance imaging (MRI), that EMF reduced infarct size, as well as changed expression of genes encoding pro- and anti-inflammatory cytokines in the hemisphere with ischemic injury. After EMF exposure, genes encoding IL-1 and TNF superfamily were downregulated, while IL-10 expression was upregulated. Thus, the authors suggested that application of EMF to poststroke patients could have been beneficial through anti-inflammatory effect and reduction of injury size [42].

On the basis of our results, we suggest that the observed increase in NO level is associated with nNOS and/or eNOS activities, but not with iNOS expression. Our research is consistent with evidence shown by Cho et al., who established that ELF-EMF (60Hz, 2mT) increased the expression and activation of nNOS in rat brains [43].

The activities of nNOS and eNOS depend on calcium ions. There are many reports that the biological effect of ELF-EMF is related to the control of calcium channels [44–48]. In view of these findings, the observed mechanism of increased NO generation and metabolism may be associated with calcium-ion flux.

Additionally, we noticed that ELF-EMF treatment enhances the effectiveness of poststroke rehabilitation (Table 2). Some researchers suggest that electromagnetic fields have a beneficial effect on ischemic/reperfusion injury, and in some places, therapeutic programs using ELF-EMF are considered to be standard therapy for poststroke patients [49, 50]. The beneficial effects of ELF-EMF include the following: improvement in the transport of cellular and mitochondrial membranes; normalization of blood rheological values; counteraction of tissue oxidation; intensification of regenerative processes; stimulation of axon growth in undamaged neurons; intensification of neuronal dissociation and differentiation; reduction of stress-induced emotional reactions and free radicals; acceleration of the return of fibre function in functional disorders; reduction of periapical scarring; and increase of the level of energetic substances in the brain tissue and erythrocytes [48–53]. Grant et al. estimated the impact of low-frequency pulsed electromagnetic field on cerebral ischemia in rabbit. They observed using MRI that exposure to electromagnetic field caused extenuation of cortical ischemia oedema and reduction of neuronal injury in cortical area [54].

In conclusion, ELF-EMF therapy increases the metabolism and generation of NO, which has both neuroprotective and cytotoxic properties. An increase in NO level is probably associated with nNOS and/or eNOS activities, but not with iNOS expression, which increases mainly during inflammation. We suggested that in poststroke patients, NO demonstrated a protective effect due to significant improvement in patient functional status. Thus, our studies promote the validity of this method in poststroke rehabilitation therapy.

Acknowledgments

This study was supported by the Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz (no. 506/1136), and Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz (no. B161100000004601), and Grants for Young Scientists and PhD Students, Faculty of Biology and Environmental Protection, University of Lodz (B1611000001145.02).

Conflicts of Interest

The authors declare that there is no conflict of interest regarding the publication of this article.

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Neurosci Behav Physiol. 2010 Oct;40(8):920-5.

The potential of transcranial magnetotherapy in color and rhythm therapy in the rehabilitation of ischemic stroke.

Sholomov II, Cherevashchenko LA, Suprunov OV, Raigorodskii YM.

Saratov State Medical University, Saratov, Russia.

Abstract

A total of 116 patients with ischemic stroke were studied during the early recovery period. The patients were divided into four groups – three experimental groups and one control group. Of these, 87 patients in the first three groups received transcranial magneto- and/or color and rhythm therapy (TcMT, CRT) along with traditional treatment, while the 29 patients of the control group received basal treatment only. TcMT was performed using a bitemporal method, with a running field regime with a modulation frequency of 1-10 Hz. CRT consisted of an alternating scheme of stimulation of the left and right eyes with green and/or blue light with a period of 2-4 sec and an on time of 1 sec. Each of the three experimental groups (group 1 received TcMT, group 2 received CRT, and group 3 received TcMT + CRT) received two courses of treatment separated by 1.5 months. After treatment, all experimental groups, particularly group 3, showed more marked improvements than the control group. Regression of neurological symptomatology on the Lindmark scale in group 3 was 9.5% greater than that in controls; improvements in impairments to activity and self-care ability on the Barthel scale were greater by 8.8%; memory and intellectual changes were also seen on the MMSE and the Luriya and Schulte tests. Rheography and electroencephalography demonstrated significant improvements in hemodynamics and alpha-rhythm differentiation and a 14.6% reduction in the proportion of patients with dysrhythmia in group 3 compared with the control group. The best result on all measures were obtained in patients given the combination of TcMT and CRT; TcMT had the greater influence on hemodynamics, while CRT had the greater effect on psychoemotional status. Both treatments were well tolerated and produced no side effects.

Clin Neurophysiol. 2010 Mar;121(3):441-7. Epub 2010 Jan 13.

Reduced motor cortex plasticity following inhibitory rTMS in older adults.

Todd G, Kimber TE, Ridding MC, Semmler JG.

Discipline of Physiology, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, SA, Australia. gabrielle.todd@adelaide.edu.au

Abstract

OBJECTIVE: Ageing is accompanied by diminished practice-dependent plasticity. We investigated the effect of age on another plasticity inducing paradigm, repetitive transcranial magnetic stimulation (rTMS).

METHODS: Healthy young (n=15; 25+/-4 years) and old (n=15; 67+/-5 years) adults participated in two experiments. Motor evoked potentials (MEPs) were measured in the target muscle (first dorsal interosseus, FDI) and a remote muscle (abductor digiti minimi) during a set of single stimuli. Subjects then received real or sham inhibitory rTMS (intermittent subthreshold trains of 6Hz stimulation for 10min). MEPs were measured for 30min after rTMS.

RESULTS: In young adults, MEPs in the target FDI muscle were approximately 15% smaller in the real rTMS experiment than in the sham rTMS experiment (P<0.026). In old adults, FDI MEP size did not differ between experiments.

CONCLUSIONS: Advancing age is associated with reduced efficacy of inhibitory rTMS.

SIGNIFICANCE: This work has important implications for the potential therapeutic use of rTMS in stroke and neurological disease.

Zh Nevrol Psikhiatr Im S S Korsakova. 2009;109(7):23-8.

Possibilities of transcranial magnetic therapy and color and rhythm therapy in rehabilitation of ischemic stroke.

[Article in Russian]

Sholomov II, Cherevashchenko LA, Suprunov OV, Ra?gorondski? IuM.

Abstract

One hundred and sixteen post-stroke patients were studied in the early rehabilitation period. All patients were divided into 4 groups: 3 main and 1 control groups. Three main groups (87 patients) received transcranial magnetic therapy (TMT) and/or color and rhythm therapy (CRT) along with traditional treatment and the control group (29 patients) received only basic therapy. TMT was conducted using bitemporal technique, running regime with modulation frequency 1-10 Hz. In CRT, the alternating stimulation of the right and left eye with green and/or blue color with a period of 2-4 s and duration of luminescence 1s was applied. Each of 3 main groups received 2 treatment sessions with an interval of 1,5 month (1st – TMT, 2nd – CRT, 3rd – TMT + CRT). After the treatment, the marked positive changes were seen in all main groups, in particular in group 3. The improvement of neurologic symptoms on the B. Lindmark scale was higher by 9,5% in group 3 compared to the control one, on the Barthel index – by 8,8%, on MMSE and A. Luria and Schulte test – by 5,4 and 14,3%, respectively. Rheographic and encephalographic study revealed the significant improvement of hemodynamics and alpha-rhythm differentiation, decrease of patients with dysrhythmia by 14,6% in group 3 as compared to the control group. The best results were seen in the combination of TMT and CRT, TMT exerted a higher effect on the hemodynamics and CRT – on the psychoemotional state. Both therapies were well tolerated and had no side-effects.

Stroke. 2009 Jan;40(1):309-12. Epub 2008 Oct 9.

Safety and behavioral effects of high-frequency repetitive transcranial magnetic stimulation in stroke.

Yozbatiran N, Alonso-Alonso M, See J, Demirtas-Tatlidede A, Luu D, Motiwala RR, Pascual-Leone A, Cramer SC.

Abstract

BACKGROUND AND PURPOSE: Electromagnetic brain stimulation might have value to reduce motor deficits after stroke. Safety and behavioral effects of higher frequencies of repetitive transcranial magnetic stimulation (rTMS) require detailed assessment.

METHODS: Using an active treatment-only, unblinded, 2-center study design, patients with chronic stroke received 20 minutes of 20 Hz rTMS to the ipsilesional primary motor cortex hand area. Patients were assessed before, during the hour after, and 1 week after rTMS.

RESULTS: The 12 patients were 4.7+/-4.9 years poststroke (mean+/-SD) with moderate-severe arm motor deficits. In terms of safety, rTMS was well tolerated and did not cause new symptoms; systolic blood pressure increased from pre- to immediately post-rTMS by 7 mm Hg (P=0.043); and none of the behavioral measures showed a decrement. In terms of behavioral effects, modest improvements were seen, for example, in grip strength, range of motion, and pegboard performance, up to 1 week after rTMS. The strongest predictor of these motor gains was lower patient age.

CONCLUSIONS: A single session of high-frequency rTMS to the motor cortex was safe. These results require verification with addition of a placebo group and thus blinded assessments across a wide spectrum of poststroke deficits and with larger doses of 20 Hz rTMS.

Lancet Neurol. 2008 Jun;7(6):507-13. Epub 2008 May 1.

Contralesional repetitive transcranial magnetic stimulation for chronic hemiparesis in subcortical paediatric stroke: a randomised trial.

Kirton A, Chen R, Friefeld S, Gunraj C, Pontigon AM, Deveber G.

Division of Neurology, Department of Pediatrics, Alberta Children’s Hospital, University of Calgary, Calgary, Canada. adam.kirton@calgaryhealthregion.ca

Abstract

BACKGROUND: Arterial ischaemic stroke (AIS) can cause disabling hemiparesis in children. We aimed to test whether contralesional, inhibitory repetitive transcranial magnetic stimulation (rTMS) could affect interhemispheric inhibition to improve hand function in chronic subcortical paediatric AIS.

METHODS: Patients were eligible for this parallel, randomised trial if they were in the SickKids Children’s Stroke Program and had subcortical AIS more than 2 years previously, had transcallosal sparing, were more than 7 years of age, had hand motor impairment, had no seizures or dyskinesia, and were taking no drugs that alter cortical excitability. Patients were paired for age and weakness and were randomised within each pair to sham treatment or inhibitory, low-frequency rTMS over contralesional motor cortex (20 min, 1200 stimuli) once per day for 8 days. An occupational therapist did standardised tests of hand function at days 1 (baseline), 5, 10, and 17 (1 week post-treatment), and the primary outcomes were changes in grip strength and the Melbourne assessment of upper extremity function (MAUEF) between baseline and day 10. Patients, parents, and occupational therapists were blinded to treatment allocation. Analysis was per protocol.

FINDINGS: Ten patients with paediatric stroke were enrolled (median age 13.25 [IQR 10.08-16.78] years, mean time post-stroke 6.33 [SD 3.56] years): four with mild weakness, two with moderate weakness, and four with severe weakness. A repeated-measures ANOVA showed a significant interaction between time and the effect of treatment on grip strength (p=0.03). At day 10, grip strength was 2.28 (SD 1.01) kg greater than baseline in the rTMS group and 2.92 (1.20) kg less than baseline in the sham group (p=0.009). Benefits in mean grip strength persisted at day 17 (2.63 [0.56] kg greater than baseline with rTMS and 1.00 [0.70] kg less than baseline with sham treatment; p=0.01). Day 10 MAUEF score improved by more in the rTMS group than in the sham group (7.25 [3.8] vs 0.79 [1.3] points greater than baseline; p=0.002), but this benefit did not persist to day 17. Function of the unaffected hand remained stable. rTMS was well tolerated with no serious adverse events.

INTERPRETATION: Contralesional inhibitory rTMS was safe and feasible for patients with paediatric subcortical AIS, and seemed to improve hand function in patients with hemiparesis. Further studies are required to confirm the potential role of rTMS in paediatric neurorehabilitation.

FUNDING: Canadian Stroke Consortium; Canadian Institutes of Health Research; American Academy of Neurology Foundation; Alberta Heritage Foundation for Medical Research.

Arch Neurol. 2008 Jun;65(6):741-7.

Effects of low-frequency repetitive transcranial magnetic stimulation of the contralesional primary motor cortex on movement kinematics and neural activity in subcortical stroke.

Nowak DA, Grefkes C, Dafotakis M, Eickhoff S, Küst J, Karbe H, Fink GR.

Department of Neurology, University Hospital Cologne, University of Cologne, Kerpener Strasse 62, D-50924 Cologne, Germany. dennis.nowak@uk-koeln.de

Abstract

BACKGROUND: Following the concept of interhemispheric competition, downregulation of the contralesional primary motor cortex (M1) may improve the dexterity of the affected hand after stroke.

OBJECTIVE: To determine the effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) of the contralesional M1 on movement kinematics and neural activation within the motor system in the subacute phase after subcortical stroke.

DESIGN: Crossover investigation.

SETTING: A university hospital.

METHODS: Fifteen right-handed patients with impaired dexterity due to subcortical middle cerebral artery stroke received 1-Hz rTMS for 10 minutes applied to the vertex (control stimulation) and contralesional M1. For behavioral testing, patients performed finger and grasp movements with both hands at 2 baseline conditions, separated by 1 week, and following each rTMS application. For functional magnetic resonance imaging, patients performed hand grip movements with their affected or unaffected hand before and after each rTMS application.

RESULTS: Application of rTMS to the contralesional M1 improved the kinematics of finger and grasp movements in the affected hand. At the neural level, rTMS applied to the contralesional M1 reduced overactivity in the contralesional primary and nonprimary motor areas. There was no significant correlation between the rTMS-induced reduction in blood oxygen level-dependent responses within the contralesional M1 and the degree of behavioral improvement of the affected hand. Overactivity of the contralesional dorsal premotor cortex, contralesional parietal operculum, and ipsilesional mesial frontal cortex at baseline predicted improvement of movement kinematics with the affected hand after rTMS of the contralesional M1.

CONCLUSION: The functional magnetic resonance imaging data suggest that rTMS of the contralesional M1 may normalize neural activation within the cortical motor network after subcortical stroke. Identifying patients suitable for rTMS intervention based on individual patterns of cortical activation may help to implement rTMS in motor rehabilitation after stroke.

Przegl Lek. 2007;64(2):74-7.

Effect of low frequency magnetic fields used in magnetotherapy and magnetostimulation on the rehabilitation results of patients after ischemic stroke.

[Article in Polish]

Wolda?ska-Oko?ska M, Czernicki J.

Z Katedry Rehabilitacji Akademii Swietokrzyskiej, filii w Piotrkowie Trybunalskim. marta.okonska@poczta.onet.pl

Abstract

New methods of rehabilitation should be introduced in order to reduce disability resulting from stroke. During the twelve months of follow-up, effect of low frequency magnetic field (If mf) on the course of patient rehabilitation following ischemic stroke was evaluated on in-patient (acute and subacute period of the stroke) and outpatient (chronic period) basis with the use of Mathew et al’s and Barthel’s scales. Lf mf (20 procedures of 20-min. duration) of magnetotherapy (I group–placebo, II–group 5.6 mT induction, 10 Hz frequency and sinusoidal shape, III group–2.8 mT induction, 10 Hz frequency and sinusoidal shape) and magnetostimulation (IV group–M1P1 program of Viofor JPS system, 16 min a day) was applied as early as in the subacute period of the stroke (1-8 weeks). The data obtained were presented in the form of percentage changes in the pain levels as well as in the form of the arithmetical mean and standard deviation (X +/- SD). The ANOVA test was used for a statistical evaluation of the data obtained in the tests. The results obtained indicate beneficial effects of If mf in the III and IV group of patients in the Barthel’s scale and Mathew scale, which were observed during the examination 12 months after the stroke. The recommended doses of If mf seem to be adequate to obtain therapeutic effects and may be used in the early period of rehabilitation. The neurological and functional improvement persisted for a long-period of the out-patient treatment, which was confirmed during the control examination 12 months after the ischemic stroke. As no adverse effects (which could be attributed to If mf), were observed, this method of physical therapy can be recognized as a safe one and worth making popular in clinical practice.

Restor Neurol Neurosci. 2007;25(5-6):461-5.

Improvement of dexterity by single session low-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex in acute stroke: a double-blind placebo-controlled crossover trial.

Liepert J, Zittel S, Weiller C.

Department of Neurology, University Hospital, Freiburg, Germany. j.liepert@kliniken-schmieder.de

Abstract

PURPOSE: Increasing evidence suggests that the contralesional motor cortex (M1) inhibits the ipsilesional M1 in stroke patients. This inhibition could impair motor function of the affected hand. We investigated if inhibitory 1~Hz repetitive transcranial magnetic stimulation (rTMS) over the contralesional M1 improved motor performance of the affected hand in acute stroke.

METHODS: A double-blind study of real versus placebo rTMS was conducted. Twelve patients early after subcortical stroke (mean: 7 days) received 1200 stimuli of real and placebo rTMS in a crossover design. The sequence of stimulations was counterbalanced across subjects. Stimulus intensity was subthreshold (90% of motor threshold at rest). Motor function was tested by grip strength recordings and Nine Hole Peg Test (NHPT) executions before and after each rTMS session.

RESULTS: Compared to sham stimulation, real rTMS improved NHPT results but not grip strength in the affected hand. No change of performance was observed for the unaffected hand. NHPT baseline repetitions in a subgroup of patients indicated stable motor performance prior to the rTMS sessions.

CONCLUSIONS: The study suggests that therapeutic rTMS applications over the contralesional hemisphere are feasible in acute stroke patients and can transiently improve dexterity of the affected hand. RTMS may become an additional tool for early neurorehabilitation.

Prog Brain Res. 2005;150:527-35.

Neural plasticity and recovery of function.

Ward NS.

Wellcome Department of Imaging Neuroscience, Institute of Neurology, University College London, 12 Queen Square, London WC1N 3BG, UK.

Recovery of the function after stroke is a consequence of many factors including resolution of oedema and survival of the ischaemic penumbra. In addition there is a growing interest in the role of central nervous system (CNS) reorganization. Much of the evidence supporting this comes from animal models of focal brain injury, but non-invasive techniques such as functional magnetic resonance imaging, transcranial magnetic stimulation, electroencephalography and magnetoencephalography now allow the study of the working human brain. Using these techniques it is apparent that the motor system of the brain adapts to damage in a way that attempts to preserve motor function. This has been demonstrated after stroke, as part of the ageing process, and even after disruption of normal motor cortex with repetitive transcranial magnetic stimulation. The result of this reorganization is a new functional architecture, one which will vary from patient to patient depending on the anatomy of the damage, the biological age of the patient and lastly the chronicity of the lesion. The success of any given therapeutic intervention will depend on how well it interacts with this new functional architecture. Thus it is crucial that the study of novel therapeutic strategies for treating motor impairment after stroke take account of this. This review maps out the attempts to describe functionally relevant adaptive changes in the human brain following focal damage. A greater understanding of how these changes are related to the recovery process will allow not only the development of novel therapeutic techniques that are based on neurobiological principles and designed to minimize impairment in patients suffering from stroke, but also to target these therapies at the appropriate patients.

Neurology. 2005 Aug 9;65(3):466-8.

Therapeutic trial of repetitive transcranial magnetic stimulation after acute ischemic stroke.

Khedr EM, Ahmed MA, Fathy N, Rothwell JC.

Department of Neurology, Assiut University Hospital, Assiut, Egypt. emankhedr99@yahoo.com

Repetitive transcranial magnetic stimulation (rTMS) or sham stimulation was given over the motor cortex daily for 10 days to two randomly assigned groups of 26 patients with acute ischemic stroke. Patients otherwise continued their normal treatment. Disability scales measured before rTMS, at the end of the last rTMS session, and 10 days later showed that real rTMS improved patients’ scores more than sham.

Stroke. 2005 Oct 27; [Epub ahead of print]

Repetitive Transcranial Magnetic Stimulation of Contralesional Primary Motor Cortex Improves Hand Function After Stroke.

Takeuchi N, Chuma T, Matsuo Y, Watanabe I, Ikoma K.

From the Department of Rehabilitation Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-0814, Japan.

BACKGROUND AND PURPOSE: A recent report has demonstrated that the contralesional primary motor cortex (M1) inhibited the ipsilesional M1 via an abnormal transcallosal inhibition (TCI) in stroke patients. We studied whether a decreased excitability of the contralesional M1 induced by 1 Hz repetitive transcranial magnetic stimulation (rTMS) caused an improved motor performance of the affected hand in stroke patients by releasing the TCI.

METHODS: We conducted a double-blind study of real versus sham rTMS in stroke patients. After patients had well- performed motor training to minimize the possibility of motor training during the motor measurement, they were randomly assigned to receive a subthreshold rTMS at the contralesional M1 (1 Hz, 25 minutes) or sham stimulation.

RESULTS: When compared with sham stimulation, rTMS reduced the amplitude of motor-evoked potentials in contralesional M1 and the TCI duration, and rTMS immediately induced an improvement in pinch acceleration of the affected hand, although a plateau in motor performance had been reached by the previous motor training. This improvement in motor function after rTMS was significantly correlated with a reduced TCI duration.

CONCLUSIONS: We have demonstrated that a disruption of the TCI by the contralesional M1 virtual lesion caused a paradoxical functional facilitation of the affected hand in stroke patients; this suggests a new neurorehabilitative strategy for stroke patients.

Stroke. 2005 Nov 3; [Epub ahead of print]

Motor Strokes.  The Lesion Location Determines Motor Excitability Changes.

Liepert J, Restemeyer C, Kucinski T, Zittel S, Weiller C.

From the Departments of Neurology and Neuroradiology, University Medical Center Eppendorf, Hamburg, and Department of Neurology, University Hospital, Freiburg, Germany.

BACKGROUND AND PURPOSE: The purpose of this research was to investigate the impact of lesion location on motor excitability and motor performance.

METHODS: We studied patients with pure motor strokes in 4 different brain areas: motor cortex lesions (n=7), striatocapsular lesions (n=13), lacunar lesions of the internal capsule (n=13), and paramedian pontine lesions (n=10). Motor performance tests included the 9-hole-peg test and grip strength recordings. Motor excitability was determined by transcranial magnetic stimulation. Motor thresholds, stimulus-response curves, silent periods, motor cortical inhibition, and facilitation were investigated.

RESULTS: The 4 groups were clinically similar but showed major differences in motor excitability. Only motor cortex lesions had a loss of intracortical inhibition in the affected hemisphere. In the internal capsule lesion group and the pontine lesion group, stimulus-response curves were depressed on the affected side. All of the subcortical lesions showed a prolongation of the silent period in the paretic side. Motor thresholds were predominantly elevated in the lesioned hemisphere of patients with internal capsule or pontine lesions. Motor performance was correlated with silent period duration in internal capsule lesions and with motor thresholds in internal capsule and pontine lesions.

CONCLUSIONS: Motor cortex lesions exhibited deficient inhibitory properties. In contrast, subcortical lesions displayed an enhancement of inhibition. Internal capsule and pontine lesions affecting the corticospinal tract on different levels particularly impaired neuronal recruitment. Our results suggest that the lesion location determines a specific pattern of motor excitability changes.

i Yi Jun Yi Da Xue Xue Bao. 2004 Aug;24(8):946-9, 952.

Effect of power-frequency electromagnetic fields on stroke during rehabilitation.

[Article in Chinese]

Deng AW, Yuang XG, Wei D, Zhang JH, Ran CF, Wang M.

Department of Rehabilitation, Longgang center Hospital of Shenzhen City, Shenzhen 518116, China. aiwen@fimmu.com

Abstract

OBJECTIVE: To explore the effects and mechanism of power-frequency electromagnetic fields on lipoprotein metabolism and homodynamic during stroke rehabilitation.

METHODS: One hundred fifteen patients with stroke were divided into 2 groups, 55 cases of them were treated by exposure to power-frequency electromagnetic fields, 60 cases were treated as control group. Barthel index and Functional Independence Measure (FIM) were used to evaluate rehabilitation outcome. The lipoprotein and its subclasses, homodynamic parameters were compared at pre- and post-rehabilitation.

RESULTS: The treatment group showed a statistically significant better prognosis compared with the control group(P<0.01). The score of Barthel index also increased after treatment(P<0.001). Total cholesterol(Tc), triglycerides(TG), low-density lipoprotein cholesterol(LDL-c) levels dropped and high-density lipoprotein cholesterol(HDL-c) increased significantly. The Tc/HDL-c, LDL-c/HDL-c ratio along with the blood and plasma viscosity decreased significantly compared with the controls (P<0.01). The ratio of stroke recurrence decreased significantly after the treatment compared with the control group (P<0.05).

CONCLUSION: The power-frequency electromagnetic fields can improve lipoprotein metabolism and homodynamic parameters. It can improve the ADL and FIM of stroke patients, which may have significant implications for stroke patients.

Vopr Kurortol Fizioter Lech Fiz Kult. 2003 Mar-Apr;(2):19-20.

Magnetic and laser therapy of acute ischemic stroke.

[Article in Russian]

Samosiuk NI.

The paper presents the technique of frequency-modulated magnetolaser therapy (FMMLT) used in combined treatment of 121 patients with ischemic stroke in acute period. The results were compared with those in the control group of 30 patients who received conventional drug treatment. The results of the comparison allowed the author to recommend FMMLT in ischemic stroke especially in the period of “therapeutic window”.

Vopr Kurortol Fizioter Lech Fiz Kult. 2001 Mar-Apr;(2):23-6.

Magnet therappy in rehabilitation of patients with cerabral ischemia.

[Article in Russian]

Provotorov VM, Putilina MV.

Abstract

Basing on the results of clinical examination and treatment of 420 patients with aftereffects of acute circulatory disturbance, the authors propose a pathogenetically grounded approach to correction of the residual phenomena following stroke. The method proposed includes three courses of impulse electromagnetotherapy used in combination with either standard chemotherapy or massage and therapeutic exercise

Vopr Kurortol Fizioter Lech Fiz Kult. 2001 Nov-Dec;(6):21-3.

The use of extremely high frequency electromagnetic fields during acute period of ischemic stroke.

[Article in Russian]

Podoliako VA, Makarchik AV.

Abstract

The rheological, coagulatory and clinical examination of 70 patients with acute ischemic stroke has demonstrated that EHF therapy (53.53 GHz) improves rheological and coagulatory parameters in such patients, has a positive effect on hemostasis and clinical course of acute ischemic stroke. The technique and doses are presented.

Stroke. 2000 Jun;31(6):1210-6.

Treatment-induced cortical reorganization after stroke in humans.

Liepert J, Bauder H, Wolfgang HR, Miltner WH, Taub E, Weiller C.

Department of Neurology, Friedrich-Schiller-University of Jena, Germany. liepert@neuro.uni-jena.de

Abstract

BACKGROUND AND PURPOSE: Injury-induced cortical reorganization is a widely recognized phenomenon. In contrast, there is almost no information on treatment-induced plastic changes in the human brain. The aim of the present study was to evaluate reorganization in the motor cortex of stroke patients that was induced with an efficacious rehabilitation treatment.

METHODS: We used focal transcranial magnetic stimulation to map the cortical motor output area of a hand muscle on both sides in 13 stroke patients in the chronic stage of their illness before and after a 12-day-period of constraint-induced movement therapy.

RESULTS: Before treatment, the cortical representation area of the affected hand muscle was significantly smaller than the contralateral side. After treatment, the muscle output area size in the affected hemisphere was significantly enlarged, corresponding to a greatly improved motor performance of the paretic limb. Shifts of the center of the output map in the affected hemisphere suggested the recruitment of adjacent brain areas. In follow-up examinations up to 6 months after treatment, motor performance remained at a high level, whereas the cortical area sizes in the 2 hemispheres became almost identical, representing a return of the balance of excitability between the 2 hemispheres toward a normal condition.

CONCLUSIONS: This is the first demonstration in humans of a long-term alteration in brain function associated with a therapy-induced improvement in the rehabilitation of movement after neurological injury.

Vopr Kurortol Fizioter Lech Fiz Kult. 2000 May-Jun;(3):17-21.

The optimization of an early rehabilitation program for cerebral stroke patients: the use of different methods of magneto- and laser therapy.

[Article in Russian]

Kochetkov AV, Gorbunov FE, Minenkov AA, Strel’tsova EN, Filina TF, Krupennikov AI.

Magnetotherapy and laser therapy were used in complex and complex-combined regimens in 75 patients after cerebral ischemic or hemorrhagic stroke starting on the poststroke week 4-5. Clinico-neurologic, neurophysiological and cerebrohemodynamic findings evidence for the highest effectiveness of neurorehabilitation including complex magneto-laser therapy in hemispheric ischemic and hemorrhagic stroke of subcortical location in the absence of marked clinico-tomographic signs of dyscirculatory encephalopathy. Complex-combined magneto-laser therapy is more effective for correction of spastic dystonia. Mutual potentiation of magnetotherapy and laser therapy results in maximal development of collateral circulation and cerebral hemodynamic reserve (84% of the patients). Complex effects manifest in arteriodilating and venotonic effects. Complex magneto-laser therapy is accompanied by reduction of hyperthrombocythemia and hyperfibrinogenemia.

Electromyogr Clin Neurophysiol. 1999 Oct-Dec;39(7):405-10.

Motor hand recovery after stroke. Prognostic yield of early transcranial magnetic stimulation.

Cruz Martínez A, Tejada J, Díez Tejedor E.

Unidad de Electromiografía, Hospital La Luz, Madrid, Spain.

Abstract

Transcranial magnetic stimulation (TMS) was performed in 20 patients within the first days after stroke. Motor evoked potentials (MEPs) were bilaterally recorded over thenar eminence muscles, and central motor conduction time (CMCT), amplitude of the MEPs (A%M) and threshold intensity compared between both sides. Six months later the patients were reexamined. Within the first days after stroke the obtention of MEPs at rest or during voluntary muscle activation have a favorable prognostic value. All patients with early response by TMS reached a good motor function in the following months. The follow-up showed that the electrophysiological improvement was closely related to clinical recovery of the hand function. However, even in cases with a good recovery, the CMCT and, mainly, the A%M, may be significantly different related to those in normal hand. TMS may be an early and valuable prognostic indicator of hand function recovery after stroke, and their prognostic yield is higher than clinical evaluation and CT study. TMS is a quantifiable method of motor disability and may have practical application in the management and rehabilitation therapy in stroke patients.

Vopr Kurortol Fizioter Lech Fiz Kult. 1996 May-Jun;(3):21-4.

The effect of combined transcerebral magnetic and electric impulse therapy on the cerebral and central hemodynamic status of stroke patients in the early rehabilitation period.

[Article in Russian]

Gorbunov FE, Orekhova EM, Isaev SV, Bugaev SA.

75 clinical cases of acute impairment of cerebral circulation treated with sinusoidal modulated currents in combination with transcerebral magnetic field have been analysed. Functional and clinical findings indicate that the above combination is much more effective than magnetic field and sinusoidal modulated currents alone: 62% against 35% and 33%, respectively.

Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(9):41-3.

Magnetic and electrical stimulation in the rehabilitative treatment of patients with organic nervous system lesions.

[Article in Russian]

Tyshkevich TG, Nikitina VV.

89 patients with organic damages of nervous system with paralyses and pareses as the main symptoms in clinical pattern were treated. Their treatment was complex with application of impulse magnetic field and electrostimulation which permitted to achieve multilevel electrostimulation. The control group was formed by 49 patients with analogous diseases which were treated by sinusoidal current electrostimulation only. Combined application of magnetic stimulation and electrostimulation was more effective. That was confirmed by data of roentgenographic and electromyographic studies.

Bioelectromagnetics. 1994;15(3):205-16.

Protection against focal cerebral ischemia following exposure to a pulsed electromagnetic field.

Grant G, Cadossi R, Steinberg G.

Department of Neurosurgery, Stanford University, California 94305.

There is evidence that electromagnetic stimulation may accelerate the healing of tissue damage following ischemia. We undertook this study to investigate the effects of low frequency pulsed electromagnetic field (PEMF) exposure on cerebral injury in a rabbit model of transient focal ischemia (2 h occlusion followed by 4 h of reperfusion). PEMF exposure (280 V, 75 Hz, IGEA Stimulator) was initiated 10 min after the onset of ischemia and continued throughout reperfusion (six exposed, six controls). Magnetic resonance imaging (MRI) and histology were used to measure the degree of ischemic injury. Exposure to pulsed electromagnetic field attenuated cortical ischemia edema on MRI at the most anterior coronal level by 65% (P < 0.001). On histologic examination, PEMF exposure reduced ischemic neuronal damage in this same cortical area by 69% (P < 0.01) and by 43% (P < 0.05) in the striatum. Preliminary data suggest that exposure to a PEMF of short duration may have implications for the treatment of acute stroke.

Zh Nevropatol Psikhiatr Im S S Korsakova. 1992;92(1):63-7.

Magnetotherapy of initial manifestations of cerebrovascular disorders in hypertension.

[Article in Russian]

Miasnikov IG.

The paper is concerned with the data on 147 subjects who underwent magnetotherapy with the unit “Magniter-AMT-01” applied to the cervical area. The main group included 102 subjects, 45 person served as control. The purpose of the work was to base the application of MT under inpatient and home conditions with the use of the above-indicated unit. In view of this fact, a study was made of cerebral hemo- and thermodynamics with the aid of rheoencephalography and encephaloradiothermography under the action of different modes of the functioning of the unit “Magniter-AMT-01” (pulse and variable magnet induction fields 12-15 mTl and 30-35 mTl). A method of measuring magnetosensitivity of patients depending on the temperature reaction of the brain to a single MT session was elaborated. The greatest clinical effect was attained with the use of pulse magnetic field 15 mTl. Magnetotherapy with the use of the unit “Magniter-AMT-01” provided good results under inpatient and home conditions. The magnetosensitive patients demonstrated the highest effect.

J Cell Biochem. 1993 Apr;51(4):387-93.

Beneficial effects of electromagnetic fields.

Bassett CA.

Bioelectric Research Center, Columbia University, Riverdale, New York 10463.

Selective control of cell function by applying specifically configured, weak, time-varying magnetic fields has added a new, exciting dimension to biology and medicine. Field parameters for therapeutic, pulsed electromagnetic field (PEMFs) were designed to induce voltages similar to those produced, normally, during dynamic mechanical deformation of connective tissues. As a result, a wide variety of challenging musculoskeletal disorders have been treated successfully over the past two decades. More than a quarter million patients with chronically ununited fractures have benefitted, worldwide, from this surgically non-invasive method, without risk, discomfort, or the high costs of operative repair. Many of the athermal bioresponses, at the cellular and subcellular levels, have been identified and found appropriate to correct or modify the pathologic processes for which PEMFs have been used. Not only is efficacy supported by these basic studies but by a number of double-blind trials. As understanding of mechanisms expands, specific requirements for field energetics are being defined and the range of treatable ills broadened. These include nerve regeneration, wound healing, graft behavior, diabetes, and myocardial and cerebral ischemia (heart attack and stroke), among other conditions. Preliminary data even suggest possible benefits in controlling malignancy.