Tuberculosis

Lik Sprava. 2004 Oct-Nov;(7):41-6.Links

Effect of magnetic and ultrasound therapy on clinical manifestations and general parameters of efficiency in the treatment of pulmonary tuberculosis.

[Article in Ukrainian]

Savchenko VI, Samosiuk IZ.

The authors have analized general efficiency coefficients of the treatment of 117 patients with the first diagnized pulmonary tuberculosis. The patients were divided into a control and main group. 61 patients of the main group at the initial stage of complex treatment in addition to a standard chemotherapy have recieved magnetic and ultrasound therapy. During the treatment the patients underwent complex clinical and X-ray examination. The patients of the main group have been detected to have better signs of recovering compared with the control group. The signs were the following: more rapid disappearing of main clinical symptoms, radiological marks of tuberculosis such as focal and infiltrative alterations and decay cavity closing, cessation of bacterioexcretion.

Probl Tuberk. 2000;(2):18-21.

Magnetic laser therapy in combination with lymphotropic drugs administration in treating teenagers with common forms of tuberculosis.

[Article in Russian]

Ovsiankina ES, Dobkin VG, Kobulashvili MG, Rusakova LI, Gubkina MF.

The paper shows the efficiency of combined use of magnetic laser therapy (MLT) and lymphotropic drug therapy in 40 teenagers with common forms of tuberculosis. The use of laser makes it possible to modify methods of regional lymphotropic therapy, to prolong its use and increase indications for it. MLT in combination with lymphotropic drug therapy accelerates positive changes and hence enhances the efficiency of tuberculosis treatment.

Probl Tuberk. 2001;(2):11-2.

Very high frequency electromagnetic irradiation in multimodal treatment of patients with disseminated infiltrative pulmonary tuberculosis.

[Article in Russian]

Iakovleva LP, Lineva ZE, Mozhokina GN.

Multimodality treatment involving very high-frequency electromagnetic radiation (VHFER) in combination with the antioxidants alpha-tocopherol and sodium thiosulfate, which had been performed in 27 patients with disseminated infiltrative pulmonary tuberculosis, was effective. As compared to patients receiving chemotherapy in combination with electromagnetic radiation (n = 29) and routine chemotherapy alone (n = 29), these patients had more benefits from the multimodality treatment in terms of bacterial isolation cessation and reduced hospital stay by 1.5-2 months, minimal pneumofibrotic changes occurred in 63% of the patients. Combined VHFER and antioxidative therapy were found to exert a normalizing effect on lipid peroxidation and immunity.

Probl Tuberk. 1999;(6):30-2.

Impact of combined magnetic and laser radiation of regional pulmonary blood flow in patients with destructive pulmonary tuberculosis.

[Article in Russian]

Iakubenia ON, Tostik SI, Iakubenia GI.

Rheopulmonography was used to study regional pulmonary blood flow in 30 patients with destructive pulmonary tuberculosis before and after combined magnetic and laser radiation (an experimental group) and in 28 patients receiving the routine chemotherapy (a control group). The use of combined exposure of a constant magnetic field and laser radiation was found to promote pulmonary vascular tone, better microcirculatory blood flow, and increased pulse blood filling in the affected portion of the lung.

Probl Tuberk. 1997;(6):50-3.Links

Use of centimetric range microwave therapy in multimodality of treatment patients with destructive pulmonary tuberculosis.

[Article in Russian]

Savula MM, Kravchenko NS.

Centimeter microwave therapy (CMWT) was employed in the multimodality treatment of 50 patients with destructive pulmonary tuberculosis. Its results were compared with a matched control group comprising 43 patients. CMWT increased the rate of decay cavity closure, improved bronchial patency and prevented its deterioration. This was followed by improved lipid peroxidation, antioxidative activity, and an immunological responsiveness of the body.

Probl Tuberk. 1995;(6):17-20.

Significance of the functional state of blood phagocytes in the choice of optimal regime of EHF therapy of patients with pulmonary tuberculosis.

[Article in Russian]

Novikova LN, Kaminskaia GO, Efimova LN.

A trial entered 136 patients with active tuberculosis of the lungs. 86 patients received conventional chemotherapy and a course of microwave therapy. Control patients received chemotherapy alone. Phagocyte cell viability and NB-test served as assessment laboratory criteria. Millimetric waves in the treatment of pulmonary tuberculosis potentiate the treatment efficacy documented as more rapid infiltration resolution and cavern closure through the mechanism of normalization of phagocyte cell function. The choice of wave length is principal: 5.6 mm waves affect phagocyte function negatively, 6.4 mm waves produce more significant positive effect in young patients with new local lesions while 7.1 mm waves in older patients and in severe involvement. In vitro radiation of the patients’ blood using different wave lengths and subsequent performance of NB-test provides objective information for choice of optimal treatment regimen.

Probl Tuberk. 1994;(4):2-4.

Effectiveness of chemotherapy combined with ultrahigh-frequency electromagnetic radiation for the treatment of patients with pulmonary tuberculosis.

[Article in Russian]

Khomenko AG, Chukanov VI, Novikova LN.

A procedure was developed to determine the optimum wavelength used for each patient individually. Ultrahigh-frequency electromagnetic radiation was studied in 54 patients with various pulmonary tuberculosis forms for its impact on the course of the disease. Treatment was performed by using a YAVOR device at 6.4 and 7.1 mm. Is was found that following 10 sessions of UHF therapy used in combination with specific chemicals, caverns were closed in 50% of patients 2-3 months after therapy and in the controls 5-6 months later. Infiltrates in the lesion areas were resolved 2-3 weeks after UHF exposure, whereas in the controls 1-2 months following drug therapy alone.

Tubal Pregnancy

Vopr Kurortol Fizioter Lech Fiz Kult. 1996 Jan-Feb;(1):21-2.

Tubal pregnancy: the experience of early rehabilitative treatment.

[Article in Russian]

Strugatskii VM, Strizhakov AN, Shmeleva SV.

The surgical treatment for tubal pregnancy including laparoscopy and antibacterial therapy were combined in 30 females with early start (on postoperative day 1) of rehabilitation: psychotherapy, diet, therapeutic exercise, low-frequency magnetotherapy. Hysterosalpingography and dynamic dopplerography assessed the effect as good.

Trophic Ulcer

Klin Khir. 1993;(7-8):31-4.

Use of magnetic therapy combined with galvanization and tissue electrophoresis in the treatment of trophic ulcers.

[Article in Russian]

Alekseenko AV, Gusak VV, Stoliar VF, Iftodii AG, Tarabanchuk VV, Shcherban NG, Naumets AA.

The results of treatment of 86 patients with the use of magnetotherapy in combination with galvanization and intratissue electrophoresis are presented. To create an electric field, the “Potok-1” apparatus with a density of current equal to 0.05-0.1 mA/cm2 was employed. Simultaneously, the “MAG-30” apparatus for low-frequency magnetotherapy with induction of 30 mT and area of exposure of 20 cm2 was applied to a trophic ulcer site. The use of magnetogalvanotherapy in the complex of treatment of trophic ulcers of the lower extremities is recommended.

Pol Tyg Lek. 1991 Sep 9-30;46(37-39):717-9.

Use of magnetic field in treatment of trophic leg ulcers.

[Article in Polish]

Sieron A, Zmudzinski J, Cieslar G, Adamek M.

III Katedry i Kliniki Chorob Wewnetrznych Sl. AM w Bytomiu.

Theoretical basis and favourable therapeutical application of magnetic field in case of trophic ulcerations of the lower limbs are discussed. As a clinical example of such action a case of a 39-year old female patient with trophic ulceration of the leg is presented. Practical advantages of magnetotherapy in similar to the described case patients are suggested.

Klin Khir. 1991;(7):60-3.

Treatment of trophic ulcers of the lower extremities using a magnetic field.

[Article in Russian]

Alekseenko AV, Gusak VV.

The experience with treatment of 126 patients with ulcerous-necrotic lesion of the lower extremities of different genesis was summarized. A comparative evaluation of the effectiveness of treatment depending on a type of the magnetic field: the constant, alternating, or travelling impulse one was carried out. The most effective was the use of a travelling impulse magnetic field. The results of the investigation performed give grounds to recommend the wide use of magnetotherapy in the complex treatment of trophic ulcers of the lower extremities

Transcranial Magnetic Stimulation

Front Hum Neurosci. 2015 Jun 16;9:303. doi: 10.3389/fnhum.2015.00303. eCollection 2015. Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation. Chervyakov AV1, Chernyavsky AY2, Sinitsyn DO3, Piradov MA1. Author information 1Research Center of Neurology , Moscow , Russia. 2Moscow Institute of Physics and Technology, Russian Academy of Sciences , Moscow , Russia ; Faculty of Computational Mathematics and Cybernetics, Moscow State University , Moscow , Russia. 3Research Center of Neurology , Moscow , Russia ; Semenov Institute of Chemical Physics, Russian Academy of Sciences , Moscow , Russia. Abstract Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson’s disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols. Brain.  2012 Oct 5. [Epub ahead of print] Magnetic flimmers: ‘light in the electromagnetic darkness’ Martens JW, Koehler PJ, Vijselaar J. Source 1 Department of Humanities, Utrecht University, Utrecht, The Netherlands. Abstract Transcranial magnetic stimulation has become an important field for both research in neuroscience and for therapy since Barker in 1985 showed that it was possible to stimulate the human motor cortex with an electromagnet. Today for instance, transcranial magnetic stimulation can be used to measure nerve conduction velocities and to create virtual lesions in the brain. The latter option creates the possibility to inactivate parts of the brain temporarily without permanent damage. In 2008, the American Food and Drugs Administration approved repetitive transcranial magnetic stimulation as a therapy for major depression under strict conditions. Repetitive transcranial magnetic stimulation has not yet been cleared for treatment of other diseases, including schizophrenia, anxiety disorders, obesity and Parkinson’s disease, but results seem promising. Transcranial magnetic stimulation, however, was not invented at the end of the 20th century. The discovery of electromagnetism, the enthusiasm for electricity and electrotherapy, and the interest in Beard’s concept of neurasthenia already resulted in the first electromagnetic treatments in the late 19th and early 20th century. In this article, we provide a history of electromagnetic stimulation circa 1900. From the data, we conclude that Mesmer’s late 18th century ideas of ‘animal magnetism’ and the 19th century absence of physiological proof had a negative influence on the acceptance of this therapy during the first decades of the 20th century. Electromagnetism disappeared from neurological textbooks in the early 20th century to recur at the end of that century. 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.

Schizophr Bull. 2005 Oct 27; [Epub ahead of print]

Therapeutic Effects of Individualized Alpha Frequency Transcranial Magnetic Stimulation ({alpha} TMS) on the Negative on the Negative Symptoms of Schizophrenia.

Jin Y, Potkin SG, Kemp AS, Huerta ST, Alva G, Thai TM, Carreon D, Bunney WE Jr.

Department of Psychiatry and Human Behavior, University of California, Irvine, School of Medicine.

Previous research in clinical electroencephalography (EEG) has demonstrated that reduction of alpha frequency (8-13 Hz) EEG activity may have particular relevance to the negative symptoms of schizophrenia. Repetitive Transcranial Magnetic Stimulation (rTMS) was utilized to investigate this relationship by assessing the therapeutic effects of stimulation set individually at each subject’s peak alpha frequency (alphaTMS). Twenty-seven subjects, with predominantly negative symptom schizophrenia, received 2 weeks of daily treatment with either alphaTMS, 3 Hz, 20 Hz, or sham stimulation bilaterally over the dorsolateral prefrontal cortex. Individualized alphaTMS demonstrated a significantly larger (F 3,33 = 4.7, p = .007) therapeutic effect (29.6% reduction in negative symptoms) than the other 3 conditions (< 9%). Furthermore, these clinical improvements were found to be highly correlated (r = 0.86, p = .001) with increases (34%) in frontal alpha amplitude following alphaTMS. These results affirm that the resonant features of alpha frequency EEG play an important role in the pathophysiology of schizophrenia and merit further investigation as a particularly efficacious frequency for rTMS treatments.

Neuroreport. 2005 Nov 7;16(16):1839-42.

Effects of repetitive transcranial magnetic stimulation in depression: a magnetoencephalographic study.

Maihofner C, Ropohl A, Reulbach U, Hiller M, Elstner S, Kornhuber J, Sperling W.

Departments of aNeurology bPsychiatry and Psychotherapy cInstitute for Experimental Physiology and Pathophysiology, University of Erlangen – Nuremberg, Erlangen, Germany.

Recently, repetitive transcranial magnetic stimulation has evolved as a potential therapeutic tool to interfere with brain changes associated with neurological and psychiatric diseases. Little is known about its mode of action, however. Here, we investigated effects of repetitive transcranial magnetic stimulation on spontaneous magnetoencephalographic activity in patients with major depression. Before treatment, depressed patients showed a significant increase in slow magnetoencephalographic activity (2-6 Hz) over the left prefrontal cortex, compared with healthy controls. This activity significantly decreased during 10 days of repetitive transcranial magnetic stimulation, paralleled by clinical improvement. We conclude that therapeutic repetitive transcranial magnetic stimulation effects can be mirrored by changes of spontaneous magnetoencephalographic activity.

Psychiatry Res. 2005 Nov 15;137(1-2):1-10. Epub 2005 Oct 12.

Transcranial magnetic stimulation in treatment-resistant depressed patients: A double-blind, placebo-controlled trial.

Rossini D, Lucca A, Zanardi R, Magri L, Smeraldi E.

Department of Psychiatry, School of Medicine, Vita-Salute University, San Raffaele Hospital, via Stamira d’Ancona 20, Milan 20127, Italy.

This 5-week, randomized, double-blind, placebo-controlled trial investigated the efficacy and tolerability of high frequency repetitive transcranial magnetic stimulation (rTMS) directed to the left prefrontal cortex in drug-resistant depressed patients. Fifty-four patients were randomly assigned to receive 10 daily applications of either real or sham rTMS. Subjects assigned to receive active stimulation were divided into two further subgroups according to the intensity of stimulation: 80% vs. 100% of motor threshold (MT). At study completion, the response rates were 61.1% (n=11), 27.8% (n=5) and 6.2% (n=1) for the 100% MT group, 80% MT group and sham group, respectively. A significant difference (Pearson chi(2) test) was found between the 100% MT and sham groups, while the 80% MT group did not differ significantly from the sham group. Between the two active groups, a marginally significant difference was observed. Analysis of variance with repeated measures on Hamilton Depression Rating Scale scores revealed a significantly different decrease over time of depressive symptomatology among the three treatment groups. Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded, and on the whole the technique was well tolerated. The results of this double-blind trial showed that rTMS may be a useful and safe adjunctive treatment for drug-resistant depressed patients.

Neuroreport. 2005 Nov 7;16(16):1849-1852.

Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex affects strategic decision-making.

Wout MV, Kahn RS, Sanfey AG, Aleman A.

aDepartment of Psychonomics, Helmholtz Research Institute, University of Utrecht bDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht cBCN NeuroImaging Center, Groningen, The Netherlands dDepartment of Psychology, University of Arizona, Tucson, Arizona, USA.

Although decision-making is typically seen as a rational process, emotions play a role in tasks that include unfairness. Recently, activation in the right dorsolateral prefrontal cortex during offers experienced as unfair in the Ultimatum Game was suggested to subserve goal maintenance in this task. This is restricted to correlational evidence, however, and it remains unclear whether the dorsolateral prefrontal cortex is crucial for strategic decision-making. The present study used repetitive transcranial magnetic stimulation in order to investigate the causal role of the dorsolateral prefrontal cortex in strategic decision-making in the Ultimatum Game. The results showed that repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex resulted in an altered decision-making strategy compared with sham stimulation. We conclude that the dorsolateral prefrontal cortex is causally implicated in strategic decision-making in healthy human study participants.

Psychiatry Res. 2005 Nov 15;137(1-2):113-21. Epub 2005 Oct 11.

Chronic repetitive transcranial magnetic stimulation is antidepressant but not anxiolytic in rat models of anxiety and depression.

Hargreaves GA, McGregor IS, Sachdev PS.

School of Psychiatry, University of New South Wales, Sydney, 2052, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Barker Street, Randwick, NSW 2031, Australia.

Transcranial magnetic stimulation (TMS) has been proposed as a treatment for depression and anxiety disorders. While the antidepressant effect has been modelled in animals, there have been few attempts to examine a possible anxiolytic effect of repetitive TMS (rTMS) in animal models. We administered 18 days of rTMS to male Sprague-Dawley rats. On days 10 through 18, rats were tested in several anxiety models (social interaction, emergence, elevated plus-maze, and predator odor avoidance) and in the forced swim test. No group differences were apparent on any of the anxiety models, while TMS produced an antidepressant effect in the forced swim test. Interestingly, on day 1 of the forced swim test, the home cage control group displayed increased swimming behaviour compared with sham-treated animals, suggesting an observable level of stress may have accompanied sham treatment. The results from the forced swim test suggested that TMS had modest antidepressant properties, but it did not show anxiolytic properties in the models examined. The study also suggested that stress associated with handling should be taken into account in the interpretation of TMS studies in animals.

PLoS Biol. 2005 Oct 18;3(11):e362 [Epub ahead of print]

Improvement of Tactile Discrimination Performance and Enlargement of Cortical Somatosensory Maps after 5 Hz rTMS.

Tegenthoff M, Ragert P, Pleger B, Schwenkreis P, Forster AF, Nicolas V, Dinse HR.

Department of Neurology, Ruhr-University Bochum, BG-Kliniken Bergmannsheil, Bochum, Germany.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used to investigate mechanisms of brain functions and plasticity, but also as a promising new therapeutic tool. The effects of rTMS depend on the intensity and frequency of stimulation and consist of changes of cortical excitability, which often persists several minutes after termination of rTMS. While these findings imply that cortical processing can be altered by applying current pulses from outside the brain, little is known about how rTMS persistently affects learning and perception. Here we demonstrate in humans, through a combination of psychophysical assessment of two-point discrimination thresholds and functional magnetic resonance imaging (fMRI), that brief periods of 5 Hz rTMS evoke lasting perceptual and cortical changes. rTMS was applied over the cortical representation of the right index finger of primary somatosensory cortex, resulting in a lowering of discrimination thresholds of the right index finger. fMRI revealed an enlargement of the right index finger representation in primary somatosensory cortex that was linearly correlated with the individual rTMS-induced perceptual improvement indicative of a close link between cortical and perceptual changes. The results demonstrate that repetitive, unattended stimulation from outside the brain, combined with a lack of behavioral information, are effective in driving persistent improvement of the perception of touch. The underlying properties and processes that allow cortical networks, after being modified through TMS pulses, to reach new organized stable states that mediate better performance remain to be clarified.

Exp Neurol. 2005 Sep 26; [Epub ahead of print]

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex excitability in patients with major depressive disorder.

Bajbouj M, Brakemeier EL, Schubert F, Lang UE, Neu P, Schindowski C, Danker-Hopfe H.

Department of Psychiatry, Charite-University Medicine Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex is a relatively non-invasive technique with putative therapeutic effects in major depression. However, the exact neurophysiological basis of these effects needs further clarification. Therefore, we studied the impact of ten daily sessions of left, dorsolateral prefrontal rTMS on motor cortical excitability, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 30 patients. As compared to the non-responders, responders (33%) showed changes in parameters pointing towards a reduced cortical excitability. These results suggest that repetitive transcranial magnetic stimulation of the dorsolateral, prefrontal cortex may have inhibitory effects on motor cortical neuronal excitability in patients with major depressive disorder. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of antidepressant stimulation techniques like rTMS.

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.

Prog Neuropsychopharmacol Biol Psychiatry. 2005 Oct 19; [Epub ahead of print]

A double-blind sham controlled study of right prefrontal repetitive transcranial magnetic stimulation (rTMS): Therapeutic and cognitive effect in medication free unipolar depression during 4 weeks.

Januel D, Dumortier G, Verdon CM, Stamatiadis L, Saba G, Cabaret W, Benadhira R, Rocamora JF, Braha S, Kalalou K, Vicaut PE, Fermanian J.

Unite de recherche clinique, EPS de Ville Evrard a Saint Denis, G03, 5 Rue du Dr Delafontaine 93200 Saint-Denis, France.

BACKGROUND: Transcranial magnetic stimulation (TMS) has become a therapeutic tool in psychiatric diseases.

METHODOLOGY: The objective was to evaluate the efficacy of TMS in unipolar depression: the percentage of responders (>50% HDRS reduction) and remission (HDRS score </=8, after four weeks of active TMS treatment in depressed patients free of any antidepressive agent versus placebo-TMS.

RESULTS: 27 patients were randomized in two groups: rTMS (N=11) versus sham TMS (N=16). Statistical differences were detected between sham and TMS treated groups on remission (0/16 versus 4/11 p=0.032, 1/16 versus 6/11 0.028 and 1/16 versus 7/11 p=0.011 at day 14, day 21 and day 28, respectively) and on response (2/16 versus 5/11 at day 14 (NS), 2/16 versus 7/11 p=0.0115 at day 21 and 1/16 versus 7/11 (p=0.025) day 28, respectively, using the exact Fisher test). Significant differences were observed between day 1 versus day 8 (p<0.01), day 15, day 21 and day 28 (p<0.001) in TMS group and only versus day 21 (p<0.01) and day 28 (p<0.05) for the sham group. ANOVA comparison between TMS and sham groups was significant at day 14 and day 28 (p<0.05).

LIMITATIONS: The few number of patients.

CONCLUSION: Our study has shown an efficacy of right rTMS in free medication unipolar depression over a month. Nevertheless, number of patients included is limited and multicentric studies will be necessary to specify the antidepressive action of TMS.

Ann Neurol. 2005 Oct 20; [Epub ahead of print]

Altered plasticity of the human motor cortex in Parkinson’s disease.

Ueki Y, Mima T, Ali Kotb M, Sawada H, Saiki H, Ikeda A, Begum T, Reza F, Nagamine T, Fukuyama H.

Human Brain Research Center, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan.

Interventional paired associative stimulation (IPAS) to the contralateral peripheral nerve and cerebral cortex can enhance the primary motor cortex (M1) excitability with two synchronously arriving inputs. This study investigated whether dopamine contributed to the associative long-term potentiation-like effect in the M1 in Parkinson’s disease (PD) patients. Eighteen right-handed PD patients and 11 right-handed age-matched healthy volunteers were studied. All patients were studied after 12 hours off medication with levodopa replacement (PD-off). Ten patients were also evaluated after medication (PD-on). The IPAS comprised a single electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1 with an interstimulus interval of 25 milliseconds (240 paired stimuli every 5 seconds for 20 minutes). The motor-evoked potential amplitude in the right abductor pollicis brevis muscle was increased by IPAS in healthy volunteers, but not in PD patients. IPAS did not affect the motor-evoked potential amplitude in the left abductor pollicis brevis. The ratio of the motor-evoked potential amplitude before and after IPAS in PD-off patients increased after dopamine replacement. Thus, dopamine might modulate cortical plasticity in the human M1, which could be related to higher order motor control, including motor learning. Ann Neurol 2006.

HNO. 2005 Sep 17; [Epub ahead of print]

Treatment of chronic tinnitus with neuronavigated repetitive Transcranial Magnetic Stimulation (rTMS).

[Article in German]

Kleinjung T, Steffens T, Langguth B, Eichhammer P, Marienhagen J, Hajak G, Strutz J.

Klinik fur HNO-Heilkunde der Universitat Regensburg, .

BACKGROUND AND OBJECTIVE: Idiopathic tinnitus is a frequent and debilitating disorder of largely unknown pathophysiology. Focal brain activation in the auditory cortex has recently been demonstrated in chronic tinnitus. Low-frequency rTMS can reduce cortical hyperexcitability.

PATIENTS AND METHODS: In 12 patients with chronic tinnitus, fusion of [(18)F]deoxyglucose-PET and structural MRI (T1, MPRAGE) scans allowed the area of increased metabolic activity in the auditory cortex to be exactly identified; this area was selected as the target for rTMS. A neuronavigational system adapted for TMS positioning enabled the relative positions of the figure-8 coil and the target area to be monitored. Repetitive TMS (110% motor threshold; 1 Hz; 2000 stimuli per day over 5 days) was performed using a placebo-controlled crossover design. A sham coil system was used for the placebo stimulation. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller).

RESULTS: In all 12 patients an asymmetrically increased metabolic activation of the gyrus of Heschl was detected. The tinnitus score was significantly improved after 5 days of active rTMS, an effect not seen after placebo stimulation.

CONCLUSION: These preliminary results show that neuronavigated rTMS may improve our understanding and treatment of chronic tinnitus.

Clin Neurophysiol. 2005 Oct 24; [Epub ahead of print]

Transcranial magnetic and electrical stimulation compared: Does TES activate intracortical neuronal circuits?

Brocke J, Irlbacher K, Hauptmann B, Voss M, Brandt SA.

Department of Neurology, Berlin NeuroImaging Center, Charite, 10117 Berlin, Germany.

OBJECTIVE: To determine whether, and under which conditions, transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) can activate similar neuronal structures of the human motor cortex, as indicated by electromyographic recordings.

METHODS: Focal TMS was performed on three subjects inducing a postero-anterior directed current (p-a), TES with postero-anteriorly (p-a) and latero-medially (l-m) oriented electrodes. We analyzed the onset latencies and amplitudes (single-pulse) and intracortical inhibition and excitation (paired-pulse).

RESULTS: TMS p-a and TES p-a produced muscle responses with the same onset latency, while TES l-m led to 1.4-1.9ms shorter latencies. Paired-pulse TMS p-a and TES p-a induced inhibition at short inter-stimulus intervals (ISI) (maximum: 2-3ms) and facilitation at longer ISIs (maximum: 10ms). No inhibition but a strong facilitation was obtained from paired-pulse TES l-m (ISIs 1-5ms).

CONCLUSIONS: Our findings support the hypothesis, that current direction is the most relevant factor in determining the mode of activation for both TMS and TES: TMS p-a and TES p-a are likely to activate the corticospinal neurons indirectly. In contrast, TES l-m may preferentially activate the corticospinal fibres directly, distant of the neuronal body. SIGNIFICANCE: TES is a suitable tool to induce intracortical inhibition and excitation.

Neurosci Behav Physiol. 2005 Mar;35(3):313-7.

The effects of L-DOPA and transcranial magnetic stimulation on behavioral reactions in kindled rats.

Godlevskii LS, Kobolev EV.

Odessa State Medical University, 2 Valikhovskii Lane, 65026 Odessa, Ukraine.

Acute experiments were performed on rats to produce a model of chronic epileptic activity–pharmacological kindling by repeated doses of picrotoxin (1.0-1.2 mg/kg, i.p.). During the early period following kindling (24 h from the last dose of epileptogen), animals showed decreases in measures of investigative behavior as measured in an open field test, along with reductions in sexual and feeding behavior. The severity of these impairments had decreased by two weeks from the last picrotoxin dose. Both treatment with L-DOPA (100 mg/kg, i.p.) and transcranial magnetic stimulation (20 impulses with induction, peak 1.5 T) were accompanied by increases in measures of investigative, sexual, and feeding behavior in the animals, suggesting that mechanism of action of transcranial magnetic stimulation in relation to kindling-induced behavioral abnormalities is mediated by activation of the dopaminergic system of the brain.

Eur J Neurosci. 2005 Nov;22(9):2392-6.

High-frequency repetitive transcranial magnetic stimulation over the hand area of the primary motor cortex disturbs predictive grip force scaling.

Nowak DA, Voss M, Huang YZ, Wolpert DM, Rothwell JC.

Sobell Department of Motor Neuroscience and Movements Disorders, Institute of Neurology, University College London, London, UK.

When we repetitively lift an object, our grip force is influenced by the mechanical object properties of the preceding lift, irrespective of whether the subsequent lift is performed with the same hand or the hand opposite to the preceding lift. This study investigates if repetitive high-frequency transcranial magnetic stimulation (rTMS) over the dominant primary motor cortex affects this relationship. After completion of 10 lifts of an object using the dominant hand, rTMS was applied over the dominant primary motor cortex for 20 s. On the first lift following rTMS, the peak grip force was significantly higher than on the lift preceding rTMS. Moreover, this measure remained elevated throughout the following set of lifts after rTMS. rTMS did not change the peak lift force generated by more proximal arm muscles. The same effect was observed when the lifts following rTMS over the dominant motor cortex were performed with the ipsilateral hand. These effects were not observed when subjects rested both hands on their lap or when a sham stimulation was applied for the same period of time. These preliminary data suggest that rTMS over the sensorimotor cortex disturbs predictive grip force planning.

J Psychiatr Res. 2005 Oct 28; [Epub ahead of print]

Striatal dopamine release after prefrontal repetitive transcranial magnetic stimulation in major depression: Preliminary results of a dynamic [(123)I] IBZM SPECT study.

Pogarell O, Koch W, Popperl G, Tatsch K, Jakob F, Zwanzger P, Mulert C, Rupprecht R, Moller HJ, Hegerl U, Padberg F.

Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstr. 7, D-80336 Munich, Germany.

Though there is considerable evidence that prefrontal repetitive transcranial magnetic stimulation (rTMS) exerts antidepressant effects, the neurobiological action of rTMS in patients with depression is poorly understood. Preclinical studies in animals and humans have demonstrated that prefrontal rTMS can induce dopamine release in mesostriatal and mesolimbic regions. We therefore investigated whether rTMS also modulates striatal dopaminergic neurotransmission in depressed patients using a dynamic [(123)I] iodobenzamide (IBZM) single photon emission computed tomography (SPECT) approach. Five patients with a major depressive episode (DSM-IV) underwent an acute 10Hz rTMS challenge with 3000 stimuli over the left dorsolateral prefrontal cortex during an [(123)I] IBZM-SPECT bolus and constant infusion protocol. In four subjects the protocol was repeated after a three week rTMS standard treatment. Striatal IBZM binding to dopamine D(2) receptors was assessed with a region-of-interest (ROI) technique. The change in striatal IBZM binding after the rTMS challenge was regarded as measure of change in endogenous striatal dopamine. Data of nine SPECT investigations showed a significant reduction by 9.6+/-6.2% in IBZM binding to striatal dopamine D(2) receptors after rTMS challenge compared to baseline (p=0.01, Wilcoxon test). In this preliminary study, the reduction of IBZM binding observed after rTMS challenge is suggestive of a release in endogenous dopamine induced by prefrontal rTMS. In future, this approach can be used to differentiate specific and non-specific reward-related effects of rTMS on dopaminergic neurotransmission.

Vision Res. 2005 Oct 26; [Epub ahead of print]

Processing of global form and motion in migraineurs.

Ditchfield JA, McKendrick AM, Badcock DR.

School of Psychology, University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia.

Previous studies have identified anomalies of cortical visual processing in migraineurs that appear to extend beyond V1. Migraineurs respond differently than controls to transcranial magnetic stimulation of V5, and can demonstrate impairments of global motion processing. This study was designed to assess the integrity of intermediate stages of both motion and form processing in people with migraine. We measured the ability to integrate local orientation information into a global form percept, and to integrate local motion information into a global motion percept. Control subjects performed significantly better than migraineurs on both tasks, suggesting a diffuse visual cortical processing anomaly in migraine.

J Clin Neurosci. 2005 Oct 25; [Epub ahead of print]

The use of transcranial magnetic stimulation in the clinical evaluation of suspected myelopathy.

Chan YC, Mills KR.

Department of Clinical Neurophysiology, King’s College Hospital, London SE5 9RS.

Central motor conduction time (CMCT) and motor evoked potential (MEP) latencies measured by using transcranial magnetic stimulation (TMS) are parameters used to evaluate electrophysiologic function of the corticospinal motor tract. We present 5 cases to illustrate how the use of TMS had contributed to clinical management. CMCT and MEP latency measurements were found to be useful in determining the significance of lesions seen on neuroimaging and helped clinical decisions in the presence of multiple lesions or multiple clinical conditions that cause similar clinical manifestations. TMS study is particularly useful in localizing levels of conduction defect.

Exp Brain Res. 2005 May;163(1):21-31. Epub 2005 Feb 3.

Silent period to transcranial magnetic

Kimiskidis VK, Papagiannopoulos S, Sotirakoglou K, Kazis DA, Kazis A, Mills KR.

Department of Neurology III, G. Papanikolaou Hospital, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece. kimiskid@med.auth.gr

Silent period (SP) is widely used in transcranial magnetic stimulation studies. Methodologically, SP is usually elicited at stimulus intensities corresponding to a certain percentage of corticomotor threshold. Because this approach might lead to factitious SP changes, the present study was designed to develop, in a stepwise manner, a method for investigating SP independently of corticomotor threshold. First, stimulus-response (S-R) curves of SP against stimulus intensity (SI) were constructed and quantitatively described in healthy volunteers. Second, various methodological issues such as the optimum model for describing the relationship between SP duration and SI and the importance of the type of stimulating coil were addressed. Finally, the proposed method and a commonly used method (eliciting SPs at 130% MT SI) were directly compared for a group of epileptic patients for whom administration of oxcarbazepine resulted in significant corticomotor threshold elevation. Twenty-one subjects (eleven females, median age, 38 years) were studied. SPs were obtained with a figure-of-eight coil using a standardized procedure (recording, FDI). Pilot experiments indicated that at least four trials were required, at each intensity level, to estimate the mean SP duration within 10% of the true mean. Therefore, SPs were determined from the average of four trials with 5% increments from 5 to 100% maximum SI. In a second set of experiments, SPs were obtained for fifteen subjects using a circular coil. In a third set of experiments, eight epileptic patients were studied before and after administration of oxcarbazepine (mean dose 1553 mg, range 900-1800 mg). The S-R curves were fitted to a Boltzman function and to first-order to fourth-order polynomial and sigmoid functions. The Boltzman function described the data accurately (R2=0.947-0.990). In addition, direct comparison of the six models with an F-test proved the superiority of the first. The best-fit parameters of the reference curve, i.e. the maximum and minimum values, the slope, and V50 (the SI at which SP duration is halfway between Min and Max) were 230.8+/-3.31 ms (x+/-SEM), -11.51+/-3.31 ms, 11.56+/-0.65%, and 49.82+/-0.65%, respectively. When the curves obtained with the circular coil were compared with those obtained with the figure-of-eight coil, there were differences between V50 (51.69+/-0.72 vs 47.95+/-0.82, P<0.001) and SP threshold (31.15 vs 24.77, P<0.01) whereas the other best-fit values did not differ significantly. Oxcarbazepine increased corticomotor threshold from 45.3+/-5.8% at baseline to 59.4+/-10.4% (P<0.001). According to the commonly used method, the drug significantly prolonged SP (from 117.6+/-42.4 ms to 143.5+/-46.5 ms, P<0.001) and, consequently, enhanced brain inhibition. In contrast, study of the SP curves led to the conclusion that oxcarbazepine does not affect the Max value and slope but significantly increases V50 and SP threshold (from 54.5+/-4.9% to 59.9+/-7.2% and from 29.1+/-6.4% to 34.6+/-6.8%, respectively, P<0.01). These findings imply that oxcarbazepine does not enhance brain inhibitory mechanisms. Thus, in situations characterized by significant changes in corticomotor threshold the proposed method provides results clearly different from a commonly used approach. It is concluded that S-R curves obtained with a figure-of-eight coil in 5% increments and fitted to a Boltzman function provide an accurate, comprehensive, and clinically applicable method for exploring SP.

Invest Radiol. 1998 Jun;33(6):336-40.

Echoplanar BOLD fMRI of brain activation induced by concurrent transcranial magnetic stimulation.

Bohning DE, Shastri A, Nahas Z, Lorberbaum JP, Andersen SW, Dannels WR, Haxthausen EU, Vincent DJ, George MS.

Department of Radiology, Medical University of South Carolina, Charleston 29425, USA. bohninde@musc.edu

RATIONALE AND OBJECTIVES: The authors demonstrate the feasibility of combining transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) inside an MR scanner to noninvasively stimulate and image regional brain activity.

METHODS: Echoplanar blood oxygen level dependent (BOLD)-based fMRI studies of TMS response were performed on three human volunteers inside a standard 1.5 T MR scanner using independent computer control to interleave echoplanar image acquisition and stimulation of right thumb primary motor cortex with a nonferromagnetic TMS coil.

RESULTS: Significant (P< 0.001) response was observed in motor cortex under the TMS coil during stimulation compared to rest, as well in auditory cortex, the latter presumably due to the loud “snap” when the coil was pulsed.

CONCLUSIONS: Concurrent TMS stimulation and echoplanar BOLD fMRI imaging is possible. This method has potential for tracing neural circuits with brain imaging, as well as investigating the effects of TMS.

Int J Neurosci. 1998 May;94(1-2):41-54.

Transcranial AC pulsed applications of weak electromagnetic fields reduces freezing and falling in progressive supranuclear palsy: a case report.

Sandyk R.

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

Freezing is a common and disabling symptom in patients with Parkinsonism. It affects most commonly the gait in the form of start hesitation and sudden immobility often resulting in falling. A higher incidence of freezing occurs in patients with progressive supranuclear palsy (PSP) which is characterized clinically by a constellation of symptoms including supranuclear ophthalmoplegia, postural instability, axial rigidity, dysarthria, Parkinsonism, and pseudobulbar palsy. Pharmacologic therapy of PSP is currently disappointing and the disease progresses relentlessly to a fatal outcome within the first decade after onset. This report concerns a 67 year old woman with a diagnosis of PSP in whom freezing and frequent falling were the most disabling symptoms of the disease at the time of presentation. Both symptoms, which were rated 4 on the Unified Parkinson Rating Scale (UPRS) which grades Parkinsonian symptoms and signs from 0 to 4, with 0 being normal and 4 being severe symptoms, were resistant to treatment with dopaminergic drugs such as levodopa, amantadine, selegiline and pergolide mesylate as well as with the potent and highly selective noradrenergic reuptake inhibitor nortriptyline. Weekly transcranial applications of AC pulsed electromagnetic fields (EMFs) of picotesla flux density was associated with approximately 50% reduction in the frequency of freezing and about 80-90% reduction in frequency of falling after a 6 months follow-up period. At this point freezing was rated 2 while falling received a score of 1 on the UPRS. In addition, this treatment was associated with an improvement in Parkinsonian and pseudobulbar symptoms with the difference between the pre-and post EMF treatment across 13 measures being highly significant (p < .005; Sign test). These results suggest that transcranial administration AC pulsed EMFs in the picotesla flux density is efficacious in the treatment of PSP.

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

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

Sandyk R.

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

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

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

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

Sandyk R.

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

A 74 year old retired building inspector with a 15 year history of Parkinson’s disease (PD) presented with severe resting tremor in the right hand, generalized bradykinesia, difficulties with the initiation of gait with freezing, mental depression and generalized cognitive impairment despite being fully medicated. Testing of constructional abilities employing various drawing tasks demonstrated drawing impairment compatible with severe left hemispheric dysfunction. After receiving two successive transcranial applications, each of 20 minutes duration, with AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla flux density and frequencies of 5Hz and 7Hz respectively, his tremor remitted and there was dramatic improvement in his drawing performance. Additional striking improvements in his drawing performance occurred over the following two days after he continued to receive daily treatments with EMFs. The patient’s drawings were subjected to a Reliability Test in which 10 raters reported 100% correct assessment of pre- and post drawings with all possible comparisons (mean 2 = 5.0; p < .05). This case demonstrates in PD rapid reversal of drawing impairment related to left hemispheric dysfunction by brief transcranial applications of AC pulsed picotesla flux density EMFs and suggests that cognitive deficits associated with Parkinsonism, which usually are progressive and unaffected by dopamine replacement therapy, may be partly reversed by administration of these EMFs. Treatment with picotesla EMFs reflects a “cutting edge” approach to the management of cognitive impairment in Parkinsonism.

Tinnitus – Hyperacusis – Hearing Loss

Photomed Laser Surg. 2010 Jun;28(3):371-7.

Pain threshold improvement for chronic hyperacusis patients in a prospective clinical study.

Zazzio M.

Audio Laser-Kliniken, Flygeln, Hovmantorp, Sweden. audiolaser@mail.nu

Abstract

OBJECTIVE: The aim of this study was to investigate if laser therapy in combination with pulsed electromagnetic field therapy/repetitive transcranial magnetic stimulation (rTMS) and the control of reactive oxygen species (ROS) would lead to positive treatment results for hyperacusis patients.

BACKGROUND DATA: Eight of the first ten patients treated for tinnitus, who were also suffering from chronic hyperacusis, claimed their hyperacusis improved. Based upon that, a prospective, unblinded, uncontrolled clinical trial was planned and conducted. ROS and hyperacusis pain thresholds were measured.

MATERIALS AND METHODS: Forty-eight patients were treated twice a week with a combination of therapeutic laser, rTMS, and the control and adjustment of ROS. A magnetic field of no more than 100 microT was oriented behind the outer ear, in the area of the mastoid bone. ROS were measured and controlled by administering different antioxidants. At every treatment session, 177-504 J of laser light of two different wavelengths was administered toward the inner ear via meatus acusticus.

RESULTS: The improvements were significantly better in the verum group than in a placebo group, where 40% of the patients were expected to have a positive treatment effect. The patients in the long-term follow-up group received significantly greater improvements than the patients in the short-term follow-up group.

CONCLUSION: The treatment is effective in treating chronic hyperacusis.

HNO. 2006 Jun;54(6):439-44.

Treatment of chronic tinnitus with neuronavigated repetitive Transcranial Magnetic Stimulation (rTMS).

[Article in German]

Kleinjung T, Steffens T, Langguth B, Eichhammer P, Marienhagen J, Hajak G, Strutz J.

Klinik für HNO-Heilkunde der Universität Regensburg, Regensburg. tobias.kleinjung@klinik.uni-regensburg.de

Abstract

BACKGROUND AND OBJECTIVE: Idiopathic tinnitus is a frequent and debilitating disorder of largely unknown pathophysiology. Focal brain activation in the auditory cortex has recently been demonstrated in chronic tinnitus. Low-frequency rTMS can reduce cortical hyperexcitability.

PATIENTS AND METHODS: In 12 patients with chronic tinnitus, fusion of [18F]deoxyglucose-PET and structural MRI (T1, MPRAGE) scans allowed the area of increased metabolic activity in the auditory cortex to be exactly identified; this area was selected as the target for rTMS. A neuronavigational system adapted for TMS positioning enabled the relative positions of the figure-8 coil and the target area to be monitored. Repetitive TMS (110% motor threshold; 1 Hz; 2000 stimuli per day over 5 days) was performed using a placebo-controlled crossover design. A sham coil system was used for the placebo stimulation. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller).

RESULTS: In all 12 patients an asymmetrically increased metabolic activation of the gyrus of Heschl was detected. The tinnitus score was significantly improved after 5 days of active rTMS, an effect not seen after placebo stimulation.

CONCLUSION: These preliminary results show that neuronavigated rTMS may improve our understanding and treatment of chronic tinnitus.

HNO. 2005 Sep 17; [Epub ahead of print]

Treatment of chronic tinnitus with neuronavigated repetitive Transcranial Magnetic Stimulation (rTMS).

[Article in German]

Kleinjung T, Steffens T, Langguth B, Eichhammer P, Marienhagen J, Hajak G, Strutz J.

Klinik fur HNO-Heilkunde der Universitat Regensburg, .

BACKGROUND AND OBJECTIVE: Idiopathic tinnitus is a frequent and debilitating disorder of largely unknown pathophysiology. Focal brain activation in the auditory cortex has recently been demonstrated in chronic tinnitus. Low-frequency rTMS can reduce cortical hyperexcitability.

PATIENTS AND METHODS: In 12 patients with chronic tinnitus, fusion of [(18)F]deoxyglucose-PET and structural MRI (T1, MPRAGE) scans allowed the area of increased metabolic activity in the auditory cortex to be exactly identified; this area was selected as the target for rTMS. A neuronavigational system adapted for TMS positioning enabled the relative positions of the figure-8 coil and the target area to be monitored. Repetitive TMS (110% motor threshold; 1 Hz; 2000 stimuli per day over 5 days) was performed using a placebo-controlled crossover design. A sham coil system was used for the placebo stimulation. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller).

RESULTS: In all 12 patients an asymmetrically increased metabolic activation of the gyrus of Heschl was detected. The tinnitus score was significantly improved after 5 days of active rTMS, an effect not seen after placebo stimulation.

CONCLUSION: These preliminary results show that neuronavigated rTMS may improve our understanding and treatment of chronic tinnitus.

Otol Neurotol. 2005 Jul;26(4):616-9.

Transcranial magnetic stimulation for tinnitus: influence of tinnitus duration on stimulation parameter choice and maximal tinnitus suppression.

De Ridder D, Verstraeten E, Van der Kelen K, De Mulder G, Sunaert S, Verlooy J, Van de Heyning P, Moller A.

Department of Neurosurgery and Otorhinolaryngology, University Hospital Antwerp, Belgium. dirk.de.ridder@uza.be

OBJECTIVE: Tinnitus is a distressing symptom for which few treatments exist. It leads to an important decrease in quality of life in 2 to 3% of the population. Tinnitus is considered a phantom sound, the result of cortical reorganization. Transcranial magnetic stimulation (TMS) is a noninvasive method to modulate cortical reorganization and has been shown to be able to influence tinnitus perception.

STUDY DESIGN: Retrospective analysis.

SETTING: Tertiary referral center.

PATIENTS: The effect of TMS of the contralateral auditory cortex in 114 patients with unilateral tinnitus is investigated as one of the selection criteria used for surgical implantation of electrodes on the auditory cortex.

INTERVENTION: TMS is performed at 90% of motor threshold at 1, 3, 5, 10, and 20 Hz, with each stimulation session consisting of 200 pulses. Results were classified as no effect (0-19% improvement), partial effect (20-79% improvement), and good effect (80-100 suppression). MAIN OUTCOME MEASURES: TMS had a good effect in 25% of the patients studied, partial effect in 28% patients, and no effect in 47%.

RESULTS: TMS at 200 pulses is capable of tinnitus suppression for seconds only. The results were influenced by tinnitus duration: the longer the tinnitus exists, the lower the stimulation frequency that yields maximal tinnitus suppression (p < 0.001). The maximal amount of tinnitus suppression decreases in time (p < 0.01), resulting in a 2% decrease of potential tinnitus suppression per year.

CONCLUSION: TMS of the auditory cortex is capable of modifying tinnitus perception for a very short time. The maximal amount of suppression and best stimulation frequency depends on the tinnitus duration.

Clin Otolaryngol Allied Sci. 1993 Aug;18(4):278-81.

Electromagnetic stimulation as a treatment of tinnitus: a pilot study.

Roland NJ, Hughes JB, Daley MB, Cook JA, Jones AS, McCormick MS.

Department of Otolaryngology, Royal Liverpool University Hospital, UK.

This paper reports the results of a study to determine whether pulsed electromagnetic stimulation, applied over the mastoid bone, caused an improvement in the level of tinnitus in long-standing tinnitus sufferers. Fifty-eight patients from the Liverpool Tinnitus Association volunteered to take part in a double-blind placebo controlled trial. Active and placebo devices were randomly allocated to these patients on their first visit. At the end of one week of treatment, each patient noted whether their tinnitus had completely disappeared, was improved, unchanged or made worse by the treatment Forty-five per cent of the patients who completed the trial were improved by the active device, but only 9% by placebo (P = 0.0013, Mann-Whitney test). We suggest that electromagnetic stimulation may be an effective treatment in some tinnitus sufferers.

Vestn Otorinolaringol. 2002;(1):11-4.

Electrophysical effects in combined treatment of neurosensory hypoacusis.

[Article in Russian]

Morenko VM, Enin IP.

The authors consider different methods of electrobiophysical impacts on the body in the treatment of neurosensory hypoacusis: laser beam, laser puncture, electrostimulation, magnetotherapy, magnetolasertherapy, electrophoresis, etc. These methods find more and more intensive application in modern medicine. Further success of physiotherapy for neurosensory hypoacusis depends on adequate knowledge about mechanisms of action of each physical method used and introduction of novel techniques.

Vestn Otorinolaringol. 2001;(4):10-2.

Cerebral hemodynamics in patients with neurosensory hearing loss before and after magnetotherapy.

[Article in Russian]

Morenko VM, Enin IP.

Magnetotherapy effects on cerebral hemodynamics were studied using rheoencephalography (REG). When the treatment results and changes in cerebral hemodynamics were compared it was evident that normalization or improvement of vascular status in vertebrobasilar and carotid territories registered at REG results in better hearing. This confirms the role of vascular factor in pathogenesis of neurosensory hypoacusis of different etiology and effectiveness of magnetotherapy in such patients.

Vestn Otorinolaringol. 1996 Nov-Dec;(6):23-6.

The treatment of hypoacusis in children by using a pulsed low-frequency electromagnetic field.

[Article in Russian]

Bogomil’skii MR, Sapozhnikov IaM, Zaslavskii AIu, Tarutin NP.

The authors provide specifications of the unit INFITA supplied with ELEMAGS attachment of their own design; the technique of treating hypoacusis in children with utilization of impulse low-frequency electromagnetic field; the results of this treatment in 105 hypoacusis children. The method was found highly effective and valuable for wide practice.

Med Tekh. 1995 Mar-Apr;(2):40-1.

ELEMAGS apparatus and clinical experience in its use in the treatment of children with hypoacusis and otalgia.

[Article in Russian]

Zaslavskii AIu, Sapozhnikov IaM, Markarov GS, Gelis IuS.

To enhance effectiveness of magnetotherapy in the treatment of otic diseases the authors propose to use impulse low-frequency electromagnetic field in combination with constant magnetic field. ELEMAGS equipment based on the above principles is introduced to treat cochlear neuritis and neurosensory hypoacusis in children.

Tinnitus

HNO. 2005 Sep 17; [Epub ahead of print]

Treatment of chronic tinnitus with neuronavigated repetitive Transcranial Magnetic Stimulation (rTMS).

[Article in German]

Kleinjung T, Steffens T, Langguth B, Eichhammer P, Marienhagen J, Hajak G, Strutz J.

Klinik fur HNO-Heilkunde der Universitat Regensburg, .

BACKGROUND AND OBJECTIVE: Idiopathic tinnitus is a frequent and debilitating disorder of largely unknown pathophysiology. Focal brain activation in the auditory cortex has recently been demonstrated in chronic tinnitus. Low-frequency rTMS can reduce cortical hyperexcitability.

PATIENTS AND METHODS: In 12 patients with chronic tinnitus, fusion of [(18)F]deoxyglucose-PET and structural MRI (T1, MPRAGE) scans allowed the area of increased metabolic activity in the auditory cortex to be exactly identified; this area was selected as the target for rTMS. A neuronavigational system adapted for TMS positioning enabled the relative positions of the figure-8 coil and the target area to be monitored. Repetitive TMS (110% motor threshold; 1 Hz; 2000 stimuli per day over 5 days) was performed using a placebo-controlled crossover design. A sham coil system was used for the placebo stimulation. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller).

RESULTS: In all 12 patients an asymmetrically increased metabolic activation of the gyrus of Heschl was detected. The tinnitus score was significantly improved after 5 days of active rTMS, an effect not seen after placebo stimulation.

CONCLUSION: These preliminary results show that neuronavigated rTMS may improve our understanding and treatment of chronic tinnitus.

Otol Neurotol. 2005 Jul;26(4):616-9.

Transcranial magnetic stimulation for tinnitus: influence of tinnitus duration on stimulation parameter choice and maximal tinnitus suppression.

De Ridder D, Verstraeten E, Van der Kelen K, De Mulder G, Sunaert S, Verlooy J, Van de Heyning P, Moller A.

Department of Neurosurgery and Otorhinolaryngology, University Hospital Antwerp, Belgium. dirk.de.ridder@uza.be

OBJECTIVE: Tinnitus is a distressing symptom for which few treatments exist. It leads to an important decrease in quality of life in 2 to 3% of the population. Tinnitus is considered a phantom sound, the result of cortical reorganization. Transcranial magnetic stimulation (TMS) is a noninvasive method to modulate cortical reorganization and has been shown to be able to influence tinnitus perception.

STUDY DESIGN: Retrospective analysis. SETTING: Tertiary referral center.

PATIENTS: The effect of TMS of the contralateral auditory cortex in 114 patients with unilateral tinnitus is investigated as one of the selection criteria used for surgical implantation of electrodes on the auditory cortex.

INTERVENTION: TMS is performed at 90% of motor threshold at 1, 3, 5, 10, and 20 Hz, with each stimulation session consisting of 200 pulses. Results were classified as no effect (0-19% improvement), partial effect (20-79% improvement), and good effect (80-100 suppression).

MAIN OUTCOME MEASURES: TMS had a good effect in 25% of the patients studied, partial effect in 28% patients, and no effect in 47%.

RESULTS: TMS at 200 pulses is capable of tinnitus suppression for seconds only. The results were influenced by tinnitus duration: the longer the tinnitus exists, the lower the stimulation frequency that yields maximal tinnitus suppression (p < 0.001). The maximal amount of tinnitus suppression decreases in time (p < 0.01), resulting in a 2% decrease of potential tinnitus suppression per year.

CONCLUSION: TMS of the auditory cortex is capable of modifying tinnitus perception for a very short time. The maximal amount of suppression and best stimulation frequency depends on the tinnitus duration.

Clin Otolaryngol Allied Sci. 1993 Aug;18(4):278-81.

Electromagnetic stimulation as a treatment of tinnitus: a pilot study.

Roland NJ, Hughes JB, Daley MB, Cook JA, Jones AS, McCormick MS.

Department of Otolaryngology, Royal Liverpool University Hospital, UK.

This paper reports the results of a study to determine whether pulsed electromagnetic stimulation, applied over the mastoid bone, caused an improvement in the level of tinnitus in long-standing tinnitus sufferers. Fifty-eight patients from the Liverpool Tinnitus Association volunteered to take part in a double-blind placebo controlled trial. Active and placebo devices were randomly allocated to these patients on their first visit. At the end of one week of treatment, each patient noted whether their tinnitus had completely disappeared, was improved, unchanged or made worse by the treatment Forty-five per cent of the patients who completed the trial were improved by the active device, but only 9% by placebo (P = 0.0013, Mann-Whitney test). We suggest that electromagnetic stimulation may be an effective treatment in some tinnitus sufferers.

Thyroid

Vopr Kurortol Fizioter Lech Fiz Kult. 1993 Jul-Aug;(4):15-8.

The effect of the siting of exposure to decimeter-range electromagnetic waves on the function of the hypophyseal-thyroid and adrenal systems in viral hepatitis.

[Article in Russian]

Mavrodi? VM.

Abstract

The author studied time course of changes in the thyroid and adrenal systems as shown by the levels of T3, T4, T3/T4, TTH, hydrocortisone, ACTH in response to exposure to decimetric microwaves (460 MHz, 30 mW/cm2). The microwaves were directed to the area of hepatic, thyroid, adrenal projections and combinations thereof. An optimal effect was achieved at the course exposure of the adrenal projection.

Tendinopathy – Tendonitis

Eur J Med Res. 2014; 19(1): 37. Published online 2014 Jul 5. doi:  10.1186/2047-783X-19-37 PMCID: PMC4096547

Low-frequency pulsed electromagnetic fields significantly improve time of closure and proliferation of human tendon fibroblasts

Claudine Seeliger,1 Karsten Falldorf,2 Jens Sachtleben,2 and Martijn van Griensven

corresponding author

11Department of Trauma Surgery, Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, D-81675 Munich, Germany 2Sachtleben GmbH, Falkenried 88, 20251 Hamburg, Germany

corresponding author

Corresponding author. Claudine Seeliger: ed.mut.em.rihcu@regilees; Karsten Falldorf: ed.hcraesertic@frodllaf; Jens Sachtleben: ed.hcraesertic@nebelthcas; Martijn van Griensven: ed.mut.em.rihcu@nevsneirGnav Author information ? Article notes ? Copyright and License information ? Received 2013 Aug 1; Accepted 2014 Jun 19. Copyright © 2014 Seeliger et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This article has been cited by other articles in PMC.

Abstract

Background

The promotion of the healing process following musculoskeletal injuries comprises growth factor signalling, migration, proliferation and apoptosis of cells. If these processes could be modulated, the healing of tendon tissue may be markedly enhanced. Here, we report the use of the Somagen™ device, which is certified for medical use according to European laws. It generates low-frequency pulsed electromagnetic fields that trigger effects of a nature that are yet to be determined.

Methods

A 1.5-cm wide, linear scrape was introduced into patellar tendon fibroblast cultures (N?=?5 donors). Treatment was carried out every second day. The regimen was applied three times in total with 30 minutes comprising pulsed electromagnetic field packages with two fundamental frequencies (10 minutes of 33 Hz, 20 minutes of 7.8 Hz). Control cells remained untreated. All samples were analyzed for gap closure time, proliferation and apoptosis one week after induction of the scrape wound.

Results

The mean time for bridging the gap in the nontreated cells was 5.05?±?0.33 days, and in treated cells, it took 3.35?±?0.38 days (P <0.001). For cell cultures with scrape wounds, a mean value for BrdU incorporation of OD?=?0.70?±?0.16 was found. Whereas low-frequency pulsed electromagnetic fields treated samples showed OD?=?1.58?±?0.24 (P <0.001). However, the percentage of apoptotic cells did not differ between the two groups.

Conclusions

Our data demonstrate that low-frequency pulsed electromagnetic fields emitted by the Somagen™ device influences the in vitro wound healing of patellar tendon fibroblasts and, therefore, possibly increases wound healing potential.Keywords: wound healing, proliferation, apoptosis, low-frequency pulsed electromagnetic fields

Background

One of the most important advances in promotion of the healing process following musculoskeletal injuries has evolved from the insight that treatment of these injuries with prolonged immobilization may delay recovery and adversely affect normal tissues. Conversely, controlled early resumption of activity can promote restoration of function. Experimental studies in the several past decades confirm and help explain the deleterious effects of prolonged immobilization and the beneficial effects of activity on the musculoskeletal tissues [1,2]. At the beginning of the healing process, controlled motion and loading of tendon and ligament repair tissue help align the regeneration of cells and collagen fibers, stimulate collagen synthesis and increase strength [36]. Early or excessive strain, however, can increase the inflammatory reaction and may damage repair tissue, leading to failure of the healing process [7].

However, not only mechanical loading or growth factor signalling is important for healing processes. DNA activity concerning transcription and translation, as well as cell cycle mechanisms, plays a pivotal role. Those activities comprise proliferation, migration and apoptosis of cells. If these processes could be modulated, the healing of tendon tissue may be enhanced markedly. This modulation could prevent the occurrence of excessive strain by accelerating tendon healing.

In order to study such processes in vitro, wound-healing assays have been carried out in tissue cultures for many years. These assays monitored cell behavior, including appraising the migration and proliferative capacities of different cells under various culture conditions. They generally involve growing cells to a confluent monolayer as a first step. The layer is ‘wounded’ by a scraping device (razor-blade, pipette tip, needle or cell-scraper). This penning in the cell layer gets repopulated because the cells on the wound edge are no longer contact-inhibited. At the cellular level, healing involves the cells’ detachment from and attachment to the matrix adjacent to the wound area, migration, and proliferation. This repopulation is microscopically observed over a time course to assess the gap closure time, the occupied area over time, or the rate of migration [810]. Moreover, proliferation and apoptosis are investigated regularly. Depending on the cell type, the growth factors present, and the extent of the wounded region, wound repair ranges from several hours to days.

Until the 1980s it was believed that biological information within cell systems was being transferred not only chemically but also physically via electromagnetic waves. Information of this nature activates or inhibits biochemical processes [11,12].

Led by these findings in the early 1990s, Sachtleben GmbH, Hamburg, Germany developed the Somagen™ device, which supposedly stimulates the communication mechanisms of cells (Figure 1). The low-frequency pulsed electromagnetic fields (PEMF) electromagnetic signals have been described as affecting enzymes, cells, tissues and whole organisms. Even though the effects exerted by PEMF could be measured, the reasons for the reactions of the biological systems remain unidentified. However, several theories exist to explain these effects, for example the Larmor precession [13,14], the hypothesis of Gartzke and Lange [15] or radical pair mechanism [1618] (for review see [19]). The application of the PEMF induces changes in cellular processes, among others, differentiation [20], apoptosis [21], DNA synthesis [22], protein expression [23], protein phosphorylation [24], anti-inflammatory effects [25] and hormone production [26].

Figure 1

Figure 1The low-frequency pulsed electromagnetic fields (PEMF) emitting Somagen™ device. In this work, a specific ‘wound healing’ program lasting 30 minutes was used. The applied program consisted of two PEMF signal packages of

PEMF instruments like the Somagen™ device generate low-frequency electromagnetic signals in order to accelerate, among others, wound healing response. This enhances the regeneration potential of the destroyed tissue, especially the stimulation of new formation of connective tissue, something for which the vasodilatation and increased cell division are likely responsible [27]. Furthermore, growth factor signalling, which is important for healing processes, can be influenced by low-frequency electromagnetic signals. Zhao et al. could demonstrate a stimulation of the VEGF receptor signaling pathway by applying an electric field on vascular endothelial cells [28]. Another study demonstrated an increased type I collagen expression in fibroblasts after exposure to pulsing electric fields [29]. Zhao et al. summarized that electric fields polarize the activation of multiple signalling pathways, including the PI3 kinases/Pten, membrane growth factor receptors and integrins, both key players in the wound healing processes [30].

However, the effect of low-frequency PEMF emitted by the Somagen™ device on fibroblasts as key players in wound healing remains to be investigated. Therefore, this study focuses on the effects of PEMF on the healing process of tendon fibroblasts in an in vitro wound healing model. Our findings may be helpful in the field of ligament tissue engineering and may support the development of new strategies for ligament repair.

Methods

Cell culture

Fibroblasts were isolated from five patients undergoing surgical treatment of the knee joint. The study protocol is in accordance with the standards of the Declaration of Helsinki. Following approval by the ethical committee of Hannover Medical School, written informed consent was obtained from the patients. The specimens of approximately 4?×?2 mm were aseptically collected from the patellar tendon. The obtained patellar tendon specimen was divided into 0.5 mm2 pieces and transferred into petri dishes with a roughened bottom. Dulbecco’s Modified Eagle’s Medium (DMEM) was used as culture medium containing 10% fetal calf serum, 1% gentamicin and 1% amphotericin B (Biochrom, Berlin, Germany). Tissue specimens were cultured in a humidified environment with 5% CO2 at 37°C. Medium was replenished every second day. After six to eight days, fibroblasts started to grow out of the patellar tendon specimens. After another three to four weeks, the cells reached 80 to 90% confluence. The cells were trypsinized and subcultured in 75 cm2 flasks (13?×?103 cells/cm2). Concomitantly, they were counted and an overall viability of more than 90% was observed using the trypan blue exclusion test. This procedure was repeated once. Cells in the second passage were harvested and 1.5?×?105 fibroblasts were transferred into six-well tissue culture plates (Corning, Vienna, Austria).

Induction of the scrape wound

Scrape wounds were performed in confluent monolayer cultures of the patellar tendon fibroblasts. A 1.5 cm wide, linear scrape was introduced with a cell scraper over the entire diameter of the well. The wound area was marked with three black ink dots on each side of the wound for reference. Cultures were rinsed with culture medium to remove floating cellular debris, and fresh culture medium was added.

Low-frequency pulsed electromagnetic fields treatment protocol

Cell cultures were treated every second day, three times in total, with a registered and certified Somagen™ device, according to company’s protocol (Sachtleben GmbH, Hamburg) In this work, a specific “wound healing” program was used. The applied program consisted of two PEMF signal packages of 10 minutes at a fundamental frequency of 33 Hz and 20 minutes at 7.8 Hz. This ‘wound healing’ program was developed by Sachtleben GmbH in cooperation with different dermatology clinics and has been successfully used before in a clinical setting [31]. The signals have the shape of spike pulses with varying send/pause intervals. Thereby, a magnetic flux density of 0.25 ?T up to 3.16 ?T emerged. At a 5-mm distance from the applicator, electric field strength up to 6.3 mV/cm was measurable (Additional file 1). Applicators attached to the Somagen™ device were placed in the incubator. The six-well tissue culture dishes were put directly on top of the applicators, thereby having a distance to the fibroblast monolayer of approximately 1 to 2 mm. Control cells were also put on the applicator without starting the program and were cultivated in a separate incubator to avoid interactions between the stimulated and nonstimulated cells.

In order to measure any deviation between the treated versus the control cell cultures, time to closure of the gap, proliferation and apoptosis were determined.

Time to closure

The wound was microscopically examined daily for repopulation of the wound area (Figure 2A). The end point of observation was the complete bridging of the scrape wound. Therefore, before the scratch was initiated, a photograph as control with a 20× magnification was captured with the microscope (Zeiss). Afterwards, a photograph with the same magnification was made every day. For quantification, the free area was highlighted, calculated and compared to the control with the software ImageJ 1.42q (National Institute of Health, Maryland, USA). Three independent calculations of each donor were made.

Figure 2

Figure 2The use of low-frequency pulsed electromagnetic fields (PEMF) lead to a significantly lower time to closure. Scrape wound of patellar tendon fibroblasts caused by a cell scraper (A), magnification 60×. For the analysis of the time to closure,

Proliferation

The analysis of cell proliferation was performed one week after induction of the scrape wound using a standard BrdU kit for spectrophotometry (Roche, Mannheim, Germany). BrdU is a thymidine analog that is incorporated into the DNA during the synthesis phase (S1) of the cell cycle. At 0, 6 and 12 hours after application of BrdU, the amount of inserted BrdU was analyzed according to a modified protocol for the larger dishes. To remove non-incorporated BrdU, cells were washed twice with DMEM. Washed cells were fixed with 70% ethanol in 0.5 M HCl at -20°C for 30 min and washed three more times with DMEM. Nucleases were added to the cells at 37°C for 30 min to increase the accessibility of the incorporated BrdU for detection by anti-BrdU Fab-fragment. This incubation was performed in a buffer containing 66 mM Tris, 0.66 mM MgCl2, and 1 mM 2-mercaptoethanol to permeate the cells and disintegrate disulphide bonds. After washing the cells three times with DMEM, a mouse monoclonal Fab-fragment against BrdU conjugated with horse-radish peroxidase was added to the cells together with 10 mg/ml BSA in phosphate-buffered saline. The cells were incubated at 37°C for 30 min and subsequently washed three times with DMEM. The bound conjugate was visualized using 1 mg/ml of the soluble chromogenic substrate 2,2′-Acinobis [3-ethylbenzthiazoline-sulfonic acid] (ABTS). The signal was increased by adding 1 mg/ml of ABTS-substrate enhancer. The optical density of each sample was measured at 405 nm and 490 nm.

Apoptosis rate

Analysis of apoptosis was performed one week after induction of the scrape wound according to the protocol provided by the manufacturer (Bender Med systems, Vienna, Austria). Briefly, adherent cells were detached from the cell culture dishes by carefully scratching with a cell scraper. The cells were centrifuged at 1500?×?g and 4°C; afterwards, the pellet was carefully resuspended in 100 ?l binding buffer (10 mM HEPES, pH 7.4; 140 mM NaCl; 5 mM CaCl2) and stained with 6 ?l recombinant human annexin-V-FITC and 6 ?l of propidium iodide for discrimination of living, apoptotic and necrotic cells (Bender Med Systems, Vienna, Austria). After incubation for 20 min at 4°C in darkness, the cells were centrifuged and resuspended in 100 ?l binding buffer. Flow cytometry was carried out on a FACS-calibur (Becton-Dickinson, Heidelberg, Germany). The software Cellquest-pro V1.1 from Becton-Dickinson was used for data analysis.

Statistical analysis

All experiments were performed in duplicates for each of the five patients. Furthermore, cells of each donor were divided into two groups: treated and nontreated. Data are presented as mean?±?standard deviation. Differences between the treated and nontreated patellar tendon fibroblasts were analyzed using Student’s t-test. A P value of less than 0.05 was considered statistically significant.

Results

Characterization of the patellar tendon fibroblasts

Patellar tendon fibroblasts were used for cell culture. Characterization of the cells was carried out as described before [32].

Time to closure

A uniform 1.5-cm-wide scrape wound was observed in every well of the six-well tissue culture plates. The edges of the wounds were sharply delineated. Damaged cells were observed in the edges that still adhered to the bottom of the well. On the consecutive days, the wound area was occupied by fibroblasts. The mean time for bridging the gap in the nontreated cells was 5.05?±?0.33 days (Figure 2B). Treatment with the specific ‘wound healing’ program emitted by Somagen™ device significantly accelerated the bridging time to 3.35?±?0.38 days (P <0.001).

Apoptosis rate

The percentage of Annexin-V positive cells did not differ between the two groups (nontreated 38.5?±?6.5% versus Somagen™ device-treated 38.7?±?7.7%) as depicted in Figure 3A.

Figure 3

Figure 3The low-frequency pulsed electromagnetic fields (PEMF) did not affect the apoptotic rate but significantly increased the proliferation. Apoptosis level in patellar tendon fibroblasts in the scrape wound after 1 week (B). Apoptosis was measured

Proliferation

Proliferation was determined by BrdU incorporation. The obtained values are optical density values corrected for unspecific backgrounds (Figure 3B). Untreated cell cultures with scrape wounds showed a mean value of 0.70?±?0.16. A significant increase was observed after application of the specific ‘wound healing’ program emitted by Somagen™ device (1.58?±?0.24, P <0.001).

Discussion

We investigated that certain low-frequency PEMF sequences influence in vitro wound healing of patellar tendon fibroblasts possibly via increasing the proliferation rate. In a similar model of scrape wounding of human foreskin fibroblasts, the 0.8-mm-wide gap was closed within 36 hours due to a preassembled matrix-containing fibrinogen. Moreover, this accelerated closure of the gap was associated with an 8-fold increase in 3H-thymidine incorporation, indicating a high proliferation rate [10]. Rodemann et al., who treated skin fibroblasts with electromagnetic fields, could detect a significant increase of the collagen synthesis and the protein content [33]. The proliferation capacity of the cells probably plays a role in the secondary wound healing phase. As noted in similar models using intestinal epithelial cells or endothelial cells, the rate of cell proliferation, determined by BrdU incorporation, did not differ between migrating and stationary cells over the initial 24-h period [3436]. This indicates that early epithelial and endothelial restitution is independent of proliferation. After the migration phase that allows cells to go beyond the wound edges, cells have to proliferate in order to repopulate the wound area.

These processes are modulated by signal transduction pathways. The second messenger Ca2+ seems to be involved, as brief treatment with increased extracellular Ca2+ during scrape wounding accelerated wound area closure rates by 50% [37,38]. In our study, the tendon fibroblasts display 30% better wound area closure rates by low-frequency PEMF treatment. The differences may be due to the different cell origin, namely skin fibroblasts in the literature and tendon fibroblasts in our study. Furthermore, the multi-functional signal transducer NF-?B was activated as soon as 30 minutes after scrape wounding [35]. Especially at the wound edges, the subunit p65 was found. Within 5 minutes after wounding, ERK activation was evident. Again, this activation was particularly prominent in cells residing at the scrape edge [9]. These signal transduction molecules are important during adaptation and healing processes of tendon fibroblasts. This has been observed using cyclic, longitudinal strain in patellar tendon fibroblasts. Fifteen minutes of strain elicit NF-?B binding to DNA and is associated with increased proliferation [39,40]. c-fos and JNK are also activated [41]. Therefore, low-frequency PEMF may activate these signal transduction pathways.

These signal transduction pathways are not only involved in proliferation but also in apoptosis. In our model, 30 to 40% apoptosis of patellar tendon fibroblasts was observed. This is in concert with earlier observations using the same type of cells [41]. Treatment with the specific ‘wound healing’ low-frequency PEMF program did not result in any changes in apoptosis rates. Epithelial cells showed induction of apoptosis originating at the wound edges, but this apoptotic effect subsequently spread over a 24-hour period to encompass areas not originally damaged [42].

Our study included only five replicates; therefore, more studies are necessary to further investigate the positive effect of low-frequency PEMF in a larger cohort of samples. Additionally, in vivo studies should confirm these results in a whole organism with tendon pathology.

Nevertheless, the treatment with low-frequency PEMF enhances the wound healing potential of patellar tendon fibroblasts in vitro. The incidence of tendon and ligament injuries grows due to the increasingly sports-oriented society. Treatment of such injuries is still a challenge to orthopedic trauma surgeons as a restitutio ad integrim can hardly be achieved. Therefore, new modes of treatment are investigated to improve the outcome of such pathologies. Low-frequency PEMF seems to have no adverse effects when applied in the human situation [31]. Furthermore, it is non-invasive, easy to handle, and has a short application time.

Conclusions

These results may be extrapolated to wound-healing phenomena in other soft tissues, for example skin and muscle. Wound healing is a complex process involving many different cell types and coordinated signalling responses, but fibroblasts, as a part of this complexity, support the healing process and in our study show an improved wound area closure rate under the influence of low-frequency PEMF. Thus, low-frequency electromagnetic signals could be an interesting new treatment option for wound-healing processes in vivo by accelerating closure of the wounds. Based on the positive results, further in vivo studies using low-frequency PEMF generated by the Somagen™ device for modulating wound healing

Abbreviations

ABTS 2: 2′-Acinobis [3-ethylbenzthiazoline-sulfonic acid]; BrdU: Bromodesoxyuridin; DMEM: Dulbecco’s Modified Eagle’s Medium; FITC: fluorescein isothiocyanate; OD: optical density; PEMF: pulsed electromagnetic fields.

Competing interests

The authors declare that they have no competing interests. Sachtleben GmbH provided the Somagen™ device for this project free of charge. Jens Sachtleben and Karsten Falldorf are both managing directors of Sachtleben GmbH.

Authors’ contributions

CS and MvG conceived and designed the study. CS and MvG performed the experiments and analyzed the data. KF and JS provided data on the device and reviewed the manuscript. All authors read and approved the final manuscript.

Supplementary Material

Additional file 1:

Somagen™ measured field data.Click here for file(644K, pdf)

Acknowledgements

The authors would sincerely like to thank Sachtleben GmbH for providing the Somagen™ device for this project. We would also like to thank Fritz Seidl, M.A. Interpreting and Translating, for proofreading this paper.

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Low frequency pulsed electromagnetic field affects proliferation, tissue-specific gene expression, and cytokines release of human tendon cells.

de Girolamo L1, Stanco D, Galliera E, Viganò M, Colombini A, Setti S, Vianello E, Corsi Romanelli MM, Sansone V.

Author information

  • 1Orthopaedic Biotechnologies Laboratory, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy. laura.degirolamo@grupposandonato.it

Abstract

Low frequency pulsed electromagnetic field (PEMF) has proven to be effective in the modulation of bone and cartilage tissue functional responsiveness, but its effect on tendon tissue and tendon cells (TCs) is still underinvestigated. PEMF treatment (1.5 mT, 75 Hz) was assessed on primary TCs, harvested from semitendinosus and gracilis tendons of eight patients, under different experimental conditions (4, 8, 12 h). Quantitative PCR analyses were conducted to identify the possible effect of PEMF on tendon-specific gene transcription (scleraxis, SCX and type I collagen, COL1A1); the release of pro- and anti-inflammatory cytokines and of vascular endothelial growth factor (VEGF) was also assessed. Our findings show that PEMF exposure is not cytotoxic and is able to stimulate TCs’ proliferation. The increase of SCX and COL1A1 in PEMF-treated cells was positively correlated to the treatment length. The release of anti-inflammatory cytokines in TCs treated with PEMF for 8 and 12 h was significantly higher in comparison with untreated cells, while the production of pro-inflammatory cytokines was not affected. A dramatically higher increase of VEGF-A mRNA transcription and of its related protein was observed after PEMF exposure. Our data demonstrated that PEMF positively influence, in a dose-dependent manner, the proliferation, tendon-specific marker expression, and release of anti-inflammatory cytokines and angiogenic factor in a healthy human TCs culture model. Knee Surg Sports Traumatol Arthrosc. 2008 Jun; 16(6): 595–601. Published online 2008 Apr 2. doi:  10.1007/s00167-008-0519-9 PMCID: PMC2413121

Effects of biophysical stimulation in patients undergoing arthroscopic reconstruction of anterior cruciate ligament: prospective, randomized and double blind study

Francesco Benazzo,1 Giacomo Zanon,1 Luigi Pederzini,2 Fulvio Modonesi,2 Carlo Cardile,3 Francesco Falez,4 Luigi Ciolli,4 Filippo La Cava,4 Sandro Giannini,5 Roberto Buda,5 Stefania Setti,

corresponding author

6 Gaetano Caruso,7 and Leo Massari71IRCCS Foundation, Orthopaedic and Traumatology Department, S. Matteo Hospital Institute, University of Pavia, Pavia, Italy 2Orthopaedic Department of Nuovo Ospedale di Sassuolo, Modena, Italy 3Orthopaedic Department of University of Milano – Bicocca, San Gerardo Hospital, Monza, Italy 4Orthopaedic Department of S. Spirito Hospital Institute, Roma, Italy 5Orthopaedic Department of Rizzoli Orthopaedic Institute, Bologna, Italy 6IGEA, Clinical Biophysics, Via Parmenide 10/A, 41012 Carpi (Mo), Italy 7Department of Biomedical Science and Advanced Therapy, University of Ferrara, Ferrara, Italy Stefania Setti, Phone: +39-059699600, Fax: +39-059695778, Email: moc.lacidemaegi@ittes.s.

corresponding author

Corresponding author. Author information ? Article notes ? Copyright and License information ? Received 2007 Nov 28; Accepted 2008 Feb 28. Copyright © The Author(s) 2008 This article has been cited by other articles in PMC.

Abstract

Pre-clinical studies have shown that treatment by pulsed electromagnetic fields (PEMFs) can limit the catabolic effects of pro-inflammatory cytokines on articular cartilage and favour the anabolic activity of the chondrocytes. Anterior cruciate ligament (ACL) reconstruction is usually performed by arthroscopic procedure that, even if minimally invasive, may elicit an inflammatory joint reaction detrimental to articular cartilage. In this study the effect of I-ONE PEMFs treatment in patients undergoing ACL reconstruction was investigated. The study end-points were (1) evaluation of patients’ functional recovery by International Knee Documentation Committee (IKDC) Form; (2) use of non-steroidal anti-inflammatory drugs (NSAIDs), necessary to control joint pain and inflammation. The study design was prospective, randomized and double blind. Sixty-nine patients were included in the study at baseline. Follow-up visits were scheduled at 30, 60 and 180 days, followed by 2-year follow-up interview. Patients were evaluated by IKDC Form and were asked to report on the use of NSAIDs. Patients were randomized to active or placebo treatments; active device generated a magnetic field of 1.5 mT at 75 Hz. Patients were instructed to use the stimulator (I-ONE) for 4 h per day for 60 days. All patients underwent ACL reconstruction with use of quadruple hamstrings semitendinosus and gracilis technique. At baseline there were no differences in the IKDC scores between the two groups. At follow-up visits the SF-36 Health Survey score showed a statistically significant faster recovery in the group of patients treated with I-ONE stimulator (P < 0.05). NSAIDs use was less frequent among active patients than controls (P < 0.05). Joint swelling resolution and return to normal range of motion occurred faster in the active treated group (P < 0.05) too. The 2-year follow-up did not shown statistically significant difference between the two groups. Furthermore for longitudinal analysis the generalized linear mixed effects model was applied to calculate the group × time interaction coefficient; this interaction showed a significant difference (P < 0.0001) between the active and placebo groups for all investigated variables: SF-36 Health Survey, IKDC Subjective Knee Evaluation and VAS. Twenty-nine patients (15 in the active group; 14 in the placebo group) underwent both ACL reconstruction and meniscectomy; when they were analysed separately the differences in SF-36 Health Survey scores between the two groups were larger then what observed in the whole study group (P < 0.05). The results of this study show that patient’s functional recovery occurs earlier in the active group. No side effects were observed and the treatment was well tolerated. The use of I-ONE should always be considered after ACL reconstruction, particularly in professional athletes, to shorten the recovery time, to limit joint inflammatory reaction and its catabolic effects on articular cartilage and ultimately for joint preservation.Keywords: Anterior cruciate ligament, Chondroprotection, Biophysical stimuli, Pulsed electromagnetic fields, Joint preservation

Introduction

Articular cartilage performs mechanical functions absorbing the different loads applied to a joint in the course of daily activity [19]. Homeostasis and mechanical competence of cartilage are regulated by the activity of the chondrocytes that maintain the function and the integrity of the extracellular matrix, proteoglycans and collagen.

In consideration of the scant repairability of the cartilage, even modest damages resulting from trauma or inflammation may be the starting point for cartilage degeneration leading over time to extensive lesions that deepen into the thickness of the cartilage itself, ultimately exposing the subchondral bone tissue [3, 17].

Joint injury may involve synovial tissue, cartilage and subchondral bone leading to joint inflammation, swelling and pain. Surgical interventions must certainly be included among the triggers of inflammatory reaction in a joint [12]. The development of arthroscopic procedures has undoubtedly limited joint damage associated to surgery for reconstruction of ligaments; nevertheless, it does not avoid the inflammatory response. Thus, while arthroscopic procedures make surgery less invasive, the inflammatory response at the joint remains and the release of pro-inflammatory cytokines in the synovial fluid is associated with an increase in the aggrecanase activities that lead to a degradation of the cartilage matrix, and also inhibit proteoglycan synthesis [11, 15, 18]. To prevent cartilage damage, current pharmacological therapies aim to control the catabolic effects of the pro-inflammatory cytokines and enhance anabolic activity, proteoglycan synthesis and proliferation of chondrocytes. Drugs that combine the above effects are called chondroprotectors; in this category should be included drugs with A2A adenosine receptor agonist activity, able to stimulate the physiological pathways that control inflammation and promote chondrocyte anabolic activities. Nevertheless, these drugs are in early stages of clinical testing [5].

Pre-clinical studies have shown that pulsed electromagnetic fields (PEMFs) in vitro favour the proliferation of chondrocytes [6, 16], stimulate proteoglycan synthesis [7] and demonstrate an A2A adenosine receptor agonist activity [20, 21]. Electromagnetic fields in vivo prevent degeneration of articular cartilage and down-regulate the synthesis and release of pro-inflammatory cytokines in the synovial fluid [2, 4, 8, 9]. These findings suggest that electromagnetic fields may be used to control joint inflammation and to stimulate cartilage anabolic activities, finally resulting in chondroprotection.

A clinical study performed in patients undergoing arthroscopic treatment for cartilage lesions showed that biophysical treatment with PEMFs was well tolerated by the patients and led to a decrease in the use of non-steroidal anti-inflammatory drugs (NSAIDs) and to an early functional recovery; the positive effect of the treatment was maintained at a 3-year follow-up [22].

Arthroscopic reconstruction is the treatment of choice following anterior cruciate ligament (ACL) rupture; although minimally invasive, the procedure is associated with joint reaction involving the synovia and it is expected to lead to an increase of pro-inflammatory cytokines in the synovial fluid with catabolic effect on articular cartilage. In this study, we evaluated whether the treatment with PEMFs could be used to control joint inflammatory response in patients undergoing ACL reconstruction. The end points of the study were: (1) patients’ functional recovery evaluated by International Knee Documentation Committee (IKDC) form; (2) use of NSAIDs, necessary to control joint pain and inflammation.

Materials and methods

Patients and study design

In 2004–2005, 84 patients undergoing ACL reconstruction were evaluated for inclusion in the study at five clinical centres. Of these, 69 gave their informed consent to participate in the study. The prospective randomized and double-blind study was approved by the local ethical committees. Inclusion criteria were the following: age between 18 and 45 years, ACL complete lesion following acute trauma or consequence of ligament chronic degeneration. All lesions were documented by MRI and confirmed during the intervention. The following were the exclusion criteria: osteonecrosis of the femoral condyle, rheumatoid arthritis, autoimmune disease, systemic disease and patients requiring meniscus repair.

The patients were assigned to the active or placebo group according to the following randomization criteria: age (18–30 or 31–45), sex, smoking status, origin of ACL rupture (traumatic or degenerative). For randomization of patients, a computer-generated schedule was prepared by a biostatistician. In this process, a random number seed was entered into the computer to generate a list that assigned equal numbers of active and placebo stimulators. The minimum number of patients per group required was calculated by power analysis taking into account the results of a previous study [22].

Of the 69 patients included, two never started the therapy, two dropped out within 2 weeks of therapy, and five did not return at follow-up visits; a total of 60 patients were therefore available for subsequent analysis. The ACL rupture occurred during sports activity in 49 patients (24 active and 25 placebo), daily activity in eight patients (four active and four placebo) and traffic accident in three patients (three active). At the time of ACL reconstruction 29 patients underwent also meniscectomy: 15 in the active group and 14 in the placebo.

Clinical evaluation

The patients were evaluated by IKDC Form before the intervention and at 30, 60 and 180 days afterwards. The different parts of the questionnaire, IKDC Current Health Assessment Form (SF-36 Health Survey), IKDC Subjective Knee Evaluation Form and IKDC Knee Examination Form were analysed separately. As regards the scores of the questionnaires, for each subject we considered the changes at follow-up visits with respect to the values recorded at baseline, before surgery.

Pain intensity was evaluated by visual analogue scale (VAS) of 10-cm length: 0 cm no pain, 10 cm maximum pain. The patients were allowed to use NSAIDs to control knee pain when present and had to report doing so.

A 2-year follow-up telephone interview was conducted and the patients were asked: (a) if they had undergone further surgery at the knee, (b) if they had pain at the knee, (c) if they had functional limitation in daily activity, (d) if they returned to previous sport activity level.

Surgical technique

ACL arthroscopic repair was performed by quadruple hamstrings semitendinosus and gracilis technique. Tendons were harvested with the tendons stripper through a 2–3 cm vertical incision on the antero-medial tibial area. Diameter of the quadruple hamstrings semitendinosus and gracilis tendons was measured, while the tibial tunnel and same size femoral tunnel (30 mm length) were prepared. The graft was pulled up through the tibial tunnel with the knee at 90° of flexion and suspended on the external femoral cortex (Endobutton, Smith and Nephew, London, UK). Distally, the graft was fixed with an interference absorbable screw at the tibia at 10° of flexion.

Rehabilitation

All the patients underwent standard rehabilitation using passive knee flexion daily. Exercises started within the third post-operative day with isometric quadriceps contractions and then progressed to active closed-chain exercises by 4–6 weeks postoperatively. During the first 20 days patients were instructed to use two crutches and then progressive weight bearing until the end of the second month.

Biophysical stimulation

The patients were treated with active or placebo devices. The active stimulators (I-ONE; IGEA, Carpi, Italy) generated a magnetic field of peak intensity of 1.5 mT at a frequency of 75 Hz; no heat or vibration was felt by the patient during treatment (Fig. 1).

Fig. 1

Fig. 1Left I-ONE PEMFs generator. Right wave form of magnetic field, 1.5 mT peak value (top); electric field induced in a standard coil probe made of 50 turns (0.5 cm ?) of copper wire (0.2 mm ?), peak value 3 mV/cm

The patients were instructed to use the stimulator for 4 h per day, not necessarily consecutively, for 60 days. Treatment started within 7 days from the surgery. Each device contained a clock to monitor the hours of use.

Statistical analysis

The results were analysed with SPSS 13.0 (Statistical Packages for Social Sciences Inc, Chicago, IL, USA). Comparison among the continuous variables in the two groups was performed with Student’s heteroschedastic t test; comparison of continuous variables within each group during follow-up was performed with Student’s paired t test.

Binomial and categorical variables were compared by contingency tables applying the chi-square test for 2 × 2 tables and the Cochran Mantel Haenszel test for larger size tables.

Generalized linear mixed effects model was applied to the SF-36 Health Survey, IKDC Subjective Knee Evaluation and VAS data to test if a different trend between the two groups was present during follow-up by correcting for the following covariates: sex, age, weight, height, hours of treatment, smoking status, use of NSAIDs. In this analysis, a mathematical model is built which takes into account the trend over time of individual patients belonging to each group (Group × Time interaction) and determines if a statistical difference exists between the groups during the follow-up [10].

The minimum significance level for all the statistical tests was set at P < 0.05.

Results

At baseline, the two groups of study were homogeneous for age, weight, height, VAS, SF-36 Health Survey and IKDC Subjective Knee Evaluation score (Table 1).

Table 1

Table 1 Characteristics of the groups at baseline

Average daily treatment was the same in both groups: 3.92 ± 0.5 h/die versus 3.13 ± 0.3 h/die in the I-ONE group and the placebo group, respectively (P = n.s.).

The average pain was modest and almost absent at 6 months’ follow-up: 0.7 ± 0.2 cm among placebo and 0.9 ± 0.2 cm among active. At 30 days, less patients in the active group used NSAIDs: 8% in the I-ONE group versus 27% in the placebo group (P < 0.05).

The SF-36 Health Survey score decreased significantly at 30 days, in both groups (P < 0.0005). At 60 days the mean SF-36 Health Survey score in the I-ONE patients already exceeded the initial value (by 3.2 points), whereas in the patients of the placebo group SF-36 Health Survey score was slightly below the initial mean value (by ?0.7 units). At 6 months a significant (P < 0.005) increase was observed for SF-36 Health Survey average values in both groups; the patients of the I-ONE group were above the initial values by 10.1 units, while the placebo group exceeds the baseline value by 7.2 units. The mean changes of SF-36 Health Survey score in the I-ONE group are systematically higher with respect to placebo during follow-up, P < 0.05 (Fig. 2).

Fig. 2

Fig. 2 Mean changes of SF-36 Health Survey (±SE) versus baseline in the two groups (P < 0.05)

The IKDC Subjective Knee Evaluation score increased over 6 months and did not show significant differences between the two groups at any follow-up visit.

The IKDC Knee Examination Form outlined both groups including subjects with joint swelling before surgery (one in placebo and two in I-ONE group, P = n.s.) and at 30 days’ follow-up (five in placebo and six in I-ONE group, P = n.s.). On day 60, joint swelling was observed in the placebo group (two patients) only. Joint swelling was not observed any more at 6 months’ follow-up. Limitation in the passive range of motion of the knee was more frequent in the placebo group than in the I-ONE group (P < 0.05) (Fig. 3).

Fig. 3

Fig. 3 Patients with limitation in passive range of motion in the two groups, P < 0.05

Finally, the generalized linear mixed effects analysis revealed a significantly different trend (group × time interaction, P < 0.0001) between the two groups for SF-36 Health Survey score, IKDC Subjective Knee Evaluation score and for VAS, showing a positive effect of I-ONE treatment. The estimate coefficients and significance of independent variables for three models are displayed in Table 2.

Table 2

Table 2 Generalized linear mixed effects models in which the dependent variables considered are: SF-36 Health Survey score, IKDC Subjective Knee Evaluation score and VAS, respectively

At the 2-year follow-up interview 86% of the patients in the I-ONE group and 75% in the placebo group reported complete functional recovery, no knee pain and return to sport activity.

ACL reconstruction and meniscectomy

When the cohort of patients, undergoing both ACL reconstruction and meniscectomy, was analysed separately, the SF-36 Health Survey score confirmed the faster recovery trend among I-ONE treated patients compared to placebo, P < 0.05 (Fig. 4). At 6 months, SF-36 Health Survey average score increase was 11.4 in the I-ONE group (P < 0.005 vs. baseline) and 7.1 in placebo group (P = ns vs. baseline). Further, the average values of SF-36 Health Survey were significantly higher in the I-ONE group compared to the placebo (45.2 ± 1.5 vs. 37 ± 2.7, P < 0.05).

Fig. 4

Fig. 4 Patients undergoing ACL and meniscectomy: mean changes of SF-36 Health Survey (±SE) versus baseline in the two groups (P < 0.05)

The percent of patients with limitation in the passive range of motion was lower in the I-ONE group compared to the placebo one (34% I-ONE vs. 50% placebo at day 30 and 4% I-ONE vs. 17% placebo at day 60, P < 0.05).

Discussion

Arthroscopic surgery has gained a large success and led to a significant increase in its use: about 650,000 procedures are performed in the USA each year [14]. However, the access into the joint space is always associated to an inflammatory reaction that may jeopardize the benefits expected from surgery. Joint inflammation has a catabolic effect on extracellular matrix and inhibits chondrocyte activity; thus, all means capable of locally controlling the inflammation should be adopted to prevent the onset and limit the progression of cartilage damage. Furthermore, unlike bone tissue after damage, the cartilage will not completely recover its competence: once lost, the articular cartilage does not reform [13].

Many efforts are made to develop strategies able to control joint inflammation and to favour the anabolic activities of chondrocytes; these are challenging objectives, and up to now the pharmacological approaches based on the use of drugs, whether by systemic or by local route, have not yet been able to demonstrate a genuine chondroprotective effect in humans [19].

Pre-clinical studies have shown PEMFs to have a chondroprotective effect, mediated by the control of inflammation and by the stimulation of chondrocyte activity; thus, we hypothesized that after arthroscopic surgery PEMFs treatment can be used for articular cartilage protection and ultimately joint preservation.

This prospective, randomized and double-blind study investigated whether and to what extent the employment of I-ONE, by controlling joint reaction to arthroscopy, could accelerate functional recovery in patients undergoing ACL reconstruction. The I-ONE treatment was well tolerated by the patients and no adverse side effects were observed. The results show that, at 30 days after surgery, in I-ONE group significantly fewer patients used NSAIDs to control pain, compared to patients in the placebo group; afterwards, the use of NSAIDs was not necessary in either group.

When IKDC Subjective Knee Evaluation average scores were analysed, we found no statistically significant difference between the I-ONE and placebo group; this is in agreement with the findings of other authors who reported that this parameter does not correlate with the other clinical information collected using the SF-36 Health Survey form [1]. However, when the results of the two groups were analysed by generalized linear mixed effects model, which takes into account the trend of each patient in both groups and the effect of confounding factors, we could evidence a positive significant effect of I-ONE treatment also in the Subjective Knee Evaluation (Table 2).

The SF-36 Health Survey average scores at baseline were the same in the I-ONE and placebo groups; however, the high standard deviation testify the large distribution of initial score values. To monitor patient’s recovery after ACL reconstruction, we considered the SF-36 Health Survey score changes with respect to baseline for each individual subject. At 2 and 6 months SF-36 Health Survey increase is undoubtedly higher in I-ONE group than in the placebo group. This result indicates a faster recovery in the treated patients. This positive effect of I-ONE treatment is confirmed by the generalized linear mixed effects analysis. Further, when the cohort of patients who underwent both ACL reconstruction and meniscectomy was analysed, we observed that the average increase of SF-36 Health Survey at 60 days in the I-ONE group was the same as that of placebo group at 6 months (6.0 vs. 7.1, P = n.s.).

The IKDC Knee Examination Form showed how in the placebo group the resolution of joint swelling and the recovery of complete range of motion occur later compared to the I-ONE group; no significant difference in scoring was observed among centres.

The study end-points were thus demonstrated: fewer patients in the I-ONE group required the use of NSAIDs and their functional recovery was faster.

At 2-year follow-up no statistically significant difference was observed between two groups, although the percent of patients with complete recovery was slightly higher in the I-ONE group.

In this study we applied a statistical analysis specifically developed for longitudinal studies that allows to calculate the group × time interaction. This test, that considers individual patient’s score at different time points and the possible influence of confounding factors, supports the positive effect of I-ONE treatment on the recovery of patients undergoing ACL reconstruction.

Our data confirm the results reported by Zorzi et al. [22] in a group of patients treated with I-ONE following an arthroscopic treatment for cartilage lesions. To the authors’ knowledge, there are no other reports of use of biophysical stimulation after surgical procedures of the knee.

Biophysical stimulation allows treating individual joints, permeating the whole cartilage surface and thickness, the synovia and the subchondral bone. The effectiveness of biophysical stimulation is not limited by considerations such as diffusion ability and concentration gradient, which are present and important in the dynamic of a pharmacological intervention; joint tissues are paramagnetic, they do not attenuate the biophysical signal and thus are all homogenously exposed to the treatment efficacy. Biophysical stimulation is an effective therapeutic intervention to control the detrimental consequences of the inflammation over articular cartilage in the absence of negative side effects.

I-ONE should always be considered after ACL reconstruction, particularly in professional athletes, to shorten the recovery time, to limit joint inflammatory reaction and ultimately for joint preservation.

Acknowledgments

Supported by Igea through a grant of Research funding of Regione Emilia Romagna. Setti is Igea employ; the other authors have no conflict of interest.

Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

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Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2008 Nov;22(11):1318-22.

Effects of decimeter wave and sodium hyaluronate product on postoperative adhesions in flexor tendon.

[Article in Chinese]

Tian D, Luo J, Zhang Q, Zhang Y, Liu K, Yu K, Han J, Han J.

Department of Hand Surgery, Third Hospital of Hebei Medical University, Shijiazhuang Hebei 050051, PR China.

Abstract

OBJECTIVE: To compare the effect of decimeter wave with sodium hyaluronate product (SHP) on preventing and treating peritendinous adhesion and promoting tendon healing.

METHODS: Totally 96 healthy male white 6-month-old Leghorn chickens weighing (2.24 +/- 0.07) kg were randomized into group A (decimeter wave therapy group, n = 32), in which decimeter wave therapy was applied 1 to 21 days after operation at a frequency of 915 MHz, a power of 8 W, radiation distance of 10 cm, for 10 minutes once per day; group B (SHP group, n = 32), in which 5 mL and 1.2% SHP was applied; and group C (control group, n = 32), in which injury received no treatment. The III and IV toes of left feet of all chickens were made into tendon injury model. The general condition of animal was observed after operation; gross and histological observations were made 7, 10, 14, 18, 21 and 28 days after operation, and the biomechanical analysis was done 14 and 28 days after operation.

RESULTS: Operative incision healed well, no infection and death occurred. Peritendinous adhesions in groups A, B were looser, and tendon healing was better than that of group C 14 and 28 days after operation. More fibroblasts with active metabolism and more collagen formation in groups A, B than that in group C. The Pmax of group A was better than that of group B 14 and 28 days after operation (P < 0.05); the delta max of group A was better than that of group B 18 and 21 days after operation (P < 0.05), and the W0 of group A was better than that of group B 18, 21 and 28 days after operation (P < 0.05). There was no significant difference between group A and group B at the other time points.

CONCLUSION: Topical decimeter wave therapy and application of SHP after flexor tendon repair can promote intrinsic healing, meanwhile they can prevent the adhesion of tendon and reduce extrinsic healing. Decimeter wave therapy can improve the qualities of tendon’s wound healing.

J Hand Surg Am. 2006 Sep;31(7):1131-5.

Pulsed magnetic field therapy increases tensile strength in a rat Achilles’ tendon repair model.

Strauch B, Patel MK, Rosen DJ, Mahadevia S, Brindzei N, Pilla AA.

Department of Plastic and Reconstructive Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10461, USA. bstrauch@montefiore.org

Abstract

PURPOSE: To examine the effect of pulsing electromagnetic fields on the biomechanic strength of rat Achilles’ tendons at 3 weeks after transection and repair.

METHODS: This noninvasive modality was tested in a prospective, randomized, double-blinded, placebo-controlled study to evaluate the effect of a specific noninvasive radiofrequency pulsed electromagnetic field signal on tendon tensile strength at 21 days post transection in a rat model.

RESULTS: In the animals receiving PMF exposure, an increase in tensile strength of up to 69% was noted at the repair site of the rat Achilles’ tendon at 3 weeks after transection and repair compared with nonstimulated control animals.

CONCLUSIONS: The application of electromagnetic fields, configured to enhance Ca(2+) binding in the growth factor cascades involved in tissue healing, achieved a marked increase of tensile strength at the repair site in this animal model. If similar effects occur in humans, rehabilitation could begin earlier and the risk of developing adhesions or rupturing the tendon in the early postoperative period could be reduced.

Radiologe. 2004 Jun;44(6):597-603.

Conservative treatment and rehabilitation of shoulder problems.

[Article in German]

Paternostro-Sluga T, Zöch C.

Klinik für Physikalische Medizin und Rehabilitation, Allgemeines Krankenhaus der Medizinischen Universität Wien. tatjana.paternostro-sluga@univie.ac.at

Abstract

The shoulder joint has an important influence on arm- and hand function. Therefore, activities of daily living, working and leisure time can be negatively influenced by diseases of the shoulder joint. Problems of the shoulder joint can be induced by muscular dysbalance and poor body posture. There is a strong relationship between shoulder function and body posture. Conservative treatment and rehabilitation of the shoulder joint aims at improving the local dysfunction of the shoulder joint as well as at improving function and social participation. Antiinflammatory and pain medication, exercise, occupational, electro-, ultrasound and shock wave therapy, massage, thermotherapy and pulsed electromagnetic fields are used as conservative treatments. Exercise therapy aims at improving muscular performance, joint mobility and body posture. Occupational therapy aims at improving functional movements for daily living and work. Electrotherapy is primarily used to relieve pain. Shock wave and ultrasound therapy proved to be an effective treatment for patients with calcific tendinitis. The subacromial impingement syndrome can be effectively treated by conservative therapy.

Biomed Sci Instrum. 2002;38:157-62.

Quantitative characterization of rat tendinitis to evaluate the efficacy of therapeutic interventions.

Wetzel BJ, Nindl G, Swez JA, Johnson MT.

Terre Haute Center for Medical Education, Indiana University School of Medicine, Indiana State University, Terre Haute, IN 47809, USA.

Abstract

Tendinitis is a painful soft tissue pathology that accounts for almost half of all occupational injuries in the United States. It is often caused by repeated movements and may result in loss of work and income. Current treatments for tendinitis are aimed at reducing inflammation, the major cause of the pain. Although anti-inflammatory drugs and various alternative therapies are capable of improving tendinitis, there are no quantitative scientific data available regarding their impact on inflammation. The objective of this study is to determine the time course for healing of rat tendinitis without intervention to be able to assess the efficacy of tendinitis treatments. We are interested in evaluating the therapeutic use of pulsed electromagnetic fields (PEMFs), a therapeutic modality that has been found to be beneficial for healing soft tissue injuries. Tendinitis was induced in Harlan Sprague Dawley rats by collagenase injections into the Achilles tendon, and tendons were collected for four weeks post-injury. To determine the amount of edema, we used caliper measurements of the rat ankles and quantified the tendon water content. To determine the extent of inflammation, we estimated the number of inflammatory cells on histological sections applying stereological methods. The data reveal that edema is maximal 24 hours after injury accompanied by a massive infiltration of inflammatory cells. Inflammatory cells are then gradually replaced by fibroblasts, which are responsible for correcting damage to the extracellular matrix. This natural time course of tendon healing will be used to evaluate the use of PEMFs as a possible therapeutic modality.

Arch Phys Med Rehabil. 1997 Apr;78(4):399-404.

Pulsed magnetic and electromagnetic fields in experimental achilles tendonitis in the rat: a prospective randomized study.

Lee EW, Maffulli N, Li CK, Chan KM.

Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.

OBJECTIVE: To investigate the effects of pulsed magnetic fields (PMF) and pulsed electromagnetic fields (PEMF) on healing in experimental Achilles tendon inflammation in the rat.

DESIGN: Prospective randomized trial.

SETTING: University medical school.

METHODS: Exposure of the Achilles tendon and injury by a weight of 98.24 g falling from a height of 35cm in 180 male Sprague-Dawley rats.

INTERVENTION: A daily 15-minute session with PMF of 17Hz or 50Hz, or PEMF of 15Hz or 46Hz, or a sham session.

OUTCOME MEASURES: Random sacrifice 2 hours after the operation, and at 1, 3, 7, 14, or 28 days. Assessment of water content, weight, and histological appearance of the tendons.

RESULTS: The time from injury and the various treatment modalities exerted a significant influence on the water content of the tendon after the injury (two-way ANOVA, p = .02). At day 3, the water content of the PEMF 46Hz group was significantly higher than in the other groups, decreasing sharply by day 7, and being similar to the other groups thereafter. By the end of the experiment, the PEMF 15Hz group was not significantly different from the control group. At day 7, the PMF 50Hz group showed significantly lower water content than the control group (p = .03), but at 14 days the PMF 50Hz group was not significantly different from the control group. PMF 50Hz suppressed the extravascular edema during early inflammation. PMF 17Hz showed a similar initial trend, producing a consistent lower water content throughout the experiment, reaching statistical significance by the end of treatment. By the end of the experiment, the collagen fibers had nearly regained their normal alignment in all groups, with a more physiological alignment seen in the PEMF 17Hz group.

CONCLUSIONS: The tendon returned to histological normality in all groups, but the PMF 17Hz group showed better collagen alignment by the end of the study. PMF 17Hz resulted in a greater reduction of inflammation, with a better return of the tendon to histological normality. Different PMF and PEMF could be applied according to when treatment is started after the injury. If there is no delay between injury and beginning of pulsed magnetic treatment, PMF 17 should be used.

Lancet. 1984 Mar 31;1(8379):695-8.

Pulsed electromagnetic field therapy of persistent rotator cuff tendinitis.  A double-blind controlled assessment.

Binder A, Parr G, Hazleman B, Fitton-Jackson S.

The value of pulsed electromagnetic fields (PEMF) for the treatment of persistent rotator cuff tendinitis was tested in a double-blind controlled study in 29 patients whose symptoms were refractory to steroid injection and other conventional conservative measures. The treated group (15 patients) had a significant benefit compared with the control group (14 patients) during the first 4 weeks of the study, when the control group received a placebo. In the second 4 weeks, when all patients were on active coils, no significant differences were noted between the groups. This lack of difference persisted over the third phase, when neither group received any treatment for 8 weeks. At the end of the study 19 (65%) of the 29 patients were symptomless and 5 others much improved. PEMF therapy may thus be useful in the treatment of severe and persistent rotator cuff and possibly other chronic tendon lesions.

Stroke

Logo of oximed

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,

corresponding author

 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

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

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

Table 1

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 2Ct, 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

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

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

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

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

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 [2122]. 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 [2527]. 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 [2829].

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 [3132]. 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 [4448]. 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 [4950]. 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 [4853]. 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.

Stress-related disorders

Health Qual Life Outcomes.  2011 Jul 19;9:54.

Stress-related psycho-physiological disorders: randomized single blind placebo controlled naturalistic study of psychometric evaluation using a radio electric asymmetric treatment.

Rinaldi S, Fontani V, Aravagli L, Mannu P, Castagna A, Margotti ML, Rosettani B.

Source

Department of Neuro-Psycho-Physio Pathology and Neuro Psycho Physical Optimization, Rinaldi Fontani Institute, Viale Belfiore 43, Florence 50144, Italy. srinaldi@irf.it

Abstract

BACKGROUND:

The aim of this study is to investigate the effects of a radio electric asymmetric treatment on psycho-physiological disorders (PPD). PPD are often stress related and are under the unconscious control of the patient and cannot be traced back to any serious physical disease. The brain stimulation treatment protocol used is called Neuro Psycho Physical Optimization (NPPO) with a Radio Electric Asymmetric Conveyer (REAC) device.

METHODS:

Psychological stress and PPD were measured for a group of 888 subjects using the Psychological Stress Measure (PSM) test, a self-administered questionnaire. Data were collected immediately before and after the 4-weeks of REAC treatment cycle.

RESULTS:

This study showed a significant reduction in scores measuring subjective perceptions of stress for subjects treated with a cycle of NPPO REAC treatment. At the end-point the number of subjects reporting symptoms of stress-related PPD on the PSM test was significantly reduced, whereas in the placebo group the difference was not significant.

CONCLUSION:

A cycle of NPPO treatment with REAC was shown to reduce subjective perceptions of stress measured by the PSM test and in particular on PPD.

TRIAL REGISTRATION:

This trial has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) with the number: ACTRN12607000463471.