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Pico-Tesla TMS Therapy on Multiple Sclerosis


1 Laboratory of Medical Physics, Department of Medicine, School of Health Sciences and Department of Electrical Engineering, Polytechnic School, Democritus University of Thrace Alexandroupoli 68100, Greece
*Corresponding author: Photios Anninos, Laboratory of Medical Physics, Dept of Medicine, School of Health Sciences, Democritus University of Thrace, University Campus, Alexandroupoli 68100, Greece. Tel/Fax: +30-2551030392, E-mail: pans.photios.anninos@gmail.com.
Avicenna Journal of Neuro Psych Physiology. In Press(In Press): e43249 , DOI: 10.5812/ajnpp.43249
Article Type: Research Article; Received: Jul 22, 2016; Accepted: Aug 21, 2016; epub: Aug 27, 2016;

Abstract


Background: Magnetoencephalography (MEG) is a well-established noninvasive method for investigating human brain activity.

Objectives: The present study aimed at identifying any change in the brain state after pico- Tesla Transcranial Magnetic Stimulation (pT-TMS) on patients with multiple sclerosis (MS).

Methods: A whole-head 122 - channel MEG system in a magnetically shielded room with low magnetic noise was used. The study population comprised of 2 male and 8 female volunteers with MS, with a mean age of 41.3 ± 9.5 years. External magnetic field of pT-TMS was applied on the above patients with proper field characteristics (magnetic field amplitude: 1 - 7.5 pT, frequency: the alpha rhythm of the patient 8 - 13 Hz), obtained prior to the application of pT-TMS.

Results: A significant effect was observed with an increase of frequencies in the range of 2 - 7 Hz among the participants. The results were statistically significant in 7 out of 10 patients (70%).

Conclusions: The pT-TMS has the prospective to be a significant noninvasive secure and effective means in managing MS symptoms.

Keywords: MEG; Multiple Slerosis; pT-TMS; Brain Frequencies

1. Background


We tried to manage the symptoms of MS patients applying pico-Tesla transcranial magnetic stimulation (pT-TMS). After pT-TMS, an increase in the frequencies of the participants’ brain activity in the range of 2 - 7 Hz was noted. Most of the MS patients reported a benefit from the pT-TMS treatment.


Transcranial magnetic stimulation (TMS) is a noninvasive and well-tolerated method without any direct contact with the underlying skin and has been used to investigate a variety of clinical conditions (1). TMS have been applied in the study of a variety of neurological diseases including MS (2). Magnetoencephalography (MEG) is a well-established noninvasive method for investigating human brain activity with whole head neurophysiological measurements. MEG measures weak magnetic fields generated at the scalp surface by the underlying electrical activity in the brain and it is very important for diagnostic purposes.


Anninos and Tsagas (3), using a pico- Tesla (pT) TMS electronic device, increased the abnormal (2 - 7 Hz) frequencies of the brain activity towards frequencies of less than or equal to those frequencies of the alpha frequency range (8 - 13 Hz) of each participant (4-16). The pT-TMS electronic device is a modified helmet containing up to 122 coils arranged in 5 array groups to cover the main 5 brain regions (frontal, vertex, right and left temporal, and occipital regions). It is designed to create pT-TMS range modulations of magnetic flux in the alpha frequency range (8 - 13 Hz) of each patient. The pT-TMS device was configured for each individual to generate a square wave to resemble the firing activity of neurons in the brain.


The present study aimed at identifying any change in the brain state after pT-TMS application on MS patients.

2. Methods


Biomagnetic measurements were performed using a whole-head 122-channel SQUID gradiometer device (Neuromag-122, Neuromag Ltd. Helsinki, Finland) in an electromagnetically shielding room. The spontaneous MEG recordings were taken with a sampling frequency rate of 256 Hz, with associated Nyquist frequency of 128 Hz. The MEG signal was filtered with cutoff frequencies at 0.3 and 40 Hz. The participants were 10 volunteers (2 males and 8 females) with the mean age of 41.3 ± 9.5 years. Informed consent was obtained from all participants. The research committee of the Democritus University of Thrace approved the research (code: 80347). All patients were referred to our Lab by practicing neurologists. They were asked not to take their medication for 24 hours during their participation in the study. In this study, we did not include healthy participants as controls because this research was published by Troebinger et al. (17), with our pico-Tesla electronic device (3) to determine an effect of pT-TMS in healthy participants. The time taken for each recording was 2 minutes to ensure alertness for each participant. A software program was developed in our laboratory to detect the amplitude of the primary dominant frequency of the power spectra of the MEG recordings obtained from each migraine patient and channel after the application of Fast Fourier Transform (FFT).

3. Results


Table 1 displays the brain regions and the corresponding channels in each brain region. Table 2 demonstrates the symptoms in each of the 10 MS patients before and after the application of the pT-TMS as evaluated by clinicians through interviews. Table 3 shows the maximum effect before pT-TMS (1st day in our lab) and after pT-TMS (2nd day in our lab) for each of the 10 MS patients. P is for the patient number, RT for the right temporal brain region, LT for the left temporal brain region, RP for the right parietal region, LP for the left parietal region, F for the frontal region, V for the vertex region, and O for the occipital brain region. Table 4 demonstrates the statistical analysis of the results using t test, being statistically significant in 7 out of 10 patients (70%). Figure 1A displays the 122-channel MEG system, Figure 1B exhibits the pT-TMS electronic device, whereas Figure 1C shows a MEG record obtained from Patient 1 from whom the primary dominant frequency was 3.2 Hz.


Table 1.
This Shows Shows the Brain Regions and the Corresponding Channels in Each Brain Region

Table 2.
The Symptoms of the 10 MS Patients Evaluated by Interview by Clinicians According to Expanded Disability Status Scale (EDSS), Before pT-TMS (1st Day in Our Lab) and After pT-TMS (2nd Day in Our Lab)

Table 3.
It Is Shown the Maximum Effect Before (BS) and After Real (AS) Stimulations for Each of the 10 Multiple Sclerosis Patients

Table 4.
Statistical Analysis of the Results (T-Test)a,b

Figure 1.
A, The 122-Channel MEG System; B, the pT-TMS Electronic Device; C, a MEG Record of 9 seconds Obtained from Patient 1 from Which in B, after FFT Analysis the Primary Dominant Frequency is 3.2 Hz

4. Discussion


In the present study, we did not include healthy controls because this was investigated by Troebinger et al. (17), who used an experimental design with our pT-TMS electronic device (3).


The time frame of our clinical investigations was as follows:


1st day: MEG measurements in our lab. Interview by clinicians (Table 2).


2nd day: Application of pT-TMS. MEG measurements in our lab. Interview by clinicians (Table 2).


10th day: MEG recordings and evaluation by the same clinicians. Most of the the patients reported a progressive deterioration of their pretreatment status.


The examination with the MEG in the 2nd day in our lab and after pT-TMS shows that most of the highly abnormal frequencies in the 2-7Hz frequency band were absent. All the MS patients were evaluated clinically and once again in the 10th day with the MEG. Most of the patients reported that they progressively deteriorated to their pretreatment status. To ascertain if the responses elicited in our lab were reproducible, the patients were advised to apply the pT-TMS treatment nightly at home at 11 PM with the electronic device mentioned before. Then, all the MS patients were evaluated again after a month and they all reported to have benefited from this treatment.


The mechanisms by which the application of the pT-TMS attenuated the MS syndrome are unknown. However, one possible explanation is that these magnetic fields have been shown to influence the activity of the pineal gland (PG), which regulates the endogenous opioid functions (18) and the dopaminergic modulator (19), GABA (20, 21).


In conclusion, this method of pT-TMS has some prospective to be an important noninvasive, secure and efficacious modality in managing MS. However, additional investigations are necessary with more participants to evaluate its possible beneficial contribution to manage MS symptoms.

Acknowledgments

Funding for this work was provided by a collaboration of GGET (general secretariat of research and technology, GR) and ERGO AEBE, INC., GR under the research program titled, “Foundation of a laboratories network and purchase of a multichannel biomagnetometer SQUID (superconducting quantum interference device) to develop an expert system for automatic acquisition, analysis, evaluation, and exploitation of MEG signals that are emitted from different organs of the human body” (grant number: 80623). The funding organization had no role in designing and conducting this study or in collecting, managing, analyzing the data, preparing, reviewing, or approving the manuscript.

Footnotes

Conflict of Interest: The authors have declared that no conflicts of interest exist.
Authors’ Contribution: Study concept and design: Photios Anninos; acquisition of data: Photios Anninos; analysis and interpretation of data: Athanasia Kotini, Adam Adamopoulos; drafting of the manuscript: Photios Anninos; critical revision of the manuscript for important intellectual content: Nicolaos Tsagas; statistical analysis: Athanasia Kotini; administrative, technical, and material support: Adam Adamopoulos; study supervision: Photios Anninos.

References


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Table 1.

This Shows Shows the Brain Regions and the Corresponding Channels in Each Brain Region

Brain Regions Channels
Right Temporal 1 - 14, 111 - 120
Left Temporal 43 - 50, 55 - 62, 67 - 74
Right Parietal 5 - 6, 11 - 16, 97 - 100, 109, 110, 115 - 122
Left Parietal 47 - 52, 59 - 64, 71 - 74, 79, 80, 87 - 90
Frontal 17 - 42
Occipital 75 - 86, 91 - 96, 101 - 110
Vertex 13 - 16, 49 - 54, 61 - 66, 73, 74, 89, 90, 99, 100, 117 - 122

Table 2.

The Symptoms of the 10 MS Patients Evaluated by Interview by Clinicians According to Expanded Disability Status Scale (EDSS), Before pT-TMS (1st Day in Our Lab) and After pT-TMS (2nd Day in Our Lab)

Patients Sex Symptoms Before pT-TMS Symptoms After pT-TMS
1 F Pyramidal Functions: 1. Abnormal signs without disability. Pyramidal functions: 0. normal
Cerebellar Functions: 3. Limb ataxia Cerebellar functions: 0. normal
Brain Stem Functions: 5. Inability to shallow or to speak Brain stem functions: 0. normal
Sensory Functions: 3. Moderate decrease in touch Sensory functions: 0. normal
Bowel and Bladder Functions:1. Mild urinary hesitancy Bowel and bladder functions: 0. normal
Visual Functions: 3.moderate decrease in fields Visual functions: 0.normal
Cerebral Functions: Mild decrease in mentation Cerebral functions: 0.normal
2 F Pyramidal Functions: 1. Abnormal signs without disability. Cerebellar functions: 3. moderated
Cerebellar Functions: 1. Abnormal signs without disability Brain stem functions: 5. inability to speak
Brain Stem Functions: 5. Inability to speak Sensory functions: 3. moderate decrease of pain
Sensory Functions: 3. Moderate decrease in pain Bowel and bladder functions: 1. mild urinary hesitancy
Bowel and Bladder Functions: 1. Mild urinary hesitancy Visual functions: 0. Normal
Visual Functions: 0. Normal Cerebral functions: 1. mood alteration only
Cerebral Functions: 1. Mood alteration only Pyramidal functions: 1. abnormal
3 M Pyramidal Functions: 2. Minimal disability Pyramidal functions: 0. normal
Cerebellar Functions: 2. Mild ataxia Cerebellar Functions: 0. Normal
Brain stem functions: 5. inability to speak Brain stem functions: 0. normal
Sensory Functions: 3.Moderate decrease in position Sensory functions: 0. normal
Bowel and bladder functions: 1. mild urinary hesitancy Bowel and bladder functions: 0. normal
Visual Functions: 0. Normal Visual functions: 0. normal
Cerebral Functions: 2. Mild decrease in mentation Cerebral functions: 0. normal
4 F Pyramidal Functions: 2. Minimal disability. Pyramidal functions: 2. minimal disability
Cerebellar functions: 2. mild ataxia Cerebellar functions: 2. mild ataxia
Brain Stem Functions: 5. Inability to swallow Brain stem functions: 5. inability to shallow
Sensory Functions: 3. Moderate decrease in pain Sensory functions: 0. normal
Bowel and bladder functions: 1. mild urinary hesitancy Bowel and bladder functions: 0. normal
Visual functions: 0. normal Visual functions: 0. normal
Cerebral Functions: 1. mood alteration only Cerebral functions: 0. normal
5 F Pyramidal functions: 2. minimal disability. Pyramidal functions: 0. normal
Cerebellar Functions: 2. Mild ataxia Cerebellar functions: 0. normal
Brain stem functions: 5. inability to swallow Brain stem functions: 0. normal
Sensory functions: 3. moderate decrease in touch Sensory functions: 0. normal
Bowel and bladder functions: mild urinary hesitancy Bowel and bladder functions: 0. normal
Visual functions: 0. normal Visual functions: 0. normal
Cerebral functions: 1. mood alteration only Cerebral functions: 0. normal
6 F Pyramidal functions: 1. abnormal signs without disability. Pyramidal functions: 0. normal
Cerebellar functions: 1. abnormal signs without disability Cerebellar functions: 0. normal
Brain stem functions: 5. inability to swallow Brain stem functions: 0. normal
Sensory Functions: 3. Moderate decrease in position Sensory functions: 0. normal
Bowel and bladder functions: mild urinary retention Bowel and bladder functions: 0. normal
Visual functions: 0. normal Visual functions: 0. normal
Cerebral functions: 2. mild decrease in mentation Cerebral functions: 0. normal
7 F Pyramidal functions: 2. minimal disability. Pyramidal functions: 0.normal
Cerebellar functions 2. mild ataxia Cerebellar functions: 0. normal
Brain Stem Functions: 5. Inability to speak Brain stem functions: 0. normal
Sensory functions: 3. moderate decrease in position Sensory functions: 0. normal
Bowel and bladder functions: 2. mild urinary retention Bowel and bladder functions: 0. normal
Visual functions: 0. normal Visual functions: 0. normal
Cerebral functions: 2. mild decrease in mentation Cerebral functions: 0. normal
8 M Pyramidal functions: 3. mild paraparesis Pyramidal functions: 3. mild paraparesis
Cerebellar functions: 1. abnormal signs without disability Cerebellar functions: 1. abnormal signs
Brain stem functions: 5. inability to speak Brain stem functions: 5. inability to speak
Sensory Functions: 3. Moderate decrease in position Sensory functions: 0. normal
Bowel and bladder functions: 3. mild urinary hesitancy hesitancy bowel and bladder functions: 3. mild urinary
Visual functions: 0. normal Visual functions: 0. normal
Cerebral functions: 1. mood alteration only Cerebral functions: 1. mood alteration only
9 F Pyramidal functions: 1. abnormal signs without disability. Pyramidal functions: 0. normal
Cerebellar functions: 1. abnormal signs without disability Cerebellar functions: 0. normal
Brain stem functions: 5. inability to speak Brain stem functions: 0. normal
Sensory Functions: 3.Moderate decrease in touch Sensory functions: 0. normal
Bowel and Bladder Functions: 8. Mild urinary urgency Bowel and bladder functions: 0. normal
Visual Functions: 0. Normal Visual functions: 0. normal
Cerebral functions: 1. mood alteration only Cerebral functions: 0. normal
10 F Pyramidal functions: 2. minimal disability. Pyramidal functions: 0. normal
Cerebellar Functions: 2. Mild ataxia Cerebellar functions: 0. normal
Brain stem functions: 2. moderate nystagmus Brain stem functions: 0. normal
Sensory functions: 1. figure writing decrease only Sensory functions: 0. normal
Bowel and bladder functions: 9. mild urinary urgency Bowel and bladder functions: 0. normal
Visual functions: 0. normal Visual functions: 0. normal
Cerebral functions: 1. mood alteration only Cerebral functions: 0. normal
Abbreviations: F, female; M, male.

Table 3.

It Is Shown the Maximum Effect Before (BS) and After Real (AS) Stimulations for Each of the 10 Multiple Sclerosis Patients

P RT BS RT AS LT BS LT AS RP BS RP AS LP BS LP AS F BS F AS V BS V AS O BS O AS
1 2.75 5.63 1.75 5.63 2.50 4.88 2.63 5.75 1.13 5.50 2.63 3.38 0.63 5.75
2 0.94 0.59 2.00 0.97 2.09 0.88 2.0 1.5 4.03 3.75 1.63 3.00 -0.03 0.47
3 2.41 2.72 2.34 3.72 4.81 5.25 1.88 4.53 3.63 4.97 5.47 5.25 2.88 3.53
4 2.84 5.34 4.56 5.60 3.13 4.78 4.91 3.75 4.21 3.03 5.1 3.38 2.47 3.53
5 3.81 4.34 3.78 5.41 3.81 4.34 2.16 5.41 3.94 2.1 2.1 3.94 3.25 5.31
6 5.1 5.13 5.13 3.25 4.75 5.00 5.13 3.25 3.56 3.44 5.13 2.81 5.56 3.00
7 4.84 5.31 3.47 4.91 4.84 5.31 3.94 5.63 2.63 5.13 4.84 5.31 3.28 4.88
8 2.69 3.63 3.1 3.56 2.1 4.13 3.31 4.50 4.75 2.75 3.31 3.63 4.75 5.19
9 1.94 4.81 0.56 4.00 4.56 4.81 4.19 4.00 2.88 2.88 4.56 4.81 5.31 4.88
10 3.91 5.19 1.69 4.66 2.34 5.19 2.88 4.81 3.53 4.21 1.69 5.19 4.81 5.22
Abbreviations: F, frontal region; LP, left parietal region; LT, left temporal brain region; O, occipital brain region; P, patient number; RP, right parietal region; RT, right temporal brain region; V, vertex region.

Table 4.

Statistical Analysis of the Results (T-Test)a,b

Patient BS AS P Value
1 2.003 ± 0.85 5.22 ± 0.86 0.0001
2 1.81 ± 1.24 1.98 ± 1.28 0.75
3 3.33 ± 1.36 4.3 ± 1.00 0.05
4 4.17 ± 0.99 4.20 ± 1.02 0.58
5 3.26 ± 0.8 4.41 ± 1.2 0.05
6 3.7 ± 0.95 4.87 ± 0.65 0.019
7 3.98 ± 0.9 5.21 ± 0.26 0.0043
8 3.43 ± 0.9 3.92 ± 0.8 0.33
9 3.38 ± 1.7 4.4 ± 0.75 0.05
10 2.96 ± 1.17 4.93 ± 0.39 0.001
a Values are expressed as mean ± SD.
b The results were statistical significant in 7 out of 10 patients (70%).

Figure 1.

A, The 122-Channel MEG System; B, the pT-TMS Electronic Device; C, a MEG Record of 9 seconds Obtained from Patient 1 from Which in B, after FFT Analysis the Primary Dominant Frequency is 3.2 Hz