WO2008038325A1

WO2008038325A1 - SCREEN FOR SIMULATING REPETITIVE TRANSCRANIAL MAGNETIC SIMULATION (rTMS) AND DEVICE FOR GIVING AND SIMULATING rTMS PROVIDED WITH SAID SCREEN

Info

Publication number: WO2008038325A1
Application number: PCT/IT2007/000659
Authority: WO
Inventors: Simone Rossi; Marisa Ferro
Original assignee: Universita' Degli Studi Di Siena
Priority date: 2006-09-29
Filing date: 2007-09-21
Publication date: 2008-04-03
Also published as: ITRM20060514A1

Abstract

The present invention relates to a screen (3) for simulating repetitive transcranial magnetic stimulation (rTMS), said screen being comprised of magnetically inert material, suitable to be coupled with an active element for administering rTMS, comprising electromagnetic means (2, 2') for generating a magnetic field along a direction, the screen (3) having a shape substantially identical to the section of the active element orthogonal to the direction of generation of magnetic field, the screen (3) being characterised in that it comprises at least a pair of electrodes (5, 5') on a surface facing outward. The present invention further relates to the device (1) for administering and simulating repetitive transcranial magnetic stimulation (rTMS) provided with said screen.

Description

SCREEN FOR SIMULATING REPETITIVE TRANSCRANIAL MAGNETIC SIMULATION (rTMS) AND DEVICE FOR GIVING AND SIMULATING rTMS PROVIDED WITH SAID SCREEN

The present invention relates to a screen for simulating repetitive transcranial magnetic simulation (rTMS) and device for giving and simulating rTMS provided with said screen.

More specifically, the invention concerns a screen of the above kind and the relevant device, studied and realised in such a way not to induce any biological effect on patient, but generating all sound and tactile sensations of a real stimulation, besides the same visual impact.

As it is well known, at present different therapeutical strategies exist for patients affected by neuropsychiatry diseases such as mood disturbs, depression and like. Said patients are usually subjected to treatment by drugs. However, many of them are resistant to drugs patients.

Different methods exist in order to solve the problem of resistance to drugs. Among these, one of the more known is the one based on an electro - subsultory therapy (ECS). ; Notwithstanding electro - subsultory therapy has given a| valid therapeutical help for treatment of some drug-resistant psychiatric pathologies, its particularly invasive nature and presence of serious and persistent collateral effects has widely limited its use as / routine therapeutical method. As an alternative to the electro - subsultory therapy, it is presently widely used the Ripetitive Transcranial Magnetic Stimulation - rTMS.

This is a not invasive technique and does not provide particular collateral effects. Said technique widespread thanks to/introduction of stimulators able to administering high frequency pulse trains and to create a suitable magnetic field.

Various kind of said rTMS devices are avaj/able on the market, such as the one described in US patent 6,179,770, concerning a magnetic stimulator for neuron-muscular tissue, compripig a stimulation coil generating a series of pulsed electrical discharges for producing magnetic pulses, inducing electric tissues within the tissv©- Coil is preferably a circular coil, placed within a frame or cover and connected with a duct through which wires start for electric supply. Duct and frame permit passage of refrigerating liquids on the coil surface.

At present, rTMSs technique are still studied. Therefore, both neurophysiologic searches and therapeutical test require a suitable control of real efficiency of the treatment. It is particularly necessary carrying out administering in cerebral time/areas by which a real magnetic effect is not induced in the patient. In other words, it is necessary evaluating if therapy permits obtaining an effective medical result and how much the possible benefice result obtained is a placebo effect. This evaluation is also necessary taking into consideration the kind of patients to which the treatment is administered.

At present, devices that can be used do not have satisfying use conditions under "placebo mode". This is mainly due to: • lack of biological sensations induced in the patient;

• not reproducibility of sensations on scalp, particularly due to stimulations of trydimus; and

• lack of discharge noise typical of real rTMS.

Among the presently available modes to obtain placebo effect, it is possible mentioning: those based on the variation of the position of the stimulation coil with respect to scalp with different direction and intensity of induced current (e.g. "8" shaped coil with its edge resting on scalp with an angle of 45° - 90° (Pasqual - Leone et al. 1996); circular coil, perpendicular to the scalp without any direct contact (Klein et al. 1999); tangential circular coil and output reduction at 0.05 T (Kolbinger et al.

1995).

Devices are also used permitting realising an administering of both a real and placebo treatment, with two circular coils adjacent each other, wherein direction of electric current can be changed. In the simulated operative mode, magnetic field is almost equal to zero. In this case, sounds produced during the stimulation simulation are similar to the real applications (Ruohonen et al. 2000; IEEE Trans Biomed Eng; 47: 145 - 8).

Another kind of solution is the one using real and not adjacent coils ("sandwich') with an interposed metallic magnetic screen.

Main technical problem of the available technologies is that of not being able to reproduce sensation on scalp that, for correct administering as placebo of an rTMS treatment, is essential for a proper and safe interpretation of statistic and experimental results during searches.

In view of the above, it is object of the present invention that of suggesting a device that can be used for making administering rTMS treatments both in a real and placebo or simulated mode, permitting, in the second case, reproducing all the physical sensations of the patient during the real treatment, maintaining unchanged visual impact of the stimulation apparatus. It is therefore specific object of the present invention a screen for simulating repetitive transcranial magnetic stimulation (rTMS), said screen being comprised of magnetically inert material, suitable to be coupled with an active element for administering rTMS, comprising electromagnetic means for generating a magnetic field along a direction, the screen having a shape substantially identical to the section of the active element orthogonal to the direction of generation of magnetic field, the screen being characterised in that it comprises at least a pair of electrodes on a surface facing outward.

Always according to the invention, said electrodes can be comprised of copper.

Still according to the invention, said electrodes can have a circular shape and have a diameter ranging between 1 and 3 cm, preferably a diameter of 2 cm. /

Furthermore, according to the invention, the screen can substantially have an 8 shape. I

Always according to the invention, said at least a pair of electrodes can be placed centrally between two circles creating /said 8 shape. /

Still according to the invention, said magnetically inert/material can also be electrically inert. j

Furthermore, according to the invention, said material can be wood and/or plastic. /

Always according to the invention, the screer/ can have a thickness ranging between 2 and 5 cm, preferably ranging between 2 and 4 cm, more preferably a thickness of 3 cm.

It is still object of the present invention a device for administering and simulating repetitive transcranial plagnetic stimulation (rTMS), including an active element comprising electromagnetic means for generating a magnetic field along a direction, and supply means connected with said electromagnetic means, characterised in that it further comprises a screen as described in the above, said supply means being also connected with said at least a pair of screen electrodes, so that the device is suitable to operate according to a first operative mode, wherein a surface of said active element is positioned in correspondence of a cranial surface for applying the magnetic field on the latter, and to operate according to a second operative mode, wherein the surface faced outward the screen is positioned in correspondence of the cranial surface so that screen is interposed between the same and the active element.

Always according to the invention, said electromagnetic means can comprise at least a coil, preferably housed within a container, more preferably within a handle. Still according to the invention, said electromagnetic means can comprise two adjacent coils so that section of active element orthogonal to the magnetic field generation direction substantially has an "8" shape.

Furthermore, according to the invention, said supply means can provide a pulsed electric signal, so that said electromagnetic means generates a corresponding pulsed magnetic field. I

Always according to the invention, said pulsed electric/signal can comprise a pulsed monophase and/or a pulsed biphase waveform

Said supply means can provide the same electric signal both to the electromagnetic means and to said at least one pair of elect/odes on the screen. /

Furthermore, according to the invention, said supply means can comprise at least a cable, that can be preferably connected with a trigger generator apparatus, more preferably an electromiograph instrument.

The present invention will be now described, for illustrative but not limitative purposes, according to its preferred embo/iments, with particular reference to the figures of the enclosed drawings J/vherein: figure 1 shows a front perspective view ,of a preferred embodiment of the device for administering and sirailating repetitive transcranial magnetic stimulation according to the present invention; figure 2 shows a rear perspective view of the device of figure 1 ; figure 3 shows a graph showing result/ of a test aiming to determine subjective equivalence between sensation on scalp from electrical pulses of device according to the invention and a real repetitive transcranial magnetic stimulation; figures 4a and 4b are graphs representing results of test aiming to detect properties of electric fields, respectively monophase and biphase fields, induced by administering of real or simulated transcranial magnetic stimulation by the device according to the invention; figure 5 shows an embodiment of a probe for detection of the electric field; figure 6 shows two graphs representing values of electric field due to administering of transcranial magnetic stimulation by the device according to the invention, with respect to other known modes; and figure 7 shows statistical results of responses of persons to questions relevant to recognition of real stimulations with respect to simulated stimulations by the device according to the invention or by known methods.

Making reference to figures 1 and 2, it is possible observing a preferred embodiment of device 1 for administering ad simulating repetitive transcranial magnetic stimulation (rTMS) according to the present invention. / Device 1 of the present embodiment provides a magnetically active element, comprising two adjacent coils 2 and 2', substantially placed along a plane so as to create a "8" shape. Other embodiments can use a different number of coils and/or other shapes and/or other devices of the same coils. A screen 3 is placed over the plane individuated by said coils 2,

2'. Said screen has substantially the same shape of the active element section, so that it is provided with two holes 3' in correspondence of the coils 2, 2' centre. Obviously, in case active element has a different number of coils and/or other shapes and/or other positioning of/the same coils, screen will have a correspondent different shape with respect to the shape shown in figures 1 and 2 (e.g. a round shape), to confirm to every kind of coils available on the market. Screen 3 is coupled win active element by device 1 , preferably by gluing.

Said screen 3 is painted with the same colour of coil 2, 2' container 1'. Thus, screen 3 cannot be distinguished by the patient with respect to container V and to coils 2, 2'. It is jτofed that container V has a handle. Screen 3 is comprised of magnetically/electrically inert material. In the present embodiment, said material is wood and has a thickness of 3 cm.

Said screen has two main functions. The first one is that of being a physical divider between coils 2, 2' and patient skin, so as to remarkably attenuate intensity of magnetic field applied on the patient cranium. It is in fact known that intensity of magnetic field emitted by rTMS devices decreases in space by a factor inversely proportional with respect to the square of distance. By this configuration, magnetic field attenuation occurs along axis orthogonal to the coil 2, 2' plane.

Thickness of 3 cm permits sufficiently attenuating most of induced electric current reaching patient brain or biological tissues. Other embodiments of the screen according to the invention can have different thickness. It must be noted that magnetic field in rTMS is a pulsed field.

Pulses can be of the monophase kind, with only a positive or negative pulse supplying coils 2, 2', obviously repeated, or biphase, comprised of a negative - positive oscillation (e.g. sinusoidal or quadratic or any other waveform). Screen 3 is provided with two electrodes, one negative electrode 5' and one positive electrode 5", that, if suitably supplied ,j act as electric stimulator. Preferably, said electrodes 5', 5" are comprised of copper, have a circular shape and a diameter of 2 cm each.

In the preferred embodiment, said electrodes 5', 5" are' aligned with the vertical symmetry axis of the device 1 , passing between the two coils 2, 2'.

Width of said electrodes 5', 5" permits obtaining an electric stimulation of the patient skin subjectively equivalent to the one created by administering a real magnetic stimulation. Particularly, dimensions of electrodes 5', 5" is preferably sufficiently large not to permit to the patient recognising position of the same electrodes, so as Xo' make electric stimulation of scalp diffuses as it occurs with the real rTMS stimulation.

Supply means are connected with device A by cables 6, for supplying coils 2, 2' and electrodes 5', 5". Further; it is also possible making by said cables 6 a real time connection witJf an electromyograph, permitting controlling magnetic stimulation. TMs, electric pulses for supplying electrodes 5', 5" and coils 2, 2' are_/sent synchronises for the wished frequency and intensity, so as to reproduce on the patient scalp a sensation reproducing at most the one of a real rTMS.

Tests data are represented in the following figures, for searches carried out comparing biologic effects caused by device 1 in the simulated operative configuration and other methods presently used for making simulated transcranial magnetic stimulations available on the market. Said methods are particularly the use of Magstim^® magnetic stimulator for real rTMS with coils at 90° with respect to scalp.

Thus, figure 3 shows a series of curves (ten curves) representing results of a test for determining the opinion of subject relevant to sensation on scalp due to electric pulses generated by electric stimulator 5 of device 1 , with respect to the one caused in case of a real stimulation with different intensities.

To the above ten selected subjects, skilled in the rTMS field (average age 34.8 ± 7.8 years, range 28 - 49 years), real monophase pulses have been administered by a device with two coils of 70 mm having an "8" configuration. Coils have been placed tangentially with respect to the scalp.

Zones subjected to treatment are not motor zones of the brain, for permitting to the subjects concentrating on the scalp sensations, preventing muscular contractions of muscles following to the stimulation of the same motor zones.

Real pulses administered have been casually generated with an intensity between 10% and 100% of stimulation that can be realised with device in the real or active operative mode. .

Then, electric pulses have been applied to each subject, after every rTMS pulse, by the electric stimulator 5 by device 1 according to the invention in a rTMS simulation mode (placebo effect), with a growing current intensity, thus realising a stimulation of scalp. ( Sensation has been verified for each pulse by verbal responses of patients, thus determining value of electric stimulator 5 supply current intensity reproducing the sensation most similar to the real one previously sensed, caused by real rTMS. Kind of used electric pulse has been a square wave with a length of 250 μsec. Stimulation intensities are in ordinate (milliAmperes) with respect to the percentage value of magnetic stimulation intensity induced reported as the percentage of maximum intensity that can be delivered by real rTMS device. Curves show that ten subjects have given substantially in-agreement responses.

By interpolation of curves, it is possible obtaining value of current intensity having the greatest chances of causing stimulations better simulating sensations of a real rTMS.

Interpolation relationship obtained is the following: y = 0.347 const»e^0047x y= current intensity necessary for supplying electric stimulator 5 (milliAmperes) x= desired magnetic stimulation intensity (percentage of maximum deliverable by device).

Figures 4a and 4b are the result of tests aiming detecting properties of electric field induced by respectively monophase and biphase fields, induced by administering of real rTMS, or rTMS simulated by the device 1 or simulated by Magstim^® device.

Intensity of field employed was 60% of maximum intensity that can be realised.

Field induced has been detected by a probe 7 (see figure 5) under the following conditions: • real repetitive transcranial magnetic stimulation, curve

A;

• repetitive transcranial magnetic stimulation simulated by device according to the invention, curve B (with or without electric stimulator 5); and • repetitive transcranial magnetic stimulation simulated by an rTMS simulation device like Magstim^® stimulator, curve C. it is observed that device 1 in a simulation mode (curve B) produces a very attenuated field both for monophase and biphase pulses with respect to a real rTMS administering.

Making reference to figure 5, above probe 7 is comprised of two insulated wires 7, T, helically braided each other, placed along axis perpendicular to coils 2, 2' surface (axis z).

Figure 6 shows two graphs wherein values of electric field (milliVolts) are represented, measured by probe 7 when administering rTMS at high density between 10% and 100% of maximum stimulation intensity that can be administered respectively for monophase and biphase pulses, in case of real rTMS (curve A), device 1 without activation of electrodes 5, 5' (curve B), device 1 with activation of electrodes 5, 5' (curve C), and rTMS simulated by Magstim^® stimulator (curve D).

It is noted that induced electric field is very similar to the one that can be obtained by rTMS simulated by Magstim^® stimulator. Advantage of device 1 with respect to Magstim^® stimulator is that of simulating very well sensations on scalp and sound effects in a much more realistic way. In fact, Magstim^® stimulator does not generate sensations on scalp and discharge noise is provided by a remote box. In figure 7, columns represent percentage of responses given to the question "Which one of the four stimulations (real rTMS, device 1 with activation of electrodes 5, 5', rTMS with 90° rotation of coil, and rTMS simulated by Magstim^® stimulator) do you deem is real rTMS?". It is to be noted that none of the subjects has identified as real rTMS obtained by placebo simulation methods presently available on the market (Magstim^® and 90° rotated probe). Real rTMS has been identified by 60% of pulse sequence in the four different conditions. rTMS by device 1 in a simulated operative mode has been deemed as real in 25-40% of the administered pulse sequences. For every experimental condition, there are , four columns, given by combination of frequency values of administered pulses (1Hz and 20 Hz) and intensity of stimulation (as Resting Motor Threshold terms, values 90% and 120%).

On the basis of the previous specification, it can be observed that basic feature of the present invention is that of shielding magnetic field really realised by a device for rTMS, also creating, by an electric stimulator, shock sensation on scalp, simulating a real stimulation. /

An advantage of the present invention is that the sarne rTMS device can be used both for a real administering of magnetic pulses, both in placebo mode, reproducing the same physiological effects, niaintaining unaltered the global visual impact.

Another advantage of the present invention is that/of obtaining the same acoustic effects and sensations on scalp of a real Administering of magnetic pulses.

Another advantage of the present invention is tbat the device is a physically and neurophisiologically reliable instrumpπt and can be realised with low costs. The present invention has been described for illustrative but not limitative purposes, according to its preferred embodiments, but it is to be understood that modifications and/or changes can be introduced by those skilled in the art without departing from the relevant scope as defined in the enclosed claims.

Claims

1. Screen (3) for simulating repetitive transcranial magnetic stimulation (rTMS), said screen being comprised of magnetically inert material, suitable to be coupled with an active element for administering rTMS, comprising electromagnetic means (2, 2') for generating a magnetic field along a direction, the screen (3) having a shape substantially identical to the section of the active element orthogonal to the direction of generation of magnetic field, the screen (3) being characterised in that it comprises at least a pair of electrodes (5, 5') on a surface facing outward.

2. Screen (3) according to claim 1 , characterised in that said electrodes (5, 5') are comprised of copper.

3. Screen (3) according to claim 1 or 2, characterised in that said electrodes (5, 5') have a circular shape and have a diameter ranging between 1 and 3 cm, preferably a diameter of 2 cm.

4. Screen (3) according to one of the preceding claims, characterised in that it substantially has an 8 shape. ,

5. Screen (3) according to claim 4, characterised in that said at least a pair of electrodes (5, 5') is placed centrally between two circles creating said 8 shape.

6. Screen (3) according to one of the preceding claims, characterised in that said magnetically inert material is electrically inert.

7. Screen (3) according to claim 6, characterised in that said material is wood and/or plastic. /

8. Screen (3) according to one of the preceding/ claims, characterised in that it has a thickness ranging between 2 and 5 cm, preferably ranging between 2 and 4 cm, more preferably a thicjcness of 3 cm.

9. Device (1) for administering and simulating repetitive transcranial magnetic stimulation (rTMS), including an a/tive element comprising electromagnetic means (2, 2') for generating a/magnetic field along a direction, and supply means (6) connected with said electromagnetic means (2, 2'), characterised in that it fu Irther comprises a screen (3) according to one of the claims 1 - 8, said supply means being also connected with said at least a pair of screen electpdes (5, 5'), so that the device (1) is suitable to operate according to a irst operative mode, wherein a surface of said active element is positioned in correspondence of a cranial surface for applying the magnetic fied on the latter, and to operate according to a second operative mode, wherein the surface faced outward the screen (3) is positioned in correspondence of the cranial surface so that screen (3) is interposed between the same and the active element.

10. Device (1) according to claim 9, characterised in that said electromagnetic means comprise at least a coil, preferably housed within a container, more preferably within a handle.

11. Device (1) according to claim 10, characterised in that said electromagnetic means comprise two adjacent coils so that section of active element orthogonal to the magnetic field generation direction substantially has a "8" shape.

12. Device (1) according to one of the preceding claims 9 - 11 , characterised in that said supply means provide a pulsed electric signal, so that said electromagnetic means (2, 2') generates a corresponding pulsed magnetic field.

13. Device (1) according to claim 12, characterised in that said pulsed electric signal comprises a pulsed monophase and/or a pulsed biphase waveform.

14. Device (1) according to one of the preceding claims 9 - 12, characterised in that said supply means provide the same electric signal both to the electromagnetic means (2, 2') and to said at least one pair of electrodes (5, 5') on the screen (3). !

15. Device (1) according to one of the preceding claims 9 J 14, characterised in that said supply means comprise at least a cable (6) that can be preferably connected with a trigger generator apparatus, ijnore preferably an electromiograph instrument.