CN112535806A

CN112535806A - Activation system

Info

Publication number: CN112535806A
Application number: CN201911094856.9A
Authority: CN
Inventors: K·扎贝尔; 高莹
Original assignee: Seville Ltd
Current assignee: Seville Ltd
Priority date: 2019-09-20
Filing date: 2019-11-11
Publication date: 2021-03-23
Also published as: DE102019127098A1

Abstract

The present invention relates to an activation system for locally activating the nervous system in the human eye and brain by non-invasive pulse therapy to enhance residual vision in the presence of visual field defects, comprising an applicator for directing a current flow to the eye and/or brain and for stimulating a blood flow and activating nerve cells, in particular nervous cells of the visual system and retinal ganglion cells; a pulse generator for generating an electrical stimulation signal; a data processing and control unit for providing a patient-specific sequence of stimulation signals, the applicator having at least two electrodes abuttable on the subject's head. The replaceable stimulation electrodes are fixed on the applicator such that the stimulation electrodes rest against the left and right sides of the eye in the temple area of the patient's head. The applicator has at least one placement device for non-invasively determining blood flow of the skin and brain and determining oxygen saturation in order to improve the stimulation effect in use of the activation system in this regard.

Description

Activation system

Technical Field

The present invention relates to an activation system for local activation of the human eye and brain for visual ability training, in particular for activation of nerve cells in the human eye and brain by non-invasive pulse therapy, in particular alternating current pulse therapy (transcranial alternating current stimulation, tACS), to enhance residual vision in the presence of visual field defects, comprising an applicator for directing current flow to the eye and/or brain and for stimulating blood flow and activating nerve cells of the visual system, in particular retinal ganglion cells; a pulse generator for generating an electrical stimulation signal; and a data processing and control unit for providing a patient-specific stimulation signal sequence, wherein the applicator has at least two electrodes which can be placed against the head of the subject according to the preamble of claim 1.

Background

To date, visual field defects have been considered irreversible due to the inability of retinal, optic nerve and brain nerve cells to regenerate. However, it has been shown that partial restoration of visual field defects is possible because the brain, which evaluates and interprets retinal signals, can permanently amplify the residual signal by some mechanism. Also, there are nerve cells in the retina that reduce and "silence" their function after a pathological event because they are no longer able to send out more neural signals, but do not die.

Since experience has shown that almost all patients still have residual visual ability, so-called residual vision, it is recommended to reactivate "silent" nerve cells and enhance residual visual ability by improving synaptic transmission. Clinical studies have shown the success of treatment methods of visual training or alternating current stimulation. In alternating current therapy, parts of the entire retina and brain are activated and synchronized. The vast majority of patients respond well to the above forms of treatment. Physiological studies of the mechanisms of alternating current and electroencephalography (EEG) and functional magnetic resonance imaging (fMRT) have demonstrated a large number of local and global changes in blood flow and neural network reorganization in the brain. Local activation of nerve cells occurs in the eye and in the visual system of the brain through global reorganization of the neural network. Since residual vision can be enhanced by reactivation of nerve cells and modulation of neural plasticity, not only the eye but also the brain are of great significance for visual rehabilitation in ophthalmology.

For some time, brain adaptability, also known as plasticity, has been used in ophthalmology. By means of neuromodulation methods by means of weak alternating currents, it is possible to enhance partially impaired visual function by a neuroplasticity process.

Recently, methods for improving the resynchronization of blood flow and brain network activity by means of alternating current pulses have been tested and tried in patients with partial blindness. In this case, the alternating current is applied in a non-invasive manner over several days during the prescribed treatment by means of special electrodes on the forehead. In this case, an alternating current flows from the electrode to the eye where it stimulates retinal ganglion cells to emit at a predetermined frequency to resynchronize the brain network. This is because damage to the optic nerve leads to a disruption of the functional network within the brain, which can be manifested by a dyssynchrony of neurophysiology in the electroencephalogram. Treatment by means of alternating current can significantly improve this condition by improving blood flow and resynchronizing brain network activity.

However, the resynchronization of visual ability is very different and depends on very different factors, respectively.

In addition to optimizing the stimulation pulses, it is also necessary to keep the patient largely stress-free, at least during the treatment. To this end, there is a need to provide an optimized configuration of stimulation electrodes that includes a technical means of supporting the electrodes on the patient's head. It is therefore necessary to provide an applicator which is both ergonomically optimal and particularly suitable and satisfactory in terms of treatment technique for all requirements.

It is also important that the stimulation is optimally designed such that the therapeutic outcome is maintained outside the stimulation time, and as long as possible.

With respect to the prior art, reference is made in the aforementioned respect to EP 1603633B 1, which shows a special fastening means for a stimulation device in a desired position on the head of a patient, wherein the adjustment structure is made of a deformable material, which adjustment structure enables the device to adapt to the contours of the head of the patient.

Furthermore, fastening devices or arrangements for contact abutment of stimulation electrodes are described in EP 1708787 and EP 1734877B 1.

With respect to the prior art in brain stimulation with additional control of the blood flow behavior of adjacent vessels, attention is also paid to WO 2011/106660 a1 and WO 2016/115392 a 1.

In WO 2011/106660 a1 efforts are made to identify the effect of stimulation and in particular to stimulate and detect the effect of stimulation simultaneously in real time. For this purpose, functional near-infrared spectroscopy is used in a non-invasive manner during stimulation. Here, functional near infrared spectroscopy is used to measure the oxygenation status of hemoglobin.

WO 216/115392 a1 relates to devices and methods for determining neurovascular responsiveness using stimulation of the neurovascular system while recording neuronal hemodynamic responses thereto.

With regard to the various possible approaches to forming stimulation electrodes and corresponding applicators, attention is directed to the prior art briefly outlined below.

US 5522864 a discloses a forehead-head-band-shaped electrode holder. The first electrode is applied to a closed eyelid of the patient. The second electrode is fixed in the forehead decorative band. A third electrode is mounted in the neck region. Such electrode configurations, particularly the mounting of the electrodes to the closed eyelids, are considered uncomfortable by the patient and place the patient in tension that is detrimental to the outcome of the treatment.

Also in the family of EP 3013414B 1, which shows a stimulation device for transcutaneous electrical stimulation, a plurality of electrodes are fixed at positions significantly distant from each other. The first electrode is secured to the forehead region of the patient. The second electrode is located on the patient's neck or shoulder. These electrode arrangements are difficult to personalize and can only be optimally positioned by the patient with the aid of a third party, which represents a significant disadvantage for home therapy.

EP 3349844 a1 relates to treatment by using micro-currents. In this regard, punctiform stimulation electrodes are placed above and below the eye in the eyelid area. For many patients, it is uncomfortable to perform this positioning directly in the sensitive eye region, in particular also because the electrodes are relatively small and therefore do not achieve sufficient current intensity. Even small currents are evident, but are not therapeutically effective. Especially in the area above and below the eye, the human skin is very sensitive to irritation, and therefore this electrode configuration is not widely spread.

EP 2981326B 1 shows a headset-like arrangement for electrically stimulating the skin surface of the head.

DE 102011055844B 4 discloses a spectacle-like support for a stimulating electrode, wherein in addition a nose pad similar to a typical spectacle is present. The electrodes are embodied so as to be detachable there, that is to say interchangeable. However, the use of hair electrodes directly on the cornea of the eyeball in such an arrangement carries the risk of corneal damage.

In EP 2651504B 1, a forehead band is provided as an electrode carrier for nerve stimulation, wherein the forehead band rests against the head region of the patient and the associated electrodes rest symmetrically on the back head of the patient. Furthermore, there are electrical connections for connecting the electrodes to a separate pulse generator.

In the device for electrically stimulating ganglion cells according to US 2006/129207a, again a spectacle-like configuration is assumed with electrodes connected to the eyelid of the subject. The otherwise uncomfortable pressure on the eyelid can be reduced by the support, but this has the disadvantage that the magnitude of the contact resistance between the electrode and the skin of the subject is not always uniquely reproducible.

In summary, even in the case of local activation of the eye and brain here relevant, the prior art shows a multiplicity of different applicators for electrical stimulation, of which most known applicators for home therapy, that is to say in the sense of reproducible, simple and risk-free use by the patient without medical or medical support, are unsuitable.

For this reason, and ultimately also for cost reasons, nowadays large-area adhesive stimulation electrodes are largely used which are mounted on the respective subject or patient according to the empirical values of the medical staff. The advantage of larger electrodes is that sufficient current intensity can be provided since the current can enter the skin, eye or skull over a larger area. In this respect, trial and error methods are often used, the result being only very limited reproducibility. Even with the very base of adhesive electrodes, home use is almost excluded, so that in principle outpatient treatment preparations must be carried out.

Thus, the prior art discloses very different electrode sizes and positioning, but they vary greatly in their effect and are therefore not adequately reproducible. It is therefore desirable to be able to achieve a suitable electrode arrangement that is able to modulate the visual system even at lower currents and with less variability.

Disclosure of Invention

In summary, it is an object of the invention to perform individual electrode fitting according to a patient-specific physical condition. To this end, a novel activation system should be provided which on the one hand provides an optimal arrangement of the stimulation electrodes and ensures a lasting effect not only during but also after the stimulation treatment.

The object of the invention is achieved by an activation system according to the combination of features of claim 1 and by a special application according to the teaching of claim 18 or 19, wherein the dependent claims comprise at least suitable constructional variants and modifications.

A main aspect of the invention is to allow intuitive use of applicators, wherein an optimal stimulation sequence can be found by a placement device for non-invasively determining the blood flow of the skin and brain of a subject and for determining the oxygen saturation, which stimulation sequence causes the greatest increase in blood flow and the longest lasting after-effect, so that even after stimulation, the blood flow increase and the neuron activation last as long as possible, which is a clear indication for the sought outcome of the treatment.

The pulse generator for generating the stimulation signal sequence may be a single-channel or multi-channel stimulator interacting with a data processing and control unit to generate the patient-specific stimulation signal sequence.

The temple positioning according to the invention enables simultaneous stimulation of both eyes through only one channel, which reduces the cost of manufacturing the stimulation generator and improves the effectiveness and reliability, i.e. less variability of the outcome.

The optimal stimulation signal sequence may be determined during the first treatment under medical supervision, then stored on the patient memory card and transmitted to the patient for home use. It is also possible to store data directly in the storage unit of the applicator.

The applicator is constructed according to the invention such that it can be used intuitively, especially in the home area, also after a brief explanation of the operation.

Since it has been shown that the result of the treatment is manifested in particular when the patient remains stress-free shortly before the treatment and during the treatment, the applicator has a sound-generating device in the constructive solution of the invention, in particular constructed as an ear-worn earphone or as a headset. On the one hand, the patient may be communicated by the sound-producing device how he should manipulate the applicator, which procedure is to be selected, how long the treatment lasts, etc. In addition, the playing of a voice message, a sound sequence or music may also be performed in the sense of the desired relaxation response.

The applicator according to the invention therefore comprises an electrode holder which can be adapted in particular individually to the head shape. In addition, the temple positioning of the electrodes is performed for optimal stimulation. The advantage is thereby obtained that the current intensity of the pulse sequence can be reduced and at the same time sufficient phosphenes can still be generated. Post-effects of hemodynamics can be maximized in non-invasive ocular and brain simulations via Near Infrared (NIR) feedback systems.

In the course of extensive research and learning, and going back to the applicant, it has been shown that the arrangement of the electrodes plays a decisive role in the stimulation success of the visual system.

In this respect, a so-called F7-F8 arrangement according to the nomenclature of the electroencephalogram 10-20 system in the temple region of a patient (Nomenklatur) is proposed according to the invention. In such an arrangement optical pseudoscopic vision is recorded, in particular at an alternating frequency in the range of 8-25Hz at a very low current intensity in the range of less than 2 mA. If the electrodes are positioned within the range of F7-F8, the patient may close the eyes or open the eyes in a dark room. No uncomfortable pressure is generated in the eyelid area or above or below the eye due to the electrodes being attached or applied.

If wet electrodes are used and classified in the range of F7-F8, a very comfortable cooling effect is also produced, which results in a reduced pressure, reduced skin resistance and also improved treatment outcome.

In accordance with what has been described above, the present invention relates to an activation system for locally activating the human eye and brain to reorganize neural networks to enhance residual vision and improve blood flow in the presence of visual field defects. Pulsed current therapy, in particular non-invasive alternating current pulse therapy, is used in this respect.

The activation system includes an applicator for directing electrical current to the eye and brain, and stimulating blood flow and activating nerve cells, particularly retinal ganglion cells.

The activation system further comprises a pulse generator for generating an electrical stimulation signal and a data processing and control unit for providing a sequence of patient-specific stimulation signals.

The applicator has at least two electrodes which can be placed against the head of the subject in the manner to be explained below.

According to the invention, replaceable stimulation electrodes are fixed on the applicator such that they rest or rest against the left and right eye sides in the region of the temple of the patient's head, that is to say in the region of the so-called F7-F8.

Furthermore, the applicator has at least one arrangement for non-invasively determining the blood flow of the skin and brain and for determining the oxygen saturation, in particular based on functional near infrared (fNIR) spectroscopy.

The near-infrared emitter and at least one associated near-infrared detector are located on the patient's head in a location remote from the stimulation electrodes and are located separately from the stimulation electrodes.

Near infrared spectral data are collected, in particular at the pauses or at the ends of the stimulation signal sequences, in order to determine the duration of a permanent, improved blood flow and/or oxygen saturation, so that the data processing and control unit can thereafter be run up-to-date by means of the activation system according to the invention.

In a variant of the invention, the applicator can be adapted individually to the shape of the patient's head. For this purpose, adjusting devices known per se are designed on the front and rear head region of the patient with regard to the fixation.

In a constructive solution of the present invention, the applicator is designed in a ring or crown configuration applicable on the head, wherein a nasal bridge support and/or an ear support and/or a posterior head support are provided.

In addition, receptacles for electronic components and for weight compensation can be provided in the rear head region. Here, the electronic component may comprise a battery pack or accumulator, thus the applicator is used without external wiring for a power supply.

In one embodiment of the invention, the stimulation electrode is configured as a dry-pad electrode or as a wet-pad electrode.

In wet pad electrodes, an electrolyte may be used as an aqueous solution to reduce the contact resistance between the respective electrically conductive component of the electrode and the surface of the patient's skin. The smaller the contact resistance, the smaller the current selected for the pulse sequence can be and without causing uncomfortable effects in the sense of the typical tingling sensation in the sensed current flow. A fixing point for fixing, in particular clamping, the other electrode can be provided on the applicator, which fixing point enables the application of an electric current, in particular also an alternating current, in the region below the eye of the patient, as long as this is advantageous from a therapeutic point of view.

At least one interface for wired or wireless data transmission is formed on or in the applicator.

In this way, the applicator can exchange information with the superordinate system over a so-called air interface, record the course of the treatment duration and the treatment outcome, and provide or transmit this data to the attending physician for evaluation and further optimization of the treatment.

In a particular embodiment of the invention, a sound-generating device, in particular in the form of an ear-piece or a headset, is provided on the applicator in order to guide the patient during the treatment by means of the information, in particular to manipulate the applicator and/or to acoustically relax the patient.

For autonomous operation, the applicator comprises both a pulse generator, in particular an alternating current pulse generator, and a data processing and control unit and a power supply, wherein the treatment process and/or the stimulation signal sequence can be realized by means of a computer program product. Thus, in this regard, the applicator has all the technical means necessary for use and treatment. It is therefore no longer necessary to provide a separate pulse generating unit which is either wired next to the patient or carried by the patient, which is achieved, for example, in the known prior art by means of a device which is fixed or carried on the patient belt or pocket.

On or in the applicator, an electrolyte reservoir for electrode wetting may be provided. Thus, the patient gets the possibility to easily wet the electrode itself when it starts to dry out. Alternatively, the supply of electrolyte via a tube communicating with the electrode holder may also be automatically controlled by a suitable sensor.

In a configuration of the invention, the applicator and/or the holder for accommodating the electrode are made of a deformable plastic material. This makes it possible to adapt the applicator individually to a specific head shape, in particular in the forehead, nose or neck region of the patient, and thus to actually personalize the applicator for the patient concerned.

The stent and/or the stimulation electrodes may be made of a conductive plastic material, thus simplifying the construction of the applicator, and the delivery of the power or stimulation pulse sequences may be achieved by such conductive material.

In the sense of the present invention, there is a pocket or similar receptacle on the applicator for replacing the electrode. In the event of a loss of the replaceable electrode, the treatment can be continued, which is particularly advantageous if the patient to be treated is not in the vicinity of a medical clinic where his care is usually taken.

The applicator may be combinatorially configured to be combined with electroencephalographic electrode covers known per se, particularly for stationary or clinical applications.

As already indicated, the applicator may have a unit for determining the contact resistance between the stimulation electrode and the patient's skin surface in order to switch off the pulse generator or reduce the current in case of an abnormal, in particular excessively high contact resistance.

It has been shown that the activation system according to the invention for locally activating the human eye and brain can also be used for visual ability exercises, in particular for activating nerve cells in the human eye and brain of persons or subjects who have to perform complex activities under extreme gravitational and/or environmental conditions, as is the case, for example, in pilots, astronauts and deep-sea divers.

By treating these persons before, during and/or after use in the extreme conditions described, these persons can maintain visual abilities and can work intensively and safely.

In a constructive solution of the present invention, the proposed applicator may be constructed or adapted such that it may be integrated into a dedicated device for the aforementioned personnel. In particular, this involves integrating the applicator into a pilot helmet, an astronaut helmet or a deep sea diver helmet.

Drawings

The invention will be further elucidated by means of embodiments and by means of the drawings.

Here:

FIG. 1 is a front view of an exemplary applicator mounted on a subject's head; and is

Fig. 2 is a rear view of the applicator looking toward the back of the subject's head.

Detailed Description

According to fig. 1 and 2, the applicator 1 comprises a base body 2 made of an at least partially elastic material and which is able to adapt individually to the shape of the head of the subject 3 shown.

The base body 2 is realized in a ring-shaped or crown-shaped configuration which can be placed against the head of the subject 3, wherein a nose bridge support 4 is provided which has adjustment possibilities for adapting to anatomical conditions.

Furthermore, the base body 2 is connected with ear supports 5 for the left and right ears 6 of the subject 3.

In the rear head region, the base body 2 is provided with a receptacle for electronic components.

In this case, on the one hand, a memory unit 7 can be provided, which has a stimulation program. Furthermore, a pulse generator for generating an electrical stimulation signal and a control unit for providing a patient-specific stimulation signal sequence can be preferably arranged or mounted in the posterior head region

Data transmission is possible via the interface 8 (for example embodied as a USB interface), but it is also possible to charge the secondary battery 9 in order to supply the necessary electrical power or electronic components.

Such a secondary battery 9 can be, for example, a replaceable lithium battery, which is arranged in a recess in the base body 2 associated therewith.

The stimulation electrodes 10 are fastened to the base body 2 in an exchangeable manner and are arranged such that they rest or rest on the left and right eye sides in the temple region of the head of the patient shown.

In the front region of the base body 2, an adjustment device 12 is provided, which can be provided with a marking field 11 in order to provide space for a company logo, instructions for operation, and even also for the application of a user name or a user identification.

Sensors 13 may be mounted or embedded in the substrate 2 for non-invasive determination of blood flow in the skin and brain and for determining oxygen saturation. The sensor may be located remotely from the stimulating electrode 10.

Claims

1. An activation system for local activation of the human eye and brain for visual ability training, in particular for activation of nerve cells in the human eye and brain by non-invasive alternating current impulse therapy to enhance residual vision in the presence of visual field defects, comprising: an applicator for directing electrical current to the eye and brain and for stimulating blood flow and activating nerve cells, particularly retinal ganglion cells; a pulse generator for generating an electrical stimulation signal; and a data processing and control unit for providing a patient-specific stimulation signal sequence, wherein the applicator has at least two electrodes which can be placed against the head of the subject,

it is characterized in that the preparation method is characterized in that,

in particular replaceable, the stimulation electrodes are fixed to the applicator such that they rest against the left and right eye sides in the temple region of the patient's head.

2. Activation system according to claim 1, characterized in that the applicator is individually adaptable to the shape of the patient's head and for this purpose the adjustment means are configured on the patient's front and rear head regions with respect to fixation.

3. Activation system according to claim 1 or 2, characterized in that the applicator is configured in a ring-shaped or crown-shaped configuration which can rest against the head, wherein a nose bridge support and/or an ear support and/or a posterior head support are provided, and in the posterior head region a receptacle for electronic components and for weight compensation is provided.

4. The activation system according to claim 1, 2 or 3, wherein the stimulation electrode is configured as a dry pad electrode or a wet pad electrode.

5. Activation system according to one of the preceding claims, characterized in that fixing points for mounting, in particular clamping, further electrodes are provided on the applicator, which fixing points enable an alternating current application even in the region below the eyes of the patient.

6. Activation system according to any one of the preceding claims, characterised in that an interface for wired or wireless data transmission is configured on or in the applicator.

7. Activation system according to one of the preceding claims, characterized in that a sound-generating device is provided on the applicator, in particular configured as an ear-piece or headset, in order to guide the patient with information and/or acoustically relax the patient during alternating current pulse therapy.

8. Activation system according to one of the preceding claims, characterized in that for self-sufficient operation the applicator comprises an alternating current pulse generator as well as a data processing and control unit and a power supply, wherein the treatment process and/or the stimulation signal sequence can be realized by means of a computer program product.

9. An activation system as claimed in any one of the preceding claims, wherein a water reservoir for electrode wetting is provided on or in the applicator.

10. Activation system according to any one of the preceding claims, wherein the applicator and/or the holder for accommodating the electrodes are made of a deformable plastic material.

11. The activation system according to claim 10, wherein the holder and/or the stimulation electrode are made of an electrically conductive plastic material.

12. Activation system according to any one of the preceding claims, characterised in that there is a pocket on the applicator for accommodating a replacement electrode.

13. Activation system according to any one of the preceding claims, characterised in that the applicator is configured to be combinable for combination with electroencephalographic electrode masks known per se.

14. Activation system according to any one of claims 3-13, characterised in that the electronic component has a power source, in particular a battery or an accumulator.

15. Activation system according to any one of the preceding claims, characterized in that the unit for determining the contact resistance between the stimulation electrode and the patient's skin surface is configured for switching off the pulse generator in case of an abnormal resistance, in particular an excessively high resistance.

16. Activation system according to one of the preceding claims, characterized in that the applicator has at least one arrangement for non-invasively determining the blood flow of the skin and brain and for determining the oxygen saturation, in particular based on functional near infrared spectroscopy, wherein the near infrared emitter and the at least one associated near infrared detector can be positioned in a location on the patient's head remote from the stimulation electrodes and separated from the stimulation electrodes, and in particular at the pauses or the ends of the stimulation signal sequence, near infrared spectral data are collected to determine the duration of the permanent, improved blood flow and/or oxygen saturation, whereby an updated operation of the data processing and control unit can be achieved.

17. Activation system according to any one of the preceding claims, characterised in that the position of the stimulation electrodes corresponds to the arrangement of F7-F8 according to the nomenclature of the electroencephalogram 10-20 system.

18. An activation system for locally activating the human eye and brain by means of non-invasive alternating current electrical pulse therapy for visual ability exercises, in particular for activating nerve cells in the human eye and brain, comprising: an applicator for directing current to the eye and brain and for stimulating blood flow and activating nerve cells; a pulse generator for generating an electrical stimulation signal; and a data processing and control unit for providing a subject-specific stimulation signal sequence, wherein the applicator has at least two electrodes which can be placed against the head of the subject and which are fixed such that they are placed against the left and right eye sides in the temple region of the head of the patient, wherein these are applied on persons who are active in gravity or environmental conditions that exacerbate difficulties, such as in particular pilots, astronauts, deep sea divers, etc., before, during and/or after use.

19. The applicator according to any one of claims 2 to 17, characterized in that it is applied on persons, such as, in particular, pilots, astronauts, deep-sea divers, etc., who are active under gravity or environmental conditions that exacerbate difficulties, before, during and/or after use of these persons.

20. The applicator according to claim 19, wherein the applicator is an integral part of a head-mounted or head-protecting dedicated device, in particular a pilot helmet, an astronaut helmet or a deep-sea diver helmet.