METHOD AND APPARATUS OF ASSESSING OR MONITORING SKIN SYMPATHETIC NERVE ACTIVITY IN A LIVING SUBJECT
20230233134 · 2023-07-27
Inventors
Cpc classification
A61N1/36014
HUMAN NECESSITIES
A61B5/7264
HUMAN NECESSITIES
A61B5/2415
HUMAN NECESSITIES
International classification
A61B5/00
HUMAN NECESSITIES
Abstract
A method of assessing or monitoring the normal skin sympathetic nerve activity in a living subject, the subject having a skin, comprises assessing or measuring electrodermal activity, wherein the electrodermal activity is skin conductance, galvanic skin response, electrodermal response, psychogalvanic reflex, skin conductance response, sympathetic skin response or skin conductance level. Skin conductance may be assessed by calculating skin conductance fluctuation peaks per time unit, and when the skin conductance fluctuations peaks are above a certain predefined value, the normal skin sympathetic nerve activity is defined in an analyzing window with a length of about 15 to 60 seconds, the normal skin sympathetic nerve activity is assessed as being obtained or successful. Alternatively, the skin conductance may be assessed by calculating rise time of the mean skin conductance level, the area under the skin conductance fluctuations or the size of the amplitude of the skin conductance fluctuation.
Claims
1. A method of assessing or monitoring the normal skin sympathetic nerve activity in a living subject, the subject having a skin, the method comprising assessing or measuring electrodermal activity, wherein the electrodermal activity is chosen from the group consisting of skin conductance, galvanic skin response, electrodermal response, psychogalvanic reflex, skin conductance response, sympathetic skin response and skin conductance level.
2. The method of claim 1, wherein the electrodermal activity assessed or measured is skin conductance.
3. The method of claim 2, wherein the skin conductance is assessed or measured by calculating skin conductance fluctuation peaks per time unit and wherein when the number of the skin conductance fluctuations is above or equal to a predefined threshold level in the analyzing window the skin sympathetic nerve activity is assessed and obtained and defined as successful or normal.
4. The method of claim 3, wherein the predefined threshold level is 0.13 skin conductance fluctuations per sec.
5. The method of claim 3, wherein the skin conductance is assessed or measured by calculation the rise time of mean skin conductance level or the skin conductance fluctuations and wherein the rise time decreases or increases with a predefined threshold level in the analyzing window the skin sympathetic nerve activity is assessed and obtained and defined as successful or normal.
6. The method of claim 5, wherein the predefined threshold level is 0.02 microsiemens per time.
7. The method of claim 5, wherein the skin conductance is assessed or measured by calculating the area under the fluctuations and wherein the area has a predefined threshold level in the analyzing window the skin sympathetic nerve activity is assessed and obtained and defined as successful or normal.
8. The method of claim 7, wherein the predefined threshold is 2 microsiemensSec.
9. The method of claim 7, wherein the skin conductance is assessed or measured by calculating the amplitude of the skin conductance fluctuations, and wherein the mean amplitude of the skin conductance fluctuations has a predefined threshold level in the analyzing window the skin sympathetic nerve activity is assessed and obtained and defined as successful or normal.
10. The method of claim 9, wherein the predefined threshold level is 0.02 microsiemens.
11. The method of any claims 3-10 wherein the length of the analyzing window is 15 to 60 second.
12. The method of claim 11, wherein the length of the analyzing window is about 15 seconds.
13. The method of claim 1, wherein the skin conductance is measured in an entire body of the subject.
14. The method of claim 1, wherein the subject is an animal.
15. The method of claim 1, wherein the subject is a human.
16. The method of claim 1, wherein the skin sympathetic nerve activity is for a mixed nerve activity where all or some of skin conductance variables are chosen from the group consisting of skin conductance fluctuations per sec, amplitude of the skin conductance fluctuations, area under the skin conductance fluctuations and changes in rise time of the mean skin conductance level.
17. The method of claim 1, wherein the normal skin sympathetic nerve activity is obtained when the nerves are not disturbed by injuries, toxicity or nerve blocking agencies.
18. The method of claim 1, wherein the normal skin sympathetic nerves are assessed or measured at a skin level of the subject.
19. The method of claim 1, wherein the normal skin sympathetic nerve activity is assessed or measured in the subject's limbs, a palmar side of the subject's wrist, the subject's palm, the subject's ankle area, or a plantar part of the subject's foot.
20. The method of claim 1, further comprising the use of an additional process to assess or measure normal skin sympathetic nerve activity, wherein the additional process is chosen from the group consisting of unilateral thermometry monitoring, bilateral comparative thermometry monitoring, change in waveform amplitude in pulse oximetry plethysmography, and any combination thereof.
21. The method of claim 1, wherein the electrodermal activity at two or more extremities of the subject is assessed or measured, wherein in the electrodermal activity of one extremity injured or blocked nerves and one or more extremity(ies) without injured or blocked nerves are compared.
22. The method of claim 1, further comprising stimulating electrodermal activity in the subject that shows normal skin sympathetic nerve activity is assessed or measured to have been obtained or successful.
23. An apparatus configured to performing the method of any of claims 1-22.
24. The apparatus of claim 23, wherein the apparatus comprises a wireless sensor with Bluetooth connection to a computer or cell phone wherein a signal is processed through a computer software application and wherein the apparatus can send wireless information through a wireless technology to other computers, or mobile devices or tablets with computer software program.
25. The apparatus of claim 23, comprising a measuring box with electrodes and computer software display on any computer tablets.
26. The apparatus of claim 23, wherein the apparatus is configured to be used together with an accelerometer which will inform about movements to and give information about movement artefacts.
27. The apparatus of claim 23, wherein the apparatus is further configured to perform another process which can assess normal nerve activity, wherein the additional process is chosen from the group consisting of unilateral thermometry monitoring, bilateral comparative thermometry monitoring, change in waveform amplitude in pulse oximetry plethysmography, and any combination thereof.
28. The apparatus of claim 23, wherein the apparatus is configured to assess electrodermal activity at two or more extremities to compare the extremity with normal skin sympathetic nerve activity to one or more extremities without normal skin sympathetic nerve activity.
29. The apparatus of claim 23, wherein the apparatus further comprises an electrodermal activity stimulator which is configured to give information about when the normal skin sympathetic nerve activity to define that the nerve activity can be used for clinical assessment like pain and awakening.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0032] Embodiments, aspects and principles of the invention will now be described in more detail with reference to the attached drawings, in which
[0033]
[0034]
[0035]
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[0039]
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[0042]
DETAILED DESCRIPTION
[0043] Normal nerve activity has to be secured before the skin sympathetic nerves are used for pain assessment, awakening assessment or nerve block assessment:
[0044] Normal nerve activity has to be assessed before: [0045] 1. Regional nerve block. There are three types of nerves that are bundled together within the same neural element. These nerves are sympathetic nerves, sensory nerves and motor nerves. Local anesthetic application to neural structures in the living body, e.g. the human body, creates a differential nerve blockade depending on the dose of the local anesthetic. In general, small fibers are blocked faster than those of large ones because of the time course of drug diffusion into the nerves. When e.g. a local anesthetic block is applied to the nerve, the first nerve fibers to be blocked are C-fibers including the postganglionic sympathetic fibers. C-fibers are also involved in the slow pain transmission. Myelinated fibers are blocked later than unmyelinated fibers. The smallest diameter myelinated fibers are B-fibers, also known as preganglionic sympathetic fibers are blocked next. Therefore, the first nerve fibers to be blocked by a local anesthetic nerve block are mainly sympathetic fibers including small diameter unmyelinated C-fibers postganglionic sympathetic fibers), and lightly myelinated mid sized B-fibers (pre-ganglionic sympathetic fibers), along with C fibers for slow transmission of pain. [0046] 2. Epidural anaesthesia and spinal anaesthesia may hit the skin sympathetic nerves and block these. [0047] 3. Similar for diseases, there are both nerve toxic agents and diseases developing nerve injuries or neurpathies, e.g. diabetes. Nerve injury or diseases as neuropathy may decrease the functionality in the skin sympathetic nerves, and normal nerve activity should be secured before using the skin sympathetic nerves to assess e.g. pain or awakening. If such diseases have affected the skin sympathetic nerves, the method should not be used to assess e.g. pain (number of skin conductance peaks) and awakening (area under the skin conductance peaks), illustrated in
[0048] Based on such knowledge, the inventor has found that it is possible to monitor the sympathetic activity at the skin level by the use of a skin conductance monitor, thereby to directly monitor the normal nerve activity to secure that the nerves are without blocking agents and also without nerve diseases. This application is of extreme importance if this technology shall be used safe to assess e.g. pain and awakening. First of all, the clinician will immediately note that the skin sympathetic nerves have normal activity before these nerves are used for diagnostic purposes.
[0049] The inventor has found that electrodermal activity and skin conductance monitoring may be used to monitor and document the normal activity in the skin sympathetic nerves.
[0050]
[0051] Potential Use of Electrodermal Activity to Monitor Neuromodulation Techniques.
[0052] Neuromodulation techniques including spinal cord stimulator with various stimulation modes, including but not limited to, DRG stimulation meaning dorsal root ganglion stimulation, high density stimulation, high frequency stimulation, peripheral nerve stimulation, and any other stimulation techniques used in the clinical practice and also in experiment models.
[0053] One of the mechanisms that these neuromodulation techniques provide is the sympathectomy in the limbs. There is potential use of monitoring electric-dermal activity to find out if changes in sympathetic activity in the body is achieved.
[0054]
[0055] In this example, the subject is a human patient. Alternatively, the subject may be a human non-patient or an animal. In the context of this example, monitoring normal skin sympathetic nerve activity in the human patient includes determining the successful of defining the different skin conductance variables (skin conductance fluctuations per sec, amplitude of the skin conductance fluctuations, area under the skin conductance curve, the rise time of the skin conductance level):
[0056] Validation study, total of 25 recordings from volunteers were included in the analysis from the 25 volunteers recruited for this trial to secure normal skin conductance activity. The electrodes were placed 5 min on each extremity among the volunteers who were scheduled for the test. The technology is non-invasive and the test was not meant to be published, only to be used for internal purposes.
[0057] Inclusion ages were 18-99 years. Exclusion criteria were defined to any injury or disease affecting the skin sympathetic nerves. After the SCM was placed, the extremities were tested for 5 min each, in randomly chosen order.
[0058] The skin conductance measurement was performed using three self-adhesive noninvasive electrodes attached to the participants' plantar (under the sole) and palmar (inside hand) for each extremity. The skin conductance responses were assessed using the SCM equipment provided by Med-Storm Innovation, Oslo, Norway, software 1.0.6.33, The SCM is a device that primarily measures changes in skin conductance real time. A skin conductance response is defined as a minimum followed by a maximum in conductance values (mS). The measurement is performed using three self-adhesive electrodes, denoted C (current), R (reference) and M (measurement) attached to plantar skin (
[0059] The 3-electrode system used in our study allow us to only assess skin conductance activity underneath the M electrode. The system can measure conductance values in the range 1-200 mS, with a noise level (1 SD) below 0.002 mS. The threshold we used to define a skin conductance response was 0.02 microsiemens.
[0060] This device has been issued a European Community declaration of conformity but not FDA approved.
[0061] Stored skin conductance recordings were analyzed, there was not found any differences between the extremities when analyzing rise time of the mean skin conductance level, number of skin conductance fluctuations per sec, area under the skin conductance curve, and amplitude of the skin conductance fluctuations. The preset skin conductance analyzing window of 15 second was used on the SCM, and the assessment lasted for 5 min for each volunteer.
[0062] Non-paired statistical tests were used to study differences between the extremities in the different volunteers, no differences were found between the extremities. The results show the following values on normal skin sympathetic nerve activity:
TABLE-US-00001 1 minute analyzing time 5 minute analyzing time Skin conductance 0.21 +/− 0.05 0.19 +/− 0.04 peaks per sec: Amplitude of the 0.07 +/− 0.03 0.04 +/− 0.02 skin conductance fluctuations: Area under the 5.3 +/− 1.2 9.6 +/− 2.2 skin conductance curve: Rise time of the +/−0.04 +/− 0.2 +/−0.03 +/− 0.1 mean skin conductance level:
[0063]
[0064] The method includes the measuring step 120 of measuring electrodermal activity. Advantageously, the measured electrodermal activity is skin conductance. In alternative aspects, the electrodermal activity may be galvanic skin response, electrodermal response, psychogalvanic reflex, skin conductance response, sympathetic skin response or skin conductance level.
[0065] The method further proceeds to a calculating step 130, wherein the skin conductance measurement data are processed by calculating skin conductance fluctuation peaks per time unit.
[0066] The method further proceeds to the determining step 140. In the determining step 140, when the skin conductance fluctuations peaks are determined and counted in an analyzing window and the number of peaks is determined to be a above a predefined threshold level, the method proceeds to the establishing step 150. In establishing step 150, the normal nerve activity is established as being obtained and successful.
[0067] Advantageous, the analysis window has a length in time of about 15 to 60 seconds. Particularly advantageous, the length of the analyzing window is about 15 seconds.
[0068] When the normal nerve activity has been established to be successful in step 150, the method may be terminated at terminating step 160, or alternatively, repeated from the initiating step 110.
[0069] In the determining step 140, if the skin conductance fluctuations peaks are determined to be normal in the analyzing window, the measurement step 120, calculating step 130 and determining step 140 may be repeated.
[0070]
[0071] In the context of this example, monitoring an effectiveness of normal nerve activity in the human patient includes determining the successful achievement of normal nerve activity in a clinical setting.
[0072] The method starts at the initiating step 210.
[0073] The method includes the measuring step 220 of measuring electrodermal activity, wherein the measured electrodermal activity is skin conductance. In alternative aspects, the electrodermal activity could have been galvanic skin response, electrodermal response, psychogalvanic reflex, skin conductance response, sympathetic skin response or skin conductance level.
[0074] The method further proceeds to a calculating step 230, wherein a rise time of skin conductance level or fluctuations are calculated.
[0075] The method further proceeds to the determining step 240. In the determining step 240, when the rise time decreases or increases in an analyzing window according to a predefined threshold level, the method proceeds to the establishing step 250.
[0076] In establishing step 250, the normal nerve activity is established as being obtained or successful.
[0077] Advantageous, the analysis window has a length in time of about 15 to 60 seconds. Particularly advantageous, the length of the analyzing window is about 15 to 30 seconds.
[0078] When the normal nerve activity has been established to be successful in step 250, the method may be terminated at terminating step 260, or alternatively, repeated from the initiating step 210.
[0079] In the determining step 240, if the rise time of the mean skin conductance level or fluctuations do not decrease or increase, the measurement step 220, calculating step 230 and determining step 240 may be repeated (not illustrated).
[0080]
[0081] Also in this example, the subject is a human patient. Alternatively, the subject may be a human non-patient or an animal. In the context of this example, monitoring an effectiveness of normal nerve activity in the human patient includes determining the successful achievement of using the skin conductance activity in a clinical setting.
[0082] The method starts at the initiating step 310.
[0083] The method includes the measuring step 320 of measuring electrodermal activity, wherein the measured electrodermal activity is skin conductance. In alternative aspects, the electrodermal activity could have been galvanic skin response, electrodermal response, psychogalvanic reflex, skin conductance response, sympathetic skin response or skin conductance level.
[0084] The method further proceeds to a calculating step 330, wherein the area under the skin conductance fluctuations in an analyzing window are calculated.
[0085] The method further proceeds to the determining step 340. In the determining step 340, when the area under the skin conductance fluctuations increases above certain predefined threshold values in the analyzing window, the method proceeds to the establishing step 350.
[0086] In establishing step 350, the normal nerve activity is established as being obtained or successful.
[0087] Advantageous, the analysis window has a length in time of about 15 to 60 seconds. Particularly advantageous, the length of the analyzing window is about 15 seconds.
[0088] When the normal nerve activity has been established to be successful in step 350, the method may be terminated at terminating step 360, or alternatively, repeated from the initiating step 310.
[0089] In the determining step 340, if the area under the skin conductance fluctuations are above certain predefined threshold values in the analyzing window, the measurement step 320, calculating step 330 and determining step 340 may be repeated (not illustrated).
[0090]
[0091] Also in this example, the subject is a human patient. Alternatively, the subject may be a human non-patient or an animal. In the context of this example, monitoring an effectiveness of normal nerve activity in the human patient includes determining the successful achievement of using the skin conductance activity in a clinical setting.
[0092] The method starts at the initiating step 410.
[0093] The method includes the measuring step 420 of measuring electrodermal activity, wherein the measured electrodermal activity is skin conductance. In alternative aspects, the electrodermal activity could have been galvanic skin response, electrodermal response, psychogalvanic reflex, skin conductance response, sympathetic skin response or skin conductance level.
[0094] The method further proceeds to a calculating step 430, wherein the amplitude of the skin conductance fluctuations in an analyzing window are calculated.
[0095] The method further proceeds to the determining step 440. In the determining step 340, when the amplitude of skin conductance fluctuations increases above certain predefined threshold values in the analyzing window, the method proceeds to the establishing step 450.
[0096] In establishing step 450, the normal nerve activity is established as being obtained or successful.
[0097] Advantageous, the analysis window has a length in time of about 15 to 60 seconds. Particularly advantageous, the length of the analyzing window is about 15 seconds.
[0098] When the normal nerve activity has been established to be successful in step 450, the method may be terminated at terminating step 460, or alternatively, repeated from the initiating step 410.
[0099] In the determining step 440, if the amplitude of the skin conductance fluctuations are above certain predefined threshold values in the analyzing window, the measurement step 420, calculating step 430 and determining step 440 may be repeated (not illustrated).
[0100] The step of calculating if the area under the curve of the skin conductance, rise time and amplitude of fluctuations combined with the step of calculating skin conductance fluctuation peaks per time unit, as has been described above with reference to
[0101] In any of the methods and aspects described above with reference to
[0102] In any of the methods and aspects described above with reference to
[0103] In any of the methods described above with reference to
[0104] In any of the methods described above with reference to
[0105] In any of the methods described above with reference to
[0106] Any of the methods described above with reference to
[0107] In any of the methods described above with reference to
[0108] Any of the disclosed methods may further comprise stimulating electrodermal activity that is activated when normal nerve activity is assessed or measured to be defined as normal. Alternatively, such stimulating of electrodermal activity may be made separately from the method, e.g., before the method is performed. In the latter case, stimulating electrodermal activity is not part of the method of assessing or monitoring the normal nerve activity in the subject. The stimulation should not be performed in the extremity where the skin conductance activity is assessed.
[0109]
[0110] The apparatus includes an internal bus, which is interconnected to a processor, a memory, a first and a second I/O device, and optionally to a communication adapter. The communication adapter may e.g. enable communication between the apparatus and an external computer, network or system. The first I/O device is interconnected to a user interface, which enables the operation of the apparatus by a user, including providing input data to the apparatus via input devices such as a keyboard, and/or keys, switches, etc. The second I/O device is interconnected to a measurement device, which is adapted to measure electrodermal activity of a subject, in particular to measure skin conductance of an area of a human patient's skin.
[0111] The method of assessing or monitoring the normal nerve activity in the subject, e.g. the human patient, as has been disclosed in the present specification, an in particular as described above with reference to
[0112]
[0113] As shown in
[0114] The stimulating devices may be arranged to stimulate electrodermal activity in the subject (e.g., the patient). When normal nerve activity has to be tested electrodermal activity is assessed, a stimulator to secure electrodermal responses may be used as an additional option. This stimulating device should be a sensor stimulator of a certain strength which gives rise to one or several electrodermal response(s) in the subject. It could be e.g sound, pressure, electrical, light, or smell stimulus/stimuli.
[0115] As shown in
[0116] More specifically, the features of
[0117] As indicated in
[0118] The arrangement illustrated in
[0119]
[0120]
[0121] Although a three-electrode arrangement has been shown in
[0122]
[0123]