Method and apparatus for assessing or monitoring skin sympathetic nerve activity in a living subject

Abstract

A method for assessing or monitoring normal skin sympathetic nerve activity in a living subject, the subject having skin, comprising assessing or measuring electrodermal activity, the electrodermal activity being skin conductance, galvanic skin response, electrodermal response, psychogalvanic reflex, skin conductance response, sympathetic skin response, or skin conductance level. Skin conductance is assessed by calculating the peak of skin conductance fluctuation per time unit, defining normal skin sympathetic nerve activity in an analysis window approximately 15 to 60 seconds long, and assessing normal skin sympathetic nerve activity as having been obtained or successfully achieved when the skin conductance fluctuation peak exceeds a predefined value. Alternatively, skin conductance may be assessed by calculating the rise time of the average skin conductance level, the area under the skin conductance fluctuation, or the magnitude of the amplitude of the skin conductance fluctuation.

Description

[Technical Field]

[0001] The present invention relates to a method for assessing or monitoring skin sympathetic nerve activity in a living subject, and to an associated apparatus. [Background technology]

[0002] In current clinical practice, commonly used monitoring methods for assessing normal nerve activity include observation of clinical signs, skin temperature monitoring in pulse oximetry, plethysmography, pulse amplitude monitoring, and combinations of such monitoring methods. These background art methods often exhibit unpredictable or delayed responses and other drawbacks. Therefore, it is desirable to develop an objective monitoring method in clinical practice that is reliable, has a rapid response, and is not affected by other drawbacks of the background art. More specifically, there is no assessment tool for assessing skin sympathetic nerve activity. Therefore, there is a need for improved methods and devices for assessing skin sympathetic nerve activity in subjects, such as human patients. Summary of the Invention

[0003] It is an object of the present invention to provide an improved method and apparatus for assessing or monitoring skin sympathetic nerve activity in a living subject.

[0004] The invention is set out in the accompanying claims.

[0005] The present disclosure relates to a method for assessing or monitoring cutaneous sympathetic nerve activity in a living subject having skin. In an advantageous aspect, the subject is a human, e.g., a human patient. In an alternative aspect, the subject may be an animal.

[0006] Assessing or monitoring skin sympathetic nerve activity in a subject, such as a human patient, can include determining whether normal skin sympathetic nerve activity is successfully defined in a clinical setting.

[0007] One advantageous aspect relates to a method for monitoring and ensuring normal skin sympathetic nerve activity in a subject. An alternative aspect relates to a method for assessing the effects or damage of drugs or diseases, respectively, that may affect the skin sympathetic nerves of a subject.

[0008] The method comprises the step of assessing or measuring electrodermal activity, the electrodermal activity being selected from the group consisting of skin conductance, galvanic skin response, galvanic skin response, psychogalvanic reflex, skin conductance response, sympathetic skin response and skin conductance level.

[0009] In an advantageous embodiment, electrodermal activity is measured. In an alternative embodiment, electrodermal activity is assessed.

[0010] Advantageously, the electrodermal activity evaluated or measured is skin conductance. Advantageously, the skin conductance is evaluated or measured by calculating the skin conductance fluctuation peak per time unit, and normal skin sympathetic nerve activity is defined as being unaffected by drugs or diseases when the skin conductance fluctuation peak is present in an analysis window having a length of about 15 to 60 seconds. The acquired and evaluated nerve activity is successful.

[0011] Particularly advantageously, the length of the analysis window is approximately 15 seconds.

[0012] Skin conductance can be evaluated or measured by calculating the rise time of skin conductance fluctuation, the frequency of skin conductance fluctuation, the area under the curve of skin conductance fluctuation, or the amplitude of skin conductance fluctuation.In this case, evaluating skin conductance fluctuation in an analysis window having a length of about 15 seconds to 60 seconds ensures normal skin sympathetic nerve activity.The length of the analysis window is preferably about 15 seconds to 30 seconds.

[0013] Skin conductance can be evaluated or measured by calculating the peak number (frequency) of skin conductance fluctuation per unit of time.When the number of skin conductance fluctuations is greater than or equal to 0.13 per second in the analysis window having a length of about 15 seconds to 60 seconds, the nerve activity is evaluated, acquired and defined as normal.Particularly advantageously, the length of the analysis window is about 15 seconds.

[0014] Skin conductance can be evaluated or measured by calculating the amplitude of the skin conductance fluctuation peak.When the amplitude is greater than a threshold value of 0.02 microsiemens in an analysis window having a length of about 15 seconds to 60 seconds, the nerve activity is evaluated, acquired, and defined as normal.Particularly preferably, the length of the analysis window is about 15 seconds.

[0015] Skin conductance can be evaluated or measured by calculating the area under the curve of the skin conductance fluctuation peak.When the area under the curve of the skin conductance fluctuation peak in the analysis window having a length of about 15 seconds to 60 seconds is greater than 2 microsiemens-seconds, normal nerve activity is evaluated and obtained, and is defined as normal.Particularly advantageously, the length of the analysis window is about 15 seconds.

[0016] Skin conductance can be evaluated or measured by calculating the rise time of the curve of the average skin conductance level.When the rise time is higher or lower than 0.02 microsiemens / second in an analysis window having a length of about 15 seconds to 60 seconds, normal nerve activity is evaluated and obtained, and is defined as normal.Particularly preferably, the length of the analysis window is about 15 seconds.

[0017] Skin conductance can be assessed over the entire body of a subject, but it is advantageous to assess skin sympathetic nerve activity on the palm (inside of the hand) and plantar (sole of the foot).

[0018] In any of the methods and aspects described above, the neural activity may be to sympathetic nerves, but the neural activity may also be to mixed nerves selected from the group consisting of motor and sympathetic nerves, sensory and sympathetic nerves, and motor, sensory and sympathetic nerves.

[0019] In either of the above methods, normal activity can be achieved while local or general anesthesia continues.

[0020] In any of the above methods, normal skin conductance activity can be assessed or measured at the skin level.

[0021] In any of the above methods, normal skin sympathetic nerve activity can be assessed or measured in the extremities, including, but not limited to, the volar aspect of the wrist, the palm, the ankle, the dorsum of the knee, or the plantar aspect of the foot.

[0022] Any of the above methods may further comprise using an additional method for assessing neural activity, which may be selected from the group consisting of unilateral thermometry monitoring, bilateral comparative thermometry monitoring, changes in waveform amplitude in pulse oximetry plethysmography, and any combination thereof.

[0023] In any of the disclosed methods, electrodermal activity can be assessed or measured in two or more limbs, where electrodermal activity in one limb or limbs is compared with and without a drug or disorder.

[0024] Any of the disclosed methods may further comprise the step of stimulating electrodermal activity, which is abolished in the presence of local anesthesia or neurological disease.

[0025] The present invention also relates to apparatus configured to carry out the disclosed methods.

[0026] The device may comprise a wireless sensor with a Bluetooth® connection to a computer or cell phone, where signals are processed through a computer software application and the device can transmit wireless information via wireless technology to another computer or mobile device or tablet with a computer software program.

[0027] The device may comprise a measurement box with electrodes and computer software displayed on any computer tablet.

[0028] The device can be used with an accelerometer, which reports information about the movement and provides information about the movement of the artifact.

[0029] The device can be connected to other methods capable of assessing nerve blockade, nerve injury, or normal nerve activity, the additional methods being selected from the group consisting of unilateral thermometry monitoring, bilateral comparative thermometry monitoring, changes in waveform amplitude in pulse oximetry plethysmography, and any combination thereof.

[0030] The device can be used to assess electrodermal activity in two or more limbs and compare the limbs for normal nerve activity.

[0031] The apparatus can be used in conjunction with an electrical stimulation device that can be used to provide information about the normal activity of the nerve (response to nerve stimulation). [Brief explanation of the drawings]

[0032] Embodiments, aspects and principles of the present invention will now be described in more detail with reference to the accompanying drawings. [Figure 1] FIG. 1 is a schematic flow chart illustrating a method for assessing or monitoring normal neural activity in a subject in a first embodiment. [Figure 2] FIG. 2 is a schematic flow chart illustrating a method for assessing or monitoring normal neural activity in a subject in a second embodiment. [Figure 3] FIG. 3 is a schematic flow chart illustrating a method for assessing or monitoring normal neural activity in a subject in a third embodiment. [Figure 4] FIG. 4 is a schematic flow chart illustrating a method for assessing or monitoring normal neural activity in a subject in a fourth embodiment. [Figure 5] FIG. 5 is a schematic block diagram showing the apparatus. [Figure 6] FIG. 6 is a schematic block diagram illustrating a further possible embodiment of the method and apparatus. [Figure 7] FIG. 7 is a schematic block diagram illustrating a further possible embodiment of the method and apparatus. [Figure 8] FIG. 8 is a diagram of an embodiment of a measurement arrangement. [Figure 9] FIG. 9 is a schematic block diagram illustrating a further embodiment of the apparatus. [Figure 10] FIG. 10 is a graph showing normal skin sympathetic nerve activity as assessed by microneurography and reflected by changes in skin conductance. DETAILED DESCRIPTION OF THE INVENTION

[0033] Before using the skin sympathetic nerves to assess pain, arousal, or nerve blockade, normal nerve activity must be ensured.

[0034] Normal neurological activity should be assessed beforehand.

[0035] 1. Local nerve blockade. There are three types of nerves bundled within the same nerve element. These nerves are sympathetic, sensory, and motor nerves. Application of local anesthetics to nerve structures in vivo (e.g., in the human body) results in selective nerve blockade depending on the dose of local anesthetic. Generally, due to the time course of drug diffusion into the nerve, thin fibers are blocked faster than thick fibers. For example, when applying local anesthetic blockade to a nerve, the first nerve fibers to be blocked are C-fibers, which include sympathetic postganglionic fibers. C-fibers are also involved in slow pain transmission. Myelinated fibers are blocked later than unmyelinated fibers. The smallest diameter myelinated fibers are B-fibers (also known as sympathetic preganglionic fibers), which are blocked next. Therefore, the first nerve fibers to be blocked during nerve blockade with local anesthetics are primarily sympathetic fibers. Sympathetic nerve fibers include small diameter unmyelinated C-fibers (postganglionic sympathetic fibers), lightly myelinated medium-sized B-fibers (preganglionic sympathetic fibers), and C-fibers for slow pain transmission. 2. Epidural and spinal anesthesia can directly affect and block the sympathetic nerves in the skin. 3. Similarly, there are both neurotoxins and diseases that can lead to nerve damage or neuropathy, such as diabetes. Diseases such as nerve damage or neuropathy can impair the function of the skin sympathetic nerves, and normal nerve activity should be ensured before using the skin sympathetic nerves to assess, for example, pain or arousal. If such diseases affect the skin sympathetic nerves, this method should not be used to assess, for example, pain (number of skin conductance peaks) or arousal (area under the skin conductance peaks), as shown in Figure 10.

[0036] Based on these findings, the inventors have discovered that sympathetic nerve activity can be monitored at the skin level using a skin conductance monitor. This allows for direct monitoring of normal nerve activity and confirms the absence of nerve blockers and neurological disorders. This application is crucial for the safe use of this technology, for example, in the assessment of pain and arousal. First, clinicians will immediately recognize the normal activity of skin sympathetic nerves before using them for diagnostic purposes.

[0037] The inventors have discovered that electrodermal activity and skin conductance monitoring can be used to monitor and record normal activity of the skin sympathetic nerves.

[0038] FIG. 10 shows normal skin sympathetic nerve activity assessed by microneurography and reflected by changes in skin conductance.

[0039] The potential use of electrodermal activity for monitoring neuromodulation techniques.

[0040] Neuromodulation technologies include spinal cord stimulation devices 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 technology used in clinical practice or experimental models.

[0041] One mechanism these neuromodulation techniques offer is sympathectomy of the limbs, and electrodermal activity could potentially be used to monitor whether changes in sympathetic nerve activity in the body have been achieved.

[0042] 1-4 are schematic flow charts illustrating a method for monitoring the effectiveness of normal skin sympathetic nerve activity.

[0043] In this example, the subject is a human patient. Alternatively, the subject may be a non-human patient or an animal. In the context of this example, a method for monitoring normal skin sympathetic nerve activity in a human patient includes determining whether various skin conductance variables (skin conductance fluctuations per second, amplitude of skin conductance fluctuations, area under the skin conductance curve, and time of rise in skin conductance level) are successfully defined.

[0044] For validation testing, 25 volunteers were recruited for this study to ensure normal skin conductance activity. A total of 25 recordings from the volunteers were included in this analysis. Electrodes were placed on each limb of the volunteers scheduled for testing for 5 minutes. This technique is non-invasive, and this study is not intended to be published and is for internal use only.

[0045] Subjects ranged in age from 18 to 99 years. Exclusion criteria were defined as any injury or disease affecting the skin sympathetic nerves. After SCM placement, the four limbs were tested in randomized order for 5 minutes each.

[0046] Skin conductance measurements were performed using three self-adhesive noninvasive electrodes attached to the plantar (sole of the foot) and palmar (inside of the hand) of each participant's limbs. Skin conductance responses were assessed using an SCM device provided by Med-Storm Innovation (Oslo, Norway, software 1.0.6.33). The SCM primarily measures changes in skin conductance in real time. Skin conductance responses are defined as a minimum conductance value (mS) followed by a maximum. Measurements were performed using three self-adhesive electrodes labeled C (current), R (reference), and M (measurement) attached to the plantar skin (Figure 8). The measurement unit applied a precise and constant alternating voltage between the R and M electrodes, with the C and R electrodes in a feedback configuration. The return current from the M electrode was recorded because it provides direct information about skin conductance. The recorded AC signals were subjected to advanced filtering to remove noise and interference before the signals were sent to the display computer (Figure 8).

[0047] The three-electrode system used in this study allowed us to evaluate only the skin conductance activity beneath the M electrode. This system was capable of measuring conductance values ​​ranging from 1 to 200 mS with a noise level (1 SD) of less than 0.002 mS. The threshold used to define a skin conductance response was 0.02 microsiemens.

[0048] The device has been issued a European Community Declaration of Conformity but is not FDA approved.

[0049] Analysis of the stored skin conductance recordings revealed no differences between limbs when analyzing the rise time of the mean skin conductance level, the skin conductance fluctuation per second, the area under the skin conductance curve, or the amplitude of the skin conductance fluctuation.A 15-second skin conductance analysis window was pre-set in the SCM, and the assessment lasted 5 minutes for each volunteer.

[0050] To examine differences between limbs in different volunteers, a non-paired statistical test was used, but no differences were found between limbs. The results showed the following values ​​for normal skin sympathetic nerve activity:

[0051] [Table 1]

[0052] 1 is a schematic flow chart illustrating a method for monitoring the effectiveness of normal neural activity in a subject in a first embodiment. The method begins at a start step 110.

[0053] The method includes a measuring step 120 of measuring electrodermal activity. Advantageously, the measured electrodermal activity is skin conductance. In alternative embodiments, the electrodermal activity may be galvanic skin response, galvanic skin response, psychogalvanic reflex, skin conductance response, sympathetic skin response, or skin conductance level.

[0054] The method further proceeds to a calculation step 130 where the skin conductance measurement data is processed by calculating the peak skin conductance variation per time unit.

[0055] The method further proceeds to a decision step 140. In the decision step 140, skin conductance variation peaks are determined and counted in the analysis window, and if the number of peaks is determined to be above a predefined threshold level, the method proceeds to an establishment step 150. In the establishment step 150, normal neural activity is obtained and established as successful.

[0056] Advantageously, the analysis window has a time length of approximately 15 to 60 seconds, and particularly advantageously, the length of the analysis window is approximately 15 seconds.

[0057] When normal neural activity is successfully established in step 150, the method may end in end step 160 or may repeat from start step 110.

[0058] If the skin conductance variation peaks within the analysis window are determined to be normal in the decision step 140, then the measuring step 120, the calculating step 130 and the decision step 140 may be repeated.

[0059] 2 is a schematic flow chart illustrating a method for monitoring the effectiveness of normal neural activity in a subject according to a second embodiment. The subject, in this example, is a human patient. Alternatively, the subject may be a non-human patient or an animal.

[0060] In the context of this example, a method of monitoring the effectiveness of normal neural activity in a human patient includes determining whether normal neural activity has been successfully achieved in a clinical setting.

[0061] The method begins at a start step 210 .

[0062] The method includes a measuring step 220 of measuring electrodermal activity, the measured electrodermal activity being skin conductance. In alternative embodiments, the electrodermal activity may be a galvanic skin response, a galvanic skin response, a psychogalvanic reflex, a skin conductance response, a sympathetic skin response, or a skin conductance level.

[0063] The method further proceeds to a calculation step 230 where the skin conductance level or rise time of the skin conductance variation is calculated.

[0064] The method further proceeds to a decision step 240. In the decision step 240, when the rise time within the analysis window decreases or increases according to a predefined threshold level, the method proceeds to an establishing step 250.

[0065] In an establishment step 250, normal neural activity is obtained or established as successful.

[0066] Advantageously, the analysis window has a time length of approximately 15 to 60 seconds, and particularly advantageously, the length of the analysis window is approximately 15 to 30 seconds.

[0067] When normal neural activity is successfully established in step 250, the method may end in end step 260 or may repeat from start step 210.

[0068] If, in determining step 240, the rise time of the mean skin conductance level or variability does not decrease or increase, measuring step 220, calculating step 230 and determining step 240 may be repeated (not shown).

[0069] FIG. 3 is a schematic flow chart illustrating a method for monitoring the effectiveness of normal neural activity in a subject in a third embodiment.

[0070] Also in this example, the subject is a human patient. Alternatively, the subject may be a non-human patient or an animal. In the context of this example, a method of monitoring the effectiveness of normal neural activity in a human patient includes determining whether normal neural activity has been successfully achieved using skin conductance activity in a clinical setting.

[0071] The method begins at a start step 310 .

[0072] The method includes a measuring step 320 of measuring electrodermal activity. The measured electrodermal activity is skin conductance. In alternative embodiments, the electrodermal activity may be a galvanic skin response, a galvanic skin response, a psychogalvanic reflex, a skin conductance response, a sympathetic skin response, or a skin conductance level.

[0073] The method further proceeds to a calculation step 330 where the area under the skin conductance variation in the analysis window is calculated.

[0074] The method further proceeds to a decision step 340. At the decision step 340, when the area under the skin conductance variation increases beyond some predefined threshold within the analysis window, the method proceeds to an establishment step 350.

[0075] In an establishment step 350, normal neural activity is obtained or established as successful.

[0076] Advantageously, the analysis window has a time length of approximately 15 to 60 seconds, and particularly advantageously, the length of the analysis window is approximately 15 seconds.

[0077] When normal neural activity is successfully established in step 350, the method may end in end step 360 or may repeat from start step 310.

[0078] In a determining step 340, if the area under the skin conductance variation in the analysis window exceeds some predefined threshold, the measuring step 320, calculating step 330 and determining step 340 may be repeated (not shown).

[0079] FIG. 4 is a schematic flow chart illustrating a method for monitoring the effectiveness of normal neural activity in a subject in a fourth embodiment.

[0080] Also in this example, the subject is a human patient. Alternatively, the subject may be a non-human patient or an animal. In the context of this example, a method of monitoring the effectiveness of normal neural activity in a human patient includes determining whether normal neural activity has been successfully achieved using skin conductance activity in a clinical setting.

[0081] The method begins at start step 410 .

[0082] The method includes a measuring step 420 of measuring electrodermal activity. The measured electrodermal activity is skin conductance. In alternative embodiments, the electrodermal activity may be galvanic skin response, galvanic skin response, psychogalvanic reflex, skin conductance response, sympathetic skin response, or skin conductance level.

[0083] The method then proceeds to a calculation step 430 where the amplitude of the skin conductance variation in the analysis window is calculated.

[0084] The method further proceeds to a decision step 440. If, at decision step 340, the amplitude of the skin conductance variation increases above some predefined threshold within the analysis window, the method proceeds to an establishing step 450.

[0085] In an establishment step 450, normal neural activity is obtained or established as successful.

[0086] Advantageously, the analysis window has a time length of approximately 15 to 60 seconds, and particularly advantageously, the length of the analysis window is approximately 15 seconds.

[0087] When normal neural activity is successfully established in step 450, the method may end in end step 460 or may repeat from start step 410.

[0088] In a decision step 440, if the amplitude of the skin conductance variation in the analysis window exceeds some predefined threshold, the measuring step 420, the calculating step 430 and the deciding step 440 may be repeated (not shown).

[0089] As described above with reference to Figure 1, the calculation steps of calculating the area under the curve of the skin conductance, the rise time of the fluctuation and the amplitude of the fluctuation are combined with the step of calculating the skin conductance fluctuation peak per time unit.

[0090] In any of the methods and embodiments described above with reference to Figures 1, 2, 3 and / or 4, skin conductance monitoring may be performed over the entire body of the subject.

[0091] In any of the methods and embodiments described above with reference to Figures 1, 2, 3 and / or 4, normal sympathetic nerve activity is concluded.

[0092] Normal neural activity can be obtained and defined in any of the methods described above with reference to Figures 1, 2, 3, and / or 4. Normal neural activity may be defined a priori by the subject (e.g., a human patient). That is, normal neural activity can be defined other than as part of a method for assessing or monitoring skin sympathetic nerve efficacy.

[0093] In any of the methods described above with reference to Figures 1, 2, 3 and / or 4, normal nerve activity can be assessed or measured at the skin level.

[0094] In any of the methods described above with reference to Figures 1, 2, 3 and / or 4, normal nerve activity can be assessed or measured at various locations on the extremities, including, but not limited to, the volar aspect of the wrist, the palm, the ankle, the dorsal aspect of the knee, or the plantar aspect of the foot.

[0095] Any of the methods described above with reference to Figures 1, 2, 3 and / or 4 may use or further comprise additional methods for assessing or measuring normal neural activity, which may be selected from the group consisting of unilateral thermometry monitoring, bilateral comparative thermometry monitoring, changes in pulse oximetry plethysmography waveform amplitude, and any combination thereof.

[0096] In any of the methods described above with reference to Figures 1, 2, 3 and / or 4, electrodermal activity (e.g., skin conductance) may be assessed or measured in more than one limb, where electrodermal activity (e.g., skin conductance) may be compared between one limb with nerve blockage or nerve injury and one or more limbs without nerve blockage or nerve injury.

[0097] Any of the disclosed methods may further comprise a step of stimulating electrodermal activity that is activated when normal neural activity is assessed or measured and defined as normal. Alternatively, such a step of stimulating electrodermal activity may be performed separately from the method, for example, before the method is performed. In the latter case, the step of stimulating electrodermal activity is not part of the method of assessing or monitoring normal neural activity of the subject. Stimulation should not be applied to the extremity on which skin conductance activity is assessed.

[0098] FIG. 5 is a schematic block diagram illustrating an apparatus that can be used to assess or monitor normal skin sympathetic nerve activity in a subject.

[0099] The device includes an internal bus interconnected to a processor, memory, a first I / O device, a second I / O device, and optionally a communications adapter. The communications adapter may, for example, enable communication between the device and an external computer, network, or system. The first I / O device is interconnected to a user interface, which allows a user to operate the device, including providing input data to the device via input devices such as a keyboard and / or keys, switches, etc. The second I / O device is connected to a measurement device. The measurement device is adapted to measure electrodermal activity of a subject, in particular, to measure skin conductance of an area of ​​skin of a human patient.

[0100] As disclosed herein, and in particular as described above with reference to Figures 1, 2, 3 and 4, the method for assessing or monitoring normal nerve activity in a subject (e.g., a human patient) may advantageously be implemented as a set of processing instructions, i.e., a computer program, that may be stored in a memory interconnected to a bus within a device, such that when the processing instructions are executed by a processor within the device, the device performs the method for assessing and monitoring normal skin sympathetic nerve activity according to the present disclosure.

[0101] FIG. 6 is a schematic block diagram illustrating a further possible embodiment of the method and apparatus.

[0102] As shown in Figure 6, the device may be interconnected to a PC with a display, for example, via a communications cable. The device may also be connected to electrodes and a stimulation device via connections shown as electrode cables. As shown, the interconnected stimulation device may include audio equipment for providing acoustic stimulation to the subject and / or electrodes for providing electrical stimulation to the subject. Electrodes attached to the subject (patient) for measuring electrodermal activity (e.g., skin conductance) are also shown.

[0103] The stimulation device can be positioned to stimulate the electrodermal activity of a subject (e.g., a patient). When normal nerve activity must be tested to evaluate electrodermal activity, a stimulation device for ensuring electrodermal responses can be used as an additional option. The stimulation device is a sensor stimulation device of a certain strength that induces one or more electrodermal responses in the subject. The stimulation can be, for example, sound, pressure, electricity, light, or odor.

[0104] 7 is a schematic block diagram illustrating a further possible embodiment of the method and apparatus, where the electrical stimulation device is located on a different limb from the location where skin sympathetic nerve activity is assessed.

[0105] As shown in Figure 7, the device is used in a configuration to assess or monitor normal skin sympathetic nerve activity in a subject (illustrated as a human nervous system) using electrodermal activity measured from multiple limbs.

[0106] 7 allows for the assessment or measurement of electrodermal activity (e.g., skin conductance) of two or more limbs, where electrodermal activity of one limb having normal nerve activity and electrodermal activity of one or more limbs to be tested for normal skin sympathetic nerve activity can be assessed or measured.

[0107] As shown in Figure 7, separate electrodes are positioned to measure electrodermal activity (e.g., skin conductance) on both hands of a person. Optionally, electrodes can be positioned as shown by the dotted lines to measure electrodermal activity (e.g., skin conductance) on both feet of a person. The electrodes are connected to the device. The device is further connected to a PC and a display via a communication cable.

[0108] The arrangement shown in Figure 7 provides the additional capability to assess / monitor the effects of normal skin sympathetic nerve activity in one limb, with one or more limbs not used in clinical evaluation serving as controls for the limbs being tested for normal nerve activity.

[0109] FIG. 8 is a diagram of an embodiment of a measurement arrangement.

[0110] FIG. 8 shows a target limb, i.e., the foot of a human patient. Three electrodes are attached to the skin of the sole of the patient's foot. The electrodes are a current (C), reference (R), and measurement (M) electrode. The electrodes may be self-adhesive electrodes. They are interconnected by an electrode cable to a device that may be configured to implement a method for assessing or monitoring the effectiveness of a patient's normal neural activity, as disclosed herein.

[0111] It should be noted that although three electrode configurations are shown in FIG. 8, the electrodes used to measure electrodermal activity such as electrodermal response, galvanic skin response, skin resistance or skin conductance are two electrode configurations.

[0112] FIG. 9 is a schematic block diagram illustrating a further embodiment of the apparatus.

[0113] Figure 9 shows an overview of the apparatus in use and the devices interconnected thereto. The apparatus 1 is interconnected via an electrode cable 2 with electrodes for measuring the electrodermal activity of a subject (e.g., a patient). The arrangement of three electrodes shown is suitable for measuring skin conductance on a portion of the patient's skin. The apparatus is powered by a power supply 4 with a mains cable 6. A communications cable 3 interconnects the apparatus 1 and a PC 7 with a display and stand 10. The PC can be powered by a power supply 8 with a mains cable 9.

Claims

1. 1. A method of operating an apparatus, comprising: The apparatus comprises a measuring device configured to measure skin conductance of a living subject; and a processor; The method comprises: measuring the skin conductance with the measuring device; The processor: receiving the skin conductance; Calculating the number of skin conductance fluctuation peaks per second in the skin conductance; determining that the skin sympathetic nerve activity is normal when the number of skin conductance variation peaks is equal to or greater than a predefined threshold level in an analysis window; and outputting information indicating the determination result, The method, wherein the predefined threshold level is 0.13 skin conductance fluctuations / second.

2. 10. The method of claim 1, The processor: calculating a rise time of a curve of an average skin conductance level based on the skin conductance; comparing the rise time in the analysis window to a predefined threshold level for rise time; and outputting information indicative of the rise time comparison.

3. 3. The method of claim 2, The method of claim 1, wherein the predefined threshold level for rise time is 0.02 microsiemens / second.

4. 3. The method of claim 2, The processor: calculating an area under the curve of the skin conductance variation peak based on the skin conductance; comparing said area to a predefined threshold level for area in said analysis window; and outputting information indicative of the area comparison.

5. 5. The method of claim 4, The method of claim 1, wherein the predefined threshold is 2 microsiemens-seconds.

6. 5. The method of claim 4, The processor: calculating an amplitude of the skin conductance variation based on the skin conductance; determining whether the amplitude of the skin conductance variation has a predefined threshold level in the analysis window for the amplitude; and outputting information indicative of the amplitude determination.

7. 7. The method of claim 6, The method, wherein the predefined threshold level for amplitude is 0.02 microsiemens.

8. The method according to any one of claims 1 to 7, A method wherein the analysis window is between 15 and 60 seconds in length.

9. 9. The method of claim 8, A method wherein the analysis window is 15 seconds long.

10. 10. The method of claim 1, A method wherein, in the measuring step, the measuring device measures the skin conductance at the limbs of the living subject, the palmar side of the wrist of the living subject, the palm of the living subject, the ankle of the living subject, or the sole of the foot of the living subject.

11. 10. The method of claim 1, The method, wherein the living subject is an animal.

12. 10. The method of claim 1, The method, wherein the living subject is a human.

13. 10. The method of claim 1, acquiring temperature data of the living subject and / or acquiring a pulse oximetry plethysmography signal with the measurement device; The processor: Calculating information about one-sided temperature measurement monitoring, two-sided comparative temperature measurement monitoring based on the temperature data; and / or and analyzing changes in pulse oximetry plethysmography waveform amplitude based on the pulse oximetry plethysmography signal.

14. 10. The method of claim 1, the measuring step is performed on two or more limbs of the living subject; The processor: performing the determining step for each of the two or more limbs; and The method further comprises the step of comparing the skin conductance of one limb with nerve damage or interruption to one or more limbs without nerve damage or interruption.

15. 10. The method of claim 1, The method further includes controlling, by the processor, a stimulation device to output a signal to stimulate the skin of the living subject.

16. 1. An apparatus comprising: a measurement device and a processor, the measuring device is configured to measure skin conductance of a living subject; The processor: receiving the skin conductance; Calculating the number of skin conductance fluctuation peaks per second in the skin conductance; and The method is configured to determine that the skin sympathetic nerve activity is normal when the number of skin conductance variation peaks is equal to or greater than a predefined threshold level in an analysis window; The predefined threshold level is 0.13 skin conductance fluctuations / second.

17. 17. The apparatus of claim 16, the processor further comprises wireless communication capability having a Bluetooth connection to a computer or a mobile phone; The device is capable of transmitting information regarding the skin conductance through the wireless communication capability to another computer, or to a mobile device or tablet having a computer software program.

18. 17. The apparatus of claim 16, The apparatus, wherein the measuring device comprises an electrode.

19. 17. The apparatus of claim 16, the device further comprises a temperature sensor and / or a pulse oximeter; The processor: calculating information for one-sided temperature measurement monitoring and / or two-sided comparative temperature measurement monitoring from the temperature data acquired by the temperature sensors; and / or Analyzing changes in waveform amplitude in pulse oximetry plethysmography from the signal acquired by the pulse oximeter; The apparatus determines whether the cutaneous sympathetic nerve activity is normal or not further based on the calculated information and / or data indicating changes in the analyzed waveform amplitude.

20. 17. The apparatus of claim 16, The device is configured to evaluate the skin conductance of two or more limbs and compare one limb having normal skin sympathetic nerve activity with one or more limbs not having normal skin sympathetic nerve activity.

21. 17. The apparatus of claim 16, The apparatus further comprises a skin electrodermal activity stimulation device configured to provide information on normal skin sympathetic nerve activity to define the skin sympathetic nerve activity that can be used for clinical assessments such as pain and arousal.

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