# US 2021/0275818 A1 · Neuromodulation for neuroinflammation treatments with parameters controlled using biomarkers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0275818 A1 - Document ID: US20210275818A1 - Status: Published application - Kind: A1 - Application number: 17/330,756 - Filed: 2021-05-26 - Published: 2021-09-09 - Earliest claimed: 2015-11-19 - Assignees: Boston Scientific Neuromodulation Corporation - Applicants: Boston Scientific Neuromodulation Corporation - Inventors: Bradley Lawrence Hershey; Changfang Zhu - Web page: https://patentgrep.com/patent/US20210275818A1 ## CPC - A61N 1/36139: {with automatic adjustment} - A61M 5/1723: {using feedback of body parameters, e.g. blood sugar or pressure} - A61N 1/36103: {Neuro-rehabilitation; Repair or reorganisation of neural tissue, e.g. after stroke} - A61N 2/002: {in combination with another treatment} - A61N 2/006: {for magnetic stimulation of nerve tissue} - A61N 5/0622: {Optical stimulation for exciting neural tissue} - A61M 5/14: Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor - A61N 2005/0626: {Monitoring, verifying, controlling systems and methods} - A61N 2005/0659: {infrared} - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} ## Abstract An example of a system for modulating neuroinflammation at a tissue site in a patient includes a neuromodulation output circuit, a memory, and a control circuit. The neuromodulation output circuit may be configured to deliver the neuromodulation. The memory may be configured to store a neuromodulation parameter set selected to modulate neural activity at the tissue site and a sensed biomarker parameter. The biomarker parameter may include a measure of a biomarker or a measure of a derivative of the biomarker. The biomarker may be indicative of the neuroinflammation at the tissue site. The control circuit may be configured to control the delivery of the neuromodulation using the neuromodulation parameter set and adjust one or more parameters of the neuromodulation parameter set using the biomarker parameter. ## Claims ### Claim 1 A method for delivering neuromodulation energy to a patient having a spinal cord, the method comprising: delivering the neuromodulation energy from an implantable neuromodulation device to the spinal cord through one or more implantable electrodes placed over the spinal cord to modulate neuroinflammation in the patient; controlling the delivery of the neuromodulation energy using neuromodulation parameters using a control circuit of the implantable neuromodulation device; determining a measure of a biomarker of neuroinflammation or a derivative of the biomarker of neuroinflammation; and adjusting the neuromodulation parameters using the determined measure of the biomarker using the control circuit. ### Claim 2 (depends on 1) The method of claim 1, wherein determining the measure of the biomarker of neuroinflammation or the derivative of the biomarker of neuroinflammation comprises determining the measure of the biomarker of neuroinflammation or the derivative of the biomarker of neuroinflammation using an imaging system. ### Claim 3 (depends on 1) The method of claim 1, wherein determining the measure of the biomarker of neuroinflammation or the derivative of the biomarker of neuroinflammation comprises sensing one or more biomarker parameters using one or more sensors. ### Claim 4 (depends on 3) The method of claim 3, wherein sensing the one or more biomarker parameters comprises sensing a quantitative measure of neuroinflammation in the spinal cord. ### Claim 5 (depends on 3) The method of claim 3, further comprising: comparing the one or more biomarkers each to a reference value or value range; and adjusting the neuromodulation parameters using an outcome of the comparison. ### Claim 6 (depends on 5) The method of claim 5, wherein the reference value or value range represents a threshold indicative of a need for treating the neuroinflammation, and the outcome of the comparison indicates the need. ### Claim 7 (depends on 5) The method of claim 5, wherein the reference value or value range represents a degree of the neuroinflammation, and the outcome of the comparison indicates an intensity of the neurostimulation needed for treating the neuroinflammation at the indicated degree. ### Claim 8 (depends on 1) The method of claim 1, wherein determining the measure of the biomarker of neuroinflammation or the derivative of the biomarker of neuroinflammation comprises determining a quantification of microglial cell activation. ### Claim 9 (depends on 1) The method of claim 1, wherein determining the measure of the biomarker of neuroinflammation or the derivative of the biomarker of neuroinflammation comprises determining a cytokine concentration. ### Claim 10 (depends on 1) The method of claim 1, wherein determining the measure of the biomarker of neuroinflammation or the derivative of the biomarker of neuroinflammation comprises determining a quantification of translocator protein levels. ### Claim 11 (depends on 1) The method of claim 1, wherein determining the measure of the biomarker of neuroinflammation or the derivative of the biomarker of neuroinflammation comprises determining a spatial measure indicative of a spatial distribution of the biomarker. ### Claim 12 (depends on 1) The method of claim 1, wherein determining the measure of the biomarker of neuroinflammation or the derivative of the biomarker of neuroinflammation comprises determining a temporal measure indicative of a change in the biomarker over time. ### Claim 13 (depends on 1) The method of claim 1, wherein determining the measure of the biomarker of neuroinflammation or the derivative of the biomarker of neuroinflammation comprises determining a measure of metabolism. ### Claim 14 A non-transitory computer-readable storage medium including instructions, which when executed by a system, cause the system to perform a method for delivering neuromodulation energy to a patient having a spinal cord, the method comprising: delivering the neuromodulation energy from an implantable neuromodulation device to the spinal cord through one or more implantable electrodes placed over the spinal cord to modulate neuroinflammation in the patient; controlling the delivery of the neuromodulation energy using neuromodulation parameters using a control circuit of the implantable neuromodulation device; determining a measure of a biomarker of neuroinflammation; and adjusting the neuromodulation parameters using the determined measure of the biomarker using the control circuit. ### Claim 15 (depends on 14) The non-transitory computer-readable storage medium of claim 14, wherein determining the measure of the biomarker of neuroinflammation or the derivative of the biomarker of neuroinflammation comprises sensing one or more biomarker parameters using one or more sensors. ### Claim 16 (depends on 15) The non-transitory computer-readable storage medium of claim 15, wherein sensing the one or more biomarker parameters comprises sensing a quantitative measure of neuroinflammation in the spinal cord. ### Claim 17 A system for delivering neuromodulation energy to a patient having a spinal cord, the system comprising: one or more implantable electrodes configured to be placed over the spinal cord; a neuromodulation output circuit configured to be coupled to the one or more implantable electrodes and to deliver neuromodulation energy to the spinal cord through the one or more implantable electrodes; and a control circuit configured to control the delivery of the neuromodulation energy using neuromodulation parameters, to determining a measure of a biomarker of neuroinflammation, and to adjust the neuromodulation parameters using the determined measure of the biomarker. ### Claim 18 (depends on 17) The system of claim 17, further comprising a biomarker sensor configured to sense the biomarker parameter, wherein the biomarker sensor is configured to sense the biomarker parameter being a measure of at least one of a translocator protein concentration, a measure of a temporal activation of the microglial cell, a measure of a spatial activation of the microglial cell, or a measure of or a cytokine concentration. ### Claim 19 (depends on 18) The system of claim 18, wherein the biomarker sensor is configured to sense a biomarker parameter indicative of an intensity of pain. ### Claim 20 (depends on 18) The system of claim 18, wherein the biomarker sensor is configured to sense a quantitative measure of neuroinflammation in the spinal cord.