# US 10,500,398 B2 · Neurostimulation titration process via adaptive parametric modification > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,500,398 B2 - Document ID: US10500398B2 - Status: Granted - Kind: B2 - Application number: 15/360,188 - Filed: 2016-11-23 - Published: 2017-04-20 - Granted: 2019-12-10 - Earliest claimed: 2014-11-12 - Assignees: LivaNova USA, Inc. - Applicants: LivaNova USA, Inc. - Inventors: Imad Libbus; Bruce H. KenKnight; Badri Amurthur; Scott R. Stubbs - Web page: https://patentgrep.com/patent/US10500398B2 ## CPC - A61N 1/36139: {with automatic adjustment} - A61B 5/355: Detecting T-waves - A61N 1/0551: {Spinal or peripheral nerve electrodes} - A61N 1/36114: {Cardiac control, e.g. by vagal stimulation (stimulating the heart A61N1/362)} - A61N 1/36132: {using patient feedback} - A61N 1/3615: {Intensity} - A61N 1/36167: {Timing, e.g. stimulation onset} - A61N 1/3702: {Physiological parameters (A61N1/365 takes precedence; evoked response A61N1/371)} - A61N 1/37223: {Circuits for electromagnetic coupling} - A61N 1/37235: {Aspects of the external programmer} - G16H 20/30: relating to physical therapies or activities, e.g. physiotherapy, acupressure or exercising - G16H 20/40: relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture - G16H 40/20: for the management or administration of healthcare resources or facilities, e.g. managing hospital staff or surgery rooms - G16H 40/63: for local operation - G16Z 99/00: Subject matter not provided for in other main groups of this subclass - 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) - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA - G16Z: INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS, NOT OTHERWISE PROVIDED FOR ## Abstract Systems and methods are provided for delivering neurostimulation therapies to patients. A titration process is used to gradually increase the stimulation intensity to a desired therapeutic level. Between titration sessions one or more parameters, such as, for example, an acclimation interval, may be adjusted based on the patient's response to the stimulation. This personalized titration process can minimize the amount of time required to complete titration so as to begin delivery of the stimulation at therapeutically desirable levels. ## Claims ### Claim 1 A method of operating an implantable medical device (IMD) comprising a neurostimulator coupled to an electrode assembly, said method comprising: initiating a plurality of titration sessions, each titration session separated from an adjacent titration session by an acclimation interval, wherein the titration sessions comprise activating the IMD to deliver a stimulation signal of gradually increasing intensity until the patient exceeds a side effect tolerance zone boundary, wherein the stimulation signal comprises a frequency in a range of 5 Hz to 10 Hz; analyzing an outcome measure of the plurality of titration sessions including determining whether the outcome measure indicates expected patient adaptation; and modifying one or more stimulation parameters based on the analyzed outcome measure relative to the expected patient adaptation. ### Claim 2 (depends on 1) The method according to claim 1, wherein modifying one or more stimulation parameters comprises modifying the acclimation interval until a subsequent titration session based on the analyzed outcome measure. ### Claim 3 (depends on 2) The method according to claim 2, wherein modifying the acclimation interval comprises at least one of: increasing the acclimation interval in response to the outcome measure indicating slower than expected patient adaptation, increasing the acclimation interval in response to the outcome measure indicating a failure to achieve a target increase in stimulation intensity, increasing the acclimation interval in response to the outcome measure indicating a failure to achieve a target increase in output current over the plurality of titration sessions, wherein the stimulation signal comprises the output current, or decreasing the acclimation interval before the subsequent titration session in response to the outcome measure indicating faster than expected patient adaptation. ### Claim 4 (depends on 2) The method according to claim 2, further comprising, during the acclimation intervals, activating the IMD to deliver the stimulation signal at an intensity resulting in an acceptable side effect level. ### Claim 5 (depends on 1) The method according to claim 1, further comprising: determining a maintenance dosage level corresponding to a tolerable stimulation intensity achieving adequate adaptation; and delivering stimulation at the maintenance dosage level. ### Claim 6 (depends on 1) The method according to claim 1, further comprising receiving a patient input indicating the side effect tolerance zone boundary by at least one of: receiving a radio frequency (RF) signal from an external communications device, said RF signal indicating that the patient has reached the side effect tolerance zone boundary, detecting a magnetic field indicating that the patient has reached the side effect tolerance zone boundary, detecting an acoustic signal indicating that the patient has reached the side effect tolerance zone boundary, or detecting a motion signal with a motion sensor indicating that the patient has reached the side effect tolerance zone boundary. ### Claim 7 (depends on 1) The method according to claim 1, further comprising: initiating an elevated stimulation session at an elevated stimulation intensity for a first period of time; and after the first period of time, initiating sustained stimulation at a sustained stimulation intensity for a second period of time, wherein the elevated stimulation intensity is greater than the sustained stimulation intensity. ### Claim 8 A method of operating an implantable medical device (IMD) comprising a neurostimulator coupled to an electrode assembly, said method comprising: initiating a plurality of titration sessions, each titration session separated from an adjacent titration session by an acclimation interval, wherein the titration sessions comprise activating the IMD to deliver a stimulation signal of gradually increasing intensity until the patient exceeds a side effect tolerance zone boundary, wherein the stimulation signal comprises a frequency in a range of 5 Hz to 10 Hz; analyzing an outcome measure of the plurality of titration sessions; and modifying one or more stimulation parameters based on the analyzed outcome measure. ### Claim 9 (depends on 8) The method according to claim 8, further comprising: delivering the frequency of the stimulation signal at 10 Hz; and upon the patient exceeding the side effect tolerance zone boundary, decreasing the frequency to 5 Hz. ### Claim 10 (depends on 8) The method according to claim 8, wherein modifying one or more stimulation parameters comprises modifying the acclimation interval until a subsequent titration session based on the analyzed outcome measure. ### Claim 11 (depends on 10) The method according to claim 10, wherein modifying the acclimation interval comprises at least one of: increasing the acclimation interval in response to the outcome measure indicating slower than expected patient adaptation, increasing the acclimation interval in response to the outcome measure indicating a failure to achieve a target increase in stimulation intensity, increasing the acclimation interval in response to the outcome measure indicating a failure to achieve a target increase in output current over the plurality of titration sessions, wherein the stimulation signal comprises the output current, or decreasing the acclimation interval before the subsequent titration session in response to the outcome measure indicating faster than expected patient adaptation. ### Claim 12 (depends on 10) The method according to claim 10, further comprising, during the acclimation intervals, activating the IMD to deliver the stimulation signal at an intensity resulting in an acceptable side effect level. ### Claim 13 (depends on 8) The method according to claim 8, further comprising: determining a maintenance dosage level corresponding to a tolerable stimulation intensity achieving adequate adaptation; and delivering stimulation at the maintenance dosage level. ### Claim 14 (depends on 8) The method according to claim 8, further comprising receiving a patient input indicating the side effect tolerance zone boundary by at least one of: receiving a radio frequency (RF) signal from an external communications device, said RF signal indicating that the patient has reached the side effect tolerance zone boundary, detecting a magnetic field indicating that the patient has reached the side effect tolerance zone boundary, detecting an acoustic signal indicating that the patient has reached the side effect tolerance zone boundary, or detecting a motion signal with a motion sensor indicating that the patient has reached the side effect tolerance zone boundary. ### Claim 15 (depends on 8) The method according to claim 8, further comprising: initiating an elevated stimulation session at an elevated stimulation intensity for a first period of time; and after the first period of time, initiating sustained stimulation at a sustained stimulation intensity for a second period of time, wherein the elevated stimulation intensity is greater than the sustained stimulation intensity. ### Claim 16 An implantable medical device comprising: an electrode assembly; a neurostimulator coupled to the electrode assembly, the neurostimulator configured to: initiate a plurality of titration sessions, each titration session separated from an adjacent titration session by an acclimation interval, wherein the titration sessions comprise activating the implantable medical device to deliver a stimulation signal of gradually increasing intensity until the patient exceeds a side effect tolerance zone boundary, wherein the stimulation signal comprises a frequency in a range of 5 Hz to 10 Hz; analyze an outcome measure of the plurality of titration sessions; and modify one or more stimulation parameters based on the analyzed outcome measure. ### Claim 17 (depends on 16) The implantable medical device according to claim 16, wherein the neurostimulator is configured to: deliver the frequency of the stimulation signal at 10 Hz; and upon the patient exceeding the side effect tolerance zone boundary, decrease the frequency to 5 Hz. ### Claim 18 (depends on 16) The implantable medical device according to claim 16, wherein the neurostimulator is configured to modify the acclimation interval until a subsequent titration session based on the analyzed outcome measure. ### Claim 19 (depends on 18) The implantable medical device according to claim 18, wherein the neurostimulator is configured to modify the acclimation interval by at least one of: increasing the acclimation interval in response to the outcome measure indicating slower than expected patient adaptation, increasing the acclimation interval in response to the outcome measure indicating a failure to achieve a target increase in stimulation intensity, increasing the acclimation interval in response to the outcome measure indicating a failure to achieve a target increase in output current over the plurality of titration sessions, wherein the stimulation signal comprises the output current, or decreasing the acclimation interval before the subsequent titration session in response to the outcome measure indicating faster than expected patient adaptation. ### Claim 20 (depends on 16) The implantable medical device according to claim 16, wherein the neurostimulator is configured to receive a patient input indicating the side effect tolerance zone boundary by at least one of: receiving a radio frequency (RF) signal from an external communications device, said RF signal indicating that the patient has reached the side effect tolerance zone boundary, detecting a magnetic field indicating that the patient has reached the side effect tolerance zone boundary, detecting an acoustic signal indicating that the patient has reached the side effect tolerance zone boundary, or detecting a motion signal with a motion sensor indicating that the patient has reached the side effect tolerance zone boundary.