# US 11,992,298 B2 · Systems and methods for predicting and treating neurological condition relapses > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,992,298 B2 - Document ID: US11992298B2 - Status: Granted - Kind: B2 - Application number: 18/495,656 - Filed: 2023-10-26 - Published: 2024-02-29 - Granted: 2024-05-28 - Earliest claimed: 2018-01-12 - Assignees: The Board of Trustees of the Leland Stanford Junior University - Applicants: The Board of Trustees of the Leland Stanford Junior University - Inventors: Nolan Williams; Keith Sudheimer - Web page: https://patentgrep.com/patent/US11992298B2 ## CPC - A61B 5/02405: {Determining heart rate variability} - A61B 5/165: {Evaluating the state of mind, e.g. depression, anxiety} - A61B 5/4836: {Diagnosis combined with treatment in closed-loop systems or methods (A61B5/0036 takes precedence)} - A61N 2/004: {specially adapted for a specific therapy} - A61N 2/006: {for magnetic stimulation of nerve tissue} - A61N 2/02: using magnetic fields produced by coils, including single turn loops or electromagnets (A61N2/12 takes precedence) - G01R 33/4806: {Functional imaging of brain activation} - G01R 33/4808: {Multimodal MR, e.g. MR combined with positron emission tomography [PET], MR combined with ultrasound or MR combined with computed tomography [CT]} - G01R 33/565: Correction of image distortions, e.g. due to magnetic field inhomogeneities - G16H 20/30: relating to physical therapies or activities, e.g. physiotherapy, acupressure or exercising - A61B 5/681: {Wristwatch-type devices} - A61B 2576/026: for the brain - G16H 50/30: for calculating health indices; for individual health risk assessment - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - 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) - G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12) - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA ## Abstract Systems and methods for predicting and treating relapses for neurological conditions in accordance with embodiments of the invention are illustrated. One embodiment includes a method for predicting and treating a clinical neurological condition relapse. The method includes steps for selecting a threshold heart rate variability value for a patient suffering from a clinical neurological condition, monitoring, using a cardiac monitor, the heart rate variability of the patient over time, providing an indicator that a relapse is imminent when the heart rate variability of the patient falls below the threshold heart rate variability value, and treating the patient using a transcranial magnetic stimulation device by applying an accelerated theta burst stimulation protocol where the transcranial magnetic stimulation target is the left prefrontal dorsolateral cortex. ## Claims ### Claim 1 A closed-loop neurostimulation system, comprising: an implantable neurostimulator; a heart rate monitor; and a controller, where the controller is configured to: receive a threshold heart rate variability value for a patient; continuously monitor the patient's heart rate variability using the heart rate monitor; and apply at least two accelerated intermittent theta burst stimulation (aiTBS) sessions to a brain of the patient using the implantable neurostimulator in response to the patient's heart rate variability rising above the threshold heart rate variability value in order to treat a neuropsychiatric condition of the patient, where the at least two sessions are separated by an intersession interval of between 25 and 120 minutes. ### Claim 2 (depends on 1) The closed-loop neurostimulation system of claim 1, wherein the controller is further configured to continuously apply aiTBS sessions separated by the intersession interval until the patient's heart rate variability drops below the threshold heart rate variability value. ### Claim 3 (depends on 1) The closed-loop neurostimulation system of claim 1, wherein to obtain the threshold heart rate variability value, the controller is configured to: obtain a baseline asymptomatic heart rate variability value for the patient and a baseline symptomatic heart rate variability value for the patient; and determine the midpoint between the asymptomatic heart rate variability value for the patient and the symptomatic heart rate variability value for the patient. ### Claim 4 (depends on 1) The closed-loop neurostimulation system of claim 1, wherein the cardiac monitor is a smart watch. ### Claim 5 (depends on 1) The closed-loop neurostimulation system of claim 1, wherein the controller, the neurostimulator, and the cardiac monitor are wirelessly coupled. ### Claim 6 (depends on 1) The closed-loop neurostimulation system of claim 1, wherein the implantable neurostimulator is configured to deliver electrical neurostimulation. ### Claim 7 (depends on 1) The closed-loop neurostimulation system of claim 1, wherein the controller is further configured to deliver an alert when the patient's heart rate variability rises above the threshold heart rate variability value. ### Claim 8 (depends on 7) The closed-loop neurostimulation system of claim 7, wherein the alert is transmitted to a medical server in order to alert medical professionals responsible for care of the patient. ### Claim 9 (depends on 1) The closed-loop neurostimulation of claim 1, wherein the implantable neurostimulator is implanted as to stimulate the left dorsolateral prefrontal cortex of the brain of the patient. ### Claim 10 (depends on 1) The closed-loop neurostimulation of claim 1, wherein the implantable neurostimulator is implanted as to stimulate anterior cingulate cortex of the brain of the patient. ### Claim 11 A method for closed-loop neurostimulation, comprising: receiving a threshold heart rate variability value for a patient; continuously monitoring the patient's heart rate variability using a heart rate monitor and a controller; and applying at least two accelerated intermittent theta burst stimulation (aiTBS) sessions to a brain of the patient using an implantable neurostimulator in response to the patient's heart rate variability rising above the threshold heart rate variability value in order to treat a neuropsychiatric condition of the patient, where the at least two sessions are separated by an intersession interval of between 25 and 120 minutes. ### Claim 12 (depends on 11) The method of closed-loop neurostimulation of claim 11, further comprising continuously applying aiTBS sessions separated by the intersession interval until the patient's heart rate variability drops below the threshold heart rate variability value. ### Claim 13 (depends on 11) The method of closed-loop neurostimulation of claim 11, further comprising obtaining the threshold heart rate variability by: obtaining a baseline asymptomatic heart rate variability value for the patient and a baseline symptomatic heart rate variability value for the patient; and determining the midpoint between the asymptomatic heart rate variability value for the patient and the symptomatic heart rate variability value for the patient. ### Claim 14 (depends on 11) The method of closed-loop neurostimulation of claim 11, wherein the cardiac monitor is a smart watch. ### Claim 15 (depends on 11) The method of closed-loop neurostimulation of claim 11, wherein the controller, the neurostimulator, and the cardiac monitor are wirelessly coupled. ### Claim 16 (depends on 11) The method of closed-loop neurostimulation of claim 11, wherein the implantable neurostimulator is configured to deliver electrical neurostimulation. ### Claim 17 (depends on 11) The method of closed-loop neurostimulation of claim 11, further delivering an alert when the patient's heart rate variability rises above the threshold heart rate variability value. ### Claim 18 (depends on 17) The method of closed-loop neurostimulation of claim 17, further comprising transmitting the alert to a medical server in order to alert medical professionals responsible for care of the patient. ### Claim 19 (depends on 11) The method of closed-loop neurostimulation of claim 11, wherein the implantable neurostimulator is implanted as to stimulate the left dorsolateral prefrontal cortex of the brain of the patient. ### Claim 20 (depends on 11) The method of closed-loop neurostimulation of claim 11, wherein the implantable neurostimulator is implanted as to stimulate anterior cingulate cortex of the brain of the patient.