IP Library Granted Patent US 12,224,049
Granted Patent B2
US 12,224,049 · App. 17/643,363 · Granted Feb 11, 2025

Systems and methods for monitoring and managing neurological diseases and conditions

Inventors: Rachel Kuperman (Piedmont, CA); Parth Amin (Cary, NC); Bikramjit Sarkar (San Diego, CA)
Assignee: Eysz, Inc.
G16H20/10G16H40/63
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Quick Facts
Patent No.
US 12,224,049
App. No.
17/643,363
Granted
Feb 11, 2025
Kind
B2
Abstract

Systems and methods for monitoring and managing neurological diseases and conditions are disclosed herein. In some embodiments, a method for monitoring a patient having a neurological disease or condition includes receiving, from one or more patient monitoring devices, first patient data for a baseline time period. The method can include determining, based on the first patient data, first seizure data and first side effect data during the baseline time period. The method can further include receiving, from the one or more patient monitoring devices, second patient data for a treatment time period, and determining, based on the second patient data, second seizure data and second side effect data during the treatment time period. The method can also include generating a personalized dose-response profile for the patient based on the first and second seizure data and the first and second side effect data.

Claims (37)

1. A computer-implemented method for monitoring a patient having a neurological disease or condition, the method comprising:

receiving, from one or more patient monitoring devices configured to produce eye movement data, first patient data for a baseline time period before the patient has started taking medication for the neurological disease or condition;

determining, based on the first patient data, first seizure data and first side effect data during the baseline time period;

receiving, from the one or more patient monitoring devices, second patient data for a treatment time period in which the patient is taking the medication;

determining, based on the second patient data, second seizure data and second side effect data during the treatment time period;

generating and outputting a visualization of a personalized dose-response profile for the patient, wherein the visualization of the personalized dose-response profile comprises: (1) a visual representation of a therapeutic profile representing a relationship between seizure control and different dosages of the medication determined based on the first and second seizure data, and (2) a visual representation of a toxicity profile representing a relationship between side effect severity and the different dosages of the medication determined based on the first and second side effect data; and

outputting a treatment recommendation for the patient, wherein the treatment recommendation comprises administering a dose of the medication to the patient to treat the neurological disease or condition, and wherein the dosage is selected based on the personalized dose-response profile.

2. The computer-implemented method of claim 1 , wherein the neurological disease or condition comprises epilepsy or a disorder having epilepsy as a symptom.

3. The computer-implemented method of claim 1 , wherein the one or more patient monitoring devices comprise an eye tracking device.

4. The computer-implemented method of claim 1 , wherein the eye movement data includes one or more of the following: blink rate, blink duration, eye eccentricity, eye gaze angle, pupil size, pupil constriction amount, pupil constriction velocity, pupil dilation amount, pupil dilation velocity, pupil location, pupil rotation, pupil area to iris area ratio, hippus, eyelid movement rate, eyelid openings, eyelid closures, eyelid height, upward eyeball movements, downward eyeball movements, lateral eyeball movements, eye rolling, jerky eye movements, saccadic velocity, saccadic direction, torsional velocity, torsional direction, gaze direction, gaze scanning patterns, or eye activity during sleep.

5. The computer-implemented method of claim 1 , wherein the one or more patient monitoring devices comprise one or more of the following: a facial tracking device, a brain monitoring device, a mobile device, an implantable device, a wearable device, or a computing device.

6. The computer-implemented method of claim 1 , wherein the first and second seizure data include data representing one or more of a type, a timing, an ictal duration, a postictal duration, a frequency, a severity, or a variability of at least one seizure event experienced by the patient.

7. The computer-implemented method of claim 6 , wherein the at least one seizure event comprises one or more of the following: an absence seizure, an atypical absence seizure, a tonic-clonic seizure, a clonic seizure, a tonic seizure, an atonic seizure, a myoclonic seizure, a simple partial seizure, a complex partial seizure, a secondary generalized seizure, or an infantile spasm.

8. The computer-implemented method of claim 1 , further comprising comparing the first and second seizure data to determine a change in seizure burden between the baseline time period and the treatment time period.

9. The computer-implemented method of claim 1 , wherein the first and second side effect data include data representing one or more of a type, a timing, a duration, a frequency, or a severity of at least one side effect experienced by the patient.

10. The computer-implemented method of claim 9 , wherein the at least one side effect comprises one or more of the following: drowsiness, a decrease in cognition, a decrease in attention, a decrease in concentration, a change in mood, a change in behavior, a change in memory loss of consciousness, suicidality, homicidality, irritability, or a change in vision.

11. The computer-implemented method of claim 1 , further comprising comparing the first and second side effect data to determine a change in side effect severity between the baseline time period and the treatment time period.

12. A computer-implemented method for managing epilepsy, the method comprising:

receiving, from an eye tracking device, first eye movement data of a patient during a baseline period before the patient has started taking a medication for the epilepsy;

determining, based on the first eye movement data, first seizure burden data and first neurocognitive data for the patient during the baseline period;

receiving, from the eye tracking device, second eye movement data of the patient during a treatment period in which the patient is taking the medication;

determining, based on the second eye movement data, second seizure burden data and second neurocognitive data for the patient during the treatment period;

generating and outputting a visualization of a personalized dose-response profile for the patient, wherein the visualization of the personalized dose-response profile comprises: (1) a visual representation of a therapeutic profile representing a relationship between seizure control and different dosages of the medication determined based on the first and second seizure burden data, and (2) a visual representation of a toxicity profile representing a relationship between neurocognitive state and the different dosages of the medication determined based on the first and second neurocognitive data; and

outputting a treatment recommendation for the patient, wherein the treatment recommendation comprises administering a dosage of the medication to the patient to treat the epilepsy, and wherein the dosage is selected based on the personalized dose-response profile.

13. The computer-implemented method of claim 12 , wherein:

the first and second seizure burden data are determined from the first and second eye movement data using a first set of algorithms, and

the first and second neurocognitive data are determined from the first and second eye movement data using a second set of algorithms.

14. The computer-implemented method of claim 13 , wherein the first set of algorithms includes at least one machine learning algorithm trained on seizure data from a plurality of patients, and the second set of algorithms includes at least one machine learning algorithm trained on interictal data from a plurality of patients.

15. The computer-implemented method of claim 12 , further comprising:

receiving, from the eye tracking device, third eye movement data for a subsequent treatment period during which the patient is taking a different dosage of the medication, and

determining, based on the third eye movement data, third seizure burden data and third neurocognitive data during the subsequent treatment period,

wherein the personalized dose-response profile for the patient is generated based on the third seizure burden data and the third neurocognitive data.

16. The computer-implemented method of claim 12 , further comprising receiving additional patient data, wherein one or more of the first seizure burden data, first neurocognitive data, second seizure burden data, or second neurocognitive data are determined based on the additional patient data, and wherein the additional patient data is received from one or more of the following: a facial tracking device, a brain monitoring device, a mobile device, an implantable device, a wearable device, or a computing device.

17. The computer-implemented method of claim 12 , wherein the treatment recommendation is determined using a machine learning algorithm trained on dose-response profiles from a plurality of patients.

18. The computer-implemented method of claim 12 , wherein the first and second neurocognitive data include data representing one or more of a type, a timing, a duration, a frequency, or a severity of at least one change to the patient's attention, mood, or memory.

19. The computer-implemented method of claim 12 , wherein the eye tracking device comprises a camera of a mobile device.

20. The computer-implemented method of claim 12 , wherein the visualization of the personalized dose-response profile further comprises a visual representation of a natural history curve indicating changes to the patient's baseline neurocognitive state.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 25, 2022
From: KUPERMAN, RACHEL; AMIN, PARTH; SARKAR, BIKRAMJIT
To: EYSZ, INC.
Reel/Frame 061522/0888 →
Continuity (2)
Provisional Application 63123402 · Dec 9, 2020
Related Publication 20220180993A1 · Jun 9, 2022
References Cited (122)
US 6315740B1 · Singh · 2001 [cited by applicant]
US 7643655B2 · Liang et al. · 2010 [cited by applicant]
US 8852100B2 · Osorio · 2014 [cited by applicant]
US 8868172B2 · Leyde et al. · 2014 [cited by applicant]
US 9460400B2 · De Bruin et al. · 2016 [cited by applicant]
US 9655515B2 · Schroeder et al. · 2017 [cited by applicant]
US 10039445B1 · Torch · 2018 [cited by applicant]
US 10172550B2 · Osorio · 2019 [cited by applicant]
US 10685748B1 · Chappell et al. · 2020 [cited by applicant]
US 20020010352A1 · Llatas et al. · 2002 [cited by applicant]
US 20020103512A1 · Echauz et al. · 2002 [cited by applicant]
US 20040234103A1 · Steffein · 2004 [cited by applicant]
US 20040267152A1 · Pineda · 2004 [cited by applicant]
US 20060190419A1 · Bunn et al. · 2006 [cited by applicant]
US 20080208072A1 · Fadem et al. · 2008 [cited by applicant]
US 20090005860A1 · Gale et al. · 2009 [cited by applicant]
US 20090058660A1 · Torch · 2009 [cited by applicant]
US 20110257517A1 · Guttag et al. · 2011 [cited by applicant]
US 20110263946A1 · El et al. · 2011 [cited by applicant]
US 20120008370A1 · Yasuda et al. · 2012 [cited by applicant]
US 20120083700A1 · Osorio · 2012 [cited by examiner]
US 20120101401A1 · Faul et al. · 2012 [cited by applicant]
US 20140275840A1 · Osorio · 2014 [cited by applicant]
US 20150126845A1 · Jin et al. · 2015 [cited by applicant]
US 20150223731A1 · Sahin · 2015 [cited by examiner]
US 20150227702A1 · Krishna et al. · 2015 [cited by applicant]
US 20160022136A1 · Ettenhofer et al. · 2016 [cited by applicant]
US 20170049395A1 · Cao · 2017 [cited by applicant]
US 20170150930A1 · Shikii et al. · 2017 [cited by applicant]
US 20170164893A1 · Narayan et al. · 2017 [cited by applicant]
US 20170188895A1 · Nathan · 2017 [cited by examiner]
US 20170196497A1 · Ray · 2017 [cited by examiner]
US 20170258390A1 · Howard · 2017 [cited by applicant]
US 20170347878A1 · Milea · 2017 [cited by examiner]
US 20180012090A1 · Herbst · 2018 [cited by applicant]
US 20180088669A1 · Ramaprakash et al. · 2018 [cited by applicant]
US 20180125404A1 · Bott et al. · 2018 [cited by applicant]
US 20180184002A1 · Thukral et al. · 2018 [cited by applicant]
US 20180247119A1 · Ryan et al. · 2018 [cited by applicant]
US 20180289285A1 · Vardas et al. · 2018 [cited by applicant]
US 20190019581A1 · Vaughan et al. · 2019 [cited by applicant]
US 20190076657A1 · Stubbs · 2019 [cited by examiner]
US 20190254580A1 · Bonneh et al. · 2019 [cited by applicant]
US 20190328262A1 · Osorio · 2019 [cited by applicant]
US 20200085369A1 · Vu et al. · 2020 [cited by applicant]
US 20200187845A1 · Nathan et al. · 2020 [cited by applicant]
US 20210000341A1 · Kuperman · 2021 [cited by applicant]
US 20210319872A1 · Valentine · 2021 [cited by examiner]
US 20220022805A1 · Kuperman et al. · 2022 [cited by applicant]
US 20230062081A1 · Kuperman et al. · 2023 [cited by applicant]
AU 2021102414A4 · 2021 [cited by applicant]
EP 3761849A4 · 2022 [cited by applicant]
GB 2571265A · 2019 [cited by applicant]
IN 202041027872A · 2020 [cited by applicant]
JP 2017100039A · 2017 [cited by applicant]
KR 20120053389A · 2012 [cited by applicant]
WO 2010015029A1 · 2010 [cited by applicant]
WO 2017087680A1 · 2017 [cited by applicant]
WO 2019013456A1 · 2019 [cited by applicant]
WO 2019173106A1 · 2019 [cited by applicant]
WO 2019207510A1 · 2019 [cited by applicant]
WO 2022126114A1 · 2022 [cited by applicant]
WO 2023034816A1 · 2023 [cited by applicant]
Thomson KE, Metcalf CS, Newell TG, Huff J, Edwards SF, West PJ, Wilcox KS. Evaluation of subchronic administration of antiseizure drugs in spontaneously seizing rats. Epilepsia. Jun. 2020;61(6):1301-1311. doi: 10.1111/e… [cited by examiner]
Lunn J, Donovan T, Litchfield D, Lewis C, Davies R, Crawford T. Saccadic Eye Movement Abnormalities in Children with Epilepsy. PLoS One. Aug. 2, 2016;11(8):e0160508. doi: 10.1371/journal.pone.0160508. PMID: 27483011; PM… [cited by examiner]
Akman, et al., “Seizure Frequency in Children with Epilepsy: Factors Influencing Accuracy and Parental Awareness”, Seizure; 18(7); pp. 524-529, 2009. [cited by applicant]
Devinsky, “Effects of Seizures on Autonomic and Cardiovascular Function”, Epilepsy Curr, 4(2); pp. 43-46, 2004. [cited by applicant]
Malone, et al., “Interobserver Agreement in Neonatal Seizure Identification”, Epilepsia 50(9); pp. 2097-2101.(2009). [cited by applicant]
Meier, et al., “Detecting Epileptic Seizures in Long-Term Human EEG: A New Approach to Automatic Online and Real-Time Detection and Classification of Polymorphic Seizure PatternH”, J Clin Neurophysiol., 25(3); pp. 119-1… [cited by applicant]
Scaramelli, et al., “Prodromal Symptoms in Epileptic Patients: Clinical Characterization of the Pre-Ictal Phase”, Seizure 18(4); pp. 246-250.(2009). [cited by applicant]
European Patent Office, International Search Report and Written Opinion for PCT/US2021/072810, issued Apr. 12, 2022, 12 pages. [cited by applicant]
“Epihunter Absence: Phase 3, prospective, multicenter validation study”, retrieved from URL: https://www.epihunter.com/hubfs/Epihunter%20Absence%20Phase%203%2C%20prospective%2C%20multicenter%20validation%20study.pdf, 2 … [cited by applicant]
Adams , et al., “Hyperventilation and 6-hour EEG recording in evaluation of absence seizures”, Neurology, vol. 31, Sep. 1981, pp. 1175-1177. [cited by applicant]
Afifi , et al., “Seizure-Induced Miosis and Ptosis: Association with Temporal Lobe Magnetic Resonance Imaging Abnormalities”, Journal of Child Neurology, vol. 5, No. 2, Apr. 1990, pp. 142-146. [cited by applicant]
Bauder , et al., “Neonatal Seizures: Eyes Open or Closed?”, Epilepsia, vol. 48, No. 2, 2007, pp. 394-396. [cited by applicant]
Centeno , et al., “Epilepsy causing pupillary hippus: an unusual semiology”, Epilepsia, vol. 52, No. 8, 2001, pp. e93-e96. [cited by applicant]
Chung , et al., “Ictal eye closure is a reliable indicator for psychogenic nonepileptic seizures”, Neurology, vol. 66, 2006, pp. 1730-1731. [cited by applicant]
Detoledo , et al., “Patterns of involvement of facial muscles during epileptic and nonepileptic events: Review of 654 events”, Neurology, vol. 47, 1996, pp. 621-625. [cited by applicant]
Elmali , et al., “Evaluation of absences and myoclonic seizures in adults with genetic (idiopathic) generalized epilepsy: a comparison between self-evaluation and objective evaluation based on home video-EEG telemetry”,… [cited by applicant]
Eyeware , “Head & Eye Tracker Software”, AI-powered head and eye tracking software that supercharges webcams and 3D sensors, 9 Pages. [cited by applicant]
Hunter , “epihunter Video”, retrieved from URL: https://www.epihunter.com/en/epihunter-video?hsLang=en-US, Aug. 12, 2022, 4 Pages. [cited by applicant]
Kaplan , “Gaze Deviation from Contralateral Pseudoperiodic Lateralized Epileptiform Discharges (PLEDs)”, Epilepsia, vol. 46, No. 6, 2005, pp. 977-979. [cited by applicant]
Kaplan , et al., “Neurophysiologic and clinical correlations of epileptic nystagmus”, Neurology, vol. 43, No. 12, Dec. 1993, pp. 2508-2514. [cited by applicant]
Kaplan , et al., “Vertical and horizontal epileptic gaze deviation and nystagmus”, Neurology, vol. 39, No. 10, Oct. 1989, pp. 1391-1393. [cited by applicant]
Korff , et al., “Paroxysmal Events in Infants: Persistent Eye Closure Makes Seizures Unlikely”, Pediatrics, vol. 116, No. 4, Oct. 2005, pp. e485-e486. [cited by applicant]
Lal , “Non-EEG Physiological Signal Based Seizure Monitoring System”, Embrace (K172935), Dec. 27, 2017, 8 Pages. [cited by applicant]
Lee , et al., “Epileptic nystagmus: A case report and systematic review”, Epilepsy & Behavior Case Reports, vol. 18, No. 2, 2014, pp. 156-160. [cited by applicant]
Orren , et al., “Relation Between Ocular Manifestations and Onset of Spike-and-Wave Discharges in Petit Mal Epilepsy”, Epilpesia, vol. 16, Aug. 25, 1975, pp. 771-779. [cited by applicant]
Rafal , et al., “Seizures triggered by blinking in a non-photosensitive epileptic”, Journal of Neurology, Neurosurgery, and Psychiatry, vol. 49, 1986, pp. 445-447. [cited by applicant]
Seizure Tracker LLC , “Seizure Tracker™—Record and share videos of seizures with your care providers”, retrieved from URL: https://seizuretracker.com, 3 Pages. [cited by applicant]
Stafstrom , et al., “Diagnosing and managing childhood absence epilepsy by telemedicine”, Epilepsy & Behavior, 2020, 3 Pages. [cited by applicant]
Stolz , et al., “Epileptic Nystagmus”, Epilepsia, vol. 32, No. 6, 1991, pp. 910-918. [cited by applicant]
Thurston , et al., “Epileptic gaze deviation and nystagmus”, Neurology, vol. 35, No. 10, Oct. 1985, pp. 1518-1521. [cited by applicant]
Tusa , et al., “Ipsiversive eye deviation and epileptic nystagmus”, Neurology, vol. 40, No. 4, Apr. 1990, pp. 662-665. [cited by applicant]
Umoove , “Software only Face and Eye Tracking on mobile devices”, The Technology, URL: umoove.me/technology.html, retrieved on Aug. 18, 2022, 3 Pages. [cited by applicant]
Watanabe , et al., “Epileptic Nystagmus Associated with Typical Absence Seizures”, Epilepsia, vol. 25, No. 1, 1984, pp. 22-24. [cited by applicant]
Watemberg , et al., “Adding Video Recording Increases the Diagnostic Yield of Routine Electroencephalograms in Children with Frequent Paroxysmal Events”, Epilepsia, vol. 46, No. 5, 2005, pp. 716-719. [cited by applicant]
“Soldier Mounted Eye Com 7 & 8 Eye Monitoring Biosensor, Communicator & Controller”, SBIR.gov, 4 pages, https://www.sbir.gov/sbirsearch/detail/349032; accessed May 13, 2020. [cited by applicant]
An, Na, Decline of Dosage Regimen Patents in Light of Emerging Next-Generation DNA Sequencing Technology and Possible Strategic Responses, 17 Minn. J.L. Sci. & Tech. 907 (2016). [cited by applicant]
Coelho et al., Electrooculogram and Submandibular Montage to Distinguish Different Eye, Eyelid, and Tonge Movements in Electroencephalographic Studies, Clinical Neurophysiology, 129(11), pp. 2380-2391 (2018). [cited by applicant]
St. Louis, EK, Minimizing AED Adverse Effects: Improving Quality of Life in the Interictal State in Epilepsy Care, Current Neuropharmacology, 2009, 7, 106-114. [cited by applicant]
Eckstein, Maria K. et al., Beyond eye gaze: What else can eyetracking reveal about cognition and cognitive development?, Development Cognitive Neuroscience 25 (2017) 69-71. [cited by applicant]
Fishman, Jesse et al., Antiepileptic Drug Titration and Related Health Care Resource Use and Costs, Journal of Managed Care & Specialty Pharmacy, 2018; 24(9):929-38. [cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/US2019/020116; dated May 13, 2019; 10 pages. [cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/US2021/042517; dated Nov. 9, 2021; 10 pages. [cited by applicant]
Kane, N., et al., Hyperventilation during electroencephalography: Safety and efficacy, Seizure 23 (2014) 129-134. [cited by applicant]
Kessler, Sudha Kilaru et al., A Practical Guide to Treatment of Childhood Absence Epilepsy, Pediatric Drugs, (2019) 21:15-24. [cited by applicant]
Kessler, Suha Kilaru et al., Pretreatment seizure semiology in childhood absence epilepsy, American Academy of Neurology, 89, 2017, 673-679. [cited by applicant]
Lee et al., Automated epileptic seizure waveform detection method based on the feature of the mean slope of wavelet coefficient counts using a hidden Markov model and EEG signals, ETRI Journal, 42(2):217-229 (2020). [cited by applicant]
Lempert, Thomas et al., The eye movements of syncope, American Academy of Neurology, 1996; 46: 1086-1088. [cited by applicant]
Luke, Steven G. et al., Predicting eye-movement characteristics across multiple tasks from working memory and executive control, Memory & Cognition, (2018), 46: 826-839. [cited by applicant]
Lunn et al., Saccadic Eye Movement Abnormalities in Children with Epilepsy, PLoS One,11(8): e0160508 (2016). [cited by applicant]
Van Dijkman et al., Pharmacotherapy in pediatric epilepsy: from trial and error to rational drug and dose selection—a long way to go, Expert Opinion on Drug Metabolism & Toxicology, 12:10, 1143-1156, 2016. [cited by applicant]
Panayiotopoulos, C.P., Typical absence seizures and their treatment, Arch Dis Child, 1999, 81: 351-355. [cited by applicant]
Perucca, Emilio et al., Overtreatment in Epilepsy How It Occurs and How It Can Be Avoided, CNS Drugs, 2005, 19(11): 897-908. [cited by applicant]
Rayner, Keith, Eye Movements in Reading and Information Processing: 20 Years of Research, Psychological Bulletin, 1998, vol. 124, No. 3, 372-422. [cited by applicant]
Reilly, James L., Pharmacological treatment effects on eye movement control, Brain Cognition, Dec. 2008; 68(3): 415-435. [cited by applicant]
Van De Val, et al., Non-EEG Seizure Detection Systems and Potential SUDEP Prevention: State of the Art, Seizure 41,141-153 (2016). [cited by applicant]
Richardson, Elizabeth J. et al., Structural and functional neuroimaging correlates of depression in temporal lobe epilepsy, Epilepsy & Behavior, 10 (2007), 242-249. [cited by applicant]
Rozenblat, T. et al., Absence seizure provocation during routine EEG: Does position of the child during hyperventilation affect the diagnostic yield, Seizure: European Journal of Epilepsy 79 (2020) 86-89. [cited by applicant]
Salvati, K., Out of thin air: Hyperventilation-triggered seizures, Brain Res. Jan. 15, 2019; 1703: 41-52. [cited by applicant]
Dinges, David F. et al., Final Report: Evaluation of Techniques for Ocular Measurement as an Index of Fatigue and as the Basis for Alertness Management, U.S. Department of Transportation, Report No. 808 762, Apr. 1998, … [cited by applicant]