Quantitative multivariate analysis of seizures

• US 10,321,841 B2
• Filed: 05/26/2011
• Issued: 06/18/2019
• Est. Priority Date: 05/26/2010
• Status: Active Grant

• Current Assignee: Flint Hills Scientific, LLC
• Original Assignee: Flint Hills Scientific, LLC
• Inventors: Osorio, Ivan
• Primary Examiner(s): Porter, Allen
• Application Number:
  US13/116,873
• Publication Number:
  US 20110295332A1
• Time in Patent Office: 2,945 Days
• Field of Search: 600544, 600545, 607 45
• CPC Class Codes: A61B 5/369 Electroencephalography [EEG] devices for psychotechnics A61B5/16
• CPC Class Codes: A61B 5/4094 Diagnosing or monitoring seizure diseases, e.g. epilepsy
• CPC Class Codes: A61B 5/4833 Assessment of subject's compliance to treatment
• CPC Class Codes: A61N 1/36064 Epilepsy
• CPC Class Codes: A61N 1/36139 with automatic adjustment
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems

Abstract

Methods, including a method, comprising selecting a plurality of dependent variables relating to each of a plurality of seizures in a patient; selecting a plurality of independent variables, wherein each independent variable comprises a therapy parameter, a therapy delivery parameter, a temporal factor, an environmental factor, or a patient factor; quantifying at least one relationship between each of at least two dependent variables and each of at least two independent variables; and performing an action in response to said quantifying, selected from reporting said at least one relationship, assessing an efficacy of a therapy, assessing an adverse effect of said therapy, providing a therapy modification recommendation, or adjusting said therapy. A medical device system capable of implementing a method. A non-transitory computer readable program storage medium containing instructions that, when executed by a computer, perform a method.

Claims

1. A method of assessing an effect of a therapy on a severity of a detected epileptic seizure, comprising:

detecting and treating a plurality of seizures in a patient;

selecting by an internal controller of an implantable medical device an intensity associated with each of a first detected and treated seizure, a second detected and treated seizure, and a third detected and treated seizure;

selecting by the internal controller of the implantable medical device a duration associated with each of the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

selecting by the internal controller of the implantable medical device an extent of spread associated with each of the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

determining by the internal controller of the implantable medical device an index of the severity associated with each of the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure, wherein the index of severity is determined using one or more of an autonomic index, a metabolic index, a neurologic index, a tissue stress marker, a musculoskeletal index, or an endocrine index;

determining by the internal controller of the implantable medical device a severity associated with each of the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure based at least in part on the intensity associated with the corresponding detected and treated seizure, the duration associated with the corresponding detected and treated seizure, and the extent of spread associated with the corresponding detected and treated seizure, and the index of the severity associated with the corresponding detected and treated seizure;

selecting by the internal controller of the implantable medical device one or more of;

a parameter of the therapy for the plurality of detected and treated seizures, a parameter of a delivery of the therapy for the plurality of detected and treated seizures, a temporal factor for the plurality of detected and treated seizures, an environmental factor for the plurality of detected and treated seizures, or a patient factor for the plurality of detected and treated seizures;

quantifying by the internal controller of the implantable medical device at least one effect of;

the therapy parameter for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

the therapy delivery parameter for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

the temporal factor for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

the environmental factor for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure; and

the patient factor for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure on at least one of;

the intensity associated with the corresponding detected and treated seizure, the duration associated with the corresponding detected and treated seizure, and the extent of spread associated with the corresponding detected and treated seizure; and

performing an action by the implantable medical device in response to the quantification of the parameter of therapy associated with the corresponding detected and treated seizure, the parameter of the delivery of the therapy associated with the corresponding detected and treated seizure, the temporal factor associated with the corresponding detected and treated seizure, the environmental factor associated with the corresponding detected and treated seizure, or the patient factor associated with the corresponding detected and treated seizure, where the action is at least one of;

reporting at least one effect of the therapy for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

determining if the therapy effect is beneficial, neutral, or adverse the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

providing a modification recommendation for the therapy for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

or termination of the therapy for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

wherein the therapy is an electrical stimulation of a cranial nerve.

2. The method of claim 1, further comprising ranking by the implantable medical device the plurality of detected and treated seizures, according to at least one of a magnitude or a direction of change.

3. The method of claim 1, further comprising logging by the implantable medical device to memory data relating to the plurality of detected and treated seizures.

4. The method of claim 1, further comprising determining:

that a detected seizure was treated with any therapy, a time elapsed since a previous treatment with any therapy, a number of detected seizures since a previous treatment with any therapy, a time of day the detected seizure occurred, a time of month the detected seizure occurred, a time of year the detected seizure occurred, a type of any previous therapy, a dose of any previous therapy, a current density, a degree of tissue cooling, a degree of tissue warming, a level of consciousness, a level and type of cognitive activity, a level and type of physical activity, a state of health, a concentration of medicaments or chemicals in a tissue, or two or more of the foregoing.

5. The method of claim 1, further comprising delivering at least one additional therapy for one or more of the plurality of detected and treated seizures, where the additional therapy is selected from an electrical stimulation of a target structure of a brain, a drug, a thermal treatment of a neural structure, a cognitive therapy, or two or more thereof.

6. The method of claim 1, wherein the quantifying comprises a regression analysis.

7. The method of claim 1, further comprising determining with the implantable medical device the effect of the parameter of the therapy for each of the plurality of detected and treated seizures, the parameter of a delivery of the therapy for each of the plurality of detected and treated seizures, the temporal factor for each of the plurality of detected and treated seizures, the environmental factor for each of the plurality of detected and treated seizures, or the patient factor for each of the plurality of detected and treated seizures on:

the intensity corresponding with each of the plurality of detected and treated seizures, the duration corresponding with each of the plurality of detected and treated seizures, the extent of spread corresponding with each of the plurality of detected and treated seizures is beneficial, neutral, or adverse and ranking a beneficial effect and an adverse effect.

8. An implantable medical device system, comprising:

an implantable medical device, comprising;

a data acquisition unit configured to acquire data relating each of a plurality of detected and treated seizures in a patient where the data is at least one of;

an intensity of a detected and treated seizure or a severity of the detected and treated seizure, wherein the severity of the detected and treated seizure is determined based at least in part on the intensity of the detected seizure, a duration of the detected seizure, and an extent of spread of the detected and treated seizure and an index of the severity of the plurality of detected and treated seizures comprises one or more of an autonomic index, a metabolic index, a neurologic index, a tissue stress marker, a musculoskeletal index, or an endocrine index, and the data acquisition unit is further configured to acquire a therapy parameter associated with each of the plurality of detected and treated seizures, a therapy delivery parameter associated with each of the plurality of detected and treated seizures, a temporal factor associated with each of the plurality of detected and treated seizures, an environmental factor associated with each of the plurality of detected and treated seizures, or a patient factor associated with each of the plurality of detected and treated seizures;

a data quantification unit configured to quantify at least one effect of;

a therapy parameter associated with each of the plurality of detected and treated seizures, a therapy delivery parameter associated with each of the plurality of detected and treated seizures, a temporal factor associated with each of the plurality of detected and treated seizures, an environmental factor associated with each of the plurality of detected and treated seizures, or a patient factor associated with each of the plurality of detected and treated seizures on;

the intensity of the corresponding seizure, the severity of the corresponding seizure, the duration of the corresponding seizure, or the extent of spread for the corresponding seizure;

a therapy unit configured to administer at least one therapy to the patient, wherein the therapy is an electrical stimulation of a cranial nerve; and

an efficacy assessment unit configured to determine a magnitude of efficacy based on the quantification of the parameter of therapy associated with the corresponding detected and treated seizure, the parameter of the delivery of the therapy associated with the corresponding detected and treated seizure, the temporal factor associated with the corresponding detected and treated seizure, the environmental factor associated with the corresponding detected and treated seizure, or the patient factor associated with the corresponding detected and treated seizure, the efficacy assessment unit further configured perform and action in response to determining the magnitude of efficacy, where the action is at least one of;

report at least one effect of the therapy for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

determine if the therapy effect is beneficial, neutral, or adverse the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

provide a modification recommendation for the therapy for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

or

terminate the therapy for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure.

9. The implantable medical device system of claim 8, wherein the data quantification unit comprises a regression analysis unit configured to perform a regression analysis.

10. The implantable medical device system of claim 8, further comprising at least one sensor configured to sense at least one body signal relating to the intensity of each of a plurality of detected and treated seizures, the severity of each of a plurality of detected and treated seizures, the duration of each of a plurality of detected and treated seizures, or the extent of spread of each of a plurality of detected and treated seizures.

11. The implantable medical device system of claim 8, further comprising at least one sensor configured to sense at least one signal relating to a therapy parameter associated with each of the plurality of detected and treated seizures, a therapy delivery parameter associated with each of the plurality of detected and treated seizures, a temporal factor associated with each of the plurality of detected and treated seizures, an environmental factor associated with each of the plurality of detected and treated seizures, or a patient factor associated with each of the plurality of detected and treated seizures.

12. The implantable medical device system of claim 8, further comprising an additional therapy unit configured to administer at least one additional therapy including at least one of:

an electrical stimulation to a target structure of a brain of the patient;

a drug to a body of the patient;

a thermal therapy to a target structure of the brain, a target portion of a cranial nerve, or both of the patient;

a sensory therapy to a sensory organ of the patient;

or a cognitive therapy to the patient.

13. A non-transitory computer readable program storage medium containing instructions that, when executed by an implantable medical device, perform a method of assessing an efficacy of an epilepsy therapy on detected and treated seizures, the method comprising:

selecting an intensity of a detected and treated seizure or a severity of the detected and treated seizure, wherein the severity is determined based at least in part on the intensity of the detected and treated seizure, a duration of the detected and treated seizure, and an extent of spread of the detected and treated seizure and an index of the severity of the detected seizure, which comprises one or more of an autonomic index, a metabolic index, a neurologic index, a tissue stress marker, a musculoskeletal index, or an endocrine index;

selecting a parameter of the therapy associated with each detected and treated seizure, a parameter of a delivery of the therapy associated with each detected and treated seizure, a temporal factor associated with each detected and treated seizure, an environmental factor associated with each detected and treated seizure, or a patient factor associated with each detected and treated seizure;

quantifying at least one effect of the parameter of the therapy associated with each detected and treated seizure, the parameter of a delivery of the therapy associated with each detected and treated seizure, the temporal factor associated with each detected and treated seizure, the environmental factor associated with each detected and treated seizure, or the patient factor associated with each detected and treated seizure on;

the intensity of the corresponding seizure, the severity of the corresponding seizure, the duration of the corresponding seizure, or the extent of spread for the corresponding seizure; and

determining a magnitude of efficacy based on the quantification of the parameter of therapy associated with the corresponding detected and treated seizure, the parameter of the delivery of the therapy associated with the corresponding detected and treated seizure, the temporal factor associated with the corresponding detected and treated seizure, the environmental factor associated with the corresponding detected and treated seizure, or the patient factor associated with the corresponding detected and treated seizure; and

performing an action in response to determining the magnitude of efficacy, where the action is at least one of;

report at least one effect of the therapy for at least one of;

the first detected and treated seizure, the second detected and treated seizure and the third detected and treated seizure;

determine if the therapy effect is beneficial, neutral, or adverse the first detected and treated seizure the second detected and treated seizure, and the third detected and treated seizure;

provide a modification recommendation for the therapy for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure;

or

terminate the therapy for at least one of;

the first detected and treated seizure, the second detected and treated seizure, and the third detected and treated seizure,

wherein the therapy is an electrical stimulation of a cranial nerve.

14. The non-transitory computer readable program storage medium of claim 13, wherein the method further comprises ranking the detected and treated seizures, according to at least one of a magnitude or a direction of change.

15. The non-transitory computer readable program storage medium of claim 13, the method further comprising determining a frequency of the detected and treated seizures, an interval(s) between detected and treated seizures, or an adverse effect of a therapy on detected and treated seizures.

16. The non-transitory computer readable program storage medium of claim 13, the method further comprising determining:

that a detected seizure was treated with any therapy, a time elapsed since a previous treatment with any therapy, a number of detected seizures since a previous treatment of a previously detected seizure with any therapy, a time of day the detected seizure occurred, a time of month the detected seizure occurred, a time of year the detected seizure occurred, a type of any previous therapy of detected seizures, a dose of any previous therapy of detected seizures, a current density, a degree of tissue cooling, a degree of tissue warming, a level of consciousness, a level and type of cognitive activity, a level an type of physical activity, a state of health, a concentration of medicaments or chemicals in a tissue, or two or more of the foregoing.

17. The non-transitory computer readable program storage medium of claim 13, the method further comprising delivering at least one additional therapy for detected and treated seizures where the additional therapy is selected from an electrical stimulation of a target structure of a brain, a drug, a thermal treatment of a target portion of a neural structure, or a cognitive therapy.

18. The non-transitory computer readable program storage medium of claim 13, wherein the quantifying comprises a regression analysis.

19. The non-transitory computer readable program storage medium of claim 13, further comprising at least one of modifying and initiating a therapy based on the determination of the magnitude of efficacy.