Detecting, assessing and managing a risk of death in epilepsy

• US 9,808,207 B2
• Filed: 10/25/2016
• Issued: 11/07/2017
• Est. Priority Date: 03/04/2011
• Status: Active Grant

• Current Assignee: Flint Hills Scientific, LLC
• Original Assignee: Flint Hills Scientific, LLC
• Inventors: Osorio, Ivan
• Primary Examiner(s): Gedeon, Brian T
• Application Number:
  US15/333,802
• Publication Number:
  US 20170035368A1
• Time in Patent Office: 378 Days
• Field of Search: None
• CPC Class Codes: A61B 5/0205 Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
• CPC Class Codes: A61B 5/02055 Simultaneously evaluating both cardiovascular condition and temperature
• CPC Class Codes: A61B 5/021 Measuring pressure in heart or blood vessels A61B5/0205 takes precedence
• CPC Class Codes: A61B 5/02455 provided with high/low alarm devices
• CPC Class Codes: A61B 5/0826 Detecting or evaluating apnoea events A61B5/4818 takes precedence
• CPC Class Codes: A61B 5/1118 Determining activity level
• CPC Class Codes: A61B 5/162 Testing reaction times
• CPC Class Codes: A61B 5/349 Detecting specific parameters of the electrocardiograph cycle
• CPC Class Codes: A61B 5/4094 Diagnosing or monitoring seizure diseases, e.g. epilepsy
• CPC Class Codes: A61B 5/4836 Diagnosis combined with treatment in closed-loop systems or methods A61B5/0036 takes precedence
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: A61B 5/746 Alarms related to a physiological condition, e.g. details of setting alarm thresholds or avoiding false alarms alarms per se G08B
• CPC Class Codes: A61F 7/00 Heating or cooling appliances for medical or therapeutic treatment of the human body heating or cooling means in connection with bedsteads or mattresses A47C21/00 ; massage, therapeutic baths A61H; hyperthermia using electric or magnetic fields or ultrasound A61N; electric heating elements H05B
• CPC Class Codes: A61M 2230/06 Heartbeat rate only
• CPC Class Codes: A61M 2230/20 Blood composition characteristics
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: A61M 2230/208 pH-value
• CPC Class Codes: A61M 2230/30 Blood pressure A61M2230/04 takes precedence
• CPC Class Codes: A61M 2230/42 Rate
• CPC Class Codes: A61M 2230/63 : Motion, e.g. physical activity
• CPC Class Codes: A61M 5/1723 : using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61N 1/36064 : Epilepsy
• CPC Class Codes: A61N 1/36139 : with automatic adjustment
• CPC Class Codes: A61N 1/36142 : for improving safety
• CPC Class Codes: A61N 1/36514 : controlled by a physiological quantity other than heart potential, e.g. blood pressure controlled by two or more physical parameters A61N1/36585
• CPC Class Codes: A61N 1/36585 : controlled by two or more physical parameters
• CPC Class Codes: A61N 1/37247 : User interfaces, e.g. input or presentation means
• CPC Class Codes: A61N 1/37258 : Alerting the patient
• CPC Class Codes: A61N 1/3987 : characterised by the timing or triggering of the shock
• CPC Class Codes: G16H 50/30 : for calculating health indices; for individual health risk assessment

Abstract

A method for determining and responding in real-time to an increased risk of death relating to a patient with epilepsy is provided. The method includes receiving cardiac data and determining a cardiac index based upon the cardiac data. The method includes determining an increased risk of death associated with epilepsy if the indices are extreme, issuing a warning of the increased risk of death and logging information related to the increased risk of death. Also presented is a second method for determining and responding in real-time to an increased risk of death relating to a patient with epilepsy comprising receiving at least one of arousal data, responsiveness data or awareness data and determining an arousal index, a responsiveness index or an awareness index, where the indices are based on arousal data, responsiveness data or awareness data respectively. The second method includes determining an increased risk of death related to epilepsy if indices are extreme values, issuing a warning of the increased risk of death and logging information related to the increased risk of death. A computer readable program storage device is also provided. Also provided is a method for receiving body data, determining a cardiac, an arousal, a responsiveness, or a kinetic index, determining an increased or increasing risk of death over a first time window relating to a patient with epilepsy and issuing a warning and logging relevant information.

Claims

1. A method for determining and responding in real-time to an increased risk of death relating to a patient with epilepsy, comprising:

receiving cardiac data into a medical device;

determining, at least one cardiac index based upon said cardiac data;

determining whether said cardiac index is an extreme cardiac index by determining whether said cardiac index is below a low cardiac threshold value or above a high cardiac threshold value;

determining, using the medical device, the increased risk of death associated with epilepsy in response to a determination that said cardiac index is the extreme cardiac index; and

performing a responsive action based upon an occurrence of the increased risk of death, said responsive action comprises at least one of issuing automatically a warning;

providing a therapy, or logging automatically information related to the increased risk of death.

2. The method of claim 1, wherein determining the increased risk of death relating to the patient with epilepsy comprises determining at least one of a time at which at least one cardiac index becomes the extreme cardiac index or if there is a likelihood of said at least one cardiac index becoming the extreme cardiac index.

3. The method of claim 1, wherein providing said therapy comprises providing at least one of an electrical therapy, a chemical therapy, a thermal therapy, a cardiac defibrillation, a cardiac pacing or a supportive treatment.

4. The method of claim 1, further comprising at least one of:

wherein the cardiac index is selected from a group consisting of a heart rate, a heart rhythm, an EKG complex morphology, and a blood pressure;

wherein the cardiac index becomes an extreme value based at least upon one of;

the cardiac index is above an eightieth percentile of a plurality of reference autonomic index values;

the cardiac index is below a twentieth percentile of the plurality of reference autonomic index values;

or

the cardiac index is beyond two standard deviations to a right or a left of a mean for a normal or a normalized distribution of autonomic index values for the patient or a population of patients;

or

determining an additional autonomic index based upon a respiratory index, wherein the respiratory index is at least one of a respiratory rate, a respiratory rhythm, a respiratory pattern, a breath morphology, an oxygen saturation of the patient or a carbon dioxide concentration in the patient.

5. The method of claim 1, further comprising determining at least one additional index from at least one of a metabolic index, an endocrine index, a tissue stress index, a neurologic index, or a physical fitness/integrity index, said at least one additional index being based upon body data;

wherein the metabolic index comprises a blood index selected from an arterial pH, a lactic acid concentration, a serum potassium concentration, a serum glucose concentration, a lactate-pyruvate ratio, at least one electrolyte concentration, and a bicarbonate concentration;

wherein the endocrine index is a level or a concentration of at least one of an epinephrine or epinephrine'"'"'s metabolites, a norepinephrine or norepinephrine'"'"'s metabolites, a dopamine or dopamine'"'"'s metabolites, an acetyl-choline or acetyl-choline'"'"'s metabolites, a serotonin or serotonin'"'"'s metabolites, a growth hormone, a cortisol, a prolactin, an ACTH, a vasopressin, a beta-endorphin, or a lipotropin;

wherein the tissue stress index is at least one of a serum creatine kinase (CK), a troponin, a reactive oxygen species, a reactive nitrogen species, a neuroprostane, or a gluthatione;

wherein the neurologic index is selected from a kinetic index, an arousal index, a responsiveness index, and an awareness index, wherein the kinetic index is at least one of a body activity, a head activity, an eyelid activity, an eye activity, a facial activity, a limb activity, a trunk activity, a fall impact severity index, a change in body posture or a change in body position as determined over a time scale, wherein the arousal index is at least one of an increase in a muscle activity, a heart rate, a blood pressure, a respiratory rate, an eye opening, or an eyelid blinking associated with at least one arousal stimulus, a responsiveness and awareness indices are at least one of an ability of the patient to reflexely react to a simple stimulus, to react to a complex stimulus, to comprehend symbols, to memorize symbols, to behave adaptively, and wherein the at least one arousal stimulus is at least one of a sensory, an acoustic, a visual, an olfactory noxious or a non-noxious stimulus, the simple stimulus is at least one of a sensory stimuli, a noxious or a non-noxious, the complex stimulus is at least one of a cognitive stimuli, the symbol is at least one of a verbal, a geometric, a graphic or a visuo-spatial symbol and an adaptive behavior is motor or cognitive;

wherein the physical fitness/integrity index is at least one of one or more strength tests, one or more speed and power tests, one or more physical endurance tests, or one or more flexibility tests; and

wherein the additional index becomes an extreme state based at least upon one of;

the additional index is above an eightieth percentile of a plurality of reference index values;

the additional index is below a twentieth percentile of the plurality of reference index values;

or

the additional index is beyond two standard deviations to a right or a left of a mean for a normal or a normalized distribution of index values for the patient or a population of patients.

6. The method of claim 1, wherein determining said increased risk of death associated with epilepsy comprises identifying at least one of:

at least one of a decreasing heart rate variability (HRV) or pulmonary hypertension over a macroscopic time scale;

at least one of pulmonary edema or respiratory distress syndrome over a mesoscopic time scale;

or

at least one of an ST complex depression, an ST complex elevation, a QT elongation, multi-focal premature ventricular contractions (PVCs), a ventricular tachycardia, a fibrillation, over a microscopic time scale.

7. The method of claim 1, wherein the warning comprises indicating a severity indication commensurate with the increased risk of death;

and

wherein automatically logging information comprises logging information indicative of the severity indication commensurate with the increased risk of death.

8. The method of claim 7, wherein the severity indication is based on at least one of one or more environmental factors, one or more patient activity factors, or one or more patient conditions.

9. A non-transitory computer readable program storage unit encoded with instructions that, when executed by a computer, perform a method for determining and responding in real-time to an increased risk of death relating to a patient with epilepsy, comprising:

receiving cardiac data into a medical device;

determining, at least one cardiac index based upon said cardiac data;

determining whether said cardiac index is an extreme cardiac index by determining whether said cardiac index is below a low cardiac threshold value or above a high cardiac threshold value;

determining, using the medical device, the increased risk of death associated with epilepsy in response to a determination that said cardiac index is the extreme cardiac index; and

performing a responsive action based upon an occurrence of the increased risk of death, said responsive action comprises at least one of issuing automatically a warning;

providing a therapy, or logging automatically information related to the increased risk of death.

10. The non-transitory computer readable program storage unit of claim 9, wherein determining the increased risk of death relating to the patient with epilepsy comprises determining at least one of a time at which at least one cardiac index becomes the extreme cardiac index or if there is a likelihood of said at least one cardiac index becoming the extreme cardiac index.

11. The non-transitory computer readable program storage unit of claim 9, wherein providing said therapy comprises providing at least one of an electrical therapy, a chemical therapy, a thermal therapy, a cardiac defibrillation, a cardiac pacing or a supportive treatment.

12. The non-transitory computer readable program storage unit of claim 9, further comprising at least one of:

wherein the cardiac index is selected from a group consisting of a heart rate, a heart rhythm, an EKG complex morphology, and a blood pressure;

wherein the cardiac index becomes an extreme value based at least upon one of;

the cardiac index is above an eightieth percentile of a plurality of reference autonomic index values;

the cardiac index is below a twentieth percentile of the plurality of reference autonomic index values;

or

the cardiac index is beyond two standard deviations to a right or a left of a mean for a normal or a normalized distribution of autonomic index values for the patient or a population of patients;

or

determining an additional autonomic index based upon a respiratory index, wherein the respiratory index is at least one of a respiratory rate, a respiratory rhythm, a respiratory pattern, breath morphology, an oxygen saturation of the patient or a carbon dioxide concentration in the patient.

13. The non-transitory computer readable program storage unit of claim 9, further comprising determining at least one additional index from at least one of a metabolic index, an endocrine index, a tissue stress index, a neurologic index, or a physical fitness/integrity index, said at least one additional index being based upon body data;

wherein the metabolic index comprises a blood index selected from an arterial pH, a lactic acid concentration, a serum potassium concentration, a serum glucose concentration, a lactate-pyruvate ratio, at least one electrolyte concentration, and a bicarbonate concentration;

wherein the endocrine index is a level or a concentration of at least one of an epinephrine or epinephrine'"'"'s metabolites, a norepinephrine or norepinephrine'"'"'s metabolites, a dopamine or dopamine'"'"'s metabolites, an acetyl-choline or acetyl-choline'"'"'s metabolites, a serotonin or serotonin'"'"'s metabolites, a growth hormone, a cortisol, a prolactin, an ACTH, a vasopressin, a beta-endorphin, or a lipotropin;

wherein the tissue stress index is at least one of a serum creatine kinase (CK), a troponin, a reactive oxygen species, a reactive nitrogen species, a neuroprostane, or a gluthatione;

wherein the neurologic index is selected from a kinetic index, an arousal index, a responsiveness index, and an awareness index, wherein the kinetic index is at least one of a body activity, a head activity, an eyelid activity, an eye activity, a facial activity, a limb activity, a trunk activity, a fall impact severity index, a change in body posture or a change in body position as determined over a time scale, wherein the arousal index is at least one of an increase in a muscle activity, a heart rate, a blood pressure, a respiratory rate, an eye opening, or an eyelid blinking associated with at least one arousal stimulus, a responsiveness and awareness indices are at least one of an ability of the patient to reflexely react to a simple stimulus, to react to a complex stimulus, to comprehend symbols, to memorize symbols, to behave adaptively, and wherein the at least one arousal stimulus is at least one of a sensory, an acoustic, a visual, an olfactory noxious or a non-noxious stimulus, the simple stimulus is at least one of a sensory stimuli, a noxious or a non-noxious, the complex stimulus is at least one of a cognitive stimuli, the symbol is at least one of a verbal, a geometric, a graphic or a visuo-spatial symbol and an adaptive behavior is motor or cognitive;

wherein the physical fitness/integrity index is at least one of one or more strength tests, one or more speed and power tests, one or more physical endurance tests, or one or more flexibility tests; and

wherein the additional index becomes an extreme state based at least upon one of;

the additional index is above an eightieth percentile of a plurality of reference index values;

the additional index is below a twentieth percentile of the plurality of reference index values;

or

the additional index is beyond two standard deviations to a right or a left of a mean for a normal or a normalized distribution of index values for the patient or a population of patients.

14. The non-transitory computer readable program storage unit of claim 9, wherein determining said increased risk of death associated with epilepsy comprises identifying at least one of:

at least one of a decreasing heart rate variability (HRV) or pulmonary hypertension over a macroscopic time scale;

at least one of pulmonary edema or respiratory distress syndrome over a mesoscopic time scale;

or

at least one of an ST complex depression, an ST complex elevation, a QT elongation, multi-focal premature ventricular contractions (PVCs), a ventricular tachycardia, a fibrillation, over a microscopic time scale.

15. The non-transitory computer readable program storage unit of claim 9, wherein the warning comprises indicating a severity indication commensurate with the increased risk of death;

and

wherein automatically logging information comprises logging information indicative of the severity indication commensurate with the increased risk of death.

16. The non-transitory computer readable program storage unit of claim 15, wherein the severity indication is based on at least one of one or more environmental factors, one or more patient activity factors, or one or more patient conditions.

17. A medical device system, comprising:

a body data collection module configured to receive cardiac data into a medical device;

a controller configured to determine at least one cardiac index based upon said cardiac data, and whether said cardiac index is an extreme cardiac index by determining whether said cardiac index is below a low cardiac threshold value or above a high cardiac threshold value;

a death/SUDEP risk determination unit configured to determine the increased risk of death associated with epilepsy in response to a determination that said cardiac index is an extreme cardiac index; and

at least one of;

a warning unit configured to issue a warning,

a therapy unit configured to provide a therapy, or

a logging/reporting module configured to log information related to the increased risk of death.

18. The medical device system of claim 17, wherein the death/SUDEP risk determination unit is configured to determine the increased risk of death relating to the patient with epilepsy at least in part by determining at least one of a time at which at least one cardiac index becomes the extreme cardiac index or if there is a likelihood of said at least one cardiac index becoming the extreme cardiac index.

19. The medical device system of claim 17, wherein said therapy unit is configured to provide at least one of an electrical therapy, a chemical therapy, a thermal therapy, a cardiac defibrillation, a cardiac pacing or a supportive treatment.

20. The medical device system of claim 17, further comprising at least one of:

wherein the cardiac index is selected from a group consisting of a heart rate, a heart rhythm, an EKG complex morphology, and a blood pressure;

wherein the cardiac index becomes an extreme value based at least upon one of;

the cardiac index is above an eightieth percentile of a plurality of reference autonomic index values;

the cardiac index is below a twentieth percentile of the plurality of reference autonomic index values;

or

the cardiac index is beyond two standard deviations to a right or a left of a mean for a normal or a normalized distribution of autonomic index values for the patient or a population of patients;

or

determining an additional autonomic index based upon a respiratory index, wherein the respiratory index is at least one of a respiratory rate, a respiratory rhythm, a respiratory pattern, a breath morphology, an oxygen saturation of the patient or a carbon dioxide concentration in the patient.

21. The medical device system of claim 17, wherein the controller is further configured to determine at least one additional index from at least one of a metabolic index, an endocrine index, a tissue stress index, a neurologic index, or a physical fitness/integrity index, said at least one additional index being based upon body data;

wherein the metabolic index comprises a blood index selected from an arterial pH, a lactic acid concentration, a serum potassium concentration, a serum glucose concentration, a lactate-pyruvate ratio, at least one electrolyte concentration, and a bicarbonate concentration;

wherein the endocrine index is a level or concentration of at least one of an epinephrine or epinephrine'"'"'s metabolites, a norepinephrine or norepinephrine'"'"'s metabolites, a dopamine or dopamine'"'"'s metabolites, an acetyl-choline or acetyl-choline'"'"'s metabolites, a serotonin or serotonin'"'"'s metabolites, a growth hormone, a cortisol, a prolactin, an ACTH, a vasopressin, a beta-endorphin, or a lipotropin;

wherein the tissue stress index is at least one of a serum creatine kinase (CK), a troponin, a reactive oxygen species, a reactive nitrogen species, a neuroprostane, or a gluthatione;

wherein the neurologic index is selected from a kinetic index, an arousal index, a responsiveness index, and an awareness index, wherein the kinetic index is at least one of a body activity, a head activity, an eyelid activity, an eye activity, a facial activity, a limb activity, a trunk activity, a fall impact severity index, a change in body posture or a change in body position as determined over a time scale, wherein the arousal index is at least one of an increase in a muscle activity, a heart rate, a blood pressure, a respiratory rate, an eye opening, or an eyelid blinking associated with at least one arousal stimulus, a responsiveness and awareness indices are at least one of an ability of the patient to reflexely react to a simple stimulus, to react to a complex stimulus, to comprehend symbols, to memorize symbols, to behave adaptively, and wherein the at least one arousal stimulus is at least one of a sensory, an acoustic, a visual, an olfactory noxious or a non-noxious stimulus, the simple stimulus is at least one of a sensory stimuli, a noxious or a non-noxious, the complex stimulus is at least one of a cognitive stimuli, the symbol is at least one of a verbal, a geometric, a graphic or a visuo-spatial symbol and an adaptive behavior is motor or cognitive;

wherein the physical fitness/integrity index is at least one of one or more strength tests, one or more speed and power tests, one or more physical endurance tests, or one or more flexibility tests; and

wherein the additional index becomes an extreme state based at least upon one of;

the additional index is above an eightieth percentile of a plurality of reference index values;

the additional index is below a twentieth percentile of the plurality of reference index values;

or

the additional index is beyond two standard deviations to a right or a left of a mean for a normal or a normalized distribution of index values for the patient or a population of patients.

22. The medical device system of claim 17, wherein said death/SUDEP risk determining unit is configured to determine said increased risk of death associated with epilepsy at least in party by identifying at least one of:

at least one of a decreasing heart rate variability (HRV) or pulmonary hypertension over a macroscopic time scale;

at least one of pulmonary edema or respiratory distress syndrome over a mesoscopic time scale;

or

at least one of an ST complex depression, an ST complex elevation, a QT elongation, multi-focal premature ventricular contractions (PVCs), a ventricular tachycardia, a fibrillation, over a microscopic time scale.

23. The medical device system of claim 17, wherein the warning unit is configured to issue the warning comprising indicating a severity indication commensurate with the increased risk of death;

and

wherein the logging/reporting module is configured to log information indicative of the severity indication commensurate with the increased risk of death.

24. The medical device system of claim 23, wherein the severity indication is based on at least one of one or more environmental factors, one or more patient activity factors, or one or more patient conditions.