Seizure prediction

• US 20080269631A1
• Filed: 04/30/2007
• Published: 10/30/2008
• Est. Priority Date: 04/30/2007
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Denison, Timothy J., Santa, Wesley A.
• Granted Patent: US 9,788,750 B2
• Time in Patent Office: Days
• US Class Current: 600/544
• CPC Class Codes: A61B 5/024 Detecting, measuring or recording pulse rate or heart rate A61B5/0205, A61B5/021 take precedence
• CPC Class Codes: A61B 5/053 Measuring electrical impedance or conductance of a portion of the body
• CPC Class Codes: A61B 5/291 for electroencephalography [EEG]
• CPC Class Codes: A61B 5/318 Heart-related electrical modalities, e.g. electrocardiography [ECG]
• CPC Class Codes: A61B 5/389 Electromyography [EMG]
• CPC Class Codes: A61B 5/4094 Diagnosing or monitoring seizure diseases, e.g. epilepsy
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/7228 Signal modulation applied to the input signal sent to patient or subject; demodulation to recover the physiological signal modulation H03C
• 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: A61N 1/36025 for treating a mental or cerebral condition
• CPC Class Codes: A61N 1/36082 Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment

Abstract

Seizure prediction systems and methods include measuring impedance within a brain of a patient to determine whether the brain is in a state indicative of a possibility of an onset of a seizure. In some embodiments, the measured impedance is compared to a predetermined threshold in order to determine whether the brain is in a state indicative of a possibility of a seizure. In other embodiments, a trend of the impedance measurements is correlated to a template. In other embodiments, a frequency component of a waveform of the impedance measurement amplitudes over time is correlated to frequency components of a template waveform. Upon detecting a state in which a seizure is likely to occur, a seizure indicator may be generated, which, in some embodiments, may be used to activate therapy delivery to the patient or, in other embodiments, activate an alarm.

Claims

1. A method comprising:

measuring an impedance of a brain of a patient; and

determining whether the brain is in a state indicative of a possibility of seizure based on the measured impedance.

2. The method of claim 1, wherein measuring the impedance of the brain of the patient comprises delivering a stimulation current in a range of about 500 nanoamps to about 10 microamps across tissue in one or more regions of the brain of the patient.

3. The method of claim 1, wherein determining whether the brain is in the state indicative of the possibility of seizure comprises comparing an amplitude of the measured impedance to a predetermined threshold value.

4. The method of claim 3, wherein comparing the amplitude of the measured impedance to the predetermined threshold value comprises comparing an average amplitude of the measured impedance over a period of time to the predetermined threshold value.

5. The method of claim 3, further comprising determining the predetermined threshold value, wherein determining the predetermined threshold value comprises:

measuring the impedance of the brain of the patient during a finite period of time;

storing impedance measurements measured during the finite period of time;

detecting an actual occurrence of the seizure during the finite period of time; and

associating the actual occurrence of the seizure with at least one of the impedance measurements stored during the finite period of time.

6. The method of claim 1, wherein determining whether brain is in the state indicative of the possibility of seizure comprises comparing a trend in the measured impedance to a template, wherein if the trend substantially correlates to the template, the impedance indicates the state indicative of the possibility of seizure.

7. The method of claim 6, wherein the trend indicates a rate of change of the measured impedance over time.

8. The method of claim 1, wherein determining whether the brain is in the state indicative of the possibility of seizure comprises analyzing a first frequency component of a waveform of the measured impedance and comparing the first frequency component to a second frequency component of a waveform template.

9. The method of claim 1, further comprising delivering therapy to the patient when it is determined that the brain is in the state indicative of the possibility of seizure.

10. The method of claim 9, wherein delivering therapy comprises at least one of delivering a pharmaceutical agent or delivering electrical stimulation to tissue of the patient.

11. The method of claim 9, further comprising selecting the therapy to inhibit an onset of the seizure.

12. The method of claim 9, further comprising selecting the therapy to reduce severity or duration of the seizure.

13. The method of claim 1, wherein the state is a first state, the method further comprising selecting a therapy to return the brain to a second state indicative of a lower possibility for seizure than the first state.

14. The method of claim 1, wherein measuring the impedance comprises measuring a complex impedance over at least one frequency.

15. The method of claim 14, wherein the at least one frequency in a range of approximately 1 kilohertz to approximately 100 kilohertz.

16. The method of claim 15, wherein the at least one frequency in a range of approximately 4 kilohertz to approximately 16 kilohertz.

17. The method of claim 1, wherein measuring an impedance of a brain of a patient comprises measuring the impedance within at least two regions of the brain.

18. The method of claim 17, wherein the at least two regions are selected from a group comprising:

a cortex, brainstem, anterior thalamus, ventrolateral thalamus, globus pallidus, substantia nigra pars reticulata, subthalamic nucleus, neostriatum, cingulated gyrus or cingulate gyrus.

19. The method of claim 1, wherein measuring an impedance of a brain of a patient comprises measuring the impedance within at least one of a cortex, brainstem, anterior thalamus, ventrolateral thalamus, globus pallidus, substantia nigra pars reticulata, subthalamic nucleus, neostriatum, cingulated gyrus or cingulate gyrus.

20. The method of claim 1, further comprising generating a notification when it is determined that the brain is in the state indicative of the possibility of seizure.

21. The method of claim 1, wherein measuring the impedance of the brain of the patient comprises:

generating an alternating current (ac) stimulation current at a frequency;

applying the stimulation current to a brain tissue load to produce an input signal;

amplifying the input signal to produce an amplified signal;

demodulating the amplified signal at the frequency to produce an output signal;

modulating an amplitude of the output signal at the frequency to produce a feedback signal; and

applying the feedback signal to the input signal via a first feedback path.

60. The method of claim 21, wherein the input signal comprises a differential input signal.

22. A system comprising:

one or more electrodes implantable in a brain of a patient;

an impedance sensing module that delivers an electrical stimulus to the brain via the electrodes to measure an impedance of the brain; and

a processor coupled to the impedance sensing module, wherein the processor receives impedance measurements from the impedance sensing module and determines whether the brain is in a state indicative of a possibility of seizure based on the measured impedance.

23. The system of claim 22, further comprising a therapy delivery module coupled to the processor, wherein the processor controls delivery of therapy to the patient via the therapy delivery module when it is determined that the brain is in the state indicative of the possibility of seizure.

24. The system of claim 23, wherein the therapy comprises at least one of delivery of a pharmaceutical agent or electrical stimulation.

25. The system of claim 23, wherein the state indicative of the possibility of seizure is a first state, and wherein the processor selects the therapy to return the brain to a second state indicative of a lower possibility for seizure than the first state.

26. The system of claim 22, wherein the impedance sensing module delivers a stimulation current in a range of about 500 nanoamps to about 10 microamps across tissue in one or more regions of the brain of the patient to measure the impedance.

27. The system of claim 22, wherein the processor determines whether the measured impedance indicates the brain is in the state indicative of the possibility of seizure by comparing an amplitude of the measured impedance to a predetermined threshold value.

28. The system of claim 22, wherein the processor determines whether the measured impedance indicates the brain is in the state indicative of the possibility of seizure by comparing a trend in the measured impedance to a template, wherein if the trend substantially correlates to the template, the brain is in the state indicative of the possibility of the seizure.

29. The system of claim 28, wherein the trend indicates a rate of change of the measured impedance over time.

30. The system of claim 22, wherein the impedance sensing module generates a waveform of the measured impedance, and wherein the processor determines whether the measured impedance indicates the brain is in the state indicative of the possibility of seizure by analyzing a first frequency component of the waveform of the measured impedance and comparing the first frequency component to a second frequency component of a waveform template.

31. The system of claim 22, wherein the impedance sensing module measures the impedance of the brain by measuring a complex impedance over at least one frequency.

32. The system of claim 31, wherein the at least one frequency in a range of approximately 1 kilohertz to approximately 100 kilohertz.

33. The system of claim 22, wherein the impedance sensing module measures the impedance within at least two regions of the brain.

34. The system of claim 22, wherein the impedance sensing module measures the impedance within at least one of a cortex, brainstem, anterior thalamus, ventrolateral thalamus, globus pallidus, substantia nigra pars reticulata, subthalamic nucleus, neostriatum, cingulated gyrus or cingulate gyrus of the brain.

35. The system of claim 22, further comprising a notification device, wherein the processor activates the notification device when it is determined that the brain is in the state indicative of the possibility of seizure.

36. The system of claim 22, wherein the impedance sensing module comprises a chopper-stabilized instrumentation amplifier comprising:

an alternating current (ac) source that generates an ac stimulation current at a frequency for application to a brain tissue load;

a mixer amplifier coupled to receive an input signal from the brain tissue load in response to the stimulation current, wherein the mixer amplifier amplifies the input signal to produce an amplified signal and demodulates the amplified signal at the frequency to produce an output signal;

a modulator that modulates an amplitude of the output signal at the frequency; and

a feedback path that applies the modulated output signal as a feedback signal to the input signal.

61. The system of claim 36, wherein the input signal comprises a differential input signal.

37. A system comprising:

means for measuring an impedance of a brain of a patient; and

means for determining whether the measured impedance indicates the brain is in a state indicative of a possibility of seizure.

38. The system of claim 37, further comprising means for delivering therapy to the patient when the measured impedance indicates the brain is in the state indicative of the possibility of seizure.

39. The system of claim 37, further comprising means for providing a notification to the patient when the measured impedance indicates the brain is in the state indicative of the possibility of seizure.

40. The system of claim 37, wherein the means for determining whether the measured impedance indicates the brain is in the state indicative of the possibility of seizure comprises means for determining a trend of the measured impedance over time and means for correlating the trend to a template.

41. The system of claim 37, wherein the means for determining whether the measured impedance indicates the brain is in the state indicative of the possibility of seizure comprises means for comparing an amplitude of the measured impedance to a predetermined threshold value.

42. The system of claim 37, wherein the means for measuring the impedance of the brain of the patient comprises a chopper-stabilized instrumentation amplifier comprising:

means for generating an alternating current (ac) stimulation current at a frequency for application to a brain tissue load, wherein the application of the stimulation current to the brain tissue load produces an input signal;

means for amplifying the input signal to produce an amplified signal;

means for demodulating the amplified signal at the frequency to produce an output signal;

means for modulating an amplitude of the output signal at the frequency; and

means for applying the modulated output signal as a feedback signal to the input signal.

62. The system of claim 42, wherein the input signal comprises a differential input signal.

43. A computer-readable medium comprising instructions that cause a programmable processor to:

receive a signal indicative of a measured impedance of a brain of a patient; and

determine whether the brain is in a state indicative of a possibility of seizure based on the measured impedance.

44. The computer-readable medium of claim 43, wherein the instructions further cause the processor to control a therapy delivery module to deliver therapy to the patient when the measured impedance indicates the brain is in the state indicative of the possibility of seizure.

45. The computer-readable medium of claim 43, wherein the instructions that cause the processor to determine whether the brain is in the state indicative of the possibility of seizure based on the measured impedance cause the processor to compare an amplitude of the measured impedance to a predetermined threshold value.

46. The computer-readable medium of claim 43, wherein the instructions that cause the processor to determine whether the brain is in the state indicative of the possibility of seizure cause the processor to compare a trend exhibited by the measured impedance over time to a template, wherein if the trend substantially correlates to the template, the brain is in the state indicative of the possibility of seizure.

47. A method comprising:

measuring an impedance of a brain of a patient;

detecting an occurrence of a seizure;

associating the occurrence of the seizure with at least one impedance measurement; and

recording the at least one impedance measurement associated with the occurrence of the seizure.

48. The method of claim 47, wherein detecting the occurrence of the seizure comprises analyzing electroencephalogram data or electrocorticogram data.

49. The method of claim 47, further comprising determining a threshold value that indicates the brain is in a state indicative of a possibility of the seizure based on the at least one impedance measurement associated with the occurrence of the seizure.

50. The method of claim 49, wherein determining the threshold value comprises determining a lowest impedance measurement of the at least one impedance measurements associated with the occurrence of the seizure.

51. The method of claim 47, wherein associating the occurrence of the seizure with at least one impedance measurement comprises associating the occurrence of the seizure with a plurality of impedance measurements measured during a period of time beginning before the occurrence of the seizure, the method further comprising determining a trend in the plurality of impedance measurements over time.

52. The method of claim 51, wherein the period of time begins before the occurrence of the seizure and ends at an onset of the seizure.

53. The method of claim 47, wherein measuring the impedance of the brain of the patient comprises measuring the impedance within at least two regions of the brain.

54. The method of claim 47, further comprising generating a waveform including amplitudes of at least one impedance measurement associated with the occurrence of the seizure and determining a frequency component of the waveform to generate a template.

55. A system comprising:

an impedance sensing module that measures an impedance of a brain of a patient;

a seizure detection module that detects an occurrence of a seizure; and

a processor coupled to the impedance sensing module and the seizure detection module, wherein the processor associates the occurrence of the seizure with at least one impedance measurement.

56. The system of claim 55, wherein the seizure detection module monitors electrical activity of the brain via at least one of electroencephalography or electrocorticography to detect the occurrence of the seizure.

57. The system of claim 55, wherein the processor determines a threshold value that indicates a brain is in a state indicative of a possibility of the seizure based on the at least one impedance measurement associated with the occurrence of the seizure.

58. The system of claim 55, wherein the processor associates the occurrence of the seizure with a plurality of impedance measurements measured during a period of time beginning before the occurrence of the seizure, and determines a trend in the plurality of impedance measurements over time.

59. The system of claim 55, wherein the processor generates a waveform including amplitudes of at least one impedance measurement associated with the occurrence of the seizure and determines a frequency component of the waveform to generate a template.