Modulation and analysis of cerebral perfusion in epilepsy and other neurological disorders

• US 20060265022A1
• Filed: 04/14/2006
• Published: 11/23/2006
• Est. Priority Date: 12/15/2004
• Status: Active Grant

• Current Assignee: Neuropace Inc.
• Original Assignee: Neuropace Inc.
• Inventors: Pless, Benjamin D., John, Michael S.
• Granted Patent: US 7,819,812 B2
• Time in Patent Office: Days
• US Class Current: 607/45
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/02 Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• 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 5/6868 Brain
• CPC Class Codes: A61B 5/7217 of noise originating from a therapeutic or surgical apparatus, e.g. from a pacemaker
• CPC Class Codes: A61B 8/06 Measuring blood flow measuring volume flow in general G01F, e.g. G01F1/66, G01F1/72; measuring speed of fluids in general G01P5/00
• CPC Class Codes: A61B 8/12 in body cavities or body tracts, e.g. by using catheters catheters per se A61M25/00
• CPC Class Codes: A61B 8/488 involving Doppler signals
• 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: A61F 7/12 Devices for heating or cooling internal body cavities
• CPC Class Codes: A61N 1/36057 adapted for stimulating afferent nerves
• CPC Class Codes: A61N 1/36064 Epilepsy
• CPC Class Codes: A61N 1/36082 Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
• CPC Class Codes: A61N 1/36139 with automatic adjustment
• CPC Class Codes: A61N 1/3614 based on impedance measurement
• CPC Class Codes: A61N 2/006 for magnetic stimulation of nerve tissue
• CPC Class Codes: A61N 2/02 using magnetic fields produced by coils, including single turn loops or electromagnets A61N2/12 takes precedence
• CPC Class Codes: A61N 2007/0043 : intra-cavitary
• CPC Class Codes: A61N 5/0622 : Optical stimulation for exciting neural tissue
• CPC Class Codes: A61N 7/00 : Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092

Abstract

A system including an implantable neurostimulator device capable of modulating cerebral blood flow to treat epilepsy and other neurological disorders. In one embodiment, the system is capable of modulating cerebral blood flow (also referred to as cerebral perfusion) in response to measurements and other observed conditions. Perfusion may be increased or decreased by systems and methods according to the invention as clinically required.

Claims

1. An implantable device for responding to a neurological disorder in a human patient, the device comprising:

a detection subsystem coupled to at least one sensor, wherein the sensor generates a signal representative of a cerebral perfusion measurement, and wherein the detection subsystem is operative to receive and process the signal;

a processor operative to identify a condition in the signal, wherein the condition is representative of a step in a sequence characterizing the neurological disorder; and

a subsystem operative to provide therapy in response to the condition.

2. The implantable device of claim 1, wherein the neurological disorder is epilepsy.

3. The implantable device of claim 1, wherein the condition is representative of a symptom of one of:

a neurological;

psychiatric; and

mood disorder.

4. The implantable device of claim 1, wherein the signal indicates the onset of an epileptic seizure.

5. The implantable device of claim 1, wherein the signal represents a precursor anticipating an epileptic seizure.

6. The implantable device of claim 1, wherein the condition comprises an unwanted change in the cerebral perfusion measurement.

7. The implantable device of claim 1, wherein at least one said condition is used by a detection algorithm, by a control law, or by a threshold comparison operation in order to provide responsive therapy.

8. The implantable device of claim 1, wherein the subsystem comprises a therapy subsystem coupled to at least one therapy output, wherein the therapy subsystem is operative to selectively initiate delivery of a therapy to the therapy output.

9. The implantable device of claim 8, wherein the processor is programmed to cause the therapy subsystem to initiate application of the therapy in response to the identified condition.

10. The implantable device of claim 8, wherein the therapy subsystem is adapted to modulate at least one of:

cerebral perfusion;

electrical activity; and

, chemical activity.

11. The implantable device of claim 8, wherein the sensor comprises an optical oximetry measurement component.

12. The implantable device of claim 11, wherein the therapy output comprises an optical stimulator.

13. The implantable device of claim 8, wherein the sensor comprises an electromagnetic field measurement component.

14. The implantable device of claim 13, wherein the therapy output comprises an electromagnetic stimulator.

15. The implantable device of claim 8, wherein the sensor comprises a thermographic measurement component.

16. The implantable device of claim 15, wherein the therapy output comprises a thermal stimulator.

17. The implantable device of claim 8, wherein the sensor comprises an ultrasonic transducer.

18. The implantable device of claim 17, wherein the therapy output comprises an ultrasonic transducer.

19. The implantable device of claim 8, wherein the sensor comprises an electrochemical oxygen concentration measurement component.

20. The implantable device of claim 8, wherein the sensor comprises a sensing electrode.

21. The implantable device of claim 20, wherein the therapy output comprises a stimulation electrode.

22. The implantable device of claim 20, wherein the sensing electrode is adapted to measure an electrical impedance.

23. The implantable device of claim 20, wherein the sensing electrode is adapted to measure an electrographic signal.

24. The implantable device of claim 1, wherein the sensor is selected from the group including an optical oximetry measurement component, a thermographic measurement component, an electromagnetic field sensor, an ultrasonic transducer, an electrochemical oxygen concentration sensor, and a sensing electrode.

25. The implantable device of claim 1, wherein the condition comprises a representation of cortical depression.

26. The implantable device of claim 1, wherein the condition comprises a representation of oxygen availability.

27. An implantable device for modulating cerebral blood flow in a human patient, the device comprising:

a therapy output adapted to receive a signal and deliver a corresponding stimulation to the patient'"'"'s brain, wherein the stimulus changes a characteristic of the patient'"'"'s cerebral blood flow; and

a therapy controller for generating a signal representative of the stimulation and communicating the signal to the therapy output.

28. The implantable device of claim 27, wherein the stimulation is adapted to increase perfusion.

29. The implantable device of claim 27, wherein the stimulation is adapted to decrease perfusion.

30. The implantable device of claim 27, wherein the therapy output comprises an optical stimulator.

31. The implantable device of claim 27, wherein the therapy output comprises a thermal stimulator.

32. The implantable device of claim 27, wherein the therapy output comprises an electromagnetic stimulator.

33. The implantable device of claim 27, wherein the therapy output comprises an ultrasonic transducer.

34. The implantable device of claim 27, wherein the therapy output comprises a stimulation electrode.

35. The implantable device of claim 27, wherein the signal is generated at least one of:

intermittently; and

, regularly.

36. The implantable device of claim 27, wherein the signal is generated in response to a detected change in a neurological condition.

37. A system for responding to a neurological disorder in a human patient, the device comprising:

a control unit comprising a detection subsystem coupled to at least one sensor, wherein the sensor generates a signal representative of a cerebral perfusion measurement, and wherein the detection subsystem is operative to receive and process the signal;

a processor coupled to receive the signal and identify a condition in the signal.

38. The system of claim 37, wherein the control unit comprises an implantable module.

39. The system of claim 38, wherein the control unit is adapted to communicate with an external apparatus.

40. The system of claim 39, wherein the external apparatus includes the processor.

41. The system of claim 39, wherein the control unit is adapted to receive a command signal from the external apparatus.

42. The system of claim 41, wherein the control unit further comprises a therapy subsystem coupled to at least one therapy output, and wherein the therapy subsystem is operative to selectively initiate delivery of a therapy to the therapy output.

43. A method for responding to a neurological disorder in a human patient, the method comprising the steps of:

obtaining a perfusion measurement with an implantable device;

identifying a change in the cerebral perfusion measurement; and

in response to the change, performing an action.

44. The method of claim 43, wherein the measurement is performed at a measurement location.

45. The method of claim 44, wherein the measurement location comprises a seizure focus.

46. The method of claim 44, wherein the measurement location comprises an artery feeding a seizure focus.

47. The method of claim 43, further comprising the step of calculating a perfusion trend.

48. The method of claim 47, further comprising the step of updating the perfusion trend to account for a long-term change.

49. The method of claim 47, wherein the step of identifying a change comprises comparing the trend to a threshold.

50. The method of claim 47, wherein the change comprises a decrease in the perfusion measurement in comparison to the trend.

51. The method of claim 50, wherein the action comprises initiating delivery of a therapy at a therapy location.

52. The method of claim 51, wherein the therapy is selected from the group including optical stimulation, thermal stimulation, sonic stimulation, pressure stimulation, ultrasonic stimulation, electrical stimulation, and transcranial magnetic stimulation.

53. The method of claim 51, wherein the therapy comprises focal electrical stimulation.

54. The method of claim 51, wherein the therapy comprises electrical stimulation, and wherein the method further comprises the step of selecting a set of electrical stimulation parameters adapted to increase perfusion.

55. The method of claim 51, wherein the therapy comprises electrical stimulation of the caudate nucleus.

56. The method of claim 51, wherein the therapy comprises electrical stimulation, and wherein the method further comprises the step of selecting a set of electrical stimulation parameters adapted to decrease perfusion.

57. The method of claim 51, wherein the therapy location is selected from the group including the cerebral cortex, the hippocampus, the white matter, the basal ganglia, the brain stem, the cerebellum, the spinal cord, and a peripheral nerve.

58. The method of claim 51, wherein the therapy has a therapy parameter, and wherein the method further comprises the step of using the measurement to calculate a therapy parameter before initiating delivery of the therapy.

59. The method of claim 58, wherein the step of using the measurement to calculate a therapy parameter comprises applying a control law to the measurement.

60. The method of claim 59, wherein the control law is derived from a plurality of measurements taken from the patient.

61. The method of claim 60, further comprising the step of using the plurality of measurements to classify the neurological disorder suffered by the patient.

62. The method of claim 58, wherein the therapy parameter is selected from a group of parameters including intensity, amplitude, frequency, duration, and therapy type.

63. The method of claim 62, wherein the therapy type comprises one or more of optical stimulation, thermal stimulation, sonic stimulation, pressure stimulation, ultrasonic stimulation, electrical stimulation, and transcranial magnetic stimulation.

64. The method of claim 43, wherein the step of identifying a change in the perfusion measurement employs information from at least one sensor located to sense from a left hemisphere of the patient'"'"'s brain and at least one sensor located to sense from a right hemisphere of the patient'"'"'s brain.

65. The method of claim 64, wherein the step of identifying a change in the perfusion measurement further comprises detecting a change in relative activation between at least one structure in the left hemisphere and at least one structure the right hemisphere having a magnitude that exceeds a threshold.

66. The method of claim 43, further comprising the step of identifying a structure in a hemisphere demonstrating increased blood flow, and wherein the step of performing an action comprises stimulating a neural structure in a hemisphere contralateral to the hemisphere demonstrating a structure with the increased blood flow.

67. The method of claim 43, wherein the action comprises changing a device mode from a first mode to a second mode.

68. The method of claim 67, wherein the second mode enables deferred therapy delivery.

69. The method of claim 68, wherein the deferred therapy delivery comprises scheduled therapy.

70. The method of claim 43, further comprising the step of identifying a neurological state, and in response to the neurological state, altering the action to be performed.

71. The method of claim 70, wherein the step of identifying a neurological state comprises identifying a measure of seizure likelihood in an epileptic patient.

72. The method of claim 70, wherein the step of altering the action comprises increasing a cerebral blood flow threshold.

73. The method of claim 70, wherein the step of altering the action comprises decreasing a cerebral blood flow threshold.

74. The method of claim 70, wherein the step of altering the action comprises selecting a therapy to be provided.

75. The method of claim 70, wherein the step of altering the action comprises modifying a parameter for a therapy to be provided.

76. The method of claim 43, wherein the step of obtaining a cerebral perfusion measurement comprises observing a first signal from a first implanted sensor, observing a second signal from a second implanted sensor, and calculating the perfusion as a composite of the first signal and the second signal.

77. The method of claim 76 wherein the first implanted sensor is positioned to measure the first signal from an artery feeding a location and the second implanted sensor is positioned to measure the second signal from a vein leaving the location.

78. The method of claim 76 wherein the composite comprises a difference between the first signal and the second signal.

79. The method of claim 76 wherein the composite comprises a measure of correlation between the first signal and the second signal.

80. The method of claim 76 wherein the composite comprises a measure of coherence between the first signal and the second signal.

81. The method of claim 76 wherein the step of performing an action comprises delivering a therapy to modulate the cerebral perfusion measurement.

82. The method of claim 81, wherein the step of delivering a therapy causes a change in an index related to the perfusion measurement, wherein the index comprises at least one of a non-linear measure, a measure of chaos, and a measure of synchronization.

83. The method of claim 81, wherein the step of delivering a therapy causes the first signal to more closely resemble the second signal.

84. The method of claim 81, wherein the step of delivering a therapy causes a change in an NIRS signal characteristic observed at a location in the brain.

85. The method of claim 84, wherein the characteristic is selected from characteristics representative of light absorption, light scattering, or oxygen saturation.

86. The method of claim 84, wherein the characteristic is based on oxyhemoglobin and deoxyhemoglobin concentrations.

87. The method of claim 84, wherein the NIRS signal characteristic is observed using near-infrared wavelengths of approximately 650 to approximately 950 nm.

88. The method of claim 87, wherein the NIRS signal characteristic is observed using at least two near-infrared wavelengths, a first near-infrared wavelength being above approximately 805 nm and a second near-infrared wavelength being below approximately 805 nm.

89. The method of claim 84, wherein the NIRS signal characteristic is calculated via a forward solution, a backward solution, or both.

90. The method of claim 81, wherein the therapy has a therapy parameter, and wherein the method further comprises the steps of obtaining an updated perfusion measurement after delivering the therapy, and using the updated perfusion measurement to adjust the therapy parameter.

91. The method of claim 90, wherein the updated perfusion measurement includes a component representative of evoked activation.

92. The method of claim 91, further comprising the step of calculating a measure of evoked activation by comparing at least a portion of the perfusion measurement with at least a portion of the updated perfusion measurement.

93. The method of claim 92, wherein each of the perfusion measurement and the updated perfusion measurement comprises an NIRS signal.

94. The method of claim 92, wherein the perfusion measurement and the updated perfusion measurement are separated by an interval of time.

95. The method of claim 92, wherein the perfusion measurement is performed before the step of performing an action, and the updated perfusion measurement is performed after the step of performing an action.

96. The method of claim 43, wherein the step of performing an action comprises increasing a data sampling rate.

97. The method of claim 43, further comprising an initial step of calculating an initial perfusion state.

98. The method of claim 97, wherein the step of calculating an initial perfusion state comprises performing a measurement with external equipment.

99. The method of claim 98, wherein the external equipment comprises an imaging apparatus.

100. The method of claim 98, wherein the external equipment comprises an NIRS apparatus.