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

• US 7,819,812 B2
• Filed: 04/14/2006
• Issued: 10/26/2010
• Est. Priority Date: 12/15/2004
• Status: Expired due to Fees

• Current Assignee: Neuropace Inc.
• Original Assignee: Neuropace Inc.
• Inventors: John, Michael Sasha, Wingeier, Brett, Pless, Benjamin D.
• Primary Examiner(s): Layno; Carl H
• Assistant Examiner(s): PATEL, NATASHA
• Application Number:
  US11/404,579
• Publication Number:
  US 20060265022A1
• Time in Patent Office: 1,656 Days
• Field of Search: 607/45, 607/46, 607/3, 607/141, 600/378, 600/544, 600/300, 600/309, 600/322, 600/323, 600/333, 600/334, 600/439, 600/454, 600/504
• US Class Current: 600/504
• 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 and configured to be implanted in the human patient, comprising:

a detection subsystem coupled to at least one sensor,

wherein the sensor is adapted to generate a signal representative of a cerebral perfusion measurement, and

wherein the detection subsystem is adapted to receive and process the signal at predetermined times;

a processor adapted to identify automatically a condition in the signal and adapted to generate automatically an instruction for therapy based on the identified condition, wherein the condition is a predetermined change in cerebral perfusion; and

a subsystem in operative communication with the processor and adapted to provide a therapy to the human patient in response to the condition when instructed by the processor, wherein the therapy is intended to return cerebral perfusion measurement to a desired value or range of values.

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

3. The implantable device of claim 1, wherein the condition corresponds to an onset of an epileptic seizure.

4. The implantable device of claim 1, wherein the condition corresponds to a precursor anticipating an epileptic seizure.

5. The implantable device of claim 1, wherein the detection subsystem is further adapted to continuously monitor the signal, the processor further comprises an algorithm to identify the predetermined change in cerebral perfusion which algorithm uses at least one of a control law or a threshold comparison to determine whether to cause the processor to be instructed to provide responsive therapy.

6. The implantable device of claim 1, wherein the therapy is adapted to modulate cerebral perfusion by modulating at least one of electrical activity or chemical activity in the brain.

7. The implantable device of claim 1, wherein the sensor comprises an optical sensor adapted to acquire an oximetry measurement.

8. The implantable device of claim 7, wherein the therapy subsystem further comprises an optical stimulator and delivers optical stimulation as a therapy in response to the condition when instructed by the processor.

9. The implantable device of claim 1, wherein the sensor comprises an electromagnetic sensor adapted to acquire an electromagnetic field measurement.

10. The implantable device of claim 9, wherein the therapy subsystem further comprises an electromagnetic stimulator and delivers electromagnetic stimulation as a therapy in response to the condition when instructed by the processor.

11. The implantable device of claim 1, wherein the sensor comprises an thermographic sensor adapted to acquire an temperature measurement.

12. The implantable device of claim 11, wherein the therapy subsystem further comprises a thermal stimulator and delivers thermal stimulation as a therapy to cool or heat a region of the patient'"'"'s brain in response to the condition when instructed by the processor.

13. The implantable device of claim 1, wherein the sensor comprises an ultrasonic transducer.

14. The implantable device of claim 13, wherein the therapy comprises delivery of ultrasonic waves to a region of the patient'"'"'s brain through a component adapted to deliver ultrasonic waves.

15. The implantable device of claim 1, wherein the sensor comprises an electrochemical sensor adapted to acquire a measurement of oxygen concentration.

16. The implantable device of claim 1, wherein the sensor comprises an electrode.

17. The implantable device of claim 16, wherein the therapy comprises delivery of electrical stimulation through a stimulation electrode.

18. The implantable device of claim 16, wherein the electrode is adapted to measure an electrical impedance.

19. The implantable device of claim 16, wherein the electrode is adapted to measure an electrographic signal.

20. The implantable device of claim 1, wherein the sensor is selected from the group consisting of an optical oximeter, a thermographic sensor, an electromagnetic field sensor, an ultrasonic transducer, an electrochemical oxygen sensor, and an electrode.

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

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

23. The implantable device of claim 1, wherein the processor is adapted to calculate a perfusion trend and to identify the condition in the signal based the calculated perfusion trend.

24. The implantable device of claim 23, wherein the processor is adapted to update the perfusion trend to account for a long-term change and to identify the condition in the signal based on the updated perfusion trend.

25. The implantable device of claim 23, wherein the processor is adapted to identify a change by comparing the trend to a threshold and to identify the condition in the signal based the compared trend.

26. The implantable device of claim 23, wherein the change comprises a decrease in the perfusion measurement in comparison to the trend.

27. The implantable device of claim 26, wherein the subsystem is adapted to initiate delivery of a therapy at a therapy location.

28. The implantable device of claim 27, wherein the therapy comprises electrical stimulation, and wherein the subsystem is adapted to select a set of electrical stimulation parameters adapted to decrease perfusion.

29. The implantable device of claim 27, wherein the processor is adapted to calculate a therapy parameter of the therapy by applying a control law to the measurement.

30. The implantable device of claim 29, wherein the control law is derived from a plurality of measurements taken from the patient.

31. The implantable device of claim 30, wherein the processor is adapted to use the plurality of measurements to classify the neurological disorder suffered by the patient.

32. The implantable device of claim 1, wherein the processor is adapted to calculate a variable baseline value for cerebral perfusion by sequentially measuring a first set of signals indicative of cerebral perfusion level from the sensor, and averaging the first set of cerebral perfusion measurements to obtain a variable baseline value, the processor is adapted to further set a threshold value of cerebral perfusion which threshold value comprises a fixed relationship between a predetermined value and the variable baseline value, measure a second set of at least one cerebral perfusion measurement, compare the second set to the threshold value and if the second set is not greater than the threshold value, and update the variable baseline value by the relationship between the predetermined value and the variable baseline value.

33. The implantable device of claim 32, wherein the processor is adapted to generate an instruction to take at least one action if the second set is greater than the threshold value wherein the at least one action comprises initiating delivery of a therapy at a predetermined therapy location.

34. The implantable device of claim 33, wherein the therapy is selected from the group including optical stimulation, thermal stimulation, ultrasonic stimulation, electrical stimulation, and transcranial magnetic stimulation.

35. The implantable device of claim 33, wherein the therapy comprises electrical stimulation delivered at or near the focus of a seizure.

36. The implantable device of claim 33, 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.

37. The implantable device of claim 33, wherein the therapy comprises electrical stimulation of the caudate nucleus.

38. The implantable device of claim 33, 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.

39. The implantable device of claim 33, wherein the therapy location is selected from the group consisting of the cerebral cortex, the hippocampus, the white matter, the basal ganglia, the brain stem, the cerebellum, the spinal cord, and a peripheral nerve.

40. The implantable device of claim 33, wherein the action comprises changing a device mode from a first mode to a second mode.

41. The implantable device of claim 40, wherein the second mode enables deferred therapy delivery.

42. The implantable device of claim 41, wherein the deferred therapy delivery comprises scheduled therapy.

43. The implantable device of claim 33, wherein the processor is adapted to identify a neurological state, and in response to the neurological state, alter the action to be performed.

44. The implantable device of claim 43, wherein the processor is adapted to identify the neurological state by identifying a measure of seizure likelihood in an epileptic patient.

45. The implantable device of claim 43, wherein the processor is adapted to alter the action by selecting a therapy to be provided.

46. The implantable device of claim 43, wherein the processor is adapted to alter the action by modifying a parameter for a therapy to be provided.

47. The implantable device of claim 1, wherein the processor is adapted to obtain a first set of a plurality of measurements of cerebral perfusion measurements from the sensor, obtain a second set of at least one measurement of cerebral perfusion, take an average of the measurements in the first set to establish a baseline level, set a threshold to be a value having a fixed relationship with the baseline level, compare the second set of at least one measurement of cerebral perfusion to the threshold, if the second set of at least one measurement of cerebral perfusion is greater than the threshold, then take an action in response to the change in cerebral perfusion, and if the second set of at least one measurement of cerebral perfusion is not greater than the threshold, then recalculate the baseline level to be the average of the at least one measurement in the second set and a subset of the plurality of measurements in the first set.

48. The implantable device of claim 47, wherein the subset of the plurality of measurements in the first set is a subset containing the most recently obtained measurements in the first set.

49. The implantable device of claim 47, wherein the fixed relationship with the baseline level is one of a predetermined difference between the threshold and the baseline level and a predetermined factor by which the baseline level is multiplied.

50. The implantable device of claim 47, wherein the processor is adapted to take an action in response to the change in cerebral perfusion includes the processor is adapted to generate one or more instructions to initiate delivery of electrical stimulation to a predetermined target site in the body of a patient, register detection of a neurological condition, and initiate delivery of a drug to the patient.

51. The implantable device of claim 47, wherein the processor is adapted to take an action in response to the change in cerebral perfusion includes the processor is adapted to initiate delivery of electrical stimulation intended to decrease the level of cerebral perfusion at or around a predetermined target site in the brain of a patient.

52. The implantable device of claim 47, wherein the processor is adapted to take an action in response to the change in cerebral perfusion includes the processor is adapted to initiate delivery of electrical stimulation intended to increase the level of cerebral perfusion at or around a predetermined target site in the brain of a patient.

53. The implantable device of claim 1, wherein the processor is configured to obtain a first set of a plurality of measurements of cerebral perfusion measurements from the sensor, obtain a second set of at least one measurement of cerebral perfusion, take an average of the measurements in the first set to establish a baseline level, set a threshold to be a fixed relationship from the baseline level, compare the second set of at least one measurement of cerebral perfusion to the threshold, if the second set of at least one measurement of cerebral perfusion is less than the threshold, then take an action in response to the change in cerebral perfusion, and if the second set of at least one measurement of cerebral perfusion is not less than the threshold, then recalculate the baseline level to be the average of the at least one measurement in the second set and a subset of the plurality of measurements in the first set.

54. The implantable device of claim 53, wherein the subset of the plurality of measurements in the first set is a subset containing the n most recently obtained measurements in the first set.

55. The implantable device of claim 53, wherein the fixed relationship with the baseline level is one of a predetermined difference between the threshold and the baseline level and a predetermined factor by which the baseline level is multiplied.

56. The implantable device of claim 53, wherein the processor is adapted to take an action in response to the change in cerebral perfusion includes the processor is adapted to generate one of more instructions to initiate delivery of electrical stimulation to a predetermined target site in the body of a patient, register detection of a neurological condition, and initiate delivery of a drug to the patient.

57. The implantable device of claim 53, wherein the processor is adapted to take an action in response to the change in cerebral perfusion includes the processor is adapted to initiate delivery of electrical stimulation intended to decrease the level of cerebral perfusion at or around a predetermined target site in the brain of a patient.

58. The implantable device of claim 53, wherein the processor is adapted to take an action in response to the change in cerebral perfusion includes the processor is adapted to initiate delivery of electrical stimulation intended to increase the level of cerebral perfusion at or around a predetermined target site in the brain of a patient.

59. The implantable device of claim 1, wherein the processor is configured to obtain a first set of a plurality of measurements of cerebral perfusion measurements from at least one sensor implanted in a human patient, obtain a second set of at least one measurement of cerebral perfusion, take an average of the measurements in the first set to establish a baseline level, set a first threshold to be a value having a first fixed relationship with the baseline level and a second threshold to be a value having a second fixed relationship with the baseline level, compare the second set of at least one measurement of cerebral perfusion to the first threshold, if the second set of at least one measurement of cerebral perfusion is greater than the first threshold, then take a first action in response to the change in cerebral perfusion, compare the second set of at least one measurement of cerebral perfusion to the second threshold, if the second set of at least one measurement of cerebral perfusion is less than the second threshold, then take a second action in response to the change in cerebral perfusion, and if the second set of at least one measurement of cerebral perfusion is not greater than the first threshold and is not less than the second threshold, then recalculate the baseline level to be the average of the at least one measurement in the second set and a subset of the plurality of measurements in the first set.

60. The implantable device of claim 59, wherein the fixed relationship with the baseline level is one of a predetermined difference between the threshold and the baseline level and a predetermined factor by which the baseline level is multiplied.

61. The implantable device of claim 59, wherein the processor is adapted to take the first action or the second action in response to the change in cerebral perfusion includes the processor is adapted to generate one of more instructions to initiate delivery of electrical stimulation to a predetermined target site in the body of a patient, register detection of a neurological condition, and initiate delivery of a drug to the patient.

62. The implantable device of claim 59, wherein the processor is adapted to take the first action or the second action in response to the change in cerebral perfusion includes the processor is adapted to initiate delivery of electrical stimulation intended to decrease the level of cerebral perfusion at or around a predetermined target site in the brain of a patient.

63. The implantable device of claim 59, wherein the processor is adapted to take the first action or the second action in response to the change in cerebral perfusion includes the processor is adapted to initiate delivery of electrical stimulation intended to increase the level of cerebral perfusion at or around a predetermined target site in the brain of a patient.

64. A system for responding to a neurological disorder in a human patient, comprising:

a control unit implantable in the patient and comprising a detection subsystem coupled to at least one sensor,

wherein the sensor is adapted to generate a signal representative of a cerebral perfusion measurement, and

wherein the detection subsystem is adapted to regularly receive and process the signal;

a processor operatively coupled to the control unit and adapted to receive the signal and automatically identify a condition in the signal corresponding to an abnormal cerebral perfusion level; and

a therapy subsystem operatively coupled to the processor and to at least one therapy output, wherein the therapy subsystem is adapted to selectively initiate delivery of a therapy to the therapy output when the condition is identified in the signal and wherein the therapy is intended to normalize the cerebral perfusion level.

65. The system of claim 64, wherein the control unit is adapted to communicate with an external apparatus.

66. The system of claim 65, wherein the external apparatus includes the processor.

67. The system of claim 65, wherein the control unit is adapted to receive a command signal from the external apparatus which command signal enables the therapy subsystem to selectively initiate the therapy.