Devices and methods for assessing motor point electromyogram as a biomarker

• US 9,820,671 B2
• Filed: 05/16/2008
• Issued: 11/21/2017
• Est. Priority Date: 05/17/2007
• Status: Active Grant

• Current Assignee: Synapse Biomedical Inc.
• Original Assignee: Synapse Biomedical Inc.
• Inventors: Ignagni, Anthony R., Onders, Raymond P.
• Primary Examiner(s): CERIONI, DANIEL LEE
• Application Number:
  US12/122,482
• Publication Number:
  US 20080287820A1
• Time in Patent Office: 3,476 Days
• Field of Search: 600546, 607 42
• CPC Class Codes: A61B 5/389 Electromyography [EMG]
• CPC Class Codes: A61N 1/3601 of respiratory organs

Abstract

Described herein are methods of detecting the presence or progression of neuromuscular disorders (including ALS) based at least in part on diaphragm EMG signals taken at different points in time from the same implanted electrode(s). Signals may be used to diagnose or to monitor progression of a disorder or to track a treatment. Thus, diaphragm EMG signal may be used as a marker (e.g., a “biomarker”) for the detection or progression of a neurological disorder such as ALS. The characteristics or parameters of diaphragm EMG signals may be used to create an activity index, which may be output or compared and further analyzed. These signals may also be analyzed to show a difference between the left and right sides of the diaphragm.

Claims

1. A method of diagnosing or tracking the progression or treatment of a neurological disorder that affects the function of a diaphragm, the method comprising:

measuring a first EMG signal during a volitional breathing maneuver at an initial recording time before the start of therapy from one or more electrodes chronically implanted in a diaphragm;

measuring a second EMG signal from the same one or more electrodes at a later recording time during a volitional breathing maneuver after the start of the therapy; and

comparing one or more characteristics of the first EMG signal and the second EMG signal and characterizing the presence, progression or treatment of a neurological disorder based on the comparison.

2. The method of claim 1, wherein the disorder comprises any of a centrally-mediated breathing disorder or a neurodegenerative disease.

3. The method of claim 1, wherein the comparing step comprises comparing one or more of amplitude, frequency, power spectrum, time-to-peak rise time, relaxation time, compound action potential rise time, compound action potential fall time, fast twitch muscle contribution, and slow-twitch muscle contribution.

4. The method of claim 1, further comprising:

mapping the diaphragm to determine an active region of the diaphragm; and

implanting the one or more electrodes at an active region of the diaphragm.

5. The method of claim 1, further comprising:

mapping the diaphragm to determine a phrenic nerve motor point of the diaphragm; and

implanting the one or more electrodes at the phrenic nerve motor point.

6. The method of claim 5, wherein the mapping step includes applying electrical stimuli to an area of diaphragm surface and identifying a site within the area that provokes a maximal physiological response to the stimuli.

7. The method of claim 6, wherein the mapping step includes observing a physiological response to the stimuli including any of:

abdominal pressure or airway pressure, and diaphragm contraction.

8. The method of claim 1, wherein measuring the first EMG signal comprises:

selecting a duration and/or period of time for collection, wherein the duration and/or period of time for collection for the first EMG signal is the same for the second EMG signal; and

quantifying at least one characteristic of the EMG signal over the selected time.

9. The method of claim 8, wherein the time duration of collection of the EMG signal is selected from the group consisting of:

a single breath and a particular number of breaths.

10. The method of claim 8, wherein the characteristic of the EMG signal quantified is selected from the group consisting of:

amplitude, frequency, power spectrum, time-to-peak rise time, relaxation time, compound action potential rise time, compound action potential fall time, fast twitch muscle contribution, and slow-twitch muscle contribution.

11. The method of claim 1, wherein the steps of measuring the first EMG signal and measuring the second EMG signal comprises filtering the EMG signals to remove or reduce electrical signals not arising from the diaphragm.

12. The method of claim 1, further comprising correlating the EMG signals with a measurement of another physiological parameter.

13. The method of claim 12, wherein the physiological parameter comprises one or more blood gas level, airway pressure, abdominal pressure, and abdominal movement.

20. The method of claim 1, further comprising determining and presenting a score based on the comparison.

23. The method of claim 8, wherein the time duration of collection of the EMG signal is during a predetermined portion of the respiratory cycle.

14. A method of diagnosing or tracking the progression or treatment of a neurological disorder that affects the function of a patient'"'"'s diaphragm, the method comprising:

determining a first activity index from a patient'"'"'s diaphragm motor point EMG at a first time during a volitional breathing maneuver before the start of a therapy, wherein the first activity index is a first measure of a first component of the EMG that is combined with a first measure of a respiratory parameter value;

determining a second activity index from the patient'"'"'s diaphragm motor point EMG at a second time during a volitional breathing maneuver after the start of the therapy, wherein the second activity index is a second measure of the first component of the EMG that is combined with a second measure of the respiratory parameter value;

comparing the first activity index and the second activity index; and

characterizing the presence, progression or treatment of a neurological disorder based on the comparison between the first activity index and the second activity index,

wherein the first activity index and the second activity index are determined from a chronically implanted electrode for measuring the patient'"'"'s diaphragm motor point EMG at a first time and at a second time.

15. The method of claim 14, further comprising mapping the patient'"'"'s diaphragm to determine a phrenic nerve motor point.

16. The method of claim 14, further comprising implanting a diaphragm electrode in or adjacent to the patient'"'"'s diaphragm at a phrenic nerve motor point.

17. The method of claim 14, wherein first and second activity indexes are determined based at least in part on one or more of:

amplitude, frequency, power spectrum, time-to-peak rise time, relaxation time, compound action potential rise time, compound action potential fall time, fast twitch muscle contribution, and slow-twitch muscle contribution.

18. The method of claim 14, wherein the volitional maneuver is a sniff or a maximal inhalation.

19. The method of claim 14, wherein the respiratory parameters are selected from the group consisting of:

tidal volume, airway pressure, abdominal movement, abdominal pressure, and blood gas level.

21. The method of claim 14, further comprising determining and presenting a score based on the comparison.

22. The method of claim 21, wherein the score indicates a degree of change between the first activity index and the second activity index.

24. The method of claim 14, wherein the first time and the second time are separated by a predetermined time interval of at least one hour.

25. The method of claim 14, wherein the first time and the second time are separated by a predetermined time interval of at least one day.

26. The method of claim 14, wherein the first time and the second time are separated by a predetermined time interval of at least one week.

27. The method of claim 14, wherein the first time and the second time are separated by a time interval with an end that is manually triggered.

28. The method of claim 14, wherein the respiratory parameter value is a tidal volume.