Techniques for controlling abnormal involuntary movements by brain stimulation and drug infusion

• US 6,227,203 B1
• Filed: 09/09/1998
• Issued: 05/08/2001
• Est. Priority Date: 02/12/1998
• Status: Expired due to Term

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Inserm (institut national de la sant et de la recherche mdicale, Medtronic Incorporated (Medtronic Plc)
• Inventors: Benabid, Alim, Caparros-Lefebvre, Dominique, Rise, Mark T.
• Primary Examiner(s): Isabella, David J.
• Application Number:
  US09/150,088
• Time in Patent Office: 972 Days
• Field of Search: 128/898, 128/899, 607/1, 607/2, 607/3, 607/4, 607/46, 607/45, 604/891.1
• US Class Current: 128/898
• CPC Class Codes: A61M 2210/0693 Brain, cerebrum
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61N 1/0534 Electrodes for deep brain stimulation
• CPC Class Codes: A61N 1/36082 Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease

Abstract

The present invention discloses techniques for controlling abnormal involuntary movement (AIM) disorders as experienced by persons with Parkinson'"'"'s disease under high dosage of levodopa by electrical stimulation and/or drug infusion. The present invention utilizes an implantable signal generator and an electrode and/or an implantable pump and catheter. High electrical stimulation pulses and/or drug therapy is provided to predetermined portions of the brain to blocking neural activity in the Centremedian-Parafasicularis nucleus thereby reducing activity in the medial pallidal nucleus (GPi) which, in turn, reduces the AIM disorder. A sensor may be used to detect the symptoms resulting from the AIM disorder. A microprocessor or algorithm may then analyzes the output from the sensor to regulate the stimulation and/or drug therapy delivered to the brain.

Claims

1. A therapeutic treatment method for reducing the occurrence of abnormal involuntary movements by means of an implantable pump and a catheter having a proximal end coupled to the pump and a discharge portion for infusing therapeutic dosages of at least one drug, as well as a signal generator and at least one implantable electrode having a proximal end and a stimulation portion, the method comprising the steps of:

(a) implanting at least one electrode so that the stimulation portion lies in communication with a first predetermined site in a brain;

(b) implanting the catheter so that the discharge portion lies in communication with a second predetermined site in the brain;

(c) coupling the proximal end of the implanted electrode to the signal generator;

(d) coupling the catheter to the pump; and

(e) operating the signal generator and pump to block or reduce activity of a Centremedian-Parafasicularis nucleus in the brain by delivering electrical stimulation to the first predetermined site and at least one drug to the second predetermined site.

2. A method, as claimed in claim 1, further comprising the steps of:

(f) positioning a sensor at a third predetermined site of a body;

(g) sensing the extent of the abnormal involuntary movements;

(h) generating a sensor signal indicating the extent of the abnormal involuntary movements; and

(i) regulating the operation of the signal generator and the pump in response to the sensor signal to treat or reduce the abnormal involuntary movements.

3. A method, as claimed in claim 2, wherein said step of sensing includes the step of detecting changes in electromagnetic waves generated by muscle or nerve tissue.

4. A method, as claimed in claim 2, wherein said step of regulating comprises the step of executing a control algorithm to regulate the operation of the signal generator and the pump.

5. A method, as claimed in claim 4, wherein said step of sensing includes the step of communicating by telemetry the extent of the abnormal involuntary movements for use by the control algorithm.

6. A method, as claimed in claim 1, flier comprising the step of

(f) delivering electrical stimulation to a first determined site;

and

(g) delivering drug the to a second predetermined site.

7. A method as claimed in claim 6, wherein steps (f) and (g) are achieved using a combined electrode-catheter.

8. A method, as claimed in claim 1, wherein the first predetermined site is selected from the group consisting of Centremedian-parafasicularis nucleus of the thalamus (CM-Pf complex), ventrolateral thalamus (Thal), substantia nigra pars reticulata (SNr), subthalamic nucleus (STN), external segment of globus pallidus (GPe) and neostriatum, and wherein said stimulation and said discharge are selected to reduce thalamic output.

9. A method, as claimed in claim 1, wherein the second predetermined site is selected from the group consisting of Centremedian-parafasicularis nucleus of the thalamus (CM-Pf complex), ventrolateral thalamus (Thal), substantia nigra pars reticulata (SNr), subthalamic nucleus (STN), external segment of globus pallidus (GPe) and neostriatum, and wherein said stimulation and said discharge are selected to reduce thalamic output.

10. A method, as claimed in claim 1, wherein the step of operating includes the step of operating the signal generator and pump to block or reduce activity in an internal segment of globus pallidus (GPi) by delivering electrical stimulation to the first predetermined site and at least one drug to the second predetermined site.

11. A method, as claimed in claim 1, wherein said step of operating includes the step of operating the signal generator to pulse at a repetition rate of 2 to at least 2500 Hz.

12. A method, as claimed in claim 1, wherein the step of operating includes the step of delivering to the brain at least one drug selected from the group consisting of an anesthetic, a GABA agonist, a GABA antagonist, a glutamate antagonist, a glutamate agonist, a degrading enzyme, a reputake blocker, and a dopamine antagonist.

13. A method, as claimed in claim 1, wherein the brain comprises a first neural tissue responsive to a first type of neurotransmitter and a second neural tissue responsive to a second type of neurotransmitter, and wherein the step of operating includes the step of selecting at least one drug to act on the first and second type of neurotransmitter so that the stimulation required to create an action potential in the neural tissue is reduced compared to the stimulation required to create an action potential in the second neural tissue.

14. A method, as claimed in claim 1, wherein the brain comprises a first neural tissue responsive to a first type of neurotransmitter and a second neural tissue comprising fibers of passage, and wherein the step of operating includes the step of selecting at least one drug to act on the first neural tissue so that the stimulation required to create an action potential in the first neural tissue is raised, whereby said fibers of passage can be stimulated without creating action potentials in the first neural tissue.

15. A method, as claimed in claim 1, wherein the brain comprises a first nerve comprising an axon that terminates in axon terminals and a second nerve comprising a cell body including a receiving cell that communicates with the axon terminals across a synapse by means of a neurotransmitter, wherein the step of implanting the electrode includes that step of positioning the electrode so that the stimulation site is in communication within the axon and wherein the step of implanting the includes the step of positioning so that the infusion site is in communication with the synapse, whereby the stimulation of the axon results in increased excitment of the second nerve.

36. A method, as claimed in claim 1, wherein the first predetermined site overlaps with the second predetermined site.

16. A therapeutic treatment method for reducing the occurrence of abnomal involuntary movements by means of a signal generator and at least one implantable electrode having a proximal end and a stimulation portion, the method comprising the steps of:

(a) implanting at least one electrode so that the stimulation portion lies in communication with a predetermined site in a brain;

(b) coupling the proximal end of the implanted electrode to the signal generator;

(c) operating the signal generator to block activity of a Centremedian-Parafasicularis nucleus in the brain.

17. A method, as claimed in claim 16, wherein the step of operating includes the step of selecting amplitude, width and frequency of stimulation by the electrode.

18. A method, as claimed in claim 16, further comprising the steps of:

(f) sensing the extent of the abnormal involuntary movements and generating a sensor signal; and

(g) regulating the operation of the electrode in response to the sensor signal.

19. A method, as claimed in claim 18, wherein the step of sensing includes the step of sensing a physiological symptom of the abnormal involuntary movement.

20. A method, as claimed in claim 18, wherein the step of regulating includes the step of adjusting a parameter of the stimulation, the parameter being selected from the group consisting of amplitude, width and frequency.

21. A method, as claimed in claim 20, further comprising the step of readjusting over time at least one parameter of the stimulation downward to decease the effects of the stimulation.

22. A method, as claimed in claim 16, wherein the predetermined site is selected from the group consisting of Centremedian-parafasicularis nucleus of the thalamus (CM-Pf complex), ventrolateral thalamus (Thal), substantia nigra pars reticulata (SNr), subthalamic nucleus (STN), external segment of globus pallidus (GPe) and neostriatum, and wherein said stimulation and said discharge are selected to reduce thalamic output.

23. A method, as claimed in claim 16, wherein the step of operating includes the step of blocking activity in an internal segment of globus pallidus (GPi).

24. A method, as claimed in claim 16, wherein the step of operating includes the step of operating the signal generator to pulse at a repetition rate of 10-2500 Hertz.

25. A therapeutic treatment method for reducing the occurrence of abnormal involuntary movements by means of an implantable pump and a catheter having a proximal end coupled to the pump and a discharge portion for infusing therapeutic dosages of at least one drug, the method comprising the steps of:

(a) implanting the catheter so that the discharge portion lies in communication with a predetermined site in the brain;

(b) coupling the catheter to the pump;

(c) operating the pump to block or reduce activity of a Centremedian-Parafasicularis nucleus in the brain by delivering at least one drug to the predetermined site.

26. A method, as claimed in claim 25, wherein the step of operating includes the step of selecting a drug dosage.

27. A method, as claimed in claim 26, wherein the step of operating includes the step of selecting a time interval for drug delivery.

28. A method, as claimed in claim 25, further comprising the steps of:

(d) positioning a sensor at a third predetermined site of a body;

(e) sensing the extent of the abnormal involuntary movements;

(f) generating a sensor signal indicating the extent of the abnormal involuntary movements; and

(g) regulating the operation of the pump in response to the sensor signal to treat or reduce the abnormal involuntary movements.

29. A method, as claimed in claim 28, wherein the step of regulating includes the step of adjusting drug dosage and time interval for drug delivery.

30. A method, as claimed in claim 25, wherein the predetermined site is selected from the group consisting of Centramedian-Parafascularis nucleus of the thalamus (CM-Pf complex), ventrolateral thalamus (Thal), substantia nigra pars reticulata (SNr), subthalamic nucleus (STN), external segment of globus pallidus (GPe) and neostriatum, and wherein said stimulation and said discharge are selected to reduce thalamic output.

31. A method, as claimed in claim 25, wherein the step of operating includes the step of operating the pump to block or reduce activity in an internal segment of globus pallidus (GPi) by delivering at least one drug to the predetermined site.

32. A method, as claimed in claim 25, further comprising the steps of:

(d) implanting a second catheter to discharge a second drug to a second predetermined site in the brain;

(e) coupling the second catheter to a second pump; and

(f) operating the second pump to block or reduce activity of the Centremedian-Parafasicularis nucleus in the brain by delivering the second drug to the second predetermined site.

33. A therapeutic treatment method for reducing the occurrence of abnormal involuntary movements by means of an implantable pump and a catheter having a proximal end coupled to the pump and a discharge portion for infusing therapeutic dosages of at least one drug, as well as a signal generator and at least one implantable electrode having a proximal end and a stimulation portion, the method comprising the steps of:

(a) implanting at least one electrode so that the stimulation portion lies in communication with a first predetermined site in a brain;

(b) implanting the catheter so that the discharge portion lies in communication with a second predetermined site in the brain;

(c) coupling the proximal end of the implanted electrode to the signal generator;

(d) coupling the catheter to the pump;

(e) detecting the extent of the abnormal involuntary movements or the extent of a symptom of the abnormal involuntary movements;

(f) operating the signal generator and pump to block or reduce activity of a Centremedian-Parafasicularis nucleus in the brain by delivering electrical stimulation to the first predetermined site and at least one drug to the second predetermined site, whereby the abnormal involuntary movements are treated or reduced.

34. A method, as claimed in claim 33, wherein the first predetermined site overlaps with the second predetermined site.

35. A therapeutic treatment method for reducing the occurrence of abnormal involuntary movements by means of an implantable pump and a catheter having a proximal end coupled to the pump and a discharge portion for infusing therapeutic dosages of at least one drug, the method comprising the steps of:

(a) implanting the catheter so that the discharge portion lies in communication with a predetermined site in the brain;

(b) coupling the catheter to the pump;

(c) detecting the extent of the abnormal involuntary movements or the extent of a symptom of the abnormal involuntary movements;

(d) operating the pump to block or reduce activity of a Centremedian-Parafasicularis nucleus in the brain by delivering at least one drug to the predetermined site, whereby the abnormal involuntary movements are treated or reduced.