Cerebrospinal Fluid Purification System

• US 20100305492A1
• Filed: 10/09/2007
• Published: 12/02/2010
• Est. Priority Date: 10/09/2006
• Status: Active Grant

• Current Assignee: Neurofluidics, Inc. (Minnetronix Medical, Inc.)
• Original Assignee: Neurofluidics, Inc. (Minnetronix Medical, Inc.)
• Inventors: Nikolich, Karoly, Lad, Shivanand, Saul, Thomas, Mobley, William C.
• Granted Patent: US 8,435,204 B2
• Time in Patent Office: Days
• US Class Current: 604/9
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 2025/0007 Epidural catheters
• CPC Class Codes: A61M 2027/004 with at least a part of the circuit outside the body
• CPC Class Codes: A61M 2202/0021 removed from and reintroduced into the body, e.g. after treatment
• CPC Class Codes: A61M 2202/0464 Cerebrospinal fluid
• CPC Class Codes: A61M 2202/203 Bacteria
• CPC Class Codes: A61M 2202/206 Viruses
• CPC Class Codes: A61M 2206/16 Rotating swirling helical flow, e.g. by tangential inflows
• CPC Class Codes: A61M 2210/0693 Brain, cerebrum
• CPC Class Codes: A61M 2210/1003 Spinal column
• CPC Class Codes: A61M 25/0026 Multi-lumen catheters with stationary elements catheter assemblies comprising a catheter in combination with a guide tube, sheath or sleeve A61M2025/0681; catheters comprising telescoping coaxial elements A61M2025/0175
• CPC Class Codes: A61M 27/006 Cerebrospinal drainage; Accessories therefor, e.g. valves

Abstract

The present invention provides methods and systems for conditioning cerebrospinal fluid (CSF). The methods provide for efficiently removing target compounds from CSF. The systems provide for a multilumen flow path and exchange of a majority volume portion of CSF in the CSF space. The removal and/or delivery of specific compounds can be tailored to the pathology of the specific disease. The removal is targeted and specific, for example, through the use of specific size-exclusion thresholds, antibodies against specific toxins, and other chromatographic techniques, as well as delivery and/or removal of targeted therapeutic agents. The invention finds use as a diagnostic, therapeutic and drug delivery platform for a variety of diseases affecting the CNS by accessing the CSF space. Exemplified disease conditions treatable by the present CSF processing systems and methods include, but are not limited to: Cerebral Vasospasm, Guillain Bane Syndrome, illustrating multi-lumen lumbar approach Alzheimer'"'"'s, Parkinson'"'"'s, Huntington'"'"'s, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Spinal Cord Injury, Traumatic Brain Injury, Stroke, Cancer affecting the brain or spinal cord, Prion disease, Encephalitis from various causes, Meningitis from various causes, diseases secondary to enzymatic or metabolic imbalances, Biological Warfare, etc. For the first time, the present invention offers patients a disease-modifying, disruptive technology treatment platform that addresses the known disease pathogenesis of a number of neurologic conditions to which there are presently limited and ineffective treatment options.

Claims

1. A method for conditioning cerebrospinal fluid (CSF) in a patient, said method comprising:

removing CSF from a first location in a CSF space of the patient;

conditioning the removed CSF; and

returning the conditioned CSF to the patient at a second location in the CSF space;

wherein the removing and returning steps are performed concurrently during at least a portion of a conditioning treatment.

2. A method as in claim 1, wherein the CSF is removed and returned at substantially the same flow rate.

3. A method as in claim 2, wherein the flow rate is in the range from 0.04 ml/min to 30 ml/min.

4. A method as in claim 3, wherein the volume of CSF removed from the patient never exceeds 40 ml.

5. A method as in claim 1, wherein the distance between the first location and the second location is at least 4 cm.

6. A method as in claim 5, wherein the first location is at S1 or above and the second location is at L3 or above.

7. A method as in claim 6, wherein the second location is in the cervical CSF space.

8. A method as in claim 6, wherein the second location is in a ventricle.

9. A method as in claim 1, wherein the flow directions of removing and returning CSF are periodically reversed so that CSF is returned to the first location and removed from a second location during a portion of the treatment.

10. A method as in claim 9, wherein the flow reversal is a pulse to dislodge debris from removal or return ports.

11. A method as in claim 1, further comprising mixing the conditioned CSF with endogenous CSF as the conditioned CSF is returned to the CSF space.

12. A method as in claim 11, wherein mixing comprises inducing a turbulent flow as the conditioned CSF is returned.

13. A method as in claim 1, wherein conditioning comprises removing a targeted molecule.

14. A method as in claim 13, further comprising the step of isolating the targeted molecule.

15. A method as in claim 1, wherein conditioning comprises one or more separation processes selected from the group consisting of biospecific affinity, immunoaffinity, cationic exchange, anionic exchange, hydrophobicity and size exclusion.

16. A method as in claim 1, wherein the conditioning step is performed externally to the patient'"'"'s body.

17. A method as in claim 1, wherein the conditioning step is performed using a conditioning unit implanted in the patient'"'"'s body.

18. A method for conditioning cerebrospinal fluid (CSF) in a patient, said method comprising:

introducing a catheter apparatus through a lumbar access site into a spinal CSF space of the patient;

advancing the catheter apparatus through the spinal CSF space toward the brain so that a distal port and a proximal port on the catheter apparatus are disposed within the CSF space and spaced-apart by a preselected distance;

withdrawing CSF through one of said ports;

conditioning the withdrawn CSF; and

returning the conditioned CSF through the other of said ports.

19. A method as in claim 18, wherein the distal port on the catheter is advanced to a location in the cervical CSF space.

20. A method as in claim 18, wherein the distal port on the catheter is advanced to a location in the cranial subarachnoid space.

21. A method as in claim 18, wherein the distal port and proximal port are spaced-apart by a distance of at least 4 cm.

22. A method as in claim 18, wherein the catheter apparatus consists essentially of a single catheter body having a lumen connected to the distal port and a separate lumen connected to the proximal port.

23. A method as in claim 18, wherein the CSF is returned under conditions which enhance mixing of the returned CSF with the unconditioned CSF.

24. A method as in claim 23, wherein the conditions that enhance mixing or the returned CSF include one or more selected from the group consisting of directed outflow, high pressure injection, injection though multiple ports, a helical catheter, a T-catheter, bellows, ribbed catheter, fins and balloons.

25. A method for conditioning cerebrospinal fluid in a patient, said method comprising:

introducing a catheter apparatus into a brain ventricle;

adjusting spacing between a pair of ports on the catheter apparatus so one port lies on one side of the ventricle and the other port lies on another side of the ventricle;

withdrawing CSF through one of said ports;

conditioning the withdrawn CSF; and

returning the conditioned CSF to the ventricle through the other of said ports.

26. A method as in claim 25, wherein the spacing between the pair of ports is at least 4 cm.

27. A method as in claim 25, wherein each port is in a different ventricle.

28. A method as in claim 25, wherein both ports are in the same ventricle.

29. A method as in claim 25, wherein adjusting the spacing between the pair of ports comprises axially translating a pair of tubular members relative to each other.

30. A system for conditioning cerebrospinal fluid (CSF) in a patient, said system comprising:

a catheter assembly having a first lumen with a distal port and a second lumen with a proximal port, said catheter being adapted to be introduced in a CSF space and said ports being spaced axially apart;

a pump connectable between the first and second lumens to induce a flow of CSF therebetween; and

a conditioning component connectable between the first and second lumens to condition the CSF flowing therebetween.

31. A system as in claim 30, wherein said catheter assembly consists essentially of a single tubular member having the first lumen and distal port and the second lumen and proximal port fixedly disposed therein.

32. A system as in claim 30, wherein said catheter comprises a first tubular member having the first lumen and the distal port therein and a second tubular member having the second lumen and proximal port therein.

33. A system as in claim 32, wherein the first and second tubes may be axially translated relative to each other to adjust the distance therebetween.

34. A system as in claim 30, wherein the pump has a flow rate adjustable between 0.04 ml/min to 30 ml/min.

35. A system as in claim 34, wherein the pump comprises a peristaltic pump which is isolated from the CSF flow.

36. A system as in claim 30, wherein the condition component is selected from the group consisting of biospecific affinity, immunoaffinity, cationic exchange, anionic exchange, hydrophobicity and size exclusion.

37. A system as in claim 30, wherein the system has a CSF retention volume below 40 ml.

38. A system as in claim 30, wherein the system is implantable.

39. A method for ameliorating the symptoms of Alzheimer'"'"'s Disease in a patient, said method comprising:

removing CSF from a first location in a CSF space of the patient;

removing at least one of beta-amyloid or tau proteins from the removed CSF, thereby conditioning the CSF; and

returning the conditioned CSF to the patient at a second location in the CSF space;

wherein the removing and returning steps are performed concurrently during at least a portion of a conditioning treatment.

40. A method for ameliorating the symptoms of Parkinson'"'"'s Disease in a patient, said method comprising:

removing CSF from a first location in a CSF space of the patient;

removing at least one of alpha-synuclein fibrils and oligomers from the removed CSF, thereby conditioning the CSF; and

returning the conditioned CSF to the patient at a second location in the CSF space;

wherein the removing and returning steps are performed concurrently during at least a portion of a conditioning treatment.

41. A method for ameliorating the symptoms of Amyotrophic lateral sclerosis (ALS) in a patient, said method comprising:

removing CSF from a first location in a CSF space of the patient;

removing at least one of insoluble superoxide dismutase-1 (SOD1), glutamate, neurofilament protein, and anti-GM1 ganglioside antibodies from the removed CSF, thereby conditioning the CSF; and

returning the conditioned CSF to the patient at a second location in the CSF space;

wherein the removing and returning steps are performed concurrently during at least a portion of a conditioning treatment.

42. A method for ameliorating the symptoms of cerebral vasospasm in a patient, said method comprising:

removing CSF from a first location in a CSF space of the patient;

removing at least one of erythrocytes, hemoglobin, oxyhemoglobin and endothelin from the removed CSF, thereby conditioning the CSF; and

returning the conditioned CSF to the patient at a second location in the CSF space;

wherein the removing and returning steps are performed concurrently during at least a portion of a conditioning treatment.

43. A method for ameliorating the symptoms of encephalitis in a patient, said method comprising:

removing CSF from a first location in a CSF space of the patient;

removing at least one of tumor necrosis factor-alpha (TNFα

) and IgG from the removed CSF, thereby conditioning the CSF; and

returning the conditioned CSF to the patient at a second location in the CSF space;

wherein the removing and returning steps are performed concurrently during at least a portion of a conditioning treatment.

44. A method for ameliorating the symptoms of Guillain Barre Syndrome (GBS) in a patient, said method comprising:

removing CSF from a first location in a CSF space of the patient;

removing at least one of cells and inflammatory mediators selected from the group consisting of C5a, TNF α

, IL-2, IL-6, interferon-γ

, IgG, and endotoxins from the removed CSF, thereby conditioning the CSF; and

returning the conditioned CSF to the patient at a second location in the CSF space;

wherein the removing and returning steps are performed concurrently during at least a portion of a conditioning treatment.

45. A method for ameliorating the symptoms of Multiple Sclerosis (MS) in a patient, said method comprising:

removing CSF from a first location in a CSF space of the patient;

removing at least one of T cells, B cells, anti-myelin antibodies and inflammatory mediators selected from the group consisting of TNF-α

, IL-2, IL-6, interferon-γ

from the removed CSF, thereby conditioning the CSF; and

returning the conditioned CSF to the patient at a second location in the CSF space;

wherein the removing and returning steps are performed concurrently during at least a portion of a conditioning treatment.

46. A method for ameliorating the symptoms of stroke in a patient, said method comprising:

removing CSF from a first location in a CSF space of the patient;

removing at least one of endothelin and enolase from the removed CSF, thereby conditioning the CSF; and

returning the conditioned CSF to the patient at a second location in the CSF space;

wherein the removing and returning steps are performed concurrently during at least a portion of a conditioning treatment.

47. The method of claim 46, further comprising the step of cooling the CSF.