U.S. patent application number 13/137071 was filed with the patent office on 2011-11-17 for catheter and guide tube for intracerebral application.
This patent application is currently assigned to RENISHAW (IRELAND) LIMITED. Invention is credited to Steven Streatfiled Gill.
Application Number | 20110282319 13/137071 |
Document ID | / |
Family ID | 9932788 |
Filed Date | 2011-11-17 |
United States Patent
Application |
20110282319 |
Kind Code |
A1 |
Gill; Steven Streatfiled |
November 17, 2011 |
Catheter and guide tube for intracerebral application
Abstract
A catheter for use in neurosurgery, and a method of positioning
neurosurgical apparatus. The catheter has a fine tube arranged for
insertion into the brain parenchyma of a patient with an external
diameter of not more than 1.0 mm. The catheter and method may be
used in stereotactically targeting treatment of abnormalities of
brain function, and for the infusion of therapeutic agents directly
into the brain parenchyma. This is advantageous when a therapeutic
agent would have widespread unwanted effects which could be avoided
by confining the delivery to the malfunctioning or damaged brain
tissue.
Inventors: |
Gill; Steven Streatfiled;
(Bristol, GB) |
Assignee: |
RENISHAW (IRELAND) LIMITED
SWORDS
IE
|
Family ID: |
9932788 |
Appl. No.: |
13/137071 |
Filed: |
July 19, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10505240 |
Feb 22, 2005 |
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PCT/GB03/01030 |
Mar 11, 2003 |
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13137071 |
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Current U.S.
Class: |
604/500 |
Current CPC
Class: |
A61M 25/00 20130101;
A61P 35/00 20180101; A61B 90/11 20160201; A61B 2090/103 20160201;
A61P 25/28 20180101; A61M 2210/0693 20130101; A61M 39/0247
20130101; A61M 2039/0273 20130101; A61M 2039/0282 20130101; A61M
25/02 20130101; A61M 2025/0233 20130101; A61M 2025/0042 20130101;
A61M 2039/025 20130101; A61P 9/10 20180101 |
Class at
Publication: |
604/500 |
International
Class: |
A61M 5/142 20060101
A61M005/142 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 12, 2002 |
GB |
0205772.7 |
Claims
1. A method for delivering a therapeutic agent to a desired target
in the brain of a subject, the method comprising the steps of:
inserting a neurosurgical catheter comprising a fine tube with an
external diameter of not more than 1.0 mm into the brain parenchyma
of a patient; and intermittently pumping a therapeutic agent
through the catheter to the desired target.
2. A method according to claim 1, wherein the therapeutic agent
comprises a neurotrophic factor.
3. A method according to claim 2, wherein the neurotrophic factor
is delivered to treat at least one of Parkinson's disease,
Alzheimer's disease and multiple sclerosis.
4. A method according to claim 2, wherein the neurotrophic factor
is delivered to treat stroke or a brain injury.
5. A method according to claim 2, wherein the neurotrophic factor
comprises recombinant-methionyl human glial cell line derived
neurotrophic factor (r-met Hu GDNF).
6. A method according to claim 1, wherein the therapeutic agent
comprises at least one of a Gamma-amino-butyric-acid, an opiate or
an analgesic.
7. A method according to claim 1, wherein the therapeutic agent
comprises a cytotoxic agent and the desired target in the brain
comprises a brain tumour.
8. A method according to claim 1, further comprising a step of
identifying the desired target from diagnostic images of the
patient.
9. A method according to claim 1, wherein the step of inserting a
neurosurgical catheter comprises the steps of forming a hole in the
skull of the subject and stereotactically guiding the catheter to
the desired target.
10. A method according to claim 1, wherein the desired target is
located within at least one of a mesencephalon, a subthalamic
nucleus, a nucleus basalis, a substantia nigra, a pedunculopontine
nucleus, a brain stem, a peri-aqueductal grey matter and a thalamic
nucleus.
11. A method according to claim 1, further comprising a step of
securing the catheter to the skull of the subject after
insertion.
12. A method according to claim 1, wherein the step of
intermittently pumping a therapeutic agent through the catheter to
the desired target in the brain comprises a step of chronically
infusing therapeutic agent to the desired target in the brain.
13. A method according to claim 1, wherein the step of
intermittently pumping a therapeutic agent through the catheter to
the desired target comprises the step of pumping therapeutic agent
through the catheter at, during periods of infusion, a flow rate of
between 2 and 8 micro-litres per hour.
14. A method according to claim 1, further comprising a step of
implanting a pump, a reservoir and tubing into the subject, wherein
the pump, the reservoir and the tubing are used to intermittently
pump the therapeutic agent to the catheter.
15. A method according to claim 1, wherein the step of
intermittently pumping a therapeutic agent through the catheter to
the desired target comprises the step of using a peristaltic
pump.
16. A method according to claim 1, wherein the fine tube has an
external diameter of not more than 0.7 mm.
17. A method according to claim 1, wherein the fine tube has an
external diameter of not more than 0.65 mm.
18. A method according to claim 1, wherein the fine tube has an
external diameter of not more than 0.5 mm.
19. A method according to claim 1, wherein the fine tube is
constructed from polyurethane plastic.
20. A method according to claim 1, wherein the step of inserting a
neurosurgical catheter comprises the step of inserting the fine
tube of the neurosurgical catheter into the brain parenchyma
through a previously inserted guide tube.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent application is a Continuation of application
Ser. No. 10/505,240, filed Feb. 22, 2005, which is a National Phase
filing of PCT/GB03/01030, filed Mar. 11, 2003, which claims the
benefit of priority of Great Britain Patent Application No.
0205772.7, filed Mar. 12, 2002. The disclosures of the prior
applications are hereby incorporated by reference herein in their
entirety.
TECHNICAL FIELD
[0002] The present invention relates to apparatus for use in
neurosurgery, and to a method of positioning neurosurgical
apparatus. The apparatus and method are particularly useful in
stereotactically targeting treatment of abnormalities of brain
function, and for the infusion of therapeutic agents directly into
the brain parenchyma. This would be particularly useful when a
therapeutic agent given systemically will have widespread unwanted
side effects which would be avoided by confining the delivery to
the malfunctioning or damaged brain tissue.
BACKGROUND OF THE INVENTION
[0003] Examples of treating abnormalities of brain function include
the acute infusion of Gamma-amino-butyric-acid agonists into an
epileptic focus or pathway to block transmission, and the chronic
delivery of opiates or other analgesics infused directly to the
peri-aqueductal grey matter or to thalamic targets for the
treatment of intractable pain. Also, cytotoxic agents can be
delivered directly into a brain tumour. Intraparenchymal infusion
could also be used to deliver therapeutic agents to brain targets
that could not be delivered systemically because they will not
cross the blood-brain barrier. For example, the treatment of
patients with Parkinson's disease, Alzheimer's disease, head
injury, stroke and multiple sclerosis may be carried out by the
infusion of neurotrophic factors to protect and repair failing or
damaged nerve cells. Neurotrophins may also be infused to support
neural grafts transplanted into damaged or malfunctioning areas of
the brain in order restore function.
[0004] Intraparenchymal drug delivery has been demonstrated in non
human primates and in rats. For intraparenchymal drug delivery to a
human or non-human brain, it is proposed that a catheter be
implanted, and the drug be pumped intermittently or continuously to
the desired brain target. For long term drug delivery, a pump
containing a reservoir would be implanted subcutaneously and the
reservoir refilled as necessary percutaneously through a palpable
port.
[0005] In particular U.S. Pat. No. 6,042,579 discloses techniques
for treating neurodegenerative disorders by the infusion of nerve
growth factors into the brain.
[0006] In order to perform neurosurgery, the surgeon needs, in the
first instance, to identify the position of the desired target.
This is normally achieved by fixing a stereotactic reference frame
to the patient's head which can be seen on diagnostic images, and
from which measurements can be made. The stereotactic frame then
acts as a platform from which an instrument is guided to a desired
target using a stereoguide that is set to the measured coordinates.
Once an instrument is guided to the desired target, treatment can
begin.
[0007] A number of difficulties are encountered in such
neurosurgical procedures. Sub-optimal placement of the instrument
being inserted may lead to significant morbidity or treatment
failure. Brain targets for treating functional disorders are
usually deeply situated and have small volumes. For example, a
desired target for treating Parkinson's disease is situated in the
sub-thalamic nucleus and is 3-4 mm in diameter, or an ovoid of 3-4
mm in diameter and 5-6 mm in length. Other targets such as the
globus palladus or targets in the thalamus are usually no more than
1-2 mm larger. For such a small target sub-optimal placement of as
little as 1 mm will not only reduce the effectiveness of the
treatment, but may also induce unwanted side affects such as
weakness, altered sensation, worsened speech and double vision.
However, functional neurosurgical targets are often difficult or
impossible to visualize on diagnostic images, and so that actual
position may be need to be inferred with the reference to visible
landmarks in the brain and using a standard atlas of the brain to
assist the process. Anatomical variations between an individual and
the atlas, and even between different sides of the same brain of an
individual means that placement may be sub-optimal. Other reasons
for sub-optimal placement may result from patient movement during
image acquisition, or geometric distortion of imaging which can be
intrinsic to the images method. Also, during surgery, brain shift
can occur which might result from the change in the head position
from that during image acquisition to the position on the operating
table, from leakage of cerebrospinal fluid when a burr hole is made
with a subsequent sinking of the brain, and also from the passage
of the instrument through the brain. Surgeons attempt to correct
these errors by performing electrophysiological studies on the
patient undergoing functional neurosurgery, kept awake during the
procedures.
[0008] Intraparenchymal catheters may be guided to their targets in
the brain using stereotactic techniques. Typically, stereotactic
localization of a brain target is accomplished by fixing the
stereotactic base ring to the skull and identifying the position of
the target using imaging techniques. The position of the target is
identified using three dimension co-ordinates by making
measurements from radio-opaque fiducials attached to the
stereotactic base ring. The stereotactic base ring may then be used
as a platform from which to guide instruments to the target using a
stereoguide on the stereotactic base ring that is set to the
measured co-ordinates. The catheter may then be guided towards the
target through the brain tissue after rigidifying it by the
insertion of a stiff wire through its bore. Alternatively, a
straight wire may be guided to the target first, and the catheter
introduced around the wire so that one end (i.e. the inserted or
distal end) is located within the brain, and the opposite end (i.e.
the external or proximal end) remains outside the brain. Once
positioned, the external end of the catheter can be fixed to the
skull, and connected to a pump whereby the therapeutic agent may be
administered. It will be appreciated that the outer diameter of the
catheter tubing should be as small as possible, particularly when
especially sensitive parts of the brain are to be treated, such as
the mesencephalic targets, and are therefore to be passed through
by the catheter. Such highly sensitive regions of the brain tend to
be located in deep positions typically between 70 and 100 mm from
the surface of the skull, such as the brain stem. Of course, the
thinner the catheter tubing, the greater the deflection during
insertion to those deep targets within the brain, and the increased
likelihood that placement will be sub-optimal.
SUMMARY OF THE INVENTION
[0009] The present invention seeks to optimize the placement of the
catheter whilst minimizing the trauma to the brain by utilizing
small diameter catheter tubing.
[0010] According to a first aspect of the invention there is
provided a neurosurgical catheter having a fine tube arranged for
insertion into the brain of a patient with an external diameter of
not more than 1.0 mm. It is preferred that the external diameter of
the catheter is not more than 0.7 mm, and even more preferred that
it is not more than 0.65 mm. Most preferably, its external diameter
if not more than 0.5 mm. The catheter is preferably generally
circular in cross section.
[0011] It is also preferred that the catheter is a deep target
neurosurgical catheter and has a length of at least 40 mm, more
preferably at least 70 mm and most preferably at least 90 mm.
[0012] Since the fine tube is so fine, it is desirable for the
catheter to further comprise a connector tube connected to one end
of the fine tube, the connector tube being of greater diameter than
the fine tube. Preferably the connector tube has an outer diameter
of about 2 mm. Connection may be achieved by the inclusion of a hub
disposed between the fine tube and the connector tube. According to
a preferred embodiment, the hub includes a passageway connecting
the fine tube and the connector tube, the passageway including a
first passage in which the fine tube is securely inserted, a second
passage in which the connector tube is securely inserted and a
further link passage disposed between the first and second
passages.
[0013] In a preferred embodiment, the hub includes a cylindrical
body and one or more flanges by which the hub can be secured to the
skull of the patient. The hub may be secured using any fixing
arrangement, including glue and screws. It is particularly
preferred that each flange includes an internal surface defining a
countersunk hole by which the hub can be secured to the skull of a
patient by screws.
[0014] Preferably, the hub includes a stop surface adjacent to
where the fine tube is secured to the hub. It is also preferred
that the hub is tapered towards that stop.
[0015] According to a second aspect of the invention, there is
provided a neurosurgical instrument comprising a tube for insertion
into the brain of a patient towards a desired target, the tube
having a distal end for insertion into the brain, a proximal end
and a head disposed at the proximate end of the tube for attachment
to the skull of the patient; and a catheter according to the
present invention for insertion into the brain of the patient via
the tube. Other advantageous or preferred features of the catheter
are described above.
[0016] Preferably, the head of the guide tube includes an
externally threaded surface for engagement with the skull of the
patient via an acrylic cement. According to a preferred embodiment,
the head includes a slotted dome structure, and the catheter has a
hub having a stop at one end which abuts the dome structure once
the fine tube has been inserted into the guide tube. The slot is
preferably shaped such that, as the catheter is bent over in the
slot, it resists kinking. The domed structure is preferably shaped
such that, as the catheter is bent over in the slot with the stop
abutting the domed surface, the distal end of the catheter will
remain accurately located at its target. Reference is made to
GB-A-2357700 which discloses a guide tube with a head having a
domed structure, the disclosure of which is incorporated herein by
reference.
[0017] According to a third aspect of the invention there is
provided a neurosurgical guide device comprising a tube for
insertion into the brain of a patient towards a desired target, the
tube having distal end for insertion, an opposite proximal end and
a head disposed at the proximate end of the tube for attachment to
the skull of the patient, characterized in that the internal
diameter of the tube is not more than 1 mm; wherein the tube is of
a length such that the distal end falls short of the target by
between 1 and 20 mm. Preferably the length is such that the distal
end falls short by between 5 and 10 mm.
[0018] According to a fourth aspect of the invention, there is
provided a method of positioning a catheter at a target in the
brain of a patient comprising; inserting a neurosurgical guide tube
according to the third aspect of the present invention into the
brain towards the target, wherein the distal end falls short of the
target by between 5 and 20 mm; securing the head of the guide
device to the skull; and inserting a catheter according to the
present invention through the tube and to the target.
[0019] It is preferred that the catheter is positioned at a deeply
positioned target of at least 40 mm from the surface of the skull,
more preferably at least 70 mm from the surface, and most
preferably at least 90 mm from the surface of the skull.
[0020] The present application comprises a kit comprising:
[0021] one or more neurosurgical catheters according to the present
invention;
[0022] one or more guide tubes for insertion into the brain of a
patient towards a desired target, each tube having distal and
proximate ends and a head disposed at the proximate end of the tube
for attachment to the skull of the patient; and
[0023] one or more guide wires.
[0024] Preferably, the kit according is provided in a pack having
separately marked sections, wherein each section contains one
catheter, one guide tube and one guide wire. This enables each set
of elements (i.e. the catheter, the guide tube and the guide wire)
can be distinguished from other sets of the elements. This is
important when different sets of elements are used on different
sites of the brain.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] Embodiments of the present invention will be described by
way of example only with reference to the accompanying drawings in
which:
[0026] FIG. 1 is a view of a catheter according to the present
invention;
[0027] FIG. 2 is a view showing part of the catheter of FIG. 1 with
internal features shown in dotted lines;
[0028] FIG. 3 is an end view of the catheter from the right hand
end of FIG. 2;
[0029] FIG. 4 shows a first phase of stereotactic insertion;
[0030] FIG. 5 shows a second phase of stereotactic insertion;
[0031] FIG. 6 shows a third phase of stereotactic insertion;
[0032] FIG. 7 shows a fourth phase of stereotactic insertion;
[0033] FIG. 8 is a perspective view of a guide tube with a
dome-shaped head;
[0034] FIG. 9 is a sectional view of the guide tube of FIG. 8 with
the dome-shaped head;
[0035] FIG. 10 is a schematic view showing the catheter of FIG. 1
inserted through a guide tube; and
[0036] FIG. 11 is a view of the catheter in situ once insertion is
complete.
DETAILED DESCRIPTION OF THE INVENTION
[0037] As explained above, insertion of a catheter into
particularly sensitive regions of the brain leads to trauma on
insertion which surgeons wish to minimize. The finer the catheter
the less trauma the brain experiences. However, since the accuracy
of insertion is crucially important, and since these particularly
sensitive areas of the brain are a considerable distance from the
skull surface, larger diameter catheters have been considered to be
necessary in order to accurately place the distal end of the
catheter. However, the present invention allows much finer
catheters to be used.
Example 1
[0038] FIGS. 1, 2 and 3 show a catheter 1 according to the present
invention. The catheter 1 includes a length of fine tubing 2, the
outer diameter which is no more than 1 mm, and most preferably no
greater than 0.7 mm. It is even more preferred that the outer
diameter be no more than 0.5 mm. In this instance, the catheter
tubing 2 is constructed from polyurethane plastic and preferably
from carbothane 55 DB20 (Thermedics Polymer Products, Woburn Mass.,
USA). The fine tubing 2 is linked to a length of connector tubing 3
having an outer diameter of about 2 mm, via a hub 4. The connector
tubing 3 is, in this case, made from polyurethane plastic, such as
carbothane 85AB20, although other materials could also be used.
[0039] The hub 4 in this case is also constructed using
polyurethane, such as carbothane 72 DB20. Again, other materials
may also be appropriate.
[0040] The fine tubing 2 is intended to be inserted into the brain
of a patient, whereas the connector tubing 3 is intended to be
connected to outflow tubing of a pump by which a therapeutic agent
may be pumped intermittently or continuously to a desired brain
target. For long term drug delivery, the pump would be implanted
subcutaneously and the reservoir refilled as necessary
percutaneously through a palpable port. In this case, the connector
tubing 3 would be connected to outflow tubing of the pump which
would be tunneled subcutaneously from the pump to the catheter.
It's length will depend on particular installations and will be cut
to length appropriately.
[0041] The hub 4 includes a central body 5, which is generally
cylindrical and a pair of diametrical opposing wings 6 each a
containing a countersunk hole whereby the hub may be screwed to the
outer surface of the skull of the patient.
[0042] The cylindrical body 5 of the hub 4 includes a passageway
passing through its complete length. The passageway includes a
first narrow passage 8 of uniform diameter into which the fine
tubing is inserted and securely held. The passageway also includes
a second wide passage 9 of uniform diameter into which the
connector tubing 3 is inserted and securely held. Between the first
and second passages 8, 9 is a third linking passage 10 which is
generally tapered in order to take account of the different
internal diameters of the fine tubing 2 and the connector tubing 3.
It will be noted that the ends of the third passage 10 are of the
same or very similar diameter to the internal diameters of the fine
tubing 2 and the connector tubing 3.
[0043] From FIG. 2, it can be seen that the right hand end of the
hub 4 is frustoconical, and the end of the hub is planar and forms
a stop 11, the significance of which will be understood from the
description below.
Example 2
[0044] The insertion of the catheter will now be described.
Firstly, a stereotactic frame is attached to the patient's skull
and the position of the intracranial target is identified by
imaging the patient wearing the stereotactic frame and defining the
position of the target as three dimensional co-ordinates. This step
is explained in more detail in the introduction to this patent
specification and is a standard technique within the field of
neurosurgery.
[0045] Once the target has been defined, a stereoguide is used
which is set to the target coordinates. An appropriately sized
guide tube having an internal diameter of no more that 1 mm is
directed into the brain in the direction of the target. The guide
tube is arranged with a head at one end, which, once inserted, can
be attached to the patient's skull, for example by being bonded
into a burrhole in the skull using an acrylic cement.
[0046] Before insertion, the guide tube is cut to a length short of
the target, and sufficiently short that, while it passes through
brain tissue, it does not enter those parts of the brain which are
particularly sensitive to trauma. The distal end of the guide tube
will typically fall several millimeters short of the target. The
distance from the top of the head of the guide tube to the target
is then measured, and a radio-opaque stylette is cut to length such
that, when inserted down the guide tube it's distal end reaches the
planned target. This means that the stylette will extend beyond the
distal end of the guide tube.
[0047] The patient is then re-imaged in order to confirm the
satisfactory placement of the stylette prior to removing the
stylette and replacing it with the intraparenchymal catheter cut to
the same length as the stylette. Again, the catheter will have an
outer diameter of no more than one millimeter although it will be
appreciated that the catheter, the stylette and the guide tube will
all be matched so that the catheter and stylette will fit properly
within the guide tube. If it is desired to use a very fine catheter
of, say, 0.65 mm in outer diameter, an appropriate guide tube will
also be used with an internal diameter of 0.75 mm.
[0048] When the catheter is inserted, it is expected that it will
be reinforced during insertion by the location of a stiff wire
through it's bore, most likely made from tungsten. Once the
catheter has been inserted in the guide tube, the stop 11 on the
hub 4 will abut the head of the guide tube meaning that the distal
end of the catheter has reached the target. The stiff wire is
removed, and the fine tubing 2 is bent through about 90.degree. so
that the hub 4 can be secured to the outer surface of the skull
using screws passing through the countersunk holes 7. To facilitate
the bending, the head of the guide tube is dome shaped and arranged
such that, during bending, not only will the fine tubing 2 not
kink, but also the distal end of the fine tubing will not move.
This will be explained in more detail later in this
specification.
[0049] The connector tubing 3 can then be connected to the outflow
tubing of a pump. Generally, the connector tubing 3, will be
tunneled subcutaneously to the remotely positioned pump.
Example 3
[0050] In an alternative insertion technique, a number of phases or
steps are taken which are shown in FIGS. 4 to 7. As will be
appreciated, small diameter catheters have a tendency to drift off
the planned trajectory during insertion as a result of the
flexibility inherent in a small diameter instrument. Since
neurosurgical targets are often deeply situated, typically 70-80 mm
from the surface of the skull, and sometimes as much as 100 mm from
the skull surface, the catheter must normally be very rigid, and
therefore of a larger diameter.
[0051] Examples of possible targets include parts of the
mesencephalon including the subthalamic nucleus, the substantia
nigra and the pedunculor-pontine nucleus. This is a particularly
critical region of the brain, where it is important to minimize
trauma from the passage of an instrument, which is typically
situated about 70-80 mm from the skull surface and contained within
a volume which has a height of approximately 20-25 mm.
[0052] To facilitate insertion of very fine catheters into
mesencephalic targets, insertion takes place as follows.
[0053] Firstly, a small diameter tungsten guide wire 22 of 0.6 mm
in diameter is inserted in a tube 21 with an outer diameter of 1.7
mm and fixed within the tube 21 with a finger-tightened grub screw
23 such that the wire 22 protrudes from the distal end of the tube
21 by 25 mm. The tube 21 is tapered towards its end for a length of
20 mm. The tube 21 and wire 22 can be seen in FIG. 4 showing the
first phase of insertion in which the tube 21 with the wire 22
projecting from its end can be seen. The finger tightened grub
screw 23 can be seen at the top of tube 21, in which the wire 22 is
held. Insertion takes place from a stereotactic frame in which the
target has been identified and defined in terms of three
dimensional coordinates. The stereotactic frame carries a
stereoguide which has been modified in order to permit this
technique. During the first phase of insertion shown in FIG. 4, the
tube and wire are together lowered towards the target. In this
case, the tube is 165 mm in length, and since the tube 21 and the
wire are inserted as a unit, the distance from the top of the tube
to the tip of the guide wire 22 is 190 mm. The wire 22 extends
above the top of the tube by approximately 150 mm. The stereoguide
includes an upper clamp 24 and a lower clamp 25, and each of these
clamps can be swiveled between a position of engagement with the
wire or tube which is being inserted or removed, and a position
remote from that.
[0054] Once the guide wire 22 has reached its target, the upper
clamp 24 is swiveled to clamp the proximal end of the guide wire
22. Once the grub screw 23 has been loosened, the tube 21 can be
withdrawn from the brain leaving the wire 22 in situ. Once the tube
21 has been raised up towards the upper clamp, the lower clamp can
be swung across to clamp the now exposed wire 22, and the upper
clamp 24 can be released, as shown in FIG. 5. This allows the tube
21 to be removed altogether from the top of the wire 22.
[0055] A guide tube 31 is threaded onto the wire 22, and the upper
clamp 24 is then swung around and closed on the wire 22. The lower
clamp 25 can then be released to allow the guide tube 31 to be
inserted into the brain so that its distance is approximately 1 or
2 cm short of the target, also shown in FIG. 7. The guide tube 32
has at its upper end a head with a threaded outer surface which
permits the head to be screwed into the tapped burrhole in the
patient's skull, thereby securing the guide tube 31 securely in
position. Further features of the head will become clear later in
this description.
[0056] Once the guide tube 31 is installed, the guidewire 22 may be
removed and FIG. 7 shows that a 0.65 mm catheter 36 can then be
inserted down the guide tube 31 to the target.
[0057] This method has the particular advantage that, on the first
pass, the guide wire being stiffened by the tube 21 will hit the
target, and then by inserting a guide tube short of the target, the
brain target will be fixed and the guide tube will facilitate the
insertion of a very fine instrument to the target. For the
treatment of certain conditions such as Alzheimer's disease it is
necessary to deliver nerve growth factors to targets in the nucleus
basalis through several in-dwelling catheters. If each catheter is
only 0.65 mm in diameter, multiple fine catheters can be inserted
without substantially disrupting the tissue it is intended to
regenerate.
[0058] In this insertion method, certain diameters of the wire 22,
the inside of the tube 21, the outside of the tube 21 and the
diameters of the guide tube 31 and the catheter 36 have been
referred to. Of course, it will be appreciated that different
diameters may be suitable and that the important factor is that the
outer diameter of the wire 22 and of the fine catheter 36 which
passed through the mesencephalon are as fine as possible, and no
larger than 1 mm in cross section. It is preferred that the
diameter is no more than 0.7 mm, and even more preferred that it is
not more than 0.65 mm.
[0059] The top part of the guide tube 31 is shown in FIGS. 8 and 9
from which it will been seen that the top of the tube 41 carries a
head 42 which has a threaded outer surface which can be screwed
into the burrhole in the skull through which instruments are
inserted. The top of the tube 41 opens into a slot 44 in the head
42. The head 42 is formed with a dome structure 45 in which the
slot 44 is located.
[0060] As will been seen from FIG. 9, once the head has been
secured into the skull, the catheter is located in the tube 41 and
is then bent from position small y to position small z. The inner
edge around which the catheter is bent is radiused and is shaped in
the slot 44 such that the catheter will not kink and such that the
distance from x to y is the same as the distance from x to z so
that the distal end of the catheter is not moved during the bending
process.
[0061] It will be understood from FIGS. 8 and 9, that, in this
embodiment, the guide tube 31 is formed with the head 42 including
the threaded surface 43 and the domed structure 45 as an integral
unit.
[0062] Referring now to FIGS. 10 and 11, it will be seen that a
catheter has been inserted into the brain on a stiff wire (not
shown) such that the stop 11 abuts the top of the dome structure
45. At this point, the stiff wire is removed and the distal end of
the catheter is in the correct position for treatment. The catheter
is then bent over to the position shown in FIG. 11 maintaining the
stop 11 against the dome structure 45. FIG. 11 also shows how the
hub 4 is attached via screws to the skull, and how the connector
tubing 3 is directed off towards the pump.
[0063] It is preferred that the catheter delivers drugs through a
single port at its distal end. This has advantages over catheters
with multiple ports at their distal end that may be used for
intraparenchymal delivery to the brain. In particular, the use of a
single port minimizes the risk of the port becoming obstructed at
the low flow rate anticipated for intraparenchymal delivery from
the build up of proteinaceous material or gliotic ingrowth. A
further advantage of having a single port at the distal end of the
intraparenchymal catheter is that it ensures drug delivery at the
defined target. The site of drug delivery from a multiport catheter
is unpredictable, particularly at low flow rates. This is because
flow will be maximal through the port with the lowest resistance.
Even though the ports may be of an identical size, the degree to
which tissue obstructs any individual port will vary. The net
result will be off-axis drug delivery, probably from a single port,
which will be sub-optimal for drug delivery to a small target.
[0064] Trauma to the brain is minimized upon insertion as a result
of using a very fine catheter of no more that 1 mm in diameter and
preferably less than 0.7 mm in diameter. In addition, the small
diameter catheter makes it suitable for drug delivery to small
targets in the brain stem such as the substantia nigra and the
pedunculopontine nucleus as well as to other small targets such as
the nucleus basalis, the peri-aqueductal grey matter and various
thalamic nuclei.
[0065] During infusion of a therapeutic substance, the substance
flowing from the catheter port or ports will preferably follow the
path of least resistance, i.e. flow back along the tissue/catheter
interface, up to the cortical surface and then into the CSF
compartment.
[0066] Depending on the flow rate it will defuse variably into the
tissues with an ovoid volume of distribution. Containing the drug
within a small brain target can therefore be a problem. If,
however, the catheter has been inserted into the brain down an
indwelling guide tube as in the present invention, then drug
exiting the distal port flows back along the tissue/catheter
interface until it reaches the guide tube. It then flows preferably
along the interface between the guide tube and the catheter and out
of the skull into the subgaleal compartment of the scalp. The
volume of brain tissue exposed to the drug can therefore be
controlled by adjusting the length of the catheter that projects
beyond the guide tube as well as adjusting the flow rate. Such fine
control is essential if one is to contain delivery of thugs such as
neurotrophins within small brain targets.
Example 4
[0067] In a trial the intraparenchymal catheter of the present
invention was implanted into the brains of five patients with
advanced Parkinson's disease via a guide tube, the distal end of
which was positioned just short of the desired target. One patient
had the catheter implanted unilaterally and four had bilateral
implants into the dorsal putamen (i.e. the desired target).
Recombinant-methionyl human glial cell line derived neurotrophic
factor (r-met Hu GDNF) was chronically infused through the
catheters into their dorsal putamen via remotely positioned pumps
(8626 Synchromed Pumps, Medtronic Inc, Minneapolis), implanted
subcutaneously in the abdominal wall. GDNF is a neurotrophic factor
that has been shown to reverse the symptoms of experimentally
induced Parkinson's disease in animals. In this trial in humans it
was infused at flow rates ranging from 2 to 8 .mu.l per hour and
doses between 10.8 and 43.2 micrograms/putamen/day. The patients
were assessed preoperatively and at six months using the
internationally recognized and validated scoring system for
assessing the severity of Parkinson's disease, the Unified
Parkinson's Disease Rating Score (UPDRS). At six months there was a
40% improvement in the patients UPDRS scores. The infusions were
well tolerated and there were no major side affects.
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