Patent Application
20170203083
The present application claims foreign priority to European Patent Application EP 16151558.0 that was filed on Jan. 15, 2016, the contents thereof being herewith incorporated by reference in its entirety.
The present invention relates to a method and system adapted to adjust in vivo an implanted valve for hydrocephalus treatment. The method includes a test method performed in vivo which is adapted to detect a failure of such valve.
Some people have abnormal accumulation of cerebrospinal fluid (CSF) in the spine and ventricles, or cavities, of the brain. This may cause increased intracranial pressure (ICP) inside the skull. The elevated intracranial pressure may cause compression of the brain, leading to brain damage and other complications. This neurological disease is called hydrocephalus.
For a healthy person, CSF continuously circulates through the ventricles of the brain and the spinal cord. The CSF is continuously drained away into the circulatory system. Hydrocephalus is related to an accumulation of CSF in the brain ventricles. Hydrocephalus is usually caused by a blockage of CSF outflow in the ventricles or in the subarachnoid space over the brain. Even if the outflow passages are blocked, the production of CSF continues, consequently causing an excess of pressure that compresses the nervous tissue and expands the ventricles. Compression of the nervous tissue usually results in irreversible brain damage. If the skull bones are not completely ossified when hydrocephalus occurs, the pressure may also severely enlarge the head. Alternatively, the condition may result from an overproduction of the CSF fluid, from a congenital malformation blocking normal drainage of the fluid, or from complications of head injuries or infections.
Theoretically, hydrocephalus can be successfully treated by placing a drainage tube (shunt) between the brain ventricles and another cavity (often the peritoneum) to eliminate the high internal pressures. Once the hydrocephalus has been diagnosed, a physician performs several tests so as to characterize the cerebrospinal fluid (CSF) dynamics and then he can implant the shunt. It involves the placement of a ventricular catheter into the cerebral ventricles to bypass the flow obstruction and/or drain the excess fluid into other body cavities, from where it can be reabsorbed. Most shunts drain the fluid into the peritoneal cavity (ventriculo-peritoneal shunt, or VP shunt), but alternative sites include the right atrium (ventriculo-atrial shunt), pleural cavity (ventriculo-pleural shunt), and gallbladder. A shunt system can also be placed in the lumbar space of the spine and have the CSF redirected to the peritoneal cavity (LP Shunt).
With the VP shunt, a surgical procedure provides an opening in the skull through which an entry catheter is introduced and passed through the brain tissue into the ventricles. The catheter is fluidly connected to the valve, which is implanted toward the back of the patient's head to control fluid flow. A second exit catheter is also fluidly connected to the valve and leads to the peritoneal cavity.
In a general manner, any information about CSF flow or pressure is fundamental to diagnose and to characterize cerebral disease. In case of abnormal function of the cerebrospinal fluid outflow system (which is reviewed by M. Pollay (Pollay M., The function and structure of the cerebrospinal fluid outflow system, Cerebrospinal Fluid Research 2010, 7:9)), several methods are used to diagnose hydrocephalus. In practice, the constant-rate infusion test is the most frequently used, said method has been proposed by S. Sokolowski (Sokolowski S., Bolus injection test for measurement of cerebrospinal fluid absorption, Journal of the Neurological Sciences 28: 491-504 (1976)). A mathematical modelling of the rise of ICP after injection of a saline solution in the subarachnoid space has been described by Marmarou A. et al., “A nonlinear analysis of the cerebrospinal fluid system and intracranial pressure dynamics,” J. Neurosurg. 48, 332-344 (1978). Other mathematical modeling has been described by M. Clarke et al., “The history of mathematical modeling in hydrocephalus,” Neurosurg. Focus 22 (4):E3, 2007 for a review of the history of mathematical modeling in hydrocephalus CSF dynamics, and other refined models are proposed in Smillie A. et al., “A hydro-elastic model of hydrocephalus,” Journal of Fluid Mechanics 539: 417-443 (2005) and Raman K., “A stochastic differential equation analysis of cerebrospinal fluid dynamics,” Fluids Barriers CNS 8:9 (2011). A review of the different improvements of this initial model is also proposed by M. Czosnyka et al., “Czosnyka M. et al., Modeling of CSF dynamics: Legacy of Professor Anthony Marmarou, Acta Neurochirurgica Supplementum, Vol. 113, 9 (2012).” All of these models could be used as a theoretical basis for differential diagnosis in hydrocephalus. Nevertheless, these models require infusing a fluid in the cranial cavity so as to increase artificially the fluid in the ventricles which may cause risks for the patient.
Usually, two distinct types of valve are provided to the patient:
The first type of valve allows adjusting the CSF outflow. This valve cannot be regulated after implantation. Thus the physician has to estimate the patient requirement before the surgery. Unfortunately, despite the numerous studies, these valves cannot perfectly be customized before implantation. A cause may be related to the fact that the characterization of the CSF dynamics cannot be 100% accurate; another cause may be that the CSF dynamics changes over time. In many cases, the shunt shall be adjusted after its implantation.
The second type of valve allows adjusting the intracranial pressure (ICP). The valve opens when the fluid pressure reaches a threshold pressure and some of these valves may be tuned in vivo to adjust this threshold. The methods used for the adjustment require infusing a fluid in the valve (or upstream the valve). Said adjustment is a critical step and, in most cases, the physician adjusts the setting only depending on the patient feeling. Few shunts comprise an absolute pressure sensor to monitor the ICP and the data of the measurement help the caregiver to adjust the setting of the shunt.
Another drawback of these valves is that the valve may open when the patient stands up due to the pressure gradient between the cranial cavity and the peritoneal cavity. Indeed, when the patient is in upright position, the differences in height between the head and the peritoneal cavity (for CP shunt) cause over drainage of CSF. Such over-drainage of CSF could have a negative impact as that would lead to very low ICP (i.e. below −10 mmHg) potentially causing tearing of bridging veins or subdural hematomas. Thus, these shunts may comprise an anti-siphon device which stops the flow when the pressure gradient reaches a determined threshold. The physician has to determine said determined threshold which allows closing the valve. Thus, such shunt stops the flow when the patient is in upright position, this induces a progressive growth of the ICP (because when the patient is in upright position, the valve is closed) and it may as well pose an extra risk of the shunt becoming blocked due to a malfunction of the device (constantly closed).
Thus, the shunt has to be regularly monitored so as to re-adjust the setting according to the feedback patient and to check proper functioning of the valve. Furthermore, with the prior art device, it is difficult to detect a failure and it is impossible to determine the type of failure. This induces, if a potential failure is detected, the device is changed and a surgical procedure has to be performed.
Accordingly, in light of all these deficiencies of the background art, advanced solutions as a device and a method for adjusting a hydrocephalus valve are desired.
According to one aspect of the present invention, the drawbacks of the background art is overcome by offering a device and method which improve the patient life by limiting surgical procedures and by offering a valve which is easy to set and which allows detecting several failures and a non-invasive characterization of the CSF dynamics.
Moreover, the present invention relates to a method of using an adjustable valve for the treatment of hydrocephalus. The adjustable valve includes a fluid path which comprises an inlet in fluid communication with the cranial cavity of a patient and an outlet in fluid communication with in the other cavity of the patient. The adjustable valve may further include an adjustment element adapted to adjust the flow (flow rate or pressure) of the fluid body in the fluid path. A first method may comprise the following steps:
The step of measuring may be performed over a determined period of time. During the step of measuring, no modulating of the setting may be performed. The body of the patient may be initially placed in a determined position which can be decubitus, upright or inclined.
In the step of determining, the optimal setting of the adjustment element or the failure of the adjustable valve or the characterizing of the CSF dynamics may be further determined based on a determined position of a body of the patient and/or may be further determined based on a first setting and a second setting of the adjustment element, the second setting being different from the first setting.
The method may further comprise a step of analyzing a profile of the pressure data of the gradient.
The step of determining or the step of characterizing may use a mathematical model based on at least one of the following parameters: a previous setting, a variation of the fluid pressure, a determined period of time, a derivative dP/dt of the fluid pressure, pressure data measured with previous and current settings, a curve slope of the pressure data, a reference of pressure data, the amplitude or the frequency of the pressure curve or a position of a body of a patient.
The method may further comprise a step of changing a position of a patient for a determined period of time. The step of modulating the setting and the step of changing the position may be performed successively and repeatedly. The position of the patient may be chosen to be decubitus, upright, or inclined.
The method may further comprise a step of determining a sign of a time derivative of the fluid pressure. The adjustable valve may be in communication with a remote controller for adjusting the valve, and the adjustable valve may configured to communicate the pressure data to the remote controller in a wireless manner. The pressure sensor may be arranged in the fluid path.
The step of characterizing may further comprise the computing of E (brain elastance), Rout (residual drainage resistance), P0 (the pressure in the extradural venous system) and/or PP (peritoneum pressure).
A second method may comprise the following steps:
The steps of measuring may be performed over a determined period of time.
The method may further comprise the step of modifying a setting of the adjustment element. In this case, the optimal setting of the adjustment element or the failure of the adjustable valve or the characterizing of the CSF dynamics may be further determined based on a first setting and a second setting of the adjustment element. The method may comprise a successive and repeated steps of modifying the setting and the patient position. And the first and the second determined position may be decubitus, upright or inclined.
The step of characterizing may further comprise the computing of E (brain elastance), Rout (residual drainage resistance), P0 (the pressure in the extradural venous system) and/or PP (peritoneum pressure).
The present invention further relates to a method of sensing a failure of a valve for the treatment of hydrocephalus, a third method may comprise the following steps:
The failure of the medical device may be further determined based on the first and the second position of the body. The failure of the medical device may be an occlusion, a partial occlusion or a leakage.
The method may further comprise a step of determining the location of the failure in the medical device.
The medical device further may comprise an adjustment element adapted to adjust the flow of the fluid body in the fluid path, and the method may further comprise a step of modifying the setting of the adjustment element.
The method may further comprise a successive steps of modifying the setting and the patient position. The first and the second determined position can be decubitus, upright or inclined.
An occlusion in the medical device may be determined when the difference between first data and the second data is equal or close to zero or lower in absolute value to a reference value.
A fourth method may comprise the following steps:
The step of analyzing may comprise the characterization of the amplitude and/or the frequency of the pressure peak.
The step of determining may be based on the comparison of the curve of the measured pressure profile and a reference curve. In this case, the reference curve may be obtained by a step of measuring a set of data related to the pressure gradient between the inlet and the outlet with an initial setting of the adjustment element before the changing step. And the initial setting of the adjustment element may be the optimal setting after the implantation of the medical device.
The failure of the medical device may be one of following failure: occlusion, partial occlusion and a leakage.
The method may comprise a step of determining the location of the failure in the medical device. The measuring steps may be performed over a determined period of time. The failure of the medical device is further determined based on the position of the patient body. The patient position can be decubitus, upright or inclined. The method may comprise a step of changing the patient position. The method may comprise a successive and repeated steps of modifying the setting and the patient position.
A fifth method may comprise the following steps:
For example, a first aspect of the invention is a method of adjustment for in vivo a medical device which may comprise the following steps:
The method may further comprise the following step: determine the sign of the time derivative of the monitored differential pressure. The curve analysis may be the analysis of the curve slope. The curve may be compared to a reference curve which may be obtained via a previous analysis.
The first setting may be characterized by a first flow rate. The second setting may be characterized by a second flow rate which may be less than the first flow rate. The adjusting step and/or the monitoring step may be repeated until the curve is substantially planar.
The patient may be placed in a supine position or in a stand up position during a predetermined period of time. The patient position may be changed, for example: from a supine position to a stand up position or from a stand up position to a supine position.
A medical system may comprise said medical device and a remote controller which comprises a screen displaying the data of the monitored differential pressure. The medical device may be adapted to communicate the data to the remote controller in a wireless manner. The pressure sensor may be arranged in the medical device.
Preferentially, the fluid variable may be the fluid pressure or the flow rate. The medical device may be an adjustable flow regulator.
To illustrate the method, an example of an adjustable flow regulator is given. Similar flow regulator has been described in the European Patent Applications EP 09709010.4, EP 09807973.4, EP 11710307.7, EP 14706081.8 and EP 15175963.6 filed by Debiotech SA, these references being herewith incorporated by reference in their entirety. The contents of these documents are incorporated by reference in the present account. The principle of such device is based on the elastic distortion of a membrane that goes into contact with a substrate. These flow regulators types comprise a fluid inlet adapted to be connected to a fluid reservoir (for example the cranial cavity) and a fluid outlet adapted to be connected to a delivery location (for example the peritoneal cavity). Said regulators may comprise a substrate and a flexible membrane tightly linked together in predefined linking areas so as to define a cavity there between. Said cavity is fluidly connected to the fluid outlet and to the fluid inlet. The substrate and/or the membrane may comprise a through hole contiguous with said cavity, to define a pathway for a fluid from said fluid inlet to said fluid outlet. Thus, the flexible membrane allows regulating the flow rate (at the outlet) for a predetermined range of a pressure (for example: the transmembrane pressure, i.e. the gradient pressure between the inlet and the outlet). Said flow rate may be substantially constant for said predetermined range of pressure gradient.
The substrate may be at least partially flexible. For example, the substrate may comprise a rigid mesa surrounded by a flexible ring. Thus the mesa may move in a same direction of membrane movement. The bottom of the mesa (for example the mesa side which is not in contact with the cavity) may be operatively coupled (for example attached, glued . . . ) to an element, which allows adjusting the relative position of the mesa. Said adjustment may be performed without contact using adjusting means such as a magnetic rotor. The increase (resp. decrease) of the preload inducing an increase (resp. decrease) of said valve openings and therefore a decrease (resp. an increase) of the flow rate. Thus, the flow rate (at the outlet) can be adjusted by adjusting the relative position of the substrate. In this way, the device can adjust and regulate the flow rate, for a predetermined pressure range. Several pre-settings may be available and the user selects a setting corresponding to a desired flow rate for a pressure range.
Such adjustable valve (i.e. CSF flow regulation as described above) is of a major interest compared to purely passive device because, for a given patient, the production rate of ICP may be not known a priori and it is therefore highly desirable to have a flow regulator having a flow rate that can be adjusted after implantation.
A sensor may monitor the pressure gradient between the two opposed surfaces of the membrane. In case of hydrocephalus shunt, said pressure gradient may be substantially equal or very close to the pressure gradient between the proximal catheter (i.e. the ICP (intracranial pressure)) and the distal catheter. The sensor may made of strain gages arranged on a surface of or in the flexible membrane.
For example, a second aspect of the invention is a method of detecting a failure of the device. The monitoring of the variation of pressure when the patient moves from horizontal to vertical position may be used as indicator of failure.
Starting from the premise that:
ΔPh−ΔPv=HP (1)
The value of HP is directly proportional to the head height between the device and the outlet of the distal catheter in the peritoneum (for example from 20 to 40 cm of water corresponding to HP=20 to 40 mbar). This value can be determined just after implantation to “calibrate” the device, for example by measuring the fluid pressure in upright position and decubitus position.
This mathematical model may be used to detect at least one following failures: total occlusion, partial occlusion and leakage.
For example, a third aspect of the invention is a method for a non-invasive characterization of the CSF dynamics on the logical approach described above.
The above and other objects, features and advantages of the present invention and the manner of realizing them will become more apparent, and the invention itself will best be understood from a study of the following description with reference to the attached drawings showing some preferred embodiments of the invention.
The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate the presently preferred embodiments of the invention, and together with the general description given above and the detailed description given below, serve to explain features of the invention.
Herein, identical reference numerals are used, where possible, to designate identical elements that are common to the figures. Also, the images are simplified for illustration purposes and may not be depicted to scale.
In the following detailed description, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration several embodiments of devices, systems and methods. It is to be understood that other embodiments are contemplated and may be made without departing from the scope or spirit of the present disclosure. The following detailed description, therefore, is not to be taken in a limiting sense. The invention is set forth and characterized in the independent claims, while the dependent claims describe other characteristics of the invention.
All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. The definitions provided herein are to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.
As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” encompass embodiments having plural referents, unless the content clearly dictates otherwise.
As used in this specification and the appended claims, any direction referred to herein, such as “top”, “bottom”, “left”, “right”, “upper”, “lower”, and other directions or orientations are described herein for clarity in reference to the figures and are not intended to be limiting of an actual device or system. Devices and systems described herein may be used in a number of directions and orientations.
As used herein, “have”, “having”, “include”, “including”, “comprise”, “comprising” or the like are used in their open ended sense, and generally mean “including, but not limited to.
As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.
The term “proximal” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, near to a point of reference such as an origin or a point of attachment.
The term “distal” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, spaced relatively far from a point of reference, such as an origin or a point of attachment. The term “substantially” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, being largely but not necessarily wholly that which is specified.
The wording “position”, “human position” or “patient position” refer to the physical configuration that the human body can take. For example, the human body can take the following basic position: standing, sitting, squatting, lying, . . . .
In this document, the “decubitus position” or “horizontal position” refers to a position taken by the patient which may be a lying position and more generally a position where the axis formed by the inlet of the implanted medical device (for example located in the cranial cavity of the patient) and the outlet of the implanted medical device (for example located in the peritoneal cavity) is substantially horizontal.
In this document the “upright position” or “vertical position” refers to a position taken by the patient which may be a standing position or a sitting position and more generally a position where the axis formed by the inlet of the implanted medical device (for example located in the cranial cavity of the patient) and the outlet of the implanted medical device (for example located in the peritoneal cavity or near the heart) is substantially vertical.
A “change of position” or “postural change” refers to a modification of the physical configurations taken by the human body. For example: from a horizontal position to a vertical position or from a vertical position to a horizontal position.
As employed herein, the term “adjustment element” refers to an element configured to adjust a parameter of the valve, for example but not limited to a parameter or setting to regulate the flow rate, the pressure threshold of the valve, open or close, open or closed position of the valve. In other terms, an adjustment element allows to regulate a variable of the fluid which flows from the cranial cavity to another cavity of the body patient, at least a part via the medical device.
As employed herein, the terms “modulate” and “modulating” refer to at least one change of a setting, for example the setting of the adjustment element of the medical device.
Examples of Medical Device Used by the Method
According to an example of the flow regulator, said membrane 1 comprises a lower face 11 which faces the cavity 10 and an upper face 12 on which the pressure of the fluid (also called P) is applied before said fluid enters in the cavity. Said membrane 1 comprises a flexible part in such a way that said membrane 1 comes into contact with said substrate 2 depending on the pressure of the fluid. Said contact may be total or partial, the main goal of this contact is to increase the fluidic resistance in such a way that the flow can be controlled even if the pressure of said fluid increases. When the pressure of the fluid increases, the depth of the cavity (gap G) decreases until the membrane 1 comes into contact, at least partially, to the substrate 2, thus the fluidic resistance increases for hindering said fluid flow.
The regulator may comprise several inlet holes 3. The holes positions and dimensions are arranged so that the fluid flow rate is passively regulated, depending on the fluid pressure, at least in a range of fluid pressure going from a first and at least a second predefined threshold values.
Advantageously, the substrate 2 comprises a rigid part 6 and a flexible part 5. The rigid part may be surrounded by the flexible part. Due to the flexible part 5, a part of the substrate 6 is able to move downwardly and/or upwardly. In other words, a part of the substrate (to simplify the description, the rigid part refers to this part) can move to the membrane 1 or move away from the membrane 1 in such a way as to decrease or increase the gap G. Thus, the rigid part may come into contact with said membrane.
The regulator may comprise an adjustment means (also called adjustment element) designed to move and/or to maintain at least temporarily said rigid part at a given position. Said adjustment means allows applying a force F on the rigid part of substrate to adjust the gap G of the cavity.
Thanks to said adjustment means, the gap G is adjustable, the graph of
The membrane may be much more flexible than the substrate. The pressure force transmitted by the membrane after contact with the substrate should be negligible compared to the restoring force of the substrate.
A force may be exerted by a spring, e.g. a flexible blade 14 in compression against a hard ball 13 glued on the mesa 6 as shown in
The medical device may further comprise a pressure sensor. For example, a sensor configured to measure a pressure gradient between the inlet of the medical device (for example the inlet catheter located in the cranial cavity, also called proximal catheter) and the outlet of the medical device (for example, the outlet catheter which may be located in the peritoneal cavity, also called distal catheter). This sensor may be a strain gages in a full Wheatstone configuration and may be implanted directly in or on the silicon membrane. The sensor may be connected to an electronic circuit comprising a coil to power externally the system, signal processing and wireless means to format and transfer the data to the end user (physician).
A push-pull system may be made by gluing a flexible blade onto the mesa and by attaching the spring onto this blade. The blocking of the substrate due to a flexure may be prevented by the flexibility of the blade attached to the mesa. The spring and the flexible blade may be a single preformed blade.
An adjustable valve, such shown by
Example of Numerical Simulations
An equivalent electrical model, based on the original study of Marmarou, has been used to simulate cerebrospinal fluid dynamics. A variable resistance has been added to simulate the shunt itself.
The CSF continuously produced by the patient is either stored in the ventricles or reabsorbed via the arachnoid villi or drained through the valve toward the peritoneum cavity. We do not consider here the fluctuations of ICP induced by the vasogenic system. For the sake of clarity, we assume first that the residual outflow resistance is infinite, the CSF being only diverted towards the peritoneum in steady state. The evolution of the pressure in the brain is derived by solving a differential equation, based on the diagram provided in
The numerical constants used in the simulations are provided in Table 1 that shows numerical constants for the simulation of the active tuning of a hydrocephalus valve:
We consider a flow regulator set at 20 ml/h, the initial value of the ICP being equal to 10 mbar. In case of a sudden increase of the production rate, from 20 to 22 ml/h at t=0, the evolution of the ICP with time could be simulated as reported in the
The time t0 and t2 could correspond for instance to two successive patient's waking at 7 am while the time t1 and t3 could correspond to two successive patient's bedtime at 11 pm.
Unacceptable increase of ICP due to underdrainage is observed, in particular during the night (decubitus). This curve illustrates the interest in fine tuning the valve setting after implant.
A reference curve corresponding to the typical evolution of the pressure (for example ICP) in case of postural change, following the scenario of Table 2, but without increase of the nominal flow rate which remains equal to 20 mL/h, is provided in the
The evolution of ICP, for a decrease of the production rate of 2 ml/h at t=0, leading to Qf=18 ml/h, are provided in the
The following simulation is based on the numerical simulation described above.
Method of Setting of the Regulator
We work on the principle that the pressure gradient monitored by the pressure sensor is equal to the difference of pressure between the top surface of the membrane (assumed to be equal to ICP) and the bottom surface of the membrane which is in pressure communication with the peritoneum. Thus, we assume the following rule:
ΔP=ICP+HP−PP (2)
Where ICP is the intra-cranial pressure, HP the hydrostatic pressure and PP the peritoneum pressure. Ideally, to set a hydrocephalus valve, the physician is mainly interested in the knowledge of the ICP and the flow rate (of CSF production rate) but the ICP cannot be measured by the sensor of our device (because our sensor is not an absolute pressure sensor). Other patient dependent parameters as the residual drainage resistance Rout may be used and will be discussed hereafter.
As a general trend, but not limited to, the present invention is based on the combination of device setting change with patient postural change to make fast and reliable valve adjustment using the integrated pressure sensor. Furthermore, this new method is based on the use of a pressure gradient sensor, not to adjust the pressure at which the anti-siphon valve closes but to adjust the desired flow rate of the device. Thus, this new method consists in the combination of the change of the device setting (e.g. flow rate) with patient postural change. The monitoring and the analysis of the pressure gradient values during these changes allows the tuning of the device in accordance with the patient physiological characteristics.
For example, for a device initially set at 20 ml/h, and for a patient generating 25 ml/h of CSF, the differential pressure sensor will indicate a very large value (typically >20 mbar). For a patient generating 15 ml/h, the differential pressure measured will be small (typically <10 mbar).
According to one example,
Optionally, the initial setting of the device correspond to a high flow rate setting (for example the greatest gap corresponding to the maximum flow rate of the device) so as to drain the excess of CSF in the patient's brain. Preferentially after the surgery, the patient stays in decubitus during several hours and the ICP stabilizes at around 10 mbar (for example).
A first method may comprise the following steps:
A second method may comprise the following steps:
A third method may consists in changing setting alternatively in positive and negative direction with respect the foreseen nominal value I0, in order to limit the change of ICP during the adjustment procedure. Indeed the ICP alternatively increases and decreases, limiting the overall change of the mean ICP value. The third method may comprise the following steps (j is the range of setting that will be used to adjust the device, k is the step of the setting search and n is the iterative number of adjustment steps):
The method is still valid if a setting change does not correspond exactly to a fixed value of flow rate change. The mandatory requirement is just that an increase/decrease of the actual setting I will induce an increase/decrease of the mean flow rate.
As a general trend, the analysis of the sign of dP/dt is valid essentially when the pressure gradient is comprised in its regulation range, or in other words the functioning point of the device is located onto the “plateau”, where the flow is expected to be constant. The different methods are therefore more effective when the patient is in vertical or tilted position. The analysis of the evolution of pressure in case of partial or total occlusion is discussed hereafter.
Example of a Simulation Using the Method 1
We consider a valve having a nominal flow rate Q0 of 20 mL/h for the setting 0, the increase/decrease of 1 setting corresponding to an increase/decrease of 1 mL/h for the nominal flow rate through the valve (e.g. Q2=22 mL/h and Q−4=16 mL/h). We assume now that the patient exhibits a production rate of 22 mL/h, while the other constants necessary to perform the simulations are given in Table 1.
After implant the patient is in decubitus with the valve wide open in order to reduce the ICP to a value slightly lower than its basal pressure Pb. The patient is then placed in upright position while the setting is decreased until stabilization and finally an increase of the pressure, the best setting being here the penultimate one.
After the stabilization period at the best setting the patient comes back in decubitus to check out that the ICP is not affected by postural change and that its value is within the initial range estimated during an Infusion Test. A typical protocol is given in the Table 3 showing an adjustment protocol for the determination of the best setting of the valve using the method.
The ideal setting of the device is the setting +2, leading to a flow rate through the valve equal to the production rate. The evolutions of the ICP and the sensor signal during the valve tuning are provided in
Example of a Simulation Using the Method 2
We still assume a production rate of 22 mL/h. This production rate is estimated during an Infusion Test. Therefore we are able to limit the range of setting during the tuning at +/−3 around this estimated value. The tuning procedure is summarized in Table 4 showing an adjustment protocol for the determination of the best setting of the valve using the method 2 (best Setting=+2). The best tuning is +2. To increase the change of pressure during the change of setting, the patient is ideally placed in upright (resp. decubitus) position during an increase (resp. decrease) of the setting.
Example of a Simulation Using the Method 3
We still assume a production rate of 22 mL/h. This production rate is estimated during an Infusion Test. Therefore we are able to limit the range of setting during the tuning at +/−3 around this estimated value. The tuning procedure is summarized in Table 5 showing an adjustment protocol for the determination of the best setting of the valve using the method 2 (best Setting=+2). The best tuning is +2. To increase the change of pressure during the change of setting, the patient is ideally placed in upright (resp. decubitus) position during an increase (resp. decrease) of the setting.
Modelling the Arterial Pressure Oscillations
In order to get a more realistic picture of the pressure trend during the device setting, the change of the cerebral artery volume due to heart action shall be considered. It is assumed that this volume change is balanced by the same CSF volume fluctuations.
The production rate of CSF includes therefore an additional term in cos (ωt):
Q
f
=Q
f0
+ωC
A
δP
A cos(ωt) (3)
Where ω is the heart rate angular frequency, CA the cerebral artery compliance and δPA the amplitude of the sinusoidal perturbation:
P
A(t)=PAO+δPA sin(ωt) (4)
The numerical constants used in the simulations are provided in Table 6 showing simulations constants for modelling the effect of cerebral artery compliance on ICP, while the adjustment protocol the given in Table 5:
The evolution of the ICP after the 12 h of ICP stabilization is provided in
Failure Detection Methods, in Case of Total Occlusion:
Two methods may be used: the DC analysis method (stationary) and/or the AC analysis method.
1. DC Analysis Method
If the total occlusion is located in the proximal (i.e. before the valve) and/or distal (i.e. after the valve) catheter, the pressure between the top and bottom surfaces of the membrane will equilibrate, leading to a pressure gradient equal to zero in both positions (horizontal or vertical position). After stabilization, we have: ΔPh−ΔPv=0.
For an occlusion near the device (i.e. proximal or just after the device outlet), we do not expect a change of pressure by postural changes. But, an occlusion at the end of the distal catheter induces a sudden increase of pressure and then quickly relax to zero. In that latter case, a total liquid volume corresponding to the change of volume of the fluidic line upward the regulator will pass through the device, inducing a movement of the membrane which can be detected by the sensor.
Because of the elasticity of the fluidic line it could be possible to discriminate between proximal or distal occlusion if this latter occlusion takes place just after the device (i.e. the valve) and not at the end of the distal catheter. But, if the elasticity of the proximal cavity (in communication with the top surface of the flexible membrane of the valve) is small, the pressure will remain equal to zero during the postural change of the patient and the possibility to distinguish between proximal and distal occlusions is lost.
Thus, a total occlusion diagnosis can be detected or confirmed by these observations. The method for detecting an occlusion may comprise:
For example, an occlusion may be detected when the difference between said first and second pressure measurements is equal or close to zero, or lower in absolute value to a reference value. The location of the occlusion (distal or proximal) may be based on the presence of a transient peak of pressure during postural change.
A purge may be necessary to release this occlusion. The purge is made possible by a filling port that is externally accessible via a syringe.
2. AC Analysis Method
The total occlusion may be detected by analyzing the AC signal of the ICP pressure (for example via a mathematical model). The AC component of ICP due to change of blood volume in the brain are no longer transmitted to the device for proximal occlusion. This method is the best way to distinguish proximal and distal occlusion.
The method for detecting an occlusion may comprise:
In Case of Partial Occlusions:
1. If the Partial Occlusion is Located Inside the Valve:
Because the device shows the smallest restriction in the fluidic pathway between the brain and the peritoneum, this kind of occlusion have the highest probability to occur. These restrictions are the holes in the membrane and the gap between the membrane and the pillars. Any occlusion in the device (e.g. located in the holes) leads to an increase of the measured value of the pressure gradient through the device.
For a given device correctly adjusted to the patient CSF production rate, this kind of occlusion will lead to an increase of the pressure at least equivalent to a change of position because of the translation of the Q(P) curve towards the low flow rate. This increase of pressure can be observed in decubitus, and a change of position will increase again the measured value.
The method for detecting an occlusion may comprise:
A purge may be necessary to flush the device from any protein residual. A new valve adjustment may be required after detection of partial occlusion.
2. If the Partial Occlusion is Located in Proximal and/or Distal Catheter:
We consider now a partial occlusion equivalent to a fluidic resistance of 3.8E11 Pa·s/m3 (for example). The change of the device characteristics is shown in
In normal situation the sensor shall experience a negative pressure while in case of partial occlusion, considering the former case with an ICP of 30 mbar induced by said occlusion, the pressure will equilibrate and the sensor will not measure this negative pressure.
A first approach consists in using a tilting chair and placing the patient not at −90° but at an angle comprised between −10° to −60° and to analyze the decrease of the measured pressure as a function of this angle, after a stabilization period. Other methods to confirm the hypothesis of a partial occlusion may be used, for example a change of setting or a AC method.
“Change of Setting” Methods
The typical patient characteristics (E, p0 and Rout) have been determined before or after the shunt implantation to characterize the CSF dynamics of the patient. Where E is the cerebral elasticity or elastance coefficient, p0 is the pressure in the extradural venous system and Rout is the residual drainage resistance. The initial p(t) curve could be therefore used as a reference.
In order to check the eventual presence of an occlusion it is possible to use the method described previously consisting in changing the setting of the device and monitoring the evolution of the pressure.
In case of occlusion the pressure measured by the sensor is no longer equal to the ICP even when the patient is in decubitus and when we neglect the peritoneum pressure.
In case of partial occlusion that leads to an increase of ICP, we expect a change of the CSF dynamics because of the decrease of the brain compliance at high ICP.
The fitting of the curve p(t) during the test of setting change will give the best coefficient of determination R2 for a reduced value of E.
Moreover, in case of occlusion, the slope of the curve Q(P) before and after the plateau will decrease. This decrease will result in a change of the typical curve p(t) during a test according to the previous method.
The decrease of this slope induces an increase of the measured variation of pressure during these tests by a factor proportional to the ratio of the ICP.
It is therefore possible to extract the real value of the ICP by doing a simple rule of three: we use a +1 method consisting in changing the position setting of the device of +1 (to increase of 1 unit the nominal setting of the device).
The pressure change after stabilization is proportional to pb(i):
If the partial occlusion leads to an increase of the ICP of a factor 3, the relative change of pressure during the change of setting +1 will be also increased by a factor 3 according to the reference value recorded just after implantation.
In brief: a distal or proximal occlusion will be therefore detected by analyzing the curve p(t) and by comparing this curve with a reference curve obtained just after implantation.
The method for detecting an occlusion may comprise:
AC Method
According to Lemaire J. J. et al., “Slow Pressure Waves in the Cranial Enclosure,” Acta neurochirurgica Vol. 144.3 (2002), pp. 243-254, this reference herewith incorporated by reference in its entirety, the analysis of the slow pressure waves in the cranial cavity could be also used to for assessment of CSF disorders.
Just after implantation, typical AC components of the ICP signal will be recorded as reference for standard ICP, when the device is correctly adjusted to the patient production rate of ICP.
A decrease of the measured AC amplitude of the pressure could be attributed to an increase of the ICP. This change of the AC amplitude could be correlated to the former test to confirm the presence of a partial occlusion.
The method for detecting an occlusion may comprise:
The step of processing may comprise the characterization (amplitude and/or frequency) of the different components of the differential pressure oscillations, using for instance a Fourier Transform.
In Case of Leakage
According to the device design, we should consider two kinds of leakage:
1. In Case of a Leakage Due to a Membrane Crack:
By design the silicon membrane of the device is expected to sustain pressure of several bars. In case of a shock on the patient head, the pressure sensor could be used to detect a mechanical failure of the membrane. The pressure sensor is preferably made of a strain gauge implanted directly in the silicon membrane. The detector circuit at the surface of the membrane could be therefore considered as a crack-guard: any crack in the membrane will lead to an open detector circuit.
2. In Case of Valve Leakage:
The device may be not sensitive to small particles (lower than few um in diameter (for example 2 um)). In case of contamination with larger particles or residuals (proteins . . . ), we expect an increase of the derivation flow through the valve for a given ICP. In a first approximation we assume that this permanent gap is equivalent to a change of the device setting that leads to an increase of the nominal flow rate.
If typical symptoms of overdrainage are observed, the first analysis method consists in doing an adjustment of the device with a monitoring of the p(t) curve during this process.
An abnormal increase of the nominal flow rate should be rather attributed to a valve leakage rather than an increase of CSF production if this phenomenon is sudden and permanent.
The method for detecting an valve leakage may comprise:
The presence of a valve leakage may be equivalent to a positive change of setting (larger valve opening), the device is intended to be well adjusted after reduction of the valve opening (negative change of setting).
Simulation of Failure Analysis
We assume first that the volume displaced by the flexible membrane per unit of pressure is large and almost constant over the range of pressure 10 to 40 mbar. In that case, we show in
For a proximal occlusion, we expect a first peak of pressure when the patient moves from decubitus to upright position. This effect is due to the compliance of the proximal cavity that will be contracted by the negative pressure generated by the water column. A linear relaxation is then observed as shown in
We consider the presence of a distal occlusion in a device that exhibits a small compliance: the flexible membrane will remain all the time at equilibrium and there is no possibility to localize the occlusion using this method. The analysis of the short-term oscillations of the sensor signal is then required: in case of proximal occlusion a strong reduction of pressure oscillations due to the vasogenic system is expected.
Typical example considering a residual drainage function via arachnoid villi and variation around this value to simulate partial occlusion and leakage: the simulation data are summarized in Table 7 showing simulation data for failure analysis purpose. The initial ICP value is assumed to be equal to Pb0 (i.e. 10.8 mbar).
In Table 8, a typical test protocol for failure analysis is shown.
The evolution of the intracranial pressure is provided in
For sake of clarity, the values of Rout corresponding to Nominal, Leakage and Semi-occlusion curves are here significantly different (one order of magnitude).
The analysis of the pressure trends is straightforward. In case of leakage the partial closing of the valve (setting −5) is not able to generate underdrainage while in case of semi-occlusion a large increase of the pressure is observed.
Method for a Non-Invasive Characterization of the CSF Dynamics
In a general manner, any information about CSF flow or pressure is fundamental to diagnose and characterize cerebral disease. In case of abnormal function of the cerebrospinal fluid outflow system, several methods are described in the prior art part of this document.
Standard Model for CSF Dynamics
We do not consider fluctuation due to periodic changes of the cerebral arterial blood volume and changes of venous outflow generated by respiration. We assume a constant production rate of CSF. Therefore the production of CSF shall be balanced between storage and absorption. This absorption Qabs is proportional to the difference of pressure between the intracranial pressure p=ICP and the pressure in the sagittal sinuses pss (from Dawson's law, see
where Rout is the resistance to CSF absorption. The storage of CSF is proportional to the cerebrospinal compliance C(p) and the rate of change of CSF pressure
The compliance of the cerebrospinal space C(p) is constant up to given pressure popt and increases when the CSF pressure is larger than popt:
where E is the cerebral elasticity or elastance coefficient which is patient specific. The compliance of the brain decreases for high ICP. By writing the conservation of matter we finally derive:
Where Qext(t) is the rate of external volume addition; the term pb, which is the baseline CSF pressure (resting pressure), is used in the latter formula instead of pss which is difficult to measure.
This equation could be solved easily in case of constant infusion rate test with Qext(t)=Qconst:
For a bolus injection of ΔV, the evolution of the pressure becomes:
This bolus injection is usually used to determine the pressure volume index PVI:
Where pp is the peak pressure just after the bolus injection.
According to Marmarou et al. “Compartmental analysis of compliance and outflow resistance of the cerebrospinal fluid system,” J. Neurosurg. Vol. 43, 523534 (1975) and Avezaat C. J. J. et al. “Clinical observations on the relationship between cerebrospinal fluid pulse pressure and intracranial pressure,” Acta Neurochirurgica, Vol. 79, pp. 13-29 (1986), these publications herewith incorporated by references in their entirety, the evolution of the intracranial pressure for increasing volume has an exponential form:
p=(pb−p0)eEΔV+p0 (13)
Because the craniospinal space is enclosed in the rigid skull, the compliance is small, typically from 0.1 to 0.3 ml−1, according to Cieslicki, K., “Mathematical modelling of the infusion test,” Pol. J. Med. Phys. Eng Vol. 13, pp. 33-54 (2007), this publication herewith incorporated by reference in its entirety. The former relationship is useful to determine the pulse amplitude (AMF) of CSF due to the change of the blood volume in the brain after heart contraction, since this abrupt change of volume is similar to a bolus injection (see
AMP+pp−pb=(pb−p0)(eEΔV−1) (14)
The analysis of the slow pressure waves in the cranial cavity could be also used to for assessment of CSF disorders, according to Lemaire J. J. et al., “Slow Pressure Waves in the Cranial Enclosure,” Acta Neurochirurgica, Vol. 144: pp. 243-254 (2002), this publication being herewith incorporated by reference in its entirety.
Eklund A. et al., “Assessment of cerebral fluid outflow resistance,” Med. Bio. Eng. Comput. 45, 719-735 (2007) reviewed the different methods of investigation of the CSF dynamics by active infusion of artificial CSF and pressure recording, this publication being herewith incorporated by reference in its entirety. After implantation of a shunt, these methods are still used to verify the good functioning of the device, according to Weerakkody et al., “Clinical assessment of cerebrospinal fluid dynamics in hydrocephalus; Guide to interpretation based on observational study,” Acta Neurol. Scand. Vol. 124, pp. 85-98 (2011), this publication being herewith incorporated by reference in its entirety.
Because these methods usually require the placement of two needles in the lumbar canal, an in vivo (but non-invasive, i.e. without needle) determination of the shunt functionality is desirable. Methods for the in vivo adjustment of the shunt to the patient production rate of CSF are also required.
New Method for a Non-Invasive Characterization of the CSF Dynamics
The new method is related to the analysis of the pressure sensor signal to determine physiological parameters of the CSF dynamics of the patient. By adding an auto-regulated shunt in the CSF fluidic pathway, we should introduce a new term in the equation of the conservation of the matter:
Q
f
+Q
ext
=Q
abs
+Q
storage
+Q
valve (15)
where Qf is the formation rate of CSF, Qext is the externally injected flow of liquid, Qabs is the absorbed rate of CSF through the arachnoid villi, Qstorage is the rate of liquid storage due to pressure change and Qvalve the flow of CSF through the valve.
We note the following designations:
p=intracranial CSF pressure
pss=sagittal sinuses pressure
p0=pressure in the extradural venous system
pb(i)=baseline ICP pressure, at rest in decubitus, for the setting i
Qvalve(pb(i), i)=flow through the valve at equilibrium, for the setting i
Rout=fluidic resistance to CSF outflow towards physiological routes
ΔPreg=pressure range wherein the regulated flow is constant
PP=peritoneum pressure
We assume first that the compliance of the shunt is very small compared to the brain itself. To simplify the formalism of the evolution of the pressure with time, we assume that the peritoneum pressure PP is equal to zero. The real gradient of pressure through the valve is reduced of PP (typically 2 mbar). An example of a full model including PP is given in annex.
A simplified view of the CSF flow through the regulator is shown in
At rest, the former equation reduces to:
Method: setting +1 and patient in decubitus position.
We can rewrite the full equation after the change of the setting of +1:
The functioning point of de device jumps of +δQ from the curve i to i+1 after change of the selector setting of +1, the pressure being equal to pb(i) at t=0 according to
Finally, the equation of the CSF dynamics state of the system satisfies to:
We assume now that Qext=0. This equation can be written in the form:
General solutions of this equation are:
boundary conditions are:
The unknown parameters E, Rout and p0 can be determined by fitting the curve p(t) with the function tan−1.
Method: Setting +1 and Patient in Vertical Position
The same test can be performed in vertical position, the analysis being simplified in the range of pressure pb(i)+ΔPreg to pb(i) wherein the flow rate through the valve is constant:
For pb(i)<p<pb(i)+ΔPreg:
Q
valve(p+HP,i+1)=Qvalve(pb(i)+HP,i)+δQ (28)
Where the hydrostatic pressure is noted HP. We obtain
Within this plateau of pressure, the equation for the CSF dynamics becomes, if we assume that Qext=0:
we get:
Leading to similar general solutions with the parameters:
with the boundary condition
p(t=0)=pb(i) (35)
Method: setting −1 and patient in decubitus position.
By changing the setting of the device of −1, we get:
We assume again that Qext=0 and we restrict first the analysis on the plateau of the Q(p) curve, wherein the flow rate through the valve is constant. We assume also in a first approximation that ΔPreg does not depends on i (see
For pb(i)<p<pb(i)+ΔPreg the flow rate is constant:
Q
valve(p,i−1)=Qvalve(pb(i),i)−δQ (37)
For pb(i)<p<pb(i)+ΔPreg the equation of the CSF dynamics state of the system satisfies to:
we get:
Leading to similar general solutions with the parameters:
with the boundary condition
p(t=0)=pb(i) (43)
For p>pb(i)+ΔPreg the flow rate through the valve is:
This part of the curve could be analyzed using the same kind of general solutions, the boundary conditions including continuity conditions between the two ranges of pressure.
Method: Setting −1 and Patient in Vertical Position
The same test can be performed the patient being in vertical position, the same formula applies by changing −preg by HP, the hydrostatic pressure, those pressures being assumed to be equal in a first approximation. In the latter case, we get:
We assume that Qext=0. We can write, according to
Therefore the differential equation for the CSF pressure is:
We finally solve this equation using general formulae
In practice, a preliminary infusion test is performed to determine if a shunt shall be placed or not. During this test it is possible to determine these parameters E, Rout, p0 and even PP if a complete model is used.
The best strategy is therefore to use these parameters as constant and to check after implantation the good functioning of the device. In functioning, it is also possible to determine the change of E and Rout with time in a non-invasive way by simply changing the setting of the device and by monitoring the pressure signal with time.
In sum, below some of the features of the method are highlighted.
Thus the method for a non-invasive characterization of the CSF dynamics may comprise the following steps:
An alternative method could be:
A General Mathematical Approach is Given Below:
We consider the full model that includes the peritoneum pressure PP. We only derive the equation for the method +1 in decubitus, other formula can be derived easily by applying the same formalism.
At rest, the equation of mass conservation writes:
We can rewrite the full equation after the change of the setting of +1:
The functioning point of de device jumps of +δQ from the curve i to i+1 after change of the selector setting of +1, the pressure drop in the device being equal to pb(i)−PP at t=0. There is then a relaxation up to an ICP equal to pb(i+1), the flow rate being approximated by:
Finally the equation of the CSF dynamics state of the system satisfies to:
We assume now that Qext=0. This equation can be written in the form:
General solutions of this equation are:
Boundary conditions are:
The unknown parameters E, Rout, PP and p0 can be determined by fitting the curve p(t) with the function tan−1.
The following reference numerals have been used to designate some of the elements.
While the invention has been disclosed with reference to certain preferred embodiments, numerous modifications, alterations, and changes to the described embodiments, and equivalents thereof, are possible without departing from the sphere and scope of the invention. Accordingly, it is intended that the invention not be limited to the described embodiments, and be given the broadest reasonable interpretation in accordance with the language of the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 16151558.0 | Jan 2016 | EP | regional |
