Abstract:
A system and method for treating, inhibiting or ameliorating Alzheimer&#39;s disease in a patient, comprising one or more transducers operatively connected to a power source for radiating vibrational or acoustical energy to the maxilla of the patient, wherein the energy is sufficient to radiate through the paranasal sinuses of the patient to the base of the patient&#39;s skull to assist in cerebrospinal fluid clearance and inhibit localized stasis of cerebrospinal fluid in the brain.

Description:
FIELD 
       [0001]    This application relates generally to the prevention and treatment of dementia of the Alzheimer&#39;s type, and more particularly, to a method, system and apparatus for preventing localized stasis of cerebrospinal fluid. 
       BACKGROUND 
       [0002]    It has been over 100 years since the first diagnosis of Alzheimer&#39;s Disease (“AD”), yet there is still no clear understanding of the disease process. The Alzheimer&#39;s Association recently projected that 5.1 million Americans are stricken with the disease and someone is newly diagnosed every 72 seconds in the United States. AD manifests itself with progressively impaired memory leading to mental confusion or dementia as the disease systematically kills off nerve cells in the brain. The staggering anticipated figures for what is to come in the future with the aging baby boomer population demands that progress be made in preventative, diagnostic and therapeutic AD research. 
         [0003]    Cerebrospinal fluid (“CSF”) stagnation and/or failure secondary to senescence has been implicated to have a fundamental role in AD dementia. CSF is the protective fluid that fills the empty spaces around the brain and spinal cord. CSF has a crucial homeostatic circulatory role for metabolites, proteins and ions in and out of the brain. Normal CSF volume in an adult is about 140 milliliters and the entire volume turns over 3 or 4 times during the course of one day. It is known that CSF production and turnover decreases with age. CSF stagnation and/or failure will result in disruption of this tightly regulated equilibrium of fluid. 
         [0004]    CSF has to flow through a labyrinth of tightly coiled sulci and fissures deep within the brain, sometimes against gravity, in key limiting anatomic locations. However, the brain lacks any local mechanical system, such as valves or motile appendages (e.g., cilia) to promote flow in a certain direction. Instead, CSF flow and velocity are driven by the cardiac cycle and modulated by venous pressure changes during respiration. Thus, it is feasible to have conditions under which chronic, localized stasis of CSF would lead to an accumulation of toxins and metabolites, which serves as a chronic, low-grade, physiological insult that cascades into the slow and insidious pathogenesis of AD as one ages. 
         [0005]    To combat CSF stagnation, ventriculoperitoneal shunts, such as Eunoe, Inc.&#39;s COGNIShunt® system, have been surgically implanted in the brains of AD afflicted patients as an artificial means to promote better CSF flow and turnover. While the results of this surgical procedure have been promising with respect to hindering the progression of dementia, the AD patient must undergo an extremely invasive surgical procedure in which a foreign body (i.e., ventriculoperitoneal shunt and its associated drainage tubing) is introduced into the patient&#39;s body. In addition, the potential benefits of this procedure are limited since the ventriculoperitoneal shunt may promote better CSF flow at a global level, but does not address or target specific, limiting anatomic areas of the brain that are most susceptible to CSF stasis. 
         [0006]    Accordingly, there is a need for a non-invasive procedure that will prevent or reduce CSF stasis in the brain. There is also a need for a non-invasive procedure that promotes better CSF flow and turnover at specific, limiting anatomic areas of the brain that are most susceptible to CSF stasis. 
       SUMMARY 
       [0007]    A system, apparatus and method for treating, inhibiting or ameliorating Alzheimer&#39;s disease in a patient, comprising one or more transducers operatively connected to a power source for radiating vibrational or acoustical energy to the maxilla of the patient, wherein the energy is sufficient to radiate through the paranasal sinuses of the patient to the base of the patient&#39;s skull to assist in cerebrospinal fluid clearance and inhibit localized stasis of cerebrospinal fluid in the brain. 
         [0008]    These and other advantages of the present disclosure will be apparent to those of ordinary skill in the art by reference to the following detailed description and the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0009]      FIG. 1  illustrates an exemplary embodiment of a CSF stasis prevention system and apparatus in accordance with the present disclosure; 
           [0010]      FIG. 2  is a schematic illustrating the power generator for one or more driving transducers in the CSF stasis prevention system and apparatus illustrated in  FIG. 1 ; 
           [0011]      FIG. 3  illustrates a second exemplary embodiment of the CSF stasis prevention system and apparatus in accordance with the present disclosure; 
           [0012]      FIG. 4  illustrates a third exemplary embodiment of the CSF stasis prevention system and apparatus in accordance with the present disclosure; 
           [0013]      FIG. 5  illustrates a fourth exemplary embodiment of the CSF stasis prevention system and apparatus in accordance with the present disclosure; and 
           [0014]      FIG. 6  illustrates a fifth exemplary embodiment of the CSF stasis prevention system and apparatus in accordance with the present disclosure. 
       
    
    
     DETAILED DESCRIPTION 
       [0015]    Methods, apparatuses and systems for preventing CSF stasis in the brain are disclosed herein. The CSF stasis prevention methods, apparatuses and systems transfer vibrational or acoustical energy via bone conduction and/or air conduction through the paranasal sinuses to the base of the skull preferably using intraoral and/or extraoral/external devices. 
         [0016]    The paranasal sinuses are thin-walled, mucosa-lined, hollow, air-filled spaces or cavities within the craniomaxillofacial complex (i.e., the bones of the face and skull) that communicate with the nasal cavity. Humans have four paired paranasal sinuses, which are often referred to according to the bone in which the particular sinus lies. These are the maxillary, ethmoid, frontal and sphenoid sinuses. The maxillary sinuses lie in the maxillary (cheek) bones under the eyes. The ethmoid sinuses lie in the ethmoid bone between the nose and eyes. The frontal sinuses lie in the frontal bone that forms part of the forehead above the eyes. The sphenoid sinuses lie in the sphenoid bone at the center of the skull base under the pituitary gland. 
         [0017]    The biological function of the paranasal sinuses has been the subject of much debate and research, but, to date, there has been no widely accepted or, for that matter, discernible function associated with paranasal sinuses. 
         [0018]    The CSF stasis prevention apparatuses, systems and methods disclosed herein utilize the paranasal sinuses to transmit vibrational or acoustical energy via bone and/or air conduction to the forehead and base of the skull. It is believed that the paranasal sinuses are hollow, resonating structures that naturally transmit vibrational or acoustical energy to the base of the skull and forehead during activities such as chewing, singing or being exposed to loud music/noise. This energy or resonance affects CSF dynamics by creating fluid waves in the CSF to prevent localized stasis in those deeper tightly coiled parts of the brain where CSF may have to flow against gravity. 
         [0019]    This is particularly so with respect to the sphenoid sinuses, which are strategically located anterior, medial and inferior to the hippocampus. The hippocampus is a part of the brain located in the medial temporal lobe that plays a part in long-term memory and is most critically involved in AD as it is one of the first regions of the brain to suffer damage. 
         [0020]    As will be described in greater detail below, intraoral and/or external devices are disclosed herein for use by a patient to transmit vibrational or acoustical energy through the paranasal sinuses—in particular, the sphenoid sinuses—to the base of the skull and forehead. The intraoral and/or external devices include one or more transducers connected to an energy source such that vibrational or acoustical energy is applied to the maxilla, preferably at the base of the midface. The vibrational or acoustical energy may be at infrasonic, sonic, supersonic or ultrasonic frequencies. In this way, the energy will travel via bone and/or air conduction from the maxilla to the paranasal sinuses and ultimately to the base of the skull, where tightly coiled structures of the brain, such as the hippocampus lying posterior and lateral to the sphenoid sinuses, are assisted in CSF clearance and prevent localized CSF stasis. 
         [0021]    An exemplary, preferred embodiment of a CSF stasis prevention system  10  is illustrated in  FIG. 1 . The CSF stasis prevention system  10  includes a mouthpiece  20  capable of snuggly fitting over a patient&#39;s upper teeth. Alternatively, the mouthpiece  20  can be configured to fit over the upper jaw for patients without teeth. The mouthpiece  20  may be made of any suitable material that is biocompatible and safe for use within the mouth of a patient, such as polymethylmethacrylate (“PMMA”), acrylic, or other suitable plastic or thermoplastic materials. The mouthpiece  20  can be custom made to snugly, but comfortably fit over the upper teeth or upper jaw of the particular patient. 
         [0022]    The mouthpiece  20  preferably includes a generally U-shaped groove  22  for enclosing the patient&#39;s teeth or upper jaw. The groove  22  is defined by a base  22   a  and two upstanding walls  22   b,    22   c.  One or more transducers  30   a,    30   b,    30   c,    30   d  are mounted in a conventional manner on the interior side of upstanding wall  22   b.  The central portion of the mouthpiece  20  in which the transducers  30   a,    30   b,    30   c,    30   d  are located may optionally be enclosed or sealed to encapsulate the transducers. 
         [0023]    The transducers  30   a,    30   b,    30   c,    30   d  may be any type of transducer suitable for converting electrical energy into mechanical/vibrational energy, such as a resonance-type ultrasonic, sonic or supersonic transducer. These transducers produce high intensity waves or energy by, for example, applying the output of an electronic oscillator to a thin wafer of piezoelectric material (e.g., lead zirconate-titanate (PdZrTi or PZT) or barium titanate (BaTiO 3 )), which acts as a vibration element. 
         [0024]    The transducers  30   a,    30   b,    30   c,    30   d  and their respective wiring or leads are preferably coated or covered with a suitable electrical insulation material that is safe for use within the mouth of a patient, such as, for example, Teflon. The mouthpiece  20  preferably includes a hollow, elongated handle  25  through which one or more insulated electrical wires  40  pass. The insulated electrical wires  40 , which may be bundled in the form of an insulated cord or cable, electrically connect the transducers  30   a,    30   b,    30   c,    30   d  to an external power generator  50  that drives the transducers. 
         [0025]    The external power generator  50  may be powered by any conventional power source, such as, for example, conventional AC power, battery or solar operated, or 110 volt or 220 volt electric power. The external power generator  50  supplies power and provides signals for controlling the transducers  30   a,    30   b,    30   c,    30   d.  The output of the power generator  50  is preferably in the range of approximately 10 kilohertz to approximately 300 megahertz or more. In the preferred embodiment, the output of the power generator  50  can be adjusted via a frequency adjustment knob  51   a  connected to, for example, a variable controlled oscillator, to attain the optimal target frequency for the particular patient and the time of treatment can be selected via the timer  51   b,  after which time the power to the transducers  30   a,    30   b,    30   c,    30   d  is disconnected or otherwise ceases. 
         [0026]    Referring to  FIG. 2 , the external power generator  50  preferably includes a processor or microprocessor  52  to generate control signals that are amplified by an output driver or amplifier  54  to the desired power level and imparted via wiring or cabling  40  on the transducers  30   a,    30   b,    30   c,    30   d.  The processor  52  may dynamically tune the transducers  30   a,    30   b,    30   c,    30   d  to the targeted frequency based on a feedback signal  42  received from the transducers. 
         [0027]    The operation of the CSF stasis prevention system  10  is described below. The mouthpiece  20  is inserted into the patient&#39;s mouth so that the patient&#39;s upper teeth or upper jaw fit snugly in the grove  22 . The CSF stasis prevention system  10  is either preprogrammed to the desired target frequency and length of time of treatment, or a practitioner selects the desired target frequency for the patient using knob  51   a  and the length of time of treatment using knob  51   b.  The power generator  50  supplies the desired output power to the transducers  30   a,    30   b,    30   c,    30   d,  which radiate vibrational and/or acoustical energy at the desired frequency via bone and/or air conduction from the maxilla to the paranasal sinuses and ultimately to the base of the skull, where tightly coiled structures of the brain, such as the hippocampus lying posterior and lateral to the sphenoid sinuses, are assisted in CSF clearance and prevent localized CSF stasis. 
         [0028]    While the CSF stasis prevention system  10  is described and illustrated as including a plurality of transducers  30   a,    30   b,    30   c,    30   d,  it is understood that the system  10  requires a minimum of one transducer and may be utilized with any number of transducers that will produce the desired vibrational energy to be transmitted to the patient. 
         [0029]    Another embodiment of the CSF stasis prevention system  100  is illustrated in  FIG. 3 . The CSF stasis prevention system  100  is similar to that illustrated in  FIG. 1 , but the CSF stasis prevention system  100  preferably has the logic and circuitry of the external power generator  50  built into the hollow, elongated handle  125 . 
         [0030]    The CSF stasis prevention system  100  preferably includes a mouthpiece  120 , generally U-shaped channel  122 , base  122   a,  upstanding walls  122   b,    122   c,  and one or more transducers  130   a,    130   b,    130   c,    130   d  similar to the mouthpiece  20 , generally U-shaped channel  22 , base  22   a,  upstanding walls  22   b,    22   c,  and one or more transducers  30   a,    30   b,    30   c,    30   d  of the above-described CSF stasis prevention system  10 . 
         [0031]    The handle  125  is preferably constructed of a rigid or semi-rigid material. One or more batteries  140 , preferably rechargeable batteries, are located within the handle  125 . A processor or microprocessor  152  is electrically connected to the battery(s)  140  to generate control signals that are amplified by an output driver or amplifier  154  to the desired power level and imparted on the transducers  130   a,    130   b,    130   c,    130   d.  The processor  152  may dynamically tune the transducers  130   a,    130   b,    130   c,    130   d  to the targeted frequency based on a feedback signal received from the transducers. Alternatively, the device may include a variable-controlled oscillator for adjusting and/or regulating power level being imparted on the transducers  130   a,    130   b,    130   c,    130   d.    
         [0032]    The CSF stasis prevention system  100  is operated in a manner similar to that described above with respect to the CSF stasis prevention system  10 . In addition, while the CSF stasis prevention system  100  is described and illustrated as including a plurality of transducers  130   a,    130   b,    130   c,    130   d,  it is understood that the system  100  requires a minimum of one transducer and may be utilized with any number of transducers that will produce the desired vibrational energy to be transmitted to the patient. 
         [0033]    Another embodiment of the CSF stasis prevention system  200  is illustrated in  FIG. 4 . This embodiment may be particularly advantageous for patients who are edentulous. The CSF stasis prevention system  200  preferably includes an implant  230  that is surgically inserted into the maxillary bone or upper jaw  260  below the gingival tissue  265 . The implant  230  preferably includes a head portion  232 , a distal end  234 , and a threaded portion  236  between the head portion and distal end. The threaded portion  236  may have a specific surface, including, but not limited to, an acid-etched or sand blasted surface, to facilitate osseointegration with the bone  260  and may include a self-tapping region with incremental cutting edges that allow the implant  230  to be inserted into the bone  260  without the need for a bone tap. The implant  230  may, for example, be made of titanium, tantalum, cobalt, chromium, stainless steel, or alloys thereof. 
         [0034]    The head portion  232  of the implant  230  preferably includes a threaded cavity  232 a that will facilitate attachment of a transducer  210  to the implant  230 . The transducer  210  may be any type of transducer suitable for converting electrical energy into vibrational and/or acoustical energy, such as a resonance-type ultrasonic, sonic or supersonic transducer. These transducers produce high intensity waves or energy by, for example, applying the output of an electronic oscillator to a thin wafer of piezoelectric material (e.g., lead zirconate-titanate (PdZrTi or PZT) or barium titanate (BaTiO 3 )), which acts as a vibration element. 
         [0035]    The transducer  210  preferably includes a threaded portion  220  at one end thereof that is received within and releasably engages corresponding threads formed within the cavity  232   a  of the implant  230 . Alternatively, the transducer  210  may have a threaded cavity that releasably engages a threaded post or abutment extending from the head portion  232  of the implant  230 . Other conventional techniques may be used to releasably attach the transducer  210  to the implant  230 . For example, a conventional abutment or post may be attached to or integral with the implant  230 , and the transducer  210  may be releasably attached to the abutment or post extending from the implant  230 . 
         [0036]    The transducer  210  is electrically connected to an external power generator  250  via an insulated wire or cable  240 . The external power generator  250  supplies power and provides signals for controlling one or more transducers  210 . The external power generator  250  may be powered by any conventional power source, such as, for example, conventional AC power, battery or solar operated, or 110 volt or 220 volt electric power. The output of the power generator  250  is preferably in the range of approximately 10 kilohertz to approximately 300 megahertz or more. In the preferred embodiment, the output of the power generator  250  can be adjusted via a frequency adjustment knob  251   a  connected to, for example, a variable controlled oscillator, to attain the optimal target frequency for the particular patient and the time of treatment can be selected via the timer  251   b,  after which time the power to the transducer  210  is disconnected or otherwise ceases. 
         [0037]    Like the embodiment illustrated in  FIG. 2 , the external power generator  250  preferably includes a processor or microprocessor to generate control signals that are amplified by an output driver or amplifier to the desired power level and imparted via wiring or cabling  240  on the transducer  210 . The processor may dynamically tune the transducer  210  to the targeted frequency based on a feedback signal received from the transducer. 
         [0038]    The operation of the CSF stasis prevention system  200  is described below. After the implant  230  is implanted into the maxillary bone or jawbone  260  of the patient, the transducer  210  may be releasably connected to the implant  230  by, for example, inserting the threaded end  220  of the transducer  210  into the threaded cavity  232   a  formed in the implant. The CSF stasis prevention system  200  may be preprogrammed with the desired target frequency and the length of time of treatment, or a practitioner may select or adjust the desired target frequency for the patient using knob  251   a  and the length of time of treatment using knob  251   b.  The power generator  250  supplies the desired output power to the transducer  210 , which radiates vibrational energy at the desired frequency through the implant  230  and into the maxilla bone  260 . This vibration energy radiates via bone and/or air conduction from the maxilla to the paranasal sinuses and ultimately to the base of the skull, where tightly coiled structures of the brain, such as the hippocampus lying posterior and lateral to the sphenoid sinuses, are assisted in CSF clearance and prevent localized CSF stasis. 
         [0039]    While the CSF stasis prevention system  200  is described above as including a single transducer  210 , it is understood that the transducer  210  may be comprised of multiple transducers that are stacked or otherwise incorporated therein. 
         [0040]    Another embodiment of the CSF stasis prevention system  300  is illustrated in  FIG. 5 . The CSF stasis prevention system  300  includes a wand  310  having a transducer  320  located at or near one end of the wand. The wand  310  is preferably made of a rigid or semi-rigid, biocompatible material such as, for example, plastic or thermoplastic. 
         [0041]    The transducer  320  may be either mounted at the end of the wand  310  or within a cavity (not shown) in the wand  310 . While a single transducer  320  is illustrated in  FIG. 5 , it is understood that the transducer  320  may be comprised of multiple transducers that are stacked or otherwise incorporated on or within the wand  310 . The transducer  320  may be any type of transducer suitable for converting electrical energy into vibrational and/or acoustical energy, such as a resonance-type ultrasonic, sonic or supersonic transducer. These transducers produce high intensity waves or energy by, for example, applying the output of an electronic oscillator to a thin wafer of piezoelectric material (e.g., lead zirconate-titanate (PdZrTi or PZT) or barium titanate (BaTiO 3 )), which acts as a vibration element. 
         [0042]    If the transducer  320  is mounted at the end of the wand  310 , it should be preferably coated with a protective, biocompatible coating, such as, for example, Teflon, that seals and electrically insulates the transducer, and provides a smooth surface for applying the transducer to a patient&#39;s teeth, gums or other tissue. Alternatively, if the transducer  320  is located within a cavity in the wand  310 , then the end of the wand  310  where the transducer  320  is located should preferably be smooth to provide a comfortable surface for applying the end of the wand to a patient&#39;s teeth, gums or other tissue. The end of the wand may also be provided with protective, biocompatible surface or coating to provide a comfortable surface for applying the end of the wand to a patient&#39;s teeth, gums or other tissue. 
         [0043]    The transducer  320  is electrically connected to an external power generator  350  via an insulated wire or cable  340 . The external power generator  350  supplies power and provides signals for controlling the transducer  320 . The external power generator  350  may be powered by any conventional power source, such as, for example, conventional AC power, battery or solar operated, or 110 volt or 220 volt electric power. The output of the power generator  350  is preferably in the range of approximately 10 kilohertz to approximately 300 megahertz or more. In the preferred embodiment, the output of the power generator  350  can be adjusted via a frequency adjustment knob  351   a  connected to, for example, a variable controlled oscillator, to attain the optimal target frequency for the particular patient and the time of treatment can be selected via the timer  351   b,  after which time the power to the transducer  320  is disconnected or otherwise ceases. 
         [0044]    Like the embodiment illustrated in  FIG. 2 , the external power generator  350  preferably includes a processor or microprocessor to generate control signals that are amplified by an output driver or amplifier to the desired power level and imparted via wiring or cabling  340  on the transducer  320 . The processor may dynamically tune the transducer  320  to the targeted frequency based on a feedback signal received from the transducer. 
         [0045]    The operation of the CSF stasis prevention system  300  is described below. The CSF stasis prevention system  300  may be preprogrammed with the desired target frequency and the length of time of treatment, or a practitioner may select or adjust the desired target frequency for the patient using knob  351   a  and the length of time of treatment using knob  351   b.  The power generator  350  supplies the desired output power to the transducer  320 , which radiates vibrational energy at the desired frequency. The end of the wand  310  where the transducer  320  is located is preferably placed intraorally against the patient&#39;s upper teeth or gums (or externally against skin on the patient&#39;s face in proximity to the upper teeth, gums or cheekbone) and the vibrational and/or acoustical energy from the transducer  320  radiates via bone and/or air conduction from the maxilla to the paranasal sinuses and ultimately to the base of the skull, where tightly coiled structures of the brain, such as the hippocampus lying posterior and lateral to the sphenoid sinuses, are assisted in CSF clearance and prevent localized CSF stasis. 
         [0046]    Another embodiment of the CSF stasis prevention system  400  is illustrated in  FIG. 6 . The CSF stasis prevention system  400  is similar to that illustrated in  FIG. 5 , but the CSF stasis prevention system  400  preferably has the logic and circuitry of the external power generator  350  built into the wand  410 . The wand  410  is preferably hollow and has one or more transducers  420  mounted on or near the end of the wand  410 . The transducer  420  is similar to the transducer  320  described in the preceding embodiment. 
         [0047]    As with the wand  310  illustrated in  FIG. 5 , the transducer  420  may be coated with a protective, biocompatible coating, such as, for example, Teflon, that seals and electrically insulates the transducer, and provides a smooth surface for applying the transducer to a patient&#39;s teeth, gums or other tissue. Alternatively, if the transducer  420  is located inside the wand  410 , then the end of the wand where the transducer  420  is located should preferably be smooth to provide a comfortable surface for applying the end of the wand to a patient&#39;s teeth, gums or other tissue. The end of the wand may also be provided with protective, biocompatible surface or coating to provide a comfortable surface for applying the end of the wand to a patient&#39;s teeth, gums or other tissue. 
         [0048]    One or more batteries  430 , preferably rechargeable batteries, are located within the wand  410 . A processor or microprocessor  440  is electrically connected to the battery(s)  430  to generate control signals that are amplified by an output driver or amplifier  450  to the desired power level and imparted on the transducer  420 . The processor  440  may dynamically tune the transducer  420  to the targeted frequency based on a feedback signal received from the transducer. Alternatively, the device  400  may include a variable-controlled oscillator for adjusting and/or regulating power level being imparted on the transducer  420 . 
         [0049]    The CSF stasis prevention system  400  is operated in a manner similar to that described above with respect to the CSF stasis prevention system  300  illustrated in  FIG. 5 . 
         [0050]    The above-described intraoral and external devices are exemplary, preferred embodiments for generating and transferring vibrational and/or acoustical energy via bone and/or air conduction from the maxilla to the paranasal sinuses and ultimately to the base of the skull, where tightly coiled structures of the brain, such as the hippocampus lying posterior and lateral to the sphenoid sinuses, are assisted in CSF clearance and prevent localized CSF stasis. These devices will aid in preventing localized stasis of CSF in key, anatomic locations of the brain and may serve as a preventative measure against AD and/or slow its progression. 
         [0051]    The above-described intraoral and external devices may be utilized on a patient that is in a reclined or supine position to further assist CSF clearance and prevent localized CSF stasis. 
         [0052]    It is understood that other devices radiating acoustical energy can also be utilized to transfer energy via bone conduction to the base of the skull and prevent localized stasis of CSF in key, anatomic locations of the brain and may serve as a preventative measure against AD and/or slow its progression. For example, acoustical energy generated by a speaker or other type of transducer emitting acoustical energy may be utilized to achieve these results. 
         [0053]    In addition, the devices disclosed herein may also aid in distributing and dispersing intrathecal and intravenous medications, compounds, transplanted cells and tissues, and genetically engineered cells within CSF. Similarly, the devices disclosed herein may aid in clinical and scientific research involving the transport of molecules, ions and proteins in and out of CSF. 
         [0054]    Having described and illustrated the principles of this application by reference to one or more preferred embodiments, it should be apparent that the preferred embodiment(s) may be modified in arrangement and detail without departing from the principles disclosed herein and that it is intended that the application be construed as including all such modifications and variations insofar as they come within the spirit and scope of the subject matter disclosed herein.