Cerebrospinal fluid pump

Abstract

The present disclosure includes devices and methods for increasing cerebrospinal fluid (CSF) flux. In some embodiments, altering the curvature of the spine results in increased CSF flux. In some embodiments, an implantable pump is used to provide pressure waves to the CSF. In some embodiments, increased CSF flux results in improved clearance of the glymphatic system. In some embodiments, symptoms of Alzheimer's disease and other neurodegenerative diseases are improved as a result of increased CSF flux.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. patent application Ser. No. 63 / 322,180, filed March 21, 2022, and the benefit of U.S. patent application Ser. No. 63 / 354,682, filed June 22, 2022, and the benefit of U.S. patent application Ser. No. 63 / 409,619, filed September 23, 2022, which claims the benefit of U.S. patent application Ser. No. 18 / 124,388, filed March 21, 2023, the entire contents of each of which are incorporated herein by reference.

[0002] Technical Field The present application relates to devices, systems and methods for improving cerebrospinal fluid dynamics and for treating diseases associated with cerebrospinal fluid dynamics dysfunction. [Background technology]

[0003] background

[0001] Cerebrospinal fluid (CSF) is a clear, colorless liquid found in the brain and spinal cord that make up the central nervous system (CNS). The CNS controls and coordinates everything the body can do, including muscle movement, organ function, and more complex thinking and planning. CSF functions to cushion the brain and spinal cord when mechanical forces are applied to them, provide basic immune defenses for the CNS, remove metabolic waste products including beta-amyloid (a protein associated with Alzheimer's disease), and transport nutrients, neuromodulators, and neurotransmitters.

[0004]

[0002] Inside the brain are the ventricles. The ventricles are cavities filled with CSF. There are four ventricles in total: two lateral ventricles, the third ventricle, and the fourth ventricle. CSF is thought to be produced primarily by the choroid plexus epithelium and ependymal cells of the ventricles and to flow into interconnected cavities: the cisternae and the subarachnoid space. The ventricles are connected by narrow passageways. CSF flows through the four ventricles and then into an area called the subarachnoid space between the meninges. Humans produce about 600 ml of CSF every day and constantly replace it as it is absorbed.

[0005]

[0003] From the lateral ventricles, CSF flows into the third ventricle through two narrow passageways. From the third ventricle, CSF flows into the fourth ventricle through another long passageway known as the aqueduct of Sylvius. From the fourth ventricle, CSF passes through three small openings called foramina into the subarachnoid space that surrounds the brain and spinal cord. CSF circulates through a system of cavities found within the brain and spinal cord: the ventricles, the subarachnoid spaces of the brain and spinal cord, and the central canal of the spinal cord.

[0006]

[0004] Traditionally, CSF was thought to be absorbed through specialized groups of cells called arachnoid villi located at the top and midline of the brain. CSF then passes through the arachnoid villi into a large vein, the superior sagittal sinus, where it is absorbed into the bloodstream. Once in the bloodstream, CSF is transported to the kidneys and liver for filtering, just like other body fluids. However, more recent studies have shown that CSF can also be absorbed through other pathways.

[0007]

[0005] The spinal subarachnoid space is continuous with the brain subarachnoid space, so that CSF produced in the ventricles can easily reach the spinal cord. CSF flows from the fourth ventricle through the obturator into the central canal of the spinal cord. CSF passes through the median foramen (Magendie) and the lateral foramen (Luschka) to enter the interpeduncular and quadrigeminal cisterns. From here, CSF continues to flow through the spinal subarachnoid space. The spinal subarachnoid space is relatively large and contains almost half of the total volume of CSF in the CNS. It extends from the foramen magnum and ends at the level of the S2 vertebra. At approximately the L1 to L2 levels below the conus medullaris, the subarachnoid space expands into a dural sac called the lumbar cistern. The lumbar cistern extends from L1 / L2 to the S2 vertebral level and contains the dorsal and ventral roots of the spinal nerves (cauda equina) from L2 to the coccyx. Because the spinal subarachnoid space and the cranial subarachnoid space are continuous, spinal CSF drains back into the cranial subarachnoid space and is removed from there into the dural venous sinuses.

[0008]

[0006] CSF is believed to flow due to forces generated by the beating of the heart and breathing of the lungs. Several studies have found that the CSF flow associated with the heartbeat is only a small component of the total flow. Rather, breathing is the primary regulator of CSF flow. CSF flow in response to breathing shows the rise and fall of the chest wall, along with positive (towards the brain) and negative (away from the brain) flows corresponding to inspiration and expiration. One study found that forced inspiration induces a rapid and significant increase in upward CSF flow not only in the cervical and thoracic spine, but also in the cerebral aqueduct as part of the brain.

[0009]

[0007] Generally, flux is defined as the amount of flow per unit area. As described herein, CSF flows in both directions depending on the respiratory phase (inhalation or exhalation) and the cardiac cycle (systole or diastole). As used herein, flux refers to the effective flow (flow in one direction minus flow in the other direction).

[0010]

[0008] The human brain, or brain parenchyma, is surrounded by interstitial fluid (ISF). Fluid crosses the blood / brain barrier and enters the brain parenchyma from the CSF system, which includes the subarachnoid space and the ventricles. The CSF system is part of the glymphatic system. Fluid entering the brain's ISF system contains water as well as other components, nutrients. Waste products from the brain parenchyma are transferred from the ISF to the CSF system. Waste products within the CSF system enter the bloodstream through the arachnoid villi. It is believed that there are pathways for waste products to pass directly from the ISF system to the lymphatic system and also for waste products to pass directly from the CSF system to the lymphatic system.

[0011]

[0009] Neuroinflammation is an inflammatory response in the brain or spinal cord that occurs when the brain's innate immune system is triggered after inflammatory stimuli such as those caused by injury, infection, exposure to toxins, aging, or other inflammatory substances. Injury, infection, toxins, and aging are associated with a decrease in the effectiveness of the glymphatic system. Some studies have shown that increased levels of tau and beta-amyloid are associated with higher levels of neuroinflammation.

[0012]

[0010] CSF flux is involved in the pathophysiology of neurodegenerative diseases and cognitive dysfunction. CSF is known to play an important role in regulating brain homeostasis, waste removal, intracranial pressure, and blood and nutrient supply. When CSF flux and overall CSF dynamics can be impaired, whether due to aging, disease, or accident, it can lead to the pathogenesis of age-related neurocognitive disorders. These diseases / disorders include Alzheimer's disease, Parkinson's disease, Huntington's dementia, prion disease, multiple sclerosis, brain injury, trigeminal neuralgia, tremor, bipolar disorder, attention deficit disorder, seizures, and memory loss, visual construction ability, and verbal fluency.

[0013]

[0011] As mentioned above, two aspects of the cerebrospinal fluid system are the exchange of waste products with interstitial fluid and the filtration of CSF to remove these waste products. CSF / ISF exchange is most active when a person is sleeping or at rest. During sleep or relaxation such as meditation, yoga or qigong, a person's blood pressure drops and neural activity is minimal, especially at brain frequencies above 8 Hz.

[0014]

[0012] Improving CSF flux and dynamics may improve the health of individuals with neurocognitive disorders.

[0015]

[0013] A stroke occurs when the blood supply to a part of the brain is cut off or when a blood vessel in the brain ruptures. In either case, brain cells die and the brain is damaged, either temporarily or permanently. Depending on which area of ​​the brain is deprived of oxygen, a person may experience memory loss, movement or speech problems, or other disorders. If medical treatment restores blood flow or the pressure is quickly relieved, the brain may recover completely. A stroke can cause lasting brain damage, long-term disability, or even death. Summary of the Invention [Means for solving the problem]

[0016] Summary of the Disclosure

[0014] Described herein are devices and methods for increasing CSF flux and flow and improving CSF kinetics. In some embodiments, an external mechanical device is used. In some embodiments, an implantable pump is used.

[0017] In one embodiment, spinal flexion is used to increase CSF flux. In some embodiments, spinal flexion creates a peristaltic fluid movement in the CSF system. In some embodiments, spinal flexion puts pressure on the dural sac surrounding the spinal cord and cauda equina. In some embodiments, the flexion is created by mechanical movement of the spine. In some embodiments, the flexion is created by a device placed outside the body. In some embodiments, an implantable device connected to the CSF system creates a pressure gradient in the CSF system, resulting in increased CSF flux. In some embodiments, the implantable device pressurizes the cisterns and / or ventricles of the CSF system, creating a pressure gradient in the CSF system, resulting in increased CSF flux and flow. In one embodiment, the lumbar and cervical regions of the spine are flexed simultaneously.

[0018] In one embodiment, a device and method are disclosed for improving symptoms of Alzheimer's disease and other neurodegenerative diseases. By increasing the flux and flow of CSF, and therefore increasing the clearance of waste products in the brain and / or CNS, symptoms of Alzheimer's disease and other neurodegenerative diseases are improved. In an embodiment, neurodegenerative diseases include various forms of dementia, including Alzheimer's disease and Parkinson's disease, as well as other diseases such as cognitive decline, MCI (mild cognitive impairment), MS (multiple sclerosis), and migraines.

[0019] In one embodiment, a method is provided for increasing CSF flux in the region of the spine. In one embodiment, a method is provided for improving glymphatic clearance. In one embodiment, increasing CSF flux in the spine increases periarterial and perivenous (together perivascular) CSF flux in the brain.

[0020]

[0018] In one embodiment, a method of improving symptoms of depression is provided. In one embodiment, a method of improving sleep patterns is provided. In one embodiment, a method of improving memory is provided.

[0021] In one embodiment, a method is provided for increasing the rate and / or efficiency and / or effect of delivery of drugs infused into the CSF. In one embodiment, a method is provided for increasing the rate and / or efficiency and / or effect of intravenous chemotherapy drugs on brain conditions. In one embodiment, a method is provided for ameliorating the symptoms of chemobrain.

[0022]

[0020] In one embodiment, a method for improving the symptoms of cognitive decline is provided.In some subjects, the increase in the measurement of the vertical sagittal axis correlates with cognitive decline.In one embodiment, the method of the present disclosure eliminates the problems associated with this condition.

[0023] In one embodiment, a method is provided for reducing neuroinflammation, using the CSF pump of the present disclosure to improve function of the glymphatic system and reduce the effects of injury, infection, toxins, neurodegenerative disease and aging on the brain.

[0024] In one embodiment, a method is provided for increasing the effectiveness of both the glymphatic and lymphatic systems. As described herein, waste products from the brain / CNS flow into the CSF and then directly into the lymphatic system.

[0025] In one embodiment, a device and method is provided for facilitating reduction of stroke symptoms. Devices and methods for increasing CSF flow and flux after a stroke help reduce damage caused by the stroke.

[0026]

[0024] In many of the embodiments described herein, a method is provided for reducing the brain activity of a subject. In many embodiments, the methods described herein are more effective when the subject's brain activity is low and the brainwaves have frequencies lower than beta (alpha, theta, delta).

[0027] In some embodiments, the method of increasing flow to the glymphatic system includes positioning a first pump adjacent to the spine configured to change the curvature of the spine, activating the first pump, changing the curvature of the spine, and increasing the flow to the glymphatic system by increasing the flux of the cerebrospinal fluid (CSF) system. In some embodiments, no external CSF is removed from or added to the CSF system. In some embodiments, the first pump is positioned in a lumbar region of the spine, and the method further includes positioning a second pump adjacent to a cervical region of the spine, activating the second pump, and changing the curvature of the cervical region of the spine. In some embodiments, the second pump provides flexion or extension. In some embodiments, the method includes providing electrical, acoustic, electromagnetic, or mechanical stimulation to the patient. In some embodiments, the first pump is positioned on a chair back, and the first pump includes a pad configured to apply pressure to the spine. In some embodiments, the chair further includes a headrest, and the second pump is positioned to move the headrest to provide flexion and extension. In some embodiments, the device is configured to provide oscillatory pressure to the patient and is positioned on the patient's upper body to enhance function of the glymphatic system. In some embodiments, the chair is configured to provide a zero gravity position to the patient.

[0028] In some embodiments, a method of reducing neuroinflammation includes positioning a first pump adjacent to the spine, the first pump configured to change the curvature of the spine, activating the first pump, changing the curvature of the spine, and increasing the flow or flux of the cerebrospinal fluid (CSF) system. In some embodiments, increasing the flow or flux of the CSF improves the function of the glymphatic system. In some embodiments, after the pump is activated, the level of waste and biological by-products removed by the glymphatic system increases. In some embodiments, no external CSF is removed from or added to the CSF system. In some embodiments, the first pump is positioned in a lumbar region of the spine, and the method further includes positioning a second pump adjacent to a cervical region of the spine, activating the second pump, and changing the curvature of the cervical region of the spine. In some embodiments, the second pump provides flexion or extension. In some embodiments, the method further includes providing an electrical, acoustic, electromagnetic, or mechanical stimulus to the patient. In some embodiments, the first pump is positioned on a back of a chair, and the first pump includes a pad configured to apply pressure to the spine. In some embodiments, the chair further includes a headrest, and the second pump is positioned to move the headrest to provide flexion and extension. In some embodiments, the chair is configured to provide a zero gravity position for the patient.

[0029] In some embodiments, a method of improving stroke symptoms includes positioning a first pump adjacent to the spine configured to change the curvature of the spine, activating the first pump, changing the curvature of the spine, and increasing the flow or flux of the cerebrospinal fluid (CSF) system. In some embodiments, increasing the flow or flux of the CSF improves the function of the glymphatic system. In some embodiments, after the pump is activated, the level of waste and biological by-products removed by the glymphatic system increases. In some embodiments, no CSF ​​is removed from or added to the CSF system. In some embodiments, the first pump is positioned in a lumbar region of the spine, and the method further includes positioning a second pump adjacent to a cervical region of the spine, activating the second pump, and changing the curvature of the cervical region of the spine. In some embodiments, the second pump provides flexion or extension. In some embodiments, the method further includes providing an electrical, acoustic, electromagnetic, or mechanical stimulus to the patient. In some embodiments, the first pump is positioned on a back of a chair, and the first pump includes a pad configured to apply pressure to the spine. In some embodiments, the chair further includes a headrest, and the second pump is positioned to move the headrest to provide flexion and extension. In some embodiments, the chair is configured to provide a zero gravity position for the patient.

[0030] In some embodiments, a method for improving the function of both the lymphatic and glymphatic systems includes positioning a first pump adjacent to the spine, the first pump configured to change the curvature of the spine, activating the first pump, changing the curvature of the spine, and increasing the flow or flux of the cerebrospinal fluid (CSF) system. In some embodiments, the method includes positioning a device on the subject's body configured to provide gentle oscillatory pressure to the subject's body surface and muscles, and activating a pressure source to provide the oscillatory pressure. In some embodiments, increasing the flow or flux of CSF improves the function of the glymphatic system, and the oscillatory pressure improves the function of the lymphatic system. In some embodiments, after the pump is activated, the level of waste and biological by-products removed by the glymphatic system increases. In some embodiments, CSF is not removed from or added to the CSF system. In some embodiments, the first pump is positioned in a lumbar region of the spine, and the method further includes positioning a second pump adjacent to a cervical region of the spine, activating the second pump, and changing the curvature of the cervical region of the spine. In some embodiments, the second pump provides flexion or extension. In some embodiments, the method further includes providing electrical, acoustic, electromagnetic, or mechanical stimulation to the patient. In some embodiments, the first pump is positioned in a chair back, and the first pump includes a pad configured to apply pressure to the spine. In some embodiments, the chair further includes a headrest, and the second pump is positioned to move the headrest to provide flexion and extension. In some embodiments, the chair is configured to provide a zero gravity position to the patient.

[0031]

[0029] In some embodiments, a method for improving posture includes positioning a first pump configured to change the curvature of the spine adjacent to a cervical region of the spine, activating the first pump, changing the curvature of the spine, and reprogramming muscles to increase range of motion of the muscles.

[0032]

[0030] In some embodiments, a method of ameliorating Alzheimer's symptoms includes positioning a first pump adjacent to a spinal column, where the pump is configured to change the curvature of the spinal column, actuating the first pump, changing the curvature of the spinal column, and administering an antibody, where the antibody is selected to target a protein.

[0033]

[0031] In some embodiments, the therapeutic support device includes a cerebrospinal fluid pump including a frame, a first support including an aperture, a body and a pad, the body attached to the frame, the pad extending through the aperture, and the pad arranged to move between a retracted position and an extended position relative to the first support along an actuation axis. In some embodiments, the first support includes a back support. In some embodiments, the device includes a second support oriented at an angle relative to the first support. In some embodiments, the second support includes a seat. In some embodiments, the second support includes a headrest. In some embodiments, the second support is arranged to move relative to the first support. In some embodiments, the second support is arranged to rotate relative to the first support about a rotation axis. In some embodiments, the rotation axis is oriented between the first support and the second support. In some embodiments, the rotation axis is oriented perpendicular to the actuation axis. In some embodiments, the device includes a first orientation in which the pad is in a retracted position and the second support is oriented at a first angle relative to the first support. In some embodiments, the device includes a second orientation in which the pad is in an intermediate position and the second support is oriented at a second angle relative to the first support, the second angle being greater than the first angle. In some embodiments, the device includes a third orientation in which the pad is in an extended position and the second support is oriented at a third angle relative to the first support, the third angle being greater than the second angle. In some embodiments, the device includes a second cerebrospinal fluid pump including a second body and a second pad extending through the aperture, the second pad being arranged to move relative to the first support along a second actuation axis. In some embodiments, the actuation axis of the first pump is parallel to the actuation axis of the second pump. In some embodiments, the actuation axis of the first pump is non-parallel to the actuation axis of the second pump. In some embodiments, the range of motion of the first pad is greater than the range of motion of the second pad.In some embodiments, the device includes a third cerebrospinal fluid pump including a third body and a third pad extending through the aperture, the third pad arranged to move relative to the first support along a third actuation axis. In some embodiments, the therapeutic support device includes a chair.

[0034]

[0032] In some embodiments, the cerebrospinal fluid pump includes a base, a pad arranged to move along an actuation axis, and a motor arranged to rotate a drive shaft. A first slider is engaged with the drive shaft and arranged to move in a first direction relative to the base upon rotation of the drive shaft. A second slider is engaged with the drive shaft and arranged to move in a second direction relative to the base upon rotation of the drive shaft. A first connector is pivotally attached to the first slider and attached to the pad, and a second connector is pivotally attached to the second slider and attached to the pad. In some embodiments, the first direction is opposite to the second direction. In some embodiments, when the drive shaft rotates in the first direction, the first slider moves toward the second slider. In some embodiments, when the drive shaft rotates in the first direction, the pad moves away from the base. In some embodiments, when the drive shaft rotates in the second direction, the first slider moves away from the second slider. In some embodiments, when the drive shaft rotates in a second direction, the pad moves toward the base. In some embodiments, the actuation axis is oriented perpendicular to the axis of rotation of the drive shaft. In some embodiments, the drive shaft includes a first portion threaded in a first direction and a second portion threaded in a second direction.

[0035]

[0033] In some embodiments, the cerebrospinal fluid pump includes a linear actuation device arranged to move a pressure pad along a linear actuation axis. In some embodiments, the linear actuation device includes a shaft arranged to move along a central axis of the shaft. In some embodiments, the pressure pad is attached to an end of the shaft. In some embodiments, the pressure pad includes a pad including a curvature. In some embodiments, the pad includes a valley. In some embodiments, the actuation axis extends through the valley. In some embodiments, the pad includes a peak positioned beside the valley. In some embodiments, the pad includes a first peak and a second peak positioned on either side of the valley. In some embodiments, the pressure pad includes an extension positioned between the shaft and the pad. In some embodiments, multiple extensions of different lengths are provided and can be used to vary the distance between the linear actuation device and the pad.

[0036] In some embodiments, a method of increasing cerebrospinal fluid (CSF) flow in a patient's cerebrospinal fluid system includes applying pressure to a spinal region of the patient, thereby changing the curvature of the spine. In some embodiments, the method includes applying pressure with a pad. In some embodiments, the pad includes a curvature. In some embodiments, the pad includes a valley. In some embodiments, applying pressure further includes displacing the pad in a direction toward the spine. In some embodiments, the method includes displacing the pad from a first position to a second position. In some embodiments, when the pad is in the first position, the second position overlaps with a position of the spine. In some embodiments, as the pad is displaced to the second position, at least a portion of the spine is displaced away from the second position. In some embodiments, as the pad moves to the second position, the curvature of the spine increases. In some embodiments, the method further includes retracting the pad away from the spine. In some embodiments, the method further includes alternating between displacing the pad and retracting the pad. In some embodiments, the displacement of the pad is performed at a first time and the retraction of the pad is performed at a second time. In some embodiments, the second time is longer than the first time. In some embodiments, the spine includes a lumbar region and a cervical region, and applying pressure includes applying pressure to the lumbar region, thereby changing the curvature of the lumbar region. In some embodiments, the method further includes moving the patient's head to change the curvature of the cervical region. In some embodiments, the method includes increasing the curvature of the lumbar region while moving the head to provide flexion of the cervical region. In some embodiments, the method includes reducing the curvature of the lumbar region while moving the head to provide extension of the cervical region. In some embodiments, moving the head to provide flexion of the cervical region pad is performed at a first time and moving the head to provide extension of the cervical region is performed at a second time. In some embodiments, the second time is longer than the first time.In some embodiments, the method includes providing a cerebrospinal fluid pump including a pad and applying pressure with the pad. In some embodiments, the method includes controlling the cerebrospinal fluid pump to displace the pad in a direction toward the spinal column. In some embodiments, the method includes controlling the cerebrospinal fluid pump to retract the pad in a direction away from the spinal column. In some embodiments, the method includes providing a second cerebrospinal fluid pump including a second pad and applying pressure to the spinal column region with the second pad. In some embodiments, the first cerebrospinal fluid pump is offset from the second cerebrospinal fluid pump.

[0037]

[0035] These and other embodiments which characterize the invention are particularly pointed out in the claims annexed to and forming a part of this specification. However, for a better understanding of the invention, its advantages and the objects attained by its uses, reference may be made to the drawings and the accompanying descriptive text which form a further part of this specification, in which various embodiments of the invention are illustrated and described. [Brief description of the drawings]

[0038] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1A] FIG. 1 is a schematic diagram of the CSF system. [Figure 1B] FIG. 1 is a schematic diagram of the CSF system. [Figure 1C] FIG. 1 is a schematic diagram of the CSF system. [Diagram 2]

[0037] Schematic diagram of the glymphatic system. [Figure 3A] FIG. 1 shows an embodiment of a schematic diagram of a CSF pump. [Figure 3B] FIG. 1 shows an embodiment of a schematic diagram of a CSF pump. [Figure 3C] FIG. 1 shows an embodiment of a schematic diagram of a CSF pump. [Figure 4]

[0039] 1 shows one embodiment of a schematic diagram of a CSF pump. [Diagram 5]

[0040] 1 shows one embodiment of a schematic diagram of a CSF pump. [Figure 6A]

[0041] FIG. 1 is a schematic diagram of a chair-mounted CSF pump. [Figure 6B] FIG. 1 is a schematic diagram of a chair-mounted CSF pump. [Figure 7A]

[0042] FIG. 1 is a schematic diagram of an implantable CFS pump. [Figure 7B] FIG. 1 is a schematic diagram of an implantable CFS pump. [Figure 8]

[0043] FIG. 1 is a schematic diagram of a chair-mounted CSF pump. [Figure 9A]

[0044] Shows spinal curvature. [Figure 9B]

[0044] Shows spinal curvature. [Figure 10A]

[0045] FIG. 1 is a diagram of a chair-mounted CSF pump. [Figure 10B] FIG. 11 is a diagram of a second pump associated with a movable headrest. [Figure 11A]

[0046] 1 shows an embodiment of a CSF pump chair and spinal flexion. [Figure 11B]

[0046] An embodiment of a CSF pump chair and spinal flexion are shown. [Figure 11C]

[0046] An embodiment of a CSF pump chair and spinal flexion are shown. [Figure 12]

[0047] FIG. 1 is an embodiment of a schematic diagram of a CSF pump. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0039] Detailed Description

[0048] The present disclosure includes methods and devices for increasing the flux of cerebrospinal fluid (CSF). Exemplary devices include pumps configured to alter the dynamics of the CSF system. In one example, the device includes a pump configured to alternately provide and release pressure to the spine, allowing the spine to flex and return to a non-pressurized position. This pressure causes a change in the flexion or curvature of the spine, resulting in a change in the fluid dynamics of the CSF. In some embodiments, the pump is positioned external to the subject's body. In some embodiments, the pump is an implantable device that creates pressure waves that alter the dynamics of the CSF system or changes the pressure in the CSF system. In some embodiments, the altered CSF dynamics and resulting increased flux of CSF results in an improvement in the symptoms of Alzheimer's and / or other cognitive diseases.

[0040]

[0049] In the following detailed description of the present disclosure, reference is made to the accompanying drawings, which form a part hereof, that show, by way of example, how one or more embodiments of the present disclosure may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the embodiments of the present disclosure, and it will be understood that other embodiments may be used, and that process, electrical, and structural changes may be made without departing from the scope of the present disclosure.

[0041]

[0050] As used herein, designators such as "X", "Y", "N", "M", etc., particularly with reference to reference numbers in the drawings, indicate that the number of the particular feature so designated may be included. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used herein, the singular forms "a", "an" and "the" may include both singular and plural referents unless the context clearly dictates otherwise. Furthermore, "some", "at least one" and "one or more" (e.g., several pivot points) may refer to one or more pivot points, while "plurality" is intended to refer to more than one of such. Furthermore, the words "can" and "may" are used throughout this application in an enabling sense (i.e., may, could) and not in a mandatory sense (i.e., must). The word "including" and its derivatives mean "including, but not limited to". The terms "coupled" and "coupled," depending on the context, mean directly or indirectly connected for access to and movement of a physical or movable handle member.

[0042]

[0051] The mechanisms behind CSF dynamics in humans are still not fully understood. CSF circulates from its main production site, the choroid plexus, through the ventricles and reaches the subarachnoid space at the outer surface of the brain, from where it drains into the venous bloodstream and the cervical lymphatic system. According to one concept of brain fluid transport, fluid crosses the blood / brain barrier and enters the brain from the CSF system. Fluid leaves the brain through the arachnoid villus surface, also enters brain tissue along a periarterial route, and exits again through a perivenous route into the subarachnoid compartment. Fluid also flows directly from both the ISF (interstitial fluid) system and the CSF system into the lymphatic system.

[0043]

[0052] 1A, 1B, and 1C are schematic diagrams showing the flow of CSF in the human body. CSF is mainly produced by choroid plexus epithelial cells and ependymal cells in the ventricles. Shown in FIG. 1B are one of the lateral ventricles 108 (since this is a lateral view, the other lateral ventricle is not visible), the third ventricle 110, and the fourth ventricle 112. CSF flows throughout the ventricular system of the brain from its main secretory site in the choroid plexus. CSF flows from the lateral ventricle 108 through the foramen of Monro to the third ventricle 110. From here, CSF flows through the aqueduct of Sylvius to the fourth ventricle. CSF flows from the fourth ventricle through the foramen of Magendie to the dorsal spinal subarachnoid space and through the lateral foramen of Luschka to the basal cistern. Prior to CSF ​​exiting the foramen of Luschka, CSF passes through the foramen of Magendie into the cerebellar vallecula and begins to flow downward into the dorsal cervical subarachnoid space. The CSF then flows caudally through the dorsal spinal subarachnoid space 114 and into the lumbar cistern 118 , and the CSF then ascends within the ventral spinal subarachnoid space 116 .

[0044]

[0053] In the interstitial space of the brain, the CSF system removes toxic aggregates, toxins, and cellular waste products. These may include tau and beta amyloid. Accumulation of toxins and waste products has been identified in association with neurodegenerative and neurotoxic diseases, such as Alzheimer's disease. It is believed that if these toxins and waste products could be removed, the subject's symptoms would improve. As shown in FIG. 2, CSF travels to the brain in the periarterial space 204, which surrounds the arteries 202. Fluid and nutrients from the CSF flow into the interstitial space, which contains neurons 218 and astrocytes 216. A water channel called aquaporin 4 (AQP4) 206 facilitates this flow of fluid from the periarterial space 204 to the perivenous space 208, which surrounds the veins 210 of the brain. As shown in FIG. 2, in the glymphatic system, fluid enters the interstitial space of the brain from the periarterial channel 204. Fluid moves past astrocytes 216 and / or neurons 218, “flushing” toxins and cellular waste products, such as metabolic waste products 212 and beta-amyloid 214, through AQP4 206 and into the perivenous channels 208.

[0045]

[0054] Although the CSF system removes toxins and waste products, some amounts of beta amyloid 214 and other waste products may be present in the CSF supply in the periarterial space 204. Several studies have shown that following traumatic brain injury or axonal injury, concentrations of tau protein increase dramatically in the CSF.

[0046]

[0055] Increasing the flux of CSF in the CNS system improves the flux and flow of CSF in the glymphatic system, increasing the efficiency of the glymphatic system and increasing glymphatic clearance. As described herein, altering the dynamics of the CSF system results in increased flux and flow in the CSF system. This increased flux and flow increases the filtration and production of CSF by the body. The increased flux and pressure, along with increased CSF production, all contribute to increased periarterial CSF flux. Increasing periarterial flow of CSF results in increased perivenous return.

[0047]

[0056] 3A-3C show one embodiment of a schematic diagram of a CSF pump 300 that is disposed outside the body. The pump 300 includes a base 302 that supports a track 301. Extending along the base is a rotatable shaft 306 that is attached at one end to a motor 304. The shaft 306 is also connected to a pair of sliders 308A and 308B. The sliders 308A and 308B are configured to slide relative to the base 302 along the track 301 without dislodging from the track 301. When the shaft 306 rotates in a first direction, the sliders 308A and 308B move toward each other. When the shaft 306 rotates in a second direction, the sliders 308A and 308B move away from each other. A first connector 310A is pivotally connected at one end to the first slider 308A and at the other end to a pad 312. The connection of the arm 308A to the pad 312 also allows for pivoting. The second connector 310B is pivotally connected at one end to the slider 308B and at the other end to the pad 312. The connection of the arm 308B to the pad 312 also allows for pivoting. When the motor 304 rotates the shaft 306 in a first direction, the sliders 308A and 308B move towards each other, moving the pad 312 away from the base 302, for example along the actuation axis 309. When the motor 304 rotates the shaft 306 in a second direction, the sliders 308A and 308B move away from each other, moving the pad 312 towards the base. In some embodiments, the shaft 306 includes threads that connect with threads on the sliders 308A and 308B to provide movement of the pad 312. In some embodiments, pad 312 may have any suitable shape and is desirably positioned to apply pressure to the body. In some embodiments, pad 312 includes a curvature. In some embodiments, shaft 306 includes opposing threads such that threads in one direction interact with slider 308A and threads in the opposite or second direction interact with slider 308B. In some embodiments, shaft 306 includes a first portion 305 and a second portion 307. In some embodiments, first portion 305 includes a first thread and second portion 307 includes a second thread.In some embodiments, the first threaded portion includes a positive thread and the second threaded portion includes a reverse thread. In some embodiments, the actuation axis 309 is oriented perpendicular to the central axis 306 of the shaft.

[0048]

[0057] FIG. 4 shows one embodiment of a schematic diagram of a CSF pump 400 that is placed outside the body. The pump 400 includes a base 402. In this embodiment, the base 402 includes two parts that may or may not be attached to each other. In some embodiments, the base 402 includes a first track 403 and a second track 405. Extending along the base is a rotating shaft 406 that is attached at one end to the motor 304. The shaft 307 is also connected to a pair of sliders 308A and 308B. The sliders 308A and 308B are configured to slide along the base 302 without coming off the base. In some embodiments, each slider 308A, 308B is attached to the first track 403 and the second track 405. When the shaft 306 rotates in a first direction, the sliders 308A and 308B move towards each other. When the shaft 306 rotates in a second direction, the sliders 308A and 308B move away from each other. The slider 308A is pivotally connected at one end to the slider 308A and at the other end to the pad 312. The connection of the arm 308A to the pad 312 also allows for pivoting. The slider 308B is pivotally connected at one end to the slider 308B and at the other end to the pad 312. The connection of the arm 308B to the pad 312 also allows for pivoting. When the motor 304 rotates the shaft 306 in a first direction, the pads 308A and 308B move towards each other, moving the pad 312 away from the base 302. When the motor 304 rotates the shaft 306 in a second direction, the pads 308A and 308B move away from each other, moving the pad 312 towards the base.

[0049]

[0058] The pumps of Figures 3 and 4 may be used in situations where there is minimal space behind the subject's spine. For example, the pumps shown may be used with a standard home or hospital bed. These pumps may be made so that only very little space is needed between the lower surface (in some embodiments, the top surface of the bed) and the rear surface of the subject's back. In some embodiments, 3 to 6 cm. In some embodiments where there is more space or a specialized chair or bed or the like is made, a motorized cylinder (or electromechanical cylinder) pump may be used. Motorized cylinders, as is well known in the art, convert rotary mechanical force into linear motion. Although motorized cylinders have been described, pneumatic cylinders, which typically use a piston or slide to convert pressurized flow into dynamic motion, may also be used. For any of the pumps shown herein, airbags or fluid-filled bags may be used. Such airbags or fluid-filled bags may also be used to move pressure pads.

[0050]

[0059] Shown in FIG. 5 is a cylinder pump 500. In some embodiments, the cylinder pump 500 includes a linear actuator. The cylinder pump 500 includes a base 502. The base 502 includes a power source (motor) for the pump and may include a control system to allow programming of the pump. Attached to the base 502 is a cylinder 504 which cooperates with the base 502 to provide axial movement of a shaft 506 of the cylinder 540. The shaft 506 extends from and retracts into the cylinder 504 to provide the movement of the pump. Attached to the end of the shaft 506 is a pressure pad 508. In some embodiments, the pressure pad 508 includes a pad 512 and an extension 514. In some embodiments, the pad 512 includes a curvature. In some embodiments, the pad 512 includes a valley 516, or recess, oriented between a first peak 518A and a second peak 518B. In some embodiments, the valley 516 is located in the center of the pad 512. In some embodiments, the valley 516 is positioned on the shaft 506. In some embodiments, the valley 516 helps to avoid putting pressure on the center of the spine, such as the spinous processes of the vertebrae. In various embodiments, the pad 512 shape shown in FIG. 5 can be used with any type of cerebrospinal fluid pump. In some embodiments (and in any of the pumps / devices shown herein), the multiple pressure pads 508 include extensions 514 of different lengths. This allows the pump user to select a pressure pad having a length that allows the pressure pad to fit closely against the patient's back without having to extend or retract the shaft 506. In some embodiments, the pump 500 includes a user interface 510 that is electrically or wirelessly connected to the pump 500. In some embodiments, the interface 510 includes a control system for the pump 500.

[0051]

[0060] 6A and 6B are diagrams of one embodiment of a chair with a cylinder pump attached, although pumps such as those shown in FIGS. 3 and 4 can also be used. A perspective view of a chair 600 is shown in FIG. 6A. Shown is a backrest 602 and a seat 604. Positioned in the backrest 602 is an opening 606. In some embodiments, the opening 606 is located in the middle of the width of the backrest 602. In some embodiments, the pump is located in the middle of the width of the backrest 602. A pump pressure pad 614 is positioned within the opening 606. The chair 600 is shown reclined at an angle, but can also be upright. The pressure pad 614 is shown to be approximately on the top surface of the backrest 602. In use, the pressure pad 614 is positioned near the top of the backrest 602 or above the backrest 602 at a height that touches the skin / clothing surface of the rear of the subject's spine. In some embodiments, an optional headrest 632 is provided. In further embodiments, the energy supply port 632 is associated with the headrest 630. A side view of the chair 600 is shown in FIG. 6B. In this view, a cylinder pump 610 is shown. The pump 610 includes a base / power source / motor 616, a cylinder 620, a shaft 612, a pressure pad 614, and an optional user interface 618 and / or a headrest 630. In some embodiments, the movement of the pad 614 can be described as approximately perpendicular to the plane of the backrest 602. In embodiments where the backrest 602 is curved, this plane is generally within the area in which the pad 614 is positioned.

[0052]

[0061] In use, a subject (not shown) is positioned in the chair 600. The doctor / technician programs the pump to use the appropriate length of pressure pad or move the pressure pad 614 to contact the subject's clothing / skin at the posterior region of the spine. The cylinder pump 610 can be positioned within the opening 606 so that the appropriate portion of the subject's spine is positioned adjacent to the pressure pad 614. The doctor / technician programs information into the pump such as stroke length and stroke speed. In some embodiments, the stroke length is 1 to 5 cm, 2 to 4 cm, or 1, 2, 3, 4, or 5 cm, and the speed is set such that each extension and retraction is 1 to 10 or 4 to 10 seconds. The extension and retraction can be set to different speeds. In some embodiments, the extension corresponds to the subject's inspiration and the retraction corresponds to the subject's expiration (the movement of the pressure pad is synchronized to the respiratory cycle). When activated, the pressure pad extends the desired distance, flexing the spine or changing the curvature of the spine. This bending of the spine causes a change in the dynamics of the CSF system. In some embodiments, no exogenous CSF is added to the CSF system. In some embodiments, no CSF ​​is separately removed from the CSF system. In some embodiments, the bending of the spine increases the hydrostatic pressure of the CSF, resulting in increased CSF flow and flux. In some embodiments, the subject's breathing pattern automatically switches to match the movement of the pump, with the patient inhaling as the pump extends and exhaling as the pump retracts. In some embodiments, a sensor (not shown) is positioned to sense the subject's breathing pattern, and the pump is programmed to match the patient's breathing pattern. In some embodiments, more than one pump may be used. In this embodiment, the stroke of one of the more cylinder pumps may be different. In some examples, the central cylinder pump may have the longest stroke (which creates the greatest bending). In some multiple pump examples, one long flexible pad may be used instead of individual pressure pads.

[0053]

[0062] Although some embodiments show a pump positioned outside the subject's body, implantable pumps can also be used. In another embodiment, a pump or device can apply pressure to one of the CSF ventricles or cisterns or within it. To apply pressure to the ventricles or cisterns, the pump is configured to introduce a pressure gradient. Figures 7A and 7B show an embodiment of a pump used to directly apply pressure to the CSF system. In Figure 7A, a pouch 714 is surgically implanted in the ventricle or cistern of the CSF system and is attached to the pump 710 via tubing 712. In Figure 7A, the pouch is positioned in the lumbar cistern 700, but other parts of the CSF system can also be used. The spinal cord 714, spinal column 706, and CSF 702 are also shown. The pump 710 can include a power source / motor, controller, receiver, and pump for moving fluid (air, water, saline, etc.) in and out of the pouch 714. Repeated pressurization and depressurization of the pouch 714 creates pressure waves in the CSF 702, which changes the dynamics of the CSF system. These changes in dynamics result in increased flux of CSF. The pump 710 may include a replaceable or rechargeable battery or may receive power wirelessly from a power source positioned outside the subject's body (not shown). A receiver in the pump 710 allows a physician / surgeon to program the operating conditions of the pump. FIG. 7B illustrates an embodiment in which a pipette or dropper-like device 720 is implanted in fluid communication with a CSF ventricle or reservoir and fills with CSF via tubing 722. The pump 720 is configured to pressurize / depressurize the pipette or dropper to move CSF in and out of the ventricle or reservoir. In FIG. 7B, the end of the tubing 622 is positioned in the lumbar reservoir 700, although other parts of the CSF system may be used. The spinal cord 714, spinal column 706, and CSF 702 are also shown. The pump 720 may include a power source, a controller, a receiver, and a pump to move fluid (air, water, saline, etc.) in and out of the lumbar reservoir 700. This inflow and outflow of CSF creates pressure waves in the CSF system, altering the dynamics of the CSF system. Both pump 710 and pump 720 are shown with a lumbar cistern 700, however, any opening in the CSF system may be used, including the cistern or ventricles.

[0054]

[0063] FIG. 8 is a perspective view of a chair with multiple cylinder pumps attached. Shown is a backrest 802 and a seat 804. Positioned in the backrest 802 is an opening 806. A pump pressure pad 814 is positioned within the opening 806. Positioned below the backrest 802 is a corresponding pump 810. The chair 800 is shown reclined at an angle, but can also be upright. The pressure pad 14 is shown to be approximately at or slightly above the top of the backrest 802. In use, the pressure pad 814 is positioned near the top of the backrest 802 or above the backrest 802 at a height that touches the skin / clothing surface of the subject's posterior spine. In some embodiments, an optional headrest 830 is provided. In some embodiments, the movement of the pad 814 can be described as approximately perpendicular to the plane of the backrest 802. In embodiments where the backrest 802 is curved, this plane is generally within the area where the pad 814 is positioned. Although six pumps are shown in the figures, any number from one to six or more may be used. Although individual pressure pads 814 are shown, one pressure pad covering all of the pumps may also be used. In use, the subject is positioned in the chair 800 such that the rear of the subject's body is closest to the pump 810. The pumps 810 may be programmed to raise the pads 814 all at the same time, by the same distance or at different times and / or by different differences. For example, the pumps may be arranged such that the pump closest to the end of the spine raises its pad 814 first, then the next pump raises the spine further, etc. Alternatively, the pump closest to the top of the spine may do so first. The multiple adjacent pumps may have any suitable orientation. In some embodiments, the working axis of the first pump is parallel to the working axis of the second pump. In some embodiments, the working axis of the first pump is non-parallel to the working axis of the second pump.

[0055]

[0064] 9A and 9B are diagrams of a pump 904 of the present invention and a pressure pad 906 positioned adjacent to a subject's spine 900. As shown in FIG. 9A, when the pressure pad is not exerting enough pressure to flex the spine, the curvature of the spine directly above the pressure pad 906 is in a normal or resting state. When the pump 904 and pressure pad 906 exert more pressure on the spine 900, the curvature of the spine directly above the pressure pad 906 is flexed or has a greater curvature compared to the resting position. It is this change in flexion or curvature and the resulting change in CSF fluid dynamics. In some embodiments, the flexion exerts pressure on the CSF in the dural sac surrounding the spinal cord and cauda equina.

[0056]

[0065] 10A and 10B are views of a chair with a cylinder pump attached, but pumps such as those shown in FIG. 3, 4 or 12 can also be used. A perspective view of a chair 1000 is shown in FIG. 10A. Shown is a backrest 1002 and a seat 1004. Positioned in the backrest 1002 is an opening 1006. A pump pressure pad 1014 is positioned within the opening 1006. A movable headrest 1032 is positioned on top of the backrest 1002. In some embodiments, the headrest 1032 is configured to pivot when actuated to provide lateral flexion and / or rotation to a subject using the chair. In some embodiments, the headrest 1032 is configured to allow flexion and / or extension to a subject using the chair. The chair 1000 is shown reclined at an angle, but can also be upright. The pressure pad 1014 is shown to be approximately on the top surface of the backrest 1002. In use, the pressure pad 1014 is positioned near the top of the backrest 1002 or above the backrest 1002 at a height that touches the surface of the skin / clothing at the rear of the subject's spine. In a further embodiment, the energy supply port 1032 is associated with the headrest 1030. A side view of the chair 1000 is shown in FIG. 10B. In this view, a cylinder pump 1010 is shown. The pump 1010 includes a base / power source / motor 1016, a cylinder 1020, a shaft 1012, a pressure pad 1014 and an optional user interface 1018 and a movable headrest 1030. In some embodiments, the movement of the pad 1014 can be described as approximately perpendicular to the plane of the backrest 1002. An electric cylinder / actuator or other motion inducing device 1022 is pivotally attached to the headrest 1032 at reference number 1026 via a shaft 1024. When the power cylinder / actuator 1022 extends the shaft 1024, the headrest 1032 rotates upward. When the power cylinder / actuator 1022 retracts the shaft 1024, the headrest 1032 rotates downward. In embodiments where the backrest 1002 is curved, this plane is generally within the area where the pad 1014 is positioned.In some embodiments, as the pump 1010 applies pressure to the lumbar and / or thoracic regions of the spine, the head rest 1032 moves downward to impart an extension motion to the subject's head and moves upward to impart a flexion to the cervical region of the spine. As the pump 1010 moves downward to reduce pressure on the lumbar and / or thoracic portions of the spine, the head rest 1030 moves upward to impart a flexion motion to the subject's head and provide a flexion to the cervical region of the spine.

[0057]

[0066] 11A, 11B, and 11C are diagrams of an example of a pump 1104 of the present invention and a pressure pad 1106 positioned adjacent a subject's spine 1100, and a movable head rest 1108 positioned beneath the subject's head 1110. As shown in FIG. 11A, when the pressure pad is not exerting enough pressure to flex the spine, the curvature of the spine directly above the pressure pad 1106 is in a normal or resting state, and the head rest 1108 is positioned in an upward position to impart flexion to the subject's head. Curve 1112A is an approximation of the curve of the spine directly above the pressure pad 1106, and curve 1114A is an approximation of the curve of the cervical vertebrae adjacent the head 1110. As shown in FIG 11B, when the pump 1104 and pressure pad 1106 apply pressure to the spine 1100, the curvature of the spine directly above the pressure pad 1106 begins to bend or have a greater curvature compared to the resting position, and the head rest 1108 is positioned in a lower position, moving the subject's head from flexion to extension and flexing the cervical region of the spine. Curve 1112B is an approximation of the curve of the spine directly above the pressure pad 1106, and curve 1114B is an approximation of the curve of the cervical vertebrae adjacent the head 1110. As shown in FIG 11C, when the pump 1104 and pressure pad 1106 are fully extended, the curvature of the spine directly above the pressure pad 1106 has a greater curvature compared to that shown in FIG 11A and FIG 11B, and the head rest 1108 is positioned in a lower position, moving the subject's head from flexion to extension and flexing the cervical region of the spine. Curve 1112C is an approximation of the curve of the spine directly above pressure pad 1106, and curve 1114C is an approximation of the curve of the cervical spine adjacent head 1110. This change in flexion or curvature of the lumbar / thoracic and cervical regions results in a change in the fluid dynamics of the CSF. In some embodiments, the flexion applies pressure to the CSF in the dural sac surrounding the spinal cord and cauda equina. In some embodiments, the therapeutic support device includes a first orientation, for example, as shown in FIG. 11A. In some embodiments, in the first orientation, the headrest 1108 is oriented at a first angle relative to the backrest and the pressure pad 1106 is oriented in a retracted position, for example, closest to the backrest along its range of motion.In some embodiments, the therapeutic support device includes a second orientation, for example as shown in FIG. 11B. In some embodiments, in the second orientation, the headrest 1108 is oriented at a second angle relative to the backrest, and the pressure pad 1106 is oriented at an intermediate position, for example, halfway along its range of motion. In some embodiments, the therapeutic support device includes a third orientation, for example as shown in FIG. 11C. In some embodiments, in the third orientation, the headrest 1108 is oriented at a third angle relative to the backrest, and the pressure pad 1106 is oriented at an extended position, for example, farthest from the backrest along its range of motion. In some embodiments, the movement from the first orientation to the third orientation is performed in a first time, and the return movement from the third orientation back to the first orientation is performed in a second time. In some embodiments, the second time is longer than the first time.

[0058]

[0067] 12 is a diagram of a pump 1200 that applies pressure to the spine using a semi-compliant or non-compliant bag 1202. Any fluid, gas or liquid may be used to inflate the bag 1202. Shown is a fluid pump 1204 connected to the bag 1202. A controller 1206 controls the pump 1204 to inflate and deflate the bag 1202. The bag 1202 is shown in the shape of a rounded triangular prism, although other prism or pyramidal shapes could be used.

[0059]

[0068] The present invention provides a method of improving CSF flux. The method includes positioning a pump dorsally or posteriorly near the spine of a subject. In some embodiments, the pump does not require any internal access (either temporary or permanent) through the patient's skin. In some embodiments, the pump is positioned to act on L2 and / or L3, but may be positioned anywhere on the spine. The pump may apply pressure to only a portion of the spine, but a larger portion of the spine is flexed. The method includes applying pressure to the spine or moving the spine anteriorly. In some embodiments, 5 mm of movement is sufficient. In some embodiments, 5 to 20 mm, 5 to 15 mm, 5 to 10 mm, 10 to 20 mm, 5 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm, 35 mm, 40 mm, 45 mm, 50 mm, 55 mm, 60 mm, 65 mm, 75 mm or more of movement is provided. As the spine flexes in response to pressure, CSF flux increases. This bending or shifting of the spinal cord results in an increased flux of CSF. In some embodiments, the bending or changing of the spinal curvature applies pressure to the CSF in the dural sac surrounding the spinal cord and cauda equina. In some embodiments, the bending of the spinal column causes the spinal cord and CSF flow chambers to act as a peristaltic pump, pumping the CSF. In some embodiments, the pumping of CSF increases both caudally, i.e., downward, and cranially, i.e., upward. In some embodiments, the shifting is rhythmic, for example, shifting forward for 5 seconds and backward (back to normal position) for 5 seconds. In other examples, other times are used, such as 1 to 10, 3 to 8, 5 to 10, 2, 4, 6, 8, 10, 12, 14 or more seconds. In some embodiments, the backward and forward shifting are not at the same speed or for the same time. In some embodiments, the forward shifting is performed for a first time and the backward shifting is performed for a second time, which can be approximately longer than the first time. In some embodiments, the pump is electrically or wirelessly connected to a sensor for sensing the subject's breathing pattern, in this embodiment, the pump moves forward during inhalation and moves backward during exhalation.In some embodiments, even without a sensor, the subject's breathing pattern is synchronized with the movement of the pump. In some embodiments, the treatment has a duration of 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes or more.

[0060]

[0069] In some embodiments, the CSF pump is configured to change the curvature of the spinal vertebrae. The curvature includes a cervical lordotic curve, a thoracic kyphotic curve, a lumbar lordotic curve, a sacral curve, and / or a coccygeal curve. In some embodiments, the pressure pad of the pump has a length that extends over a distance of 1 to 3, 1 to 2, 1, 2, 3, 5, 10, 15 or more vertebrae. In some embodiments, a secondary pad of the same length is used with the pump pad. In some embodiments, this long pad is made of spring steel or other material that transmits force but is flexible. The long pad is positioned above the pump along the spine. As the pump exerts pressure on the spine, the long pad helps distribute the force of the pump and may be more comfortable for the subject. Using pads that extend over multiple vertebrae allows for the use of pump systems with multiple pumps and / or pressure pads. In some embodiments of a multiple pad pump system, various pads may move the spine forward by different amounts. For example, in an embodiment having three pads, the middle pad may provide greater spinal movement than the two outer pads. In some embodiments, a soft pad, such as a foam material, may be positioned over the pressure pad to make the treatment more comfortable for the subject.

[0061]

[0070] In some embodiments, magnetic resonance imaging (MRI) of a portion of the CSF system is used to show changes in the dynamics of the CSF system, as is known in the art. Quantitative CSF flow can also be measured by PC MRI (phase contrast magnetic resonance imaging).

[0062]

[0071] In some embodiments, the present invention provides a method for improving glymphatic clearance. As described above, in the glymphatic system, fluid from CSF flows from the periarterial space through neurons and astrocytes and back to the CSF in the perivenous space. By increasing the flux of CSF in the spinal region, the flow of CSF through the glymphatic system is increased. This increases the filtration of CSF, resulting in a decrease in metabolic waste products in the CSF and in the periarterial space. This allows the glymphatic system to remove more metabolic waste products, such as beta amyloid, during periods of increased CSF flux.

[0063]

[0072] The CSF system, particularly the removal of toxic aggregates and metabolic waste products from the brain (glymphatic clearance), including beta amyloid, is believed to function best when the subject's brain activity is low and brainwaves have lower frequencies (alpha, theta, delta) than beta, which typically occurs during sleep or mediation or similar mental states. When brain activity is low, such as during sleep, blood pressure decreases, allowing the periarterial and perivenous channels that carry CSF to the brain to open more, resulting in increased CSF flow. In some embodiments, a method can be used to encourage the patient to relax and enter a sleep-like state. In some examples, an energy port 632 can be used to provide electrical / mechanical energy (EME) to the subject. This EME can be in the form of electrical, electromechanical, electromagnetic, mechanical, sound, voice, pressure, visual, visible or invisible electromagnetic radiation, etc. In some embodiments, a combination of different EMEs is administered to the subject. In some embodiments, the port 632 can be connected to a face covering helmet that is placed over the subject's head / face. This can include one or more screens that provide a visual means to help relax the subject. In some embodiments, this may be a blinking light. In some embodiments, port 632 may be connected to earphones or may provide music or other sounds directly to the patient. In some embodiments, EME may be administered at frequencies that correspond to brain frequencies. Although some embodiments described herein use port 632, it should be understood that the devices and means described in this paragraph may be wirelessly or electrically connected to a user interface or controller that may or may not be connected to the pump. In some embodiments, electrical impulses may be provided to the patient.

[0064]

[0073] In some embodiments, MRI can be used to show the concentration of amyloid beta in the subject's brain. In some embodiments, Gd contrast agent is used before MRI. Positron emission tomography (PET) using agents such as radioactive agents can also be used. In these embodiments, the results of MRI or PET over time can be used to show the reduction in the concentration of amyloid beta.

[0065]

[0074] In some embodiments, tranquilizers, sedatives or other substances that reduce brain activity may be used to help the subject achieve a state of low brain activity.

[0066]

[0075] In some embodiments, the electrical or electromagnetic energy delivered to the subject has a frequency corresponding to the subject's brainwaves. In some embodiments, the frequency of the energy corresponds to the subject's alpha, theta and / or delta brainwave frequencies. In some embodiments, the sonic energy delivered to the subject comprises music having a calming effect on the patient and / or having a beat corresponding to the subject's brainwave frequencies. In some embodiments, the visual information provided to the subject comprises an image having a calming effect on the subject. In some embodiments, the visual information is a series of flashes or pulses having a frequency corresponding to the subject's brainwave frequencies.

[0067]

[0076] In some embodiments, the subject is positioned in a zero gravity position. In some embodiments, this means that the body is in a basic position with the feet raised to be in line with the heart. In some embodiments, in this position, the subject's torso and thighs are at equal angles from the hip joints, the upper body is elevated, the knees are bent, and / or the legs are raised to approximately chest height. In this position, the spine is in a relatively stress-free position, the angle of the head is such that the subject's tongue is in a normal position, making breathing easier, and / or the legs are slightly elevated so that blood flows more easily through the subject's body. In some subjects, the zero gravity position reduces stress, lowers blood pressure, and / or relaxes the brain. In some embodiments, the torso and / or thighs each deviate from a fully prone position by about 30 to 45 degrees. In some zero gravity positions, the torso and thighs have an angle of 128 + / - 8 degrees, the hamstrings and calves are at an angle of 133 + / - 8 degrees, and / or the head is positioned at an angle of 24 + / - 5 degrees forward from being in line with the torso.

[0068]

[0077] In some embodiments, the patient is positioned in the Trendelenburg position, in which the person lies face up on a surface and then the head is lowered. In some embodiments, the person is positioned at an angle of about 15° to about 20°. In some embodiments, the person is positioned at an angle of about 30° to about 40°.

[0069]

[0078] In some embodiments, the subject is laid down on a bed (flat, torso / head elevated, knees elevated, or a combination thereof) for treatment with the products described herein and / or methods described herein. Once positioned on the bed, the bed can be flat, tilted with the head elevated, or tilted with the feet elevated.

[0070]

[0079] In some embodiments, the present invention provides a method for improving symptoms of Alzheimer's disease and other neurodegenerative diseases and disorders. Reducing the level of beta amyloid and / or metabolic waste products in the neuronal space leads to the improvement of symptoms. In some embodiments, neurodegenerative diseases include various forms of dementia, including Alzheimer's disease and Parkinson's disease, as well as other diseases such as cognitive decline, MCI (mild cognitive impairment), MS (multiple sclerosis) and migraines. In some embodiments, these diseases / disorders include Alzheimer's disease, Parkinson's disease, Huntington's dementia, prion disease and multiple sclerosis, brain injury, trigeminal neuralgia, tremors, bipolar disorder, attention deficit disorder, seizures, and memory loss, visual construction ability and verbal fluency. In one embodiment, the method of the present disclosure addresses the challenges associated with these conditions.

[0071]

[0080] In one embodiment, a method for improving symptoms of cognitive decline is provided. In some subjects, an increase in the measurement of the sagittal vertical axis correlates with cognitive decline. The sagittal vertical axis is the length of a horizontal line connecting the posterior superior sacral endplate with a vertical line from the center of gravity of the C7 vertebral body. The more the head and neck protrude in front of the pelvis when viewed from the side, the greater the distance of this line from the C7 vertebral body. In some studies, the greater this distance, the more likely the subject is to show symptoms of cognitive decline. This change in posture is thought to make it more difficult for the subject to curve their spine, thus inhibiting the body's natural pumping of CSF. The use of the pump described herein can increase the flux and flow of CSF to improve symptoms of cognitive decline. In one embodiment, the use of the pump described herein can reduce the amount of the measurement of the sagittal vertical axis. In one embodiment, the method of the present disclosure eliminates the problems associated with this condition.

[0072]

[0081] In one embodiment, a device and method for improving posture is provided. The central nervous system and muscles are constantly communicating to keep joints and limbs within a "safe" range of motion. One such safety mechanism is the presence of muscle spindles, innervated by type 1A nerve fibers that surround the muscles and communicate muscle stretch to the spinal cord and brain. If the stretch becomes excessive (e.g., the arm is swung uncomfortably far behind the back), the spindle fibers activate specific motor neurons, causing the associated muscle to contract abruptly, thereby returning the muscle / joint to a normal range of motion. Another protective mechanism is provided by the Golgi Tendon Organ (GTO), which senses the amount of load or tension on the muscle. If the GTO senses that the load is too high (i.e., trying to move something that is too heavy), it communicates to the spinal cord and inhibits the motor neuron's ability to contract the muscle, thereby preventing possible injury. The GTO is sensitive to changes in tension and rate of tension, and is located at the muscle-tendon junction, and is responsible for sending information to the brain as soon as it senses an overload. Stretching is an example of how muscle tone informs the GTO response. When a low-force stretch is maintained for a period of time, the increased muscle tone activates the GTO, temporarily inhibiting muscle spindle activity (thus decreasing muscle tone) and allowing further stretching (reprogramming the spindle fibers). In one embodiment, changes in cervical flexion reprogram muscles associated with posture, allowing the subject to have improved posture, as muscles accustomed to poor posture more easily support good postural positions. In one embodiment, the spindle fibers are reprogrammed to allow increased range of motion of the affected muscles.

[0073]

[0082] In one embodiment, a method for reducing neuroinflammation is provided. Neuroinflammation is an inflammatory response in the brain or spinal cord that occurs when the brain's innate immune system is triggered after an inflammatory stimulus, such as that caused by injury, infection, exposure to toxins, various inflammatory substances, or aging. Injury, infection, toxins, various inflammatory substances, and aging are associated with a decrease in the effectiveness of the glymphatic system. Some studies have shown that elevated tau and beta amyloid levels are associated with higher levels of neuroinflammation. In one embodiment, a method for reducing neuroinflammation is provided. Use of the CSF pump of the present disclosure increases the flux of the CSF system and improves the function of the glymphatic system, thereby reducing the effects of injury, infection, toxins, various inflammatory substances, and aging on the brain.

[0074]

[0083] Some researchers believe that increased amyloid beta production and plaque formation seen in Alzheimer's and other neurodegenerative disease patients causes Alzheimer's and other neurodegenerative diseases. However, others believe that neuroinflammation of brain tissue and / or brain trauma causes increased production of amyloid beta (and other waste products) as a normal immune response. Chronic increased production leads to the formation of plaques and the development of symptoms of Alzheimer's and other neurodegenerative diseases. As described herein, the CSF pumps described herein can be used to improve symptoms of Alzheimer's and other neurodegenerative diseases by increasing the effectiveness of the glymphatic system through increased CSF flow / flux. Today, some Alzheimer's drugs are antibodies that target a protein called amyloid beta. It is believed that amyloid beta protein accumulates in the brains of Alzheimer's patients and contributes to the cognitive decline in Alzheimer's. These antibodies promote the patient's immune system to remove amyloid beta deposits from the brain. Other Alzheimer's drugs include cholinesterase inhibitors, which prevent the breakdown of acetylcholine, a brain chemical thought to be important for memory and thinking. However, other researchers believe that the production of amyloid beta is caused by neuroinflammation as a normal immune response, and is a symptom of Alzheimer's rather than a cause of Alzheimer's. These researchers propose that administering these antibodies actually causes the body to produce more amyloid beta. In one embodiment, the use of antibodies in conjunction with improved glymphatic clearance improves the symptoms of Alzheimer's and other neurodegenerative diseases. Increasing the flux and flow of CSF improves glymphatic clearance and reduces neuroinflammation. Administering the antibodies after reducing neuroinflammation helps clear the body of accumulated amyloid beta deposits, and with reduced neuroinflammation, the body's natural systems produce less beta amyloid.

[0075]

[0084] In one embodiment, a method is provided for increasing the effectiveness of both the glymphatic and lymphatic systems. As described herein, fluids and waste from the brain / CNS flow into the CSF and then directly into the lymphatic system. There is also a flow path for fluids from the ISF system directly into the lymphatic system. At the same time, fluids and wastes flow from the TSF into the CSF and then into the blood after being filtered by the arachnoid villi. Using the pump described herein increases the CSF flux. This increased CSF flux increases the pressure in the CSF system, which results in an increased flow of fluids / nutrients to the brain. With more fluid flowing to the brain, more fluids and wastes can flow out of the brain. Some of this draining fluids and wastes flow directly into the lymphatic system, while other fluids and wastes flow from the CSF to the blood through the arachnoid villi. Applying gentle oscillatory pressure to the human body, including the extremities, stimulates the lymphatic system and increases lymphatic flow. Providing this pressure improves the dynamics of the lymphatic system while increasing the flux of CSF using the pump of the present disclosure provides improvement in disease symptoms. In some embodiments, a lymphatic device that applies pressure to the upper body is used. In some embodiments, the CSF pump is used at the same time that the lymphatic device is used, and in some embodiments, they are used at different times.

[0076]

[0085] As used herein, amelioration of symptoms or ameliorating symptoms means reducing, slowing or eliminating the progression of the disease, alleviating or reducing some or all of the symptoms of the disease, palliating the disease, or curing the disease.

[0077]

[0086] As a person ages, the human body slows down and CSF flux and flow is reduced compared to when the person was younger. As with many systems, when the system is stressed (reduced CSF flow and flux), the weakest link begins to break. In humans, this may manifest as a more pronounced disease or condition to which the person is susceptible. In some people, this may be memory problems, sleep disorders, depression, or other abnormal brain activity. These conditions may also be precipitated by head or CNS trauma or injury. It is believed that brain stimulation can cause the release of growth hormone or other hormones and / or enzymes. In some embodiments, the brain is stimulated by improving the flow of CSF in the spine and / or brain. Some believe that CSF production is a passive process, with the body producing more or less as needed. With increased CSF flux and flow, the body increases filtration of CSF, resulting in increased CSF production. Increased circulation of CSF also leads to brain stimulation and increased release of growth hormone or other hormones and / or enzymes. In some embodiments, brain stimulation may occur by administering electrical / mechanical energy to a subject, as described herein.

[0078]

[0087] In one embodiment, a device and method is disclosed for improving the symptoms of Alzheimer's disease and other neurodegenerative diseases by increasing the flux and flow of CSF, thus increasing the removal of waste products from the brain and / or CNS, thereby improving the symptoms of Alzheimer's disease and other neurodegenerative diseases.

[0079]

[0088] In one embodiment, a method is provided for improving symptoms of depression. In one embodiment, a method is provided for improving sleep patterns. In one embodiment, a method is provided for improving memory. In many conditions or diseases that result from the brain not functioning optimally, it is believed that increasing CSF flux in the spinal column and / or brain will improve brain function and therefore improve the symptoms of these conditions or diseases.

[0080]

[0089] In one embodiment, a device and method are provided for increasing the rate and / or efficiency and / or effectiveness of delivery of drugs infused into the CSF. For drugs infused or perfused into the CSF system, the rate of drug transport depends on the natural flow and flux of the CSF system. By using the pump of the present disclosure to increase the flux of the CSF system, the rate of drug delivery is increased and the effectiveness of the drug may also be increased. In one embodiment, a method for increasing the rate and / or efficiency and / or effectiveness of intravenous chemotherapy drugs for brain conditions. By using the pump of the present disclosure to increase the flux of the CSF, the delivery of intravenous drugs is improved.

[0081]

[0090] In one embodiment, a device and method are provided for improving the symptoms of chemobrain. Often chemotherapy patients experience confusion in behavior or thinking, confusion, memory loss, and impaired concentration, attention, learning ability, and decision making. These signs and symptoms are called chemobrain. By using the pump of the present invention, the increased flux of CSF leads to improved glymphatic clearance, removing chemotherapy drug by-products from the brain.

[0082]

[0091] In one embodiment, a device and method are provided for improving the health of bedridden patients. A person may be bedridden due to illness or advanced age. This may include people who are in a coma, paralyzed, disabled, or otherwise immobile. One way the human body increases CSF flow and flux is through movement or motion. When bedridden, the body is unable to move and in certain conditions cannot move. Some of the pump embodiments described herein are made thin enough to be positioned on a normal or hospital bed mattress without the need for a dedicated mattress. Some pump embodiments described herein require a modified mattress, perhaps one with an opening to allow the pump to be positioned within the opening. To increase CSF flow in bedridden patients, the pump of the present invention may be positioned near the spine, in some embodiments near the lumbar region, and activated to induce a change in spinal flexion. This change in spinal flexion results in increased CSF flow and improved glymphatic clearance. Improving glymphatic clearance may also reduce symptoms of brain injury and / or neurodegenerative disease if these conditions cause the patient to be bedridden.

[0083]

[0092] In some embodiments, the control system is associated with one or more pumps. In some embodiments, when using a single pump, the spine is flexed 1 to 5 mm, or 2 to 4 mm, or about 3 mm from a resting (shallow breathing) position. In some embodiments, when using a lumbar or thoracic pump and a cervical pump, the lumbar or thoracic region of the spine is flexed 1 to 5 mm, or 2 to 4 mm, or about 3 mm from a resting (shallow breathing) position, and the cervical region of the spine is flexed by providing the subject's head with a range of flexion and extension of 10 to 40 degrees, or 15 to 35 degrees, or 20 to 30 degrees from a base position. In some embodiments, the amount of flexion may be greater than, less than, or equal to the amount of extension. In embodiments where lateral flexion is provided, an amount of flexion of 10 to 45 degrees, or 15 to 40 degrees, or 20 to 30 degrees from a base position may be used. In some embodiments, the flexion of the spine may begin at a low level and be increased over the course of treatment. Subjects may receive from 1 to 7 or more treatments per week, with each treatment lasting 15, 20, 25, 30, 35, 40, or 45 minutes or more.

[0084]

[0093] In some embodiments, the pump is used to create pressure changes and / or pressure gradients and / or pressure waves in the CSF system without removing CSF from the CSF system. In these embodiments, it may be safer for the patient to receive the benefits of increased CSF flux and flow without the surgery required to access and remove CSF from the CSF system, even if the removed CSF is ultimately returned to the CSF system.

[0085]

[0094] In one non-limiting example, a subject is placed in a chair as described herein and the subject is rotated to a weightless position. The chair may include a cervical flexion device and a lumbar flexion device. The subject is positioned in the chair and the lumbar flexion device is positioned adjacent to L2 and / or L3. While the cervical flexion device positions the subject's head in the base position, the control system controlling the two flexion devices raises the lumbar flexion device until the pad of the lumbar flexion device just touches the fabric / skin of the subject's posterior body. This is called the home position. In some embodiments of this non-limiting example, the technician raises the lumbar flexion device to a point where the pressure on the lumbar region is just above what is comfortable, but not so much that it causes pain to the patient. This distance is the range that the lumbar flexion device will travel to during treatment. In some embodiments of this non-limiting example, the technician or the control system sets the range distance to 20-30 mm or 20-25 mm. The control system has limits of about 40° extension and 40° flexion or about 30° extension and 30° flexion for the cervical flexion device. The technician then activates the control system. The first movement is for the cervical flexion device to transition to a flexed position. The control system simultaneously causes the lumbar flexion device to flex the spine a distance equal to its range while the cervical flexion device transitions from flexion to extension. The control system then simultaneously returns the lumbar flexion device to the home position while the cervical flexion device transitions from extension to flexion. These two movements are referred to as one cycle. In some embodiments of this non-limiting example, a complete cycle takes 10-15 seconds, with the upward movement of the lumbar flexion device (away from the home position) taking about 35% to 45% of the cycle time and the downward movement (back to the home position) taking 55% to 65% of the cycle time. In some embodiments of this non-limiting example, the treatment time is 30-45 minutes. In some embodiments of this non-limiting example, the subject receives 5 treatments per week. In some embodiments of this non-limiting example, the range of the wood bending device is set to 20 mm at the beginning of treatment and gradually increased to 30 mm by the end of treatment.

[0086]

[0095] Although specific embodiments are illustrated and described herein, those skilled in the art will understand that arrangements calculated to achieve the same results may be substituted for the specific embodiments shown. For example, where the present disclosure may describe a system or method having an example of a distal protection device, any distal protection device, including those disclosed herein, may be used. The present disclosure is intended to encompass modifications or variations of one or more embodiments of the present disclosure. It should be understood that the above description has been made by way of example and is not limiting. Combinations of the above embodiments and other embodiments not specifically described herein will be apparent to those skilled in the art upon reviewing the above description. The scope of one or more embodiments of the present disclosure includes other applications in which the above structures and processes are used. Thus, the scope of one or more embodiments of the present disclosure should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

[0087]

[0096] In the foregoing Detailed Description, for the purpose of streamlining the disclosure, some features are grouped together in a single embodiment. This method of disclosure is not to be interpreted as reflecting an intention that the disclosed embodiments of the disclosure must use more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separate embodiment.

Claims

1. 1. A method of increasing cerebrospinal fluid (CSF) flow within a patient's CSF system, comprising: positioning a first pump adjacent to a spinal column, the pump configured to change the curvature of the spinal column; activating the first pump; Varying the curvature of the spine. The method includes:

2. 10. The method of claim 1, wherein exogenous CSF is not removed from or added to the CSF system.

3. The first pump is positioned in a lumbar region of the spine, and the method includes: positioning a second pump adjacent to the cervical region of the spine; activating the second pump; and Varying the curvature of the cervical region of the spine. The method of claim 1 further comprising:

4. The method of claim 3 , wherein the second pump provides flexion or extension.

5. 10. The method of claim 1, further comprising providing electrical, acoustic, electromagnetic or mechanical stimulation to the patient.

6. The method of claim 1 , wherein the first pump is positioned in a chair back and the first pump includes a pad, the pad configured to apply pressure to the spine.

7. 7. The method of claim 6, wherein the chair further includes a head rest, the method including moving the head rest to provide flexion and extension of the cervical region of the spine.

8. The method of claim 1 , wherein the first pump is configured to provide an oscillatory pressure to the patient.

9. The method of claim 6 , wherein the chair is configured to provide a zero gravity position for the patient.

10. 13. The method of claim 1, comprising increasing flow to the glymphatic system, reducing neuroinflammation, ameliorating symptoms of stroke, improving function of both the lymphatic and glymphatic systems, improving posture, or ameliorating symptoms of Alzheimer's disease.

11. 10. The method of claim 1, wherein the first pump includes a pad, and actuating the first pump includes applying pressure to the spine with the pad.

12. The method of claim 11 , wherein actuating the first pump further comprises moving the pad between a first position and a second position.

13. The method of claim 12 , further comprising cyclically moving the pad between the first position and the second position.

14. 14. The method of claim 13, comprising a first time for moving the pad from the first position to the second position and a second time for moving the pad from the second position to the first position, the second time being greater than the first time.

15. A therapeutic assistance device, Frame, a first support including an aperture; 1. A cerebrospinal fluid pump comprising a body and a pad, the body attached to the frame, the pad extending through the aperture, the pad positioned for movement between a retracted position and an extended position relative to the first support along an actuation axis. A therapeutic support device comprising:

16. 16. The therapeutic assist device of claim 15, further comprising a second support, the second support arranged to rotate relative to the first support about an axis of rotation.

17. The therapeutic assist device of claim 16 , wherein the rotation axis is oriented perpendicular to the actuation axis.

18. 17. The therapeutic support device of claim 16, including a first orientation in which the pad is in the retracted position and the second support is oriented at a first angle relative to the first support, and a second orientation in which the pad is in an intermediate position and the second support is oriented at a second angle relative to the first support, the second angle being greater than the first angle.

19. 16. The therapeutic assist device of claim 15, wherein the cerebrospinal fluid pump includes a first cerebrospinal fluid pump, the body includes a first body, the pad includes a first pad, and the actuation axis includes a first actuation axis, and the therapeutic assist device further includes a second cerebrospinal fluid pump including a second body and a second pad extending through the aperture, the second pad being arranged to move relative to the first support along a second actuation axis.

20. 1. A cerebrospinal fluid pump comprising: base, a pad arranged to move along an actuation axis; a motor arranged to rotate a drive shaft; a first slider engaged with the drive shaft, the first slider being positioned to move in a first direction relative to the base upon rotation of the drive shaft; a second slider engaged with the drive shaft, the second slider being positioned to move in a second direction relative to the base upon rotation of the drive shaft; a first connector pivotally attached to the first slider, the first connector being attached to the pad; a second connector pivotally mounted to the second slider, the second connector being attached to the pad; cerebrospinal fluid pump including

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