Systems, catheters and methods for delivering treatments along the central nervous system

Abstract

Systems, catheters, and methods for accessing and treating along the central nervous system are disclosed. An example method may manage inflammation in a patient to treat the patient's condition by processing values ​​associated with one or more physiological parameters of the patient, identifying when the patient's inflammatory condition has reached a therapeutic condition based on the processed values, and automatically providing an indication that the inflammatory condition has reached the therapeutic condition. An example indication may include actuating a treatment regimen. The example method may be performed with an inflammation management system.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of priority under 35 U.S.C. §119 to U.S. Provisional Application Serial No. 62 / 716,335, filed on August 8, 2018, and U.S. Provisional Application Serial No. 62 / 844,566, filed on May 7, 2019, the entire disclosures of which are incorporated herein by reference. Technical Field

[0003] The present invention relates to systems, modules and methods for diagnosis and treatment along the central nervous system. Background Art

[0004] A wide variety of medical devices, systems and methods have been developed for medical use. Some of these devices, systems and methods include control systems, pumps, guidewires, catheters, etc. These devices and systems are manufactured by any of a variety of different manufacturing methods and can be used according to any of a variety of methods. Each of the known medical devices, systems and methods has certain advantages and disadvantages. There is a need to provide alternative medical devices and alternative methods for making and using medical devices. Summary of the invention

[0005] The present invention provides designs, materials, manufacturing methods and use alternatives for medical devices and / or systems. One example includes an inflammation management system. The system includes: a controller; a cerebrospinal fluid management module in communication with the controller; wherein the controller is configured to: monitor measurements of one or more physiological parameters of a patient; compare values ​​associated with the monitored measurements of the one or more physiological parameters with a threshold; and control the cerebrospinal fluid management module based on the comparison of the values ​​associated with the monitored measurements of the one or more physiological parameters with the threshold.

[0006] Alternatively or additionally to any of the above embodiments, the controller is configured to automatically control the cerebrospinal fluid management module to perform treatment on the patient's cerebrospinal fluid when a value associated with the monitored measurement of one or more physiological parameters reaches or exceeds a threshold value.

[0007] Alternatively or additionally to any of the above embodiments, wherein the treatment of the patient's cerebrospinal fluid is a predetermined treatment based on a type of physiological parameter associated with the monitored measurement.

[0008] Alternatively or additionally to any of the above embodiments, wherein the treatment of the patient's cerebrospinal fluid is a predetermined treatment based on a comparison of a value associated with the monitored measurements of one or more physiological parameters and a type of physiological parameter associated with the monitored measurements.

[0009] Alternatively or additionally to any of the above embodiments, wherein the value associated with the monitored measured values ​​of one or more physiological parameters is an indexed value associated with measured values ​​of two or more physiological parameters of the patient.

[0010] Alternatively or additionally to any of the embodiments above, wherein the indexed value is a value based on an index of measured values ​​of two or more physiological parameters of the patient.

[0011] Alternatively or additionally to any of the above embodiments, wherein the indexed value is based on a value of an index of two or more of the classification indices, and each of the two or more of the classification indices is based on measured values ​​of two or more physiological parameters of the patient.

[0012] Alternatively or additionally to any of the embodiments above, wherein the value associated with the monitored measured value of the one or more physiological parameters is a value of the measured value of one of the one or more physiological parameters.

[0013] Alternatively or additionally to any of the above embodiments, the one or more physiological parameters include one or more physiological parameters selected from a group consisting of intracranial pressure, cerebral perfusion pressure, mean arterial pressure, heart rate, cerebral oxygenation, cerebral blood flow, and cytokine levels.

[0014] Alternatively or additionally to any of the above embodiments, wherein the cerebrospinal fluid management module includes a cooling therapy module.

[0015] Alternatively or additionally to any of the above embodiments, wherein the cerebrospinal fluid management module includes a filtration therapy module.

[0016] Alternatively or additionally to any of the above embodiments, the cerebrospinal fluid management module includes a cooling therapy module and a filtration therapy module.

[0017] Alternatively or additionally to any of the above embodiments, wherein the cerebrospinal fluid management module includes a circulation module having a pump configured to pump cerebrospinal fluid from the patient to the treatment module.

[0018] Alternatively or additionally to any of the above embodiments, further comprising: a communication port in communication with the controller; and wherein the communication port is configured to receive measurements of one or more physiological parameters of the patient monitored by the controller.

[0019] Alternatively or additionally to any of the above embodiments, it also includes: a communication port in communication with the controller; and wherein the communication port is configured to facilitate communication between the cerebrospinal fluid management module and the controller.

[0020] Alternatively or additionally to any of the above embodiments, it also includes: a wireless communication port in communication with the controller and configured to facilitate communication between the controller and the device via a wireless network.

[0021] Alternatively or additionally to any of the above embodiments, it also includes: a user interface in communication with the controller; and wherein the user interface is configured to receive input that modifies the operation of the controller.

[0022] Alternatively or additionally to any of the above embodiments, the user interface is configured to display a medical image of the patient in a selectable pane, and to display one or both of measured values ​​of one or more physiological parameters of the patient and values ​​related to the monitored measured values ​​of the one or more physiological parameters in a real-time updating pane position on the user interface adjacent to the selectable pane.

[0023] Another example includes a cerebrospinal fluid circulation system. The system includes: a controller; a circulation management module in communication with the controller; and a cerebrospinal fluid therapy management module in communication with the controller; wherein the controller is configured to automatically control the circulation management module and the cerebrospinal fluid therapy management module based on measured values ​​of one or more physiological parameters of the patient.

[0024] Alternatively or additionally to any of the above embodiments, wherein the controller is configured to control the circulation management module to maintain a predetermined cerebrospinal fluid flow rate.

[0025] Alternatively or additionally to any of the above embodiments, wherein the controller is configured to control the circulation management module to maintain cerebrospinal fluid pressure at or below a set point level.

[0026] Alternatively or additionally to any of the above embodiments, wherein the cerebrospinal fluid management therapy module is configured to include one or more interchangeable therapy modules.

[0027] Alternatively or additionally to any of the above embodiments, wherein the one or more exchangeable therapeutic modules include one or more therapeutic modules selected from the group consisting of a cooling therapeutic module and a filtering therapeutic module.

[0028] Alternatively or additionally to any of the above embodiments, the cerebrospinal fluid therapy management module includes a cooling therapy module.

[0029] Alternatively or additionally to any of the above embodiments, the controller is configured such that when the controller determines that a value associated with a measurement of a physiological parameter of the patient meets or exceeds a threshold value, the controller adjusts the operation of the circulatory management module to actively drain cerebrospinal fluid while adjusting the operation of the cooling therapy module to cool the cerebrospinal fluid for a predetermined time period.

[0030] Alternatively or additionally to any of the above embodiments, wherein the cerebrospinal fluid therapy management module includes a filtration therapy module.

[0031] Alternatively or additionally to any of the above embodiments, the controller is configured such that when the controller determines that a value associated with a measurement of a physiological parameter of the patient reaches or exceeds a threshold value, the controller adjusts the operation of the circulation management module to circulate the cerebrospinal fluid at a predetermined rate and simultaneously adjusts the operation of the filtration therapy module to filter contaminants from the cerebrospinal fluid.

[0032] Another example includes a method of managing inflammation. The method includes: monitoring measurements of one or more physiological parameters of a patient over time; comparing a value associated with the monitored measurements of the one or more physiological parameters to a threshold; and adjusting operation of a cerebrospinal fluid management module based on the comparison of the value associated with the monitored measurements of the one or more physiological parameters to the threshold.

[0033] Alternatively or additionally to any of the above embodiments, it also includes: determining a difference between a value associated with a monitored measurement of one or more physiological parameters and a threshold; and wherein the adjustment operation of the cerebrospinal fluid management module is based on the determined difference between a value associated with a monitored measurement of one or more physiological parameters and the threshold.

[0034] Alternatively or additionally to any of the above embodiments, wherein an adjustment operation of the cerebrospinal fluid management module is automatically initiated based on a comparison of a value associated with a monitored measurement of one or more physiological parameters to a threshold value.

[0035] Alternatively or additionally to any of the above embodiments, wherein the regulating operation of the cerebrospinal fluid management module initiates a treatment initiation protocol in response to a value associated with a monitored measurement of one or more physiological parameters first reaching or exceeding a threshold.

[0036] Alternatively or additionally to any of the above embodiments, the adjustment operation of the cerebrospinal fluid management module initiates a treatment cessation protocol in response to a value associated with a monitored measurement of one or more physiological parameters reaching or exceeding a threshold a second time after the value reached or exceeded the threshold a first time.

[0037] Alternatively or additionally to any of the above embodiments, wherein the regulating operation of the cerebrospinal fluid management module initiates a therapy cessation protocol in response to a value associated with a monitored measurement of one or more physiological parameters reaching or exceeding a threshold value.

[0038] Alternatively or additionally to any of the above embodiments, wherein the adjustment operation of the cerebrospinal fluid management module initiates a predetermined treatment regimen based on a type of physiological parameter associated with the monitored measurement.

[0039] Alternatively or additionally to any of the above embodiments, the adjustment operation of the cerebrospinal fluid management module initiates a predetermined treatment regimen based on a comparison of a value associated with a monitored measurement of one or more physiological parameters and a threshold value and a type of physiological parameter associated with the monitored measurement.

[0040] Alternatively or additionally to any of the above embodiments, wherein the adjustment operation to the cerebrospinal fluid management module causes the cerebrospinal fluid management module to initiate a cooling therapy regimen.

[0041] Alternatively or additionally to any of the above embodiments, wherein the adjustment operation on the cerebrospinal fluid management module causes the cerebrospinal fluid management module to initiate a filtration therapy regimen.

[0042] Alternatively or additionally to any of the above embodiments, wherein the adjustment operation to the cerebrospinal fluid management module causes the cerebrospinal fluid management module to initiate a filtration therapy regimen and a cooling therapy regimen.

[0043] Another example includes a computer-readable medium having program code stored thereon in a non-transitory state for use by a computing device, the program code causing the computing device to perform a method for managing inflammation, the method comprising: determining a value associated with one or more measured values ​​of one or more physiological parameters; comparing the value associated with the one or more measured values ​​of the one or more physiological parameters to a threshold value; and outputting a control signal to adjust the operation of a cerebrospinal fluid management module based on the comparison of the value associated with the one or more measured values ​​of the one or more physiological parameters to the threshold value.

[0044] Alternatively or additionally to any of the above embodiments, the method also includes: determining a difference between a value associated with one or more measured values ​​of one or more physiological parameters and a threshold; wherein a control signal for adjusting the operation of the cerebrospinal fluid management module is based on the determined difference between the value associated with one or more measured values ​​of one or more physiological parameters and the threshold.

[0045] Alternatively or additionally to any of the embodiments above, wherein output of the control signal is automatically initiated based on a comparison of a value associated with one or more measured values ​​of one or more physiological parameters with a threshold value.

[0046] Alternatively or additionally to any of the above embodiments, the control signal that adjusts the output of the operation of the cerebrospinal fluid management module is configured to initiate a treatment initiation regimen in response to a value associated with one or more measurements of one or more physiological parameters reaching or exceeding a threshold for the first time.

[0047] Alternatively or additionally to any of the above embodiments, the control signal that adjusts the output of the operation of the cerebrospinal fluid management module is configured to initiate a treatment cessation regimen in response to a value associated with one or more measurements of one or more physiological parameters reaching or exceeding a threshold a second time after the value reached or exceeded the threshold a first time.

[0048] Alternatively or additionally to any of the above embodiments, the control signal that adjusts the output of the operation of the cerebrospinal fluid management module is configured to initiate a treatment cessation regimen in response to a value associated with one or more measurements of one or more physiological parameters reaching or exceeding a threshold value.

[0049] Alternatively or additionally to any of the above embodiments, wherein the control signal that adjusts the output of the operation of the cerebrospinal fluid management module is configured to initiate a predetermined treatment regimen based on a type of physiological parameter associated with the one or more measurements.

[0050] Alternatively or additionally to any of the above embodiments, the control signal that adjusts the output of the operation of the cerebrospinal fluid management module is configured to initiate a predetermined treatment regimen based on a comparison of a value associated with one or more measurements of one or more physiological parameters and a threshold value and a type of physiological parameter associated with the one or more measurements.

[0051] Alternatively or additionally to any of the above embodiments, wherein adjusting a control signal to an output of an operation of a cerebrospinal fluid management module causes the cerebrospinal fluid management module to initiate a cooling therapy regimen.

[0052] Alternatively or additionally to any of the above embodiments, wherein a control signal that adjusts an output of an operation of a cerebrospinal fluid management module causes the cerebrospinal fluid management module to initiate a filtration therapy regimen.

[0053] Alternatively or additionally to any of the above embodiments, wherein the control signal that adjusts the output of the operation of the cerebrospinal fluid management module causes the cerebrospinal fluid management module to initiate a filtration therapy regimen and a cooling therapy regimen.

[0054] Another example includes an inflammation management system for managing a patient condition based on values ​​of a physiological parameter of the patient. The inflammation system may include a port configured to communicate with one or more input devices, the port may be configured to receive values ​​associated with one or more physiological parameters of the patient from the one or more input devices; a memory for storing the received values ​​associated with the one or more physiological parameters of the patient; a processor operably coupled to the port and the memory, the processor may be configured to process the received values ​​associated with the one or more physiological parameters of the patient, and identify when the patient's inflammatory condition has reached a therapeutic condition based on the processed received values ​​associated with the one or more physiological parameters of the patient; and wherein the processor is configured to establish one or more indications that the patient's inflammatory condition has reached a therapeutic condition via the port output.

[0055] Alternatively or additionally to any of the above embodiments, the processor may be configured to output a control signal to a cerebrospinal fluid management module to perform treatment on the patient's cerebrospinal fluid in response to identifying when the patient's inflammatory condition reaches a treatment condition.

[0056] Alternatively or additionally to any of the above embodiments, the inflammation management system may also include: a user interface that communicates with the processor via a port; and wherein the processor may be configured to display a recommended treatment plan on the user interface in response to identifying that the patient's inflammatory condition has reached a treatment condition.

[0057] Alternatively or additionally to any of the above embodiments, wherein the processor may be configured to determine an indexation value based on received values ​​associated with one or more physiological parameters, and to identify when the patient's inflammatory condition reaches a therapeutic condition based on the indexation value.

[0058] Alternatively or additionally to any of the above embodiments, wherein the received values ​​may relate to two or more physiological parameters, and the indexed value may be determined based on the received values ​​for at least two physiological parameters.

[0059] Alternatively or additionally to any of the above embodiments, the indexed value may be a value of a brain inflammation index, and the values ​​for at least two physiological parameters may include a value of a white blood cell count (WBC), a value of a body temperature, a value of a heart rate variability, and a value of photoplethysmography.

[0060] Alternatively or additionally to any of the above embodiments, wherein the indexed value may be a value of a mass effect index, and the values ​​for at least two physiological parameters may include a value of a midline shift based on a CT scan, a value of a blood volume, a value of an edema volume, a value of an intracranial pressure, a value of water in the patient's brain, and a value of brain tissue.

[0061] Alternatively or additionally to any of the above embodiments, wherein the indexed value may be a value of a National Institutes of Health Stroke Scale index, and the values ​​for at least two physiological parameters may include a value for level of consciousness, a value for eye measurements obtained with a pupillometer, a value for motor skills, a value for sensation, and a value for language skills.

[0062] Alternatively or additionally to any of the above embodiments, the indexed value may be a value of a fluid management index, and the values ​​for at least two physiological parameters may include a value of blood pressure, values ​​of fluid input and output, a value of cerebral perfusion pressure, a value of sodium content, and a value of potassium content.

[0063] Alternatively or additionally to any of the above embodiments, wherein the indexed value may be a value of a Glasgow Coma Scale index, and the values ​​for the at least two physiological parameters may include a value of an eye measurement, a value of a motor skill, and a value of a language skill.

[0064] Alternatively or additionally to any of the above embodiments, wherein the indexation value may be based on a plurality of classification index values.

[0065] Alternatively or additionally to any of the above embodiments, the multiple classification index values ​​may include values ​​for two or more of an inflammation index, a mass effect index, a National Institutes of Health Stroke Scale index, a fluid management index, and a Glasgow Coma Score Scale index.

[0066] Alternatively or additionally to any of the above embodiments, the treatment condition can be a condition related to a subarachnoid hemorrhage in the patient, and the indexed value can be based on a value for an inflammation index, a value for a mass effect index, a value for a National Institutes of Health Stroke Scale index, and a value for a fluid management index.

[0067] Alternatively or additionally to any of the above embodiments, the treatment condition may be a condition associated with intracranial hemorrhage in the patient, and the indexed value may be based on a value of an inflammation index, a value of a mass effect index, and a value of a National Institutes of Health Stroke Scale index.

[0068] Alternatively or additionally to any of the above embodiments, wherein the treatment condition is a condition associated with a traumatic brain injury of the patient, and the indexed value is based on a value of an inflammation index, a value of a mass effect index, and a value of a Glasgow Coma Scale index.

[0069] Alternatively or additionally to any of the above embodiments, wherein the indexed value may indicate a trend in the patient's inflammatory condition over time.

[0070] Another example includes a method of managing inflammation to treat a patient condition, the method comprising: receiving values ​​associated with a physiological parameter of the patient; processing, with a processor, the values ​​associated with one or more physiological parameters of the patient; identifying, with the processor, based on the processed values ​​associated with the one or more physiological parameters of the patient, that the patient's inflammatory condition has reached a therapeutic condition; and in response to identifying that the patient's inflammatory condition has reached a therapeutic condition, automatically outputting an indication that the patient's inflammatory condition has reached a therapeutic condition via a port that communicates with the processor.

[0071] Alternatively or additionally to any of the above embodiments, outputting an indication that the patient's inflammatory condition has reached a treatment condition may include: outputting a control signal from the processor to the cerebrospinal fluid management module, thereby instructing the cerebrospinal fluid management module to perform treatment on the patient's cerebrospinal fluid.

[0072] Alternatively or additionally to any of the above embodiments, the method may further include automatically selecting, with a processor, a therapy for treating the patient's cerebrospinal fluid based on the processed value associated with the patient's physiological parameter.

[0073] Alternatively or additionally to any of the above embodiments, wherein outputting an indication that the patient's inflammatory condition has reached a therapeutic condition may include displaying a suggested treatment regimen for treating the inflammatory condition on a user interface.

[0074] Alternatively or additionally to any of the above embodiments, the method may also include: in response to identifying that the patient's inflammatory condition has reached a treatment condition, automatically selecting a recommended treatment plan from a treatment plan module based on processed values ​​associated with one or more physiological parameters of the patient using a processor.

[0075] Alternatively or additionally to any of the above embodiments, wherein: processing values ​​associated with one or more physiological parameters of the patient may include determining an indexation value based on the values ​​associated with one or more physiological parameters of the patient; and identifying that the patient's inflammatory condition has reached a therapeutic condition may be based on the indexation value.

[0076] Alternatively or additionally to any of the above embodiments, wherein: the received values ​​related to one or more physiological parameters of the patient may relate to two or more physiological parameters of the patient; and the indexed value may be determined based on the values ​​for at least two physiological parameters.

[0077] Alternatively or additionally to any of the above embodiments, the indexed value may be a value of a brain inflammation index, and the values ​​for at least two physiological parameters may include a value of a white blood cell count (WBC), a value of a body temperature, a value of a heart rate variability, and a value of photoplethysmography.

[0078] Alternatively or additionally to any of the above embodiments, wherein the indexed value may be a value of a mass effect index, and the values ​​for at least two physiological parameters may include a value of a midline shift based on a CT scan, a value of a blood volume, a value of an edema volume, a value of an intracranial pressure, a value of water in the patient's brain, and a value of brain tissue.

[0079] Alternatively or additionally to any of the above embodiments, wherein the indexed value may be a value of a National Institutes of Health Stroke Scale index, and the values ​​for at least two physiological parameters may include a value for level of consciousness, a value for eye measurements, a value for motor skills, a value for sensation, and a value for language skills.

[0080] Alternatively or additionally to any of the above embodiments, the indexed value may be a value of a fluid management index, and the values ​​for at least two physiological parameters may include a value of blood pressure, values ​​of fluid input and output, a value of cerebral perfusion pressure, a value of sodium content, and a value of potassium content.

[0081] Alternatively or additionally to any of the above embodiments, wherein the indexed value may be a value of a Glasgow Coma Scale index, and the values ​​for the at least two physiological parameters may include a value of an eye measurement, a value of a motor skill, and a value of a language skill.

[0082] Alternatively or additionally to any of the above embodiments, wherein determining the indexation value may include processing a plurality of classification index values.

[0083] Alternatively or additionally to any of the above embodiments, the multiple classification index values ​​may include values ​​for two or more of an inflammation index, a mass effect index, a National Institutes of Health Stroke Scale index, a fluid management index, and a Glasgow Coma Score Scale index.

[0084] Alternatively or additionally to any of the above embodiments, the treatment condition can be a condition related to a subarachnoid hemorrhage in the patient, and the indexed value can be based on a value for an inflammation index, a value for a mass effect index, a value for a National Institutes of Health Stroke Scale index, and a value for a fluid management index.

[0085] Alternatively or additionally to any of the above embodiments, the treatment condition may be a condition associated with intracranial hemorrhage in the patient, and the indexed value may be based on a value of an inflammation index, a value of a mass effect index, and a value of a National Institutes of Health Stroke Scale index.

[0086] Alternatively or additionally to any of the above embodiments, wherein the treatment condition may be a condition associated with a traumatic brain injury of the patient, and the indexed value may be based on a value of an inflammation index, a value of a mass effect index, and a value of a Glasgow Coma Scale index.

[0087] Another example includes a computer-readable medium having program code stored thereon in a non-transitory state for use by a computing device, the program code causing the computing device to perform a method for managing inflammation to treat a patient condition, the method comprising: storing values ​​associated with one or more physiological parameters of the patient in a memory; determining an indexation value based on the values ​​associated with one or more physiological parameters of the patient stored in the memory; identifying that the patient's inflammatory condition has reached a therapeutic condition based on the indexation value; and in response to identifying that the patient's inflammatory condition has reached a therapeutic condition, automatically outputting an indication that the patient's inflammatory condition has reached a therapeutic condition.

[0088] Alternatively or additionally to any of the above embodiments, automatically outputting an indication that the patient's inflammatory condition has reached a treatment condition may include outputting a control signal to a cerebrospinal fluid management module, thereby instructing the cerebrospinal fluid management module to execute a treatment regimen on the patient's cerebrospinal fluid.

[0089] Alternatively or additionally to any of the above embodiments, the method may further include automatically selecting a treatment regimen for treating the patient's cerebrospinal fluid based on the indexed value.

[0090] Alternatively or additionally to any of the above embodiments, where automatically outputting an indication that the patient's inflammatory condition has reached a therapeutic condition may include displaying a suggested treatment regimen for treating the inflammatory condition on a user interface.

[0091] Alternatively or additionally to any of the above embodiments, the method may further include: in response to identifying that the patient's inflammatory condition has reached a therapeutic condition, automatically selecting a recommended treatment regimen for treating the inflammatory condition based on the indexed value.

[0092] Alternatively or additionally to any of the above embodiments, wherein determining the indexation value may include processing a plurality of classification index values.

[0093] Alternatively or additionally to any of the above embodiments, the multiple classification index values ​​may include values ​​for two or more of an inflammation index, a mass effect index, a National Institutes of Health Stroke Scale index, a fluid management index, and a Glasgow Coma Score Scale index.

[0094] Alternatively or additionally to any of the above embodiments, wherein the indexed value may indicate a trend in the patient's inflammatory condition over time.

[0095] Another example includes an inflammation management system for managing a patient's condition based on values ​​of the patient's physiological parameters, the system may include: a port configured to communicate with one or more input devices, the port configured to receive values ​​related to the patient's physiological parameters from the one or more input devices; a memory for storing the received values ​​related to the patient's physiological parameters; a processor operably connected to the port and the memory, the processor may be configured to process the received values ​​related to the patient's physiological parameters and establish an indexed value indicating a trend of the patient's inflammatory condition over time based on the received values ​​related to the physiological parameters; and wherein the processor may be configured to output an indication based on the indexed value via the port.

[0096] Alternatively or additionally to any of the above embodiments, wherein the indication based on the indexed value may include establishing an indication that the patient's inflammatory condition has reached a therapeutic condition.

[0097] Alternatively or additionally to any of the above embodiments, wherein the indication based on the indexed value may include a control signal to a cerebrospinal fluid management module for performing a treatment on the patient's cerebrospinal fluid in response to the patient's inflammatory condition reaching a treatment condition.

[0098] Alternatively or additionally to any of the above embodiments, it may also include:

[0099] A user interface in communication with the processor via a port, the user interface may include a first pane displaying a value associated with a physiological parameter of the patient over time; and wherein the indication based on the indexed value may include a control signal from the processor to the user interface for displaying the indexed value in the first pane.

[0100] Alternatively or additionally to any of the above embodiments, wherein the indexed value may be displayed in a first pane relative to a range of possible indexed values, and the value associated with the patient's physiological parameter may be displayed in a second pane relative to a predetermined time period.

[0101] The above summary of some embodiments is not intended to describe each disclosed embodiment or every implementation of the present invention. The following figures and detailed description more particularly exemplify these embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0102] The present invention may be more fully understood by considering the following detailed description taken in conjunction with the accompanying drawings, in which:

[0103] Figure 1is a schematic diagram of an example inflammation management system for communicating with a patient;

[0104] Figure 2 is a schematic block diagram of the inflammation management system;

[0105] Figure 3 is a schematic diagram of an example display of a user interface of an inflammation management system;

[0106] Figure 4 is a schematic flow chart of an inflammation management system for use with a patient;

[0107] Figure 5 is a schematic flow chart of an example method of managing inflammation; and

[0108] Figure 6 is a schematic flow chart of an example method for managing inflammation.

[0109] Although the present invention is suitable for various modifications and alternative forms, its specific details have been shown in the drawings by way of example and will be described in more detail. However, it should be understood that it is not intended to limit the present invention to the specific embodiments described. On the contrary, it is intended to cover all modifications, equivalents and substitutes that fall within the spirit and scope of the present invention. DETAILED DESCRIPTION

[0110] The incidence of stroke, intracranial hemorrhage, traumatic brain injury (TBI), and subarachnoid hemorrhage results in more than 1.1 million hospitalizations each year. Acute ischemic stroke alone accounts for 700,000 hospitalizations each year. Acute brain injury (e.g., caused by trauma, hemorrhage, stroke, etc.) can occur in varying degrees and may require the brain to undergo a healing process.

[0111] Patients with brain injuries may experience fever, seizures, swelling, and / or elevated intracranial pressure. As discussed below, today's physicians have limited tools at their disposal to aid in the diagnosis, treatment, and rehabilitation of brain injuries.

[0112] Between a quarter and more than half of patients admitted to a neurological intensive care unit (NICU) due to acute brain injury have a fever. The cause of the fever in these patients often remains unexplained. Central fever associated with loss of physiological regulation of body temperature by the hypothalamus is generally considered a possible cause of persistent fever in patients with acute brain injury who have no signs of infection. Since hyperthermia is very detrimental to the recovery of an acutely injured brain and can lead to increased time spent in the NICU, techniques for returning body temperature to normal "operating" temperatures (e.g., ~98.6 degrees Fahrenheit (F)) play an important role in minimizing inflammation and restoring recovery to the injured brain.

[0113] Status epilepticus (SE), a condition in which seizures continue to occur without recovery of consciousness between seizures, affects up to 150,000 patients in the United States, with a mortality rate of between 3% and 33%. Initial treatment of SE with medications (e.g., benzodiazepines, phenytoin, and / or phenobarbital) typically fails to terminate SE in 30% to 50% of SE cases. SE that is not cured after treatment with medications may be particularly problematic because longer-lasting cases become more difficult to treat. Even infusions of anesthetics (e.g., doses of midazolam, pentobarbital, and propofol) that have traditionally been used to control refractory SE fail in 8% to 21% of cases. In addition, epileptic seizures, particularly prolonged seizures or epileptic seizures, have a risk of permanent neuronal damage. In view of the incomplete efficacy of current therapies and the possibility of neurological damage, improved diagnosis and earlier treatment are needed to treat and reduce brain damage in patients with SE.

[0114] Effective brain oxygenation requires adequate cerebral perfusion pressure, and patients with acute brain injury and / or other conditions may be susceptible to insufficient cerebral perfusion pressure. Cerebral perfusion pressure may depend on the "resistance" provided by intracranial pressure (ICP) or jugular venous pressure (JVP), whichever is higher. Intracranial pressure is determined by the relative proportions of soft tissue, blood and CSF within the skull. In healthy supine adults, normal ICP is 5 to 15 mmHg, which becomes lower than atmospheric pressure (about -10 mmHg) when standing. The continued rise in ICP has been shown to have an adverse effect on patient prognosis, and in this regard, intracranial hypertension (i.e., elevated ICP) provides a modifiable risk factor in the management of patients with acute brain injury or other head injuries. In most cases, relatively conservative methods (such as, head elevation, sedation and / or osmotic therapy) are sufficient to treat lower ICP. However, despite the use of these protective treatments, ICP remains elevated in more than 50,000 cases each year.

[0115] The disclosed concepts can provide an inflammation management system that can diagnose and / or administer treatment in a manner configured to improve the prognosis of a patient suffering from an acute brain injury. For example, an inflammation management system can be configured to facilitate early diagnosis of a condition associated with an acute brain injury or other head condition and / or treat a condition associated with an acute brain injury or other head condition. In some cases, an inflammation management system can be configured to address the patient's diagnosis by regulating the patient's cerebrospinal fluid.

[0116] Cerebrospinal fluid (CSF) is a generally transparent colorless liquid produced in the ventricles of the brain, particularly in the choroid plexus. The choroid plexus produces about 500 milliliters of CSF every day, so as to adapt to flushing or recycling CSF to remove toxins and metabolites, which occurs several times a day. CSF slowly flows through a channel (tube) to the space around the brain and spine from the choroid plexus, and then enters the body. Cerebrospinal fluid is found in the space between the pia mater and the arachnoid (called the subarachnoid space). CSF is also found in and around the ventricular system of the brain, which is continuous with the central canal of the spinal cord. In case of acute brain injury (for example, stroke or other brain injury) or other head injuries, it may be desirable to remove CSF from a position (for example, the cervical region or ventricle of the spine), process (for example, regulate) the CSF removed and return the CSF removed to the CSF space (for example, the lumbar region of the spine) located at the position and / or located at a second position.

[0117] Conditioning therapies, such as Neurapheresis™ therapy and / or other suitable conditioning therapies may result in the removal of substances (e.g., microorganisms, cells, viruses, foreign matter, drugs, combinations thereof, etc.) from the CSF. In addition to or as an alternative to treating conditions associated with acute brain injury (e.g., stroke, TBI, encephalitis, etc.) and / or conditions associated with other head injuries, these conditioning therapies and other therapeutic techniques may be used to treat many other neurological diseases or conditions, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), meningitis of various causes, Guillain-Barré syndrome (GBS), multiple sclerosis (MS), neurocognitive disorders associated with HIV, spinal cord injury, cerebral vasospasm, and other diseases or conditions.

[0118] Purification, conditioning and / or compound removal protocols or systems can be adjusted to a wide range of physiological parameters and flow rates. For example, protocols and / or systems can be customized for specific diseases and a group of diseases, including based on a variety of characteristics of the disease, such as size, affinity, biochemical properties, temperature and / or other characteristics. Purification protocols can be based on diffusion, size exclusion, ex vivo immunotherapy using immobilized antibodies or antibody fragments, hydrophobic / hydrophilic, anionic / cationic, high / low binding affinity, chelating agents, antibacterial, antiviral, anti-DNA / RNA / amino acid, enzymatic, and magnetic and / or nanoparticle-based systems.

[0119] With respect to an inflammation management system for monitoring a patient (e.g., monitoring a patient's condition) and / or for CSF conditioning therapy (e.g., Neurapheresis™ therapy and / or other conditioning therapies), the disclosed inflammation management system can be used to safely and quickly access the CSF space with minimal disruption to CSF ​​flow in response to diagnosing the patient's condition. The systems and devices disclosed herein provide a safe and rapid flow circuit.

[0120] The inflammation management systems and related devices disclosed herein can be used to access the CSF space to remove CSF from one location (e.g., the cervical region of the spine or the ventricles), condition or otherwise process the removed CSF, and safely and effectively return the conditioned CSF to the CSF space, including at a second location (e.g., the lumbar region of the spine). In various aspects, the inflammation management systems and related devices disclosed herein can maintain endogenous ICP or intramedullary pressure within a physiological range, for example, from about 5 to about 20 mm Hg or from about 0 to about 10 mm Hg or from about -5 to about 10 mm Hg or from about -5 to about 25 mm Hg.

[0121] In various aspects, the inflammation management systems and related devices disclosed herein can reduce or eliminate recirculating flow loops, which can improve the efficiency of the inflammation management system. In some aspects, the inflammation management system can include sensors in the catheter or within the flow loop to detect blockages or occlusions in the system, thereby providing closed-loop pressure control.

[0122] In certain aspects, the inlet-outlet spacing of the inflammation management system can be selected to maximize it while remaining below the level of the patient's cervical region. Additionally or alternatively, the inflammation management system and related devices can maintain the spacing between the inlet and outlet, for example, in the range of about 10 cm to about 40 cm. In certain embodiments, the spacing is in the range of about 10 cm to about 30 cm.

[0123] In certain aspects, the inlet-outlet spacing can be selected based on the vertebral spacing. For example, the spacing can be selected so that the inlet-outlet spacing is within the range of the length of from about five (5) vertebrae to about twelve (12) vertebrae. In certain embodiments, a spacing of about 10 vertebrae can be selected; however, other configurations (such as those described elsewhere in this specification) can also be utilized. In designing such spacing, it can be assumed that the length of the vertebrae is about 2 to 3 cm, however, other measurements and designs can also be used.

[0124] In some embodiments, the specific size, shape and / or other configuration of the lumen of the catheter used with the inflammation management system can be selected to promote the ability of the catheter to clear and / or resist obstruction. For example, the proximal outer diameter of the lumen in the range from about 0.060 inches to about 0.070 inches and the proximal inner diameter in the range from about 0.025 inches to about 0.060 inches can be selected; however, other configurations (such as those described elsewhere in this specification) can also be utilized. In some aspects, in case there is tissue that blocks a certain number of holes, there can also be multiple holes along the entrance and / or exit of the catheter to achieve redundancy. In some embodiments, the specific coil pitch of the coiled wire in the catheter can be selected to reduce the kinking of the catheter.

[0125] The disclosed inflammation management system and related devices can be used to access the CSF space and can be used at any entry point in the cervical (C1-C7), thoracic (T1-T12), or lumbar region (L1-L5) of the spine. The entry site in the cervical region can be used to access the ventricular system in the brain. In one embodiment, the system and device are used to access the lumbar region. In some embodiments, the inlet and outlet of the inflammation management system can be located in a position along the spine so that the drainage process will not cause tissue to be sucked into the catheter. For example, while the patient is lying on a table, entry can be made at a suitable angle (such as, for example, about 90 degrees) to access the spine. Conventional catheters must be pushed through a 90-degree bend at the L4 to L6 region. The components of the inflammation management system disclosed herein (e.g., catheters and associated delivery devices and / or other peripheral devices) can be curved so that they can more easily and efficiently enter and navigate the angled bend.

[0126] Turning to the attached figure, Figure 1 An inflammation management system 10 is schematically depicted in communication with a patient 14. The inflammation management system 10 may include or may be configured to be connected to one or more peripheral components 12 configured for use in conjunction with the patient 14. In some cases, the inflammation management system 10 may include a controller 16, a user interface 18, one or more communication ports 20, a CSF management module 22 (e.g., a CSF therapy management module including a cooling module, a filtration module, and / or other suitable modules), a circulation management module 23, and / or one or more other components suitable for use in the operation of the inflammation management system 10. In some cases, although the circulation management module 23 may be separate from the controller 16 and the CSF management module 22, such as Figures 1 to 3 As shown, however, part or all of the cycle management module 23 may also be incorporated into one or both of the controller 16 and the CSF management module 22 .

[0127] Each of the components of the inflammation management system 10 can be configured to communicate directly with each other. Alternatively, one or more of the components of the inflammation management system 10 can be configured to communicate with another component through the controller 16. For example, measurements from the peripheral components 12 can be received via the communication port 20 and can be provided to the controller 16. The controller 16 can then interact with the CSF management module 22 to diagnose the patient and / or perform treatment using the CSF management module 22. The controller 16 can interact with the circulation management module 23 to maintain a predetermined CSF flow rate and / or CSF fluid pressure below a set point level and / or within a range of pressure levels.

[0128] The peripheral components 12 may include components that are used and / or configured to facilitate use of the inflammation management system 10 to determine a diagnosis for the patient 14 and to apply a therapy to the patient 14. Example peripheral components 12 include, but are not limited to, catheters, sensors, electrical connectors, mechanical connectors, and / or other components that are configured to facilitate use of the inflammation management system 10 to determine a diagnosis for the patient 14 and / or to apply a therapy to the patient 14.

[0129] Peripheral assembly 12 can include an implantable portion and / or an external portion. In some cases, one or both of the implantable portion and the external portion of peripheral assembly 12 can have a single-use function and can be disposed of after use, but this is not required.

[0130] The implantable portion may include one or more sensors (e.g., composition sensors, pressure sensors, temperature sensors, flow sensors, oxygen sensors, etc.) configured to sense measurements of one or more physiological parameters of the patient 14, which can be used by the inflammation management system 10 to control fluid temperature, pressure, and / or other suitable parameters. In one example, the implantable portion of the peripheral component 12 may include a temperature transducer and a pressure transducer that send signals to the inflammation management system 10 (e.g., to the controller 16 and / or the CSF management module 22). The implantable portion of the peripheral component 12 may be placed at one or more locations of the patient, including but not limited to between the skull and the dura mater, between the dura mater and the brain, within the ventricle, in the subarachnoid space, and / or at one or more other suitable locations. In some cases, the implantable portion may include a connector that, when implanted inside the body, extends to the outside of the patient's body. Alternatively or additionally, the implantable portion may be connected or coupled to the patient's body without being implanted inside the patient's body.

[0131] The extracorporeal portion may be a suitable component configured to be connected to an input and / or output of the inflammation management system 10 and to the implantable portion so that the extracorporeal portion may serve as an interface between the inflammation management system 10 and the implantable component. The extracorporeal portion of the peripheral component 12 may be and / or may include a sensor, a catheter, a tube, other elongated components, and / or other suitable components. Exemplary sensors may be composition sensors, pressure sensors, flow sensors, temperature sensors, oxygen sensors, and / or other suitable sensors configured to monitor fluids leading to and / or from the inflammation management system 10. An example catheter may be any suitable type of catheter configured to deliver fluids to the patient 14 and / or to deliver fluids from the patient 14 to the inflammation management system 10. An example catheter that may be used with the inflammation management system 10 is described in U.S. Patent Application Serial No. 62 / 286,413 (Attorney Docket No. 1421.1010120), filed on June 18, 2018, entitled “Systems, catheters, and methods for treatment along the central nervous system,” which is incorporated herein by reference for all purposes. Other suitable catheters may be envisioned.

[0132] Figure 2 Illustrative components of the inflammation management system 10 are schematically depicted. Figure 1 As discussed, the inflammation management system 10 may include a controller 16 , a user interface 18 , a communication port 20 , a CSF management module 22 , and a circulation management module 23 , among other components.

[0133] The controller 16 may include one or more components. In one example, the controller 16 may include a processor 24, a memory 26 in communication with the processor 24, an input / output (I / O) port 28 in communication with the processor 24 and / or the memory 26, and / or one or more other suitable components. In some cases, the memory 26 may be or may include a non-transitory computer-readable medium that may include or may be programmed to include software and / or other instructions to be executed by the processor 24 and to facilitate the controller 16 to operate in an automated manner to output control signals to the CSF management module 22, to the circulation management module 23, to other components of the inflammation management system 10, and / or to other components that may be used with the inflammation management system 10 based on input received at the I / O port 28 from the CSF management module 22, the user interface 18, and / or the communication port 20 in communication with the peripheral components 12. Additionally or alternatively, controller 16 may be configured to receive information from CSF management module 22 and cycle management module 23 , and / or output control signals to peripheral components via communication port 20 , user interface 18 , and / or communication port 20 .

[0134] Processor 24 may include a single processor or more than one processor working individually or in conjunction with each other. Example processor components may include, but are not limited to, a microprocessor, a microcontroller, a multi-core processor, a graphics processing unit, and / or other suitable processor components.

[0135] The memory 26 may include a single memory component or more than one memory component that work individually or together. Example types of memory may include RAM, ROM, EEPROM, FLASH, other volatile or non-volatile memory or other suitable memory for the controller 16.

[0136] The I / O port 28 may be any type of communication port configured to communicate with the CSF management module 22, the circulation management module 23, the user interface 18, the communication port 20, and / or one or more other components of the inflammation management system 10. Example I / O port types may include a wired port, a wireless port, a radio frequency (RF) port, a Bluetooth port, a near field communication (NFC) port, an HDMI port, an Ethernet port, a VGA port, a serial port, a parallel port, a component video port, an S-video port, a composite audio / video port, a DVI port, a USB port, an optical port, and / or other suitable ports. Although the I / O port 28 is depicted as part of the controller 16 and separate from the communication port 20, in additional and / or alternative examples, the I / O port 28 may be at least part of the communication port 20 and may be separate from the controller 16.

[0137] The user interface 18 can be any suitable type of user interface configured to facilitate user interaction with the inflammation management system 10. For example, the user interface 18 can include a display 30, an input / output (I / O) device 32, and / or other suitable user interface components configured to facilitate user interaction with the inflammation management system 10. The display 30 can include a touch screen and can be an LED, LCD, OLED, or other display type. The I / O device 32 can include and / or can be incorporated into or combined with one or more of a workstation, a computer, a computing device, a tablet computer, a phone, a keypad, a display, a touch screen, a touchpad, a mouse, and / or one or more other suitable components that facilitate user interaction with the inflammation management system 10.

[0138] like Figure 3As depicted, the display 30 may include any suitable display configuration for displaying information related to a patient being monitored and / or treated by the inflammation management system 10. In some cases, the display 30 may include one or more panes (e.g., where each pane may or may not be separated by a visible border). In one example, the display 30 may include a first pane 30a for displaying one or more medical images of a patient (e.g., an MRI, CT scan, x-ray, and / or other suitable medical image of the patient); a second pane 30b adjacent to the first pane 30a that displays a measurement of one or more physiological parameters of the patient, or a value related to the measurement (e.g., which may be a measurement) and / or an indicator related to the measurement (e.g., amount of intracranial hemorrhage (ICH), brain inflammation, white blood cell count (WBC), body temperature (TMP), heart rate variability (HRV), photoplethysmography (PPG), mass effect on the brain, midline shift (MLS) from a CT scan, blood volume ( The first pane 30a and / or the second pane 30b may be configured to display patient information (e.g., age, condition, pre-morbid neurological status, coagulopathy, etc.) and / or a third pane 30c adjacent to the first pane 30a and / or the second pane 30b, which displays patient information (e.g., age, condition, pre-morbid neurological status, coagulopathy, etc.). As data and / or measurements are received and / or updated at specified or predetermined intervals, the first pane 30a, the second pane 30b, and / or the third pane 30c may be updated in real time in response to the incoming data and / or measurements. Additionally, one or more of the first pane 30a, the second pane 30b, and the third pane 30c may be selectable and if selected, a pane with more detail may be displayed on the display 30, the date range of the selected pane may be adjusted, and / or the controller 16 may cause one or more other suitable changes to the content being displayed on the display 30 and / or the manner in which the treatment is being applied.

[0139] Additionally or alternatively, the display 30 may include a header 31. The header 31 may be a pane with selectable options to select to move between different displays (eg, summary display, imaging display, PHR display, trend display, analysis display, etc.).

[0140] The communication port 20 can be separate from and / or part of other I / O ports (e.g., I / O port 28 and / or other suitable I / O ports) of the inflammation management system 10. The communication port 20 can be one or more suitable types of communication ports configured to facilitate communication between the inflammation management system 10 and one or more other components configured to interact with the inflammation management system 10 (e.g., peripheral component 12, etc.). In one example, the communication port 20 can be configured to connect to the peripheral component 12 (e.g., to receive fluids from a patient and / or to receive measurements and / or data of one or more physiological parameters of a patient that can be monitored by the controller 16, where the measurements and / or data are received from sensors), to a scanning device, to a treatment component, and / or to other diagnostic components of the inflammation management system 10 and / or to communicate with the inflammation management system 10.

[0141] In some cases, the communication port 20 may be or may include a mechanical communication port and / or an electrical communication port. Example mechanical communication ports may include, but are not limited to, connection ports configured to facilitate mechanical connection between the inflammation management system 10 and the peripheral components 12 and / or other suitable components. Such mechanical communication ports may be configured to facilitate the transfer of liquids to and / or from the CSF management module 22 and / or facilitate the transfer of electrical signals to and / or from the inflammation management system 10. Example electrical communication ports may be or may include a wired port, a wireless port, a radio frequency (RF) port, a Bluetooth port, a near field communication (NFC) port, an HDMI port, an Ethernet port, a VGA port, a serial port, a parallel port, a component video port, an S-video port, a composite audio / video port, a DVI port, a USB port, an optical port, and / or other suitable ports. In some cases, the electrical communication port may include a mechanical connection feature.

[0142] The CSF management module 22 may include one or more hardware and / or software submodules 34. In one example, the CSF management module 22 may include a first submodule 34a, a second submodule 34b, and an Nth submodule 34N, where there are N submodules. As desired, the hardware and / or software submodules 34 may be interchangeable or swappable to suit different needs. For example, in one instance, a pump, a filtration therapy module, and a waste control mechanism may be utilized for inflammation management; in another instance, a pump and a cooling therapy module may be utilized for inflammation management; and in yet another instance, a pump, a filtration therapy module, and a cooling therapy module may be utilized. Other combinations of hardware and / or software submodules 34 may form or may be part of the CSF management module 22.

[0143] The circulation management module 23 may include one or more hardware and / or software modules (e.g., stored in memory for execution by the controller 16 and / or a processor of the circulation management module 23) and may be configured to control the circulation of CSF through the inflammation management system 10, taking into account the CSF management module's regimen and other circulation requirements. In one example, the circulation management module 23 may be configured to maintain a predetermined CSF flow rate and / or CSF pressure at or below a set point level and / or within a pressure level range. The circulation management module 23 may include a pump 36, but this is not required because the circulation management module 23 may rely on other pumps of the inflammation management system 10 to pump fluid through the inflammation management system 10 according to the circulation regimen, taking into account the needs of the CSF management module 22.

[0144] In operation, the controller 16 of the inflammation management system 10 may interact with the controller of the CSF management module 22 and / or the various controllers of the hardware and / or software submodules 34 to implement the operation of one or more diagnostic and / or therapeutic protocols. In some cases, the controller 16 may be configured to interact with the hardware and / or software submodules 34 to facilitate control and / or operation of functions that may be common to multiple protocols utilizing the hardware and / or software submodules 34. Common functions that may be controlled and / or performed by the controller 16 may include, but are not limited to, real-time and trended pressure measurements and recording, total cycle volume and elapsed time cycle measurements and recording, cycle control (e.g., via pressure limiting to prevent pressure from exceeding a set point, maintaining a constant or predetermined flow rate to deliver a cycle at a specified flow rate, etc.), alarm management, communications, system status updates, and / or other common functions that may be required during operation of one or more hardware and / or software submodules 34. In one example, the controller 16 can be configured to control and / or manage circulation (e.g., by sending control signals to a pump, waste control mechanism, and / or other hardware and / or software submodules 34) during a diagnostic and / or treatment regimen that utilizes the hardware and / or software submodules 34 (e.g., controlling and / or managing fluid circulation and / or pressure monitoring in a control loop).

[0145] The hardware and / or software submodules 34 can be configured to be based on the basic or general functions provided by the controller 16 and to provide specified functions during the treatment plan for the patient. Practitioners or institutions can add hardware and / or software submodules 34 and / or remove hardware and / or software submodules 34 from the CSF management module 22 as needed to customize the functions of the CSF management module 22 for specific diagnostic and / or treatment plans. In one example, when the inflammation management system 10 is to be used to diagnose and / or treat patients with head injuries, the treatment organization and / or practitioner can install a cooling therapy module. In combination with appropriate peripheral components 12, the inflammation management system 10 can utilize its basic or general functions (e.g., the basic or general functions required by the hardware and / or software submodules 34, such as circulation management) and the functions of the cooling therapy module to cool the circulating fluid from the patient according to the cooling therapy plan. In some cases, the cooling therapy plan can be saved in the cooling therapy module, but this is not required, and the cooling therapy plan can be saved at another location and / or input to the inflammation management system 10 via the user interface 18.

[0146] In some cases, the CSF management module 22 can be housed in a housing of the inflammation management system 10. Alternatively or additionally, at least a portion of the CSF management module 22 can be separated from the housing of the inflammation management system 10. When the CSF management module 22 is housed in the housing of the inflammation management system 10, the hardware portions of the submodules can be swapped from the housing in a plug-and-play manner, but this is not required. In one example, if a cooling therapy module is required in a first configuration, but a filtering therapy module is required in a second configuration, the cooling therapy module can be removed from the housing of the inflammation management system 10 and replaced with a filtering therapy module. In addition, when the inflammation management system 10 includes all necessary hardware components, the software submodules 34 can be swapped out and / or swapped to achieve the desired solution. Other interchangeable configurations are contemplated.

[0147] Figure 4 An illustrative configuration of the CSF management module 22 of the inflammation management system 10 for use with the patient 14 via the peripheral component 12 (e.g., a catheter) is schematically depicted. As discussed, the CSF management module 22 may include one or more hardware and / or software sub-modules 34. Figure 4 In the illustrated example CSF management module 22, the hardware and / or software submodules 34 include a filtration therapy module 38, a waste control mechanism 40, and a cooling therapy module 42. As discussed above, the CSF management module 22 may include one or more additional or alternative hardware and / or software submodules 34 (e.g., up to an Nth submodule).

[0148] When the circulation management module 23 includes a pump 36, the pump 36 can pump or assist in pumping a liquid (e.g., CSF or other liquid) into, along, and / or through a liquid circuit of the inflammation management system 10. For example, the pump 36 can pump liquid into a liquid path inlet 44 and out of a liquid path outlet 46 via one or more hardware and / or software submodules 34. CSF traveling through the inflammation management system 10 can travel through various paths along the liquid circuit via a liquid line 48 having a lumen therein (e.g., tubing or other suitable mechanism that forms a lumen and is configured to facilitate maintaining a desired pressure within the liquid circuit through a liquid-tight connection at a connection point, if any), wherein the lumen can be configured to facilitate the travel of CSF along the liquid circuit from the inlet of the liquid line to the pump 36, and from the pump to the outlet of the liquid line.

[0149] The pump 36 can be configured to pump CSF through the inflammation management system 10 with or without an additional pumping mechanism (e.g., a pump of other hardware and / or software submodules 34 and / or other suitable pumps). In addition, although the pump 36 and / or circulation management module 23 are depicted and described herein as being separate from the CSF management module 22 as permanent components of the inflammation management system 10, the pump 36 and / or circulation management module 23 can also be a hardware and / or software submodule 34 of the CSF management module 22.

[0150] The pump 36 may be any suitable type of pump for pumping CSF through the inflammation management system 10. For example, the pump 36 may be a peristaltic pump or other suitable pump configured to apply pressure to the fluid line to pump CSF from the patient, through the inflammation management system 10, and back into the patient. The pump 36 may be a single pump or multiple pumps configured to achieve a desired pressure and / or flow rate within the fluid line 48. Although Figure 4 The pump 36 is located upstream of the filtration therapy module 38, the waste control mechanism 40, and the cooling therapy module 42, but the pump 36 may be located at any suitable location in the inflammation management system 10. In one example, the pump 36 may be located downstream of the liquid inlet of the inflammation management system 10 and upstream of the liquid outlet of the inflammation management system 10.

[0151] In some cases, the circulation management module 23 can utilize one or more sensors along the flow path of the CSF through the inflammation management system 10 and / or peripheral components 12. When sensors are included, the sensors can be configured to sense measurements within a lumen of a fluid line 48 extending from and / or forming the flow path. When controlling the circulation of the CSF through the fluid line 48 with a pump, the circulation management module 23 can consider measurements from a single sensor, two sensors, three sensors, or more sensors at one or more locations along the flow path of the inflammation management system 10, either alone or in conjunction with the controller 16, as desired.

[0152] The filtration therapy module 38 may include hardware components and / or software components. In one example, if the inflammation management system 10 includes a permanent filtration system, the filtration therapy module 38 of the CSF management module 22 may be a primary software module that utilizes the functionality of the permanent components (e.g., hardware and software) of the inflammation management system 10 (e.g., the permanent filtration system, the controller 16, the user interface 18, the communication port 20, the fluid line 48 and / or other flow paths and / or other hardware components) to establish a circulation rate (e.g., including but not limited to pulsation) for the filtration therapy module 38 and / or the inflammation management system 10, monitor filtration time, control an emptying function, and / or use the filtration therapy module 38 to perform one or more other suitable functions. Such a software module may establish a predetermined filtration regimen, which may be modified by a user via the user interface 18 or other user interface of the inflammation management system 10 and / or may be exchanged for a software module that establishes a different predetermined filtration regimen. The predetermined filtration regimen may be an example of a predetermined therapy or predetermined therapy regimen, as well as other example predetermined therapies or predetermined therapy regimens.

[0153] In some cases, the filtration therapy module 38 and / or permanent filtration system of the inflammation management system 10 may include a hardware filter system to be used with the software module of the filtration therapy module 38. In some cases, the hardware filter system may include one or more pump components and / or one or more filters. Although other filtration therapy module configurations are contemplated (e.g., other hardware and / or software components of the filtration therapy module), an example filtration therapy module is a pump / filter system for pumping and / or filtering CSF described in U.S. patent application serial number 62 / 693,225 (attorney docket number 1421.1015100), filed on July 2, 2018, and entitled “Systems, catheters, and methods for treatment along the central nervous system,” which is incorporated herein by reference for all purposes.

[0154] In some cases, the hardware components of the filtration therapy module 38 may include one or more filters to filter contaminants (e.g., blood and / or other contaminants) from the CSF. In one example, the filtration therapy module 38 may have a first filter and a second filter. In some cases, one or both of the first filter and the second filter may each be a tangential flow filter (TFF) or other suitable type of filter. For example, the first filter and / or the second filter may include a 5kDa TFF, a 100kDa TFF, a 0.2μm TFF, a 0.45μm TFF, etc. Alternatively or additionally, the first filter and / or the second filter may include a dead-end filter (e.g., a 5kDa dead-end filter) and / or an electrical filter (e.g., a filter based on a charge exclusion material).

[0155] In at least some cases, when both a first filter and a second filter are included, the first filter and the second filter can be of the same size and / or type (e.g., both the first filter and the second filter can be 100 kDa TFF). In other cases, the first filter and the second filter can be of different sizes and / or types (e.g., the first filter can be a 5 kDa filter and the second filter can be a 100 kDa TFF filter).

[0156] In some cases, the filtration therapy module 38 may include only one filter (e.g., a first filter). For example, the first filter may be a 5 kDa filter, and the first filter may be the only filter. Alternatively, the filtration therapy module 38 may include more than two filters (e.g., a first filter, a second filter, and one or more additional filters).

[0157] The first filter can be configured to separate the CSF into an initially cleaned CSF (e.g., conditioned CSF) and an initially discarded CSF when CSF is the received fluid. The initially cleaned CSF from the first filter can flow to the cooling therapy module 42 and the initially discarded CSF from the first filter can flow to the second filter.

[0158] When a second filter is included, the second filter can be configured to separate the received initial waste CSF into clean CSF (e.g., conditioned CSF) and waste CSF (e.g., final waste liquid). The clean CSF from the second filter can flow to the cooling therapy module 42 and the waste CSF can flow from the second filter to the waste control mechanism 40 (e.g., a manually operated or automated (e.g., via a controller) waste pump or other suitable waste control mechanism).

[0159] The waste control mechanism 40 (e.g., where the waste control mechanism 40 can be or can include a valve, a back pressure valve, a pinch valve, a flow metering mechanism, a pump, etc.) can receive waste fluid from the filter therapy module 38 via a fluid line 48, such as Figure 4 The waste control mechanism 40 is depicted as well as controlling the rate at which waste CSF is directed along a waste outlet path to a collection device 50 for disposal (e.g., the rate at which waste CSF is output from the filtered therapy module 38). The waste control mechanism 40 may be controlled manually and / or in an automated manner using a controller of the waste control mechanism 40 and / or using the controller 16 of the inflammation management system 10. Although other configurations of the waste control mechanism 40 are contemplated, an example waste control mechanism is described in U.S. Patent Application Serial No. 62 / 693,225, which is incorporated herein by reference for all purposes described above.

[0160] The cooling therapy module 42 may be configured to chill liquid passing through the inflammation management system 10 and may include hardware components and / or software components. In some cases, the cooling therapy module 42 may be configured to receive liquid from the filtering therapy module 38 via the liquid line 48, but this is not required and the cooling therapy module 42 may receive liquid via the liquid line 48 at one or more other locations along the liquid line 48.

[0161] The cooling therapy module 42 may include one or more pumps (e.g., in addition to or as an alternative to the pump 36) and / or one or more valves to facilitate controlling the circulation of fluid within the cooling therapy module 42 and / or otherwise within the inflammation management system 10, but this is not required and fluid circulation may be controlled by other pumps of the inflammation management system 10. When a pump and / or valve of the cooling therapy module 42 is included, the pump and / or valve may be configured to work in conjunction with the pump 36 and / or other pumps of the inflammation management system 10 to control the circulation of fluid through the fluid line 48.

[0162] The software components or modules of the cooling therapy module 42 may establish a cooling regimen for the inflammation management system 10. The cooling regimen may be configured to set a temperature set point for a fluid passing through the inflammation management system 10 and / or the cooling therapy module 42, set a rate at which the temperature of a fluid may be cooled (or in some cases, heated), set a circulation rate (including, but not limited to, pulsation) of a fluid passing through the cooling therapy module 42 and / or the inflammation management system 10, establish a hold time for the fluid passing through the cooling therapy module 42 (e.g., the time it takes to reach a temperature set point based on a ramp rate and a circulation rate), and / or perform one or more other suitable functions using the cooling therapy module 42. The predetermined cooling regimen established by the software modules of the cooling therapy module 42 may be modified by a user via the user interface 18 or other user interface of the inflammation management system 10 and / or may be exchanged for a software module that establishes a different predetermined cooling regimen. The predetermined cooling regimen may be an example of a predetermined therapy or predetermined therapy regimen, as well as other example predetermined therapies or predetermined therapy regimens.

[0163] The cooling therapy module 42 can be configured to cool liquid passing therethrough in any suitable manner. In some cases, the cooling therapy module 42 can cool liquid passing therethrough via radiative cooling and / or other cooling techniques. For example, the surfaces of the liquid line 48 and / or other liquid paths of the inflammation management system 10 can be cooled via coils, pre-cooled liquid cooling, and / or in one or more other ways, and the cooled surfaces can remove heat from the liquid passing through the cooling therapy module 42 by radiation and / or convection. Alternatively or additionally, the cooling therapy module 42 can cool liquid passing therethrough by adding pre-cooled liquid to the cooling therapy module. In some cases, the added pre-cooled liquid can be cooled saline, cooled artificial CSF, and / or other suitable liquids. When pre-cooled liquid is added to the liquid passing through the cooled therapy module 42, the amount (e.g., volume or other amount) of liquid added to the liquid passing through the cooled therapy module 42 can be determined based on a function of the volume of material (e.g., liquid or other material) removed from the liquid during filtering of the liquid in order to maintain a desired balance or ratio of liquid input to the inflammation management system 10 to liquid output from the inflammation management system 10. In one example, the volume of pre-cooled liquid added to the liquid passing through the cooled therapy module 42 can be equal to or substantially equal to the volume of liquid removed from the liquid passing through the filtered therapy module 38.

[0164] exist Figure 4 In the depicted example, once the fluid passing through the fluid line 48 of the inflammation management system 10 has passed through the filtering therapy module 38 and the cooling therapy module 42, the fluid can be output and returned to the patient. Figure 4As depicted, fluid may be returned to patient 14 at a location different from where it was removed from patient 14 , but this is not required and may be returned at the same location or a location adjacent to where it was removed from patient 14 .

[0165] As discussed herein, the inflammation management system 10 may be used in a method of managing inflammation associated with the brain of a patient. Figure 5 An illustrative method 500 for managing inflammation to diagnose and / or treat a patient condition is depicted. Instructions for performing the method 500 may be stored in a memory (e.g., memory 26 or other suitable memory) for execution by a processor (e.g., processor 24, a processor of a module or submodule of the inflammation management system 10, and / or other suitable processor). In some cases, the method 500 may be performed in whole or in part with an inflammation management system (e.g., inflammation management system 10 or other suitable inflammation management system).

[0166] like Figure 5 As depicted, method 500 may include receiving (e.g., obtaining) one or more values ​​502 associated with a patient's physiological parameters. The one or more values ​​associated with a patient's physiological parameters may be a measured value of the physiological parameter and / or one or more other suitable values ​​determined based on the measured value of the patient's physiological parameter. The one or more physiological parameters of the patient may be received and / or otherwise obtained from a component of an inflammation management system, a peripheral component of an inflammation management system, one or more sensors sensing the patient's physiological parameters, an image capture device (e.g., a camera, a CT scanner, an MRI machine, an X-ray machine, etc.), and / or other suitable data capture devices configured to obtain data associated with one or more physiological parameters of the patient. One or more values ​​associated with the patient's physiological parameters may be stored or saved in a memory for access by a processor. The values ​​received and / or stored or saved in the memory may relate to a single physiological parameter of the patient or two or more physiological parameters of the patient. In some cases, one or more values ​​associated with the patient's physiological parameters may be received at the processor from one or more input ports and / or from a memory for processing.

[0167] Sensors in or otherwise connected to the inflammation management system can provide monitored measurements related to physiological parameters of the patient. Example measurements of physiological parameters that can be monitored include, but are not limited to, one or more of intracranial hemorrhage (ICH) volume, brain inflammation, white blood cell count (WBC), body temperature (TMP), heart rate variability (HRV), photoplethysmography (PPG), mass effect on the brain, midline shift (MLS) from CT scan, blood volume (VOL), edema volume (PHE), intracranial pressure (ICP), water in the brain, brain tissue compliance (CMP), National Institutes of Health Stroke Scale (NIHSS), level of consciousness (LOC), eye measurements obtained with a pupillometer, motor skills (MTR), sensation (SNS), language skills (LNG), fluid management, blood pressure (BP), fluid input and output (I / O), cerebral perfusion pressure (CPP), sodium content (Na++), potassium content (K++), and / or other suitable physiological parameters.

[0168] When values ​​associated with the patient's physiological parameters are obtained, those values ​​stored in the memory and / or values ​​associated with the patient's physiological parameters can be processed 504. The values ​​associated with the patient's physiological parameters can be processed using a processor of the inflammation management system and / or other suitable processors. In some cases, the values ​​associated with the patient's physiological parameters can be processed into one or more indexed values ​​(e.g., these indexed values ​​can be based on values ​​associated with the patient's physiological parameters and discussed in more detail below), which can indicate the patient's inflammatory condition or other suitable condition at the current time, indicate how the inflammatory condition changes over time, and / or indicate how the inflammatory condition is expected to change in a future time period. In some cases, the indexed value can be based at least in part on one or more values ​​associated with one (e.g., a single) physiological parameter. Alternatively, the indexed value can be based at least in part on values ​​associated with two or more physiological parameters.

[0169] The inflammatory condition of a patient can be a condition of the patient associated with a patient condition. The patient condition can be or can be associated with traumatic brain injury, subarachnoid hemorrhage, intracranial hemorrhage and / or other patient conditions that cause inflammation in, around and / or affecting the patient's brain, and the inflammatory condition can be the level of the inflammation. Typically, the inflammatory condition of a patient may be difficult to assess or define, and using the patient's processed physiological parameters (e.g., using an index as discussed herein) can help a medical provider better understand the inflammatory condition that causes inflammation in, around and / or affecting the patient's brain condition.

[0170] As discussed above, values ​​related to one or more physiological parameters of a patient can be processed into one or more indices. Each index can have an indexed value, where the indexed value can be based on a measured value of the one or more physiological parameters of the patient. In some cases, the indexed value can be based on one or more classification indices, and each classification index of the one or more classification indices can be based on a measured value of the one or more physiological parameters of the patient.

[0171] In some cases, the values ​​of one or more physiological parameters for an index based on the values ​​of the patient's physiological parameters may be weighted equally, and in other cases, the values ​​of one or more physiological parameters for an index may be weighted differently than the values ​​of one or more other physiological parameters considered for the index. Similarly, in some cases of an index including one or more sub-indices, each value of a sub-indices used in the index may be weighted equally, and in other cases, the values ​​of one or more sub-indices for an index may be weighted differently than the values ​​of one or more other sub-indices considered for the index.

[0172] The index value may be a value obtained by processing data in a particular manner for one or more parameters. The indexed value may be a value obtained by processing data obtained over time for a single parameter, a value obtained by processing data obtained over time for multiple parameters, a value obtained by processing data obtained at time t for multiple parameters, and / or other suitable values. Time t is the current time at which the data is acquired.

[0173] Data for a single parameter may be obtained over time (e.g., from time t to time t minus N time units (time tN)), and an exponential value for the single parameter may be determined by applying an algorithm to the obtained data. In one example, the exponential value for data associated with a single parameter may be a value of a rolling average of data obtained for the single parameter and / or a value obtained by applying one or more other suitable algorithms to the data obtained for the single parameter. In another example, the exponential value for data associated with multiple parameters obtained at time t may be a value obtained by normalizing the data obtained at time t for each of the multiple parameters (e.g., normalizing the data for each parameter by a scale of 1-100 or other suitable scale and / or normalizing in one or more other suitable ways), and taking the normalized values ​​of the parameters for the multiple parameters and / or a value obtained by averaging the values ​​obtained by applying one or more other suitable algorithms to the data obtained at time t for the multiple parameters. In another example, the indexed value for data related to multiple parameters obtained over time may be a value obtained by normalizing the data obtained over time for each of the multiple parameters (e.g., normalizing the data for each parameter by a scale of 1-100 or other suitable scale and / or normalizing in one or more other suitable ways), and a value obtained by taking a rolling average of the normalized values ​​of the parameters for the multiple parameters and / or a value obtained by applying one or more other suitable algorithms to the data obtained over time for the multiple parameters. Indices other than those obtained by taking the average of data may also be contemplated.

[0174] The index based at least in part on values ​​associated with one or more physiological parameters of the patient can be any suitable index type, including but not limited to those discussed above. Example indices include but are not limited to an inflammation index, a mass effect index, a NIHSS index, a fluid management index, a Glasgow Coma Rating Scale index, and / or other suitable indices based at least in part on values ​​associated with one or more physiological parameters of the patient.

[0175] The inflammation index may indicate brain inflammation (e.g., a brain inflammation index). The inflammation index may be based on measured values ​​of one or more of the following physiological parameters, in addition to other measured values: white blood cell count (WBC), body temperature (TMP), heart rate variability (HRV), and photoplethysmography (PPG). In one example, when the inflammation index is based on a value of white blood cell count (WBC), a value of body temperature (TMP), a value of heart rate variability (HRV), and a value of photoplethysmography (PPG), the inflammation index may be based at least in part on a value of the inflammation index.

[0176] The mass effect index can indicate swelling of the brain. When the mass effect index is above a threshold level, an indication can be provided to take action to address the swelling of the brain. Alternatively or additionally, when the mass effect index reaches a threshold level, an indication that the symptoms associated with brain swelling have a specific percentage of occurrence chance will appear based on historical data and / or other suitable information. In addition to other measurements, the mass effect index can be based on one or more of the following physiological parameters: midline shift (MLS) according to a CT scan, blood volume (VOL), edema volume (PHE), intracranial pressure (ICP), water in the brain, and brain tissue compliance (CMP). In one example, when the mass effect index is based on the value of the midline shift (MLS) according to a CT scan, the value of the blood volume (VOL), the value of the edema volume (PHE), the value of the intracranial pressure (ICP), the value of the water in the brain, and the value of the brain tissue compliance (CMP), the indexed value can be based at least in part on the mass effect index.

[0177] The NIHSS index may indicate the severity of a stroke. The NIHSS index may be based on measured values ​​of one or more of the following physiological parameters, in addition to other measured values: level of consciousness (LOC), eye measurements obtained with a pupillometer, motor skills (MTR), sensation (SNS), and language skills (LNG). In one example, when the NIHSS index is based on a value for level of consciousness (LOC), a value for eye measurements obtained with a pupillometer, a value associated with motor skills (MTR), a value associated with sensation (SNS), and a value associated with language skills (LNG), the indexed value may be based at least in part on the NIHSS index.

[0178] The fluid management index can indicate fluid input into the body (e.g., fluid input by IV drip and / or other suitable fluid input methods) and fluid output from the body (e.g., fluid concentration of urine and / or other suitable fluid output methods). The fluid management index can be based on measured values ​​of one or more of the following physiological parameters, in addition to other measurements: blood pressure (BP), fluid input and output (I / O), cerebral perfusion pressure (CPP), sodium content (Na++), and potassium content (K++). In one example, when the fluid management index is based on a value of blood pressure (BP), a value associated with fluid input and output (I / O), a value of cerebral perfusion pressure (CPP), a value of sodium content (Na++), and a value of potassium content (K++), the indexed value can be based at least in part on the fluid management index.

[0179] The Glasgow Coma Scale index may indicate a state of consciousness of a patient. The Glasgow Coma Scale index may be based on, among other measurements, measurements of one or more of the following physiological parameters: eye measurements obtained with a pupillometer, motor skills (MTR), and language skills (LNG). In one example, when the Glasgow Coma Scale index is based on values ​​of eye measurements obtained with a pupillometer, values ​​associated with motor skills (MTR), and values ​​associated with language skills (LNG), the indexed value may be based at least in part on the Glasgow Coma Scale index.

[0180] Other indices based on measurements of the patient's physiological parameters and / or other suitable factors can be envisioned. Such other indices can be based on the patient's demographics, other suitable factors (e.g., other suitable physiological parameters, etc.), and / or other suitable combinations of factors.

[0181] In some cases, the values ​​of the inflammation index, mass effect index, NIHSS index, fluid management index, Glasgow Coma Scale index, and / or other suitable indices can be values ​​of a categorical index, which can be used or processed to determine a value of an index based on one or more categorical indices. The value of an index can be a function of one or more of the value of the inflammation index at a time point or over time, the value of the mass effect at a time point or over time, the value of the NIHSS index at a time point or over time, the value of the fluid management index at a time point or over time, and / or the value of the Glasgow Coma Scale index at a time point or over time.

[0182] An example of a classification index may be a NEUROWORSENINGTM index. In some cases, the NEUROWORSENINGTM index may indicate that the patient's condition is deteriorating toward a threshold level before it is actually determined that the patient's condition has deteriorated to the threshold level, (e.g., predicting that the inflammatory condition of the brain is deteriorating toward a threshold level before it can be diagnosed that the inflammatory condition of the brain has reached a threshold level based on images of the patient's brain). In one example, the index may be based on one or more different classification indices, wherein the one or more classification indices may be selected or determined based on the type of patient condition being monitored and may indicate the patient's inflammatory condition. For example, when a patient is monitored due to a patient condition of intracranial hemorrhage, an example index of the classification index may be based at least in part on an inflammation classification index, a mass effect classification index, and a NIHSS classification index; when a patient is monitored due to a patient condition of subarachnoid hemorrhage, an index of the classification index may be based at least in part on an inflammation classification index, a mass effect classification index, a fluid management classification index, and a NIHSS classification index; and when a patient is monitored due to a patient condition of traumatic brain injury, an index of the classification index may be based at least in part on an inflammation classification index, a mass effect classification index, and a Glasgow Coma Rating Scale index. Other combinations of classification indices can be used to formulate an index of classification indices based at least in part on the patient condition for which the inflammatory condition of the patient is to be monitored. In some cases, the classification indices and / or values ​​associated with the patient's physiological parameters can be selected by individual medical providers to formulate an index for the patient's condition as needed.

[0183] In some cases, the classification index and / or the index of the classification index can indicate whether the inflammatory condition is improving or worsening. In one example, if a value related to a patient's physiological parameter is determined at the current time, the value of the classification index can represent the patient's inflammatory condition at the current time, and when the value related to the patient's physiological parameter is saved, the value of the classification index at the current time can be based on the previous value related to the patient's physiological parameter and the current value related to the patient's physiological parameter, so that the value of the classification index can indicate the trend of the patient's inflammatory condition. Similarly, if the value of the classification index is determined at the current time, the value of the index of the classification index can represent the patient's inflammatory condition at the current time, and when the value of the classification index is saved, the value of the index of the classification index at the current time can be based on the previous value of the classification index and the current value of the classification index, so that the value of the index of the classification index can indicate the trend of the patient's inflammatory condition over time.

[0184] In some cases, values ​​of multiple physiological parameters of a patient, values ​​of classification indices of values ​​of multiple physiological parameters of a patient, and / or values ​​of indices of classification indices can be depicted or otherwise displayed on a user interface (e.g., user interface 18 and / or other suitable user interfaces). In one example, values ​​of multiple physiological parameters of a patient, values ​​of classification indices of values ​​of multiple physiological parameters of a patient, and / or values ​​of indices of classification indices can be depicted on a user interface using a graph of values ​​versus time, wherein a directional indicator indicates whether the corresponding value has increased, decreased, or remained unchanged from a previous time, and the current value is a range shown relative to a range of possible values; and / or depicted in one or more other suitable manners. In some cases, values ​​of an index of a classification index of values ​​associated with one or more physiological parameters of a patient can be displayed in a first pane of a display of a user interface (e.g., in a first pane of a display of a user interface) relative to a range of possible values ​​for the index of the classification index. Figure 3 The NEUROWORSENINGTM index depicted in the second pane 30b in FIG. 10 and the values ​​of the classification index associated with the values ​​of one or more physiological parameters of the patient can be displayed in the first pane of the display of the user interface (e.g., Figure 3 Displaying such values ​​associated with one or more physiological parameters of the patient in proximity to each other and / or other information (e.g., an image of the patient, patient demographic information, etc.) facilitates providing context for the values ​​of the one or more physiological parameters of the patient to a medical provider who would not typically have such information because such information is typically provided to the medical provider via multiple machines and / or printouts, if at all, which makes it difficult to understand the context of any individual value or indexed value relative to the patient's condition or the patient's inflammatory condition.

[0185] Based at least in part on the processed values ​​associated with one or more physiological parameters of the patient, method 500 may include determining whether the patient's inflammatory condition has reached a therapeutic condition 506. In one example, determining 506 whether the patient's inflammatory condition has reached a therapeutic condition may be based at least in part on an indexed value determined during processing 504 of the values ​​associated with one or more physiological parameters of the patient.

[0186] The therapeutic condition of a patient can be the level of the patient's inflammatory condition that should be treated and / or can indicate when treatment should be performed. Similar to the inflammatory condition of a patient, the therapeutic condition of a patient may be difficult to assess or define, and using the patient's processed physiological parameters (e.g., using the index discussed herein) and the associated thresholds or ranges can facilitate determining when the patient's inflammatory condition reaches or will reach the therapeutic condition. In one example, a processed value associated with one or more physiological parameters of a patient can produce a value indicating the patient's inflammatory condition (e.g., an indexed value or other value indicating the patient's inflammatory condition), and when the value indicating the patient's inflammatory condition reaches a threshold (e.g., a predetermined value, a trend level over time, a value based at least in part on one or more algorithms (e.g., a learning algorithm or other suitable algorithm) using data from multiple inflammation management systems or a global treatment regimen database, and / or other suitable thresholds), it can be determined that the patient's inflammatory condition has reached the therapeutic condition or will reach the therapeutic condition at a specified time in the future. In some cases, different decisions about the inflammatory condition relative to the therapeutic condition can be made based on values ​​indicating that the patient's inflammatory condition reaches different thresholds (e.g., different threshold levels) and / or based on the difference between the value and the threshold. When the threshold is based at least in part on an algorithm using data from multiple inflammation management systems or a global treatment regimen database, the database can be a global database that stores data on past implementations of treatment regimens from multiple remote inflammation management systems (e.g., such data may have information about, among other information, what treatment regimen was delivered for the patient's condition, the patient's demographic information, when the treatment regimen was performed relative to the inflammatory condition, what the values ​​of any relevant indexes were when the treatment regimen was implemented or decided to be implemented, what the values ​​of any relevant physiological parameters of the patient were when the treatment regimen was implemented or decided to be implemented, etc.).

[0187] When it is determined that the patient's inflammatory condition has reached a therapeutic condition based on the processed values ​​associated with the patient's physiological parameters, an indication that the patient's inflammatory condition has reached a therapeutic condition can be output 508. In some cases, the indication that the patient's inflammatory condition has reached a therapeutic condition can be output from a processor of the inflammation management system or other suitable processor via one or more ports in communication with the processor (e.g., I / O port 32, communication port 20, and / or other suitable ports). Outputting indication 508 can be performed automatically in response to identifying that the patient's inflammatory condition has reached a therapeutic condition, but this is not required in all cases.

[0188] The outputted indication 508 that the patient's inflammatory condition has reached the treatment condition may be or may include any suitable indication. Example suitable indications include, but are not limited to, a control signal from the processor to the cerebrospinal fluid management module (e.g., a control signal to one or more submodules 34 of the cerebrospinal fluid management module 22 or other suitable components of the cerebrospinal fluid management module) for executing a treatment regimen on the patient's cerebrospinal fluid to address the patient's inflammatory condition, a control signal to a user interface (e.g., the user interface 18, the display 30 of the user interface, and / or other suitable user interface) for displaying a recommended treatment regimen to treat the patient's inflammatory condition, a control signal to the user interface for displaying a value on the display of the user interface (e.g., the value of an index on a pane, such as the first pane of the display or other suitable pane), a control signal for turning on and / or off a light (e.g., a light of the user interface or other suitable light), a control signal for turning on and / or off a sound (e.g., a speaker from the user interface or other suitable speaker), initiating a delegation invitation or other suitable scheduling mechanism to schedule a medical provider to perform a treatment (e.g., a scheduled treatment and / or other suitable treatment) at a scheduled time in the future, and / or one or more other suitable indications.

[0189] A treatment regimen may be a set of instructions or a list of treatments for treating an inflammatory condition of a patient. Example treatment regimens may include, but are not limited to, actuation of CSF filtration therapy, actuation of CSF cooling therapy, actuation of CSF drainage therapy, actuation of one or more other suitable CSF therapies, surgery, etc.

[0190] When identifying, suggesting, or obtaining a treatment regimen, the processor may automatically select a treatment regimen based, at least in part, on a treatment value associated with a physiological parameter, a threshold value reached, and / or a difference between a treatment value and a threshold value. Such a treatment regimen may be automatically identified or selected by the processor from a database of treatment regimens associated in a predetermined manner with various patient conditions and values ​​of treatment values ​​associated with the patient's physiological parameters. Alternatively or additionally, the processor may automatically identify or select by the processor from a database of treatment regimens associated with various patient conditions and values ​​of treatment values ​​associated with physiological parameters based on one or more algorithms (e.g., a learning algorithm or other suitable algorithm). The database can be a global database that stores data from past implementations of treatment regimens from multiple remote inflammation management systems (e.g., such data may have information about, among other information, what treatment regimens were delivered for patient conditions, demographic information of the patient, when the treatment regimen was performed relative to the inflammatory condition, what the values ​​of any relevant indexes were when the treatment regimen was implemented or decided to be implemented, what the values ​​of any relevant physiological parameters of the patient were when the treatment regimen was implemented or decided to be implemented, etc.), which can be used by one or more algorithms to determine associations between treatment values ​​of treatment regimens and various patient conditions and values ​​associated with the patient's physiological parameters that may be associated with the patient's inflammatory condition.

[0191] When it has been determined that the patient's inflammatory condition has not yet reached a therapeutic condition (e.g., has not yet reached a threshold or other suitable benchmark) based on the processed values ​​associated with the patient's physiological parameters, the processed values ​​associated with the patient's physiological parameters can be monitored 510, and it can be determined 506 at a future time whether the patient's inflammatory condition has reached a therapeutic condition. In some cases, steps 502 to 506 and 510 of method 500 can be repeated and performed continuously, at least until it is determined that the patient's inflammatory condition has reached a therapeutic condition. However, this is not required. In some cases, one or more steps of method 500 can be repeated at predetermined time intervals and / or in response to manual actuation via a user interface or other suitable user interaction with the inflammation management system.

[0192] Figure 6 An illustrative method 600 for managing inflammation in a patient using an inflammation management system (e.g., inflammation management system 10 and / or other suitable inflammation management systems) is depicted. Instructions for performing method 600 may be stored in a memory (e.g., memory 26 and / or other suitable memory) for execution by a processor (e.g., processor 24, a processor of a module or submodule of inflammation management system 10, and / or other suitable processor).

[0193] Initially, although not required, a patient (e.g., patient 14 or other suitable patient) can be connected to the inflammation management system via one or more peripheral components (e.g., peripheral component 12 or other suitable peripheral components). Once the patient has been connected to the inflammation management system, the inflammation management system can monitor over time measurements of or values ​​associated with one or more physiological parameters of the patient 602, wherein CSF drainage, CSF cooling, CSF filtration, and / or other CSF therapies may be based on the measurements or values ​​associated with the measurements. In operation, the monitoring 602 can be performed by a controller of the inflammation management system (e.g., controller 16 or other suitable controller).

[0194] Method 600 may include correlating values ​​of monitored measurements of one or more physiological parameters of the patient (e.g., as described above with respect to Figure 5 The indexed value discussed above and / or other suitable values ​​related to one or more physiological parameters of the patient) and one or more threshold values ​​(e.g., as described above with respect to Figure 5 In one example, comparing a value associated with the monitored measurements of one or more physiological parameters of the patient with one or more threshold values ​​604 may include determining a difference between the value associated with the monitored measurements of the one or more physiological parameters and the threshold value, but this is not required. In operation, the comparison 604 may be performed by a controller of the inflammation management system and / or other suitable controller.

[0195] Then, based on the comparison of the value associated with the monitored measurement of the one or more physiological parameters and the threshold value, the method 600 may include an adjustment operation 606 of the CSF management module (e.g., the CSF management module 22 and / or other suitable CSF management module). For example, if the value associated with the monitored measurement of the one or more physiological parameters reaches or exceeds the threshold value, the operation of the CSF management module 22 may be adjusted (e.g., via a control signal) to initiate a filtering regimen using a filtering therapy module (e.g., the filtering therapy module 38 and / or other suitable filtering therapy module), a cooling regimen using a cooling therapy module (e.g., the cooling therapy module 42 and / or other suitable cooling therapy module), and / or other suitable treatment regimens using a submodule of the CSF management module (e.g., the hardware and / or software submodule 34 or other suitable submodule). In an additional or alternative example, when a difference between the value associated with the monitored measurement of the one or more physiological parameters and the threshold value is determined, the operation of the CSF management module may be adjusted based on the determined difference between the value associated with the monitored measurement of the one or more physiological parameters and the threshold value. Alternatively or additionally, the operation of the CSF management module may be adjusted based on one or more additional or alternative factors.

[0196] The adjustment operation of the CSF management module can be automatically executed 606 according to the treatment plan of the CSF management module based on the comparison of the value associated with the monitored measurement value of one or more physiological parameters with the threshold value (e.g., initiating: a treatment start plan (e.g., this starts other treatment plans), a treatment stop plan (e.g., this stops other treatment plans), a filtering treatment plan, a cooling treatment plan, a suitable predetermined treatment plan (e.g., this may or may not include a treatment start plan, a treatment stop plan, a filtering treatment plan, a cooling treatment plan and / or other suitable predetermined treatment plans), and / or other suitable treatment plans). In some cases, the treatment start plan can be initiated in response to a first determination that the value associated with the monitored measurement value of one or more physiological parameters reaches or exceeds the threshold value, and the treatment stop plan can be initiated in response to a second determination that the value associated with the monitored measurement value of one or more physiological parameters reaches or exceeds the threshold value after the threshold value is first reached or exceeded. In addition, the type of treatment regimen (e.g., the type of predetermined treatment regimen, such as a cooling treatment regimen, a filtering treatment regimen, and / or other therapies or treatment regimens, and / or the type of non-predetermined treatment regimen (e.g., a learned and / or developed treatment regimen)) can be determined by the controller of the inflammation management system based on a value having an associated value that meets or exceeds a threshold and / or a value determined to be a difference between a value associated with the monitored measurement of one or more physiological parameters and the threshold and / or as described above in relation to Figure 5 The approach discussed selects the type or types of physiological parameters associated with the monitored measurements to be automatically selected.

[0197] Automatically executing adjustments to the operation of the CSF management module can be implemented using one or more controllers of the CSF management module and / or one or more controllers of the inflammation management system to treat and / or diagnose brain injury. As an alternative to automatically executing adjustments to the operation of the CSF management module, an alarm or other notification can be issued (e.g., via email, via a noise warning, a light warning, an indication on a user interface (e.g., user interface 18 and / or other suitable user interface)), and the user can manually adjust the operation of the CSF management module and / or manually initiate adjustments to the operation of the CSF management module.

[0198] In addition to or in lieu of adjusting the operation of a CSF management module (e.g., circulatory management module 23 and / or other suitable circulatory management module) in response to a value associated with monitored measurements of one or more physiological parameters reaching or exceeding a threshold, controller 16 may adjust the operation of the circulatory management module to actively drain CSF from the patient. In some cases, the operation of the circulatory management module to actively drain CSF from the patient may occur while adjusting the operation of the cooling therapy module to cool the CSF for a predetermined amount of time, adjusting the operation of the filtering therapy module to filter the CSF at a predetermined flow rate, and / or adjusting the operation of the CSF management module in one or more other ways.

[0199] The inflammation management system 10 can be used to treat a variety of conditions. Some of the envisioned conditions include cancer. For example, leptomeningeal metastasis (LM) is a condition in which cells from a primary solid tumor or hematological tumor metastasize, invade the subarachnoid space (SAS), and spread throughout the cerebrospinal fluid (CSF), resulting in inoculation of the leptomeninges along the surface of the central nervous system (CNS). LM represents a late event in the development of cancer, and the most common symptoms include multiple cranial nerve deficits, motor deficits, altered mental status, headaches, and radicular pain. The incidence of LM is estimated to account for 3 to 5% of cancer patients and has been increasing due to the longer overall survival of cancer patients. LM presents a daunting challenge in metastatic cancer treatment plans, which results in a devastating prognosis and a median survival of 4 months due to the lack of effective access and therapy. Due to the poor permeability of the blood-brain barrier (BBB), systemic treatment with anticancer drugs (including methotrexate (MTX), cytarabine, and thiotepa) is not as effective. Intrathecal drug delivery systems, including the Ommaya reservoir, are associated with longer overall survival; however, they require repeated injections and rely on passive diffusion. Future therapies that target the entire CNS and enhance IT drug distribution may further extend survival. CSF is produced at approximately 20 ml / hour, with a total volume of ~150 ml, resulting in an average turnover of 3 times per day. The rate of CSF production is independent of intracranial pressure (ICP). Because LM blocks the outflow path of CSF, patients are at serious risk for hydrocephalus and elevated ICP. Additionally, the relative isolation of CSF by the BBB and blood-CSF barrier provides a unique environment for tumor survival.

[0200] The inflammation management system 10 can have the ability to rapidly clear many CSF pathogens and cells, as well as enhance the ability to deliver drugs in the CSF. For example, the inflammation management system 10 can be used to improve LM outcomes by: 1) enhancing exposure and circulation of a specific anticancer agent (MTX delivered via an Ommaya reservoir, catheter, or both) throughout the SAS, (2) locally filtering the CSF to remove circulating tumor cells (CTCs) that disseminate cancer, (3) controlling ICP via CSF drainage, and (4) filtering tumor cells (e.g., live and / or dead tumor cells that may block natural reabsorption of the CSF via arachnoid granulations and the lymphatic system. The inflammation management system 10 can also be used to reduce the concentration of a drug (e.g., a chemotherapeutic agent such as methotrexate) in the CSF (e.g., to remove excess drug, reduce toxicity, etc.).

[0201] As mentioned herein, it is contemplated that the treatment method including the chemotherapeutic agent is injected into the patient. In some cases, the chemotherapeutic agent is methotrexate. Other chemotherapeutic agents can be contemplated. The chemotherapeutic agent can be injected into the CNS via the Ommaya reservoir (and / or similar devices, including, for example, the Rickham device) implanted in the ventricle of the patient, which is the standard of care for these patients. Additionally or alternatively, a catheter can be used to inject the chemotherapeutic agent into the patient. For example, a separate device disposed adjacent to the catheter or in another suitable manner can be added to the CSF outlet path of the clean, to one of the ports of the catheter. The circulation of CSF through the inflammation management system 10 can help circulate the chemotherapeutic agent throughout the cerebrospinal cavity and / or CNS.

[0202] Another envisioned condition that can be treated using the inflammation management system 10 is amyotrophic lateral sclerosis (ALS). For example, the pathology of ALS may be associated with overstimulation of glutamatergic function / pathways, which has corresponding excitotoxicity, increased calcium levels and / or generation of reactive oxygen species. Oxidative stress may be involved in the pathological mechanism of ALS via the release of pro-oxidant compounds and redox-active iron associated with cell death, mitochondrial dysfunction, inflammation and excitotoxicity. The inflammation management system 10 can be used to help reduce / clear oxidants and / or inflammatory agents (e.g., including free radicals, cytokines, chemokines, leukocytes) in the CSF, such as those associated with the pathology of ALS. Some examples of substances that can be reduced / removed as part of treating ALS can include one or more of insoluble superoxide dismutase-1 (SOD1), glutamate, neurofilament proteins, and anti-GM1 ganglioside antibodies.

[0203] In some cases, oxidants and / or inflammatory agents can carry an electric charge. The removal of this material can be enhanced by electrofiltration (e.g., a filter with an electric charge). Therefore, in at least some cases, the first filter, the second filter, both and / or one or more other filters can include a charged filter (electrofilter). In some of these cases and in other cases, the first filter, the second filter or both can include an immunoaffinity column, a size exclusion column, an anion exchange column, a cation exchange column and a protein A or protein G column.

[0204] In addition to removing CSF-borne pathological mediators associated with ALS, the inflammation management system 10 can also be used to deliver one or more drugs to the CSF. Such treatment can help further reduce oxidants and / or inflammatory agents. In some cases, the drug can be added to a clean CSF outlet path (e.g., a return outlet) to one of the ports of the catheter via a separate device disposed adjacent to the catheter or in another suitable manner. The circulation of the CSF through the inflammation management system 10 can help circulate the drug throughout the cerebrospinal cavity and / or CNS. Some example drugs that can be utilized can include riluzole, edaravone, and the like.

[0205] Another envisioned condition that can be treated using the inflammation management system 10 is herpes simplex encephalitis (HSE). HSE is known to cause severe neuroinflammation, brain edema, and hemorrhagic necrosis, which leads to increased intracranial pressure (ICP). Although medical management has been standardized, due to uncontrolled ICP, neuroinflammation, and brain edema, active combined medical and surgical management including decompressive craniectomy and / or temporal lobectomy is usually performed. The generation of reactive oxygen species (ROS) is also considered to be an integral part of the natural defense against viral infection. However, the lipid-rich environment of the CNS may be susceptible to oxidative damage. Therefore, oxidative damage may be associated with HSE infection.

[0206] The inflammation management system 10 can be used to remove oxidants and / or inflammatory agents (e.g., including free radicals, cytokines, chemokines, leukocytes), such as those associated with the pathology of HSE. In some cases, the oxidants and / or inflammatory agents can carry an electrical charge. Electrical filtration (e.g., a filter with an electrical charge) can be used to enhance the removal of such substances. Therefore, in at least some cases, the first filter, the second filter, or both can include a charged filter (electrofilter).

[0207] Another contemplated condition that can be treated using the inflammation management system 10 is human immunodeficiency virus (HIV) and / or acquired immune deficiency system (AIDS). HIV infection of the CNS can lead to many complications, including meningitis, acute inflammatory polyneuropathy (AIDP), immune reconstitution inflammatory syndrome (IRIS)-initiated by the introduction of antiretroviral therapy, chronic inflammatory polyneuropathy (CIDP), distal symmetric polyneuropathy (DSP), progressive multifocal leukoencephalopathy (PML), and HIV-associated neurocognitive disorder (HAND). The inflammation management system 10 can be designed to filter / reduce / remove many different HIV strains from the CNS. This can reduce the viral load in the CSF and / or reduce complications associated with HIV infection in the CNS. In addition, the inflammation management system 10 can be designed to filter / reduce / remove many different inflammatory agents associated with HIV from the CNS.

[0208] Another contemplated condition that may be treated using the inflammation management system 10 is multiple sclerosis (MS). Two subtypes, clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS), represent a lack of progression of the disease, while primary progressive (PPMS) and secondary progressive (SPMS) represent patients with progressive disease that originates from or follows RRMS, respectively. Neuroinflammation leading to multifocal lesion formation, demyelination, axonal damage, and consequent neurodegeneration is a hallmark of the disease. Current treatments can be categorized as including: (1) anti-inflammatory natural molecules (IFN-β), (2) molecules that stimulate anti-inflammatory (glatiram acetate) or inhibit autoreactive (teriflunomide) cell proliferation, (3) immunosuppressive monoclonal antibodies (natalizumab), (4) molecules that bind transcription factors to enhance anti-inflammatory mechanisms or inhibit pro-inflammatory mechanisms (dimethyl fumarate), and (5) agents that inhibit lymphocytes from leaving lymphoid tissues to reach the CNS (fingolimod). In some cases, the inflammation management system 10 can be designed to filter / reduce / remove many different inflammatory agents associated with MS, including immune cells (immunoglobulins, neutrophils, lymphocytes, monocytes, etc.), oxidative and / or inflammatory agents (e.g., including free radicals, cytokines, chemokines, leukocytes), such as those associated with MS pathology, etc. This can help treat MS and / or improve its symptoms.

[0209] Another envisioned condition that the inflammatory management system 10 can be used for treatment is Guillain-Barre syndrome (GBS). GBS is the most common cause of acute paralytic neuropathy worldwide. Acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) are the main phenotypes. GBS may be produced in individuals by a combination of host genetic factors and environmental factors and recent infections caused by pathogens including Campylobacter jejuni and Zika virus. The general mechanism of action suggests that molecular mimicry of exogenous antigens and ganglioside residues leads to the development of autoantibodies that recognize myelin or axonal components and trigger inflammatory immune responses, including macrophage and / or lymphocyte infiltration, complement deposition, and cytokine production. Cerebrospinal fluid analysis shows elevated protein (>400 mg / L) in 90% of patients and no cerebrospinal fluid cell increase. Although the specific immunological protein spectrum of GBS CSF is heterogeneous, it has been noted that elevated levels of neuroinflammatory cytokines and other proteins involved in pathology. In some of these cases, as well as in others, a second catheter can be used to infuse medication into the skull area.

[0210] Current treatments for GBS may include supportive care with plasma exchange (PE) or intravenous immunoglobulin (IVIg). Based on the abnormality of proteins in CSF in GBS patients, including the inflammatory cytokines TNF-α and IL-6 7 , anti-ganglioside antibodies, and activated complement components, filtering CSF to reduce / remove inflammation can help reduce the GBS system and / or treat GBS. In some cases, the inflammation management system 10 can be designed to filter / reduce / remove many different inflammatory agents associated with GBS, including immune cells (immunoglobulins, neutrophils, lymphocytes, monocytes, etc.), oxidants and / or inflammatory agents (e.g., including free radicals, cytokines, chemokines, leukocytes), such as those associated with MS pathology, etc. This can help treat GBS and / or improve its symptoms. In some cases, when used to treat GBS, the inflammation management system 10 can include a 5kDa filter. Other filter sizes are also envisioned, including those disclosed herein. For example, the inflammation treatment system 10 can include a 5kDa tangential flow filter, a 100kDa tangential flow filter, an electric filter, or a combination thereof.

[0211] Another envisioned condition that can be treated using the inflammation management system 10 is meningitis. Bacterial meningitis occurs when pathogenic bacteria enter the subarachnoid space and cause a purulent inflammatory response. Gram-negative bacterial meningitis (GBM) is a devastating condition that occurs when Gram-negative bacteria invade the central nervous system (CNS). There are 30,000 U.S. cases and more than 1 million GBM cases worldwide each year. When bacterial infection manifests as GBM, it brings a great burden of mortality (usually more than 30%) and morbidity to patients, and even when caused by bacteria that are sensitive to standard antibiotics, it is difficult for clinicians to treat. It is most common in children or immunocompromised patients, such as those with HIV, after organ transplantation, or after neurosurgery. Current treatment guidelines include intravenous cephalosporins or carbapenems or polymycins for at least 10 days to 2 weeks. In the presence of Gram-negative enterobacterial meningitis (usually occurring around trauma and in neurosurgery), highly resistant bacteria can cause disease. Antibiotics, such as aminoglycosides and polymycins, are considered for treatment, but these agents have a poor treatment-to-toxicity ratio when used systemically in CNS disease and may not provide optimal therapy.

[0212] Three key Gram-negative pathogens considered as urgent priorities include Pseudomonas, Acinetobacter and Klebsiella (PAK). These Gram-negative bacteria can cause serious and usually fatal infections such as pneumonia, bloodstream infections, and especially hospital-acquired meningitis. These bacteria have developed resistance to multiple antibiotics (including carbapenems and third-generation cephalosporins - the best available antibiotics for the treatment of multi-drug resistant bacterial meningitis). The World Health Organization recognizes the need to adopt a multimodal approach, and waiting longer will lead to further public health problems and greatly affect the care and survival of patients. This increases the very real possibility of GBM infection, which cannot be treated by currently available antibiotics. Returning to the pre-antibiotic era has unfortunately become a reality in many parts of the world.

[0213] Reducing CSF bioburden is the single most important factor affecting survival and is linked to better overall clinical outcomes. It is important to rapidly reduce CSF bioburden, with CSF sterilization within the first 24 hours. Optimization of antibiotic efficacy depends directly on the bioburden present and the direct activity of antibiotic therapy initiated early in the infection. In the face of resistant bacteria, such as PAK, it is becoming increasingly difficult to determine which antibiotic agent is most effective. Clinical data for new antibiotics used solely for bacterial meningitis cannot keep pace with the rise in resistance, and there is an urgent need to develop new treatments. Additionally, experimental animal models have shown that the outcome of bacterial meningitis is associated with the severity of inflammation in the subarachnoid space (SAS) and may be improved by modulating the inflammatory response.

[0214] The inflammation management system 10 may provide an innovative new treatment option that provides direct access to the CSF and creates an active cycle combined with targeted pathogen removal. This may provide a novel treatment approach that rapidly reduces CFU and CSF bacterial burden and translates into a reduction in morbidity and mortality from bacterial meningitis.

[0215] Thus, the present method improves or alleviates the symptoms of bacterial meningitis by reducing or eliminating the presence of one or more of bacterial pathogens and / or endotoxins and / or cytokines associated therewith in CSF using an inflammation management system 10. The method comprises removing CSF from the patient, removing at least one of the bacterial pathogens and / or endotoxins and / or cytokines associated therewith from the CSF, and returning endogenous CSF to the patient, wherein the removal and return steps are performed simultaneously during at least a portion of the treatment. In some embodiments, the cytokine is selected from the group consisting of IL-1ra, IL-6, TNF, CRP, and CXCL10, or a combination thereof.

[0216] In some of these cases and in other cases, the method improves or alleviates symptoms of bacterial meningitis by: introducing a catheter into the patient's spinal CSF cavity through a spinal access site; advancing the catheter through the spinal CSF cavity toward the brain so that the openings of the catheter are positioned within the CSF cavity and are spaced apart at preselected distances or adjusted to appropriate distances; withdrawing the CSF through at least some of the openings in the catheter; removing bacterial pathogens and / or at least one of their associated endotoxins and / or cytokines from the withdrawn CSF (thereby conditioning the CSF) using an inflammation management system 10; and returning the conditioned CSF through other of the openings in the catheter.

[0217] Fungal meningitis (FM) is an infection of the meninges of the central nervous system, which is manifested by the spread of any major fungal pathogens into the subarachnoid space (SAS) via the cerebrospinal fluid (CSF). Cryptococcal meningitis (CM) is caused by Cryptococcus neoformans and is the most common cause of fungal meningitis in adults. Other pathogens of fungal meningitis include Clostridium gati, Bacillus, Histoplasma, Coccidioides. The treatment of CM is based on the induction, consolidation and maintenance methods using antifungal drugs, and is also clearly defined elsewhere, but is associated with persistent high morbidity and mortality. Drug discovery programs are limited by poor permeability of the blood-brain barrier (BBB). Therefore, we have developed an alternative catheter-based extracorporeal filtration system (neurolysis therapy) for filtering infected CSF. Here, we describe the in vitro characterization of neurolysis therapy as an alternative mechanical intervention for filtering neoformans cells, polysaccharide antigens and inflammatory mediators from infected CSF.

[0218] The inflammation management system 10 can provide an innovative new treatment option that provides direct access to the CSF and creates an active cycle combined with targeted pathogen removal. This can provide a novel treatment method that rapidly reduces CFU and CSF fungal burden and translates into a reduction in the morbidity and mortality of fungal meningitis. In at least some cases, the inflammation management system 10 may include one or more filters designed to exclude fungi, such as Cryptococcus neoformans, from passing through it. In some of these cases and in other cases, the inflammation management system 10 may include one or more filters designed to exclude fungi (e.g., Cryptococcus neoformans), associated antigens and / or inflammatory agents. In at least some cases, a single pass of the CSF through a 5kDa TFF and / or a 100kDa TFF may be sufficient to exclude Cryptococcus neoformans or otherwise reduce Cryptococcus neoformans in the CSF. In addition, the 5kDa TFF and / or the 100kDa TFF may be sufficient to exclude or otherwise reduce Cryptococcus neoformans antigens from the CSF. Furthermore, 5 kDa and / or 100 kDa TFFs can also deplete many neuroinflammatory agents from CSF, such as IL-1ra, IL-6, TNF, CRP and / or CXCL 10 / IP-10.

[0219] Therefore, the present method improves or alleviates the symptoms of fungal meningitis by reducing or eliminating the presence of one or more of fungal pathogens and / or antigens (e.g., cryptococcal antigens) and / or cytokines associated with the CSF using an inflammation management system 10. The method includes removing CSF from the patient, as described herein; removing at least one of the fungal pathogens and / or antigens and / or cytokines associated with the fungal pathogen from the CSF; and returning endogenous CSF to the patient, wherein the removal and return steps are performed simultaneously during at least a portion of the treatment. In some embodiments, the cytokine is selected from the group consisting of IL-1ra, IL-6, TNF, CRP and CXCL10 or a combination thereof. One or more filtration systems can be used to remove fungi / multiple fungi and / or antigens and / or cytokines from the CSF. 5kDa and / or 100kDa TFFs can also exclude many neuroinflammatory agents, such as IL-1ra, IL-6, TNF, CRP and / or CXCL 10 / IP-10.

[0220] In some of these cases and in other cases, the method improves or alleviates symptoms of fungal meningitis by: introducing a catheter into the patient's spinal CSF cavity through a spinal access site; advancing the catheter through the spinal CSF cavity toward the brain so that the openings of the catheter are positioned within the CSF cavity and are spaced apart at preselected distances or adjusted to appropriate distances; withdrawing the CSF through at least some of the openings in the catheter; removing fungal pathogens and / or at least one of their associated antigens and / or cytokines from the withdrawn CSF (thereby regulating the CSF) with an inflammation management system 10; and returning the regulated CSF through other of the openings in the catheter.

[0221] In at least some cases, the inflammation management system 10 can be used to deliver drugs to parts of the CNS. For example, some treatments for CM can include intravenous and oral administration of antifungal drugs, such as amphotericin B (AmB) and flucytosine. Typically, intrathecal (IT) AmB push injections may be associated with concentrations of neurotoxic drugs near the injection site. The use of the inflammation management system 10 can allow IT infusions of AmB and / or other drugs. Unexpectedly, the inflammation management system 10 can also be used to reduce, filter or otherwise remove some drugs, such as AmB. Therefore, the dose of AmB can be precisely titrated to the desired dose. If the level of AmB reaches an undesirable level (e.g., an undesirably high level), the inflammation management system 10 can be used to quickly remove unwanted amounts of AmB from the CSF.

[0222] The inflammation management system 10 can also be used to deliver many other drugs, including drugs in situations where the difference between the therapeutic dose and the toxic dose is relatively small. For example, the inflammation management system 10 can be used to inject drugs into the CSF. If signs of toxicity are observed or if the measured value of the drug concentration in the CSF is higher than expected, the inflammation management system 10 can be used to quickly remove the drug from the CSF. Therefore, the inflammation management system 10 can be used to deliver drugs to the patient's CSF and quickly remove drugs from the CSF as needed.

[0223] The inflammation management system 10 may also help reduce ICP associated with a variety of conditions. For example, some conditions (e.g., such as cancer, HSE, etc.) may be associated with higher ICP due to cells (e.g., tumor cells, etc.), inflammatory agents, etc. that block, obstruct, or otherwise affect the natural pathway for reabsorption of CSF. By using the inflammation management system 10, materials that may block the natural reabsorption pathway may be removed / reduced, thereby desirably affecting the volume of CSF and reducing ICP.

[0224] It is also conceivable to utilize a first port to provide access to the cerebrospinal cavity and / or CNS at a first position and to utilize a second port to provide access to the cerebrospinal cavity and / or CNS at a second position. Such a port can be implanted acutely or implanted over an extended period of time. In some cases, the port can allow the injection of substances into the cerebrospinal cavity and / or CNS, the removal of substances from the cerebrospinal cavity and / or CNS, or both. One or both of the ports can be an Ommaya reservoir or otherwise similar to an Ommaya reservoir. The port can be designed to be used with a tube / catheter, an inflammation management system 10. For example, a first tube and / or a first catheter can be connected to one of the ports or otherwise connectable thereto, and a second tube and / or a second catheter can be connected to another port or otherwise connectable thereto. CSF can be removed from the patient (e.g., using a tube, a first catheter, or a second catheter, etc.) and filtered by the inflammation management system 10. In some cases, the same tube / catheter can be used to return the filtered CSF to the patient. In other cases, other tubes / catheters can be used to return the filtered CSF to the patient. In other words, CSF can be removed from the patient using the catheter at the first port, filtered and then returned to the patient using the catheter at the second port. This can form a loop path that helps circulate CSF through the cerebrospinal cavity and / or CNS. The port can be positioned along the patient in a manner that helps promote CSF circulation. For example, one of the ports can be positioned at the patient's skull (for example, it can include a path provided to the cerebral ventricle) and another port can be positioned along the lumbar region of the spine (for example, it can provide a path to the cerebrospinal cavity at a position adjacent to the lumbar space). Other positions can be envisioned.

[0225] All directional references (e.g., proximal, distal, upper, lower, upward, downward, left, right, lateral, front, rear, top, bottom, above, below, vertical, horizontal, clockwise and counterclockwise) are used only for identification purposes to help the reader understand the present invention and do not create limitations, especially limitations on the position, orientation or use of the present invention. Unless otherwise indicated, connection references (e.g., attachment, connection, connection and combination) will be interpreted broadly and may include intermediate members between sets of elements and relative movement between elements. In this regard, connection references do not necessarily imply that two elements are directly connected and in a fixed relationship with each other. It should be noted that for the purposes of the present invention, delivery sheaths and delivery catheters can be used interchangeably. The exemplary drawings are for illustrative purposes only, and the dimensions, positions, orders and relative sizes reflected in the drawings attached thereto may vary.

[0226] U.S. Patent Application Publication No. US 2016 / 0051801 is incorporated herein by reference. U.S. Patent No. 8,435,204 is incorporated herein by reference. U.S. Patent Application No. 62 / 568,412 (Attorney Docket No. 1421.1010100) is incorporated herein by reference. U.S. Patent Application No. 62 / 598,846 (Attorney Docket No. 1421.1011100) is incorporated herein by reference.

[0227] The above description, examples and data provide a complete description of the structure and use of the exemplary embodiments of the invention as claimed below. Although various embodiments of the invention as claimed have been described above with a certain degree of specificity or with reference to one or more individual embodiments, many changes may be made to the disclosed embodiments by those skilled in the art without departing from the spirit or scope of the invention. Therefore, other embodiments may be considered. The invention is intended to be contained in the above description and all subject matter shown in the accompanying drawings should be interpreted as merely illustrative of specific embodiments and not limiting. Changes in detail or structure may be made without departing from the basic elements of the invention.

Claims

1. An inflammation management system, the system include: Controller; a cerebrospinal fluid management module in communication with the controller; The controller is configured as follows: monitoring measurements of one or more physiological parameters of the patient that are associated with inflammation in or around the patient's brain; comparing a value associated with the monitored measured values ​​of the one or more physiological parameters to a threshold value, wherein the value associated with the monitored measured values ​​of the one or more physiological parameters is an indexed value, and wherein the indexed value is based on a value of a mass effect index; as well as The cerebrospinal fluid management module is controlled based on the comparison of the value associated with the monitored measurements of the one or more physiological parameters with the threshold value.

2. The system of claim 1 , wherein the controller is configured to automatically control the cerebrospinal fluid management module to perform treatment on the patient's cerebrospinal fluid when the value associated with the monitored measurement of the one or more physiological parameters reaches or exceeds the threshold.

3. The system of claim 2, wherein the treatment of the patient's cerebrospinal fluid is a predetermined treatment based on a type of physiological parameter associated with the monitored measurements.

4. A system according to claim 2, wherein the treatment of the patient's cerebrospinal fluid is a predetermined treatment based on a comparison of the value associated with the monitored measurement of the one or more physiological parameters and a type of physiological parameter associated with the monitored measurement.

5. The system of any one of claims 1 to 4, wherein the indexed value is related to measured values ​​of two or more physiological parameters of the patient. 6 . The system of claim 5 , wherein the indexed value is a value based on an index of measured values ​​of the two or more physiological parameters of the patient.

7. The system of claim 5, wherein the indexed value is an index value based on two or more classification indices, and each of the two or more classification indices is based on measured values ​​of two or more physiological parameters of the patient.

8. The system according to any one of claims 1 to 4, wherein the value associated with the monitored measured values ​​of the one or more physiological parameters is a value of a measured value of one of the one or more physiological parameters.

9. The system according to any one of claims 1 to 4, wherein the one or more physiological parameters include one or more physiological parameters selected from the group consisting of intracranial pressure, cerebral perfusion pressure, mean arterial pressure, heart rate, cerebral oxygenation, cerebral blood flow and cytokine levels.

10. The system of any one of claims 1 to 4, wherein the cerebrospinal fluid management module comprises a cooling therapy module.

11. The system of any one of claims 1 to 4, wherein the cerebrospinal fluid management module comprises a filtration therapy module.

12. The system of any one of claims 1 to 4, wherein the cerebrospinal fluid management module comprises a cooling therapy module and a filtration therapy module.

13. The system of any one of claims 1 to 4, wherein the cerebrospinal fluid management module comprises a circulation module having a pump configured to pump cerebrospinal fluid from the patient to a treatment module.

14. The system according to any one of claims 1 to 4, further comprising: include: a communication port for communicating with the controller; as well as Wherein the communication port is configured to receive the measured values ​​of the one or more physiological parameters of the patient monitored by the controller.

15. The system according to any one of claims 1 to 4, further comprising: include: a communication port for communicating with the controller; as well as Wherein the communication port is configured to facilitate communication between the cerebrospinal fluid management module and the controller.

16. The system according to any one of claims 1 to 4, further comprising: include: A wireless communication port is in communication with the controller and is configured to facilitate communication between the controller and a device via a wireless network.

17. The system according to any one of claims 1 to 4, further comprising: include: a user interface in communication with the controller; as well as Wherein the user interface is configured to receive input that modifies the operation of the controller.

18. A system according to claim 17, wherein the user interface is configured to display a medical image of the patient in a selectable pane, and to display one or both of the measured values ​​of the one or more physiological parameters of the patient and the values ​​related to the monitored measured values ​​of the one or more physiological parameters in a real-time updating pane position on the user interface adjacent to the selectable pane.

19. A computer readable medium having program code stored thereon in a non-transitory state for use by a computing device, the program code causing the computing device to perform a method for managing inflammation, the method include: determining a value associated with one or more measurements of one or more physiological parameters of the patient that are associated with inflammation in or around the patient's brain; comparing the value associated with the one or more measured values ​​of the one or more physiological parameters to a threshold value, wherein the value associated with the monitored measured values ​​of the one or more parameters is an indexed value, and wherein the indexed value is based on a value of a mass effect index; as well as Based on a comparison of the value associated with the one or more measurements of the one or more physiological parameters with the threshold value, a control signal is output to adjust the operation of the cerebrospinal fluid management module.

20. The computer readable medium of claim 19, wherein the method further comprises: include: determining a difference between the value associated with the one or more measured values ​​of the one or more physiological parameters and the threshold value; Wherein the control signal to adjust operation of the cerebrospinal fluid management module is based on a determined difference between the value associated with the one or more measurements of the one or more physiological parameters and the threshold value.

21. The computer-readable medium of claim 19, wherein the outputting of the control signal is automatically initiated based on the comparison of the value associated with the one or more measurements of the one or more physiological parameters with the threshold value.

22. A computer-readable medium according to any one of claims 19 to 21, wherein the output control signal for adjusting the operation of the cerebrospinal fluid management module is configured to initiate a treatment start regimen in response to the value associated with the one or more measured values ​​of the one or more physiological parameters reaching or exceeding the threshold for the first time.

23. The computer-readable medium of claim 22, wherein the output control signal for adjusting the operation of the cerebrospinal fluid management module is configured to initiate a treatment cessation regimen in response to the value associated with the one or more measurements of the one or more physiological parameters reaching or exceeding the threshold a second time after the first time the value reached or exceeded the threshold.

24. The computer-readable medium of any one of claims 19 to 21, wherein the output control signal for adjusting the operation of the cerebrospinal fluid management module is configured to initiate a treatment cessation regimen in response to the value associated with the one or more measured values ​​of the one or more physiological parameters reaching or exceeding the threshold value.

25. The computer-readable medium of any one of claims 19 to 21, wherein the output control signal that adjusts the operation of the cerebrospinal fluid management module is configured to initiate a predetermined treatment regimen based on a type of physiological parameter associated with the one or more measurements.

26. A computer-readable medium according to any one of claims 19 to 21, wherein the output control signal for adjusting the operation of the cerebrospinal fluid management module is configured to initiate a predetermined treatment regimen based on a comparison of the value associated with the one or more measurements of the one or more physiological parameters and the threshold value and a type of physiological parameter associated with the one or more measurements.

27. The computer readable medium of any one of claims 19 to 21, wherein the output control signal that adjusts the operation of a cerebrospinal fluid management module causes the cerebrospinal fluid management module to initiate a cooling therapy regimen.

28. The computer readable medium of any one of claims 19 to 21, wherein the output control signal that adjusts the operation of a cerebrospinal fluid management module causes the cerebrospinal fluid management module to initiate a filtration therapy regimen.

29. The computer readable medium of any one of claims 19 to 21, wherein the output control signal that adjusts the operation of a cerebrospinal fluid management module causes the cerebrospinal fluid management module to initiate a filtration therapy regimen and a cooling therapy regimen.

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