Neuromodulation for neuroinflammation treatments with parameters controlled using biomarkers

Abstract

An example of a system for modulating neuroinflammation at a tissue site in a patient includes a neuromodulation output circuit, a memory, and a control circuit. The neuromodulation output circuit may be configured to deliver the neuromodulation. The memory may be configured to store a neuromodulation parameter set selected to modulate neural activity at the tissue site and a sensed biomarker parameter. The biomarker parameter may include a measure of a biomarker or a measure of a derivative of the biomarker. The biomarker may be indicative of the neuroinflammation at the tissue site. The control circuit may be configured to control the delivery of the neuromodulation using the neuromodulation parameter set and adjust one or more parameters of the neuromodulation parameter set using the biomarker parameter.

What is claimed is: 
     
         1 . A method for delivering neuromodulation to a patient, the method comprising:
 delivering the neuromodulation;   controlling the delivery of the neuromodulation using a neuromodulation parameter set selected to modulate neural activity at a tissue site;   sensing a biomarker parameter being a measure of a biomarker or a measure of a derivative of the biomarker, the biomarker indicative of neuroinflammation at the tissue site; and   adjusting the neuromodulation parameter set using the biomarker parameter.   
     
     
         2 . The method of  claim 1 , wherein the biomarker is indicative of activation of microglial cells in the tissue site. 
     
     
         3 . The method of  claim 1 , wherein adjusting the neuromodulation parameter set using the biomarker parameter comprises:
 comparing the biomarker parameter to a reference value; and   adjusting the neuromodulation parameter set using an outcome of the comparison.   
     
     
         4 . The method of  claim 3 , wherein the biomarker comprises at least one of a translocator protein concentration, a temporal activation of the microglial cell, a spatial activation of the microglial cell, or a cytokine concentration. 
     
     
         5 . The method of  claim 1 , wherein delivering the neuromodulation comprises delivering electrical pulses. 
     
     
         6 . The method of  claim 1 , wherein delivering the neuromodulation comprises emitting a light. 
     
     
         7 . The method of  claim 1 , wherein delivering the neuromodulation comprises delivering the neuromodulation to at least one of a dorsal column, a thalamus, a cortex, a peripheral nerve, a vagus nerve, a dorsal root ganglion, a dorsal longitudinal fasciculus, or a dorsal horn. 
     
     
         8 . The method of  claim 1 , wherein delivering the neuromodulation comprises delivering the neuromodulation to the tissue site. 
     
     
         9 . The method of  claim 1 , wherein delivering the neuromodulation comprises delivering the neuromodulation to an upstream or downstream pathway relative to the tissue site. 
     
     
         10 . The method of  claim 1 , wherein delivering the neuromodulation comprises delivering the neuromodulation to a nerve that modulates the neuroinflammation systemically. 
     
     
         11 . A system for modulating neuroinflammation at a tissue site in a patient, the system comprising:
 a neuromodulation output circuit configured to deliver the neuromodulation;   a memory configured to store a neuromodulation parameter set selected to modulate neural activity at the tissue site and a sensed biomarker parameter, the biomarker parameter including a measure of a biomarker or a measure of a derivative of the biomarker, the biomarker indicative of the neuroinflammation at the tissue site; and   a control circuit configured to control the delivery of the neuromodulation using the neuromodulation parameter set and adjust one or more parameters of the neuromodulation parameter set using the biomarker parameter.   
     
     
         12 . The system of  claim 11 , wherein the control circuit is configured to compare the biomarker parameter to a reference value and to adjust the neuromodulation parameter set using an outcome of the comparison. 
     
     
         13 . The system of  claim 12 , comprising an implantable neuromodulation device including the neuromodulation output circuit, the memory, and the control circuit. 
     
     
         14 . The system of  claim 12 , further comprising a biomarker sensor configured to sense the biomarker parameter, wherein the biomarker sensor is configured to sense the biomarker parameter being a measure of at least one of a translocator protein concentration, a measure of a temporal activation of the microglial cell, a measure of a spatial activation of the microglial cell, or a measure of or a cytokine concentration. 
     
     
         15 . The system of  claim 14 , wherein the biomarker sensor is configured to sense a biomarker parameter indicative of a degree of the neuroinflammation at the tissue site. 
     
     
         16 . The system of  claim 15 , wherein the biomarker sensor is configured to sense a biomarker parameter indicative of an intensity of pain. 
     
     
         17 . The system of  claim 14 , wherein the biomarker sensor is configured to sense a biomarker parameter indicative of a need for treating the neuroinflammation. 
     
     
         18 . The system of  claim 11 , wherein the neuromodulation output circuit is configured to deliver electrical pulses. 
     
     
         19 . The system of  claim 11 , further comprising a neuromodulation delivery device configured to deliver stimuli including one or more of electrical stimuli, magnetic stimuli, optical stimuli, acoustic stimuli, and chemical stimuli, and wherein the neuromodulation output circuit is configured to deliver the neuromodulation by controlling the delivery of the stimuli from the neuromodulation delivery device. 
     
     
         20 . The system of  claim 19 , wherein the neuromodulation delivery device is configured to emit a light, and wherein the neuromodulation output circuit is configured to deliver the neuromodulation by controlling the emission of the light from the neuromodulation delivery device.