Patent Publication Number: US-11648399-B2

Title: Sensing reference electrode for percutaneous neuromodulation trials

Description:
CLAIM OF PRIORITY 
     This application claims the benefit of priority under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application Ser. No. 62/859,430, filed on Jun. 10, 2019, which is herein incorporated by reference in its entirety. 
    
    
     TECHNICAL FIELD 
     This document relates generally to medical devices and more particularly to method and apparatus providing a percutaneous stimulation system with a sensing reference electrode for use during neuromodulation trials. 
     BACKGROUND 
     Neurostimulation, also referred to as neuromodulation, has been proposed as a therapy for a number of conditions. Examples of neurostimulation include Spinal Cord Stimulation (SCS), Deep Brain Stimulation (DBS), Peripheral Nerve Stimulation (PNS), and Functional Electrical Stimulation (FES). Implantable neurostimulation systems have been applied to deliver such a therapy. An implantable neurostimulation system can include an implantable neurostimulator, also referred to as an implantable pulse generator (IPG), and one or more implantable leads each including one or more electrodes. The implantable neurostimulator delivers neurostimulation energy through one or more electrodes placed on or near a target site in the nervous system. An external programming device is used to program the implantable neurostimulator with stimulation parameters controlling the delivery of the neurostimulation energy. 
     In one example, a temporary stimulation system is used to evaluate a neuromodulation therapy for a patient during a trial period for determination of whether an implantable neurostimulator is suitable for the patient. During the trial period, a trial lead is percutaneously placed with one end including electrodes in the patient and another end connected to an external trial stimulator GETS). Neurostimulation energy is delivered through the electrodes, and the delivery is controlled using stimulation parameters that specify spatial (where to stimulate), temporal (when to stimulate), and informational (patterns of stimulation directing the nervous system to respond as desired) aspects of a pattern of the neurostimulation energy. The stimulation parameters are evaluated and adjusted as needed by the patient and/or a care provider attending the patient, for therapeutic efficacy and efficiency as well as side-effects. It is desirable for the temporary stimulation system to emulate an implantable system that can be placed into the patient as a result of the evaluation of the neuromodulation therapy. 
     SUMMARY 
     An example (e.g., “Example 1”) of an apparatus for percutaneously delivering neurostimulation energy to a patient and sensing from the patient using a test device placed externally to the patient is provided. The apparatus may include an elongate stimulation lead, a sensing reference electrode, an elongate sensing wire, and a connection system. The stimulation lead may include a lead distal end including one or more electrodes and a lead proximal end including a lead connector. The lead connector may include one or more electrode contacts electrically connected to the one or more electrodes. The stimulation lead may be configured to be percutaneously introduced into the patient to place the one or more electrodes in the patient. The sensing reference electrode may be configured to be placed in the patient. The sensing wire may include a wire distal end connected to the sensing referenced electrode and a wire proximal end including a wire connector. The wire connector may include a sensing reference electrode contact electrically connected to the sensing reference electrode. The sensing wire may be configured to be percutaneously introduced into the patient to place the sensing reference electrode in the patient. At least a portion of the sensing wire may be separated from the stimulation lead. The connection system may be configured to be placed externally to the patient, to mate the lead connector, to mate the wire connector, and to provide electrical connections between the lead connector and the test device and between the wire connector and the test device. 
     In Example 2, the subject matter of Example 1 may optionally be configured such that the connection system includes a cable assembly including a cable connector and a cable. The cable connector may be configured to mate the lead connector and to mate the wire connector. The cable may be configured to be connected to the cable connector and to provide electrical connections between the cable connector and the test device. 
     In Example 3, the subject matter of any one or a combination of Examples 1 and 2 may optionally be configured such that the stimulation lead includes an implantable lead. 
     In Example 4, the subject matter of any one or any combination of Examples 1 to 3 may optionally be configured such that the sensing reference electrode is attached to the stimulation lead. 
     In Example 5, the subject matter of Example 4 may optionally be configured such that the sensing reference electrode is detachably attached to the stimulation lead. 
     In Example 6, the subject matter of Example 4 may optionally be configured such that the sensing reference electrode is permanently attached the stimulation lead, and the wire distal end of the sensing wire is releasably connected to the sensing referenced electrode. 
     In Example 7, the subject matter of any one or any combination of Examples 1 to 3 may optionally be configured such that the sensing reference electrode is integrated into the stimulation lead. 
     In Example 8, the subject matter of Example 7 may optionally be configured such that at least a portion of the sensing wire is integrated into the stimulation lead. 
     In Example 9, the subject matter of Example 8 may optionally be configured such that the sensing wire is fully integrated into the stimulation lead, and the wire connector is integrated into the stimulation connector. 
     In Example 10, the subject matter of Example 8 may optionally be configured such that the sensing wire is partially integrated into the stimulation lead, and the wire connector is separate from the stimulation connector. 
     In Example 11, the subject matter of any one or any combination of Examples 1 to 3 may optionally be configured to further include a lead introducer including an introducer distal end configured to enter the patient, an introducer proximal end, an elongate introducer body coupled between the introducer distal end and the introducer proximal end, and a lumen extending within the introducer body from an introducer distal opening at or near the introducer distal end and an introducer proximal opening at or near the introducer proximal end. The lumen is configured to accommodate a portion of the stimulation lead and to allow the lead distal end to enter the introducer primary opening and exit from the introducer distal opening. 
     In Example 12, the subject matter of Example 11 may optionally be configured such that the sensing reference electrode is attached to the stimulation lead, the lumen of the lead introducer is configured to accommodate the portion of the stimulation lead, the sensing reference electrode, and a portion of the sensing wire, and the lead introducer is removable from the patient after the stimulation lead is percutaneously placed. 
     In Example 13, the subject matter of Example 11 may optionally be configured such that the sensing reference electrode is detachably attached to the lead introducer. 
     In Example 14, the subject matter of Example 13 may optionally be configured such that the lead introducer is removable from the patient after the stimulation lead is percutaneously placed, and the sensing reference electrode is configured to be detached from the lead introducer to remain in the patient after the lead introducer is removed from the patient. 
     In Example 15, the subject matter of Example 14 may optionally be configured to further include a releasable clip and a release handle. The releasable clip is configured to attach the sensing reference electrode to the lead introducer and to detach the sensing reference electrode from the lead introducer. The release handle is coupled to the releasable clip and configured to detach the sensing reference electrode from the introducer by releasing the releasable clip. 
     In Example 16, the subject matter of any one or any combination of Examples 1 to 15 may optionally be configured such that the cable is configured to be releasably connected to the cable connector. 
     An example (e.g., “Example 17”) of a method for percutaneously delivering neurostimulation energy to a patient and sensing one or more signals from the patient using a test device placed externally to the patient is also provided. The method may include providing an elongate stimulation lead suitable for percutaneously introducing one or more electrodes into the patient for delivering the neurostimulation energy and sensing the one or more signals. The stimulation lead may include a lead distal end including the one or more electrodes and a lead proximal end including a lead connector having one or more electrode contacts electrically connected to the one or more electrodes. The method may further include providing a sensing reference electrode suitable for placing in the patient and providing an elongate sensing wire suitable for percutaneously introducing the sensing reference electrode into the patient to provide a reference for sensing the one or more signals. The sensing wire may be partially separated from the stimulation lead and may include a wire distal end connected to the sensing referenced electrode and a wire proximal end including a wire connector having a sensing reference electrode contact electrically connected to the sensing reference electrode. The method may still include providing electrical connections external to the patient for connecting the test device to the lead connector and to the wire connector. 
     In Example 18, the subject matter of providing the electrical connections between the lead connector and the test device and between the wire connector and the test device as found in Example 17 may optionally include providing a cable assembly for connecting the test device to the stimulation lead and to the sensing wire. The cable assembly may include a cable connector configured to mate the lead connector and to mate the wire connector and a cable connected to the cable connector and providing electrical connections between the cable connector and the test device. 
     In Example 19, the subject matter of providing the elongate stimulation lead as found in any one or a combination of Examples 17 and 18 may optionally include providing an implantable lead. 
     In Example 20, the subject matter of any one or any combination of Examples 17 to 19 may optionally further include attaching sensing reference electrode to the stimulation lead. 
     In Example 21, the subject matter of any one or any combination of Examples 17 to 19 may optionally further include integrating the sensing reference electrode into the stimulation lead. 
     In Example 22, the subject matter of any one or any combination of Examples 17 to 19 may optionally further include providing a lead introducer suitable for percutaneously introducing the stimulation lead for placing the one or more electrode in the patient. The lead introducer includes an introducer distal end configured to enter the patient, an introducer proximal end, an elongate introducer body coupled between the introducer distal end and the introducer proximal end, and a lumen extending within the introducer body from an introducer distal opening at or near the introducer distal end and an introducer proximal opening at or near the introducer proximal end. The lumen is configured to accommodate a portion of the stimulation lead and to allow the lead distal end to enter the introducer primary opening and exit from the introducer distal opening. 
     In Example 23, the subject matter of Example 22 may optionally further include detachably attach the sensing reference electrode to the lead introducer. 
     In Example 24, the subject matter of Example 23 may optionally further include detaching the sensing reference electrode from the lead introducer after the stimulation lead is percutaneously introduced using the lead introducer. 
     In Example 25, the subject matter of Example 24 may optionally further include providing a releasable clip to attach the sensing reference electrode to the lead introducer and a release handle coupled to the releasable clip, and the subject matter of detaching the sensing reference electrode from the lead introducer as found in Example 22 may optionally include releasing the releasable clip using the release handle. 
     In Example 26, the subject matter of any one or any combination of Examples 17 to 25 may optionally further include percutaneously introducing the stimulation lead to place the one or more electrodes subcutaneously over the spinal cord of the patient, sensing the one or more signals using the one or more electrodes placed subcutaneously over the spinal cord, and processing the sensed one or more signals using the test device. 
     In Example 27, the subject matter of Example 26 may optionally further include generating the neurostimulation energy using the test device and delivering the neurostimulation energy to the spinal cord using the one or more electrodes. 
     This Summary is an overview of some of the teachings of the present application and not intended to be an exclusive or exhaustive treatment of the present subject matter. Further details about the present subject matter are found in the detailed description and appended claims. Other aspects of the disclosure will be apparent to persons skilled in the art upon reading and understanding the following detailed description and viewing the drawings that form a part thereof, each of which are not to be taken in a limiting sense. The scope of the present disclosure is defined by the appended claims and their legal equivalents. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The drawings illustrate generally, by way of example, various embodiments discussed in the present document. The drawings are for illustrative purposes only and may not be to scale. 
         FIG.  1    illustrates an embodiment of a neurostimulation system. 
         FIG.  2    illustrates an embodiment of a stimulation device and a lead system, such as may be implemented in the neurostimulation system of  FIG.  1   . 
         FIG.  3    illustrates an embodiment of a programming device, such as may be implemented in the neurostimulation system of  FIG.  1   . 
         FIG.  4    illustrates an embodiment of an implantable pulse generator (IPG) and an implantable lead system, such as an example implementation of the stimulation device and lead system of  FIG.  2   . 
         FIG.  5    illustrates an embodiment of an IPG and an implantable lead system, such as the IPG and lead system of  FIG.  4   , arranged to provide neurostimulation to a patient. 
         FIG.  6    illustrates an embodiment of portions of a neurostimulation system. 
         FIG.  7    illustrates an embodiment of an implantable stimulator and one or more leads of an implantable neurostimulation system, such as the implantable neurostimulation system of  FIG.  6   . 
         FIG.  8    illustrates an embodiment of an external programming device of an implantable neurostimulation system, such as the implantable neurostimulation system of  FIG.  6   . 
         FIG.  9    illustrates an embodiment of portions of a neurostimulation trial system with an external sensing reference electrode. 
         FIG.  10    illustrates an embodiment of portions of a neurostimulation trial system with an implantable sensing reference electrode. 
         FIG.  11    illustrates an embodiment of portions of a neurostimulation trial system with a sensing reference electrode integrated into a stimulation lead. 
         FIG.  12    illustrates an embodiment of portions of a neurostimulation trial system with a sensing reference electrode attached to a stimulation lead. 
         FIG.  13    illustrates an embodiment of portions of a neurostimulation trial system with a sensing reference electrode attached to a lead introducer. 
         FIG.  14    illustrates an embodiment of an external trial stimulator (ETS) with sensing capabilities for use in a neurostimulation trial system, such as the neurostimulation trial system of any of  FIGS.  9 - 13   . 
         FIG.  15    illustrates an embodiment of a method for providing an interface between a patient and an ETS, such as the ETS of  FIG.  14     
     
    
    
     DETAILED DESCRIPTION 
     In the following detailed description, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustration specific embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that the embodiments may be combined, or that other embodiments may be utilized, and that structural, logical and electrical changes may be made without departing from the spirit and scope of the present invention. References to “an”, “one”, or “various” embodiments in this disclosure are not necessarily to the same embodiment, and such references contemplate more than one embodiment. The following detailed description provides examples, and the scope of the present invention is defined by the appended claims and their legal equivalents. 
     This document discusses, among other things, an external trial neurostimulation system with sensing and stimulation capabilities. In various embodiments, the external trial neurostimulation system can be used to evaluate a patient for potentially receiving a neuromodulation system that includes an implantable device configured to deliver a neurostimulation (also referred to as neuromodulation) therapy. Examples of such a neurostimulation therapy include, but are not limited to, deep brain stimulation (DBS), spinal cord stimulation (SCS), peripheral nerve stimulation (PNS), and vagus nerve stimulation (VNS). In this document, a “patient” includes a person receiving treatment delivered using a neurostimulation system according to the present subject matter, and a “user” includes a physician or other caregiver who treats the patient using the neurostimulation system. 
     The external trial neurostimulation system can use external equipment (that is to be placed externally to the patient&#39;s body) connected with percutaneous or implantable leads having electrodes placed inside the patient&#39;s body to assess potential effectiveness of a neurostimulation therapy. While SCS is discussed and illustrated as a specific example, the present subject matter can apply to any neurostimulation therapy for which the patient can benefit from the assessment of potential effectiveness using the external equipment. The external equipment can include biopotential sensing functions. Such biopotential sensing functions can include, for example, sensing functions that are available from an implantable device that delivers the neurostimulation therapy to be evaluated, such as an implantable neurostimulator including nerve signal sensing capability. It can be desirable to use the external trial neurostimulation system to emulate the sensing functions of the implantable device. 
     To sense signals arising within the patient&#39;s body using the external equipment, a reference voltage obtained from the patient&#39;s body is frequently used in the art to reduce common mode noise voltage differences between the patient&#39;s body and the external equipment. An external sensing reference electrode can be attached to the patient&#39;s skin to provide the reference voltage. However, if the external equipment is to remain connected to the patient for an extended period of time, e.g., hours or days, it can be advantageous to place an implantable electrode inside the patient&#39;s body for providing the reference voltage. This prevents the patient from wearing an external electrode on the skin for an extended period of time, which can be inconvenient to the patient while resulting in a poor referencing connection over the duration of the assessment that can last for hours to days with the patient carrying the external equipment during daily activities. An implantable lead or a percutaneous lead that can emulate the implantable lead with electrodes placed in the actual sensing and stimulation sites can be used such that the sensing and stimulation functions of the implantable device in the actual environment can be accurately evaluated. 
       FIG.  1    illustrates an embodiment of a neurostimulation system  100 . System  100  includes electrodes  106 , a stimulation device  104 , and a programming device  102 . Electrodes  106  are configured to be placed on or near one or more neural targets in a patient. Stimulation device  104  is configured to be electrically connected to electrodes  106  and deliver neurostimulation energy, such as in the form of electrical pulses, to the one or more neural targets though electrodes  106 . The delivery of the neurostimulation is controlled by using a plurality of stimulation parameters, such as stimulation parameters specifying a pattern of the electrical pulses and a selection of electrodes through which each of the electrical pulses is delivered. In various embodiments, at least some parameters of the plurality of stimulation parameters are programmable by a user, such as a physician or other caregiver who treats the patient using system  100 . Programming device  102  provides the user with accessibility to the user-programmable parameters. In various embodiments, programming device  102  is configured to be communicatively coupled to stimulation device via a wired or wireless link. 
     In this document, a “user” includes a physician or other clinician or caregiver who treats the patient using system  100 ; a “patient” includes a person who receives or is intended to receive neurostimulation delivered using system  100 . In various embodiments, the patient can be allowed to adjust his or her treatment using system  100  to certain extent, such as by adjusting certain therapy parameters and entering feedback and clinical effect information. 
     In various embodiments, programming device  102  can include a user interface  110  that allows the user to control the operation of system  100  and monitor the performance of system  100  as well as conditions of the patient including responses to the delivery of the neurostimulation. The user can control the operation of system  100  by setting and/or adjusting values of the user-programmable parameters. 
     In various embodiments, user interface  110  can include a graphical user interface (GUI) that allows the user to set and/or adjust the values of the user-programmable parameters by creating and/or editing graphical representations of various waveforms. Such waveforms can include, for example, a waveform representing a pattern of neurostimulation pulses to be delivered to the patient as well as individual waveforms that are used as building blocks of the pattern of neurostimulation pulses, such as the waveform of each pulse in the pattern of neurostimulation pulses. The GUI can also allow the user to set and/or adjust stimulation fields each defined by a set of electrodes through which one or more neurostimulation pulses represented by a waveform are delivered to the patient. The stimulation fields can each be further defined by the distribution of the current of each neurostimulation pulse in the waveform. In various embodiments, neurostimulation pulses for a stimulation period (such as the duration of a therapy session) can be delivered to multiple stimulation fields. 
     In various embodiments, system  100  can be configured for neurostimulation applications. User interface  110  can be configured to allow the user to control the operation of system  100  for neurostimulation. For example, system  100  as well as user interface  100  can be configured for DBS applications. Such DBS configuration includes various features that can simplify the task of the user in programming stimulation device  104  for delivering DBS to the patient, such as the features discussed in this document. 
       FIG.  2    illustrates an embodiment of a stimulation device  204  and a lead system  208 , such as may be implemented in neurostimulation system  100 . 
     Stimulation device  204  represents an example of stimulation device  104  and includes a stimulation output circuit  212  and a stimulation control circuit  214 . Stimulation output circuit  212  produces and delivers neurostimulation pulses. Stimulation control circuit  214  controls the delivery of the neurostimulation pulses from stimulation output circuit  212  using the plurality of stimulation parameters, which specifies a pattern of the neurostimulation pulses. Lead system  208  includes one or more leads each configured to be electrically connected to stimulation device  204  and a plurality of electrodes  206  distributed in the one or more leads. The plurality of electrodes  206  includes electrode  206 - 1 , electrode  206 - 2 , . . . electrode  206 -N, each a single electrically conductive contact providing for an electrical interface between stimulation output circuit  212  and tissue of the patient, where N≥2. The neurostimulation pulses are each delivered from stimulation output circuit  212  through a set of electrodes selected from electrodes  206 . In various embodiments, the neurostimulation pulses can include one or more individually defined pulses, and the set of electrodes can be individually definable by the user for each of the individually defined pulses or each of collections of pulse intended to be delivered using the same combination of electrodes. In various embodiments, one or more additional electrodes  207  (each of which may be referred to as a reference electrode) can be electrically connected to stimulation device  204 , such as one or more electrodes each being a portion of or otherwise incorporated onto a housing of stimulation device  204 . Monopolar stimulation uses a monopolar electrode configuration with one or more electrodes selected from electrodes  206  and at least one electrode from electrode(s)  207 . Bipolar stimulation uses a bipolar electrode configuration with two electrodes selected from electrodes  206  and none electrode(s)  207 . Multipolar stimulation uses a multipolar electrode configuration with multiple (two or more) electrodes selected from electrodes  206  and none of electrode(s)  207 . 
     In various embodiments, the number of leads and the number of electrodes on each lead depend on, for example, the distribution of target(s) of the neurostimulation and the need for controlling the distribution of electric field at each target. In one embodiment, lead system  208  includes 2 leads each having 8 electrodes. 
       FIG.  3    illustrates an embodiment of a programming device  302 , such as may be implemented in neurostimulation system  100 . Programming device  302  represents an example of programming device  102  and includes a storage device  318 , a programming control circuit  316 , and a user interface  310 . Programming control circuit  316  generates the plurality of stimulation parameters that controls the delivery of the neurostimulation pulses according to a specified neurostimulation program that can define, for example, stimulation waveform and electrode configuration. User interface  310  represents an example of user interface  110  and includes a stimulation control circuit  320 . Storage device  318  stores information used by programming control circuit  316  and stimulation control circuit  320 , such as information about a stimulation device that relates the neurostimulation program to the plurality of stimulation parameters. In various embodiments, stimulation control circuit  320  can be configured to support one or more functions allowing for programming of stimulation devices, such as stimulation device  104  including its various embodiments as discussed in this document, according to one or more selected neurostimulation programs as discussed in this document. 
     In various embodiments, user interface  310  can allow for definition of a pattern of neurostimulation pulses for delivery during a neurostimulation therapy session by creating and/or adjusting one or more stimulation waveforms using a graphical method. The definition can also include definition of one or more stimulation fields each associated with one or more pulses in the pattern of neurostimulation pulses. As used in this document, a “neurostimulation program” can include the pattern of neurostimulation pulses including the one or more stimulation fields, or at least various aspects or parameters of the pattern of neurostimulation pulses including the one or more stimulation fields. In various embodiments, user interface  310  includes a GUI that allows the user to define the pattern of neurostimulation pulses and perform other functions using graphical methods. In this document, “neurostimulation programming” can include the definition of the one or more stimulation waveforms, including the definition of one or more stimulation fields. 
     In various embodiments, circuits of neurostimulation  100 , including its various embodiments discussed in this document, may be implemented using a combination of hardware and software. For example, the circuit of user interface  110 , stimulation control circuit  214 , programming control circuit  316 , and stimulation control circuit  320 , including their various embodiments discussed in this document, may be implemented using an application-specific circuit constructed to perform one or more particular functions or a general-purpose circuit programmed to perform such function(s). Such a general-purpose circuit includes, but is not limited to, a microprocessor or a portion thereof, a microcontroller or portions thereof, and a programmable logic circuit or a portion thereof. 
       FIG.  4    illustrates an embodiment of an implantable pulse generator (IPG)  404  and an implantable lead system  408 . IPG  404  represents an example implementation of stimulation device  204 . Lead system  408  represents an example implementation of lead system  208 . As illustrated in  FIG.  4   , IPG  404  that can be coupled to implantable leads  408 A and  408 B at a proximal end of each lead. The distal end of each lead includes electrical contacts or electrodes  406  for contacting a tissue site targeted for electrical neurostimulation. As illustrated in  FIG.  1   , leads  408 A and  408 B each include 8 electrodes  406  at the distal end. The number and arrangement of leads  408 A and  408 B and electrodes  406  as shown in  FIG.  1    are only an example, and other numbers and arrangements are possible. In various embodiments, the electrodes are ring electrodes. The implantable leads and electrodes can be configured by shape and size to provide electrical neurostimulation energy to a neuronal target included in the subject&#39;s brain or configured to provide electrical neurostimulation energy to a nerve cell target included in the subject&#39;s spinal cord. 
       FIG.  5    illustrates an implantable neurostimulation system  500  and portions of an environment in which system  500  can be used. System  500  includes an implantable system  521 , an external system  502 , and a telemetry link  540  providing for wireless communication between implantable system  521  and external system  502 . Implantable system  521  is illustrated in  FIG.  5    as being implanted in the patient&#39;s body  599 . 
     Implantable system  521  includes an implantable stimulator (also referred to as an implantable pulse generator, or IPG)  504 , a lead system  508 , and electrodes  506 , which represent an example of stimulation device  204 , lead system  208 , and electrodes  206 , respectively. External system  502  represents an example of programming device  302 . In various embodiments, external system  502  includes one or more external (non-implantable) devices each allowing the user and/or the patient to communicate with implantable system  521 . In some embodiments, external  502  includes a programming device intended for the user to initialize and adjust settings for implantable stimulator  504  and a remote control device intended for use by the patient. For example, the remote control device can allow the patient to turn implantable stimulator  504  on and off and/or adjust certain patient-programmable parameters of the plurality of stimulation parameters. 
     The sizes and sharps of the elements of implantable system  521  and their location in body  599  are illustrated by way of example and not by way of restriction. An implantable system is discussed as a specific application of the programming according to various embodiments of the present subject matter. In various embodiments, the present subject matter can be applied in programming any type of stimulation device that uses electrical pulses as stimuli, regarding less of stimulation targets in the patient&#39;s body and whether the stimulation device is implantable. 
     Returning to  FIG.  4   , the IPG  404  can include a hermetically-sealed IPG case  422  to house the electronic circuitry of IPG  404 . IPG  404  can include an electrode  426  formed on IPG case  422 . IPG  404  can include an IPG header  424  for coupling the proximal ends of leads  408 A and  408 B. IPG header  424  can optionally also include an electrode  428 . Electrodes  426  and/or  428  represent embodiments of electrode(s)  207  and can each be referred to as a reference electrode. 
     Neurostimulation energy can be delivered in a monopolar (also referred to as unipolar) mode using electrode  426  or electrode  428  and one or more electrodes selected from electrodes  406 . Neurostimulation energy can be delivered in a bipolar mode using a pair of electrodes of the same lead (lead  408 A or lead  408 B). Neurostimulation energy can be delivered in an extended bipolar mode using one or more electrodes of a lead (e.g., one or more electrodes of lead  408 A) and one or more electrodes of a different lead (e.g., one or more electrodes of lead  408 B). 
     The electronic circuitry of IPG  404  can include a control circuit that controls delivery of the neurostimulation energy. The control circuit can include a microprocessor, a digital signal processor, application specific integrated circuit (ASIC), or other type of processor, interpreting or executing instructions included in software or firmware. The neurostimulation energy can be delivered according to specified (e.g., programmed) modulation parameters. Examples of setting modulation parameters can include, among other things, selecting the electrodes or electrode combinations used in the stimulation, configuring an electrode or electrodes as the anode or the cathode for the stimulation, specifying the percentage of the neurostimulation provided by an electrode or electrode combination, and specifying stimulation pulse parameters. Examples of pulse parameters include, among other things, the amplitude of a pulse (specified in current or voltage), pulse duration (e.g., in microseconds), pulse rate (e.g., in pulses per second), and parameters associated with a pulse train or pattern such as burst rate (e.g., an “on” modulation time followed by an “off” modulation time), amplitudes of pulses in the pulse train, polarity of the pulses, etc. 
       FIG.  6    illustrates an embodiment of portions of a neurostimulation system  600 . System  600  includes an IPG  604 , implantable neurostimulation leads  608 A and  608 B, an external remote controller (RC)  632 , a clinician&#39;s programmer (CP)  630 , and an external trial stimulator (ETS, also referred to as external trial modulator, or ETM)  634 . IPG  404  can be electrically coupled to leads  608 A and  608 B directly. In various embodiments in which ETS  634  includes sensing capabilities, a sensing reference electrode  660  connected to a sensing wire  662  is provided. ETS  634  can be electrically connected to each of leads  608 A and  608 B and sensing wire  662  directly or via extension cable  636  and/or external cable  638 . Various embodiments of sensing reference electrode  660  with sensing wire  662  are discussed below, with reference to  FIGS.  9 - 13   . 
     System  600  represents an example of system  100 , with IPG  604  representing an embodiment of stimulation device  104 , electrodes  606  of leads  608 A and  608 B representing electrodes  106 , and CP  630 , RC  632 , and ETS  634  collectively representing programming device  102 . 
     ETS  634  can be standalone or incorporated into CP  630 . ETS  634  can have similar pulse generation circuitry as IPG  604  to deliver neurostimulation energy according to specified modulation parameters as discussed above. ETS  634  is an external device that is typically used as a preliminary stimulator after leads  408 A and  408 B have been implanted and used prior to stimulation with IPG  604  to test the patient&#39;s responsiveness to the stimulation that is to be provided by IPG  604 . Because ETS  634  is external it can be more easily configurable than IPG  604 . 
     CP  630  can configure the neurostimulation provided by ETS  634 . If ETS  634  is not integrated into CP  630 , CP  630  can communicate with ETS  634  using a wired connection (e.g., over a USB link) or by wireless telemetry using a wireless communications link  640 . CP  630  also communicates with IPG  604  using a wireless communications link  640 . 
     An example of wireless telemetry is based on inductive coupling between two closely-placed coils using the mutual inductance between these coils. This type of telemetry is referred to as inductive telemetry or near-field telemetry because the coils must typically be closely situated for obtaining inductively coupled communication. IPG  604  can include the first coil and a communication circuit. CP  630  can include or otherwise electrically connected to the second coil such as in the form of a wand that can be place near IPG  604 . Another example of wireless telemetry includes a far-field telemetry link, also referred to as a radio frequency (RF) telemetry link. A far-field, also referred to as the Fraunhofer zone, refers to the zone in which a component of an electromagnetic field produced by the transmitting electromagnetic radiation source decays substantially proportionally to 1/r, where r is the distance between an observation point and the radiation source. Accordingly, far-field refers to the zone outside the boundary of r=λ/2π, where λ is the wavelength of the transmitted electromagnetic energy. In one example, a communication range of an RF telemetry link is at least six feet but can be as long as allowed by the particular communication technology. RF antennas can be included, for example, in the header of IPG  604  and in the housing of CP  630 , eliminating the need for a wand or other means of inductive coupling. An example is such an RF telemetry link is a Bluetooth® wireless link. 
     CP  630  can be used to set modulation parameters for the neurostimulation after IPG  604  has been implanted. This allows the neurostimulation to be tuned if the requirements for the neurostimulation change after implantation. CP  630  can also upload information from IPG  604 . 
     RC  632  also communicates with IPG  604  using a wireless link  340 . RC  632  can be a communication device used by the user or given to the patient. RC  632  can have reduced programming capability compared to CP  630 . This allows the user or patient to alter the neurostimulation therapy but does not allow the patient full control over the therapy. For example, the patient may be able to increase the amplitude of neurostimulation pulses or change the time that a preprogrammed stimulation pulse train is applied. RC  632  can be programmed by CP  630 . CP  630  can communicate with the RC  632  using a wired or wireless communications link. In some embodiments, CP  630  can program RC  632  when remotely located from RC  632 . 
       FIG.  7    illustrates an embodiment of implantable stimulator  704  and one or more leads  708  of an implantable neurostimulation system, such as implantable system  600 . Implantable stimulator  704  represents an example of stimulation device  104  or  204  and can be implemented, for example, as IPG  604 . Lead(s)  708  represents an example of lead system  208  and can be implemented, for example, as implantable leads  608 A and  608 B. Lead(s)  708  includes electrodes  706 , which represents an example of electrodes  106  or  206  and can be implemented as electrodes  606 . 
     Implantable stimulator  704  can include a sensing circuit  742  that is optional and required when the stimulator needs a sensing capability, stimulation output circuit  212 , a stimulation control circuit  714 , an implant storage device  746 , an implant telemetry circuit  744 , a power source  748 , and one or more electrodes  707 . Sensing circuit  742 , when included and needed, senses one or more physiological signals for purposes of patient monitoring and/or feedback control of the neurostimulation. Examples of the one or more physiological signals include neural and other biopotential signals each indicative of a condition of the patient that is treated by the neurostimulation and/or a response of the patient to the delivery of the neurostimulation. Stimulation output circuit  212  is electrically connected to electrodes  706  through one or more leads  708  as well as electrodes  707  and delivers each of the neurostimulation pulses through a set of electrodes selected from electrodes  706  and electrode(s)  707 . Stimulation control circuit  714  represents an example of stimulation control circuit  214  and controls the delivery of the neurostimulation pulses using the plurality of stimulation parameters specifying the pattern of neurostimulation pulses. In one embodiment, stimulation control circuit  714  controls the delivery of the neurostimulation pulses using the one or more sensed physiological signals. Implant telemetry circuit  744  provides implantable stimulator  704  with wireless communication with another device such as CP  630  and RC  632 , including receiving values of the plurality of stimulation parameters from the other device. Implant storage device  746  can store one or more neurostimulation programs and values of the plurality of stimulation parameters for each of the one or more neurostimulation programs. Power source  748  provides implantable stimulator  704  with energy for its operation. In one embodiment, power source  748  includes a battery. In one embodiment, power source  748  includes a rechargeable battery and a battery charging circuit for charging the rechargeable battery. Implant telemetry circuit  744  can also function as a power receiver that receives power transmitted from an external device through an inductive couple. Electrode(s)  707  allow for delivery of the neurostimulation pulses in the monopolar mode. Examples of electrode(s)  707  include electrode  426  and electrode  418  in IPG  404  as illustrated in  FIG.  4   . 
     In one embodiment, implantable stimulator  704  is used as a master database. A patient implanted with implantable stimulator  704  (such as may be implemented as IPG  604 ) can therefore carry patient information needed for his or her medical care when such information is otherwise unavailable. Implant storage device  746  is configured to store such patient information. For example, the patient can be given a new RC  632  and/or travel to a new clinic where a new CP  630  is used to communicate with the device implanted in him or her. The new RC  632  and/or CP  630  can communicate with implantable stimulator  704  to retrieve the patient information stored in implant storage device  746  through implant telemetry circuit  744  and wireless communication link  640  and allow for any necessary adjustment of the operation of implantable stimulator  704  based on the retrieved patient information. In various embodiments, the patient information to be stored in implant storage device  746  can include, for example, positions of lead(s)  708  and electrodes  706  relative to the patient&#39;s anatomy (transformation for fusing computerized tomogram (CT) of post-operative lead placement to magnetic resonance imaging (MRI) of the brain), clinical effect map data, objective measurements using quantitative assessments of symptoms (for example using micro-electrode recording, accelerometers, and/or other sensors), and/or any other information considered important or useful for providing adequate care for the patient. In various embodiments, the patient information to be stored in implant storage device  746  can include data transmitted to implantable stimulator  704  for storage as part of the patient information and data acquired by implantable stimulator  704 , such as by using sensing circuit  742 . 
     In various embodiments, sensing circuit  742  (if included), stimulation output circuit  212 , stimulation control circuit  714 , implant telemetry circuit  744 , implant storage device  746 , and power source  748  are encapsulated in a hermetically sealed implantable housing or case, and electrode(s)  707  are formed or otherwise incorporated onto the case. In various embodiments, lead(s)  708  are implanted such that electrodes  706  are placed on and/or around one or more targets to which the neurostimulation pulses are to be delivered, while implantable stimulator  704  is subcutaneously implanted and connected to lead(s)  708  at the time of implantation. 
       FIG.  8    illustrates an embodiment of an external programming device  802  of an implantable neurostimulation system, such as system  600 . External programming device  802  represents an example of programming device  102  or  302 , and can be implemented, for example, as CP  630  and/or RC  632 . External programming device  802  includes an external telemetry circuit  852 , an external storage device  818 , a programming control circuit  816 , and a user interface  810 . 
     External telemetry circuit  852  provides external programming device  802  with wireless communication with another device such as implantable stimulator  704  via wireless communication link  640 , including transmitting the plurality of stimulation parameters to implantable stimulator  704  and receiving information including the patient data from implantable stimulator  704 . In one embodiment, external telemetry circuit  852  also transmits power to implantable stimulator  704  through an inductive couple. 
     In various embodiments, wireless communication link  640  can include an inductive telemetry link (near-field telemetry link) and/or a far-field telemetry link (RF telemetry link). For example, because DBS is often indicated for movement disorders which are assessed through patient activities, gait, balance, etc., allowing patient mobility during programming and assessment is useful. Therefore, when system  600  is intended for applications including DBS, wireless communication link  640  includes at least a far-field telemetry link that allows for communications between external programming device  802  and implantable stimulator  704  over a relative long distance, such as up to about 20 meters. External telemetry circuit  852  and implant telemetry circuit  744  each include an antenna and RF circuitry configured to support such wireless telemetry. 
     External storage device  818  stores one or more stimulation waveforms for delivery during a neurostimulation therapy session, such as a DBS therapy session, as well as various parameters and building blocks for defining one or more waveforms. The one or more stimulation waveforms can each be associated with one or more stimulation fields and represent a pattern of neurostimulation pulses to be delivered to the one or more stimulation field during the neurostimulation therapy session. In various embodiments, each of the one or more stimulation waveforms can be selected for modification by the user and/or for use in programming a stimulation device such as implantable stimulator  704  to deliver a therapy. In various embodiments, each waveform in the one or more stimulation waveforms is definable on a pulse-by-pulse basis, and external storage device  818  can include a pulse library that stores one or more individually definable pulse waveforms each defining a pulse type of one or more pulse types. External storage device  818  also stores one or more individually definable stimulation fields. Each waveform in the one or more stimulation waveforms is associated with at least one field of the one or more individually definable stimulation fields. Each field of the one or more individually definable stimulation fields is defined by a set of electrodes through a neurostimulation pulse is delivered. In various embodiments, each field of the one or more individually definable fields is defined by the set of electrodes through which the neurostimulation pulse is delivered and a current distribution of the neurostimulation pulse over the set of electrodes. In one embodiment, the current distribution is defined by assigning a fraction of an overall pulse amplitude to each electrode of the set of electrodes. Such definition of the current distribution may be referred to as “fractionalization” in this document. In another embodiment, the current distribution is defined by assigning an amplitude value to each electrode of the set of electrodes. For example, the set of electrodes can include 2 electrodes used as the anode and an electrode as the cathode for delivering a neurostimulation pulse having a pulse amplitude of 4 mA. The current distribution over the 2 electrodes used as the anode needs to be defined. In one embodiment, a percentage of the pulse amplitude is assigned to each of the 2 electrodes, such as 75% assigned to electrode 1 and 25% to electrode 2. In another embodiment, an amplitude value is assigned to each of the 2 electrodes, such as 3 mA assigned to electrode 1 and 1 mA to electrode 2. Control of the current in terms of percentages allows precise and consistent distribution of the current between electrodes even as the pulse amplitude is adjusted. It is suited for thinking about the problem as steering a stimulation locus, and stimulation changes on multiple contacts simultaneously to move the locus while holding the stimulation amount constant. Control and displaying the total current through each electrode in terms of absolute values (e.g. mA) allows precise dosing of current through each specific electrode. It is suited for changing the current one contact at a time (and allows the user to do so) to shape the stimulation like a piece of clay (pushing/pulling one spot at a time). 
     Programming control circuit  816  represents an example of programming control circuit  316  and generates the plurality of stimulation parameters, which is to be transmitted to implantable stimulator  704 , based on a specified neurostimulation program (e.g., the pattern of neurostimulation pulses as represented by one or more stimulation waveforms and one or more stimulation fields, or at least certain aspects of the pattern). The neurostimulation program can be created and/or adjusted by the user using user interface  810  and stored in external storage device  818 . In various embodiments, programming control circuit  816  can check values of the plurality of stimulation parameters against safety rules to limit these values within constraints of the safety rules. In one embodiment, the safety rules are heuristic rules. 
     User interface  810  represents an example of user interface  310  and allows the user to define the pattern of neurostimulation pulses and perform various other monitoring and programming tasks. User interface  810  includes a display screen  856 , a user input device  858 , and an interface control circuit  854 . Display screen  856  can include any type of interactive or non-interactive screens, and user input device  858  can include any type of user input devices that supports the various functions discussed in this document, such as touchscreen, keyboard, keypad, touchpad, trackball, joystick, and mouse. In one embodiment, user interface  810  includes a GUI. The GUI can also allow the user to perform any functions discussed in this document where graphical presentation and/or editing are suitable as can be appreciated by those skilled in the art. 
     Interface control circuit  854  controls the operation of user interface  810  including responding to various inputs received by user input device  858  and defining the one or more stimulation waveforms. Interface control circuit  854  includes stimulation control circuit  320 . 
     In various embodiments, external programming device  802  can have operation modes including a composition mode and a real-time programming mode. Under the composition mode (also known as the pulse pattern composition mode), user interface  810  is activated, while programming control circuit  816  is inactivated. Programming control circuit  816  does not dynamically updates values of the plurality of stimulation parameters in response to any change in the one or more stimulation waveforms. Under the real-time programming mode, both user interface  810  and programming control circuit  816  are activated. Programming control circuit  816  dynamically updates values of the plurality of stimulation parameters in response to changes in the set of one or more stimulation waveforms and transmits the plurality of stimulation parameters with the updated values to implantable stimulator  704 . 
       FIG.  9    illustrates an embodiment of portions of a neurostimulation trial system  900 . System  900  allows for percutaneously delivering neurostimulation energy to a patient and sensing one or more signal from the patient using externally equipment during a neurostimulation trial. System  900  can be used in a neurostimulation trial to emulate functions of an implantable system such as implantable system  521  for evaluate effectiveness of the functions in treating the patient. Purposes of the neurostimulation trial can include, for example, determining whether the patient should be treated using the implantable system and/or setting parameters for the treatment. In the illustrated embodiment, system  900  includes a stimulation lead  908 , a sensing reference electrode  960  connected to a sensing wire  962 , a sensing ETS (i.e., an ETS with sensing capabilities)  934 , and a cable assembly  972 . The illustrated “TISSUE” represents portions of the body tissue of the patient including where the neurostimulation energy is delivered to and the one or more signals are sensing from and where an incision is made for inserting portions of system  900  into the patient. 
     Stimulation lead  908  has a lead distal end  967 , a lead proximal end  969 , and an elongate lead body  968  coupled between lead distal end  967  and lead proximal end  969 . In this document, “distal” and “proximal” are relative to sensing ETS  934  when the components of system  900  are connected as illustrated in  FIGS.  9 - 13   . Lead distal end  967  includes one or more electrodes  906  each useable for delivering the neurostimulation energy and/or sensing a signal. Lead proximal end  969  includes a lead connector  970 . Lead connector  970  includes one or more electrode contacts electrically connected to one or more electrodes  906  via one or more lead conductors (not shown). The one or more lead conductors each extend within elongate lead body  968  to provide the electrical connection between an electrode of one or more electrodes  906  and an electrode contact of the one or more electrode contacts. In one embodiment, stimulation lead  908  is an implantable lead, such as an implantable lead of the same type potentially used in the implantable system potentially received by the patient (e.g., any lead of lead system  208  or  508  or any of lead  408 A,  408 B,  608 A,  608 B, and  708 ). One example of such an implantable lead includes a linear array of electrodes disposed on the lead. During the neurostimulation trial, a portion of stimulation lead including lead distal end  967  are percutaneously introduced into the patient and temporarily placed in the patient. In another embodiment, stimulation lead  908  is a percutaneous lead that is similar to the implantable lead but made for temporary use. Materials for stimulation lead  908  are selected to make the lead compatible with one or more sterilization processes. Such one or more sterilization processes are required for preparing stimulation lead  908  for use with the patient. 
     Sensing reference electrode  960  is used to provide a reference voltage for sensing the one or more signals using sensing ETS  934 . In the illustrated embodiment, sensing reference electrode  960  is suitable for attachment to the patient&#39;s skin. When such skin attachment is undesirable (e.g., because it is inconvenient for the patient and/or difficult to maintain a reliable electrical connection over the duration of the neurostimulaton trial), an implantable sensing reference electrode can be provided, as further discussed with reference to  FIGS.  10 - 13   . 
     Sensing wire  962  has a wire distal end  961  connected to sensing referenced electrode  960 , a wire proximal end  963  including a wire connector  965  for connecting to cable assembly  972 , and an elongate wire body  964  coupled between wire distal end  961  and wire proximal end  963 . Wire connector  965  includes a sensing reference electrode contact electrically connected to sensing reference electrode  960 . A wire conductor extending within elongate wire body  964  provides the electrical connection between sensing reference electrode  960  and the sensing reference electrode contact. 
     Sensing ETS  934  can delivering the neurostimulation energy and sense the one or more signals using one or more electrodes  906  and sensing reference electrode  960 . Sensing ETS  934  includes an ETS connector  984  to provide for electrical connections to stimulation lead  908  and sensing wire  962  through cable assembly  972 . ETS connector  984  can be constructed as a single connector with multiple electrical contacts or multiple connectors. In the illustrated embodiment, ETS connector  984  includes a reference contact  985  and two sensing and stimulation (SENS/STIM) contacts  986  (SENS/STIM 1) and  987  (SENS/STIM 2). Reference contact  985  is for the electrical connection to sensing wire  962  through cable assembly  972 . Sensing and stimulation contacts  986  and  987  can each provide for the electrical connection(s) to a stimulation lead, such as stimulation lead  908 , through cable assembly  972 . Sensing and stimulation contacts  986  and  987  can each includes a multi-contact group allowing for separate electrical connections each for an electrode of multiple electrodes on a stimulation lead. In each of  FIGS.  9 - 13   , a neurostimulation trial system that can accommodate two stimulation leads such as stimulation lead  908 , with one stimulation lead used, is illustrated as a specific example. Various embodiments of the present subject matter can accommodate and use any number of stimulation leads as practically needed for the neurostimulation trial (e.g., the same number of stimulation leads used in the implantable system evaluated for the patient). 
     Cable assembly  972  can provide electrical connections between sensing ETS  934  and stimulation lead  908  and an electrical connection between sensing ETS  934  and sensing wire  962 . The electrical connections between sensing ETS  934  and stimulation lead  908  allow the neurostimulation energy to be transmitted from ETS connector  984  to lead connector  970  and allow the sensed one or more signals to be transmitted from lead connector  970  to ETS connector  984 . The electrical connection between sensing ETS  934  and sensing wire  962  allows sensing ETS  934  to receive the reference voltage from wire connector  965 . Cable assembly  972  can represent an example of the interface between ETS  634  and leads  608 A and  608 B and sensing wire  662  in system  600 , which as illustrated in  FIG.  6    includes extension cable  636  and external cable  638 . 
     Cable assembly  972  can include a cable connector  973  (also known as an operation room cable connector) and a cable  978  (also known as an operation room cable). In the illustrated embodiment, cable connector  973  includes two sensing and stimulation (SENS/STIM) contacts  975  and  976  each to contact lead connector  970  of a stimulation lead such as stimulation lead  908 . In various embodiments, cable connector  973  includes any number of sensing and stimulation contacts  975  and  976  that is needed for the neurostimulation trial. Cable connector  973  further includes a reference contact  974  to contact wire connector  965  of sensing wire  962 . Sensing and stimulation contacts  975  and  976  and reference contact  974  can be configured in various ways for providing the required electrical connections. For example, sensing and stimulation contacts  975  and  976  and reference contact  974  can include physically separated connectors each to mate one of lead connector  970  or wire connector  965 . Alternatively, sensing and stimulation contacts  975  and  976  and reference contact  974  can be physically integrated into a single connector. Cable  978  has a cable distal end  979  connected to cable connector  973 , a cable proximal end  981  including a device connector  982  to be connected to sensing ETS  934 , and an elongate cable body coupled between cable distal end  979  and cable proximal end  981 . Cable  978  includes cable conductors allowing for the transmission of the neurostimulation energy from ETS connector  984  to cable connector  973  and allowing for the transmission of the sensed one or more signals from cable connector  973  to ETS connector  984 . In one embodiment, cable distal end  979  can be detached from cable connector  973 , such that cable  978  and cable connector  973  are separate devices that can be detachably connected. In another embodiment, cable distal end  979  is permanently affixed to cable connector  973 , such that cable assembly  972  includes an integrated single device. 
     Cable assembly  972  can represent an example of a connection system configured to be placed outside the patient, to mate lead connector  970 , to mate wire connector  965 , and to provide electrical connections between lead connector  970  and sensing ETS  934  and between wire connector  965  and sensing ETS  934 . In various embodiments, the connection system can include any structure providing for necessary electrical connections between lead connector  970  and circuitry of sensing ETS  934  and between wire connector  965  and circuitry of sensing ETS  934  to allow for the percutaneously delivery of neurostimulation energy to the patient and the sensing of one or more signal from the patient. In various embodiments, the connection system is external to sensing ETS  934 . In various other embodiments, the connection system is included in sensing ETS  934 . In various embodiments, the connection system is affixed to or otherwise integrated with sensing ETS  934 . In various other embodiments, the connection system can be detachably connected to sensing ETS  934 . 
       FIG.  10    illustrates an embodiment of portions of a neurostimulation trial system  1000 . System  1000  includes the elements and connections of system  900  except for that sensing reference electrode  960  with sensing wire  962  is replaced by a sensing reference electrode  1060  with a sensing wire  1062 . Sensing reference electrode  1060  is an implantable sensing reference electrode made of biocompatible materials suitable for subcutaneous placement in the patient, with one or more electrode contacts made of electrically conductive and biocompatible material such as platinum. 
     Sensing wire  1062  has a wire distal end  1061  connected to sensing referenced electrode  1060 , a wire proximal end  1063  including a wire connector  1065  for connecting to cable assembly  972 , and an elongate wire body  1064  coupled between wire distal end  1061  and wire proximal end  1063 . Wire connector  1065  includes a sensing reference electrode contact electrically connected to sensing reference electrode  1060 . A wire conductor extending within elongate wire body  1064  provides the electrical connection between sensing reference electrode  1060  and the sensing reference electrode contact. 
     Sensing reference electrode  1060  can be inserted into the tissue through the incision made for inserting the portion of stimulation lead  908  including lead distal end  967  into the tissue. Then sensing reference electrode  1060  is subcutaneously placed to provide sensing ETS  934  with the reference voltage for sensing the one or more signals during the neurostimulation trial. 
     Materials for sensing reference electrode  1060 , elongate wire body  1064 , and wire connector  1065  are selected to be compatible with one or more sterilization processes. Such one or more sterilization processes are required for preparing stimulation lead  908  and sensing reference electrode  1060  with sensing wire  1062  for use with the patient. 
       FIG.  11    illustrates an embodiment of portions of a neurostimulation trial system  1100 . System  1100  includes the elements and connections of system  900  except for that sensing reference electrode  960  with sensing wire  962  is replaced by a sensing reference electrode  1160  with a sensing wire  1162 . Sensing reference electrode  1160  is an implantable sensing reference electrode made of biocompatible materials suitable for subcutaneous placement in the patient, with one or more electrode contacts made of electrically conductive and biocompatible material such as platinum. 
     Sensing reference electrode  1160  is integrated into lead elongate body  968  of lead  908 , for example as a ring electrode, and positioned such that when one or more electrodes  906  are placed in the intended site, sensing reference electrode  1160  is in a subcutaneous location suitable for providing the reference voltage for sensing the one or more signals from the patient. In various embodiments, the integration of sensing reference electrode  1160  into stimulation lead  908  does not substantially change the size of stimulation lead  908  (e.g., diameter of lead elongate body  968  when measured with sensing reference electrode  1160 ). 
     Sensing wire  1162  has a wire distal end  1161  connected to sensing referenced electrode  1160 , a wire proximal end  1163  including a wire connector  1165  for connecting to cable assembly  972 , and an elongate wire body  1164  coupled between wire distal end  1161  and wire proximal end  1163 . Wire connector  1165  includes a sensing reference electrode contact electrically connected to sensing reference electrode  1160 . A wire conductor extending within elongate wire body  1164  provides the electrical connection between sensing reference electrode  1160  and the sensing reference electrode contact. In some embodiments, at least a portion of sensing wire  1162  can be integrated into stimulation lead  908 . For example, sensing wire  1162  can be fully integrated into stimulation lead  908 , with wire connector  1165  integrated into lead connector  970 . Sensing wire  1162  can also be partially integrated into stimulation lead  908 , with wire connector  1165  being separate from lead connector  970 . Sensing wire  1162  can also be separate from stimulation lead  908 , with only wire distal end  1161  connected to sensing reference electrode  1160 . Wire distal end  1161  can be releasably connected to sensing reference electrode  1160 , if desirable, for example when stimulation lead  908  is intended to be used as part of a permanently or chronically implanted system that may be used to treat the patient as a result of the neurostimulation trial. 
     Sensing reference electrode  1160  is to be inserted into the tissue with stimulation lead  908  including lead distal end  967  being inserted into the tissue. Then sensing reference electrode  1160  is subcutaneously placed to provide sensing ETS  934  with the reference voltage for sensing the one or more signals during the neurostimulation trial. 
     Materials for sensing reference electrode  1160 , elongate wire body  1164 , and wire connector  1165  are selected to be compatible with one or more sterilization processes. Such one or more sterilization processes are required for preparing stimulation lead  908  with sensing reference electrode  1160  and sensing wire  1162  for use with the patient. 
       FIG.  12    illustrates an embodiment of portions of a neurostimulation trial system  1200 . System  1200  includes the elements and connections of system  900  except for that sensing reference electrode  960  with sensing wire  962  is replaced by a sensing reference electrode  1260  with a sensing wire  1262 . Sensing reference electrode  1260  is an implantable sensing reference electrode made of biocompatible materials suitable for subcutaneous placement in the patient, with one or more electrode contacts made of electrically conductive and biocompatible material such as platinum. 
     Sensing reference electrode  1260  is attached to lead elongate body  968  of lead  908  and positioned such that when one or more electrodes  906  are placed in the intended site, sensing reference electrode  1260  is in a subcutaneous location suitable for providing the reference voltage for sensing the one or more signals from the patient. In one embodiment, sensing reference electrode  1260  is detachably attached to lead elongate body  968 . In another embodiment, sensing reference electrode  1260  is permanently affixed to lead elongate body  968 . 
     Sensing wire  1262  has a wire distal end  1261  connected to sensing referenced electrode  1260 , a wire proximal end  1263  including a wire connector  1265  for connecting to cable assembly  972 , and an elongate wire body  1264  coupled between wire distal end  1261  and wire proximal end  1263 . Wire connector  1265  includes a sensing reference electrode contact electrically connected to sensing reference electrode  1260 . A wire conductor extending within elongate wire body  1264  provides the electrical connection between sensing reference electrode  1260  and the sensing reference electrode contact. In some embodiments, at least a portion of sensing wire  1262  can be also attached to stimulation lead  908 . For example, a portion of sensing wire  1262  can be attached to stimulation lead  908 , with wire connector  1265  being separate from lead connector  970 . Sensing wire  1262  can also be separate from stimulation lead  908 , with only wire distal end  1261  connected to sensing reference electrode  1260 . Wire distal end  1161  can be releasably connected to sensing reference electrode  1160 , if desirable, for example when stimulation lead  908  is intended to be used as part of the implantable system that may be used to treat the patient as a result of the neurostimulation trial. 
     Also shown in  FIG.  12    is a lead introducer  1290  that can be used to assist with the insertion of the portions of stimulation lead  908  into the patient. Lead introducer  1290  includes an introducer distal end  1291  to enter the tissue of the patient, an introducer proximal end  1293 , and an elongate introducer body  1292  coupled between introducer distal end  1291  and introducer proximal end  1293 . A lumen  1294  extends within elongate introducer body  1292  from an introducer distal opening at or near introducer distal end  1291  and an introducer proximal opening at or near introducer proximal end  1293 . Lumen  1294  can accommodate a portion of stimulation lead  908  and can allow lead distal end  967  to enter the introducer primary opening and exit from the introducer distal opening. In one embodiment, introducer distal end  1291  includes a sharp tip to pierce the tissue. In one embodiment, lead introducer  1290  is in a form of a hollow needle. In various embodiments, lead introducer  1290  is to be removed from the tissue after stimulation lead  908  is placed and before the neurostimulation energy is delivered and the one or more signals are sensed. 
     Sensing reference electrode  1260  is to be inserted into the tissue with stimulation lead  908  including lead distal end  967  being inserted into the tissue using lead introducer  1290 . After lead introducer  1290  is removed from the tissue, sensing reference electrode  1260  contacts the tissue, providing sensing ETS  934  with the reference voltage for sensing the one or more signals during the neurostimulation trial. Thus, sensing reference electrode  1260  when attached on lead elongate body  968  and a portion of sensing wire  1262  are configured to fit through lumen  1294  to allow for the insertion of the portions of stimulation lead  908  into the tissue and the removal of lead introducer  1290  from the tissue. In one embodiment, sensing reference electrode  1260  and lumen  1294  have sizes allowing for slipping lead introducer  1290  off over stimulation lead  908  and sensing wire  1262  (including passing lead proximal end  969  and wire proximal end  1263  through lumen  1294 ). In another embodiment, lead introducer  1290  includes at least a portion having peel-off capability to allow for removal from stimulation lead  908  and sensing wire  1261  without passing lead proximal end  969  and wire proximal end  1263  through lumen  1294 ). 
     Materials for sensing reference electrode  1260 , elongate wire body  1264 , and wire connector  1265 , as well as materials for lead introducer  1290 , are selected to be compatible with one or more sterilization processes. Such one or more sterilization processes are required for preparing stimulation lead  908 , sensing reference electrode  1260  with sensing wire  1262 , and lead introducer  1290  for use with the patient. 
       FIG.  13    illustrates an embodiment of portions of a neurostimulation trial system  1300 . System  1300  includes the elements and connections of system  900  except for that sensing reference electrode  960  with sensing wire  962  is replaced by a sensing reference electrode  1360  with a sensing wire  1362 . Sensing reference electrode  1360  is an implantable sensing reference electrode made of biocompatible materials suitable for subcutaneous placement in the patient, with one or more electrode contacts made of electrically conductive and biocompatible material such as platinum. Sensing reference electrode  1360  is detachably attached to lead introducer  1290  in a manner allowing it to be positioned in a subcutaneous location suitable for providing the reference voltage for sensing the one or more signals from the patient after lead introducer is removed from the tissue. In the illustrated embodiment, sensing reference electrode  1360  is detachably attached to elongate introducer body  1292  of lead introducer  1290  using a releasable clip  1396  and a release handle  1397 . Releasable clip  1396  allows sensing reference electrode  1360  to be detached from elongate introducer body  1292  after sensing reference electrode  1360  is in place and before lead introducer  1290  is removed from the tissue. Release handle  1397  can be used to release sensing reference electrode  1360  from releasable clip  1396 . 
     Sensing wire  1362  has a wire distal end  1361  connected to sensing referenced electrode  1360 , a wire proximal end  1363  including a wire connector  1365  for connecting to cable assembly  972 , and an elongate wire body  1364  coupled between wire distal end  1361  and wire proximal end  1363 . Wire connector  1365  includes a sensing reference electrode contact electrically connected to sensing reference electrode  1360 . A wire conductor extending within elongate wire body  1364  provides the electrical connection between sensing reference electrode  1360  and the sensing reference electrode contact. 
     Sensing reference electrode  1360  is to be inserted into the tissue with a substantial portion of lead introducer  1290  including introducer distal end  1291  being inserted into the tissue. After lead introducer  1290  is removed from the tissue, sensing reference electrode  1260  contacts the tissue, providing sensing ETS  934  with the reference voltage for sensing the one or more signals during the neurostimulation trial. 
     Materials for sensing reference electrode  1360 , elongate wire body  1364 , and wire connector  1365 , as well as materials for releasable clip  1396  and release handle  1397 , are selected to be compatible with one or more sterilization processes. Such one or more sterilization processes are required for preparing stimulation lead  908 , sensing reference electrode  1360  with sensing wire  1362 , lead introducer  1290 , releasable clip  1396 , and release handle  1397  for use with the patient. 
       FIG.  14    illustrates an embodiment of a sensing ETS  1434 , which can represent an example of ETS  634  or  934 . Sensing ETS  1434  has sensing capabilities allowing for sensing of one or more signals from the patient during a neurostimulation trial for the patient. Sensing ETS  1434  includes a sensing circuit  1442 , a stimulation circuit  1412 , a control circuit  1414 , a user interface  1410 , and an ETS connector  1484 . 
     Sensing circuit  1442  can sense one or more signals from the patient using one or more sensing electrodes, such as selected from one or more electrodes  906 . Stimulation circuit  1412  deliver the neurostimulation energy to the patient using one or more stimulation electrodes, such as selected from one or more electrodes  906 . Control circuit  1414  can control the sensing of the one or more signals by sensing circuit  1442  and control the delivery of the neurostimulation energy from stimulation  1412 . User interface  1410  can allow a user to control the sensing of the one or more signal and/or the delivery of the neurostimulation energy and/or present information to the user. The presented information can include, but are not limited to, parameters controlling the sensing of the one or more signal and/or the delivery of the neurostimulation energy and/or the sensed one or more signals. In some embodiments, the presented information can further include, for example, parameters derived from the sensed one or more signals, and/or instructions for the user to conduct the neurostimulation trial. 
     ETS connector  1484  can provide for electrical connections to the sensing and stimulation electrode(s) and the sensing reference electrode. In the illustrated embodiment, ETS connector  1484  includes a reference contact  1485  for the electrical connection to the sensing reference electrode, a first sensing and stimulation contact  1486  (SENS/STIM 1), and a second sensing and stimulation contact  1487  (SENS/STIM 2) for use in a neurostimulation trial system such as system  900 ,  1000 ,  1100 ,  1200 , or  1300  as illustrated in  FIGS.  9 ,  10 ,  11 ,  12 , and  13   , respectively. Sensing and stimulation contacts  1486  and  1487  can each includes a multi-contact group allowing for separate electrical connections each for an electrode of multiple electrodes on a stimulation lead. In various embodiments, any one or more sensing and stimulation contacts can be included to accommodate the number of stimulation leads needed for the neurostimulation trial. 
       FIG.  15    illustrates an embodiment of a method  1500  for providing an interface between a patient and an ETS during a neuromodulation trial. The neuromodulation trial uses a trial system that emulates functions of an implantable system, including delivering neurostimulation energy to the patient and sensing one or more signals from the patient, for purposes including determining whether the implantable system can provide the patient with a suitable therapy and/or determining parameters for the therapy. The trial system includes a test device placed externally to the patient and including sensing and stimulation capabilities, such as sensing ETS  934 . Method  1500  can be performed using a suitable trial system selected from systems  900 ,  1000 ,  1100 ,  1200 , and  1300 . 
     At  1501 , an elongate stimulation lead suitable for percutaneously introducing one or more electrodes into the patient for delivering the neurostimulation energy and sensing the one or more signals is provided. The stimulation lead includes a lead distal end including the one or more electrodes and a lead proximal end including a lead connector having one or more electrode contacts electrically connected to the one or more electrodes. In one embodiment, the elongate stimulation lead is an implantable lead that is suitable for chronic or permanent implantation in the patient. In one embodiment, the elongate stimulation lead is a percutaneous lead that is similar to the implantable lead but suitable for temporary use such as use for the duration of the neurostimulation trial. 
     At  1502 , a sensing reference electrode suitable for placing in the patient is provided. In one embodiment, the sensing reference electrode is an implantable electrode suitable for subcutaneous placement in the patient and connected to a sensing wire. In another embodiment, the sensing reference electrode is integrated into the stimulation lead in a location that is subcutaneous when the one or more electrodes of the stimulation lead are in place. In another embodiment, the sensing reference electrode is attached (e.g., detachably attached) to the stimulation lead in a location that is subcutaneous when the one or more electrodes of the stimulation lead are in place. In another embodiment, a lead introducer suitable for percutaneously introducing the stimulation lead for placing the one or more electrode in the patient is provided. The lead introducer includes an introducer distal end suitable for entering the patient, an introducer proximal end, an elongate introducer body coupled between the introducer distal end and the introducer proximal end, and a lumen extending within the introducer body from an introducer distal opening at or near the introducer distal end and an introducer proximal opening at or near the introducer proximal end. The lumen has a size accommodating a portion of the stimulation lead and allowing the lead distal end to enter the introducer primary opening and exit from the introducer distal opening. The sensing reference electrode is detachably attached to the lead introducer, and can be detached from the lead introducer before the lead introducer is removed from the patient. This can be achieved, for example, by providing a releasable clip to attach the sensing reference electrode to the lead introducer and a release handle coupled to the releasable clip. The sensing reference electrode is detached from the lead introducer by releasing the releasable clip using the release handle. 
     At  1503  an elongate sensing wire suitable for percutaneously introducing the sensing reference electrode into the patient to provide a reference for sensing the one or more signals is provided. The sensing wire includes a wire distal end connected to the sensing referenced electrode and a wire proximal end including a wire connector having a sensing reference electrode contact electrically connected to the sensing reference electrode. In some embodiments, the wire distal end is detachably connected to the sensing referenced electrode. 
     At  1504 , a cable assembly for connecting the test device to the stimulation lead and to the sensing wire is provided. The cable assembly is suitable for use externally to the patient and includes a cable connector and a cable connected to the cable connector and providing electrical connections between the cable connector and the test device. The cable connector is suitable for mating the lead connector and mating the wire connector, and a cable. 
     With all the system elements provided by method  1500  are interconnected as illustrated in one or more of  FIGS.  10 - 13   , the neurostimulation energy can be delivered, and the one or more signals can be sensed, according to the requirements of the neurostimulation trial. An example of such a neurostimulation trial performed for evaluating a SCS therapy includes percutaneously introducing the stimulation lead to place the one or more electrodes subcutaneously over the spinal cord of the patient, sensing the one or more signals using the one or more electrodes placed subcutaneously over the spinal cord, and processing the sensed one or more signals using the test device. The example can further include (for example, after a sensing period) generating the neurostimulation energy using the test device and delivering the neurostimulation energy to the spinal cord using the one or more electrodes. 
     It is to be understood that the above detailed description is intended to be illustrative, and not restrictive. Other embodiments will be apparent to those of skill in the art upon reading and understanding the above description. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.