WO2010069317A1

WO2010069317A1 - Bursts of electrical pulses in the treatment of pelvic disorders by electrical nerve stimulation

Info

Publication number: WO2010069317A1
Application number: PCT/DK2009/000256
Authority: WO
Inventors: Morten Fjordback; Thomas Borup; Michael Eriksen; Nico J. M. Rijkhoff; Dianna Mærsk KNUDSEN
Original assignee: Neurodan A/S
Priority date: 2008-12-19
Filing date: 2009-12-14
Publication date: 2010-06-24
Also published as: EP2376188A1; WO2010069317A8

Abstract

In a system and method for the treatment of urge urinary incontinence by electrical stimulation of pudendal nerve afferents of a living being a first sequence of electrical stimulation pulses are initially provided at a first setting. The pulses are provided continuously or cyclically to an electrode configured to be placed on a portion of a pudendal nerve or its branches. Upon an external control signal preferably provided by the patient to the pulse generator, the pulse generator enters a burst mode providing a sequence of pulses comprising a number of electrical bursts. The continuous or cyclical stimulation according to the first mode is resumed upon completion of the bursts of electrical pulses.

Description

BURSTS OF ELECTRICAL PULSES IN THE TREATMENT OF PELVIC DISORDERS BY ELECTRICAL NERVE STIMULATION

Technical field

The present invention is generally concerned with the treatment of urge urinary incontinence by electrical stimulation of pudendal nerve afferents, such as dorsal penile/clitoral nerves.

Background of the invention

The overall European prevalence of overactive bladder (OAB) syndrome is 16.6% in the general population above 40 years. Frequency (85%) is the most commonly reported symptom, followed by urgency (54%) and urge urinary incontinence (36%). These symptoms adversely affect patients' quality of life due to social and hygienic difficulties. Upper urinary tract damage caused by sustained high intravesical pressures and repeated bladder infections is another concern that causes morbidity, hospitalization or even death. Conventional treatment is typically based on drugs with dose-limiting systemic side effects. Surgical destructive intervention may be considered if patients are refractory to conventional treatment options but complication rates are often high. Alternative treatment options should be considered in refractory patients to avoid destructive surgery.

Continuous or intermittent electrical stimulation of the sacral nerves is known to be effective in the treatment of a variety of pelvic disorders, such as overactive bladder (OAB) syndrome (InterStim^® Therapy, Medtronic, MN, USA). InterStim^® Therapy is based on electrical stimulation of the sacral root(s) using a medical lead connected to an implanted pulse generator. The pulse generator is programmable by means of an external control device via wireless data transmission. Electrical stimulation of the sacral root(s) activates sacral somatic afferents that modulate the sacral reflex pathways. This effect is also known as neuromodulation and has been shown to reduce the OAB symptoms. In patients suffering from urge urinary incontinence, the time available from urge to leakage (warning time) may be too short to reach a toilet. Sacral neuromodulation does not provide means to increase warning time. As bladder volume increases, neuromodulation can eventually not sufficiently suppress involuntary bladder contractions.

Summary of the invention

It is an object of embodiments of the present invention to provide a system and a method which overcome or at least reduces the above disadvantages. It is a further object to increase the effect of treatments of urge urinary incontinence by electrical stimulation of pudendal nerve afferents of a living being.

The present invention provides a system and a method to increase warning time in patients with overactive bladder syndrome by combining the effect of neuromodulation with a burst of electrical stimulation pulses with specific stimulation parameters and which can be activated on demand.

In patients suffering from urge urinary incontinence, the time available from urgency to leakage (warning time) may be too short to reach a toilet. Sacral neuromodulation alone does not provide means to increase warning time. As bladder volume increases, neuromodulation can eventually not sufficiently suppress involuntary bladder contractions leading to urine leakage. Combining the effect of neuromodulation with an on demand triggered burst of electrical stimulation pulses has shown good results.

A burst of electrical pulses is here and in the following to be understood as a number of repetitive pulses occurring during some fixed time interval. The pulses may be delivered in rapid succession and/or with an increased charge injection as described in more details in the following. The burst stimulation both serves to provide a strong vesicoinhibitory effect but also to evoke a sacral reflex that causes contraction of pelvic muscles that aid to preserve continence. The vesicoinhibitory effect causes acute suppression of involuntary ongoing bladder contractions. Together with the evoked contraction of the pelvic floor this gives the patient the possibility to postpone bladder emptying without any risk of leakage. Thus the patient regains control of the bladder function thus enhancing quality of life. This effect is not achieved in present commercial systems which only feature sacral neuromodulation, since an ongoing bladder contraction cannot be suppressed.

The charge injection required to evoke acute bladder inhibition and pelvic floor contractions, will generally cause pain if provided continuously and may introduce severe side effects as e.g. involuntary movement of the lower extremities, when provided at sacral root level. In order to avoid the above mentioned side effects, stimulation should be provided more distally e.g. at the genital nerves and as bursts of pulses (non continuous stimulation) with a predetermined duration. Especially, the energy delivered (the charge injection) during the burst period will determine the pattern of the burst in order to stay within safety limits. Exceeding the safety limits for charge injection may cause tissue damage.

In a first aspect, the invention provides a system for the treatment of urge urinary incontinence by electrical stimulation of pudendal nerve afferents of a living being, including: - at least one implantable electrode configured to be placed on, in, at, or near a portion of a pudendal nerve or its branches;

- a pulse generator configured to receive external control signals during operation thereof and to further: provide electrical stimulation pulses to the at least one electrode in order to achieve said electrical stimulation of the pudendal nerve afferents, the pulse generator being configured to control at least one pulse parameter of the pulses, said at least one pulse parameter being selected from pulse current, pulse voltage, pulse amplitude, pulse frequency, pulse width, and pulse shape; where in a first mode the pulse generator operates to provide a first sequence of said pulses at a first setting for said at least one pulse parameter; enter a burst mode when an external control signal is provided to the pulse generator; subsequently provide a second sequence of said pulses including one or more bursts of electrical pulses, the bursts of electrical pulses being provided at a second setting for said at least one pulse parameter; re-enter said first mode when the bursts of electrical pulses have been completed.

Using neuromodulatiori to modulate the spinal reflex arches, the urge to empty the bladder or bowel is suppressed for a period of time. However, once the patient feels urgency, such urgency is a result of the detrusor activity being too powerful for the stimulation to suppress. Hence, no warning is given to the patient, who may therefore not have sufficient time to reach a toilet.

The present invention provides a system that supplements continuous or cyclic electrical stimulation of sacral nerve afferents by allowing patients to activate burst stimulation on demand e.g. in case of urgency. Burst stimulation will acutely suppress the bladder for a period of time and cause reflex contraction of pelvic musculature that aids to preserve continence. This will provide the patient additional time to reach a toilet. The bursts provided on demand, in the event of urgency, can further be repeated a number of times when the feeling of urgency reappears. The repeated suppression of involuntary bladder contractions will provide additional time to allow the patient to empty the bladder when considered socially convenient. Consequently, a prolonged warning time is achieved.

The burst stimulation both serves to provide a strong vesicoinhibitory effect but also to evoke a sacral reflex that causes contraction of pelvic muscles that aid to preserve continence. The invention is advantageous for the treatment of urge urinary incontinence, but may also be advantageously applied in the treatment of faecal incontinence. Treatment of stress incontinence is also contemplated. Further, the invention is useful for bladder voiding by stimulation of the perineal nerve afferents. Further the invention can be applied in training or rehabilitation of the pelvic floor musculature and sphincter.

The stimulation by bursts of electrical pulses is advantageous in activating additional fibres in the pudendal nerve or its branches. The changes in the stimulation train with pulses in relatively rapid succession increase the sensory response as the fibres in a nerve bundle are typically of varying sizes and diameters and will therefore react and be activated to different degrees, when stimulated by the same electrical pulse. For example, stimulation by pulses of higher amplitude will advantageously cause not only the thicker fibres but also some of the thinner fibres in a nerve bundle to react.

In an embodiment the pulse generator is configured to continuously or cyclically provide said first sequence of pulses independently from the external control signals.

In an embodiment the pulse generator is configured to provide and control the frequency of the electrical stimulation pulses within a range of about 5 Hz to about 50 Hz.

In an embodiment the pulse generator is configured to control the number of electrical pulses in a burst of about 1 to about 10.

In an embodiment the pulse generator is configured to provide bursts of electrical pulses in said burst mode in a period of time of about 5 seconds up to about 5 minutes.

In an embodiment the pulse generator is configured to provide bursts of electrical pulses wherein the pulse amplitude of current of the pulses is increased to a burst level of about

0.02 mA to about 20 mA relative to the pulse amplitude of current of the first mode of about 0.01 mA to about 10 mA.

In an embodiment the pulse generator is configured to provide bursts of electrical pulses wherein the pulse frequency is increased.

In an embodiment the pulse generator is configured to provide bursts of electrical pulses wherein the pulse width and/or the pulse amplitude is increased for at least one of the pulses in the burst.

In an embodiment the pulse generator is configured to provide pulses with a time between pulses from 1 to 5 ms. In an embodiment the pulse generator is configured to provide a series of bursts in a burst train, said burst train being provided with a repetition rate of between 2 an 20 times per second.

In an embodiment said at least one electrode comprises a first and a second electrode, and wherein the pulse generator is configured to provide said first sequence of pulses to the first electrode and the second sequence of pulses to the second electrode.

In an embodiment according to the above the pulse generator is configured to provide said first sequence of pulses simultaneously with the second sequence of pulses.

In an embodiment the at least one electrode is configured to be placed in the vicinity of a pudendal nerve branch such as closer than approximately 3 cm.

In an embodiment the system according to any of the above, further comprises a user- operable triggering mechanism configured to transmit said control signal to the implantable pulse generator in order to trigger the burst mode.

In an embodiment according to the above the triggering mechanism comprises a user- interface configured to allow the user to set one ore more burst pulse parameters.

In an embodiment the at least one electrode is implantable at a left and/or right genital nerve (dorsal penile/clitoral) or in the pudendal canal via the perineum.

In a second aspect, the invention provides a method for the treatment of urge urinary incontinence by electrical stimulation of pudendal nerve afferents of a living being, comprising the steps of: implanting at least one electrode on, in, at or near a portion of a pudendal nerve or its branches; - implanting a pulse generator configured to provide electrical stimulation pulses to the at least one electrode in order to achieve said electrical stimulation of the pudendal nerve afferents, the pulse generator further being configured to receive external control signals during operation thereof and to control at least one pulse parameter of the pulses, said at least one pulse parameter being selected from pulse current, pulse voltage, pulse amplitude, pulse frequency, pulse width, and pulse shape; in a first mode providing a first sequence of said pulses at a first setting for said at least one pulse parameter transmitting a control signal to the pulse generator causing the pulse generator to enter a burst mode; subsequently providing a second sequence of said pulses including one or more bursts of electrical pulses, the bursts of electrical pulses being provided at a second setting for said at least one pulse parameter; causing the pulse generator to re-enter said first mode when the bursts of electrical pulses have been completed.

Description of the drawings

Embodiments of the invention will be described with reference to the accompanying drawings, in which:

Fig. 1 shows an illustration of the pelvic region of a patient, including an implanted electrode, pulse generator and lead, as well as an external triggering mechanism;

Fig. 2 shows an illustration of the pulse generator shown in Fig. 1;

Figs. 3 and 4 are graphical representations of stimulus outputs from the pulse generator comprising bursts of electrical stimulation pulses;

Figs. 5 and 6 are illustrations of a wireless external programming device with an external triggering mechanism;

Fig. 7 is an anatomic view showing the implanted pulse generator of Figs. 1 and 2 in association with an external programming system; Figs. 8 and 9 are illustrations of an implanted triggering mechanism, which is activatable by mechanical impact to an outer surface portion of the patient's body;

Figs 10 is a flow chart illustrating a process of the system of the present invention;

Fig. 11 is an illustration of a sterilized kit including implantable elements as well as surgical tools for their implantation;

Fig. 12 illustrates a releasable connection between a pulse generator and the lead connecting the pulse generator to the electrode;

Fig. 13 shows a further embodiment of a system according to the invention.

Fig. 1 generally illustrates the pelvis 100 of a patient 102 and a portion of the spinal cord 104. The pudendal nerves 108 exit the sacral cord and branch into the dorsal penile/clitoral nerves 110. Fig. 1 further illustrates Alcock's Canal 112 and the pubic symphysis 114. In the illustration of Fig. 1, a cuff electrode 116 is placed around the left dorsal penile/clitoral nerve 110. The electrode 116 is connected to an implanted pulse generator 118 via an implanted lead 120. The pulse generator 118 comprises a battery (not shown in Fig. 1) and is configured to convey pulses of electrical current through the electrode 116 via the lead 120, so as to provide electrical stimulation to the dorsal penile/clitoral nerve 110. The battery may be chargeable by means of inductive wireless power transmission providing electromagnetic signals at a frequency of below 315 kHz. An external, wrist worn device 122 is provided for wirelessly communicating with the pulse generator 118. In one embodiment of the invention, the wrist worn device 122 represents a triggering mechanism for causing the pulse generator 118 to pass a series of bursts of electrical pulses to the electrode. Alternatively, or additionally, the wrist worn device 122 may be configured as a programming device for setting stimulation parameters or for otherwise programming or configuring the implanted pulse generator 118. The pulse generator 118 may be configured for providing data to the external device 122, such as e.g. a low battery warning of the pulse generator 118.

Fig. 2 generally shows the main components of the pulse generator 118. The pulse generator includes a telemetry unit 124 for receiving and/or sending information to/from an external device, such as the wrist worn device 122 shown in Fig. 1. Further, the pulse generator includes a pulse generating circuitry 126, and a battery 128. The battery 128 is preferably hermetically sealed within a housing of the pulse generator 118. The pulse generator contains a connector 130 to attach the implantable lead 120.

Figs. 3 and 4 are graphical representations of different possible stimulus outputs from the pulse generator during first mode continuous or cyclical stimulation 301 and during a burst mode 302, where bursts 303 of electrical stimulation pulses are provided. During the first mode 301 of stimulation, the pulse generator provides a first sequence of electrical pulses. Upon activation, the pulse generator sends out a second sequence 302 of electrical pulses (also referred to as a burst train) in which one or more of the pulse parameters such as the pulse current, pulse voltage, pulse amplitude 305, time interval between pulses 304, pulse frequency, pulse width 306, or pulse shape 307 have been changed relative to the setting in the first sequence. The burst train or second sequence of pulses comprises one or more bursts 303 of a number of repetitive pulses 310 occurring during a fixed time interval 311. As illustrated in the pulse train in figure 4, the individual pulses in a burst need not be of the same amplitude, width etc. In the embodiments shown the time interval 400 between subsequent pulses in the first mode and the time between subsequent bursts 410 are kept approximately constant. Further, the burst mode may also comprise a number of burst trains being cyclically or in other ways repeated at intervals. It should however be understood that these parameters may also be changed.

As mentioned above, the device 122, which may be a wrist worn device, may serve as a wireless external triggering or programming device for programming or configuring the pulse generator. As shown in Figs. 5 and 6, the patient 102 may trigger or program the pulse generator 118 by locating the wrist worn device 122 in the vicinity of the implanted pulse generator 118 and activating a programming action, so as to wirelessly transmit an appropriate triggering signal, programming or configuration data to the pulse generator 118, as shown in Fig. 6.

Fig. 7 illustrates an external programming system for a system according to the invention. The programming system includes a personal computer 132, which is typically operated by a physician, and a programming box 134. The programming box is connected to an antenna 138 via a lead 136. Programming of the implanted pulse generator 118 is performed via wireless, inductive telemetry from the inductive coil through the skin of the patient.

Figs. 8 and 9 are illustrations of an implanted triggering mechanism 140. The triggering mechanism is activatable by mechanical impact to an outer surface portion of the patient's body, e.g. by a push button 142, which is activatable by application of a finger pressure to the outer surface portion of the body, as illustrated in Fig. 9. The triggering mechanism 140 may also house the pulse generator, in which case a distal end of the lead 144 is connected to the electrode (not shown). Alternatively, the pulse generator may be provided as a separately implanted component, whereby the lead 144 interconnects the triggering mechanism and the pulse generator. An external programming device 146 is provided for programming or configuring the implanted pulse generator and/or the implanted triggering mechanism 140 via wireless data transmission.

Fig. 10 shows a flowchart of an embodiment of a process occurring in the systems described above. Initially, the pulse generator is in a first mode continuously or cyclically stimulating by a first sequence of electrical pulses according to some predefined stimulation program. Generally, if the pulse generator detects a low battery status, a wireless warning signal is provided to an external device, such as the external triggering device 122 (Fig. 1) or an external programming device (Fig. 7). When the patient activates the trigger device (triggering mechanism 122 or 140, or user activatable device 162, see Fig. 13), a control signal is provided to initiate a burst command for the pulse generator 118. At the same time, certain stimulation parameters may also be sent to the pulse generator. The control command causes the pulse generator to enter a burst mode and to provide a second sequence of pulses including one or more bursts of electrical pulses. The bursts may be provided for a predetermined period of time, in predefined number, or as long as the patient activates the trigger device. Subsequently, the pulse generator re-enters the first mode of continuous or cyclically stimulation by the first sequence of electrical pulses.

Fig. 11 illustrates an embodiment of a sterilized surgical kit. The kit includes several sterilized packages. One package contains the pulse generator 118. Another package contains the electrode 116, connected to a connector 152 via the lead 120. Further packages 148 and 150 include surgical tools for implanting the electrode 116, pulse generator 118 and lead 120. The surgical tools may for example include tunneling tools for tunneling the lead and/or electrode through the patient's body during surgical intervention. As shown in Fig. 12, the connector 152 allows the lead 120 to be releasably connected to the pulse generator 118.

In the embodiment of Fig. 13, the user-operable triggering mechanism comprises a skin- borne device 160 releasbly attached to an abdominal wall of the user in the vicinity of the implanted pulse generator 118 and electrode 116. The user-operable triggering mechanism further comprises a hand-held user activatable device 162 for transmitting radio frequency control signals to the skin-borne device 160, which in turn generates inductive wireless signals to the pulse generator 118.

Different embodiments

Using continuous or cyclic neuromodulation to modulate the spinal reflex arches, the urge to empty the bladder or bowel is suppressed for a period of time. However, once the patient feels urgency, such urgency is a result of the detrusor activity being too powerful for the stimulation to suppress. Hence, no warning is given to the patient, who may therefore not have sufficient time to reach a toilet.

The present invention provides a system that supplements continuous or cyclic electrical stimulation of sacral nerve afferents by allowing patients to activate burst stimulation on demand e.g. in case of urgency. Burst stimulation will acutely suppress the bladder for a period of time and cause reflex contraction of pelvic musculature that aids to preserve continence. This will provide the patient additional time to reach a toilet.

The invention is particularily useful for the treatment of urge urinary incontinence, but may also be applied in the treatment of faecal incontinence and pelvic pain syndromes. Treatment of stress incontinence is also contemplated. Further, the invention may be useful for bladder voiding by stimulation of the perineal nerve afferents. Further the invention may be applied in training or rehabilitation of the pelvic floor musculature and sphincter.

Nerve/electrode interface

Prior art systems are based on continuous or cyclic electrical stimulation of the sacral nerve roots. The present invention is intended to provide neuromodulation through stimulation of pudendal nerve branches, such as the dorsal penile/clitoral nerve (genital nerves); i.e. stimulation is selectively targeted towards nerve afferents that reflexively affect the bladder. Additionally, the system and method of the present invention provides bursts of direct nerve stimulation, such as direct sensory nerve stimulation, on demand to evoke a strong detrusor/bowel inhibitory reflex together with reflex mediated contraction of pelvic floor muscles that aids to preserve continence (bulbocavernosus reflex).

The at least one electrode is preferably configured to be placed at, around, near, on, or in a dorsal penile/clitoral nerve, which is a distal portion of the pudendal nerve close to the genitals. Alternatively, the electrode may be configured to be implanted in the pudendal canal (Alcock's canal) via the perineum.

In the present context, electrodes are said to be placed or placeable at, on, in, near or around nerves. It should be understood that any reference to the placement of electrodes is not limited to any specific of these locations. Hence, an electrode, which for example is said to be placed or placeable 'at' a nerve may be placed or placeable not only 'at', but also on, in, near or around that nerve, unless the present text specifically requires a certain location of the electrode. In general, the reference to any placement 'on', 'in', 'near' or 'around' nerves includes any placement 'at', On', 'in', 'near' or 'around'.

As used herein, the reference to pudendal nerve afferents includes the sensory part of the sacral nerves, dorsal penile/clitoral nerves (genital nerves), as well as any parts or branches thereof.

The at least one electrode may be implanted or implantable at a left and/or right branch of the dorsal penile/clitoral nerve, which is a distal portion of the pudendal nerve close to the genitals. The electrode may be implanted at or near the genitals or in Alcock's Canal via the perineum.

The at least one implantable electrode may be a known type such as a cuff, wire, helix, double helix, a spiral electrode, or an intra-neural electrode. Preferably, the electrode is configured to be placed as close to the nerve as possible. In another embodiment, the electrode is placed inside the nerve.

In preferred embodiments, the lead is detachably connected to the pulse generator, e.g. through a releasable connector. The lead may be permanently secured to the electrode or detachably coupled thereto.

The lead connecting the pulse generator to the at least one electrode may be a single stranded lead. Preferably, a helical hollow strand or multi-stranded lead is used in order to provide a flexible and mechanically strong connection. The lead may be made of a biocompatible material and/or coated with an insulating biocompatible material. Implanted/implantable electrical stimulator

The pulse generator may be implantable/implanted in a subcutaneous pocket in the pelvic or abdominal region at a tissue depth of approximately 4 cm or less. In other embodiments, the pulse generator may be implantable/implanted to a tissue depth of between 0.3 cm and 0.4 cm or between 0.6 cm and 1.4 cm, or between 1.6 cm and 1.9 cm or between 2.1 and 2.8 cm. The pulse generator is preferably implanted in a subcutaneous pocket in the pelvic or abdominal region, such as in the anterior pelvic or abdominal region. The implant may contain means for fixation, e.g. sutures. The implant housing may be hermetically sealed by e.g. welding two shells together. The housing contains a battery that may be provided in a hermetically sealed compartment of the housing of the pulse generator. The housing of the pulse generator may be coated with e.g. silicone and/or made from a biocompatible material, such as titanium.

In one embodiment the battery is rechargeable. For example, the battery may be rechargeable while it is left in place in the patient's body. In one embodiment the battery is inductively rechargeable, e.g. by means of the triggering device and a combined trigger and power receiver of the implanted pulse generator. Alternatively, the battery may be removed by surgical intervention and recharged outside the patient's body. In other embodiments, the battery is non-rechargeable. In such cases the battery life time may match the expected life time of the product (e.g. 5 to 10 years).

In embodiments including a mechanical triggering mechanism, the implanted/implantable battery may be provided as a separate, implantable component, or it may be provided within a housing of the triggering mechanism or within a housing of the pulse generator. Separate batteries may be provided for the triggering mechanism and the pulse generator, respectively, may be provided. The battery or batteries provide power for the control signal transmitted by the triggering mechanism, for the pulse generator and optionally also for the wireless transmission of signals from the implanted components to an external device, e.g. a control device.

The pulse generator may further include an electronic memory for storing-stimulation programs and/or stimulation parameters. The electronic memory is preferably provided as a non-volatile memory, such as EPROM, EEPROM, flash memory or the like known per se.

In order to avoid tissue damage, the implantable pulse generator may be configured to control stimulation parameters of the stimulation pulses and to charge balance the pulses. Charge balancing may be achieved by alternating polarity, by shortcircuiting the electrodes after each stimulation pulse, through a capacitor coupled in series with the electrodes, or by software-controlled means. Stimulation paradigm

The settings of a sequence of electrical pulses may be controlled by controlling one or more of pulse parameters such as: - the amplitude of current of the electrical stimulation pulses;

- the amplitude of voltage of the electrical stimulation pulses;

- the pulse rate of the electrical stimulation pulses, i.e. the length of intervals between the pulses;

- the pulse width of the electrical stimulation pulses; - the pulse frequency of the electrical stimulation pulses;

- the shape of the electrical stimulation pulses, such as square or sinusoidal pulses.

A first sequence of electrical stimulation pulses is initially provided in a fashion which may be continuous or cyclic thereby achieving a neuromodulative effect that will suppress undesired pelvic reflex activity for a period of time. In one embodiment of the invention the pulse generator is further configured to provide the first sequence of the electrical stimulation pulses independently from any external control signals. In a further embodiment of the invention the first sequence of the electrical stimulation pulses is provided in a cyclic or continuous way. Upon an external control signal which may be provided to the pulse generator by the patient, the pulse generator enters a burst mode providing a sequence of pulses comprising a number of electrical bursts which act in addition to the continuous or cyclical stimulation to suppress sudden or intense urgency to pass urine or faeces. The continuous (or cyclical) and burst mode stimulation may be applied using the same or different electrodes. The injected charge and thereby the delivered energy during burst mode is significantly higher than during normal operation whereby the sensory response is increased. Additionally, the pulse train may be changed to include additional pulses in rapid succession (e.g. 1 to 5 ms apart) to be able to trigger the sensory reflex that causes contraction of pelvic floor contraction that aids to preserve continence. The continuous or cyclical stimulation according to the first mode is resumed upon completion of the bursts of electrical pulses.

The pulse generator is in one embodiment configured to provide the pulses at a pulse rate of about 5 pulses per second to about 20 pulses per second. Further, the pulse generator may be configured to control the number of electrical pulses in a burst which is a parameter controlling the added efficiency on the nerve fibers from the stimulation with the burst. The bursts and/or burst trains of electrical pulses may advantageously be repeated several times per second (2 to 20 times) to achieve a tetanic contraction. The pulses are typically provided at a pulse width of about 50 μs to about 400 μs, such as at a pulse width of about 200 μs.

In further embodiments, the initial first mode provides currents from about 0.01 mA to about 10 mA, whereas the burst level provides currents from about 0.02 mA to about 20 mA. Similarly, the pulse frequency during the second burst sequence of the pulses may be increased.

The stimulation by bursts of electrical pulses is advantageous in activating additional fibres in the pudendal nerve or its branches. The changes in the stimulation train with pulses in rapid succession act to maximize the sensory response. The fibres in a nerve bundle are typically of varying sizes and diameters and will therefore react and be activated to different degrees, when stimulated the same electrical pulse. For example, stimulation by pulses of higher amplitude will advantageously cause not only the thicker fibres but also some of the thinner fibres in a nerve bundle to react. Thinner fibres may sometimes convey pain to the central nervous system and it may for this reason be bothersome or even painful to stimulate at the levels needed to achieve acute bladder suppression. This is the reason the burst mode stimulation is not intended for continuous use. It is known that acute bladder inhibition requires stimulation amplitude of approximately two times the threshold for evocation of the bulbocavernosus reflex.

Triggering

In order to allow user-initiated triggering, the system of the present invention may comprise a user-operable triggering mechanism configured to transmit a wired or wireless control signal to the implantable pulse generator in order to trigger a sequence of electrical pulses. The triggering mechanism may conveniently comprise a user-interface configured to allow the user to set stimulation parameters.

The control signal to the pulse generator may be provided or initiated by the patient, thereby allowing for event-triggered activation of stimulation in contrast to prior art systems relying only on continuous stimulation. The burst stimulation may be initiated frequently, commonly several times a day, and each burst stimulation period may typically last from about 5 seconds to about several minutes, such as 1, 2 or 5 minutes.

As outlined above, the burst stimulation of the present invention may be event-triggered. In other words, stimulation may be initiated by a patient, once the patient feels a compelling desire to pass urine or faeces. In some setups the system is programmed to provide a train of a predetermined number of burst pulses or to calculate the number of burst pulses (i.e. the duration of the train of burst pulses), whereby the burst train of pulses is determined by the control of the system, unless overruled by a patient-activated emergency stop. User-activated termination of the burst train of pulses may also be beneficial in cases the patient reaches a toilet facility before expiration of a predetermined or pre-programmed train of pulses, so as to expedite bladder voiding. The possibility of user-activated termination of the pulse train also constitutes a safety feature.

In other setups, it may however be desirable to allow the patient to prolong the stimulation period, whereby the system is programmed to generate electrical pulses until the patient stops the pulse generation. Prolonged stimulation periods may in particular be useful for extending the patient's continence time immediately prior to bladder voiding, usually for a period of time of 1-5 minutes prior to voiding.

The triggering mechanism, which is preferably provided as an external (i.e. non-implanted) device, may include a programmable memory for storing stimulation programs and/or stimulation parameters.

The triggering mechanism may be configured to include at least one of the following commands in the control signal:

- a burst command for the implantable pulse generator;

- a command for the pulse generator to select a particular one of a plurality of stimulation programs pre-stored in a memory of the implantable pulse generator; and - stimulation parameters of said stimulation pulses, including at least one of: an amplitude of the electrical pulses; a pulse width of the electrical pulses; a pulse rate of the electrical pulses; a pulse shape of the electrical pulses.

The triggering mechanism and the implanted pulse generator may be configured such that the wireless control signal and/or wireless triggering signal is only receivable by the pulse generator when the triggering mechanism is within a predetermined range from the implanted pulse generator, e.g within a distance of 2.5 m or less.

The triggering mechanism may be included in a portable device, for example in a device, which is sized and configured to be worn around the wrist of a human being. For example, a wrist watch may be integrated with the triggering mechanism. Other portable devices are possible, e.g. devices which may be worn in a necklace, belt clip, devices integrated in cellular telephones or in other common personal items. Supplementary to or as an alternative to wireless external control signals, the system of the invention may rely on an implantable user-operable triggering mechanism configured to transmit the control signal to the implantable pulse generator, the implantable user-operable triggering mechanism being configured to transmit said control signal in response to a mechanical impact to an outer surface portion of the user's body. Due to the provision of a wired mechanical triggering signal there is no requirement of a continuously listening receiver, and consequently less power is consumed. The implantable user-operable triggering mechanism, which is operable by a mechanical impact to an outer surface portion of the patient's body, eliminates the need for an external triggering device to be worn or carried by the patient. Hence, the patient's handling of the system is facilitated, as those parts, which are required in the case of a need for immediate operation of the stimulation system, are all implanted/implantable.

The implanted/implantable triggering mechanism may be configured to be activated in response to various types of mechanical impacts, such as pressure or acceleration, pressures/sound waves. Hence, the triggering mechanism may include at least one of: a mechanical transducer such as an accelerometer or/and a pressure sensor.

As a further option, a closed-loop system can be provided using an internal sensor measuring physiological and/or other mechanical or electrical signals. Stimulation is thereby controlled by physiological means instead of a voluntary act controlled by the user. The parameters may be measured in the pelvic or abdominal region and may include at least one of: electrical and/or mechanical impact such as volume, pressure, flow, EMG, ENG, and/or temperature, pH.

In one embodiment, the user-operable triggering mechanism comprises a skin-borne device for transmitting said inductive wireless control signal to the implantable pulse generator, and a user activatable device for transmitting a wireless radio frequency signal to the skin-borne device upon user activation of the user activatable device. The skin-borne device is preferably configured to receive the wireless radio frequency signal transmitted from the user activatable device and to generate the inductive wireless control signal for the implantable pulse generator in response thereto. Hence, the skin-borne device may be attached to a body portion of the user in the vicinity of the implantation site of the pulse generator, e.g. at the abdominal wall, whereas the user activatable device may be at a distance therefrom, e.g. around the user's wrist, integrated in a mobile phone, PDA, or provided in a separate handheld device. Hence, in comparison to embodiment, in which the inductive wireless signal is provided directly from a user-held device to the pulse generator, the present device confers the benefit that the user does not need to observe the limited range of inductive wireless transmission. A non-implanted (i.e. external) battery may be provided for powering the skin-borne device, e.g. within the skin-borne device itself.

An implantable battery may be provided for powering the pulse generator. However, as described herein the pulse generator and possibly other implantable parts may be powered solely by inductive power transmission from an external, non-implanted device, such as the skin-borne device.

For patient convenience, the triggering mechanism comprises a user interface configured to emit a signal indicative of at least one of:

- a position of the user and/or of a public toilet facility and/or a distance to the nearest public toilet facility;

- time elapsed since last bladder voiding and/or since last stimulation pulse train; - time, alarm and/or date;

- log data related to past stimulation pulse trains;

- log data related to past voiding, such as volume of voided urine.

Triggering of the pulse generation may in embodiments of the present invention be performed in response to a signal provided by a sensor for determining the bladder pressure or volume. In such embodiments, the triggering mechanism can be dispensed with, but may be provided as back-up device allowing the user to trigger pulse generation.

Communication

The wireless control signal may be transmitted to the implanted pulse generator from a position outside the living being's body in order to trigger a sequence of the electrical pulses, the control signal comprising an RF (radio frequency) wireless inductive or non-inductive signal. An implanted/implantable battery may advantageously be provided in order to power the pulse generator. Thanks to the provision of the implantable battery, the only RF signal that is required for the operation of the system of the present invention is a triggering signal. Once the pulse generator has been triggered, the power for the pulses is provided by the implantable battery. Hence, the triggering mechanism need only be placed in the vicinity of the pulse generator during the period of triggering the pulse generator.

The triggering period may be comparatively very short compared to the stimulation period. In essence, triggering merely requires an activation signal which is transmittable in less than 1 second, whereas the burst stimulation period typically lasts for a predetermined period of approximately 5-300 seconds, and the initial first mode stimulation is performed continuously, i.e. during periods of several hours or longer. The system may allow for triggering a number of times in succession thereby causing a number of bursts to be sent off correspondingly rapid in succession adding to the overall neurostimulation.

The pulse generator includes a receiver for receiving RF wireless inductive or non-inductive transmitted signals emitted by the triggering device. By provision of an inductive triggering signal there is no requirement of a continuously listening receiver, and consequently less power is consumed. This in turn extends the life time of the implantable battery or, alternatively, allows for a smaller battery to be implanted.

In one embodiment, the wireless control signal is transmittable through a body portion of the living being within a distance of at most 2.5 m, such as most 1.5 m, 1 m or at most 50 cm from the pulse generator. Thereby, the risk of false or unintended triggering is reduced, and the risk of interference of the surrounding environment is reduced. The pulse generator may be configured such that it is unable to detect the RF triggering signal if the triggering mechanism is at a distance of more than 2.5 m away from the pulse generator. Alternatively or additionally, the triggering mechanism may be configured such that the emitted RF signals are sufficiently weak in order for them to be undetectable at a distance of more than 2.5 m from the triggering mechanism.

As the triggering mechanism is external (i.e. non-implanted) the RF triggering signal has to travel through atmospheric air, clothing and body tissue. The above reach limitation of approximately 2.5 m is to be understood as a reach through atmospheric air.

In order to allow the implanted pulse generator to communicate to an external device, the triggering mechanism may comprise a signal receiver for receiving a RF wireless signal from the implantable pulse generator. The implantable pulse generator may in such an embodiment be configured to transmit a RF wireless signal to the triggering mechanism, e.g. in case of one or more predetermined conditions of the implantable components, such as upon detection of a low battery charge. In one embodiment, the pulse generator is configured only to communicate a low battery status. In other embodiments, other information may be transmitted by the implanted pulse generator, such as information about malfunctions in the implanted components or electrode impedance.

In the present context, inductive wireless signal are defined as signals transmitted at a frequency below 315 kHz. Radio frequency wireless signals are defined as signals transmitted at a frequency above 400 MHz.

Herein, inductive signals are to be understood as signals provided at a frequency below 315 kHz, such as in the ULP-AMI band of 9 - 315 kHz according to the TR 101 981 or EN 302 195 standards. Radio frequency signals are to be understood as signals provided at a frequency above 400 MHz, such as in the range of the ULP-AMI band of 401-406 MHz, or in the MICS band of 402-405 MHz, both according to the TR 102 343 standard, or according to the EN 301 839 standard (402-405 MHz).

Generally, for the purpose of charging a battery within the implantable pulse generator, wireless inductive signals should be provided at a frequency of below 315 kHz or below 300 kHz, preferably around 125 kHz. Inductive charging avoids battery replacement by surgical intervention.

Accessories

An external programming device (clinical station) may be provided in order to transmit the pulse stimulation parameters or pulse generation programs to the implantable pulse generator. The clinical station is only provided to a medical facility, operable by a trained physician only. Preferably, the external programming device includes suitable software, user interface, memory, power unit, and data processor.

The system of the present invention may comprise an external programming device for transmitting data to the pulse generator when implanted, the external programming device and the pulse generator being configured to transmit and receive said data via wireless radio communication. Generally, radio frequency signals have a wider range than inductive signals, and for certain purposes it may hence be beneficial with respect to user and programmer convenience that programming and other data transmission to the pulse generator is carried out by means of radio frequency signals.

Surgical tools may be provided in order to implant the electrode and tunnel the lead to a subcutaneous pocket in the pelvic or abdominal region. This may include tools for implanting at least one of the electrode, the lead and the pulse generator, e.g. for tunneling the lead through body tissue to a subcutaneous pocket in the pelvic or abdominal region. A tool for connecting the lead to the pulse generator may further be included. The surgical tools are packed in a sterile condition and the package may include the implantable elements (e.g. electrode, lead and pulse generator).

A non-implanted device for patient screening may further be provided, including one of the following:

A surface electrode or a percutaneous electrode configured to be placed above a portion of a pudendal nerve or its branches; An external pulse generator having a pulse-generating circuitry and a battery for providing electrical pulses to the electrode in order to achieve electrical stimulation of the pudendal nerve or its branches;

An electrical lead for connecting the pulse generator to the electrode.

Other embodiments

The foregoing is considered as illustrative only of the principles of the invention. Furthermore, since numerous modifications, combinations, and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims:

Claims

1. A system for the treatment of urge urinary incontinence by electrical stimulation of pudendal nerve afferents of a living being, including: - at least one implantable electrode configured to be placed on, in, at, around, or near a portion of a pudendal nerve or its branches;

2. A system according to claim 1, wherein the pulse generator is configured to continuously or cyclically provide said first sequence of pulses independently from the external control signals.

3. A system according to claim 1 or 2, wherein the pulse generator is configured to provide and control the frequency of the electrical stimulation pulses within a range of about 5 Hz to about 50 Hz.

4. A system according to any of the preceding claims, wherein the pulse generator is configured to control the number of electrical pulses in a burst of about 1 to about 10.

5. A system according to any of the preceding claims, wherein the pulse generator is configured to provide bursts of electrical pulses in said burst mode in a period of time of about 5 seconds up to about 5 minutes.

6. A system according to any of the preceding claims, wherein the pulse generator is configured to provide bursts of electrical pulses wherein the pulse amplitude of current of the pulses is increased to a burst level of about 0.02 mA to about 20 mA relative to the pulse amplitude of current of the first mode of about 0.01 mA to about 10 mA.

7. A system according to any of the preceding claims, wherein the pulse generator is configured to provide bursts of electrical pulses wherein the pulse frequency is increased.

8. A system according to any of the preceding claims, wherein the pulse generator is configured to provide bursts of electrical pulses wherein the pulse width and/or the pulse amplitude is increased for at least one of the pulses in the burst.

9. A system according to any of the preceding claims, wherein the pulse generator is configured to provide pulses with a time between pulses from 1 to 5 ms.

10. A system according to any of the preceding claims, wherein the pulse generator is configured to provide a series of bursts in a burst train, said burst train being provided with a repetition rate of between 2 an 20 times per second.

11. A system according to any of the preceding claims, wherein said at least one electrode comprises a first and a second electrode, and wherein the pulse generator is configured to provide said first sequence of pulses to the first electrode and the second sequence of pulses to the second electrode.

12. A system according to claim 11, wherein the pulse generator is configured to provide said first sequence of pulses simultaneously with the second sequence of pulses.

13. A system according to any of the preceding claims, wherein the at least one electrode is configured to be placed in the vicinity of a pudendal nerve branch such as closer than approximately 3 cm.

14. A system according to any of the preceding claims, further comprising a user-operable triggering mechanism configured to transmit said control signal to the implantable pulse generator in order to trigger the burst mode.

15. A system according to claim 14, wherein the triggering mechanism comprises a user- interface configured to allow the user to set one ore more burst pulse parameters.

16. A system according to any of the preceding claims, wherein the at least one electrode is implantable at a left and/or right genital nerve or in the pudendal canal via the perineum.

17. A method for the treatment of urge urinary incontinence by electrical stimulation of pudendal nerve afferents of a living being, comprising the steps of: implanting at least one electrode on, in, at, around or near a portion of a pudendal nerve or its branches; - implanting a pulse generator configured to provide electrical stimulation pulses to the at least one electrode in order to achieve said electrical stimulation of the pudendal nerve afferents, the pulse generator further being configured to receive external control signals during operation thereof and to control at least one pulse parameter of the pulses, said at least one pulse parameter being selected from pulse current, pulse voltage, pulse amplitude, pulse frequency, pulse width, and pulse shape; in a first mode providing a first sequence of said pulses at a first setting for said at least one pulse parameter transmitting a control signal to the pulse generator causing the pulse generator to enter a burst mode; - subsequently providing a second sequence of said pulses including one or more bursts of electrical pulses, the bursts of electrical pulses being provided at a second setting for said at least one pulse parameter; causing the pulse generator to re-enter said first mode when the bursts of electrical pulses have been completed..