|Publication number||US20060217780 A1|
|Application number||US 11/249,034|
|Publication date||Sep 28, 2006|
|Filing date||Oct 11, 2005|
|Priority date||Dec 9, 2002|
|Also published as||US6959215, US20040111129, WO2004058347A1|
|Publication number||11249034, 249034, US 2006/0217780 A1, US 2006/217780 A1, US 20060217780 A1, US 20060217780A1, US 2006217780 A1, US 2006217780A1, US-A1-20060217780, US-A1-2006217780, US2006/0217780A1, US2006/217780A1, US20060217780 A1, US20060217780A1, US2006217780 A1, US2006217780A1|
|Inventors||Bradford Gliner, Allen Wyler|
|Original Assignee||Gliner Bradford E, Allen Wyler|
|Export Citation||BiBTeX, EndNote, RefMan|
|Referenced by (7), Classifications (16), Legal Events (1)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present application claims priority to pending U.S. Provisional Application 60/432,073, entitled “System and Method for Treating Parkinson's Disease and other Movement Disorders,” filed December 9, 2002.
The present invention is directed toward systems and methods for treating essential tremor, associated with abnormal neural activity in the brain.
A wide variety of mental and physical processes are controlled or influenced by neural activity in particular regions of the brain. For example, various physical or cognitive functions are directed or affected by neural activity within the sensory or motor cortices. Across most individuals, particular areas of the brain appear to have distinct functions. In the majority of people, for example, the areas of the occipital lobes relate to vision; the regions of the left interior frontal lobes relate to language; portions of the cerebral cortex appear to be consistently involved with conscious awareness, memory, and intellect; and particular regions of the cerebral cortex as well as the basal ganglia, the thalamus, and the motor cortex cooperatively interact to facilitate motor function control.
Essential tremor is a frequently occurring, complex neurologic movement disorder. At this time, the causes of essential tremor are not well understood.
Essential tremor (or ET) typically affects the hands, but it can also affect the head and neck (causing shaking), the face, jaw, tongue, voice, trunk, and, on occasion, the legs and feet. The tremor can take the form of a rhythmic lateral motion or forward and aft motion produced by involuntary muscle contractions. The duration and intensity of the tremors can vary substantially from one day to the next and during the course of a given day. ET typically has two forms: postural tremor, which occurs when the patient holds the affected muscle in a particular position, and kinetic tremor, which occurs when the patient moves the affected muscle in a particular way. Most patients affected by ET have both postural and kinetic tremor symptoms.
Effectively treating ET can be very difficult. Current treatments for ET symptoms include drugs, surgical intervention, and/or neural stimulation. Drug treatments or therapies may involve the administration of a beta-adrenergic blocker or anticonvulsant medication to the patient. Drug therapies may involve propanolol, mysoline, primidone, benzodiazepine, or a weak solution of botulinum toxin A. Unfortunately, many patients cannot tolerate or fail to adequately respond to drug therapies.
Surgical intervention for ET typically includes a thalamotomy, a procedure that involves ablating or destroying a selected portion of the thalamus. Unfortunately, surgical intervention is a very time consuming and highly invasive procedure. Potential complications associated with the procedure include risk of hemorrhage, stroke, and/or paralysis. Furthermore, because the procedures permanently destroy neural tissue, the effects of such intervention cannot be readily adjusted or “fine tuned” over time.
Neural stimulation treatments have shown promising results for reducing some of the symptoms associated with ET. Neural activity is governed by electrical impulses or “action potentials” generated in and propagated by neurons. While in a quiescent state, a neuron is negatively polarized and exhibits a resting membrane potential that is typically between −70 and −60 mV. Through chemical connections known as synapses, any given neuron receives excitatory and inhibitory input signals or stimuli from other neurons. A neuron integrates the excitatory and inhibitory input signals it receives, and generates or fires a series of action potentials in the event that the integration exceeds a threshold potential. A neural firing threshold, for example, may be approximately −55 mV. Action potentials propagate to the neuron's synapses and are then conveyed to other synaptically connected neurons.
Neural activity in the brain can be influenced by neural stimulation, which involves the application of electrical and/or magnetic stimuli to one or more target neural populations within a patient using a waveform generator or other type of device. Various neural functions can thus be promoted or disrupted by applying an electrical current to one or more regions of the brain. As a result, researchers have attempted to treat certain neurological conditions, including ET, using electrical or magnetic stimulation signals to control or affect brain functions.
Deep Brain Stimulation (DBS) is a neural stimulation therapy that has been used as an alternative to drug treatments and ablative surgical therapies. In DBS, one or more electrodes are surgically implanted into the brain proximate to deep brain or subcortical neural structures. For treating ET, an electrode is typically positioned in or proximate to the ventrointermediate nucleus (VIM) of the thalamus. In a typical DBS system, a pulse generator delivers a continuous or essentially continuous electrical stimulation signal having a pulse repetition frequency of approximately 150 Hz to each of two deep brain electrodes. U.S. Pat. No. 5,883,709 discloses one conventional DBS system for treating movement disorders.
Although DBS therapies may significantly reduce ET symptoms, particularly when combined with drug treatments, they are highly invasive procedures. In general, configuring a DBS system to properly function within a patient requires a time consuming, highly invasive surgical procedure for implanting at least one, and possibly two, DBS electrodes. DBS surgical procedures have essentially the same risks as those described above for ablative surgical intervention.
Motor Cortex Stimulation (MCS) is another type of brain stimulation treatment that has been proposed for treating movement disorders, such as ET and Parkinson's disease. MCS involves the application of stimulation signals to the motor cortex of a patient. One MCS system includes a pulse generator connected to a strip electrode that is surgically implanted over a portion of only the motor cortex (precentral gyrus). The use of MCS to treat symptoms associated with Parkinson's Disease is described in Canavero, Sergio, “Extradural Motor Cortex Stimulation for Advanced Parkinson's Disease: Case Report,” Movement Disorders (Vol. 15, No. 1, 2000).
Because MCS involves the application of stimulation signals to surface regions of the brain rather than deep neural structures, electrode implantation procedures for MCS are significantly less invasive and time consuming than those for DBS. As a result, MCS may be a safer and simpler alternative to DBS for treating ET symptoms. Present MCS techniques, however, fail to address or adequately consider a variety of factors that may enhance or optimize the extent to which a patient experiences short term and/or long term relief from ET symptoms.
The following disclosure describes several embodiments and systems for treating essential tremor and other movement disorders using cortical stimulation. Several features of methods and systems in accordance with embodiments of the invention are set forth and described in
In process portion 106, the method 100 a includes at least reducing an essential tremor motion of the patient by applying an electrical stimulation at least proximate to a stimulation site, with the location of the stimulation site based at least in part on the information collected in method portion 104. For example, an operator and/or a computer-based set of instructions can apply an electrical stimulation to one or more electrodes or electrical contacts placed within the patient's brain. Further aspects of this and other embodiments of process portion 106 are also described in greater detail below with reference to
In method portion 112, the practitioner can monitor a first or baseline image of the patient's brain function while the patient is not performing the muscle action identified in method portion 110 (e.g., while the patient or relevant patient muscles are generally at rest, or the patient avoids performing the muscle action). In one embodiment, the first image can be generated using functional magnetic resonance imaging (fMRI) techniques, magnetic resonance imaging (MRI) techniques, or computed tomography (CT) techniques. In a particular aspect of this embodiment, the first image can be generated by fMRI techniques that determine the level of the patient's brain function based on a measurement of blood oxygen levels in the patient's brain. In other embodiments, the level of the patient's brain function is ascertained by other techniques. In any of these embodiments, the first image can include an image of a portion of the patient's brain upon which is superimposed some indication of the brain activity level. For example, the image can be color-coded to distinguish parts of the brain having a high level of activity (e.g., presented in one color) from portions of the brain having a relatively low level of activity (e.g., presented in another color). The image can include an image of the relative position between external markers and at least one of the central sulcus, precentral gyrus, and/or the postcentral gyrus of a patient. The external markers can be anatomical features of the patient (e.g., the patient's nose bridge or ear canal) or fiducials that are attached to the patient. For example, the external markers can be fiducials that are attached to the skull of the patient.
In method portion 114, the practitioner can monitor a second image of the patient's brain function while the patient performs the muscle action identified in method portion 110. In a particular aspect of this embodiment, the technique used to generate the second image is at least approximately identical to the technique used to produce the first image. Accordingly, the two images can be easily compared.
In method portion 116, the first and second images are compared to identify a stimulation site of the brain. For example, if a particular portion of the brain shows activity when the patient executes an essential tremor motion or assumes an essential tremor posture, this region can be identified by comparing the first image with the second image. In some cases, a portion of the brain responsible for coordinating the muscle movement required to execute the motion or assume the posture may also be a portion of the brain responsible for generating the tremor motion itself. In other embodiments, the correlation between the portions of the brain responsible for these two functions may be less clear. In these situations, the practitioner may use additional techniques (described in greater detail below with reference to
In method portion 118, the practitioner can place at least one electrode at least proximate to the stimulation site determined in method portion 116. In method portion 120, the patient's essential tremor motion is reduced or eliminated by applying an electrical stimulation at least proximate to the stimulation site. The neural stimulation can be an electrical current applied epidurally or subdurally to the stimulation site. When the neural stimulation is an electrical current applied directly to the cerebral cortex proximate to the dura, the method 100 b can include implanting an electrode at least proximate to the dura at the stimulation site. In other embodiments, the neural stimulation can be transcutaneous magnetic stimulation. Several aspects of electrodes, placement techniques, and stimulation techniques in accordance with particular embodiments of the invention are described in more detail below with respect to
In a further aspect of an embodiment of the methods 100 a, 100 b described above, an axial image of the cortex 220 is generated.
Identifying a stimulation site of the brain (method portion 116,
The linear electrode array 310 can be positioned so that the row of electrodes 320 extends in a medial to lateral direction generally parallel with the central sulcus 244. The electrodes 320 are also superimposed over the precentral gyrus 250. The linear electrode array 310 generally has a plurality of electrodes 320 to provide extensive coverage over the precentral gyrus 250 and thus activate a large number of neurons in the motor cortex (e.g., use all of the electrodes) or only discrete populations of neurons in the motor cortex with only a single implantation of an electrode array (e.g., activate only selected electrodes). The electrode array 310 can be implanted so that the electrodes are proximate to the dura such as at an epidural or subdural location.
One aspect of several embodiments of the invention is that the stimulation sites 300 a and 300 b shown on
The particular waveform of the stimuli depends upon the symptoms of the particular patients. In one embodiment, the stimulus can have a waveform with a voltage of approximately 0.25 V-5.0 V, a pulse duration of approximately 20 microseconds-500 milliseconds, and a frequency of approximately 10 Hz-200 Hz. In other embodiments, the electrical stimulus can have a voltage of 0.5 V-3.5 V, a pulse duration of 100 microseconds-200 microseconds, and a frequency of approximately 20 Hz-50 Hz. In still other embodiments, the voltage of the waveform can be approximately 2.0-3.5 V, and more particularly approximately around 3 V. Additionally, the pulse duration can be in the range of 90-180 microseconds. The stimulus can be applied for a period of 0.5 hour-4.0 hours, and in many applications the therapy is applied for a period of approximately 0.5 hour-1.5 hours. In other embodiments, the stimulation can be applied continuously, or only during waking periods but not sleeping periods. Examples of specific stimulation protocols for use with an electrode array at an epidural stimulation site over the precentral gyrus are as follows:
An electrical stimulus having a voltage of approximately 2.1 V, an impedance of 600 to 1000 Ohms, a pulse duration of 160 microseconds, and a frequency of approximately 130 Hz. The therapy is not applied continuously, but rather during 30-60 minute intervals.
The stimulus has a voltage amplitude of approximately 3 V-3.5 V, a pulse duration of approximately 150-180 microseconds, and a frequency of approximately 25 Hz-31 Hz. The stimulus is applied continuously during waking periods, but it is discontinued during sleeping periods to conserve battery life of the implanted pulse generator.
The stimulus has a voltage of approximately 3.0 V, a pulse duration of approximately 90 microseconds, and a frequency of approximately 30 Hz. This stimulus is applied continuously during waking and sleeping periods, but it can be discontinued during sleeping periods.
In a particular aspect of an embodiment of the method 700 a described above, a practitioner can make use of the frequent tendency of the patient to manifest essential tremor symptoms on one side of the body more than on the other. For example, if the patient has more essential tremor motion associated with movement of the left hand than with the right hand, the practitioner can ask the patient to move the left hand and then view an image of the right side of the patient's brain while the patient undergoes the directed movement. The practitioner can then direct the patient to move the right hand while viewing an image of the left hemisphere of the patient's brain. By comparing the two images, the practitioner can attribute common aspects of the active areas of the images to brain activity associated with non-essential tremor movement, and differences between active areas of the images with motion related to essential tremor. For example, in a particular embodiment, the common aspects of the images can include common areas or volumes indicated to have heightened neural activity. In other embodiments, the common aspects can include areas or volumes that have the same level of heightened neural activity. In either embodiment, the practitioner can compare the two images to more accurately identify the portion of the brain associated with the essential tremor motion and can therefore more accurately target this portion of the brain with electrical stimulation. In still further embodiments, (as described above), some or all of the foregoing method portions can be executed automatically by a computer and without generating a visual image.
Referring now to
In any of the embodiments described above with reference to
From the foregoing, it will be appreciated that specific embodiments of the invention have been described herein for purposes of illustration, but that various modifications may be made without deviating from the spirit and scope of the invention. For example, the leads of the electrode arrays may be coupled to an external pulse generator instead of an implanted pulse generator. Methods and systems in accordance with other embodiments of the invention are included in pending U.S. Provisional Application No. 60/432,073, (attorney docket no. 33734.8040US) entitled “System and Method for Treating Parkinson's Disease and other Movement Disorders,” filed Dec. 9, 2002 and pending U.S. application Ser. No. 10/317,002 (attorney docket no. 33734.8048US), entitled “Systems and Methods for Enhancing or Optimizing Neural Stimulation Therapy for Treating Symptoms of Parkinson's Disease and/or Other Movement Disorders,” filed Dec. 10, 2002, both incorporated herein by reference. Accordingly, the invention is not limited except as by the appended claims.
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|US7869867||Oct 27, 2006||Jan 11, 2011||Cyberonics, Inc.||Implantable neurostimulator with refractory stimulation|
|US7869884||Apr 26, 2007||Jan 11, 2011||Cyberonics, Inc.||Non-surgical device and methods for trans-esophageal vagus nerve stimulation|
|US7869885||Apr 28, 2006||Jan 11, 2011||Cyberonics, Inc||Threshold optimization for tissue stimulation therapy|
|US7904175||Apr 26, 2007||Mar 8, 2011||Cyberonics, Inc.||Trans-esophageal vagus nerve stimulation|
|US8600513 *||Dec 7, 2011||Dec 3, 2013||The Board Of Trustees Of The Leland Stanford Junior University||Seizure prediction and neurological disorder treatment|
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|International Classification||A61N1/32, A61N1/18, A61N1/05, A61N1/36, A61N1/08|
|Cooperative Classification||A61N1/36135, A61N1/36067, A61N1/0531, A61N1/08, A61N1/32|
|European Classification||A61N1/05K1C, A61N1/36Z, A61N1/32, A61N1/36, A61N1/08|
|Jun 12, 2009||AS||Assignment|
Owner name: ADVANCED NEUROMODULATION SYSTEMS, INC.,TEXAS
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:NORTHSTAR NEUROSCIENCE, INC.;REEL/FRAME:022813/0542
Effective date: 20090521