US 5752979 A
A method of preventing seizures as experienced by persons with Epilepsy. Electrical stimulation pulses are supplied to the external segment of the globus palliaus nucleus of the brain causing increased excitation thereby increasing inhibition of neural activity in the subthalamic nucleus and reducing excitatory input to the substantia nigra which leads to a reduction in the occurrence of seizures.
1. A method of therapeutically treating epilepsy resulting in a reduction in the occurrence of seizures by means of a signal generator and an implantable electrode having a proximal end and a stimulation portion comprising the steps of:
surgically implanting said electrode in the brain so that the stimulation portion lies in the external segment of the globus pallidus nucleus of the brain;
coupling said proximal end of said electrode to said signal generator; and
operating said signal generator at a predetermined stimulus repetition rate to facilitate excitation of neurons in the external segment of the globus pallidus which results in an increase in the inhibition of neurons of the subthalamic nucleus to reduce the excitatory input from the subthalamic nucleus to the substantia nigra there by reducing the occurrence of seizures.
2. A method, as claimed in claim 1, wherein said stimulus repetition rate is about 2-100 Hz.
1. Field of the Invention
This invention relates to brain stimulation techniques, and more particularly relates to such techniques for treating epilepsy.
2. Description of Related Art
Epileptic seizures are the outward manifestation of excessive and/or hyper synchronous abnormal activity of neurons in the cerebral cortex. Seizures are usually self limiting. Many types of seizures occur. The behavioral features of a seizure reflect function of the portion of the cortex where the hyper activity is occurring. Seizures can be generalized, appearing to involve the entire brain simultaneously. Generalized seizures can result in the loss of conscious awareness only and are then called absence seizures (previously referred to as "petit mal"). Alternatively, the generalized seizure may result in a convulsion with tonic-clonic contractions of the muscles ("grand mall" seizure). Some types of seizures, partial seizures, begin in one part of the brain and remain local. The person may remain conscious throughout the seizure. If the person looses consciousness the seizure is referred to as a complex partial seizure.
Researchers have developed several lines of evidence in studies with animals to demonstrate the existence of a system which can control the propagation and/or the generation of different kinds of seizures. The involvement of the substantia nigra, a particular portion of the brain considered to be part of neural circuitry referred to as the basal ganglia, was first suggested by Gale (Fed. Proc. 44, 2414-2424, 1985). Considerable evidence has been generated through research to support this observation and was reviewed by Depaulis, Vergnes and Marescaux (Progress in Neurobiology, 1994, 42:33-52). Researchers have shown that the inhibition of the substantia nigra will increase the threshold for seizure occurrence in experimental animal models of epilepsy.
Neuroscientist now have a better understanding of the neural connections that make up the basal ganglia. These connections are reviewed by (Alexander, Crutcher, and DeLong, "Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, `prefrontal` and `limbic` functions." Prog Brain Res. 85:119-146.). The substantia nigra receives input from the subthalamic nucleus(STN) which is excitatory and involves glutamate as the neurotransmitter conveying information at the synapse. Bergman et al. have shown that a lesion of the subthalamic nucleus will reduce the inhibitory output of the internal segment of the globus pallidus and substantia nigra reticulata(SN) (H. T. Bergman, T. Wichmann, and M. R. DeLong, 1990, Science, 249:1436-1438). The subthalamic nucleus receives input from the external segment of the globus pallidus(GPe). This input is inhibitory using GABA as a transmitter substance. Hence, increased activity of the neurons in GPe will increase inhibition of neurons in the subthalamic nucleus which will reduce the excitation of neurons in the substantia nigra.
Benabid et al. (The Lancet, Vol 337: Feb 16, 1991, pp 403-406) have shown that stimulation of the Vim nucleus of the Thalamus will block tremor. In this instance, stimulation at frequencies around 100 to 185 pulses per second accomplishes the same physiological response as a lesion of this region. Benabid's research team has extended this work to stimulation of the subthalamus in order to help reduce symptoms of motion disorders ("Vim and STN Stimulation in Parkinson's disease", Movement Disorders, Vol 9, Supplement 1(1994); "Effect on Parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation", The Lancet, Vol 345, Jan. 14, 1995.) It has been known for some time that electrical stimulation of neurons at lower stimulus pulse frequencies will activate the neurons.
A preferred form of the invention can treat a movement disorder resulting in abnormal motor response by means of an implantable signal generator and an implantable electrode having a proximal end coupled to the signal generator and having a stimulation portion for therapeutically stimulating the brain. The electrode is implanted in the brain so that the stimulation portion lies in the external globus pallidus. The signal generator is operated to pulse the electrode at a predetermined rate and amplitude that is sufficient to increase the activity of the neurons in the external globus pallidus causing an increased inhibition of the neurons in the subthalamic nucleus and thereby reduce the excitation of the substantia nigra by the subthalamic nucleus. The reduction in excitation of the substantia nigra reduces the occurrence of seizures.
By using the foregoing method, the occurrence of epileptic seizures in persons with epilepsy is reduced beyond the level attainable by prior art methods or apparatus.
These and other advantages and features of the invention will become apparent upon reading the following detailed description and referring to the accompanying drawings in which like numbers refer to like parts throughout and in which:
FIG. 1 is a diagrammatic illustration of a stimulation electrode implanted in a brain according to a preferred embodiment of the present invention and a signal generator coupled to the electrode.
Referring to FIG. 1, a system or device 10 made in accordance with the preferred embodiment may be implanted below the skin of a patient. Device 10 may be implanted beneath the clavicle on the chest or in the abdomen. A lead 22A is positioned to stimulate a specific site in a brain (B). Device 10 may take the form of a modified signal generator Model 7424 manufactured by Medtronic, Inc. under the trademark Itrel II which is incorporated by reference. Lead 22A may take the form of any of the leads sold with the Model 7424, for stimulating the brain, and is coupled to device 10 by a conventional conductor 22.
The distal end of lead 22A terminates in four stimulation electrodes generally designated 115 implanted into a portion of the basal ganglia of the brain by conventional stereotactic surgical techniques. However, other numbers of electrodes, such as two or six, may be used. Each of the four electrodes is individually connected to device 10 through lead 22A and conductor 22. Lead 22A is surgically implanted through a hole in the skull 123 and conductor 22 is implanted between the skull and the scalp 125 as shown in FIG. 1. Conductor 22 is joined to implanted device 10 in the manner shown.
Device 10 is programmed to produce stimulation pulses having a repetition rate of about 2-100 HZ. At the stated frequency, stimulation causes an excitation of the neurons in GPe which results in an increase in the inhibition of neurons of the subthalamic nucleus which leads to a reduction of the excitatory input conveyed by the axons projecting from the subthalamic nucleus to the substantia nigra. By reducing the excitation of the substantia nigra this method may reduce the chance that the user will have a seizure.
By using the foregoing techniques, the number of seizures experienced by persons with epilepsy can be controlled with a degree of accuracy previously unattainable.
Those skilled in the art will recognize that the preferred embodiment may be altered or amended without departing from the true spirit and scope of the invention, as defined in the accompanying claims.
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