# US 8,150,524 B2 · Selective neurostimulation for treating epilepsy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,150,524 B2 - Document ID: US8150524B2 - Status: Granted - Kind: B2 - Application number: 12/467,804 - Filed: 2009-05-18 - Published: 2009-09-17 - Granted: 2012-04-03 - Earliest claimed: 2005-10-28 - Assignees: Cyberonics, Inc. - Inventors: Steven E. Maschino; Stephen Brannan - Web page: https://patentgrep.com/patent/US8150524B2 ## CPC - A61M 5/14276: {specially adapted for implantation} - A61N 1/36082: {Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease} - A61N 2/006: {for magnetic stimulation of nerve tissue} - A61M 2005/1726: {the body parameters being measured at, or proximate to, the infusion site} - A61M 2205/054: with electrotherapy - A61M 2205/3523: using telemetric means - A61M 2205/3569: sublocal, e.g. between console and disposable - A61M 2210/0693: Brain, cerebrum - A61N 1/0529: {Electrodes for brain stimulation} - A61N 1/0531: {Brain cortex electrodes} - A61N 1/0534: {Electrodes for deep brain stimulation} - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) ## Abstract A method and device for treating epilepsy are disclosed which provide for electrical, chemical or magnetic stimulation of certain areas of the brain to modulate neuronal activity of areas associated with symptoms of epilepsy. Deep brain stimulation is combined with vagus nerve stimulation to enhance symptomatic relief of the disorder. Some embodiments also employ a sensing capability to optimize the therapeutic treatment regimen. ## Claims ### Claim 1 A method of treating an individual suffering from epilepsy, the method comprising: applying a first stimulation signal to a first stimulator configured to be coupled to a stimulation site comprising a volume of neural tissue in an area of the individual's brain selected from the group consisting of insula, subcallosal area, cingulate, thalamus, prefrontal cerebral cortex, mesial temporal lobe, cerebellum, hypothalamus, hippocampus, amygdala, brain stem, occipital lobe, temporal lobe, frontal lobe, parietal lobe, Wernicke's area, area tempestas, basal ganglia, globus pallidus, superior colliculus, striatum, ventral striatum, ventral pallidum, caudate nucleus, putamen, nucleus accumbens, substantia nigra, ventral tegmentum, Brodmann areas 24, 25, 32, piriform cortex, ventricular region, ventral pallidum, and forebrain circumventricular organs, reticulate substantia innominata, rostral midbrain, red nucleus, periaqueductal gray, and white matter tracts leading to an aforementioned area or nucleus, wherein the first stimulation signal causes modulation of the neuronal activity of neural tissue in said selected area of the brain; applying a second stimulation signal to a second stimulator configured to be coupled to a site on the vagus nerve of the individual such that said second stimulation signal causes modulation of the neuronal activity in said vagus nerve, wherein said first and/or second stimulation signal causes modulation of neuronal activity in at least one brain area of said individual different than said area coupled to said first stimulator, and wherein said combination of modulations attenuate at least one epilepsy symptom and/or deter recurrence of an epileptic event; after applying the first stimulation signal to the selected area of the brain, sensing neuronal activity in the selected area of the brain with at least one first sensor; after applying the second stimulation signal to the vagus nerve, sensing neuronal activity in the different area of the brain with at least one second sensor; and based on data collected from the sensing in at least the different area of the brain, adapting a stimulation parameter of the first and/or second stimulation signal to increase the attenuation of at least one epilepsy symptom and/or the deterrence of an epileptic event for a subsequent combination of modulations. ### Claim 2 (depends on 1) The method of claim 1 wherein said second stimulation signal causes stimulation of a site on the vagus nerve, whereby at least one vagus nerve pathway or neural activating circuit is affected causing a responsive effect on neural activity in at least one area of the brain to further attenuate the same or different epilepsy symptom and/or to further deter recurrence of an epileptic event. ### Claim 3 (depends on 2) The method of claim 2 wherein said vagus nerve pathway or neural activating circuit is chosen from the group consisting of gustatory pathways, olfactory pathways, pro-inflammatory or anti-inflammatory pathways, respiratory pathways, cardiac pathways, baroreceptor pathways, somatosensory pathways, noradrenergic pathways, serotoninergic pathways, dopaminergic pathways, catecholaminergic pathways, GABAergic pathways, opioidergic pathways, cholinergic pathways, circuit of Papez, mesolimbic pathway, mesocortical pathway and nigrostriatal pathway. ### Claim 4 (depends on 3) The method of claim 3 wherein said responsive effect on said area of the brain is excitatory or inhibitory and potentiates acute and/or long-term changes in neuronal activity of said area of the brain. ### Claim 5 (depends on 1) The method of claim 1 wherein said first stimulation signal comprises a first acute stimulation component and a first chronic stimulation component and/or said second stimulation signal comprises a second acute stimulation component and a second chronic stimulation component. ### Claim 6 (depends on 5) The method of claim 5 wherein said first acute stimulation component comprises a higher intensity level of stimulation and shorter duration than said first chronic stimulation component and/or said second acute stimulation component comprises a higher intensity level of stimulation and shorter duration than said second chronic stimulation component. ### Claim 7 (depends on 5) The method of claim 5 wherein said first and/or second acute stimulation component comprises a duration in the range of one day to six months. ### Claim 8 (depends on 1) The method of claim 1 wherein said selected area of the individual's brain comprises a portion of the cingulate gyrus comprising the anterior cingulate or the posterior cingulate. ### Claim 9 (depends on 1) The method of claim 1 wherein said selected area of the individual's brain comprises a portion of the cortex chosen from the group consisting of motor cortex, prefrontal cortex, orbitofrontal cortex, premotor cortex, somatosensory cortex, cingulate cortex, anterior cingulate cortex, insular cortical region and Brodmann areas 8, 9, 10, 11. ### Claim 10 (depends on 1) The method of claim 1 wherein said selected area of the individual's brain comprises a portion of the thalamus chosen from the group consisting of ventral medial thalamic nucleus, ventral posterior medial thalamic nucleus, parafascicular nucleus, subthalamic nucleus, dorsomedial thalamic nucleus, intralaminar thalamic nuclei, midline thalamic nuclei, anterior thalamus, anterior thalamic nuclei, nucleus reticularis thalami, and centromedian nucleus of the thalamus. ### Claim 11 (depends on 1) The method of claim 1 wherein said selected area of the individual's brain comprises a portion of the hypothalamus chosen from the group consisting of lateral hypothalamus, paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, mamillary bodies, supraoptic nucleus, dorsomedial nucleus of the hypothalamus, lateral nucleus of the hypothalamus, tuberal nucleus of the hypothalamus. ### Claim 12 (depends on 1) The method of claim 1 wherein said selected area of the individual's brain comprises a portion of the brainstem/medulla chosen from the group consisting of locus ceruleus, dorsal raphe nucleus, nucleus of the solitary tract, the entirety of the solitary tract, the caudal ventrolateral medulla, rostral ventrolateral medulla and parabrachial nucleus. ### Claim 13 (depends on 1) The method of claim 1 wherein said first stimulator is a first electrode and said second stimulator is a second electrode, and said method further comprises: providing at least one programmable electrical signal generator coupled to said first and second electrodes; programming said at least one electrical signal generator to define each of said first and second stimulation signals by a plurality of electrical parameters comprising a current magnitude, a pulse frequency, and a pulse width, wherein said parameters are selected to attenuate or deter the occurrence of at least one symptom of epilepsy. ### Claim 14 (depends on 1) The method of claim 1 wherein said first and/or second stimulator comprises at least one chemical dispensing assembly comprising a chemical filled reservoir and a catheter in communication with a pump, said catheter comprising a dispensing end located on or near said nerve or brain area, and said first and/or second stimulation signal each comprises a therapeutic pumping signal, said method comprising: operating at least one said pump such that said chemical contacts said selected brain area and/or vagus nerve, whereby the neuronal activity of the contacted brain area and/or nerve is modified, and such modification of neuronal activity causes attenuation or deterrence of at least one symptom of epilepsy. ### Claim 15 (depends on 14) The method of claim 14 wherein said chemical agent is selected from the group consisting of inhibitory neurotransmitter agonists, excitatory neurotransmitter antagonists, agents that increase the level of an inhibitory neurotransmitter, agents that decrease the level of an excitatory neurotransmitter, and local anesthetic agents. ### Claim 16 (depends on 1) The method of claim 1 wherein said selected area of the individual's brain comprises the thalamus or a white matter tract leading to a portion of the thalamus. ### Claim 17 (depends on 1) The method of claim 1 wherein the adapting of a stimulation parameter of the first and/or second stimulation signal comprises: a comparator comparing the sensed neuronal activity in the different area of the brain to a predetermined electrical state of the different area of the brain; determining from the comparison that the modulation of electrical activity in the different area of the brain was not sufficient to treat the individual's epilepsy adequately; and a controller coupled to the comparator determining a change in the stimulation parameter of the first and/or second stimulation signal to increase the attenuation of at least one epilepsy symptom and/or the deterrence of an epileptic event for a subsequent combination of modulations. ### Claim 18 A method of treating an individual suffering from epilepsy, the method comprising: applying a first stimulation signal to a first stimulator configured to be coupled to a stimulation site comprising a volume of neural tissue in an area of the individual's brain selected from the group consisting of insula, subcallosal area, cingulate, thalamus, prefrontal cerebral cortex, mesial temporal lobe, cerebellum, hypothalamus, hippocampus, amygdala, brain stem, occipital lobe, temporal lobe, frontal lobe, parietal lobe, Wernicke's area, area tempestas, basal ganglia, globus pallidus, superior colliculus, striatum, ventral striatum, ventral pallidum, caudate nucleus, putamen, nucleus accumbens, substantia nigra, ventral tegmentum, Brodmann areas 24, 25, 32, piriform cortex, ventricular region, ventral pallidum, and forebrain circumventricular organs, reticulate substantia innominata, rostral midbrain, red nucleus, periaqueductal gray, and white matter tracts leading to an aforementioned area or nucleus, wherein the first stimulation signal causes modulation of the neuronal activity of neural tissue in said selected area of the brain; applying a second stimulation signal to a second stimulator configured to be coupled to a site on the vagus nerve of the individual such that said second stimulation signal causes modulation of the neuronal activity in said vagus nerve, wherein said first and/or second stimulation signal causes modulation of neuronal activity in at least one brain area of said individual different than said area coupled to said first stimulator, and wherein said combination of modulations attenuate at least one epilepsy symptom and/or deter recurrence of an epileptic event; after applying the second stimulation signal to the vagus nerve, sensing neuronal activity in the selected area of the brain or the different area of the brain with at least one sensor; and based on data collected from the sensing and using a controller coupled to the sensor and to the first or second stimulator, adapting a stimulation parameter of the first or second stimulation signal to increase the attenuation of at least one epilepsy symptom and/or the deterrence of an epileptic event for a subsequent combination of modulations. ### Claim 19 A method of treating an individual suffering from epilepsy, the method comprising: applying a first stimulation signal to a first stimulator configured to be coupled to a stimulation site comprising a volume of neural tissue in an area of the individual's brain selected from the group consisting of insula, subcallosal area, cingulate, thalamus, prefrontal cerebral cortex, mesial temporal lobe, cerebellum, hypothalamus, hippocampus, amygdala, brain stem, occipital lobe, temporal lobe, frontal lobe, parietal lobe, Wernicke's area, area tempestas, basal ganglia, globus pallidus, superior colliculus, striatum, ventral striatum, ventral pallidum, caudate nucleus, putamen, nucleus accumbens, substantia nigra, ventral tegmentum, Brodmann areas 24, 25, 32, piriform cortex, ventricular region, ventral pallidum, and forebrain circumventricular organs, reticulate substantia innominata, rostral midbrain, red nucleus, periaqueductal gray, and white matter tracts leading to an aforementioned area or nucleus, wherein the first stimulation signal causes modulation of the neuronal activity of neural tissue in said selected area of the brain; applying a second stimulation signal to a second stimulator configured to be coupled to a site on the vagus nerve of the individual such that said second stimulation signal causes modulation of the neuronal activity in said vagus nerve, wherein said first and/or second stimulation signal causes modulation of neuronal activity in at least one brain area of said individual different than said area coupled to said first stimulator, and wherein said combination of modulations attenuate at least one epilepsy symptom and/or deter recurrence of an epileptic event; after applying the first stimulation signal to the selected area of the brain and after applying the second stimulation signal to the vagus nerve, sensing neuronal activity in the selected area of the brain or the different area of the brain with at least one sensor; and based on data collected from the sensing, adapting a stimulation parameter of the first and/or second stimulation signal to increase the attenuation of at least one epilepsy symptom and/or the deterrence of an epileptic event for a subsequent combination of modulations. ### Claim 20 (depends on 19) The method of claim 19 wherein the adapting of a stimulation parameter of the first and/or second stimulation signal comprises: a comparator comparing the sensed neuronal activity in the selected area of the brain or the different area of the brain to a predetermined electrical state of the respective selected area of the brain or different area of the brain; determining from the comparison that the modulation of electrical activity in the selected area of the brain or the different area of the brain was not sufficient to treat the individual's epilepsy adequately; and a controller coupled to the comparator determining a change in the stimulation parameter of the first and/or second stimulation signal to increase the attenuation of at least one epilepsy symptom and/or the deterrence of an epileptic event for a subsequent combination of modulations.