System, method and catheter for pituitary and brain implantation

Abstract

The present invention relates to a system, its catheter and its method for providing electrical pulses and/or therapeutic or diagnostic liquids directly to a pituitary gland of a mammal. The catheter, containing an electrode or a microcannula or both, is moved through an endovascular route of a patient to his/her sinus cavernosus and then the distal end of the electrode or microcannula is moved through an opening in the distal end of the catheter and then through a perforation in the medial wall of the sinus cavernosus, to the pituitary gland.

What is claimed herein is: 
     
         1 . A system for providing electrical pulses and/or therapeutic or diagnostic liquids directly to a pituitary gland of a mammalian patient or to a pituitary stalk, a hypothalamus, or other brain area of a mammalian patient via the pituitary gland;
 the system being movable through a catheter having a distal end comprising an opening, the catheter configured to be movable distally through blood vessels of an endovascular route of the mammalian patient and then into and through a sinus cavernosus of the mammalian patient, the system comprising:
 a (micro)electrode and/or a microcannula, a distal end of which is configured to be movable distally within the catheter through the endovascular route, and then into and through the sinus cavernosus, and then distally out of the catheter through an opening in the distal end of the catheter, and then through a perforation in a medial wall of the sinus cavernosus to the pituitary gland, and then to and into or around the pituitary gland; 
   wherein the system is capable of actively bending to a predetermined angle of from 30° to 120° when moving along the endovascular route in the catheter.   
     
     
         2 . The system of to  claim 1 , wherein the catheter is provided for, and operable to move via the endovascular route from the ileac vein or femoral vein in a groin or the cephalic vein in the arm of the patient wherein the system further comprises at least two action members and/or steering members disposed in an exterior lumen, to actively bend or pivot the catheter to a predetermined angle of no less than 75°. 
     
     
         3 . The system of to  claim 1 , wherein the catheter further comprises:
 at least a first annular wall component;   at least a second annular wall component; and   at least one of:
 a) an annular lumen disposed between the first annular wall component and the second annular wall component; and 
 b) one or more working channels incorporated into the first annular wall component and/or second annular wall component of the catheter, and at least an interior lumen disposed inside the interior of the first annular wall component and/or second annular wall component. 
   
     
     
         4 . The system of  claim 3 , further comprising at least a secondary catheter for accessing the pituitary stalk, the secondary catheter being:
 located inside the primary catheter;   provided to be operable to project distally from the first catheter; and   provided and operable for actively bending or pivoting at a predetermined angle of no less than 75°.   
     
     
         5 . The system of  claim 3 , wherein the first annular wall component and/or second annular wall component comprises at least one action member and/or steering member. 
     
     
         6 . The system according to  claim 1 , wherein at least one of the action members is a push wire having a distal end that is disposed to and operable to move:
 distally within the catheter, through the endovascular route and then into and through the sinus cavernosus; and   then distally out of the catheter through the opening in the distal end of the catheter and then through the perforation in the medial wall of the sinus cavernosus.   
     
     
         7 . The system of  claim 1 , wherein the catheter further comprises a tip containing a sharp element that can be projected distally from the opening in the distal end of the catheter to form the perforation in the medial wall of the cavernous sinus. 
     
     
         8 . The system of  claim 1 , wherein a distal-most part of the catheter further comprises a malleable cushion to allow good contact of the distal-most part with the surface of the medial wall of the sinus cavernosus;
 wherein the exterior of the distal end of the catheter, adjacent to, and proximal of, the malleable cushion, comprises an annular collar that can be inflated or otherwise deployed, so that distal surfaces of the annular collar are projected distally from the distal end of the catheter, enclosing a volume around the distal end of the catheter, around the perforation in the medial wall of the cavernous sinus to close a space around the opening in the distal end of the catheter between the distal end of the catheter and the perforation.   
     
     
         9 . The system of  claim 2 , wherein the action member comprises at least a first guide wire for pivoting or steering the distal end of the catheter in a desired direction, for controlling its distal movement through the endovascular route and then into and through the sinus cavernosus. 
     
     
         10 . The system of  claim 1 , wherein an exterior of a distal part of the catheter and/or the microcannula, comprises a radiopaque ring that can be recognized by X-ray, fluoroscopy, angiogram, MRI, or a CT-scan; and/or
 wherein a distal part of the catheter comprises an electromagnetic localizer which comprises a transmitter and receiver coil array, permitting it to transmit electromagnetic signals and receive electromagnetic energy from a transmitter coil array.   
     
     
         11 . The system of  claim 8 , wherein an exterior of the distal end of the catheter, adjacent to, and proximal of, the annular collar, also comprises a stabilizing device comprising an inflatable tripod and provided circumferentially about an exterior of the catheter and comprising inflatable, radially extendable legs. 
     
     
         12 . The system of  claim 1 , wherein a distal part of the catheter has a peel-away configuration, so that the catheter can be removed from the patient in such a way that the electrode or microcannula remains intact and in place. 
     
     
         13 . The system of  claim 1 , wherein the system further comprises an electrode or electrode array, the distal end of which has one or more contact points for electrical stimulation of endocrine tissue of the pituitary gland, the pituitary stalk, or the hypothalamus; and/or
 the system comprises a microcannula, the distal end of which has one or more central hollow channels, each central hollow channel comprising one or more side openings, through which small volumes of a fluid or gel can flow into the pituitary gland, the pituitary stalk, or the hypothalamus, preferably with side openings that can be opened and closed by a remote control.   
     
     
         14 . The system of  claim 13 , wherein the distal end of the electrode is adapted to:
 electrically stimulate the pituitary gland to produce and secrete adrenocorticotropic hormone (ACTH) and/or alpha-melanocyte stimulating hormone (MSH); and/or   electrically stimulate the pituitary gland to stimulate the magnocellular nuclei of the anterior hypothalamus through axons that descend through the pituitary stalk to the pituitary gland.   
     
     
         15 . The system of  claim 13 , wherein a distal portion of the electrode or electrode array and/or microcannula has a shape memory and thus can form a three-dimensional shape, within or about the pituitary gland. 
     
     
         16 . The system of  claim 15 , wherein the electrode array is provided for interfacing with an organ tissue in situ, the electrode array comprising:
 a) a deformable array of electrodes comprising a plurality of electrodes in electrical communication with a plurality of deformable electrical interconnects and a connector line; wherein the deformable array of electrodes provides a net bending stiffness of the electrode array low enough that the system is capable of establishing conformal contact with the tissue in situ; and   b) a connection plug at a proximal end of the connector line of the electrode array, the connection plug comprising:
 a distal end which can be attached to a bone adjacent to the organ tissue, including but not limited to an anterior wall of the sphenoid sinus and/or vomer, and 
 a proximal end which can be reversibly connected electrically to a wire that is connected electrically to a source of electrical stimulation for the organ tissue. 
   
     
     
         17 . The system of  claim 3 , wherein the first annular wall component and/or second annular wall component is removable while leaving the microcannula and/or the electrode or electrode array in place, and optionally, further comprising an optionally subcutaneously provided reservoir and/or control or pump unit for controlling and providing electrical pulses and/or therapeutic or diagnostic liquids directly to a pituitary gland via the microcannula or electrode, and/or measuring of currents in the electrode or electrode array. 
     
     
         18 . A method for providing electrical pulses and/or therapeutic or diagnostic liquids directly to a pituitary gland of a mammalian patient or to a pituitary stalk or to a hypothalamus or other basal ganglia of the brain of the mammalian patient via the pituitary gland, comprising the steps of:
 moving the distal end of a catheter of a system according to  claim 1  through an endovascular route of the mammalian patient from a vena jugularis of the mammalian patient, to an inferior or superior petrosal sinus of the mammalian patient, and then to a sinus cavernosus of the mammalian patient;   perforating a medial wall of the cavernous sinus to the pituitary gland;   moving the distal end of the electrode or microcannula or both distally from the catheter, through the opening in the distal end of the catheter and through the perforated medial wall of the sinus cavernosus, to the pituitary gland; and   removing the annular wall section of the catheter after leaving the electrode and/or microcannula in place.   
     
     
         19 . A method of alleviating an endocrinological medical condition in a mammalian patient suffering therefrom, the method comprising the steps of:
 (i) placing an electrode or electrode array in electrical contact with the pituitary gland of the mammalian patient using a system according to  claim 1 ;   (ii) detecting an activity associated with, or of relevance to, the endocrinological medical condition; and   (iii) activating the electrode or electrode array to initiate application of an electrical signal to the pituitary gland, or adjusting application of an electrical signal to the pituitary gland to alleviate, repair, or prevent worsening of the patient's endocrinological medical condition;   
       wherein the endocrinological medical condition comprises a problem related to the components of the endocrine system, including but not limited to the adrenal glands, pituitary gland, and hypothalamus, including hypoglycemia, diabetes type I and II, obesity, hyperthyroidism, hypothyroidism, amenorrhea, dysmenorrhea, infertility, impotence, anorgasmia, delayed orgasm, perimenstrual syndrome, hypercholesterolemia, hypertriglycridinemia, Cushing's disease, Addison's disease, Addison's crisis, malabsorption syndrome, dysautonomia, epilepsy, chronic fatigue syndrome, fatigue, heat exhaustion, cold extremities, hot flashes, vasomotor instability, Raynaud's syndrome, hormonal disorders, metabolic disorders such as gout, disorders of metabolism and metabolic storage diseases where there is an accumulation of abnormal amounts of various substances such as glycogen in glycogen storage diseases, iron in hemochromatosis or copper in Wilson's disease, auto-immune disorders, sleep disorders and disruptions in the circadian rhythm. In particular the present invention relates to the treatment of Adison's disease and Adison's crisis, as well as pain, pain perception, post-traumatic stress disorder, depression and anxiety. 
     
     
         20 . A method for the intra-pituitary gland administration of a pharmacologically active agent inducing or inhibiting production of steroidal hormones in the adrenal glands of a mammalian patient through change of the pituitary gland function, including but not limited to wherein the active agent comprises a corticotropin-releasing hormone (CRH) or analogue thereof, or combinations of CRH with other pharmacologically active components like vasopressin, the method comprising:
 i)a) transferring into the pituitary gland a pharmaceutical preparation comprising an effective concentration of the pharmacologically active agent through the microcannula of the catheter of the system according to  claim 1 ; and/or   i)b) electrically contacting at least a portion of the plurality of electrodes with the tissue by conformally contacting a surface of the tissue with the electrode array of a system according to  claim 1 ;   ii) spatially and temporally interfacing a brain tissue with the conformable device to monitor or actuate a spatio-temporal profile over the surface of the brain tissue in electrical contact with the plurality of electrodes; and   iii) actuating electrical activity over the surface of the brain tissue by applying an electric potential to a plurality of individual brain surface locations, each beneath an electrode of the plurality of electrodes at a plurality of different locations and/or time points.   
     
     
         21 . The method of  claim 20 , further comprising monitoring the spatio-temporal electrical brain profile with the device in conformal and electrical contact with a brain surface of the subject, wherein the monitoring comprises detecting an electric potential of a plurality of individual brain surface locations beneath each electrode of the array of electrodes at a plurality of different time points.