Deep brain stimulation in early stage Parkinson's
The present disclosure relates to the treatment of patients with Parkinson's Disease using subthalmic nucleus deep brain stimulation to a specific region of the brain. By positioning the electrode in the margin of the dorsal-lateral and anterior region of the subthalamic nucleus, improved benefits are obtained.
1. A method of treating Parkinson's Disease (PD) in an early stage PD subject comprising administering to said subject subthalamic nucleus (STN) deep brain stimulation (DBS) over a period of at least two years by positioning a DBS electrode in the margin of the dorsal-lateral and anterior region of the subthalamic nucleus and applying electrical current to said subject through said electrode, wherein treating comprises one or more of slowing of motor symptom progression, stopping motor symptom progression, and/or reversing motor symptom progression as measured at two years from the start of STN-DBS.
2. The method of claim 1 , wherein said subject is a human subject.
3. The method of claim 2 , wherein said subject is a male human subject.
4. The method of claim 2 , wherein said subject is a female human subject.
5. The method of claim 1 , wherein said subject is a non-human mammalian subject.
6. The method of claim 1 , wherein DBS is performed more than once.
7. The method of claim 6 , wherein DBS in performed on a chronic basis.
8. The method of claim 1 , further comprising treating said subject with a second PD therapy.
9. The method of claim 8 , wherein said second PD therapy is administered prior to STN-DBS.
10. The method of claim 8 , wherein said second PD therapy is administered at the same time as STN-DBS.
11. The method of claim 8 , wherein said second PD therapy is administered after STN-DBS.
12. The method of claim 8 , wherein said second PD therapy is selected from levodopa, optionally in combination with a DOPA decarboxylase inhibitor (carbidopa, benserazide) or a COMT inhibitor (tolcapone, entacapone), a dopamine agonist (e.g., apomorphine, bromocriptine, pergolide, pramipexole, ropinirole, piribedil, cabergoline, apomorphine, lisuride), an MAO-B inhibitor (e.g., safinamide, selegiline, rasagiline), amantadine, an anticholinergics cholinesterase inhibitor, and lesional surgery, or combinations thereof.
13. The method of claim 1 , wherein STN-DBS further results in one or more of lower stimulation parameters, less need for post-operative dopaminergic medication, and/or less development of levodopa associated dyskinesia or other motor fluctuations.
14. The method of claim 1 , wherein the margin of the dorsal-lateral and anterior region of the subthalamic nucleus is defined by imaging and/or micro-electrode recording that defines the subthalamic nucleus.
15. The method of claim 1 , wherein imaging comprises (a) preoperative imaging and preoperative stereotactic target planning and trajectory assignment; and (b) stereotactic mapping of the STN nucleus bilaterally.
16. The method of claim 1 , wherein the margin of the dorsal-lateral and anterior region of the subthalamic nucleus is defined electrophysiologically by the anterior border of the STN through its relationship with the internal capsule and the dorsal margin of STN.
17. The method of claim 16 , wherein electrophysiologic identification comprises the insertion of microelectrodes into the region of STN, having an exposed recording surface small enough to detect unit firing activity as measured by impedance greater than 150K ohms, and continuous measurement of spontaneous neural firing activity while passing the microelectrodes through the region dorsal to STN and into the STN.
18. The method of claim 17 , wherein the firing rate changes significantly upon transitioning from white matter tracts just above or anterior to the STN to the neuronal activity seen within the STN by a factor of 5 or more.