Benefits of putaminal GDNF infusion in Parkinson disease are maintained after GDNF cessation.

We previously reported clinical improvement, increase in putamen [(18)F]-dopa uptake on PET imaging, and neuropathologic evidence of sprouting of dopaminergic fibers following chronic intraputaminal delivery of glial cell line-derived neurotrophic factor (GDNF) in idiopathic Parkinson disease (PD).(1-3) We now provide clinical and PET evidence of persistent efficacy lasting for at least 3 years following cessation of GDNF infusion in a patient with PD. This is a single-case observational study, providing Class IV evidence.

Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study.

Background: Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal models of Parkinson disease (PD).

Objective: We conducted a phase I-II clinical study to assess the feasibility, long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with PD.

STN stimulation alters pallidal-frontal coupling during response selection under competition.

To investigate the effects of bilateral subthalamic nucleus (STN) stimulation on patterns of brain activation during random number generation (RNG), a task that requires suppression of habitual counting and response selection under competition. We used H(2)(15)O positron emission tomography to investigate the changes of regional cerebral blood flow (rCBF) induced by bilateral STN stimulation during a RNG task, in six patients with Parkinson's disease. Paced RNG at 1 Hz was compared with a control counting task.

Registered computed tomography images as an alternative to postimplantation magnetic resonance imaging in the assessment of subthalamic electrode placement.

Magnetic resonance imaging (MRI) after implantation of electrodes in the subthalamic nuclei is currently performed at a number of sites, but a recent adverse incident and changes in MRI technology may heighten safety concerns. In this report, it is demonstrated that given whole-head image data, registration of postimplantation computed tomography to preimplantation MRI can enable verification of the position of electrodes to an accuracy of 2 mm. This registration technique can remove the need for potentially risky postoperative MRI.

Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease.

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF.