Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery.

Individuals with Parkinson's disease (PD) suffer from motor and mental disturbances due to degeneration of dopaminergic and non-dopaminergic neuronal systems. Although they provide temporary symptom relief, current treatments fail to control motor and non-motor alterations or to arrest disease progression. Aiming to explore safety and possible motor and neuropsychological benefits of a novel strategy to improve the PD condition, a case series study was designed for brain grafting of human neural progenitor cells (NPCs) to a group of eight patients with moderate PD. A NPC line, expressing Oct-4 and Sox-2, was manufactured and characterized. Using stereotactic surgery, NPC suspensions were bilaterally injected into patients' dorsal putamina. Cyclosporine A was given for 10 days prior to surgery and continued for 1 month thereafter. Neurological, neuropsychological, and brain imaging evaluations were performed pre-operatively, 1, 2, and 4 years post-surgery. Seven of eight patients have completed 4-year follow-up. The procedure proved to be safe, with no immune responses against the transplant, and no adverse effects. One year after cell grafting, all but one of the seven patients completing the study showed various degrees of motor improvement, and five of them showed better response to medication. PET imaging showed a trend toward enhanced midbrain dopaminergic activity. By their 4-year evaluation, improvements somewhat decreased but remained better than at baseline. Neuropsychological changes were minor, if at all. The intervention appears to be safe. At 4 years post-transplantation we report that undifferentiated NPCs can be delivered safely by stereotaxis to both putamina of patients with PD without causing adverse effects. In 6/7 patients in OFF condition improvement in UPDRS III was observed. PET functional scans suggest enhanced putaminal dopaminergic neurotransmission that could correlate with improved motor function, and better response to L-DOPA. Patients' neuropsychological scores were unaffected by grafting. Trial Registration: Fetal derived stem cells for Parkinson's disease https://doi.org/10.1186/ISRCTN39104513Reg#ISRCTN39104513.

Microelectrode-guided posteroventral medial radiofrequency pallidotomy for Parkinson's disease.

The outcome of radiofrequency-guided posteroventral medial pallidotomy was investigated in 29 patients with recalcitrant Parkinson's disease. Extracellular recordings were obtained in the target region to differentiate the internal from the external globus pallidus, and distinct waveforms were recorded in each region. Stimulation of the target site further verified the lesion location. Of the 29 patients treated during the course of 1 year, none showed any adverse side effects (such as hemianopsia or hemiparesis) from the procedure. Significant and immediate improvement in motor involvement (dyskinesia, rigidity, dystonia, freezing, and tremor) was observed as measured by the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Patients experienced improvements in their condition as measured on a self-rating scale, and their ability to perform the activities of daily living was also significantly improved. Although the onset and duration of the effect of a single dose of levodopa did not change, the number of hours in an "off" state of dyskinesia per day was significantly decreased. These results provide further evidence, in a large group of patients, that posteroventral medial pallidotomy results in significant control of the motor symptoms of Parkinson's disease with a minimum of undesirable side effects.