Persistent GDNF Expression 45 Months after Putaminal Infusion of AAV2-GDNF in a Patient with Parkinson's Disease.

OBJECTIVE: Gene therapy by convection-enhanced delivery of type 2 adeno-associated virus-glial cell derived neurotrophic factor (AAV2-GDNF) to the bilateral putamina seeks to increase GDNF gene expression and treat Parkinson's disease (PD). METHODS: A 63-year-old man with advanced PD received AAV2-GDNF in a clinical trial. He died from pneumonia after anterior cervical discectomy and fusion 45 months later. An autopsy included brain examination for GDNF transgene expression. Putaminal catecholamine concentrations were compared to in vivo 18F-Fluorodopa (18F-FDOPA) positron emission tomography (PET) scanning results before and 18 months after AAV2-GDNF infusion. RESULTS: Parkinsonian progression stabilized clinically. Postmortem neuropathology confirmed PD. Bilateral putaminal regions previously infused with AAV2-GDNF expressed the GDNF gene. Total putaminal dopamine was 1% of control, confirming the striatal dopaminergic deficiency suggested by baseline 18F-DOPA-PET scanning. Putaminal regions responded as expected to AAV2-GDNF. CONCLUSION: After AAV2-GDNF infusion, infused putaminal regions showed increased GDNF gene expression, tyrosine hydroxylase immunoreactive sprouting, catechol levels, and 18F-FDOPA-PET signal, suggesting the regenerative potential of AAV2-GDNF in PD.

Developing Semiautomated Methods to Measure Pre- and Postoperative Syrinx Volumes.

Neurosurgeons evaluate MRI scans to document whether surgical treatment has reduced syrinx size. Manual measurement of syrinx volume is time-consuming and potentially introduces operator error and bias. Developing convenient semiautomated volumetric analysis methods may encourage their clinical implementation and improve syringomyelia monitoring. We analyzed 30 SPGR axial MRI scans from 15 pre- and postoperative Chiari I and syringomyelia patients using two semiautomated (SCAT and 3DQI) methods and a manual Cavalieri (CAV) method. Patients' spinal cord and syrinx volumes pre- and postoperatively were compared by paired t-test. A decrease in syrinx volume (mm3) after surgery was detected across all methods. Mean syrinx volume (± SD) measured by CAV (n = 30) was, preoperatively, 4515 mm3 ± 3720, postoperatively 1109 ± 1469; (p = 0.0004). SCAT was, pre, 4584 ± 3826, post, 1064 ± 1465; (p = 0.0007) and 3DQI was, pre, 4027 ± 3805, post, 819 ± 1242; (p = 0.001). 3DQI and CAV detected similar mean spinal cord volumes before (p = 0.53) and after surgery (p = 0.23), but SCAT volumes differed significantly (p = 0.005, p = 0.0001). The SCAT and 3DQI semiautomated methods recorded surgically related syrinx volume changes efficiently and with enough accuracy for clinical decision-making and research studies.