Pallidal neuronal discharge in Parkinson's disease following intraputamenal fetal mesencephalic allograft

J Neurol Neurosurg Psychiatry. 2011 Mar;82(3):266-71. doi: 10.1136/jnnp.2009.201129. Epub 2010 Aug 27.

Abstract

Background: Human intrastriatal fetal allografts survive over long periods of time in the brains of Parkinson's disease (PD) patients and integrate into host circuitry. However, some grafted patients with a prior history of levodopa-induced dyskinesias have developed off-medication dyskinesias and dystonias following allografting whose mechanism remains poorly understood. The authors present single-unit discharge characteristics in the external and internal globus pallidus (GPe and GPi) in an awake patient with PD undergoing microelectrode-guided surgery for pallidal deep brain stimulation, 10 years following bilateral intraputamenal fetal mesencephalic allografting in an NIH-funded protocol.

Methods: Pallidal single-unit activity at 'rest' and during active movement was evaluated and compared with data sets from 13 PD patients in the 'off-medication' state and from one non-dyskinetic PD patient in the 'on-medication' state.

Results and discussion: Analysis of firing rate, bursting discharge and oscillatory activity showed that the graft corrected some, but not all, of the abnormalities associated with the off-medication state. Additionally, in the transplanted patient, voluntary hand movement produced a marked reduction in pallidal discharge rate at multiple GPi recording sites, which was not observed during active movement in other patients. These findings are consistent with a persistent effect of transplanted dopamine cells on basal ganglia outflow and suggest a mechanism for the graft-induced dystonic phenotype.

MeSH terms

  • Action Potentials / physiology
  • Adult
  • Aged
  • Brain Tissue Transplantation*
  • Deep Brain Stimulation
  • Fetal Tissue Transplantation*
  • Globus Pallidus / physiopathology*
  • Humans
  • Middle Aged
  • Neurons / physiology
  • Parkinson Disease / physiopathology
  • Parkinson Disease / surgery*
  • Positron-Emission Tomography
  • Putamen / embryology
  • Putamen / transplantation