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Pallidal neuronal discharge in Parkinson's disease following intraputamenal fetal mesencephalic allograft
  1. R Mark Richardson1,
  2. Curt R Freed2,
  3. Shoichi A Shimamoto1,
  4. Philip A Starr1
  1. 1Department of Neurological Surgery, University of California, San Francisco, California, USA
  2. 2Division of Clinical Pharmacology and Toxicology, Departments of Medicine, Pharmacology, and Neurosurgery, University of Colorado Denver, Denver, Colorado, USA
  1. Correspondence to Dr R Mark Richardson, Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, Box 0112, San Francisco, CA 94143, USA; richardsonma{at}neurosurg.ucsf.edu

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.

  • Electrical stimulation
  • movement disorders
  • neurophysiology
  • motor
  • neurosurgery
  • Parkinson's disease

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Footnotes

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the University of California, San Francisco Committee on Human Research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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