The role of inheritance in sporadic Parkinson's disease: evidence from a longitudinal study of dopaminergic function in twins.

Despite the major finding of a genetic defect being responsible for the Parkinson's disease (PD) phenotype in some kindreds with dominantly transmitted PD, the role of inheritance in the cause of the more widespread sporadic form of the disease is still unclear. Twin studies are a classic tool for assessing the influence of hereditary factors in diseases; however, the application of this approach to late-onset illnesses, like PD, poses some problems because of the identification of subclinical cases. In the present longitudinal study we have used [18F]dopa and positron emission tomography to study dopaminergic function in twin pairs at baseline clinically discordant for PD. At baseline, the concordance for subclinical striatal dopaminergic dysfunction was found to be significantly higher in 18 monozygotic than in 16 dizygotic twin pairs (55% vs 18%, respectively). The asymptomatic monozygotic cotwins all showed progressive loss of dopaminergic function over 7 years and 4 developed clinical PD. None of the dizygotic twin pairs became clinically concordant. At follow-up, the combined concordance levels for subclinical dopaminergic dysfunction and clinical PD were 75% in the 12 monozygotic and 22% in the 9 dizygotic twin pairs evaluated twice. Our findings suggest a substantial role for inheritance in sporadic PD

Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts.

Intrastriatal transplantation of dopaminergic neurones aims to repair the selective loss of nigrostriatal projections and the consequent dysfunction of striatocortical circuitries in Parkinson's disease (PD). Here, we have studied the effects of bilateral human embryonic dopaminergic grafts on the movement-related activation of frontal cortical areas in 4 PD patients using H2 15O positron emission tomography and a joystick movement task. At 6.5 months after transplantation, mean striatal dopamine storage capacity as measured by 18F-dopa positron emission tomography was already significantly elevated in these patients. This was associated with a modest clinical improvement on the Unified Parkinson's Disease Rating Scale, whereas the impaired cortical activation was unchanged. At 18 months after surgery, there was further significant clinical improvement in the absence of any additional increase in striatal 18F-dopa uptake. Rostral supplementary motor and dorsal prefrontal cortical activation during performance of joystick movements had significantly improved, however. Our data suggest that the function of the graft goes beyond that of a simple dopamine delivery system and that functional integration of the grafted neurones within the host brain is necessary to produce substantial clinical recovery in PD