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OBJECTIVE A small group of Parkinson's disease (PD) patients compulsively use dopaminergic drugs despite causing harmful social, psychological, and physical effects and fulfil core Diagnostic and Statistical Manual (of Mental Disorders) Fourth Edition criteria for substance dependence (dopamine dysregulation syndrome [DDS]). We aimed to evaluate(More)
Synaptic dopamine release from embryonic nigral transplants has been monitored in the striatum of a patient with Parkinson's disease using [11C]-raclopride positron emission tomography to measure dopamine D2 receptor occupancy by the endogenous transmitter. In this patient, who had received a transplant in the right putamen 10 years earlier, grafts had(More)
Levodopa-induced dyskinesias remain a major challenge in the therapeutic management of Parkinson's disease (PD). Their etiology is unknown although dysfunction of striatal opioid transmission has been implicated in experimental models of PD. To determine whether the opioid system is involved in human dyskinetic PD, we measured in vivo opioid receptor(More)
The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these(More)
Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and it is not known whether they are the same(More)
BACKGROUND Huntington disease (HD) is characterized by the progressive death of medium spiny dopamine receptor bearing striatal GABAergic neurons. In addition, microglial activation in the areas of neuronal loss has recently been described in postmortem studies. Activated microglia are known to release neurotoxic cytokines, and these may contribute to the(More)
We have established that the frequency of LRRK2 mutations in a series of 118 cases of familial Parkinson's disease is 5.1%. In the largest family with autosomal dominant, late-onset Parkinson's disease where affected subjects share a Y1699C missense mutation we provide a detailed clinical, pathological and imaging report. The phenotype in this large British(More)
Severe dyskinesias during the 'off' phases (periods of increased Parkinson's disease (PD) disability) have been observed following intrastriatal transplantation of human embryonic mesencephalic tissue. Here we retrospectively analyzed 14 patients who were followed for up to 11 years after grafting, and found that dyskinesias (abnormal involuntary movements(More)
Graft-induced dyskinesias are a serious complication after neural transplantation in Parkinson's disease. One patient with Parkinson's disease, treated with fetal grafts 14 years ago and deep brain stimulation 6 years ago, showed marked improvement of motor symptoms but continued to suffer from OFF-medication graft-induced dyskinesias. The patient received(More)
BACKGROUND Depression associated with Parkinson disease (PD) has a different symptom profile to endogenous depression. The etiology of depression in PD remains uncertain though abnormal serotonergic neurotransmission could play a role. OBJECTIVE To assess with PET serotonergic function via in vivo serotonin transporter (5-HTT) availability in(More)