Homozygosity for Machado-Joseph disease gene enhances phenotypic severity.

Six months before she was seen by us, the referring physician started her on treatment with Sinemet-plus 125 mg (carbidopa 25 mg, levodopa 100 mg) four times a day with a dramatic initial benefit.Within a few months, however, she noticed wearing off problems with each dose lasting only three hours and the dose was increased to six Sinemet plus a day with one Sinemet CR (carbidopa 50 mg, levodopa 200 mg) at night.The differential diagnosis in this patient was between dopa responsive dystonia and young onset Parkinson's disease.The initial presentation with what seemed to be a spastic paraparesis and the positive family history suggested dopa responsive dystonia.Later evaluation suggested the possibility of young onset Parkinson's disease as she had developed wearing off dose responses early after initiation of treatment with Sinemet.5By contrast, patients with dopa responsive dystonia are known to have a sustained long term benefit without complications on small doses of levodopa.For purposes of progno- sis and further management it was important to distinguish between the two conditions.This was achieved with '8F-dopa PET which showed significantly reduced tracer uptake in the putamen (averaged side to side, Ki values using an occipital reference; patient caudate = 0-0080 (0-0108 ± 0-0017), patient putamen = 0-0034 (0 0099 ± 0-0011)).These findings were suggestive of a diagnosis of young onset Parkinson's disease.3 4 With a diagnosis of young onset Parkinson's disease established the drug therapy was modified by giving her levodopa sparing drugs such as amantadine, dopamine agonists, and anticholinergic drugs to avoid the levodopa induced motor fluctuations for as long as possible.This case shows the part functional imaging can play in selected cases and the prognostic and therapeutic implications made possible by this technique.