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Abstract
The term SWEDD (scans without evidence for dopaminergic deficit) refers to the absence,
rather than the presence, of an imaging abnormality in patients clinically presumed
to have Parkinson's disease (PD). However, such a term has since been widely used
in the medical literature, even as a diagnostic label. While many authors have suggested
that different disorders of PD lookalikes may account for a proportion of SWEDD cases,
others have claimed that some of them may have a benign subtype of PD. Thus, there
has been ensuing controversy and confusion and the use of this term continues without
clarity of what it represents. We have systematically reviewed all the studies involving
patients with SWEDD with the aim of shedding light on what these patients actually
have. It becomes clear from this systematic review that while most 'SWEDD' cases are
due to a clinical misdiagnosis of PD, there exists a small proportion of patients
with SWEDD who may have PD on the basis of a positive levodopa response, clinical
progression, imaging and/or genetic evidence. The latter challenge the seemingly incontrovertible
relationship between dopaminergic tracer binding and the diagnosis of nigrostriatal
parkinsonism, particularly PD. Patients with SWEDD are unlikely to reflect a single
clinical entity and we suggest that the term SWEDD should be abandoned.
Despite the known benefit of levodopa in reducing the symptoms of Parkinson's disease, concern has been expressed that its use might hasten neurodegeneration. This study assessed the effect of levodopa on the rate of progression of Parkinson's disease. In this randomized, double-blind, placebo-controlled trial, we evaluated 361 patients with early Parkinson's disease who were assigned to receive carbidopa-levodopa at a daily dose of 37.5 and 150 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinson's Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamine-transporter density with the use of iodine-123-labeled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) uptake. The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the mean difference between the total score on the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those receiving 300 mg daily, and -1.4 in those receiving 600 mg daily (P<0.001). In contrast, in a substudy of 116 patients the mean percent decline in the [123I]beta-CIT uptake was significantly greater with levodopa than placebo (-6 percent among those receiving levodopa at 150 mg daily, -4 percent in those receiving it at 300 mg daily, and -7.2 percent among those receiving it at 600 mg daily, as compared with -1.4 percent among those receiving placebo; 19 patients with no dopaminergic deficits on the baseline scans were excluded from the analysis) (P=0.036). The subjects receiving the highest dose of levodopa had significantly more dyskinesia, hypertonia, infection, headache, and nausea than those receiving placebo. The clinical data suggest that levodopa either slows the progression of Parkinson's disease or has a prolonged effect on the symptoms of the disease. In contrast, the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long-term effects of levodopa on Parkinson's disease remain uncertain. Copyright 2004 Massachusetts Medical Society.
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