A scan without evidence is not evidence of absence: Scans without evidence of dopaminergic deficit in a symptomatic leucine‐rich repeat kinase 2 mutation carrier

Some patients diagnosed with Parkinson’s disease (PD) have intact dopaminergic function by PET or single-photon emission computed tomography (SPECT) imaging, most notably in four large trials using PET with 6-[18F]-fluoro-L-dopa (18F-dopa)1 or SPECT with [123I] β-CIT,2–4 where it occurred in 5% to 15% of studied patients; this phenomenon has been called scans without evidence of dopaminergic deficit (SWEDD). The basis for SWEDD is controversial and could in theory be the result of imaging error, clinical (diagnostic) error, or occurrence of a different process clinically similar to PD; true PD presenting without dopaminergic deficit has not been favored as an explanation, given that symptoms of disease generally emerge only after substantial loss of nigral dopamine neurons and striatal dopamine.5,6 Longitudinal studies of patients with SWEDD have shown that the majority of these patients do not develop a dopaminergic deficit7,8; final diagnoses include other tremor syndromes (essential tremor, dystonic tremor, and fragile X tremor ataxia syndrome) and other causes of parkinsonism (other degenerative causes, vascular, medication induced, and psychogenic).9 However, a minority of patients with SWEDD subsequently do develop dopaminergic deficits—2 of 16 patients in one report,8 4 of 30 in another,9 and 6 of 72 in the PRECEPT study.7 In 248 patients with unclassified parkinsonism studied with [123I] β-CIT scans at baseline and followed for a mean 18 months, 22 of 112 eventually diagnosed with PD had SWEDD.10 Furthermore, SWEDD has been associated with a higher than expected frequency of nonmotor features of PD, including depression, sleep disorders, autonomic dysfunction, and hyposmia.11 The basis for SWEDD is therefore varied, with most representing PD mimics, but rare cases may, for unclear reasons, represent early PD.