Is transcranial sonography useful to distinguish scans without evidence of dopaminergic deficit patients from Parkinson's disease?

Recent clinical trials using [123I]β-CIT single-photon emission computed tomography (SPECT) and [18F]-dopa PET as surrogate markers for disease progression have found that 5.7% to 14.7% of cases clinically diagnosed as early Parkinson's disease (PD) have normal scans (scans without evidence of dopaminergic deficit; SWEDD).1, 2 In a European multicenter prospective study including diagnostically uncertain cases and performing FP-CIT-SPECT, the rate of SWEDD was 21%.3 The proportion of SWEDD in general practice is currently unknown, and the significance of normal imaging in patients with a clinical diagnosis of PD is still debated. There is growing evidence that these patients suffer from conditions not affecting the nigrostriatal dopaminergic system and may therefore have different pathophysiology, prognosis, and treatment requirements. SWEDD subjects in the ELLDOPA study lacked clinical responsiveness to levodopa,4 and follow-up dopamine transporter (DAT) scans after 4 years remained normal.5 Recently, it was shown that abnormality in cortical plasticity, assessed by paired associative stimulation, was markedly different in PD and tremulous SWEDD.6 Alternative diagnoses have been considered as essential tremor (ET), depression, vascular or psychogenic parkinsonism, dopa-responsive dystonia, supranigral parkinsonism,4 and primary adult-onset dystonic tremor.7–9 Certain clinical features point toward a diagnosis of tremulous SWEDD, such as lack of true bradykinesia and presence of dystonia or head tremor, whereas reemergent tremor, true fatiguing or decrement, good response to dopaminergic drugs, and the presence of nonmotor symptoms favor a diagnosis of PD.6, 10, 11 However, clinical distinction of tremulous SWEDD from PD remains difficult in some cases.12 Hyperechogenic alterations in the area of the midbrain have been consistently found in up to 90% of patients with PD in a variety of studies using transcranial sonography (TCS).13–15 Midbrain hyperechogenicity has also been observed in approximately 10% of the healthy population. Recent studies have suggested an increased risk of developing PD in a subgroup of people with midbrain hyperechogenicity.16, 17 In addition, midbrain hyperechogenicity has been associated with the development of PD in patients with idiopathic REM sleep behavior disorder.18, 19 In the present study, we aimed to investigate the prevalence of midbrain hyperechogenicity in SWEDD, in comparison to patients with PD.