Basal ganglia sonography: Will it mature into a preclinical diagnostic tool for parkinson's disease?

In the majority of patients with Parkinson's disease (PD), transcranial sonography (TCS) reveals an enlarged midbrain hyperechogenicity projecting to the anatomical site of the substantia nigra (SN). There is evidence that an enlarged SN hyperechogenicity may occur prior to the onset of PD-related motor symptoms. An enlarged SN hyperechogenicity has been more often observed in those with a family history of PD and in asymptomatic mutation carriers of PD-related genes as well as in conditions known to be associated with an increased risk of developing PD including depression, idiopathic olfactory loss and rapid eye movement sleep behavior disorder. However, there remain open questions such as: the onset time of enlarged SN hyperechogenicity that precedes the development of motor signs, the unknown morphological correlate of the SN signal alteration, and the specificity of TCS in an unselected study population. This review article highlights recent TCS findings in control and different disease populations as well as in carriers of mutations in PD-linked genes and discusses the limitations of TCS. Finally, we illustrate how TCS may be useful as a preclinical diagnostic tool for identifying subjects at high risk of developing PD in combination with screening tools for non-motor or subtle motor signs. We point out that future research should address the biological correlate of the enlarged SN hyperechogenicity and the time lag between the first occurrence of an enlarged SN hyperechogenicity and the development of both, non-motor and motor signs of PD.