Transcranial sonography reveals cerebellar, nigral, and forebrain abnormalities in Friedreich's ataxia

Background: Friedreich’s ataxia (FA) is essentially characterized by degeneration of the dorsal root ganglia, the dorsal nuclei of Clarke, and the long spinal fiber tracts, yet there is accumulating evidence that neurodegeneration extends beyond these predilection sites. Transcranial sonography (TCS) has evolved as a valuable complementary neuroimaging tool in the assessment of neurodegenerative diseases due to its capacity to well depict structural changes and the accumulation of heavy metals. Its use for assessing cerebellar neurodegeneration, however, has not yet been investigated.Here we investigated whether TCS allows to assess particular features of cerebellar as well as midbrain and forebrain abnormalities in FA. Methods: Comprehensive TCS imaging of 34 FA patients and 34 age-matched healthy controls. Results: Hyperechogenicity of the dentate nucleus was very frequent in FA patients (85%) and could even be observed in patients with short disease duration, suggesting that dentate alterations are a common and probably early feature of FA. Substantia nigra was significantly hypoechogenic, possibly indicating regional changes in subcellular brain iron regulation. FA patients showed significantly enlarged 4th, 3rd, and lateral ventricles, thus corroborating earlier MRI and postmortem findings of substantial cerebellar and forebrain atrophy in FA. Conclusions: TCS provides a quick-to-apply and inexpensive in vivo assessment of both cerebellar and noncerebellar abnormalities in FA, in particular highlighting dentate hyperechogenicity as a core feature. It might serve as a promising tool for imaging aspects of cerebellar neurodegeneration also in other neurodegenerative disorders.