Brain susceptibility imaging provides valuable in vivo insights into cerebellar diseases, but biological interpretations remain elusive

Abstract

This scientific commentary relates to: ‘Quantitative susceptibility mapping reveals alterations of dentate nuclei in common types of degenerative cerebellar ataxias’ by Deistung et al. (https://doi.org/10.1093/braincomms/fcab306).

What Is the Role of the Dentate Nucleus in Normal and Abnormal Cerebellar Function?

“…97 Several studies indicate that there is a dissociation between iron accumulation and atrophy in the DN. [90][91][92] In general, DN atrophy is more severe in SCA6 than in Friedreich ataxia and less severe in SCA3. 90 Iron accumulation is prominent in SCA1 and cerebellar-type multiple system atrophy, circumscribed in Friedreich ataxia, similar to controls in SCA3, and low in SCA6 despite its reduced volume.…”

“…The DN is affected in several ataxic disorders, as shown at autopsy and in studies using susceptibility-weighted imaging for iron accumulation and morphometry to assess DN atrophy. [90][91][92] Neuropathologic studies show atrophy of the DN in Friedreich ataxia 87,93 and in spinocerebellar ataxia type 3 (SCA3, Machado-Josephs disease). 94 Loss of large excitatory neurons and preservation of small GABAergic neurons in the DN are proportional to the reduction of frataxin level and correlate with neurologic disability in Friedreich ataxia.…”

“…91 This dissociation between iron accumulation and atrophy may reflect differential involvement of DN neurons and glial cells in these disorders. 92 Factors other than iron accumulation may render DN neurons susceptible to neurodegeneration. For example, these neurons show nuclear depletion and cytoplasmic mislocalization of the RNA-binding protein heterogeneous ribonucleoprotein K, which is similar to the case of prefrontal cortical cells affected in frontotemporal lobar degeneration.…”