Spinocerebellar ataxias types 2 and 3: degeneration of the precerebellar nuclei isolates the three phylogenetically defined regions of the cerebellum

U Rub*, K Gierga, ER Brunt, RAI de Vos, M Bauer, L Schols, K Burk, G Auburger, J Bohl, C Schultz, M Vuksic, GJ Burbach, H Braak, T Deller

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    40 Citations (Scopus)

    Abstract

    The precerebellar nuclei act as a gate for the entire neocortical, brainstem and spinal cord afferent input destined for the cerebellum. Since no pathoanatomical studies of these nuclei had yet been performed in spinocerebellar ataxia type 2 (SCA2) or type 3 (SCA3), we carried out a detailed postmortem study of the precerebellar nuclei in six SCA2 and seven SCA3 patients in order to further characterize the extent of brainstem degeneration in these ataxic disorders. By means of unconventionally thick serial sections through the brainstem stained for lipofuscin pigment and Nissl material, we could show that all of the precerebellar nuclei (red, pontine, arcuate, prepositus hypoglossal, superior vestibular, lateral vestibular, medial vestibular, interstitial vestibular, spinal vestibular, vermiform, lateral reticular, external cuneate, subventricular, paramedian reticular, intercalate, interfascicular hypoglossal, and conterminal nuclei, pontobulbar body, reticulotegmental nucleus of the pons, inferior olive, and nucleus of Roller) are among the targets of both of the degenerative processes underlying SCA2 and SCA3. These novel findings are in contrast to the current neuropathological literature, which assumes that only a subset of precerebellar nuclei in SCA2 and SCA3 may undergo neurodegeneration. Widespread damage to the precerebellar nuclei separates all three phylogenetically and functionally defined regions of the cerebellum, impairs their physiological functions and thus explains the occurrence of gait, stance, limb and truncal ataxia, dysarthria, truncal and postural instability with disequilibrium, impairments of the vestibulo-ocular reaction and optokinetic nystagmus, slowed and saccadic smooth pursuits, dysmetrical horizontal saccades, and gaze-evoked nystagmus during SCA2 and SCA3.

    Original languageEnglish
    Pages (from-to)1523-1545
    Number of pages23
    JournalJournal of Neural Transmission
    Volume112
    Issue number11
    DOIs
    Publication statusPublished - Nov-2005

    Keywords

    • ataxias
    • brainstem
    • Machado-Joseph disease
    • pathoanatomy
    • polyglutamine diseases
    • precerebellar nuclei
    • spinocerebellar ataxias
    • MACHADO-JOSEPH-DISEASE
    • HUMAN BRAIN STEM
    • CENTRAL VESTIBULAR SYSTEM
    • GERMAN SCA PATIENTS
    • ALZHEIMERS-DISEASE
    • TRINUCLEOTIDE EXPANSION
    • CYTOSKELETAL PATHOLOGY
    • RETICULAR NUCLEUS
    • RAPHE NUCLEI
    • FAMILIES

    Cite this