Spinocerebellar ataxias types 2 and 3: degeneration of the pre-cerebellar nuclei isolates the three phylogenetically defined regions of the cerebellum.
The pre-cerebellar 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 pre-cerebellar 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 pre-cerebellar 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 pre-cerebellar nuclei in SCA2 and SCA3 may undergo neurodegeneration. Widespread damage to the pre-cerebellar 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.
Rüb
U
U
Institute of Clinical Neuroanatomy, J. W. Goethe University, Frankfurt/Main, Germany. U.Rueb@em.uni-frankfurt.de
Gierga
K
K
Brunt
E R
ER
de Vos
R A I
RA
Bauer
M
M
Schöls
L
L
Bürk
K
K
Auburger
G
G
Bohl
J
J
Schultz
C
C
Vuksic
M
M
Burbach
G J
GJ
Braak
H
H
Deller
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001933:Brain Stem / Q000473:pathology* / Q000503:physiopathology; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005911:Gliosis / Q000175:diagnosis / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D017827:Machado-Joseph Disease / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000175:diagnosis* / Q000503:physiopathology; D009434:Neural Pathways / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000473:pathology; D009847:Olivary Nucleus / Q000473:pathology / Q000503:physiopathology; D012012:Red Nucleus / Q000473:pathology / Q000503:physiopathology; D012154:Reticular Formation / Q000473:pathology / Q000503:physiopathology; D020754:Spinocerebellar Ataxias / Q000175:diagnosis* / Q000503:physiopathology; D013194:Staining and Labeling; D014726:Vestibular Nuclei / Q000473:pathology / Q000503:physiopathology