Spinocerebellar ataxia type 1 (SCA1): new pathoanatomical and clinico‐pathological insights |
| |
| Authors: | U Rüb K Bürk D Timmann W den Dunnen K Seidel K Farrag E Brunt H Heinsen R Egensperger A Bornemann S Schwarzacher H‐W Korf L Schöls J Bohl T Deller |
| |
| Institution: | 1. Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe‐University;2. Dr. Senckenberg Chronomedical Institute, Goethe‐University, Frankfurt/Main;3. Department of Neurology, Philipps‐University of Marburg, Marburg;4. Department of Neurology, University of Duisburg‐Essen, Essen;5. Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen;6. Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands;7. Morphological Brain Research Unit, Psychiatric Clinic, Julius Maximilians University Würzburg, Würzburg;8. Center for Neuropathology and Prion Research, Ludwigs Maximilians University Munich, München;9. Institute of Brain Research, University of Tübingen;10. Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen;11. German Center of Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen;12. Neuropathology Division, University Clinic of Mainz, Mainz, Germany |
| |
| Abstract: | U. Rüb, K. Bürk, D. Timmann, W. den Dunnen, K. Seidel, K. Farrag, E. Brunt, H. Heinsen, R. Egensperger, A. Bornemann, S. Schwarzacher, H.‐W. Korf, L. Schöls, J. Bohl and T. Deller (2012) Neuropathology and Applied Neurobiology 38, 665–680 Spinocerebellar ataxia type 1 (SCA1): new pathoanatomical and clinico‐pathological insights Aims: Spinocerebellar ataxia type 1 (SCA1) represents the first molecular genetically characterized autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG‐repeat or polyglutamine diseases. Owing to limited knowledge about SCA1 neuropathology, appropriate pathoanatomical correlates of a large variety of SCA1 disease symptoms are missing and the neuropathological basis for further morphological and experimental SCA1 studies is still fragmentary. Methods: In the present study, we investigated for the first time serial tissue sections through the complete brains of clinically diagnosed and genetically confirmed SCA1 patients. Results: Brain damage in the three SCA1 patients studied went beyond the well‐known brain predilection sites of the underlying pathological process. Along with neuronal loss in the primary motor cortex, it included widespread degeneration of gray components of the basal forebrain, thalamus, brainstem and cerebellum, as well as of white matter components in the cerebellum and brainstem. It involved the motor cerebellothalamocortical and basal ganglia‐thalamocortical circuits, the visual, auditory, somatosensory, oculomotor, vestibular, ingestion‐related, precerebellar, basal forebrain cholinergic and midbrain dopaminergic systems. Conclusions: These findings show for the first time that the extent and severity of brain damage in SCA1 is very similar to that of clinically closely related spinocerebellar ataxias (that is, SCA2, SCA3 and SCA7). They offer suitable explanations for poorly understood SCA1 disease symptoms and will facilitate the interpretation of further morphological and experimental SCA1 studies. |
| |
| Keywords: | ataxia pathoanatomy polyglutamine diseases SCA1 spinocerebellar ataxia type 1 |
|
|
