Neuronal intranuclear inclusions in SCA2: a genetic, morphological and immunohistochemical study of two cases

• Published in: Brain (London, England : 1878) Vol. 125; no. Pt 3; pp. 656 - 663
• Main Authors: PANG, Joanna T, GIUNTI, Paola, CHAMBERLAIN, Susan, AN, Shu F, VITALIANI, Roberta, SCARAVILLI, Tomaso, MARTINIAN, Lillian, WOOD, Nicholas W, SCARAVILLI, Francesco, ANSORGE, Olaf
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2002; Oxford Publishing Limited (England)
• Subjects: Adult; Biological and medical sciences; Brain - pathology; Brain - physiopathology; Brain Stem - pathology; Brain Stem - physiopathology; Cell Nucleus - pathology; Cerebellum - pathology; Cerebellum - physiopathology; Chromosomes, Human, Pair 12 - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Humans; Immunohistochemistry; Inclusion Bodies - pathology; Male; Medical sciences; Middle Aged; Mutation - genetics; Neurology; Neurons - pathology; Spinocerebellar Ataxias - genetics; Spinocerebellar Ataxias - pathology; Trinucleotide Repeat Expansion - genetics; Human; Immunohistochemistry; Nervous system diseases; Cell nucleus; Male; Genetic determinism; Cerebral disorder; Genetic disease; Case study; Pathology; Neuron; Spinocerebellar ataxia; Autosomal character; Morphology; Central nervous system disease; Cell inclusion; Adult; Female; Degenerative disease; Dominant character; Diagnosis; Spinal cord disease
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awf060

Spinocerebellar ataxia 2 (SCA2) belongs to the family of autosomal dominant cerebellar ataxias (ADCA), a genetically heterogeneous group of neurodegenerative diseases. The SCA2 gene maps to chromosome 12q24 and the causative mutation involves the expansion of a CAG repeat within the coding region of the gene. Pathologically, SCA2 presents as olivo-ponto-cerebellar atrophy (OPCA). We present the cases of a 41-year-old man and a 54-year-old woman who died after a long illness characterized by severe cerebellar ataxia. Diagnosis of SCA2 was confirmed by genetic analysis. The brains were moderately to severely atrophic and atrophy was particularly obvious in the cerebellum and brainstem. Histological examination revealed extreme loss of pontine and olivary nuclei and Purkinje cells, with preservation of the dentate nuclei, and of the pigmented cells in the substantia nigra. The whole spinal cord was also severely affected, with shrinkage of the dorsal columns and reduction in the number of neurones in the motor pool and Clarke's nuclei. Immunohistochemistry with 1C2 antibody showed granular neuronal cytoplasmic deposits in all the areas examined and widespread intranuclear inclusions, which were particularly numerous in the residual pontine nuclei. Intranuclear inclusions were not considered a feature in SCA2. Our results support the view that intranuclear inclusions are an integral part of the pathology of this mutation.