Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3.

Twenty-six patients suffering from autosomal dominant cerebellar ataxia type I were subjected to a genotype-phenotype correlation analysis using molecular genetic assignment to the genetic loci for spinocerebellar ataxia type 1, 2 or 3 (SCA1, SCA2, SCA3) and MRI-based volumetry of posterior fossa structures and basal ganglia nuclei. There was significant atrophy of the cerebellum and brainstem in all three SCA mutations compared with a group of 31 age- and sex-matched controls. Comparison between the SCA groups showed that cerebellar and brainstem atrophy was more severe in SCA2 than in SCA1 and SCA3. Putaminal and caudate volume was reduced only in SCA3, but not in SCA1 and SCA2. A set of three morphological criteria was defined that enabled us to assign all SCA2 and SCA3 patients correctly to the underlying genotype. In contrast, these criteria did not distinguish SCA1 from SCA2 and SCA3. Regression analysis failed to reveal a significant association between CAG repeat length and the volumes of the respective brain structures in any of the SCA mutant types. The present data provide in vivo evidence that SCA2 and SCA3 lead to distinct patterns of brain atrophy, while the atrophy changes in SCA1 overlap with both SCA2 and SCA3.

[1]  F. Nüsslin,et al.  Quantifizierung des Fehlers von Volumenbestimmungen in der Kernspintomographie mit Hilfe von Agarose-Phantomen , 1995 .

[2]  H. Zoghbi,et al.  Molecular and clinical correlations in spinocerebellar ataxia type 3 and Machado‐Joseph disease , 1995, Annals of neurology.

[3]  B. Woods,et al.  Nigro-spino-dentatal degeneration with nuclear ophthalmoplegia. A unique and partially treatable clinico-pathological entity. , 1972, Journal of the neurological sciences.

[4]  J. Dichgans,et al.  Idiopathic cerebellar ataxia of late onset: natural history and MRI morphology. , 1990, Journal of neurology, neurosurgery, and psychiatry.

[5]  T Klockgether,et al.  The natural history of degenerative ataxia: a retrospective study in 466 patients. , 1998, Brain : a journal of neurology.

[6]  N. Quinn,et al.  Multiple system atrophy--the nature of the beast. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[7]  F. Persichetti,et al.  HLA‐linked spinocerebellar ataxia: a clinical and genetic study of large Italian kindreds , 1992, Acta neurologica Scandinavica.

[8]  J. Greenfield,et al.  The Spino‐Cerebellar Degenerations , 1955, Neurology.

[9]  S. Tsuji,et al.  A clinical and pathologic study of a large Japanese family with Machado‐ Joseph disease tightly linked to the DNA markers on chromosome 14q , 1994, Neurology.

[10]  K. Nakano,et al.  Machado disease , 1972, Neurology.

[11]  Georg Auburger,et al.  Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2 , 1996, Nature Genetics.

[12]  U Klose,et al.  Reliability and exactness of MRI‐based volumetry: A phantom study , 1996, Journal of magnetic resonance imaging : JMRI.

[13]  P. A. Petrov,et al.  Olivopontocerebellar atrophy in a large Iakut kinship in Eastern Siberia , 1989, Neurology.

[14]  Alexandra Durr,et al.  Spinocerebellar ataxia 3 and machado‐joseph disease: Clinical, molecular, and neuropathological features , 1996, Annals of neurology.

[15]  Sid Gilman,et al.  Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions , 1996, Annals of neurology.

[16]  G. Holmes.  AN ATTEMPT TO CLASSIFY CEREBELLAR DISEASE, WITH A NOTE ON MARIE'S HEREDITARY CEREBELLAR ATAXIA , 1908 .

[17]  J. Schut,et al.  Hereditary ataxia: a pathologic study of five cases of common ancestry. , 1951, Journal of neuropathology and clinical neurology.

[18]  M Skalej,et al.  Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3. , 1996, Brain : a journal of neurology.

[19]  S. Tsuji,et al.  Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT , 1996, Nature Genetics.

[20]  J. Schut.  HEREDITARY ATAXIA: Clinical Study Through Six Generations , 1950 .

[21]  Huda Y. Zoghbi,et al.  Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1 , 1993, Nature Genetics.

[22]  R. Rosenberg,et al.  Autosomal dominant striatonigral degeneration , 1976, Neurology.

[23]  L. Santoro,et al.  Has spinocerebellar ataxia type 2 a distinct phenotype? Genetic and clinical study of an Italian family , 1995, Neurology.

[24]  R. Elston,et al.  A family with hereditary ataxia , 1980, Neurology.

[25]  J. Dichgans,et al.  Magnetic resonance imaging in hereditary and idiopathic ataxia , 1993, Neurology.

[26]  J. Dichgans,et al.  Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[27]  M. Skalej,et al.  A new semiautomated, three‐dimensional technique allowing precise quantification of total and regional cerebellar volume using MRI , 1998, Magnetic resonance in medicine.

[28]  Shigenobu Nakamura,et al.  CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1 , 1994, Nature Genetics.

[29]  X. Estivill,et al.  Clinical, neuropathologic, and genetic studies of a large spinocerebellar ataxia type 1 (SCA1) kindred , 1995, Neurology.

[30]  H. Topka,et al.  Autosomal dominant cerebellar ataxia type I. Nerve conduction and evoked potential studies in families with SCA1, SCA2 and SCA3. , 1997, Brain : a journal of neurology.

[31]  A. Harding.  The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the 'the Drew family of Walworth'. , 1982, Brain : a journal of neurology.

[32]  Yves Agid,et al.  Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats , 1996, Nature Genetics.

[33]  Shirley Hansen,et al.  Dominantly inherited olivopontocerebellar atrophy from eastern Cuba Clinical, neuropathological, and biochemical findings , 1989, Journal of the Neurological Sciences.