Magnetic Resonance Imaging Findings of Machado–Joseph Disease: Histopathologic Correlation

Purpose To determine the characteristic magnetic resonance imaging (MRI) findings of early- and late-stage Machado–Joseph disease (MJD) and to examine correlation with pathologic specimens. Patients and Methods Four patients genetically diagnosed with MJD and a familial case of MJD were all examined using MRI. Machado–Joseph disease was pathologically confirmed in one of the four genetically diagnosed patients, and the findings were compared with the MRI results. Results In all three patients who had MJD for less than 8 years, MRI confirmed mild cerebellar atrophy, particularly in the vermis, and atrophic changes in the superior cerebellar peduncle. Mild pontine atrophy was observed in these three patients. Atrophic changes in the pontine tegmentum were more prominent than those of the pontine base in these patients. Two of the three patients showed mild frontal atrophy. Of the five total patients, two had the disease for over 10 years and showed progressive atrophy of the brainstem and mild frontal atrophy. These two patients also showed pallidal atrophy. One autopsied case in which the disease duration was 17 years showed a typical pathologic picture of MJD. Macroscopic findings for this patient showed marked atrophy of the pons, mild cerebellar atrophy (particularly in the vermis), marked atrophy of the superior cerebellar peduncle, severe involvement of motor nuclei, and atrophy and discoloration of the pallidum and subthalamic nuclei. Conclusion In the early stages of MJD, mild pontine atrophy, particularly in the tegmentum, and mild cerebellar atrophy are typical MRI findings. Atrophic changes in the brainstem may be progressive. Pallidal atrophy may be observed in patients with long disease duration. These findings correlated with the pathologic findings.

[1]  L. Farrer,et al.  Machado Joseph disease maps to the same region of chromosome 14 as the spinocerebellar ataxia type 3 locus. , 1995, Journal of medical genetics.

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

[3]  R A Zimmerman,et al.  Olivopontocerebellar atrophy: MR diagnosis and relationship to multisystem atrophy. , 1990, Radiology.

[4]  Y. Kagawa,et al.  The gene for Machado–Joseph disease maps to human chromosome 14q , 1993, Nature Genetics.

[5]  H. Sasaki,et al.  Myoclonus, cerebellar disorder, neuropathy, mitochondria1 myopathy, and ACTH deficiency , 1983, Neurology.

[6]  P. Coutinho,et al.  Clinical criteria for diagnosis of Machado‐Joseph disease , 1980, Neurology.

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

[8]  O. Onodera,et al.  Unstable expansion of CAG repeat in hereditary dentatorubral–pallidoluysian atrophy (DRPLA) , 1994, Nature Genetics.

[9]  Y. Abe,et al.  CAG repeat number correlates with the rate of brainstem and cerebellar atrophy in Machado-Joseph disease , 1998, Neurology.

[10]  T Yuasa,et al.  Progressive atrophy of cerebellum and brainstem as a function of age and the size of the expanded CAG repeats in the MJD1 gene in Machado‐Joseph disease , 1998, Annals of neurology.

[11]  M. Inoue,et al.  Clinicopathology of spinocerebellar degeneration: Its correlation to the unstable CAG repeat of the affected gene , 1997, Pathology international.

[12]  F. Cendes,et al.  Brain single-photon emission computed tomography and magnetic resonance imaging in Machado-Joseph disease. , 2001, Archives of neurology.

[13]  J. Weber,et al.  Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23–24.1 , 1993, Nature Genetics.

[14]  M. Ohta,et al.  Joseph disease in a non‐Portuguese family , 1983, Neurology.

[15]  C. Andrade,et al.  Autosomal dominant system degeneration in Portuguese families of the Azores Islands , 1978, Neurology.

[16]  G. Sobue,et al.  Molecular features of the CAG repeats and clinical manifestation of Machado-Joseph disease. , 1995, Human molecular genetics.

[17]  O. Onodera,et al.  Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy , 1997, Neurology.

[18]  L. Forno,et al.  Joseph disease , 1982, Neurology.

[19]  S. Nakamura,et al.  Characteristic magnetic resonance imaging findings in Machado-Joseph disease. , 1998, Archives of neurology.

[20]  A. Sano,et al.  Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p , 1994, Nature Genetics.

[21]  F. Leweke,et al.  Spinocerebellar ataxia, type 3 (SCA3) is genetically identical to Machado-Joseph disease (MJD) , 1995, Journal of the Neurological Sciences.