MRI‐based volumetric differentiation of sporadic cerebellar ataxia

DOI: 10.1093/brain/awh013 Advanced Access publication October 21, 2003 Brain (2004), 127, 175±181 MRI-based volumetric differentiation of sporadic cerebellar ataxia K. BuÈrk,1 C. Globas,1 T. Wahl,1 U. BuÈhring,2 K. Dietz,3 C. ZuÈhlke,4 A. Luft,1 J. B. Schulz,1 K. Voigt2 and J. Dichgans1 Departments of 1Neurology, 2Neuroradiology and 3Medical Biometry, University of TuÈbingen and 4Institute of Human Genetics, University of LuÈbeck, Germany Summary The term idiopathic cerebellar ataxia (IDCA) designates a variety of cerebellar syndromes that may present with a purely cerebellar syndrome (IDCA-C) or with additional extracerebellar features (IDCA-P). Multiple system atrophy is also a sporadic neurodegenerative disorder of unknown origin that may cause prominent cerebellar symptoms (MSA-C). The ®nal neuropathological answer to the question whether IDCA-P and MSA-C represent different varieties of one disease or two distinct entities is still lacking. Three-dimensional MRI-based volumetry allows morphological investigations intra vitam. Volumetric analysis of cerebellum, brainstem and basal ganglia was therefore performed in 46 patients with sporadic cerebellar ataxia and 16 age-matched healthy controls. Patients with dementia were excluded from the study since cognitive impairment is an exclusion criterion for the diagnosis of MSA. Cerebellar patients were clinically divided into two Correspondence to: K. BuÈrk, Department of Neurology, University of TuÈbingen, Hoppe-Seyler-Str. 3, D-72076 TuÈbingen, Germany E-mail: groups: 33 patients with multiple system atrophy with prominent cerebellar symptoms (MSA-C) and 13 patients with extracerebellar features not corresponding to MSA-C (IDCA-P). There was evidence for substantial cerebellar atrophy in both cerebellar groups while additional brainstem atrophy was signi®cantly more pronounced in MSA-C patients. Absolute caudate and putamen atrophy was found to be restricted to single MSA-C individuals while group comparisons of mean volumes did not yield signi®cant differences from controls. Based on the volumetric data, diagnosis could be correctly predicted in 94% of control, 82% of MSA-C and 100% of IDCA-P individuals. The ®nding of speci®c imaging characteristics strengthens (i) the value of MRI volumetry in separating MSA-C from other types of sporadic cerebellar ataxia, and (ii) the hypothesis of two independent neurodegenerative disorders in MSA-C and IDCA-P. Keywords: idiopathic cerebellar ataxia; multiple system atrophy; olivopontocerebellar atrophy; cerebellar atrophy Abbreviations: ANOVA = analysis of variance; CCA = cortical cerebellar atrophy; IDCA = idiopathic cerebellar ataxia; IDCA-C = IDCA with a purely cerebellar syndrome; IDCA-P = IDCA with additional extracerebellar features; MRI = magnetic resonance imaging; MSA = multiple system atrophy; MSA-C = MSA of the cerebellar type; MSA-P = MSA of the striatonigral type; OPCA = olivopontocerebellar atrophy; SCA = spinocerebellar ataxia; TurboSE = turbo spin echo Introduction The term `sporadic cerebellar ataxia' comprises a variety of non-hereditary cerebellar syndromes of unknown origin. Neuropathological features vary from isolated cerebellar degeneration (cortical cerebellar atrophy, CCA) to combined neuronal degeneration and gliosis in the inferior olives, pons and cerebellum (olivopontocerebellar atrophy, OPCA) (Gilman and Quinn, 1996). Clinically, patients may present with a purely cerebellar syndrome (IDCA-C) or with additional extracerebellar features (IDCA-P). Combined cerebellar and pontine atrophy is also a neuropathological hallmark of multiple system atrophy (MSA) (Schulz et al., 1994), a sporadic unrelentlessly progressive neurodegenerative disorder leading to incapacity and a reduced life expectancy. Neuronal loss is not restricted to the inferior olives, pontine nuclei and Purkinje cells in MSA brains, but may also be found in the putamen, caudate nucleus, substantia nigra and the autonomic nuclei of the brainstem and the intermediolateral cell columns in the spinal cord and is accompanied by the presence of glial cytoplasmic inclusions (Gilman et al., 1999). Clinically, MSA is associated with various combinations of cerebellar ataxia, basal ganglia symptoms and severe autonomic dysfunction Brain Vol. 127 No. 1 ã Guarantors of Brain 2003; all rights reserved 176 K. BuÈrk et al. (Gilman et al., 1999). Many MSA patients initially develop basal ganglia symptoms (MSA of the striatonigral type, MSA-P) while others start with a cerebellar syndrome (MSA of the cerebellar type, MSA-C). The question whether MSAC and idiopathic cerebellar ataxia with extracerebellar presentation (IDCA-P) represent the same disease has been discussed controversially in the literature (Penney, 1995; Rinne et al., 1995; Gilman and Quinn, 1996; Quinn and Daniel, 1996; Gilman et al., 2000). Meanwhile, it seems commonly accepted that sporadic ataxia is a heterogeneous disorder with at least two subgroups of patients, those who evolve to MSA-C and those who continue to show progressive deterioration of cerebellar function without developing signs of MSA-C. However, the neuropathological proof of this hypothesis has not yet been established. It is not clear which investigations may be most useful in differentiating MSA-C from other cerebellar patients. This seems the more important as prognosis of MSA is poor (Schulz et al., 1994; Gilman et al., 2000). The reliability of three-dimensional MRI-based volumetry has been demonstrated in earlier intra vitam studies (Luft et al., 1996, 1998; Schulz et al., 1999). This method is characterized by a higher exactness and reproducibility than two-dimensional planimetric evaluation or voxel-based volumetry. We have therefore performed a comparative study of the clinical and morphological characteristics in patients with sporadic cerebellar ataxia. Individuals were diagnosed as MSA-C or IDCA-P based on their clinical features. Morphological analysis included MRI-based volumetry of cerebellum, brainstem, caudate nucleus and putamen. Patients and methods Patients In order to investigate the discernment of MSA-C and IDCA-P in cerebellar patients with a clinical presentation as similar as possible, cerebellar patients with evidence for cognitive impairment were excluded from the study [dementia has to be absent in MSA according to the Guideline of the International Consensus Statement of MSA (Gilman et al., 1999)]. Forty-six cerebellar patients (mean age 60.5 6 7.2 years, range 41±75 years; mean age of onset 54.8 6 8.5 years, range 30±70 years; mean disease duration 5.7 6 3.6 years, range 1±19 years) were selected from a larger patient pool. They ful®lled the following inclusion criteria: (i) chronic progressive cerebellar dysfunction with cerebellar ataxia and dysarthria; (ii) disease onset after the age of 35 years [patients with a lower age of onset were excluded since MSA-C usually starts after the age of 35 years (Gilman et al., 19 (...truncated)