ORIGINAL COMMUNICATION Subclinical nigrostriatal dopaminergic denervation in the cerebellar subtype of multiple system atrophy (MSA-C) Esteban Mun ˜oz • Alex Iranzo • Sebastian Rauek • Francisco Lomen ˜a • Judith Gallego • Dome ´nec Ros • Joan Santamarı ´a • Eduardo Tolosa Received: 6 April 2011 / Revised: 12 May 2011 / Accepted: 13 May 2011 / Published online: 3 June 2011 Ó Springer-Verlag 2011 Abstract Nigrostriatal involvement is considered an additional feature in the new consensus criteria for the diagnosis of the cerebellar variant of multiple system atrophy (MSA-C). However, so far, only a few studies, which include a relative small number of patients, give support to this criterion. Our objective was to assess nigrostriatal dopami- nergic innervation in patients with MSA-C without parkin- sonism by use of dopamine transporter single photon emission computed tomography (DAT SPECT). Thirteen patients that fulfilled criteria for possible or probable MSA-C and presented no parkinsonian signs, and 12 age-matched healthy controls underwent ( 123 I-2-b-carbomethoxy-3b-(4- iodophenyl)-N-(3-fluoropropyl) nortropane ([ 123 I]FP-CIT) SPECT. Patients were also evaluated through the Unified Multiple System Atrophy Rating Scale (UMSARS) and brain magnetic resonance imaging (MRI). The mean dura- tion of the cerebellar syndrome was 3.8 ± 1.7 years. DAT SPECT showed a significant decrease of striatal [ 123 I]FP- CIT uptake ratios in patients (p \ 0.001). Radiotracer uptake reduction was 21% in the entire striatum, 19% in putamen, and 24% in caudate nuclei. Striatal binding ratios were within the normal range in 3 patients. We did not find cor- relation between striatal uptake and disease duration, age of patients, UMSARS-II score, and pontine diameter. [ 123 I]FP- CIT SPECT shows that most but not all MSA-C patients without parkinsonism have subclinical nigrostriatal dopa- minergic denervation which is not related to disease dura- tion, cerebellar dysfunction, or pontine atrophy. Keywords Multiple system atrophy Á MSA-C Á Dopamine transporter Á SPECT Á Nigrostriatal dopaminergic denervation Introduction Multiple system atrophy (MSA) is an adult-onset sporadic disease characterised by parkinsonism, cerebellar ataxia, pyramidal signs, and autonomic dysfunction. The different predominance of symptoms gives rise to different subtypes. The parkinsonian subtype (MSA-P) is defined when bra- dykinesia with rigidity, tremor or postural instability dominate the clinical picture. The cerebellar form (MSA- C) is considered when cerebellar ataxia is the most prom- inent symptom. In Europe and North America, more than 60% of the MSA cases correspond to the parkinsonian subtype [1, 2], whereas in Japan more than 80% of the cases present with the cerebellar form [3], thus, suggesting E. Mun ˜oz (&) Á S. Rauek Á E. Tolosa Parkinson’s Disease and Movement Disorders Unit, Neurology Service, Institut Clı ´nic de Neurocie `ncies (ICN), Hospital Clı ´nic i Universitari, Institut d’Investigacions Biome `diques August Pi i Sunyer (IDIBAPS), Centro de Investigacio ´n en Red de Enfermedades Neurodegenerativas (CIBERNED), Villarroel 170, 08036 Barcelona, Catalunya, Spain e-mail: jemunoz@clinic.ub.es A. Iranzo Á J. Santamarı ´a Sleep Disorders Unit, Neurology Service, ICN, Hospital Clı ´nic i Universitari, IDIBAPS, CIBERNED, Barcelona, Catalunya, Spain F. Lomen ˜a Nuclear Medicine Service, Centre de Diagno `stic per la Imatge (CDI), Hospital Clı ´nic i Universitari, Institut d’Investigacions Biome `diques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain J. Gallego Á D. Ros Biophysics Unit, Department of Physiological Sciences I, Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBERBBN), University of Barcelona, Barcelona, Catalunya, Spain 123 J Neurol (2011) 258:2248–2253 DOI 10.1007/s00415-011-6108-8