title: Brain MRI, lumbar CSF monoamine concentrations, and clinical descriptors of patients with spinocerebellar ataxia mutations.
abstract: OBJECTIVE
  To serially assess changes in lumbar CSF biogenic amines, radiographic characteristics, and neurological signs in 34 patients with dominantly inherited ataxia.
  
  
  METHODS
  Mutational analysis was used to identify genetic subgroups. Annual assessment of lumbar CSF monoamine metabolites using a gas chromatographic/mass spectrometric method and morphometric measurements of the cerebellum, pons, and the cervical spinal cord on MRI were analysed for each patient and compared with normal controls.
  
  
  RESULTS
  Patients with CAG trinucleotide repeat expansions on chromosome 6p (mutSCA1) and chromosome 14q (mutSCA3) had only about one half the normal concentrations of lumbar CSF homovanillic acid (HVA) whereas, 5-hydroxyindoleacetic acid (5-HIAA) concentrations were similar to those in age matched normal subjects. The HVA and 5-HIAA concentrations in clinically similar patients without mutSCA1 or mutSCA3 were normal. One year after the first study, HVA concentrations were reduced by a mean of 22% regardless of the patient's SCA mutation. Abnormalities on MRI were consistent with a spinopontine atrophy in patients with mutSCA3, spinopontocerebellar atrophy in patients with mutSCA1, and "pure" cerebellar atrophy in patients without these mutations.
  
  
  CONCLUSIONS
  Quantitative MRI measurements were not useful in monitoring progression of disease but lumbar CSF HVA concentrations and total scores on a revised version of the ataxia clinical rating scale seemed to progress in parallel.
authors.affiliation: Clinical Neurogenetics Unit, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Higgins
authors.forename: J D
authors.initials: JD
authors.lastname: Harvey-White
authors.forename: L E
authors.initials: LE
authors.lastname: Nee
authors.forename: M J
authors.initials: MJ
authors.lastname: Colli
authors.forename: T A
authors.initials: TA
authors.lastname: Grossi
authors.forename: I J
authors.initials: IJ
authors.lastname: Kopin
mesh_terms: D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid*; D001921:Brain / Q000473:pathology*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008279:Magnetic Resonance Imaging; D009154:Mutation / Q000235:genetics; D013132:Spinocerebellar Degenerations / Q000378:metabolism / Q000473:pathology*
chemical_list: D015306:Biogenic Monoamines; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid