Document Detail

Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status.
MedLine Citation:
PMID:  20310029     Owner:  NLM     Status:  MEDLINE    
Robust biomarkers of neurodegeneration are critical for testing of neuroprotective therapies. The clinical applicability of such biomarkers requires sufficient sensitivity to detect disease in individuals. Here we tested the sensitivity of high field (4 tesla) proton magnetic resonance spectroscopy ((1)H MRS) to neurochemical alterations in the cerebellum and brainstem in spinocerebellar ataxia type 1 (SCA1). We measured neurochemical profiles that consisted of 10 to 15 metabolite concentrations in the vermis, cerebellar hemispheres and pons of patients with SCA1 (N = 9) and healthy controls (N = 15). Total NAA (N-acetylaspartate + N-acetylaspartylglutamate, tNAA) and glutamate were lower and glutamine, myo-inositol and total creatine (creatine + phosphocreatine, tCr) were higher in patients relative to controls, consistent with neuronal dysfunction/loss, gliotic activity, and alterations in glutamate-glutamine cycling and energy metabolism. Changes in tNAA, tCr, myo-inositol, and glutamate levels were discernible in individual spectra and the tNAA/myo-inositol ratio in the cerebellar hemispheres and pons differentiated the patients from controls with 100% specificity and sensitivity. In addition, tNAA, myo-inositol, and glutamate levels in the cerebellar hemispheres and the tNAA and myo-inositol levels in the pons correlated with ataxia scores (Scale for the Assessment and Rating of Ataxia, SARA). Two other biomarkers measured in the cerebrospinal fluid (CSF) of a subset of the volunteers (F(2)-isoprostanes asa marker of oxidative stress and glial fibrillary acidic protein (GFAP) as a marker of gliosis) were not different between patients and controls. These data demonstrate that (1)H MRS biomarkers can be utilized to noninvasively assess neuronal and glial status in individual ataxia patients.
Gülin Oz; Diane Hutter; Ivan Tkác; H Brent Clark; Myron D Gross; Hong Jiang; Lynn E Eberly; Khalaf O Bushara; Christopher M Gomez
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Movement disorders : official journal of the Movement Disorder Society     Volume:  25     ISSN:  1531-8257     ISO Abbreviation:  Mov. Disord.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-26     Completed Date:  2010-11-04     Revised Date:  2014-03-27    
Medline Journal Info:
Nlm Unique ID:  8610688     Medline TA:  Mov Disord     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1253-61     Citation Subset:  IM    
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MeSH Terms
Analysis of Variance
Aspartic Acid / analogs & derivatives
Brain Chemistry*
Case-Control Studies
Functional Laterality
Glial Fibrillary Acidic Protein / cerebrospinal fluid
Isoprostanes / cerebrospinal fluid
Magnetic Resonance Imaging / methods
Magnetic Resonance Spectroscopy / methods
Middle Aged
Protons / diagnostic use
Severity of Illness Index
Spinocerebellar Ataxias / metabolism*,  physiopathology*
Statistics as Topic
Grant Support
1R01-AG026392/AG/NIA NIH HHS; 1R01-CA1205090/CA/NCI NIH HHS; 1R01-NR009212/NR/NINR NIH HHS; 1R21-CA133263/CA/NCI NIH HHS; 1R21-NS060253/NS/NINDS NIH HHS; 5-41230-G1/R01CA116795/CA/NCI NIH HHS; M01 RR000400/RR/NCRR NIH HHS; M01 RR000400-416988/RR/NCRR NIH HHS; M01 RR00400/RR/NCRR NIH HHS; NS35192/NS/NINDS NIH HHS; P01 HD039386/HD/NICHD NIH HHS; P01NS058901/NS/NINDS NIH HHS; P30 NS057091/NS/NINDS NIH HHS; P30 NS057091-04/NS/NINDS NIH HHS; P30-NS057091/NS/NINDS NIH HHS; P30NS057091/NS/NINDS NIH HHS; P41 RR008079/RR/NCRR NIH HHS; P41 RR008079/RR/NCRR NIH HHS; P41 RR008079-175181/RR/NCRR NIH HHS; P41RR008079/RR/NCRR NIH HHS; R01 CA131013/CA/NCI NIH HHS; R01 HD057064/HD/NICHD NIH HHS; R01 HL093077/HL/NHLBI NIH HHS; R01 NS 22920-13/NS/NINDS NIH HHS; R01 NS035192/NS/NINDS NIH HHS; R01-HL53560-05/HL/NHLBI NIH HHS; R21 AG029582/AG/NIA NIH HHS; R21 NS056172/NS/NINDS NIH HHS; R21 NS060253/NS/NINDS NIH HHS; RR00400/RR/NCRR NIH HHS
Reg. No./Substance:
0/Glial Fibrillary Acidic Protein; 0/Isoprostanes; 0/Protons; 020IUV4N33/Phosphocreatine; 30KYC7MIAI/Aspartic Acid; 4L6452S749/Inositol; 997-55-7/N-acetylaspartate

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