title: Combined Cerebellar Proton MR Spectroscopy and DWI Study of Patients with Friedreich's Ataxia.
abstract: Friedreich's ataxia (FRDA) is the commonest autosomal recessive ataxia, caused by GAA triplet expansion in the frataxin gene. Neuropathological studies in FRDA demonstrate that besides the primary neurodegeneration of the dorsal root ganglia, there is a progressive atrophy of the cerebellar dentate nucleus. Diffusion-weighted imaging (DWI) detected microstructural alterations in the cerebellum of FRDA patients. To investigate the biochemical basis of these alterations, we used both DWI and proton MR spectroscopy (1H-MRS) to study the same cerebellar volume of interest (VOI) including the dentate nucleus. DWI and1H-MRS study of the left cerebellar hemisphere was performed in 28 genetically proven FRDA patients and 35 healthy controls. In FRDA mean diffusivity (MD) values were calculated for the same1H-MRS VOI. Clinical severity was evaluated using the International Cooperative Ataxia Rating Scale (ICARS). FRDA patients showed a significant reduction of N-acetyl-aspartate (NAA), a neuroaxonal marker, and choline (Cho), a membrane marker, both expressed relatively to creatine (Cr), and increased MD values. In FRDA patients NAA/Cr negatively correlated with MD values (r = -0.396, p = 0.037) and with ICARS score (r = -0.669, p < 0.001). Age-normalized NAA/Cr loss correlated with the GAA expansion (r = -0.492, p = 0.008). The reduced cerebellar NAA/Cr in FRDA suggests that neuroaxonal loss is related to the microstructural changes determining higher MD values. The correlation between NAA/Cr and the severity of disability suggests that this biochemical in vivo MR parameter might be a useful biomarker to evaluate therapeutic interventions.
authors.affiliation: Functional MR Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy.
authors.forename: Laura Ludovica
authors.initials: LL
authors.lastname: Gramegna
authors.affiliation: Functional MR Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy. caterina.tonon@unibo.it.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy. caterina.tonon@unibo.it.
authors.forename: Caterina
authors.initials: C
authors.lastname: Tonon
authors.affiliation: Functional MR Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy.
authors.forename: David Neil
authors.initials: DN
authors.lastname: Manners
authors.affiliation: Child Neurology Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Pini
authors.affiliation: Neurology Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Rinaldi
authors.affiliation: Functional MR Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Zanigni
authors.affiliation: Functional MR Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bianchini
authors.affiliation: Functional MR Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Evangelisti
authors.affiliation: Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Fortuna
authors.affiliation: Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy.|Neurology Unit, IRCCS Istitute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.affiliation: Functional MR Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Testa
authors.affiliation: Functional MR Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Lodi
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002531:Cerebellum / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D002648:Child; D002794:Choline / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005621:Friedreich Ataxia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use; D066244:Proton Magnetic Resonance Spectroscopy; D012720:Severity of Illness Index; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D018696:Neuroprotective Agents; D014451:Ubiquinone; D001224:Aspartic Acid; C000179:N-acetylaspartate; C036619:idebenone; D002794:Choline
keywords: DWI; FRDA; Proton MRS