PMID- 32033120
OWN - NLM
STAT- MEDLINE
DCOM- 20201117
LR  - 20201117
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 3
DP  - 2020 Feb 4
TI  - Neuroimaging Biomarkers in SCA2 Gene Carriers.
LID - 10.3390/ijms21031020 [doi]
LID - 1020
AB  - A variety of Magnetic Resonance (MR) and nuclear medicine (NM) techniques have 
      been used in symptomatic and presymptomatic SCA2 gene carriers to explore,in 
      vivo, the physiopathological biomarkers of the neurological dysfunctions 
      characterizing the associated progressive disease that presents with a cerebellar 
      syndrome, or less frequently, with a levodopa-responsive parkinsonian syndrome. 
      Morphometry performed on T1-weighted images and diffusion MR imaging enable 
      structural and microstructural evaluation of the brain in presymptomatic and 
      symptomatic SCA2 gene carriers, in whom they show the typical pattern of 
      olivopontocerebellar atrophy observed at neuropathological examination. Proton MR 
      spectroscopy reveals, in the pons and cerebellum of SCA2 gene carriers,a more 
      pronounced degree of abnormal neurochemical profile compared to other 
      spinocerebellar ataxias with decreased NAA/Cr and Cho/Cr, increased mi/Cr ratios, 
      and decreased NAA and increased mI concentrations. These neurochemical 
      abnormalities are detectable also in presymtomatic gene carriers. Resting state 
      functional MRI (rsfMRI) demonstrates decreased functional connectivity within the 
      cerebellum and of the cerebellum with fronto-parietal cortices and basal ganglia 
      in symptomatic SCA2 subjects. (18)F-fluorodeoxyglucose Positron Emission 
      Tomography (PET) shows a symmetric decrease of the glucose uptake in the 
      cerebellar cortex, the dentate nucleus, the brainstem and the parahippocampal 
      cortex. Single photon emission tomography and PET using several radiotracers have 
      revealed almost symmetric nigrostriatal dopaminergic dysfunction irrespective of 
      clinical signs of parkinsonism which are already present in presymtomatic gene 
      carriers. Longitudinal small size studies have proven that morphometry and 
      diffusion MR imaging can track neurodegeneration in SCA2, and hence serve as 
      progression biomarkers. So far, such a capability has not been reported for 
      proton MR spectroscopy, rsfMRI and NM techniques. A search for the best surrogate 
      marker for future clinical trials represents the current challenge for the 
      neuroimaging community.
FAU - Mascalchi, Mario
AU  - Mascalchi M
AD  - Department of Clinical and Experimental Biomedical Sciences, University of 
      Florence, 50121 Florence, Italy.
FAU - Vella, Alessandra
AU  - Vella A
AD  - Nuclear Medicine at University Hospital, 53100 Siena, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200204
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (ATXN2 protein, human)
RN  - 0 (Ataxin-2)
RN  - 0 (Biomarkers)
SB  - IM
MH  - Ataxin-2/*genetics/*metabolism
MH  - Biomarkers/*metabolism
MH  - Brain/*diagnostic imaging/metabolism/pathology
MH  - Disease Progression
MH  - Heterozygote
MH  - Humans
MH  - Nervous System Diseases/genetics/pathology
MH  - Neuroimaging/*methods
PMC - PMC7037189
OTO - NOTNLM
OT  - Key-words: spinocerebellar ataxia type 2
OT  - brainstem
OT  - cerebellum
OT  - magnetic resonance
OT  - nuclear medicine
COIS- The authors declare no conflict of interest
EDAT- 2020/02/09 06:00
MHDA- 2020/11/18 06:00
PMCR- 2020/02/01
CRDT- 2020/02/09 06:00
PHST- 2019/12/21 00:00 [received]
PHST- 2020/01/27 00:00 [revised]
PHST- 2020/01/31 00:00 [accepted]
PHST- 2020/02/09 06:00 [entrez]
PHST- 2020/02/09 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - ijms21031020 [pii]
AID - ijms-21-01020 [pii]
AID - 10.3390/ijms21031020 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Feb 4;21(3):1020. doi: 10.3390/ijms21031020.