{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:43:16Z","timestamp":1776732196859,"version":"3.51.2"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary Spastic Paraplegias (HSP) are genetic neurodegenerative disorders affecting the corticospinal tract. No established neuroimaging biomarker is associated with this condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 46 patients affected by HSP, genetically and clinically evaluated and tested with SPRS scores, and 46 healthy controls (HC) matched by age and gender underwent a single-voxel Magnetic Resonance Spectroscopy sampling (MRS) of bilateral pre-central and pre-frontal regions. MRS data were analyzed cross-sectionally (at T<jats:sub>0<\/jats:sub> and T<jats:sub>1<\/jats:sub>) and longitudinally (T<jats:sub>0<\/jats:sub> vs. T<jats:sub>1<\/jats:sub>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Statistically significant data showed that T<jats:sub>0<\/jats:sub> mI\/Cr in the pre-central areas of HSP patients was higher than in HC. In the left (L) pre-central area, NAA\/Cr was significantly lower in HSP than in HC. In the right (R) pre-frontal area, NAA\/Cr was significantly lower in HSP patients than in HC. HSP SPG4 subjects had significantly lower Cho\/Cr concentrations in the L pre-central area compared to HC. Among the HSP subjects, non-SPG4 patients had significantly higher mI\/Cr in the L pre-central area compared to SPG4 patients. In the R pre-frontal area, NAA\/Cr was reduced, and ml\/Cr was higher in non-SPG4 patients compared to SPG4 patients. Comparing \u201cpure\u201d and \u201ccomplex\u201d forms, NAA\/Cr was higher in pHSP than in cHSP in the R pre-central and R pre-frontal areas. The longitudinal analysis, which involved fewer patients (<jats:italic>n<\/jats:italic>\u2009=\u200930), showed an increase in mI\/Cr concentration in the L pre-frontal area among HSP subjects with respect to baseline. The patients had significantly higher SPRS scores at follow-up, with a significant positive correlation between SPRS scores and mI\/Cr in the L pre-central area, while in bilateral pre-frontal areas, lower SPRS scores corresponded to higher NAA\/Cr concentrations. To explore the discriminating power of MRS in correctly identifying HSP and controls, an inference tree methodology classified HSP subjects and controls with an overall accuracy of 73.9%, a sensitivity of 87.0%, and a specificity of 60.9%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This pilot study indicates that brain MRS is a valuable approach that could potentially serve as an objective biomarker in HSP.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2024.1416093","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T20:43:20Z","timestamp":1723754600000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Metabolite profile in hereditary spastic paraplegia analyzed using magnetic resonance spectroscopy: a cross-sectional analysis in a longitudinal study"],"prefix":"10.3389","volume":"18","author":[{"given":"Domenico","family":"Montanaro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marinela","family":"Vavla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Frijia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Coi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Baratto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Pasquariello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Stefan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Martinuzzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.3174\/ajnr.A3897","article-title":"Brain white matter involvement in hereditary spastic paraplegias: analysis with multiple diffusion tensor indices","volume":"35","author":"Aghakhanyan","year":"2014","journal-title":"AJNR Am. 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