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Structural and metabolic damage in brains of patients with SPG11-related spastic paraplegia as detected by quantitative MRI

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Abstract

The goal of this work was to assess brain structural and metabolic abnormalities of subjects with SPG11 and their relevance to clinical disability by using quantitative magnetic resonance (MR) metrics. Autosomal recessive hereditary spastic paraplegia (AR-HSP) with thin corpus callosum and cognitive decline is a complex neurological disorder caused by mutations in the SPG11 gene in most cases. Little is known about the process leading to corticospinal and white matter degeneration. We performed conventional MRI/MR spectroscopic imaging (1H-MRSI) examinations in 10 HSP patients carrying an SPG11 mutation and in 10 demographically matched healthy controls (HC). We measured in each subject cerebral white matter hyperintensities (WMHs), normalized global and cortical brain volumes, and 1H-MRSI-derived central brain levels of N-acetylaspartate (NAA) and choline (Cho) normalized to creatine (Cr). Clinical disability was assessed according to patients’ autonomy in walking. Conventional MRI showed WMHs in all patients. Global brain volumes were lower in patients than in HC (p < 0.001). Decreased values were diffusely found also in cortical regions (p < 0.01). On 1H-MRSI, NAA/Cr values were lower in SPG11 patients than in HC (p = 0.002). Cho/Cr values did not differ between patients and HC. Cerebral volume decreases and NAA/Cr in the corona radiata correlated closely with increasing disability scores (p < 0.05). Quantitative MR measures propose that widespread structural and metabolic brain damage occur in SPG11 patients. The correlation of these MR metrics with measures of patients’ disease severity suggests that they might represent adequate surrogate markers of disease outcome.

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Acknowledgments

The study was supported in part by a Grant of PRIN (no. 20006063820_002) to AM and by Grants from Italian Ministry of Health, Fondazione Telethon (GGP10121A) and E-RARE Grant from European Union (EUROSPA network) to FMS.

Conflict of interest

Authors do not have financial relationship with the organizations that supported the research.

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Authors and Affiliations

  1. Neurology and Neurometabolic Unit, Department of Neurological and Behavioural Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy

    Maria Laura Stromillo, Alessandro Malandrini, Maria Teresa Dotti, Marco Battaglini, Federico Borgogni, Carmen Gaudiano, Carla Battisti, Antonio Federico & Nicola De Stefano

  2. Molecular Medicine and Neurogenetics, IRCCS Fondazione Stella Maris, Pisa, Italy

    Alessandra Tessa, Eugenia Storti & Filippo Maria Santorelli

  3. IRCCS Bambino Gesù, Rome, Italy

    Paola S. Denora

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  1. Maria Laura Stromillo
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  2. Alessandro Malandrini
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  3. Maria Teresa Dotti
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  9. Filippo Maria Santorelli
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Correspondence to Nicola De Stefano.

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Stromillo, M.L., Malandrini, A., Dotti, M.T. et al. Structural and metabolic damage in brains of patients with SPG11-related spastic paraplegia as detected by quantitative MRI. J Neurol 258, 2240–2247 (2011). https://doi.org/10.1007/s00415-011-6106-x

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  • DOI: https://doi.org/10.1007/s00415-011-6106-x

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