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Iron-sensitive MR imaging of the primary motor cortex to differentiate hereditary spastic paraplegia from other motor neuron diseases

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An Editorial Comment to this article was published on 08 September 2022

Abstract

Objectives

Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative diseases characterised by upper motor neuron (UMN) impairment of the lower limbs. The differential diagnosis with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) can be challenging. As microglial iron accumulation was reported in the primary motor cortex (PMC) of ALS cases, here we assessed the radiological appearance of the PMC in a cohort of HSP patients using iron-sensitive MR imaging and compared the PMC findings among HSP, PLS, and ALS patients.

Methods

We included 3-T MRI scans of 23 HSP patients, 7 PLS patients with lower limb onset, 8 ALS patients with lower limb and prevalent UMN onset (UMN-ALS), and 84 ALS patients with any other clinical picture. The PMC was visually rated on 3D T2*-weighted images as having normal signal intensity, mild hypointensity, or marked hypointensity, and differences in the frequency distribution of signal intensity among the diseases were investigated.

Results

The marked hypointensity in the PMC was visible in 3/22 HSP patients (14%), 7/7 PLS patients (100%), 6/8 UMN-ALS patients (75%), and 35/84 ALS patients (42%). The frequency distribution of normal signal intensity, mild hypointensity, and marked hypointensity in HSP patients was different than that in PLS, UMN-ALS, and ALS patients (p < 0.01 in all cases).

Conclusions

Iron-sensitive imaging of the PMC could provide useful information in the diagnostic work - up of adult patients with a lower limb onset UMN syndrome, as the cortical hypointensity often seen in PLS and ALS cases is apparently rare in HSP patients.

Key Points

• The T2* signal intensity of the primary motor cortex was investigated in patients with HSP, PLS with lower limb onset, and ALS with lower limb and prevalent UMN onset (UMN-ALS) using a clinical 3-T MRI sequence.

• Most HSP patients had normal signal intensity in the primary motor cortex (86%); on the contrary, all the PLS and the majority of UMN-ALS patients (75%) had marked cortical hypointensity.

• The T2*-weighted imaging of the primary motor cortex could provide useful information in the differential diagnosis of sporadic adult-onset UMN syndromes.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

HSP:

Hereditary spastic paraplegia

MND:

Motor neuron disease

PLS:

Primary lateral sclerosis

UMN:

Upper motor neuron

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Acknowledgements

We thank Prof. P. Frumento for his valuable suggestions on data analysis.

Funding

The authors state that this work has not received any funding.

Author information

Author notes

  1. Mirco Cosottini and Graziella Donatelli contributed equally to this work.

Authors and Affiliations

  1. Neuroradiology Unit, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Mirco Cosottini & Claudio D’Amelio

  2. Neuroradiology Unit, Azienda Ospedaliero-Universitaria Pisana, Via Paradisa 2, 56124, Pisa, Italy

    Graziella Donatelli, Gianmichele Migaleddu & Paolo Cecchi

  3. Imago7 Research Foundation, Pisa, Italy

    Graziella Donatelli & Paolo Cecchi

  4. Molecular Medicine Unit, IRCCS Fondazione Stella Maris, Pisa, Italy

    Ivana Ricca, Alessandra Tessa & Filippo Maria Santorelli

  5. Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Francesca Bianchi, Vincenzo Montano, Eleonora Del Prete, Gabriele Siciliano & Michelangelo Mancuso

  6. Neurology Unit, Department of Medical Specialties, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

    Daniela Frosini

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  1. Mirco Cosottini
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Corresponding author

Correspondence to Graziella Donatelli.

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The scientific guarantor of this publication is Mirco Cosottini.

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The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

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Written informed consent was obtained from all subjects (patients) in this study.

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• retrospective

• observational

• multicentre study

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Supplementary information

Supplemental Figure

Examples of the scoring system used to rate the signal intensity of the primary motor cortex. Compared to the post-central cortex, the deep layers of the primary motor cortex (arrows) were rated as isointense (A), mildly hypointense (B) or marked hypointense (C) (JPG 108 kb)

Supplemental Table

Clinical and genetic data of HSP patients (DOCX 26 kb)

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Cosottini, M., Donatelli, G., Ricca, I. et al. Iron-sensitive MR imaging of the primary motor cortex to differentiate hereditary spastic paraplegia from other motor neuron diseases. Eur Radiol 32, 8058–8064 (2022). https://doi.org/10.1007/s00330-022-08865-6

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