Sexual dimorphism in ALS: Exploring gender-specific neuroimaging signatures

Abstract

Our objective was to explore neuroanatomical differences between female and male ALS patients in the context of sexual dimorphism in healthy controls. Fourteen female ALS patients, 13 male ALS patients, 22 healthy male controls and 20 healthy female controls were recruited into a comprehensive neuroimaging study. Cortical thickness measurements and diffusion tensor imaging (DTI) were utilized to explore gender-specific anatomical vulnerability. DTI analysis across all study groups revealed higher fractional anisotropy in association with male gender in the brainstem, cerebellum, fornix, thalamus, anterior forceps and corticospinal tracts accounting for diagnosis and age. While females showed a trend of higher age-adjusted cortical thickness in the right parieto-occipital and left mid-frontal regions, males demonstrated higher cortical thickness in the left lingual and left superior temporal regions, accounting for diagnosis. Significant multifocal white matter differences have also been identified between healthy male and female controls. In conclusion, sexual dimorphism is an overlooked and potentially confounding factor in admixed ALS neuroimaging studies. Our results suggest that gender is an additional dimension of disease heterogeneity in ALS. Given the significant pre- and post-morbid gender differences, we feel that ALS imaging studies should be controlled for gender or, alternatively, single gender studies should be considered.

Key words::

• Amyotrophic lateral sclerosis
• neuroimaging
• MRI
• gender
• phenotypic heterogeneity

Acknowledgements

We acknowledge the generosity of our patients and their caregivers for kindly supporting this research study. We also acknowledge the radiographers, physicists and management of the Centre for Advanced Medical Imaging (CAMI – St James's Hospital Dublin).

Orla Hardiman’s research group has received speaking honoraria from Janssen Cilag, Biogen Idec, Sanofi Aventis and Merck-Serono. Orla Hardiman has been a member of advisory panels for Biogen Idec, Allergen, Cytokinetics, Ono Pharmaceuticals and Sanofi Aventis.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by the Elan Fellowship in Neurodegeneration, the Health Research Board and the Research Motor Neuron (RMN) foundation. The research leading to these results has received funding from the European Community’s Seventh Framework. The sponsors of the study had no role in study design, data acquisition, data analysis, data interpretation, or writing of the report.