Rare association between spinocerebellar ataxia and amyotrophic lateral sclerosis: a case series

Valerio Ferrari; Matteo Conti; Roberta Bovenzi; Rocco Cerroni; Mariangela Pierantozzi; Nicola B Mercuri; Alessandro Stefani

doi:10.1007/s10072-024-07521-9

Rare association between spinocerebellar ataxia and amyotrophic lateral sclerosis: a case series

Neurol Sci. 2024 Apr 20. doi: 10.1007/s10072-024-07521-9. Online ahead of print.

Authors

Valerio Ferrari¹, Matteo Conti¹, Roberta Bovenzi¹, Rocco Cerroni¹, Mariangela Pierantozzi², Nicola B Mercuri², Alessandro Stefani³

Affiliations

¹ Parkinson Centre, Department of Systems Medicine, University of Rome "Tor Vergata,", Rome, Italy.
² Neurology Unit, Department of Systems Medicine, University of Rome "Tor Vergata,", Rome, Italy.
³ Parkinson Centre, Department of Systems Medicine, University of Rome "Tor Vergata,", Rome, Italy. stefani@uniroma2.it.

PMID: 38642323
DOI: 10.1007/s10072-024-07521-9

Abstract

Introduction: In this work, we describe a new case of association between SCA2 and MND.

Case report: A 58-year-old man who was diagnosed with spinocerebellar ataxia type 2 presented dysphagia and a significant decline in his ability to walk, with a reduction in autonomy and the need to use a wheelchair. We performed electromyography and electroneurography of the four limbs and of the cranial district and motor-evoked potentials to study upper and lower motor neurons. Referring to the revised El Escorial criteria of 2015, ALS diagnosis was made.

Discussion: Considering different cases described in literature over the years, SCA2 could represent an important risk factor for developing ALS. In particular, the presence of alleles of ATXN2 with 27 and 28 CAG repeats seems to slightly decrease the risk of developing the disease, which would instead be progressively increased by the presence of alleles with 29, 30, 31, 32, and 33 repeats. The exact physiopathological mechanism by which the mutation increases the risk of developing the disease is currently unknown. Transcriptomic studies on mouse models have demonstrated the involvement of several pathways, including the innate immunity regulation by STING and the biosynthesis of fatty acid and cholesterol by SREBP.

Conclusion: CAG repeat expansions in the ATXN2 gene have been associated with variable neurological presentations, which include SCA2, ALS, Parkinsonism, or a combination of them. Further research is needed to understand the relationship between SCA2 and ALS better and explore molecular underlying mechanisms.

Keywords: Amyotrophic lateral sclerosis; Motor neuron disease; Spinocerebellar ataxia.