CLINICAL AND IMAGING CHARACTERIZATION IN HEREDITARY SPASTIC PARAPLEGIA TYPE 76 (HSP76)

• Grant number: 23/15514-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcondes Cavalcante Franca Junior
• Grantee: Isadora Maria Castilho da Silva Ferreira
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Hereditary spastic paraplegias are a group of neurodegenerative diseases primarily characterized by spasticity and progressive weakness in the lower limbs, resulting from axonal degeneration of the corticospinal tracts. They can be classified into pure or complicated forms, with the former exhibiting signs of pyramidal involvement, such as hyperreflexia, and the latter presenting additional neurological symptoms like movement disorders, dementia, ataxia, seizures, and muscle atrophy. Each subtype of HSP involves a different molecular mechanism, leading to a wide range of phenotypes within this group. In neuroimaging, the most common finding in hereditary spastic paraplegias is spinal cord atrophy, but each subtype has additional findings that have been described in recent studies. Identifying these specificities may aid in diagnosis. SPG76 is a subtype caused by mutations in the CAPN1 gene, and patients with this diagnosis exhibit not only spasticity and weakness but also other symptoms such as upper limb hyperreflexia, ataxia, dysarthria, and cavus feet. Neuroimaging findings in these patients are sparsely documented in the literature, although some case reports have revealed cerebellar alterations. Therefore, given the scarcity of studies evaluating the clinical profile and the pattern of brain magnetic resonance abnormalities in SPG76 patients, a larger study characterizing the clinical presentation and brain abnormalities becomes relevant. To better correlate the SPG subtype with clinical symptoms and neuroimaging findings, this study aims to describe the symptoms and evaluate cerebellar volume in SPG76 patients and a control group. We will compare the volumes of cerebellar lobes between the groups and relate them to the disease's clinical presentation. All patients are being followed at the neurogenetics and neuromuscular disease clinics at HC-UNICAMP.