Pathophysiology of neurogenic orthostatic hypotension in patients with multiple system atrophy: a functional MRI study

• Grant number: 19/23491-6
• Support Opportunities: Scholarships abroad - Research
• Start date: February 21, 2022
• End date: February 20, 2023
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Hugo Celso Dutra de Souza
• Grantee: Hugo Celso Dutra de Souza
• Host Investigator: Jens Tank
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: German Aerospace Center, Germany

Abstract

The multiple systemic atrophy (MSA) is a rare disease, with rapid and fatal evolution, affecting the central nervous system in different ways. It is characterized by being a ±-synucleinopathy with particularities of parkinsonism or cerebellar and pyramidal dysfunction, occurring in different combinations. However, one of the main symptoms is autonomic disfunction which is responsible for neurogenic orthostatic hypotension, mechanism not yet defined, but present in most cases. One of the possible hypotheses pointed as cause of autonomic dysfunction is the existence of alterations in central nuclei of cardiovascular control, mainly hypothalamic. Objectives: To analyze in patients with MSA, the involvement of central autonomic cardiovascular control neuronal nuclei in the genesis of neurogenic orthostatic hypotension, with emphasis on the paraventricular nuclei (PVN), as well as to evaluate the role of vasopressin in this condition. Methods: 30 volunteer patients with MSA and 30 volunteers with no history of neurological disorder or postural hypotension, matched for age (> 18 years) and gender, will be recruited from the University Hospital of Colonia/DE and Medicine School of Hannover/DE. All groups will undergo to the following experimental procedures; paraventricular nuclei activation (PVN) of hypothalamus - induced by a negative (0, -10, -30 mmHg) lower-body negative pressure (LBNP) condition and measured by functional magnetic resonance imaging (fMRI); vasopressin plasma levels; and assessment of cardiovascular autonomic control by analyzing baroreflex sensitivity and heart rate and blood pressure variability, before and after LBNP and cardiovascular autonomic activation by active postural change (supine to standing position). (AU)