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Gagaouzova, B.S. (2026)

The kaleidoscope of haemodynamic changes in different neurologic conditions

Doctoral Thesis
This thesis investigates autonomic dysfunction and haemodynamic regulation across neurological conditions, focusing on orthostatic hypotension (OH), synucleinopathies, and focal seizures. In Chapter 2, sudomotor testing, skin wrinkling, and OCT differentiated patients from controls but failed to distinguish pure autonomic failure (PAF) from multiple system atrophy (MSA), likely due to overlapping pathology, disease duration, and preserved acral sweating in MSA. Subsequent chapters examined classical OH (cOH), showing that low mean arterial pressure is mainly driven by insufficient increases in total peripheral resistance (TPR) and reduced stroke volume, rather than limited heart rate responses. Across studies, haemodynamic patterns varied widely, blurring distinctions between neurogenic and non-neurogenic OH and challenging the binary classification of cOH subtypes.

Supine hypertension in cOH was primarily associated with elevated TPR, despite...Show moreThis thesis investigates autonomic dysfunction and haemodynamic regulation across neurological conditions, focusing on orthostatic hypotension (OH), synucleinopathies, and focal seizures. In Chapter 2, sudomotor testing, skin wrinkling, and OCT differentiated patients from controls but failed to distinguish pure autonomic failure (PAF) from multiple system atrophy (MSA), likely due to overlapping pathology, disease duration, and preserved acral sweating in MSA. Subsequent chapters examined classical OH (cOH), showing that low mean arterial pressure is mainly driven by insufficient increases in total peripheral resistance (TPR) and reduced stroke volume, rather than limited heart rate responses. Across studies, haemodynamic patterns varied widely, blurring distinctions between neurogenic and non-neurogenic OH and challenging the binary classification of cOH subtypes.

Supine hypertension in cOH was primarily associated with elevated TPR, despite impaired TPR responses during standing, suggesting persistence of slow-acting mechanisms such as residual sympathetic tone or neurohumoral factors. Symptom perception in cOH correlated more with blood pressure decline than absolute blood pressure and was influenced by cerebral autoregulation and individual variability. The thesis also presents novel findings on focal seizures, demonstrating consistent ictal hypotension arising from diverse haemodynamic mechanisms.

Overall, the work argues that autonomic disorders exist on a haemodynamic spectrum, advocating for integrated assessment of heart rate, stroke volume, and TPR, and calling for more nuanced, personalized diagnostic frameworks.Show less
Orthostatic hypotension
Autonomic failure
Focal seizure
Alpha synucleinopathies
All authors
Gagaouzova, B.S.
Supervisor
Dijk, J.C. van
Co-supervisor
Thijs, R.D.; Rossum, I.A. van
Committee
Verschuuren, J.J.G.M.; Zijlmans, G.J.M.; Bootsma, M.; Saal, D.P.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2026-01-29
ISBN (print)
9789083641546
DOI
doi:10.60602/1887-4288228