Orthostatic hypotension

Summary

Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypotension is also often referred to as neurogenic orthostatic hypotension. The drop in blood pressure may be sudden (vasovagal orthostatic hypotension), within 3 minutes (classic orthostatic hypotension) or gradual (delayed orthostatic hypotension). It is defined as a fall in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg after 3 mins of standing. It occurs predominantly by delayed (or absent) constriction of the lower body blood vessels, which is normally required to maintain adequate blood pressure when changing the position to standing. As a result, blood pools in the blood vessels of the legs for a longer period, and less is returned to the heart, thereby leading to a reduced cardiac output and inadequate blood flow to the brain. Very mild occasional

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https://en.wikipedia.org/wiki/Orthostatic_hypotension

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Implanted System for Orthostatic Hypotension in Multiple-System Atrophy

Suje Amir, Léonie Asboth, Maxime Berney, Jocelyne Bloch, Grégoire Courtine, Robin Jonathan Demesmaeker, Grégory Didier Dumont, Nicolas Hankov, Sergio Daniel Hernandez, Jordan Squair

Orthostatic hypotension is a cardinal feature of multiple-system atrophy. The upright posture provokes syncopal episodes that prevent patients from standing and walking for more than brief periods. We implanted a system to restore regulation of blood pressure and enable a patient with multiple-system atrophy to stand and walk after having lost these abilities because of orthostatic hypotension. This system involved epidural electrical stimulation delivered over the thoracic spinal cord with accelerometers that detected changes in body position.

MASSACHUSETTS MEDICAL SOC2022

Spinal cord injury (SCI) is a life-changing event. People who suffer from it lose their abilityto move normally and are subject to life-threatening symptoms. When the insult is not toosevere, partial recovery is possible. Otherwise, for severely affected people, the perspectives toever retrieve normal functions is almost non-existent. A critically important window to promoteplasticity is in the acute phase after the trauma (weeks to months). However, at this stage,people cannot take active part in rehabilitation programs due to their incapacity to activate theirlimbs and to the apparition of severe autonomic symptoms such as orthostatic hypotension.Hence, current activity-based treatments are of little help for this population. Consequently, SCIdramatically affects their autonomy and quality of life on the life-long term.Continuous Epidural Electrical Stimulation (EES) of the spinal cord has been proposed as amethod to reactivate dormant neural networks innervated below the site of injury. It enablesrobust control over locomotion and autonomic functions. In animal models of severe lesion,continuous EES promoted long lasting recovery of motor abilities when coupled with an intensivetraining. In human, its recent application indeed supported overground walking in chronicallyand severely injured people, but only showed limited plastic effects when compared to animals.Why? Recent advances support that continuous EES abolishes proprioceptive feedback thatis essential to promote recovery. Moreover, late treatment of severe injuries consistently fail apromoting recuperation of functions. Alternatively, over the last decade, our laboratory developeda spatio-temporally patterned approach to EES. In addition to restore fine control over motorfunctions, this technique avoids the caveats of continuous EES, and hypothetically opens a windowof opportunity for plasticity to happen. In this thesis, we propose a translation of this concept tohumans. We first demonstrate that spatio-temporal EES restores robust and versatile locomotorcontrol in people with chronic incomplete, though severe, SCI. Furthermore, the results supportan aptitude of this approach to promote long lasting recovery of functions without stimulationafter 5 months of intensive training. We then report on a patient-tailored technology, thatincludes personalized computational models enabling precise pre-operative planning strategies, anew electrode-lead and control softwares. This technology enables restoration of various motorfunctions in people with chronic and motor-complete injuries within few hours after beginningof therapy. Finally, we transfer this targeted approach to the control of blood pressure. Wedemonstrate that closed-loop stimulation protocols support a precise control over arterial bloodpressure in rodents, non-humane primates and humans with severe SCI submitted to challengingcardiovascular conditions. Combined, the results presented in this manuscript open a clinicallyrealistic perspective for the application of EES acutely after injury and to potentially promoterobust recovery in severe SCI.

EPFL2021

Electrical spinal cord stimulation protocols to regulate motor and autonomic functions in people with neurological disorders

Robin Jonathan Demesmaeker

Neurological disorders such as spinal cord injury (SCI) massively reduce independence and quality of life. Most often, the majority of the nervous system is still fully or partially spared, but dysfunctional due to aberrant or absent descending input from the brain. Neuromodulation techniques restore function by artificially engaging these neuronal circuits. Given its central position and multi- functional role, the spinal cord provides an excellent gateway for such therapies.Epidural Electrical Stimulation (EES) of the spinal cord has been put forward as a potential therapy to restore motor and autonomic function after SCI. Throughout the last decade, our laboratory developed the concept of biomimetic EES. Spatiotemporal stimulation parameters are optimized to re-establish the natural dynamics of the underlying spinal circuitry. Strong evidence in rodent and non- human primate models suggests that biomimetic EES could promote locomotion and haemodynamic stability after severe SCI, leading to a push for rapid clinical translation of this potentially game-changing therapy. This clinical translation is the pivot of my thesis.The first part focuses on the recovery of leg motor control after SCI. The results of a first-in-human clinical trial in 9 participants with chronic SCI are presented. We developed a set of targeted neurotechnologies that include a new epidurally implanted electrode array, real-time communication and tailormade software systems that enable the precise delivery of biomimetic EES. We demon- strate that biomimetic EES can be optimized to immediately restore a vast number of leg motor functions such as walking and cycling, as well as trunk posture. Furthermore, after 5 months of intensive EES-enabled volitional training, participants did not only all improve their motor performance while using EES, they moreover regained volitional control over previously paralyzed muscles. This neuro- logical recovery correlated with a reduced metabolic activity in the spinal cord, suggesting spinal remodeling. A systematic pre-clinical approach identified a specific neuronal population mediating these effects.The second part of my thesis considers another critically important body function: haemodynamic management. Orthostatic hypo- tension is a major health issue after severe SCI and stems from a disconnection between the vasomotor regulatory centres in the brainstem and the sympathetic circuitry that adjusts peripheral vascular resistance. Preclinical work in rodents showed that EES ap- plied to the low-thoracic spinal cord could restore haemodynamic stability after SCI. On the path towards clinical translation, we implemented closed-loop control of EES in a non-human primate model of SCI to maintain haemodynamic stability during orthostatic challenge. I moreover present a case-study that demonstrates the transferability of thoracic EES to improve haemodynamic manage- ment in a patient with Multiple System Atrophy (MSA). A marked reduction of orthostatic hypotension led to a clinically relevant decrease in fainting episodes and considerably improved quality of life.My thesis demonstrates the prosthetic and therapeutic effects of biomimetic EES and highlights its ability to immediately restore body functions and boost neurological recovery after SCI and in MSA. These results strengthen the belief that EES holds the potential to evolve into a relevant and efficient therapeutic intervention in a plentitude of neurological disorders.

EPFL2021

Electrical spinal cord stimulation protocols to regulate motor and autonomic functions in people with neurological disorders

Robin Jonathan Demesmaeker

EPFL2021