Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Bas van Lith (Donders series 453)

16 November 2020

Promotors: prof. dr. A. Geurts, dr. B. van de Warrenburg
Co-promotors: dr. V. Weerdesteyn, dr. J. Nonnekes

Balance and gait problems in people with hereditary spastic paraplegia: patient experience, underlying mechanisms and clinical management

Hereditary spastic paraplegia (HSP) refers to a heterogeneous group of inherited disorders that are clinically characterized by progressive lower extremity spasticity and muscle weakness. The common underlying mechanism is retrograde axonal degeneration of the corticospinal tracts, posterior spinal columns, and – to a lesser extent – the spinocerebellar fibers. The first presenting symptoms are subtle with development of leg stiffness. As the disease progresses, gait and balance impairments develop, which may result in falls and fall-related injuries that increasingly affect safe and independent mobility. Yet, the influence of spasticity on gait and balance impairments remains poorly understood. This thesis provides new insights in the functional complaints and problems in individuals with HSP as well as in the underlying mechanisms and possible treatment of balance and gait problems in these people.

The results of a web-based survey showed the large functional impact of HSP on the lives of people with pure forms of HSP. Studies on the underlying mechanisms showed that standing balance control in people with HSP was not so much affected by excessive short-latency stretch reflexes, but rather by problems with timely muscle deactivation. In a gait initiation task, we found that – in terms of reaction times – the intact cortico-reticulospinal pathway was able to compensate for the defective corticospinal tract when a visual stimulus was combined with a loud auditory stimulus (StartReact effect), but that this compensation was suboptimal, because it lacked the capacity to improve the timely deactivation of muscles. In two clinical studies, we were able to show that botulinum toxin type-A (BTX-A) injected in either the calf muscles or hip adductor muscles, combined with subsequent stretching of these muscles, was able to improve gait speed. BTX-A treatment of the hip adductor muscles also showed improved lateral stepping responses to balance perturbations.

The general discussion of the thesis relates the various chapters with each other by providing an overall view of the effect of spasticity (treatment) on the control of balance and gait in people with neurological disability.