DescriptionMotor neuron disease (MND) is a devastating neurodegenerative disorder characterized by progressive motor neuron loss, leading to weakness of the muscles of arms and legs, bulbar and respiratory muscles. Depending on the involvement of the lower and the upper motor neuron, amyotrophic lateral sclerosis (ALS; both lower and upper motor neuron affected) and progressive muscular atrophy (PMA; only lower motor neuron affected) are recognized. There is no cure, despite numerous pharmaceutical trials which show promising results in mouse models, and significant advances in the field of genetics and neuropathology. One of the reasons of the failure of pharmaceutical trials is the complexity of the underlying pathophysiology of MND. There is accumulating evidence that in a fair proportion of the MND-patients accompanying non-motor symptoms occur, with an overlap with frontotemporal dementia (FTD) at the end of the spectrum. In order to fully understand the pathophysiology of MND we first need more valid descriptions of the full range of symptoms, signs and the localisation of abnormalities within the nervous system.
Despite descriptions of dementia in ALS patients in the early 20th century, the extent of brain involvement in MND, and the profile of cognitive and behavioral symptoms, is still unknown.
In this thesis we present new evidence of brain dysfunction in two subtypes of MND: ALS and PMA. We show cognitive impairment and prefrontal brain changes in PMA, hippocampus involvement in ALS and present the cognitive and behavioral profiles of MND. We designed and validated new screening instruments to detect these cognitive and behavioral changes in clinical practice. Current research aims to further improve these tests, to search for anatomical substrates by brain imaging and to investigate the effects of non- motor symptoms on survival and quality of life of patients with MND.
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