Freezing of gait: understanding the complexity of an enigmatic phenomenon.
Brain
; 143(1): 14-30, 2020 01 01.
Article
em En
| MEDLINE
| ID: mdl-31647540
ABSTRACT
Diverse but complementary methodologies are required to uncover the complex determinants and pathophysiology of freezing of gait. To develop future therapeutic avenues, we need a deeper understanding of the disseminated functional-anatomic network and its temporally associated dynamic processes. In this targeted review, we will summarize the latest advances across multiple methodological domains including clinical phenomenology, neurogenetics, multimodal neuroimaging, neurophysiology, and neuromodulation. We found that (i) locomotor network vulnerability is established by structural damage, e.g. from neurodegeneration possibly as result from genetic variability, or to variable degree from brain lesions. This leads to an enhanced network susceptibility, where (ii) modulators can both increase or decrease the threshold to express freezing of gait. Consequent to a threshold decrease, (iii) neuronal integration failure of a multilevel brain network will occur and affect one or numerous nodes and projections of the multilevel network. Finally, (iv) an ultimate pathway might encounter failure of effective motor output and give rise to freezing of gait as clinical endpoint. In conclusion, we derive key questions from this review that challenge this pathophysiological view. We suggest that future research on these questions should lead to improved pathophysiological insight and enhanced therapeutic strategies.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Encéfalo
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Transtornos Neurológicos da Marcha
Tipo de estudo:
Qualitative_research
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article