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Perinatal stroke: mapping and modulating developmental plasticity

Abstract

Most cases of hemiparetic cerebral palsy are caused by perinatal stroke, resulting in lifelong disability for millions of people. However, our understanding of how the motor system develops following such early unilateral brain injury is increasing. Tools such as neuroimaging and brain stimulation are generating informed maps of the unique motor networks that emerge following perinatal stroke. As a focal injury of defined timing in an otherwise healthy brain, perinatal stroke represents an ideal human model of developmental plasticity. Here, we provide an introduction to perinatal stroke epidemiology and outcomes, before reviewing models of developmental plasticity after perinatal stroke. We then examine existing therapeutic approaches, including constraint, bimanual and other occupational therapies, and their potential synergy with non-invasive neurostimulation. We end by discussing the promise of exciting new therapies, including novel neurostimulation, brain–computer interfaces and robotics, all focused on improving outcomes after perinatal stroke.

Key points

  • As a focal, unilateral brain injury near the beginning of life, perinatal stroke is an ideal model of human developmental plasticity.

  • The motor system is often damaged in perinatal stroke, resulting in hemiparetic or unilateral cerebral palsy and dramatic alterations in how the motor system develops.

  • Advanced neuroimaging and brain mapping techniques can define these alterations in development, which often include control of the hemiparetic limbs by the non-lesioned (ipsilateral) hemisphere.

  • The design and administration of manual therapies for hemiparetic cerebral palsy are increasingly informed by clinical trials in which pre-interventional and post-interventional imaging and motor mapping are used to help define mechanisms of interventional plasticity.

  • Non-invasive neuromodulation can safely enhance motor learning in children and emerging clinical trial data suggest synergistic effects with therapy-induced endogenous plasticity.

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Fig. 1: Perinatal stroke classification.
Fig. 2: Neurodevelopment after perinatal stroke.
Fig. 3: Models of developmental neuroplasticity after perinatal stroke.
Fig. 4: Using tractography to study developmental plasticity after perinatal stroke.
Fig. 5: Structural imaging of developmental plasticity after perinatal stroke.
Fig. 6: Functional imaging of developmental plasticity after perinatal stroke.
Fig. 7: TMS motor maps and corticospinal pathways.
Fig. 8: Manual therapies for hemiparetic cerebral palsy.

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The authors contributed equally to all aspects of the article.

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Nature Reviews Neurology thanks S. Chabrier (who co-reviewed with M. Chevin), A. Guzetta, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Review criteria

A literature search was performed on 7 August 2020. The following MeSH and keyword terms were searched in combination for relevance to the stated aims of the review: “cerebral palsy”, “hemiplegia”, “infant”, “newborn”, “child”, “neuronal plasticity”, “stroke”, “stroke rehabilitation”, “porencephaly”, “transcranial magnetic stimulation”, “transcranial direct current stimulation”, “occupational therapy” and “clinical trial” (MeSH terms); and “perinatal stroke”, “neonatal stroke”, “unilateral cerebral palsy”, “congenital hemiplegia”, “constraint-induced movement therapy” and “bimanual therapy” (independent terms). Search results were screened for results relevant to the predefined aims of the Review and incorporated accordingly.

Related links

International Alliance for Pediatric Stroke: https://iapediatricstroke.org

International Pediatric Stroke Organization: https://internationalpediatricstroke.org

Glossary

Global efficiency

A graph theory metric that quantifies the extent to which a network’s organization results in shortest path lengths between any two nodes and is equivalent to the average inverse shortest path length in the network.

Betweenness centrality

A graph theory metric that quantifies how central a node is by assessing how many connections go through a particular node to connect to other nodes within a network.

Clustering coefficient

A graph theory metric that quantifies the tendency for a node’s direct neighbours to be connected to each other, highlighting the presence of hub, or popular, structures within a network.

Mirror neurons

Neurons that depolarize during execution of goal-directed movement as well as during observation of someone else performing the same or similar movement.

Synaptic competition model

A model of developmental neuroplasticity after early injury describing competition between contralateral and ipsilateral populations of neurons that suggests that resulting organization of complex networks (motor, somatosensory, language) is dependent upon experience-dependent plasticity in early life.

Laterality

A quantification of symmetry or asymmetry between hemispheres, indicating which hemisphere has higher values of the variable of interest.

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Kirton, A., Metzler, M.J., Craig, B.T. et al. Perinatal stroke: mapping and modulating developmental plasticity. Nat Rev Neurol 17, 415–432 (2021). https://doi.org/10.1038/s41582-021-00503-x

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