The neuroanatomical–functional paradox in spinal cord injury

Nature Reviews Neurology, 2021 · DOI: 10.1038/s41582-020-00436-x · Published: January 1, 2021

Spinal Cord Injury Neurology Neurorehabilitation

Simple Explanation

Lesions of comparable size in the central nervous system can produce vastly different magnitudes of functional impairment and subsequent recovery, a phenomenon known as the neuroanatomical-functional paradox. In spinal cord injury (SCI), this paradox means that the ability to predict functional outcome based solely on anatomical or radiological data is limited, which confounds prognosis. The underlying mechanisms of this paradox include the concepts of lesion-affected and recovery-related networks, secondary complications, and the location of the lesion within functionally eloquent regions of the spinal cord.

Study Duration

Not specified

Participants

Animal models of thoracic and cervical SCI and individuals with SCI

Evidence Level

Review/Perspective

Key Findings

1
The magnitude of functional recovery can vary considerably between individuals, even if the location and size of the primary lesion seems to be similar.
2
Up to 25% of patients with motor and sensory complete SCI convert to incomplete SCI during the first year after injury, despite lesion size remaining relatively stable.
3
Small focal lesions in the spinal cord can cause almost a complete loss of function, whereas large, space-filling lesions are not always associated with marked functional impairment.

Research Summary

The neuroanatomical–functional paradox describes the discrepancy between lesion size and functional outcome after spinal cord injury (SCI). This paradox is influenced by various factors, including lesion location, lesion-affected and recovery-related networks, secondary complications (such as meta-inflammation and infections), and lesion-remote effects. Addressing the paradox requires a more comprehensive approach to preclinical and clinical SCI research, including embracing variable data, characterizing lesion-affected and regeneration-associated networks, improving data analysis, and increasing the internal and external validity of animal models.

Practical Implications

Improving Preclinical Models

Refining animal models to better represent the complexities of human SCI can improve the translatability of research findings.

Personalized Rehabilitation Strategies

Understanding the factors that contribute to the neuroanatomical-functional paradox can lead to personalized rehabilitation strategies that target specific recovery-related networks.

Novel Therapeutic Targets

Identifying modifiable factors that influence outcome can help in the discovery of new therapeutic targets for SCI.

Study Limitations

1
The exact mechanisms underlying the neuroanatomical–functional paradox are not fully understood.
2
Animal models of SCI do not perfectly replicate the complexities of human SCI.
3
It is challenging to control for all variables that influence functional recovery after SCI.

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