Natural history of neurological improvement following complete (AIS A) thoracic spinal cord injury across three registries to guide acute clinical trial design and interpretation

Alex A. Aimetti, Steven Kirshblum, Armin Curt, Joseph Mobley, Robert G. Grossman, James D Guest

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Study design: Retrospective, longitudinal analysis of motor and sensory outcomes following thoracic (T2–T12) sensorimotor complete spinal cord injury (SCI) in selected patients enrolled into three SCI) registries. Objectives: To establish a modern-day international benchmark for neurological recovery following traumatic complete thoracic sensorimotor SCI in a population similar to those enrolled in acute clinical trials. Setting: Affiliates of the North American Clinical Trial Network (NACTN), European Multicenter Study about Spinal Cord Injury (EMSCI), and the Spinal Cord Injury Model Systems (SCIMS). Methods: Only traumatic thoracic injured patients between 2006 and 2016 meeting commonly used clinical trial inclusion/exclusion criteria such as: age 16–70, T2–T12 neurological level of injury (NLI), ASIA Impairment Scale (AIS) A, non-penetrating injury, acute neurological exam within 7 days of injury, and follow-up neurological exam at least ~ 6 months post injury, were included in this analysis. International Standards for Neurological Classification of Spinal Cord injury outcomes including AIS conversion rate, NLI, and sensory and motor scores/levels were compiled. Results: A total of 170 patients were included from the three registries: 12 from NACTN, 64 from EMSCI, and 94 from SCIMS. AIS conversion rates at approximately 6 months post injury varied from 16.7% to 23.4% (21.1% weighted average). Improved conversion rates were observed in all registries for low thoracic (T10–T12) injuries when compared with high/mid thoracic (T2–T9) injuries. The NLI was generally stable and lower extremity motor score (LEMS) improvement was uncommon and usually limited to low thoracic injuries only. Conclusions: This study presents the aggregation of selected multinational natural history recovery data in thoracic AIS A patients from three SCI registries and demonstrates comparable minimal improvement of ISNCSCI-scored motor and sensory function following these injuries, whereas conversions to higher AIS grades occur at a frequency of ~20%. These data inform the development of future clinical trial protocols in this important patient population for the interpretation of the safety and potential clinical benefit of new therapies, and the potential applicability in a multinational setting. Sponsorship: InVivo Therapeutics.

Original languageEnglish (US)
JournalSpinal Cord
DOIs
StatePublished - Jan 1 2019

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Thoracic Injuries
Natural History
Spinal Cord Injuries
Registries
Clinical Trials
Wounds and Injuries
Thorax
Clinical Protocols
Multicenter Studies
Benchmarking
Population
Lower Extremity
Retrospective Studies
Safety

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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Natural history of neurological improvement following complete (AIS A) thoracic spinal cord injury across three registries to guide acute clinical trial design and interpretation. / Aimetti, Alex A.; Kirshblum, Steven; Curt, Armin; Mobley, Joseph; Grossman, Robert G.; Guest, James D.

In: Spinal Cord, 01.01.2019.

Research output: Contribution to journalArticle

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title = "Natural history of neurological improvement following complete (AIS A) thoracic spinal cord injury across three registries to guide acute clinical trial design and interpretation",
abstract = "Study design: Retrospective, longitudinal analysis of motor and sensory outcomes following thoracic (T2–T12) sensorimotor complete spinal cord injury (SCI) in selected patients enrolled into three SCI) registries. Objectives: To establish a modern-day international benchmark for neurological recovery following traumatic complete thoracic sensorimotor SCI in a population similar to those enrolled in acute clinical trials. Setting: Affiliates of the North American Clinical Trial Network (NACTN), European Multicenter Study about Spinal Cord Injury (EMSCI), and the Spinal Cord Injury Model Systems (SCIMS). Methods: Only traumatic thoracic injured patients between 2006 and 2016 meeting commonly used clinical trial inclusion/exclusion criteria such as: age 16–70, T2–T12 neurological level of injury (NLI), ASIA Impairment Scale (AIS) A, non-penetrating injury, acute neurological exam within 7 days of injury, and follow-up neurological exam at least ~ 6 months post injury, were included in this analysis. International Standards for Neurological Classification of Spinal Cord injury outcomes including AIS conversion rate, NLI, and sensory and motor scores/levels were compiled. Results: A total of 170 patients were included from the three registries: 12 from NACTN, 64 from EMSCI, and 94 from SCIMS. AIS conversion rates at approximately 6 months post injury varied from 16.7{\%} to 23.4{\%} (21.1{\%} weighted average). Improved conversion rates were observed in all registries for low thoracic (T10–T12) injuries when compared with high/mid thoracic (T2–T9) injuries. The NLI was generally stable and lower extremity motor score (LEMS) improvement was uncommon and usually limited to low thoracic injuries only. Conclusions: This study presents the aggregation of selected multinational natural history recovery data in thoracic AIS A patients from three SCI registries and demonstrates comparable minimal improvement of ISNCSCI-scored motor and sensory function following these injuries, whereas conversions to higher AIS grades occur at a frequency of ~20{\%}. These data inform the development of future clinical trial protocols in this important patient population for the interpretation of the safety and potential clinical benefit of new therapies, and the potential applicability in a multinational setting. Sponsorship: InVivo Therapeutics.",
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