Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system.

Study Design: Narrative review.

Purpose: To provide an overview of adaptive trial designs, and describe how adaptive methods can address persistent challenges encountered by randomized controlled trials of people with spinal cord injury (SCI).

Results: With few exceptions, adaptive methodologies have not been incorporated into clinical trial designs of people with SCI.

The challenge of recruitment for neurotherapeutic clinical trials in spinal cord injury.

Study Design: Narrative review by individuals experienced in the recruitment of participants to neurotherapeutic clinical trials in spinal cord injury (SCI).

Objectives: To identify key problems of recruitment and explore potential approaches to overcoming them.

Methods: Published quantitative experience with recruitment of large-scale, experimental neurotherapeutic clinical studies targeting central nervous system and using primary outcome assessments validated for SCI over the last 3 decades was summarized.

Considerations and recommendations for selection and utilization of upper extremity clinical outcome assessments in human spinal cord injury trials.

Study Design: This is a focused review article.

Objectives: This review presents important features of clinical outcomes assessments (COAs) in human spinal cord injury research. Considerations for COAs by trial phase and International Classification of Functioning, Disability and Health are presented as well as strengths and recommendations for upper extremity COAs for research.

Representativeness of the Spinal Cord Injury Model Systems National Database.

Study Design: Secondary analysis of prospectively collected observational data.

Objectives: To assess the representativeness of the Spinal Cord Injury Model Systems National Database (SCIMS-NDB) of all adults aged 18 years or older receiving inpatient rehabilitation in the United States (US) for new onset traumatic spinal cord injury (TSCI).

Setting: Inpatient rehabilitation centers in the US.

Research progress from the SCI Model Systems (SCIMS): An interactive discussion on future directions.

Context/objective: To describe current and future directions in spinal cord injury (SCI) research.

Design: The SCI Model Systems (SCIMS) programs funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) during the 2011 to 2016 cycle provided abstracts describing findings from current research projects. Discussion among session participants generated ideas for research opportunities.

Patterns of Sacral Sparing Components on Neurologic Recovery in Newly Injured Persons With Traumatic Spinal Cord Injury.

Objective: To assess the patterns of sacral sparing and recovery in newly injured persons with traumatic spinal cord injury (SCI).

Design: Retrospective analysis of data from the national Spinal Cord Injury Model Systems (SCIMS) database for patients enrolled from January 2011 to February 2015.

Setting: SCIMS centers.

Toward Inclusive Trial Protocols in Heterogeneous Neurological Disorders: Prediction-Based Stratification of Participants With Incomplete Cervical Spinal Cord Injury.

Background: Several novel drug- and cell-based potential therapies for spinal cord injury (SCI) have either been applied or will be considered for future clinical trials. Limitations on the number of eligible patients require trials be undertaken in a highly efficient and effective manner. However, this is particularly challenging when people living with incomplete SCI (iSCI) represent a very heterogeneous population in terms of recovery patterns and can improve spontaneously over the first year after injury.

Association of various comorbidity measures with spinal cord injury rehabilitation outcomes.

Objective: To investigate the amount of variation in short- and medium-term spinal cord injury (SCI) rehabilitation outcomes explained by various comorbidity measures, over and above patient preinjury characteristics and neurologic and functional status.

Design: Prospective observational cohort study of traumatic SCI patients receiving inpatient rehabilitation and followed up at 1 year postinjury.

Setting: Inpatient rehabilitation and community follow-up at 6 SCI treatment centers.

Outcome Measures for Acute/Subacute Cervical Sensorimotor Complete (AIS-A) Spinal Cord Injury During a Phase 2 Clinical Trial.

Effective treatment after cervical spinal cord injury (SCI) is imperative as so many activities of daily living (ADLs) are dependent on functional recovery of arm and hand actions. We focus on defining and comparing neurological and functional endpoints that might be used during acute or subacute Phase 2 clinical trials involving subjects with cervical sensorimotor complete SCI (ASIA Impairment Scale [AIS-A]). For the purposes of this review, the trial would examine the effects of a pharmaceutical small molecule, drug, biologic, or cell transplant on spinal tissue.

Relationship between motor recovery and independence after sensorimotor-complete cervical spinal cord injury.

Background: For therapeutics directed to the injured spinal cord, a change in neurological impairment has been proposed as a relevant acute clinical study end point. However, changes in neurological function, even if statistically significant, may not be associated with a functional impact, such as a meaningful improvement in items within the self-care subscore of the Spinal Cord Independence Measure (SCIM).

Objective: The authors examined the functional significance associated with spontaneously recovering upper-extremity motor function after sensorimotor-complete cervical spinal cord injury (SCI).

Sacral sparing in SCI: beyond the S4-S5 and anorectal examination.

Background Context: Sensory and/or motor function sparing, including the S4-S5 spinal cord segment, is central to classifying neurologic impairment after spinal cord injury (SCI) using the American Spinal Injury Association Impairment Scale (AIS) grades within the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Within the ISNCSCI protocol, which is essential for both clinical and research purposes, assessing sacral sparing requires an anorectal and S4-S5 examination. However, in situations where these data are incomplete, the relationships between anorectal/S4-S5 examinations and functional preservation at more rostral sacral segments may be useful.

Spinal cord injury and aging: challenges and recommendations for future research.

Population aging, caused by reductions in fertility and increasing longevity, varies by country and is anticipated to continue and to reach global proportions during the 21st century. Although the effects of population aging have been well documented for decades, the impact of aging on people with spinal cord injury (SCI) has not received similar attention. It is reasonable to expect that population aging features such as the increasing mean age of the population, share of the population in the oldest age groups, and life expectancy would be reflected in SCI population demographics.

Mechanical ventilation, health, and quality of life following spinal cord injury.

Objective: To examine differences in perceived quality of life (QOL) at 1 year postinjury between people with tetraplegia who required mechanical ventilation assistance at discharge from rehabilitation and those who did not.

Design: Prospective cross-sectional examination of people with spinal cord injury (SCI) drawn from the SCI Model Systems National Database.

Setting: Community.

The impact of sacral sensory sparing in motor complete spinal cord injury.

Objective: To determine the effect of sensory sparing in motor complete persons with spinal cord injury (SCI) on completion of rehabilitation on neurologic, functional, and social outcomes reported at 1 year.

Design: Secondary analysis of longitudinal data collected by using prospective survey-based methods.

Setting: Data submitted to the National SCI Statistical Center Database.

Upper- and lower-extremity motor recovery after traumatic cervical spinal cord injury: an update from the national spinal cord injury database.

Objective: To present upper- (UEMS) and lower-extremity motor score (LEMS) recovery, American Spinal Injury Association Impairment Scale (AIS) change, and motor level change in persons with traumatic tetraplegia from the Spinal Cord Injury Model Systems (SCIMS).

Design: Longitudinal cohort; follow-up to 1 year.

Setting: U.

Inpatient and postdischarge rehabilitation services provided in the first year after spinal cord injury: findings from the SCIRehab Study.

Objective: To examine the amount and type of therapy services received in inpatient and postdischarge settings during the first year after spinal cord injury (SCI).

Design: Prospective observational longitudinal cohort design. Data were obtained from systematic recording of interventions by clinicians and from patient interview.

Aging with spinal cord injury.

As more individuals with spinal cord injuries survive into the later decades of life, they are faced with a variety of potential secondary conditions that limit their physical independence and affect community integration. This article describes, body system by body system, the various health issues that people with spinal cord injuries are likely to encounter as they age. Changes also occur in one's community participation and integration, which may result in changed perceived quality of life.

Posttraumatic spinal cord tethering and syringomyelia: surgical treatment and long-term outcome.

Object: Permanent neurological loss after spinal cord injury (SCI) is a well-known phenomenon. There has also been a growing recognition and improved understanding of the pathophysiological mechanisms of late progressive neurological loss, which may occur after SCI as a result of posttraumatic spinal cord tethering (SCT), myelomalacia, and syringomyelia. A clinical study of 404 patients sustaining traumatic SCIs and undergoing surgery to arrest a progressive myelopathy caused by SCT, with or without progressive myelomalacia and cystic cavitation (syringomyelia) was undertaken.

Apolipoprotein E epsilon4 allele and outcomes of traumatic spinal cord injury.

Background/objective: To test the hypothesis that apolipoprotein E (APOE) polymorphisms are associated with outcomes after spinal cord injury (SCI).

Methods: Retrospective cohort study, from rehabilitation admission to discharge.

Participants: Convenience sample of 89 persons with cervical SCI (C3-C8) treated from 1995 through 2003.