Central cord syndrome definitions, variations and limitations.

Central cord syndrome (CCS) is the most common, yet most controversial, among the different spinal cord injury (SCI) incomplete syndromes. Since its original description in 1954, many variations have been described while maintaining the core characteristic of disproportionate weakness in the upper extremities compared to the lower extremities. Several definitions have been proposed in an attempt to quantify this difference, including a widely accepted criterion of ≥10 motor points in favor of the lower extremities. Nevertheless, recent reports have recommended revisiting the terminology and criteria of CCS as existing definitions do not capture the entire essence of the syndrome. Due to methodological differences, the full extent of CCS is not known, and a large variation in prevalence has been described. This review classifies the different definitions of CCS and describes some inherent limitations, highlighting the need for universal quantifiable criteria.

Clinical Subsets of Central Cord Syndrome: Is It a Distinct Entity from Other Forms of Incomplete Tetraplegia for Research?

Central cord syndrome (CCS) is the most prevalent and debated incomplete spinal cord injury (SCI) syndrome, with its hallmark feature being more pronounced weakness of the upper extremities than of the lower extremities. Varying definitions encapsulate multiple clinical features under the single umbrella term of CCS, complicating evaluation of its frequency, prognosis discussions, and outcomes research. Often, people with CCS are excluded from research protocols, as it is thought to have a favorable prognosis, but the vague nature of CCS raises doubts about the validity of this practice. The objective of this study was to categorize CCS into specific subsets with clear quantifiable differences, to assess whether this would enhance the ability to determine if individuals with CCS or its subsets exhibit distinct neurological and functional outcomes relative to others with incomplete tetraplegia. This study retrospectively reviewed individuals with new motor incomplete tetraplegia from traumatic SCI who enrolled in the Spinal Cord Injury Model Systems (SCIMS) database from 2010 to 2020. Through an assessment of the prevailing criteria for CCS, coupled with data analysis, we used two key criteria, including the severity of distal upper extremity weakness (i.e., hands and fingers) and extent of symmetry, to delineate three CCS subsets: full CCS, unilateral CCS, and borderline CCS. Of the 1490 participants in our sample, 17.5% had full, 25.6% had unilateral, and 9% had borderline CCS, together encompassing >50% of motor incomplete tetraplegia cases. Despite the increased sensitivity and specificity of these subsets compared with existing quantifiable criteria, substantial variability in clinical presentation was still observed. Overall, individuals meeting CCS subset criteria showed a higher likelihood of American Spinal Injury Association (ASIA) Impairment Scale (AIS) D grade than those with motor incomplete tetraplegia without CCS. Upper Extremity Motor Score (UEMS) for those with CCS was lower on admission, a difference that diminished by discharge, whereas their Lower Extremity Motor Score (LEMS) consistently remained higher than for those without CCS. However, these neurological distinctions did not result in significant functional differences, as lower and upper extremity functional outcomes at discharge were mostly similar, with some differences observed within those with AIS D grade. The AIS grade, rather than the diagnosis of CCS, remains the foremost determinant influencing neurological and functional outcomes. We recommend that future studies consider incorporating motor incomplete tetraplegia into their inclusion/exclusion criteria, instead of relying on criteria specific to CCS. Although there remains clinical value in characterizing an injury pattern as CCS and perhaps using the different subsets to better characterize the impairments, it does not appear to be a useful research criterion.

Going Virtual: A Virtual Summer Physical Medicine and Rehabilitation Externship Experience for Medical Students.

ABSTRACT: Opportunities for early medical student exposure to the field of physical medicine and rehabilitation (PM&R) are desirable for promoting the field as a career choice and are useful for introducing students to the care of people with disabilities. The COVID-19 pandemic disrupted medical education and caused the cancellation of many in-person clinical programs, including the Medical Student Summer Clinical Externship in PM&R supported by the Association of Academic Physiatrists. This article describes the process by which an in-person summer clinical externship program was effectively converted into a Virtual PM&R Experience using a combination of independent assignments and small-group sessions. A total of 87 medical students completed the Virtual PM&R Experience over two summers. The participants of the program met the program learning objectives, including enhancing their understanding of physiatry as a career and recognizing the medical and social issues that affect persons with disability.

Motor Control Changes after Utilizing Upper Extremity Myoelectric Powered Wearable Orthotics in Persons with Acute SCI.

Following spinal cord injury (SCI), upper extremity (UE) weakness may impede one's ability to carry out activities of daily living (ADLs). Such a limitation drastically lowers a person's level of independence. Additionally, therapy and the field of assistive technology continue to place a strong premium on the restoration of UE motor function in patients with SCI. The main objective of this study was to assess the benefits of an UE myoelectric-powered wearable orthosis (MPWO) produced by MyoMo, Inc. (Boston, MA) on improving UE motor function in order to enhance ADLs and quality of life in individuals with subacute SCI. A 43-year-old man with subacute incomplete SCI (iSCI), American Spinal Injury Association (ASIA) Impairment Scale (AIS) C grade received 18 sessions (over a period of six weeks) of UE mobility therapy utilizing the MPWO. The MPWO was used to enhance active range of motion (AROM) of the hand and elbow, and associated muscle activations. After training with the MPWO, hand and elbow AROM and muscle activations were enhanced. These preliminary findings imply that UE-MPWO device-assisted rehabilitation may increase participants' UE activities, leading to improved function.Clinical Relevance- These preliminary findings from a person with iSCI in the subacute phase indicate that training with UE-MPWO assistive devices may enhance UE use during ADLs for people with muscle weakness but still having some residual voluntary muscle activation ability.

The International Standards for Neurological Classification of Spinal Cord Injury: Classification Accuracy and Challenges.

Background: Successful utilization of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) requires a comprehensive understanding of its rules, terminology, and several complex concepts. There have been no studies investigating classification accuracy since the newest ISNCSCI revision (2019). Objectives: To evaluate classification accuracy of SCI professionals using the 2019 ISNCSCI edition, identify common mistakes and areas of confusion, and assess associations between experience in ISNCSCI classification and performance. Methods: Members of the International Spinal Cord Society (ISCoS) and attendees of the ISCoS Annual Scientific Meeting 2021 were invited to complete an online survey that included six ISNCSCI cases to classify. Results: A total of 107 persons completed the survey, with overall classification accuracy of 74.6%. Accuracy was highest for injury completeness (95.3%) and sensory level (91.1%) and lowest for motor zone of partial preservation (ZPP; 54.7%) and ASIA Impairment Scale (AIS) grade (57.3%). Newer concepts, including the appropriate documentation of non-SCI conditions and classification of ZPP in incomplete injuries, contributed to several common errors. There was a significant association between overall classification accuracy and self-rated experience in the ISNCSCI classification (p = .017). Experience with the ISNCSCI examination, experience in SCI medicine, and occupation were not found to be significantly associated with overall classification accuracy. Conclusion: Classification accuracy of an international cohort of SCI professionals was modest but greater than previous reports. Knowledge deficits about the 2019 ISNCSCI updates are prevalent and contribute to common classification errors. Further training in the utilization of the ISNCSCI is needed.

Inpatient rehabilitation outcomes in patients with the new diagnosis of COVID-19 tractopathy: a case series.

STUDY DESIGN: Retrospective Case Series. OBJECTIVES: Describe the inpatient rehabilitation outcomes of four patients with COVID-19 tractopathy. SETTING: Olmsted County, Minnesota, United States of America. METHODS: Retrospective review of medical records was performed to collect patient data. RESULTS: Four individuals (n = 4, 3 men and 1 woman, mean age 58.25 years [range 56-61]) completed inpatient rehabilitation during the COVID-19 pandemic. All presented after COVID-19 infection and were admitted to acute care with progressive paraparesis. None were able to ambulate on admission to acute care. All received extensive evaluations which were largely negative except for mildly elevated CSF protein and MRI findings of longitudinally extensive T2 hyperintensity signal changes in the lateral (n = 3) and dorsal (n = 1) columns. All patients experienced incomplete spastic paraparesis. All patients experienced neurogenic bowel dysfunction; a majority experienced neuropathic pain (n = 3); half experienced impaired proprioception (n = 2); and a minority experienced neurogenic bladder dysfunction (n = 1). Between rehabilitation admission and discharge, the median improvement in lower extremity motor score was 5 (0-28). All patients were discharged home, but only one was a functional ambulator at time of discharge. CONCLUSION: While the underlying mechanism is yet to be elucidated, in rare cases a COVID-19 infection can lead to a tractopathy, presenting as weakness, sensory deficits, spasticity, neuropathic pain, and neurogenic bladder/bowel. Patients with COVID-19 tractopathy would benefit from inpatient rehabilitation to enhance their functional mobility and independence.

Incomplete Spinal Cord Syndromes: Current Incidence and Quantifiable Criteria for Classification.

The demographics of acute traumatic spinal cord injury (SCI) have changed over the last few decades, with a significant increase in age at the time of injury, a higher percentage of injuries caused by falls, and incomplete tetraplegia becoming the most common type of neurological impairment. Incomplete SCI syndromes, most specifically central cord syndrome (CCS), anterior cord syndrome (ACS) and Brown-Sequard syndrome (BSS), constitute a substantial proportion of incomplete tetraplegia and SCI overall. Nevertheless, the updated incidence of these syndromes is not well known, and their estimates vary considerably, largely because of methodological inconsistencies across previous studies. A retrospective analysis of individuals with new traumatic SCI enrolled in the Spinal Cord Injury Model Systems database between January 2011 and May 2020 was performed. Using newly proposed computable definitions for ACS and BSS, as well as an existing quantitative definition of CCS, we determined the current incidence and neurological characteristics of each syndrome. Within the population of individuals with a traumatic SCI, including all levels and severity of injuries (N = 3639), CCS, ACS, and BSS accounted for 14%, 6.5%, and 2%, respectively. Of the 1649 individuals with incomplete tetraplegia in our cohort, CCS was the most common syndrome (30%), followed by ACS (10%) and BSS (3%). Using quantifiable definitions, these three syndromes now account for ∼22% and ∼44% of cases of traumatic SCI and incomplete tetraplegia, respectively, with CCS having increased over the last decade. This updated information and proposed calculable criteria for these syndromes allow for a greater understanding of the incidence and characteristics of these syndromes and enable greater study in the future.

Transcutaneous spinal stimulation in patients with intrathecal baclofen pump delivery system: A preliminary safety study.

Objective: To determine the effect of transcutaneous spinal stimulation (TSS) on an implanted intrathecal baclofen (ITB) pump in persons with traumatic spinal cord injury (SCI). Design: Prospective clinical trial. Participants: Five individuals with chronic traumatic SCI, >18 years of age, and an anteriorly implanted Medtronic SynchroMed™ II ITB pump delivery system. Intervention: Transcutaneous spinal stimulation trials with cathode at T11/12, with pump interrogation before, during and after stimulation. Results: There was no evidence of any effect of the TSS in regards to disruption of the ITB pump delivery mechanism. Communication interference with the interrogator to the pump occurred often during stimulation for log transmission most likely secondary to the electromagnetic interference from the stimulation. One individual had elevated blood pressure at the end of the trial, suspected to be unrelated to the spinal stimulation. Conclusion: Based upon this pilot study, further TSS studies including persons with an implanted Medtronic SynchroMed™ II ITB pump can be considered when stimulating at the low thoracic spine, although communication with the programmer during the stimulation may be affected.

Characterizing Natural Recovery after Traumatic Spinal Cord Injury.

The predominant tool used to predict outcomes after traumatic spinal cord injury (SCI) is the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), in association with the American Spinal Injury Association (ASIA) Impairment Scale (AIS). These measures have evolved based on analyses of large amounts of longitudinal neurological recovery data published in numerous separate studies. This article reviews and synthesizes published data on neurological recovery from multiple sources, only utilizing data in which the sacral sparing definition was applied for determination of completeness. Conversion from a complete to incomplete injury is more common in tetraplegia than paraplegia. The majority of AIS conversion and motor recovery occurs within the first 6-9 months, with the most rapid rate of motor recovery occurring in the first three months after injury. Motor score changes, as well as recovery of motor levels, are described with the initial strength of muscles as well as the levels of the motor zone of partial preservation influencing the prognosis. Total motor recovery is greater for patients with initial AIS B than AIS A, and greater after initial AIS C than with motor complete injuries. Older age has a negative impact on neurological and functional recovery after SCI; however, the specific age (whether >50 or >65 years) and underlying reasons for this impact are unclear. Penetrating injury is more likely to lead to a classification of a neurological complete injury compared with blunt trauma and reduces the likelihood of AIS conversion at one year. There are insufficient data to support gender having a major effect on neurological recovery after SCI.

Updates of the International Standards for Neurologic Classification of Spinal Cord Injury: 2015 and 2019.

The International Standards for Neurologic Classification of Spinal Cord Injury (ISNCSCI) are the most widely used classification system in spinal cord injury medicine. The purpose of the ISNCSCI is to ensure accurate and consistent communication among patients, clinicians, and researchers. Since its first publication in 1982, the ISNCSCI has continued to evolve with the latest updates and revisions published in 2015 and 2019. The updates were incorporated into the 2019 ISNCSCI worksheet and booklet, and the International Standards Training e-Learning Program. This article details the ISNCSCI update from 2015 and revision in 2019.

Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lung adenocarcinoma tumors in Kras(G12D-LSL) mice.

The role of PI3K and MAPK pathways in tumor initiation and progression is well established; hence, several inhibitors of these pathways are currently in different stages of clinical trials. Recent studies identified a PI3K/mTOR (PF-04691502) and a MEK inhibitor (PD-0325901) with strong potency and efficacy in different cell lines and tumor models. PD-0325901, however, showed adverse effects when administered at or above MTD (maximum tolerated dose) in the clinic. Here, we show in preclinical models that PD-0325901 at doses well below MTD (sub-MTD 1.5 mg/kg SID) is still a potent compound as single agent or in combination with PF-04691502. We first observed that PD-0325901 at 1.5 mg/kg SID and in combination with PF-04691502 (7.5 mg/kg; SID) significantly inhibited growth of H460 (carry Kras and PIK3CA mutations) orthotopic lung tumors. Additionally, we tested efficacy of PD-0325901 in Kras(G12D-LSL) conditional GEMMs (genetically engineered mouse models) which are a valuable tool in translational research to study tumor progression. Intranasal delivery of adenoviruses expressing Cre recombinase (Adeno-Cre) resulted in expression of mutant Kras leading to development of tumor lesions in lungs including adenomatous hyperplasia, large adenoma, and adenocarcinoma. Similar to H460 tumors, PD-0325901 as single agent or in combination with PF-04691502 significantly inhibited growth of tumor lesions in lungs in Kras(G12D-LSL) mice when treatment started at adenocarcinoma stage (at 14 weeks post-Adeno-Cre inhalation). In addition, immunohistochemistry showed inhibition of pS6 (phosphorylated ribosomal S6) in the treated animals particularly in the combination group providing a proof of mechanism for tumor growth inhibition. Finally, m-CT imaging in live Kras(G12D-LSL) mice showed reduction of tumor burdens in PD-0325901-treated animals at sub-MTD dose. In conclusion, our data suggest that PD-0325901 at doses below MTD is still a potent compound capable of tumor growth inhibition where Kras and/or PI3K are drivers of tumor growth and progression.