Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

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.

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.

Factors Associated with Higher Rates of Heterotopic Ossification after Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Heterotopic Ossification (HO) refers to the formation of bone within soft tissue. Traumatic spinal cord injury (SCI) has been shown to be associated with development of HO. However, risk factors for HO following SCI are unknown. In light of this knowledge gap, we performed a systematic review and meta-analysis to summarize available evidence and elucidate risk factors associated with heterotopic ossification. An electronic literature search was conducted using five databases. Studies containing SCI patients, with a proportion diagnosed with HO, were included. Meta-analyses were performed to assess the association between following risk factors and development of HO: sex, type of injury, spasticity, pressure ulcer, injury level, urinary tract infection (UTI), deep vein thrombosis (DVT), number of smokers, and pneumonia. Nine studies with 2,115 patients were included. It was found that males (Odds Ratio [95% Confidence Interval]: 2.25 [1.61, 3.13]), smokers (2.88 [1.62, 5.11]), patients with complete injury (3.61 [2.29, 5.71]), pneumonia (2.86 [2.18, 3.75]), pressure ulcers (2.45 [1.89, 3.18]), UTI (3.84 [2.63, 5.62]) and spasticity (2.12 [1.67, 2.68]) had significantly higher odds of developing HO after spinal cord injury. In contrast, location of injury (Cervical vs. thoracic injury; (1.03 [0.72, 1.49]) and DVT (1.37 [0.91, 2.07]) were not associated with development of HO. Pooled results from existing literature on HO development show that several factors are significantly associated with development of HO. Given the complexity of SCI management, the results might have a positive impact on the clinical practice by leading to an effective screening aproach.

Pharmacologic prophylaxis for heterotopic ossification following spinal cord injury: A systematic review and meta-analysi.

Heterotopic ossification(HO) is a common complication following spinal cord injury(SCI); however, its underlying pathophysiology remains relatively unknown. Although there are options for treating HO, prophylactic treatment is limited. Additionally, evidence supporting the effectiveness of these prophylactic treatments is scarce. Electronic literature search was conducted using four databases. Studies comparing prophylactic medication for HO versus placebo for patients with acute spinal cord injury were included. A meta-analysis comparing the incidence of HO between the two groups was conducted, with a subgroup analysis of non-steroidal anti-inflammatory drugs (NSAIDs) and non-NSAIDs. A total of 5 studies and 815 patients were included. Overall incidence of HO was 9.73 % (n = 25) in the medication group versus 16.5 %(n = 92) in the placebo group. However, the two groups do not statistcally differ(p = 0.21). In the subgroup analysis for NSAIDs, those who received prophylactic treatment with NSAIDs had a lower incidence of HO compared to those who received placebo (RR[95 % CI]:0.32[0.15, 0.68]; p = 0.003). As for studies that used bisphosphonates, a statistically significant difference in incidence of HO was not found (RR[95 % CI]:1.30[0.52, 3.24];p = 0.58) and the overall evidence was inconclusive. In present systematic review and meta-analysis comparing prophylactic medications to placebo for prevention of HO, we found similar incidence rates for both groups. However, subgroup analysis showed a significantly lower incidence rate for those who recevied NSAIDs for HO prophylaxis. Altough this finding is promising for secondary prevention of HO among patients suffering from SCI, further prospective studies with longer follow-ups are required to assess other appropriate medications for HO prevention.

Outcomes of Acute Inpatient Rehabilitation After Ventricular Assist Device Placement.

OBJECTIVE: The aim of the study was to compare outcomes of inpatient rehabilitation after ventricular assist device placement with outcomes for other cardiac diagnoses. DESIGN: This was a retrospective review of the electronic health records of 265 patients admitted to inpatient rehabilitation: 166 patients were admitted after ventricular assist device placement and 99 were admitted for other cardiac disease. Data collected included functional independence measure score on admission and discharge, dates of admission and discharge, and disposition. RESULTS: Patients admitted after ventricular assist device placement had a mean functional independence measure gain of 25.7 and length of stay of 8.7 days. Patients admitted for other cardiac diagnoses had a mean functional independence measure gain of 25.9 and length of stay of 9.4 days. These differences were not statistically significant. Change in functional independence measure from admission to discharge was statistically significant within each group (P < 0.001). Most patients were discharged home, and the proportions who returned to acute care or home were not different between groups. CONCLUSIONS: Both the ventricular assist device and nonventricular assist device groups had significant and equivalent improvements in functional outcomes after inpatient rehabilitation. This study found that ventricular assist device patients benefit from inpatient rehabilitation with similar disposition rates as patients with other cardiac diagnoses. Inpatient rehabilitation is the appropriate setting for this group. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Describe the role of rehabilitation in the care of individuals after ventricular assist device (VAD) placement; (2) Compare the outcomes of inpatient rehabilitation for individuals after VAD placement to those admitted for other cardiac reasons; and (3) Recognize potential complications that may occur during the course of a VAD patient's inpatient rehabilitation stay. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

CELLTOP Clinical Trial: First Report From a Phase 1 Trial of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating condition with limited pharmacological treatment options to restore function. Regenerative approaches have recently attracted interest as an adjuvant to current standard of care. Adipose tissue-derived (AD) mesenchymal stem cells (MSCs) represent a readily accessible cell source with high proliferative capacity. The CELLTOP study, an ongoing multidisciplinary phase 1 clinical trial conducted at Mayo Clinic (ClinicalTrials.gov Identifier: NCT03308565), is investigating the safety and efficacy of intrathecal autologous AD-MSCs in patients with blunt, traumatic SCI. In this initial report, we describe the outcome of the first treated patient, a 53-year-old survivor of a surfing accident who sustained a high cervical American Spinal Injury Association Impairment Scale grade A SCI with subsequent neurologic improvement that plateaued within 6 months following injury. Although he improved to an American Spinal Injury Association grade C impairement classification, the individual continued to be wheelchair bound and severely debilitated. After study enrollment, an adipose tissue biopsy was performed and MSCs were isolated, expanded, and cryopreserved. Per protocol, the patient received an intrathecal injection of 100 million autologous AD-MSCs infused after a standard lumbar puncture at the L3-4 level 11 months after the injury. The patient tolerated the procedure well and did not experience any severe adverse events. Clinical signs of efficacy were observed at 3, 6, 12, and 18 months following the injection in both motor and sensory scores based on International Standards for Neurological Classification of Spinal Cord Injury. Thus, in this treated individual with SCI, intrathecal administration of AD-MSCs was feasible and safe and suggested meaningful signs of improved, rather than stabilized, neurologic status warranting further clinical evaluation.

Fibrocartilaginous embolic myelopathy: demographics, clinical presentation, and functional outcomes.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To describe the demographics, clinical presentation, and functional outcomes of fibrocartilaginous embolic myelopathy (FCEM). SETTING: Academic inpatient rehabilitation unit in the midwestern United States. METHODS: We retrospectively searched our database to identify patients admitted between January 1, 1995 and March 31, 2016, with a high probability of FCEM. Demographic, clinical, and functional outcome measures, including Functional Independence Measure (FIM) information was obtained by chart review. RESULTS: We identified 31 patients with findings suggestive of FCEM (52% male), which was 2% of the nontraumatic spinal cord injury population admitted to inpatient rehabilitation. The age distribution was bimodal, with peaks in the second and sixth-to-seventh decades. The most common clinical presentation was acute pain and rapid progression of neurologic deficits consistent with a vascular myelopathy. Only three patients (10%) had FCEM documented as a diagnostic possibility. Most patients had paraplegia and neurologically incomplete injuries and were discharged to home. Nearly half of the patients required no assistive device for bladder management at discharge, but most were discharged with medications for bowel management. Median FIM walking locomotion score for all patients was 5, but most patients were discharged using a wheelchair for primary mobility. Median motor FIM subscale score was 36 at admission and 69 at discharge, with a median motor efficiency of 1.41. CONCLUSIONS: FCEM may be underdiagnosed and should be considered in those with the appropriate clinical presentation, because their functional outcomes may be more favorable than those with other causes of spinal cord infarction.

Important Clinical Rehabilitation Principles Unique to People with Non-traumatic Spinal Cord Dysfunction.

Background: Non-traumatic spinal cord dysfunction (SCDys) is caused by a large range of heterogeneous etiologies. Although most aspects of rehabilitation for traumatic spinal cord injury and SCDys are the same, people with SCDys have some unique rehabilitation issues. Purpose: This article presents an overview of important clinical rehabilitation principles unique to SCDys. Methods: Electronic literature search conducted (January 2017) using MEDLINE and Embase (1990-2016) databases for publications regarding SCDys. The focus of the literature search was on identifying publications that present suggestions regarding the clinical rehabilitation of SCDys. Results: The electronic search of MEDLINE and Embase identified no relevant publications, and the publications included were from the authors' libraries. A number of important clinical rehabilitation principles unique to people with SCDys were identified, including classification issues, general rehabilitation issues, etiology-specific issues, and a role for the rehabilitation physician as a diagnostic clinician. The classification issues were regarding the etiology of SCDys and the International Standards for Neurological Classification of Spinal Cord Injury. The general rehabilitation issues were predicting survival, improvement, and rehabilitation outcomes; admission to spinal rehabilitation units, including selection decision issues; participation in rehabilitation; and secondary health conditions. The etiology-specific issues were for SCDys due to spinal cord degeneration, tumors, and infections. Conclusions: Although there are special considerations regarding the rehabilitation of people with SCDys, such as the potential for progression of the underlying condition, functional improvement is typically significant with adequate planning of rehabilitation programs and special attention regarding the clinical condition of patients with SCDys.

International Retrospective Comparison of Inpatient Rehabilitation for Patients With Spinal Cord Dysfunction: Differences According to Etiology.

OBJECTIVES: To describe and compare epidemiologic characteristics and clinical outcomes of patients with nontraumatic spinal cord dysfunction according to etiology. DESIGN: Retrospective, multicenter open-cohort case series. SETTING: Spinal rehabilitation units (SRUs) in 9 countries. PARTICIPANTS: Patients (N=956; men, 60.8%; median age, 59.0y [interquartile range, 46-70.0y]; paraplegia, n=691 [72.3%]) with initial onset of spinal cord dysfunction consecutively admitted between January 1, 2008, and December 31, 2010. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Etiology of spinal cord dysfunction, demographic characteristics, length of stay (LOS) in rehabilitation, pattern of spinal cord dysfunction onset, discharge destination, level of spinal cord damage, and the American Spinal Injury Association Impairment Scale (AIS) grade on admission and discharge. RESULTS: The most common etiologies were degenerative (30.8%), malignant tumors (16.2%), infections (12.8%), ischemia (10.9%), benign tumors (8.7%), other vascular (8.5%), and other conditions (12.1%). There were major differences in epidemiologic characteristics and clinical outcomes of patients with different etiologies of spinal cord dysfunction. Paraplegia was more common in patients with a malignant tumor and vascular etiologies, while tetraplegia was more common in those with a degenerative etiology, a benign tumor, and infections. Patients with a malignant tumor tended to have the shortest LOS in the SRU, while those with a vascular etiology tended to have the longest. Except for patients with a malignant tumor, all patient groups had a significant change in their AIS grade between admission and discharge. CONCLUSIONS: This international study of spinal cord dysfunction showed substantial variation between the different etiologies regarding demographic and clinical characteristics, including changes in AIS between admission and discharge.

International retrospective comparison of inpatient rehabilitation for patients with spinal cord dysfunction epidemiology and clinical outcomes.

OBJECTIVE: To describe and compare epidemiologic characteristics of patients with spinal cord dysfunction admitted to spinal rehabilitation units (SRUs) in 9 countries (Australia, Canada, Italy, India, Ireland, The Netherlands, Switzerland, United Kingdom, and United States). DESIGN: Retrospective multicenter open-cohort case series. SETTING: SRUs. PARTICIPANTS: Patients (N=956) with initial onset of spinal cord dysfunction consecutively admitted between January 1, 2008, and December 31, 2010. Median age on admission was 59 years (interquartile range [IQR], 46-70), and 60.8% of patients were men. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic characteristics (eg, age, sex), time frame over which clinical symptoms of spinal cord dysfunction developed, etiology, length of stay in hospital, level of lesion and American Spinal Injury Association Impairment Scale (AIS) grade, discharge destination, and inpatient mortality. RESULTS: The time frame of onset of spinal cord dysfunction symptoms was as follows: ≤1 day (28.5%); ≤1 week (13.8%); >1 week but ≤1 month (10.5%), and >1 month (47.2%). Most common etiologies were degenerative conditions (30.8%), malignant tumors (16.2%), ischemia (10.9%), benign tumors (8.7%), and bacterial infections (7.1%). Most patients (72.3%) had paraplegia. The AIS grade on SRU admission was grade A in 14%, grade B in 6.5%, grade C in 24%, grade D in 52.4%, grade E in 0.2%, and missing in 2.9%. AIS grade significantly improved by discharge (z=-10.1, P<.0001). Median length of stay in the SRU was 46.5 days (IQR, 17-89.5). Most (80.5%) patients were discharged home. Differences between countries were found for most variables. CONCLUSIONS: This international study of spinal cord dysfunction showed substantial variation of etiology, demographic, and clinical characteristics across countries. Further research, including multiple centers per country, are needed to separate country effects from center effects.

Inpatient rehabilitation outcomes for patients receiving left ventricular assist device.

OBJECTIVE: The aim of this study was to evaluate outcomes of patients participating in inpatient rehabilitation program after left ventricular assist device (LVAD) implantation. DESIGN: Medical records of 94 patients who received LVADs between January 1, 2008, and June 30, 2010, at the Mayo Clinic in Rochester, MN, were retrospectively reviewed for demographic data, and inpatient rehabilitation functional outcomes were measured by the Functional Independence Measure scale. RESULTS: After successful implantation of LVAD, the patients were either discharged directly home from acute care (44%) or admitted to inpatient rehabilitation (56%). The patients admitted to inpatient rehabilitation were older than those discharged home. They were also more medically complex and more likely to have the LVAD placed as destination therapy. At discharge, significant improvement occurred in 17 of the 18 activities evaluated by the Functional Independence Measure scale. The mean total Functional Independence Measure scale score at admission was 77.1 compared with a score of 95.2 at discharge (P < 0.0001). CONCLUSIONS: Approximately half of the patients who received LVAD therapy were admitted in the inpatient rehabilitation. After the implantation of LVAD and inpatient rehabilitation, significant functional improvements were observed. Further studies addressing the role of inpatient rehabilitation for LVAD patients are warranted.

Inflammatory hypertrophic cauda equina following intrathecal neural stem cell injection.

INTRODUCTION: Potential benefit from stem cell treatments has more patients seeking treatment without understanding possible risks. METHODS: We describe a woman who presented with progressive bilateral leg pain, numbness, and gait difficulties. A prior stroke, macular degeneration, osteoarthritis, and depression, led her to receive intrathecal neural stem cell therapy overseas 1 year before onset of symptoms. RESULTS: Imaging showed marked enlargement of lumbosacral roots of the cauda equina, which was not seen before stem cell treatment. Electrodiagnostic studies confirmed chronic multiple lumbosacral radiculopathies. Biopsy of a lumbar dorsal sensory root showed myelinated fiber degeneration and loss, with endoneurial inflammation. The hypertrophic inflammatory cauda equina syndrome was potentially triggered by the prior intrathecal neural stem cell injection. CONCLUSIONS: Safety of intrathecal stem cell treatments is not routinely regulated in overseas stem cell facilities. We wish to bring this potential complication to the attention of health care providers.

A pilot study of spirituality and inpatient rehabilitation outcomes in persons with spinal cord dysfunction and severe neurological illnesses.

This prospective, observational pilot study was conducted on an academic inpatient rehabilitation unit. Ninety-three persons with spinal cord dysfunction or severe neurological illness participated. All completed admission surveys; 46 completed surveys six months after discharge. The aims were to describe admission and post-discharge spirituality and associations between spirituality and rehabilitation outcomes. At admission, participants reported spirituality similar to that of other samples of medical patients. After discharge, frequency of private spiritual practices increased and spiritual and existential well-being decreased. No significant associations were detected between spirituality and rehabilitation outcomes. Findings suggest the importance of spirituality to the participants and future research with a larger sample and modifications to the methodology.

Intrinsic spinal cord catheter placement: implications of new intractable pain in a patient with a spinal cord injury.

We present a case of new intractable flank pain after intrathecal infusion system placement in a 45-yr-old man with a history of a T12 spinal cord injury with dysesthetic leg pain. Pain after intrathecal infusion system placement was evaluated by magnetic resonance imaging and the catheter was found to be intraparenchymal. The patient was treated by cessation of infusion and surgical removal of the system. Before surgical removal, the pump was turned off and the patient's flank pain resolved. Increased vigilance is warranted when caring for paraplegic patients. When new pain persists, intrathecal medication tapering should be considered.