scholarly journals A Panel of CSF and Serum Biomarkers Reflecting Injury Severity and Outcome in a Human Spinal Cord Injury Study

2021 ◽  
Author(s):  
Zhihui Yang ◽  
Yueqiang Fu ◽  
Sehajpreet Kaur ◽  
Iktej Singh Jabbal ◽  
Ahmed Moghieb ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Acute Phase ◽  
Injury Severity ◽  
Spinal Injury ◽  
Serum Biomarkers ◽  
Breakdown Product ◽  
Serum Samples ◽  
Human Spinal Cord ◽  
Cord Injury

Abstract Acute spinal cord injury (SCI) results in catastrophic neurological impairment. We aimed to examine the temporal profile and severity correlation of biomarkers, and their relationship with the American Spinal Injury Association Scale (AIS) improvement in human SCI. 15 SCI and 10 non-SCI healthy subjects were classified according to the initial and discharge AIS grade. Serial cerebrospinal fluid (CSF) and serum samples were collected. Spectrin breakdown products (SBDP) 150, SBDP145, glial fibrillary acidic protein (GFAP), and GFAP breakdown product (GBDP) 38/44K were found to be elevated in the acute phase CSF samples in SCI patients on immunoblotting. SBDP150, ubiquitin C-terminal hydrolase-L1 (UCH-L1), GFAP, S100B, neurofilament light chain protein (NF-L), Tau & interleukin (IL) -6 were elevated in the acute phase CSF and serum samples on ELISA. CSF SBDP150, UCH-L1, GFAP, S100B and Tau were seen to peak on day 1 after injury, while CSF IL-6 and NF-L peaked on day 5. Serum SBDP150, IL-6, S100B, GFAP, UCHL-1 and Tau peaked on day 1, while serum NF-L peaked on day 5 post-injury. CSF alpha II-spectrin, SBDP150/145, and GBDP 44-38K levels (by immunoblots), CSF SBDP150, S100B, GFAP, UCHL-1 and Tau (ELISA) and serum UCHL-1 and Tau (ELISA) at specific time points showed SCI severity-correlation. CSF SBDP150, GFAP, and Tau and serum UCHL-1 and Tau (ELISA) were seen to have the best correlation with the severity at discharge. Receiver Operating Characteristic Curve analysis showed that CSF and serum biomarkers (SBDP150, IL-6, S100B, GFAP, NF-L, UCHL-1 and Tau) were associated with the severity of SCI.

196. Inflammatory Cytokine Expression and the Development of Injury Severity Biomarkers After Human Spinal Cord Injury

2008 ◽  
Vol 8 (5) ◽  
pp. 98S-99S ◽  
Author(s):  
Anthea Stammers ◽  
Lise Belanger ◽  
Donna Chan ◽  
Arlene Bernardo ◽  
Hamed Umedaly ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Cytokine ◽  
Injury Severity ◽  
Cytokine Expression ◽  
Human Spinal Cord ◽  
Cord Injury

scholarly journals Locomotor Training After Human Spinal Cord Injury: A Series of Case Studies

2000 ◽  
Vol 80 (7) ◽  
pp. 688-700 ◽  
Author(s):  
Andrea L Behrman ◽  
Susan J Harkema
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Sensory Information ◽  
Locomotor Training ◽  
Overground Walking ◽  
Thoracic Spinal Cord ◽  
Human Spinal Cord ◽  
Thoracic Spinal ◽  
Cord Injury

AbstractMany individuals with spinal cord injury (SCI) do not regain their ability to walk, even though it is a primary goal of rehabilitation. Mammals with thoracic spinal cord transection can relearn to step with their hind limbs on a treadmill when trained with sensory input associated with stepping. If humans have similar neural mechanisms for locomotion, then providing comparable training may promote locomotor recovery after SCI. We used locomotor training designed to provide sensory information associated with locomotion to improve stepping and walking in adults after SCI. Four adults with SCIs, with a mean postinjury time of 6 months, received locomotor training. Based on the American Spinal Injury Association (ASIA) Impairment Scale and neurological classification standards, subject 1 had a T5 injury classified as ASIA A, subject 2 had a T5 injury classified as ASIA C, subject 3 had a C6 injury classified as ASIA D, and subject 4 had a T9 injury classified as ASIA D. All subjects improved their stepping on a treadmill. One subject achieved overground walking, and 2 subjects improved their overground walking. Locomotor training using the response of the human spinal cord to sensory information related to locomotion may improve the potential recovery of walking after SCI.

scholarly journals Proteomic portraits reveal evolutionarily conserved and divergent responses to spinal cord injury

2021 ◽  
Author(s):  
Michael A. Skinnider ◽  
Jason Rogalski ◽  
Seth Tigchelaar ◽  
Neda Manouchehri ◽  
Anna Prudova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Large Scale ◽  
Injury Severity ◽  
Large Animal ◽  
Serum Samples ◽  
Neurological Improvement ◽  
Cord Injury ◽  
Evolutionarily Conserved ◽  
Proteomic Analyses

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of CSF and serum samples from 111 acute SCI patients and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at six months with an AUC of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response, and establish the CSF abundance of glial fibrillary acidic protein (GFAP) as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

scholarly journals Blood Serum Cytokines in Patients with Subacute Spinal Cord Injury: A Pilot Study to Search for Biomarkers of Injury Severity

2021 ◽  
Vol 11 (3) ◽  
pp. 322
Author(s):  
Sergei Ogurcov ◽  
Iliya Shulman ◽  
Ekaterina Garanina ◽  
Davran Sabirov ◽  
Irina Baichurina ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Pilot Study ◽  
Injury Severity ◽  
Spinal Injury ◽  
Neuron Specific Enolase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cord Injury ◽  
The Difference ◽  
Endothelial Growth Factor

Background. Despite considerable interest in the search for a spinal cord injury (SCI) therapy, there is a critical need to develop a panel of diagnostic biomarkers to determine injury severity. In this regard, there is a requirement for continuing research into the fundamental processes of neuroinflammatory and autoimmune reactions in SCI, identifying changes in the expression of cytokines. Methods. In this pilot study, an extended multiplex analysis of the cytokine profiles in the serum of patients at 2 weeks post-SCI (n = 28) was carried out, together with an additional assessment of neuron-specific enolase (NSE) and vascular endothelial growth factor (VEGF) levels by enzyme-linked immunosorbent assay. A total of 16 uninjured subjects were enrolled as controls. Results. The data obtained showed a large elevation of IFNγ (>52 fold), CCL27 (>13 fold), and CCL26 (>8 fold) 2 weeks after SCI. The levels of cytokines CXCL5, CCL11, CXCL11, IL10, TNFα, and MIF were different between patients with baseline American Spinal Injury Association Impairment Scale (AIS) grades of A or B, whilst IL2 (>2 fold) and MIP-3a (>6 fold) were significantly expressed in the cervical and thoracic regions. There was a trend towards increasing levels of NSE. However, the difference in NSE was lost when the patient set was segregated based on AIS group. Conclusions. Our pilot research demonstrates that serum concentrations of cytokines can be used as an affordable and rapid detection tool to accurately stratify SCI severity in patients.

scholarly journals Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury

2015 ◽  
Vol 113 (7) ◽  
pp. 2447-2460 ◽  
Author(s):  
Maria Knikou ◽  
Andrew C. Smith ◽  
Chaithanya K. Mummidisetty
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Reciprocal Inhibition ◽  
H Reflex ◽  
Medial Gastrocnemius ◽  
Locomotor Training ◽  
Step Cycle ◽  
Human Spinal Cord ◽  
Cord Injury

Pathologic reorganization of spinal networks and activity-dependent plasticity are common neuronal adaptations after spinal cord injury (SCI) in humans. In this work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after locomotor training in 16 people with chronic SCI. The soleus H-reflex depression following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve stimulation at short conditioning-test (C-T) intervals was assessed before and after training in the seated position and during stepping. The conditioned H reflexes were normalized to the unconditioned H reflex recorded during seated. During stepping, both H reflexes were normalized to the maximal M wave evoked at each bin of the step cycle. In the seated position, locomotor training replaced reciprocal facilitation with reciprocal inhibition in all subjects, and Ib facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During stepping, reciprocal inhibition was decreased at early stance and increased at midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was decreased at midstance and midswing phases in AIS D after training. Ib inhibition was decreased at early swing and increased at late swing in AIS C and was decreased at early stance phase in AIS D after training. The results of this study support that locomotor training alters postsynaptic actions of Ia and Ib inhibitory interneurons on soleus motoneurons at rest and during stepping and that such changes occur in cases with limited or absent supraspinal inputs.

Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome

2014 ◽  
Vol 86 (3) ◽  
pp. 273-279 ◽  
Author(s):  
J. Kuhle ◽  
J. Gaiottino ◽  
D. Leppert ◽  
A. Petzold ◽  
J. P. Bestwick ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Light Chain ◽  
Injury Severity ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Human Spinal Cord ◽  
Cord Injury

scholarly journals Increases in human motoneuron excitability after cervical spinal cord injury depend on the level of injury

2017 ◽  
Vol 117 (2) ◽  
pp. 684-691 ◽  
Author(s):  
Christine K. Thomas ◽  
Charlotte K. Häger ◽  
Cliff S. Klein
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Conduction Velocity ◽  
Spinal Injury ◽  
Cervical Spinal Cord ◽  
Motor Units ◽  
M Wave ◽  
Human Spinal Cord ◽  
Motoneuron Excitability ◽  
Cord Injury

After human spinal cord injury (SCI), motoneuron recruitment and firing rate during voluntary and involuntary contractions may be altered by changes in motoneuron excitability. Our aim was to compare F waves in single thenar motor units paralyzed by cervical SCI to those in uninjured controls because at the single-unit level F waves primarily reflect the intrinsic properties of the motoneuron and its initial segment. With intraneural motor axon stimulation, F waves were evident in all 4 participants with C4-level SCI, absent in 8 with C5 or C6 injury, and present in 6 of 12 Uninjured participants ( P < 0.001). The percentage of units that generated F waves differed across groups (C4: 30%, C5 or C6: 0%, Uninjured: 16%; P < 0.001). Mean (±SD) proximal axon conduction velocity was slower after C4 SCI [64 ± 4 m/s ( n = 6 units), Uninjured: 73 ± 8 m/s ( n = 7 units); P = 0.037]. Mean distal axon conduction velocity differed by group [C4: 40 ± 8 m/s ( n = 20 units), C5 or C6: 49 ± 9 m/s ( n = 28), Uninjured: 60 ± 7 m/s ( n = 45); P < 0.001]. Motor unit properties (EMG amplitude, twitch force) only differed after SCI ( P ≤ 0.004), not by injury level. Motor units with F waves had distal conduction velocities, M-wave amplitudes, and twitch forces that spanned the respective group range, indicating that units with heterogeneous properties produced F waves. Recording unitary F waves has shown that thenar motoneurons closer to the SCI (C5 or C6) have reduced excitability whereas those further away (C4) have increased excitability, which may exacerbate muscle spasms. This difference in motoneuron excitability may be related to the extent of membrane depolarization following SCI. NEW & NOTEWORTHY Unitary F waves were common in paralyzed thenar muscles of people who had a chronic spinal cord injury (SCI) at the C4 level compared with uninjured people, but F waves did not occur in people that had SCI at the C5 or C6 level. These results highlight that intrinsic motoneuron excitability depends, in part, on how close the motoneurons are to the site of the spinal injury, which could alter the generation and strength of voluntary and involuntary muscle contractions.

Walking During Daily Life Can Be Validly and Responsively Assessed in Subjects With a Spinal Cord Injury

2008 ◽  
Vol 23 (2) ◽  
pp. 117-124 ◽  
Author(s):  
Hubertus J. A. van Hedel ◽  
Volker Dietz ◽  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Daily Life ◽  
Human Spinal Cord ◽  
Cord Injury ◽  
Walking Capacity ◽  
European Multicenter Study ◽  
Walking Tests ◽  
Over Time

Objective. This study assessed the validity and responsiveness of the Spinal Cord Independence Measure (SCIM II) items indoor mobility, mobility for moderate distances, and outdoor mobility. Methods. The data of 886 spinal cord injury subjects were derived from the European Multicenter Study for Human Spinal Cord Injury (EM-SCI) and analyzed at 2 weeks and 1, 3, 6, and 12 months after injury. The SCIM II items were compared using the preferred walking speed and the Walking Index for Spinal Cord Injury (WISCI II). The responsiveness to assess differences over time was determined. The analyses were performed for subjects with varying impairment scales according to the American Spinal Injury Association (ASIA). Results. An initially moderate correlation between walking capacity and the SCIM II mobility items improved to excellent at 6 and 12 months after injury. The correlations were higher for indoor mobility compared with outdoor mobility. These correlations increased in ASIA C, but decreased over time in ASIA D subjects. The SCIM II mobility items showed initially positive responsiveness in ASIA A and B subjects. In ASIA C and D subjects, SCIM II responsiveness was significant within the first 6 months. Conclusions . The SCIM II items assess mobility (wheelchair and walking) during daily life. They show good validity and responsiveness, including postdischarge. They can be considered appropriate for evaluating the efficacy of new interventions on ambulatory function. Depending on the severity of the initial lesion and time of assessment, clinically applied walking tests can accurately predict walking performance during daily life.

scholarly journals Prolonged Bradycardia, Asystole and Outcome of High Spinal Cord Injury Patients

2014 ◽  
Vol 3 (3) ◽  
pp. 87-92
Author(s):  
Nissar Shaikh ◽  
Ali Raza ◽  
Atur Rahman ◽  
Adel Shabana ◽  
Faisal Malstrome ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intensive Care Unit ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Intensive Care ◽  
Injury Severity ◽  
Spinal Injury ◽  
Demographic Data ◽  
Endotracheal Suctioning ◽  
Cord Injury

ABSTRACT High spinal cord injury (HSCI) is one of the devastating traumatic injuries. Majority of these patients are young male and 93% will have major neurological disabilities. The aim of this study was to know the prevalence, risk and precipitating factors for prolonged bradycardia in the HSCI patients. Patients and methods All patients who were admitted to the intensive care unit (ICU) of tertiary hospital, with spinal cord injury above level of dorsal (D4) were enrolled in this study prospectively. Patient's demographic data, mechanism, level and type of spinal injury, associated injuries, injury severity score (ISS), spinal shock, vasopressors used, time of occurrence of bradycardia; precipitating, risk factors and outcome were recorded. Results During the study period, total 138 patients were admitted to the intensive care unit with HSCI. Majority of patients were male. The most frequently associated injury was skeletal fractures (38.4%). Pneumonia in 56 (41%) was the most common complication. Forty-five (33%) patients had prolonged bradycardia; 53.4% had cardiac asystole, 29 (21%) patients had bradycardia during endotracheal suctioning, where, as 27 (20%) patients developed bradycardia at positioning. HSCI patients with prolonged bradycardia had significantly higher, ISS score, ICU and hospitals stay. Multivariate analysis revealed that hypotension on admission; pneumonia and tracheostomy were risk factors for the development of prolonged bradycardia. Conclusion Prolonged bradycardia was associated with significantly higher incidence of asystole. Endotracheal suctioning and positioning of HSCI patients were provocative factors for prolonged bradycardia. Hypotension on admission, pneumonia and tracheostomy were the risk factors for development of prolonged bradycardia. How to cite this article Shaikh N, Raza A, Rahman A, Shabana A, Malstrome F, Al-Sulaiti G. Prolonged Bradycardia, Asystole and Outcome of High Spinal Cord Injury Patients. Panam J Trauma Crit Care Emerg Surg 2014;3(3):87-92.

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