Cerebrospinal Fluid Drainage in Patients with Acute Spinal Cord Injury: A Multi-Center Randomized Controlled Trial.

OBJECTIVE: The secondary phase of spinal cord injury (SCI) is characterized by ischemic injury. Spinal cord perfusion pressure (SCPP), calculated as the difference between mean arterial pressure (MAP) and intrathecal pressure (ITP), has arisen as a therapeutic target for improving outcomes. Cerebrospinal fluid drainage (CSFD) may reduce ITP and thereby increase SCPP. Randomized controlled trial to evaluate the safety and feasibility of CSFD to improve SCPP and outcomes after acute SCI. METHODS: Inclusion criteria included acute cervical SCI within 24 hours of presentation. All patients received lumbar drain placement and appropriate decompressive surgery. Patients randomized to the control group received MAP elevation only. Patients in the experimental group received MAP elevation and CSFD to achieve ITP <10 mmHg for 5 days. ITP and MAP were recorded hourly. Adverse events were documented and patients underwent functional assessments at enrollment, 72 hours, 90 days, and 180 days post-injury. RESULTS: Eleven patients were enrolled; 4 were randomized to receive CSFD. CSFD patients had a mean ITP of 5.3 ± 2.5 mmHg versus. 15 ± 3.0 mmHg in the control group. SCPP improved significantly, from 77 ± 4.5 mmHg in the control group to 101 ± 6.3 mmHg in the CSFD group (P < 0.01). Total motor scores improved by 15 ± 8.4 and 57 ± 24 points in the control and CSFD groups, respectively, over 180 days. No adverse events were attributable to CSFD. CONCLUSIONS: CSFD is a safe, effective mechanism for reducing ITP and improving SCPP in the acute period post-SCI. The favorable safety profile and preliminary efficacy should help drive recruitment in future studies.

Genetic Predisposition to Symptomatic Lumbar Disk Herniation in Pediatric and Young Adult Patients.

STUDY DESIGN: Case-control whole-genome sequencing analysis of a highly select, young cohort with symptomatic lumbar disk herniation (LDH) compared with the standard variation in a large reference population. OBJECTIVE: To assess genetic influences predisposing pediatric and young adult patients to symptomatic LDH. SUMMARY OF BACKGROUND DATA: LDH has traditionally been attributed to natural weakening or mechanical insult, but recent literature supports a potential genetic influence. METHODS: Young patients with symptomatic, clinically confirmed LDH who underwent surgical treatment were included. Patients were younger than the average age of presentation, limiting the influence of environmental risks. DNA collected from these patients was compared with a reference genome (1000 Genomes Project). A genome-wide association study using whole-genome sequencing was used to characterize genetic mutations potentially associated with LDH. RESULTS: Among the 61 candidate genes flagged, 20 had missense mutations in 2 or more LDH cases. Missense mutations in collagen-encoding genes were observed in 12 of 15 patients (80%). A potential association with clinical presentation was indicated by odds ratios of key single-nucleotide polymorphism (SNP) variants in genes that encode collagen. Relative to the reference population, the LDH cohort demonstrated two statistically significant SNP variants in the gene encoding for aggrecan, a protein that facilitates load-bearing properties in the cartilaginous end plate. Aggrecan genes SNPs rs3817428 and rs11638262 were significantly associated with decreased odds of symptomatic LDH: odds ratio 0.05 (0.02-0.11) and 0.04 (0-0.26), respectively (P < 1 × 10 for both). CONCLUSION: These results suggest that collagen-encoding variants may be a genetic risk factor for LDH. They also shed new light on the role of variants that impact aggrecan, which sustains the cartilaginous end plate. Genetic predisposition to LDH may therefore be related to a multimodal combination of mutations that affect the nucleus pulposus, annulus fibrosus, and the cartilaginous end plates. LEVEL OF EVIDENCE: 4.

First Human Implantation of a Bioresorbable Polymer Scaffold for Acute Traumatic Spinal Cord Injury: A Clinical Pilot Study for Safety and Feasibility.

BACKGROUND AND IMPORTANCE: A porous bioresorbable polymer scaffold has previously been tested in preclinical animal models of spinal cord contusion injury to promote appositional healing, spare white matter, decrease posttraumatic cysts, and normalize intraparenchymal tissue pressure. This is the first report of its human implantation in a spinal cord injury patient during a pilot study testing the safety and feasibility of this technique (ClinicalTrials.gov Identifier: NCT02138110). CLINICAL PRESENTATION: A 25-year-old man had a T11-12 fracture dislocation sustained in a motocross accident that resulted in a T11 American Spinal Injury Association Impairment Scale (AIS) grade A traumatic spinal cord injury. He was treated with acute surgical decompression and spinal fixation with fusion, and enrolled in the spinal scaffold study. A 2 × 10 mm bioresorbable scaffold was placed in the spinal cord parenchyma at T12. The scaffold was implanted directly into the traumatic cavity within the spinal cord through a dorsal root entry zone myelotomy at the caudal extent of the contused area. By 3 months, his neurological examination improved to an L1 AIS grade C incomplete injury. At 6-month postoperative follow-up, there were no procedural complications or apparent safety issues related to the scaffold implantation. CONCLUSION: Although longer-term follow-up and investigation are required, this case demonstrates that a polymer scaffold can be safely implanted into an acutely contused spinal cord. This is the first human surgical implantation, and future outcomes of other patients in this clinical trial will better elucidate the safety and possible efficacy profile of the scaffold. ABBREVIATIONS: AIS, American Spinal Injury Association Impairment ScaleSCI, spinal cord injurytSCI, traumatic spinal cord injury.