Lower Extremity Somatosensory Evoked Potentials Predict Functional Outcomes in Complete Traumatic Cervical Spinal Cord Injury.

BACKGROUND: Traumatic cervical spinal cord injury (tCSCI) is often a debilitating injury, making early prognosis important for medical and surgical planning. Currently, the best early predictors of prognosis are physical examination, imaging studies, and patient demographics. Despite these factors, patient outcomes continue to vary significantly. The purpose of this study was to evaluate the prognostic value of somatosensory evoked potentials (SSEPs) with functional outcomes in tCSCI patients. METHODS: A retrospective study was conducted on prospectively collected data from 2 academic institutions. Patients 18 years and older who had tCSCI and underwent posterior cervical decompression and stabilization with intraoperative neuromonitoring were reviewed. The outcomes of interest were the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade and ASIA motor score at follow-up. Outcomes measures were assessed via student t-tests, chi-squared tests, and multivariable regression analysis. RESULTS: A total of 79 patients were included. In complete injuries, detectable lower extremity SSEPs were associated with higher ASIA motor scores at follow-up (P = 0.002), greater increases in ASIA motor scores at follow-up (P = 0.009), and a greater likelihood of clinically important improvement in ASIA motor score (P = 0.024). Incomplete, AIS grade C injuries has higher rates of grade conversion (P = 0.019) and clinically important improvement in ASIA motor score (P = 0.010), compared to AIS grade A or B injuries. CONCLUSIONS: The detection of lower extremity SSEP signals during initial surgical treatment of tCSCI is associated with greater improvement in ASIA motor scores postoperatively. The association is most applicable to patients with complete injury.

Inhibition of autophagy in microglia and macrophages exacerbates innate immune responses and worsens brain injury outcomes.

Excessive and prolonged neuroinflammation following traumatic brain injury (TBI) contributes to long-term tissue damage and poor functional outcomes. However, the mechanisms contributing to exacerbated inflammatory responses after brain injury remain poorly understood. Our previous work showed that macroautophagy/autophagy flux is inhibited in neurons following TBI in mice and contributes to neuronal cell death. In the present study, we demonstrate that autophagy is also inhibited in activated microglia and infiltrating macrophages, and that this potentiates injury-induced neuroinflammatory responses. Macrophage/microglia-specific knockout of the essential autophagy gene Becn1 led to overall increase in neuroinflammation after TBI. In particular, we observed excessive activation of the innate immune responses, including both the type-I interferon and inflammasome pathways. Defects in microglial and macrophage autophagy following injury were associated with decreased phagocytic clearance of danger/damage-associated molecular patterns (DAMP) responsible for activation of the cellular innate immune responses. Our data also demonstrated a role for precision autophagy in targeting and degradation of innate immune pathways components, such as the NLRP3 inflammasome. Finally, inhibition of microglial/macrophage autophagy led to increased neurodegeneration and worse long-term cognitive outcomes after TBI. Conversely, increasing autophagy by treatment with rapamycin decreased inflammation and improved outcomes in wild-type mice after TBI. Overall, our work demonstrates that inhibition of autophagy in microglia and infiltrating macrophages contributes to excessive neuroinflammation following brain injury and in the long term may prevent resolution of inflammation and tissue regeneration.Abbreviations: Becn1/BECN1, beclin 1, autophagy related; CCI, controlled cortical impact; Cybb/CYBB/NOX2: cytochrome b-245, beta polypeptide; DAMP, danger/damage-associated molecular patterns; Il1b/IL1B/Il-1ß, interleukin 1 beta; LAP, LC3-associated phagocytosis; Map1lc3b/MAP1LC3/LC3, microtubule-associated protein 1 light chain 3 beta; Mefv/MEFV/TRIM20: Mediterranean fever; Nos2/NOS2/iNOS: nitric oxide synthase 2, inducible; Nlrp3/NLRP3, NLR family, pyrin domain containing 3; Sqstm1/SQSTM1/p62, sequestosome 1; TBI, traumatic brain injury; Tnf/TNF/TNF-α, tumor necrosis factor; Ulk1/ULK1, unc-51 like kinase 1.