Low-Dose Intravenous Heparin Infusion After Aneurysmal Subarachnoid Hemorrhage is Associated With Decreased Risk of Delayed Neurological Deficit and Cerebral Infarction

Neurosurgery 88 (3)2021: 523–530

Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily).

OBJECTIVE: To assess the safety and efficacy of LDIVH in aSAH patients.

METHODS: We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome datawere compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW).

RESULTS: The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9 vs 18%; P = .004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTWshowed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts.

CONCLUSION: This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Neuroablative Procedures for Patients With Cancer Pain

Neurosurgery 88:437–442, 2021

Managing cancer pain once it is refractory to conventional treatment continues to challenge caregivers committed to serving those who are suffering from a malignancy. Although neuromodulation has a role in the treatment of cancer pain for some patients, these therapies may not be suitable for all patients. Therefore, neuroablative procedures,whichwere once a mainstay in treating intractable cancer pain, are again on the rise. This guideline serves as a systematic review of the literature of the outcomes following neuroablative procedures.

OBJECTIVE: To establish clinical practice guidelines for the use of neuroablative procedures to treat patients with cancer pain.

METHODS: A systematic review of neuroablative procedures used to treat patients with cancer pain from 1980 to April 2019 was performed using the United States National Library of Medicine PubMed database, EMBASE, and Cochrane CENTRAL. After inclusion criteria were established, full text articles that met the inclusion criteria were reviewed by 2 members of the task force and the quality of the evidence was graded.

RESULTS: In total, 14 646 relevant abstracts were identified by the literature search, from which 189 met initial screening criteria. After full text review, 58 of the 189 articles were included and subdivided into 4 different clinical scenarios. These include unilateral somatic nociceptive/neuropathic body cancer pain, craniofacial cancer pain,midline subdiaphragmatic visceral cancer pain, and disseminated cancer pain. Class II and III evidence was available for these 4 clinical scenarios. Level III recommendations were developed for the use of neuroablative procedures to treat patients with cancer pain.

CONCLUSION: Neuroablative procedures may be an option for treating patients with refractory cancer pain. Serious adverse events were reported in some studies, but were relatively uncommon. Improved imaging, refinements in technique and the availability of new lesioning modalities may minimize the risks of neuroablation even further. The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelinesdetail/ guidelines-on-neuroablative-procedures-patients-wi.

 

Vitamin D—A New Perspective in Treatment of Cerebral Vasospasm

Neurosurgery 88 (3) 2021: 674–685

Cerebral vasospasm (CVS) is a frequent complication after subarachnoid hemorrhage (SAH), with no sufficient therapy and a complex pathophysiology.

OBJECTIVE: To explore the vitamin D system as a potential treatment for CVS.

METHODS: 25-vitamin D3 levels tested between 2007 and 2015 and data of SAH patients admitted during themonthswith a peak vs nadir of VitD3 valueswere analyzed, retrospectively. We prospectively correlated VitD3 and vasospasm/outcome data in SAH patients admitted in 2017. An experimental mice SAH model and cell culture model were used to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25-VitD3). Additionally, the mediators acting in the VitD mechanism were researched and detected.

RESULTS: Based on the retrospective analysis demonstrating an increased frequency of vasospasm in SAH patients during the low vitamin D period in winter, we started basic research experiments. Active 1,25-VitD3 hormone attenuated CVS, neurological deficit, and inflammation after intrathecal blood injection inmice. Deletion of the vitaminDreceptor in the endothelium or in myeloid cells decreased the protective 1,25-VitD3 effect. Co-culture experiments ofmyeloid and endothelial cells with blood confirmed the anti-inflammatory 1,25-VitD3 effect but also revealed an induction of stroma-cell-derived factor 1α (SDF1α), vascular endothelial growth factor, and endothelial nitric oxide synthase by 1,25-VitD3. In mice, SDF1α mimicked the protective effect of 1,25-VitD3 against CVS. From bench to bedside, CVS severity was inversely correlated with vitamin D plasma level, prospectively. Patients with more severe CVS exhibited attenuated expression of SDF1α and 1,25-VitD3- responsive genes on circulating myeloid cells.

CONCLUSION: 1,25-VitD3 attenuates CVS after SAH by inducing SDF1α. However, VitD administration should be tested as optional treatment to prevent CVS.

Occult infection in pseudarthrosis revision after spinal fusion

The Spine Journal 21 (2021) 370−376

Pseudarthrosis after attempted spinal fusion is yet not sufficiently understood and presents a surgical challenge. Occult infections are sometimes observed in patients with pseudarthrosis and no inflammatory signs of infection. The prevalence of such occult infection and its association with patient demographics and inflammatory markers are largely unknown.

PURPOSE: To determine the prevalence of unexpected low-grade infection in spinal pseudarthrosis revision surgery, and to evaluate whether such infection is associated with patient demographics and inflammatory markers.

STUDY DESIGN: Retrospective observational study.

PATIENT SAMPLE: One-hundred-and-twenty-eight patients who underwent thoracolumbar revision surgery due to presumed aseptic pseudarthrosis after spinal instrumentation.

OUTCOME MEASURES: Culture-positive infections or noninfectious pseudarthrosis. METHODS: Samples were routinely taken for microbiological examination from all adults (n=152) who underwent revision surgery for presumed aseptic thoracolumbar pseudarthrosis between 2014 and 2019. A full intraoperative microbiological workup (at least three intraoperative tissue samples) was done for 128 (84%) patients, and these patients were included in further analyses. Patient characteristics, medical history, inflammatory markers, and perioperative data were compared between those with and without microbiologically-confirmed infection based on samples obtained during pseudarthrosis revision.

RESULTS: The microbiological workup confirmed infection in 13 of 128 cases (10.2%). The predominant pathogen was Cutibacterium acnes (46.2%), followed by coagulase-negative staphylococci (38.5%). The presence of infection was associated with the body mass index (30.9§4.7 kg/m2 [infected] vs. 28.2§5.6 kg/m2 [controls], p=.049), surgery in the thoracolumbar region (46% vs. 18%, p=.019), and a slightly higher serum C-reactive protein level on admission (9.4§8.0 mg/L vs. 5.7§7.1 mg/L, p=.031). Occult infection was not associated with age, sex, prior lumbar surgeries, number of fused lumbar levels, American Society of Anesthesiologist score, Charlson Comorbidity Index, presence of diabetes mellitus, and smoking status.

CONCLUSIONS: Occult infections were found in 10% of patients undergoing pseudarthrosis revision after spinal fusion, even without preoperative clinical suspicion. Occult infection was associated with higher body mass index, fusions including the thoracolumbar junction, and slightly higher C-reactive protein levels. Intraoperative microbiological samples should be routinely obtained to exclude or identify occult infection in all revision surgeries for symptomatic pseudarthrosis of the spine, as this information can be used to guide postoperative antibiotic treatment.