Cisternal Score: A Radiographic Score to Predict Ventriculoperitoneal Shunt Requirement in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Persistent hydrocephalus requiring a ventriculoperitoneal shunt (VPS) can complicate the management of aneurysmal subarachnoid hemorrhage (aSAH). Identification of high-risk patients may guide external ventricular drain management. OBJECTIVE: To identify early radiographic predictors for persistent hydrocephalus requiring VPS placement. METHODS: In a 2-center retrospective study, we compared radiographic features on admission noncontrast head computed tomography scans of patients with aSAH requiring a VPS to those who did not, at 2 referral academic centers from 2016 through 2021. We quantified blood clot thickness in the basal cisterns including interpeduncular, ambient, crural, prepontine, interhemispheric cisterns, and bilateral Sylvian fissures. We then created the cisternal score (CISCO) using features that were significantly different between groups. RESULTS: We included 229 survivors (mean age 55.6 years [SD 13.1]; 63% female) of whom 50 (22%) required VPS. CISCO was greater in patients who required a VPS than those who did not (median 4, IQR 3-6 vs 2, IQR 1-4; P < .001). Higher CISCO was associated with higher odds of developing persistent hydrocephalus with VPS requirement (odds ratio 1.6 per point increase, 95% CI 1.34-1.9; P < .001), independent of age, Hunt and Hess grades, and modified GRAEB scores. CISCO had higher accuracy in predicting VPS requirement (area under the curve 0.75, 95% CI 0.68-0.82) compared with other predictors present on admission. CONCLUSION: Cisternal blood clot quantification on admission noncontrast head computed tomography scan is feasible and can be used in predicting persistent hydrocephalus with VPS requirement in patients with aSAH. Future prospective studies are recommended to further validate this tool.

Association of pre-admission antihypertensive agents and outcomes in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) and poor functional outcome are common complications in patients who suffer from aneurysmal subarachnoid hemorrhage (aSAH). It has been proposed that pre-admission beta-blocker therapy may lower cerebral vasospasm (cVSP) risk after aSAH; however, this association with other antihypertensives is unknown. We sought to determine the association between antihypertensives and clinical outcomes in aSAH patients. METHODS: We performed a retrospective study on a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center from 2016 to 2021. Association between pre-admission use of antihypertensives and patient outcomes was determined. Primary outcomes included DCI and poor functional outcome at 3 months after discharge defined as modified Rankin scale [mRS] 4-6. The secondary outcome was cVSP identified using transcranial Doppler (TCD). RESULTS: The cohort consisted of 306 aSAH patients with mean age 57.1 (SD 13.6) years with 187 females (61 %). Although pre-admission use of beta-blockers (OR 0.40, 95 % CI 0.21-80, p = 0.02), calcium channel blockers (OR 0.43, 95 % CI 0.19-0.93, p = 0.035), and thiazide (OR 0.31, 95 % CI 0.11-0.86, p = 0.025) were associated with lower risk of cVSP in univariate analysis, we did not find any association in a multivariate model after adjusting for age. There was no association between any class of antihypertensives and DCI or functional outcome. CONCLUSION: Pre-admission use of antihypertensive agents may affect TCD findings, however, none of them appear to be independently associated with DCI or functional outcome. Larger prospective studies are needed to establish any potential association.

Short- and long-term opioid use in survivors of subarachnoid hemorrhage.

OBJECTIVES: Opioids are frequently used for analgesia in patients with acute subarachnoid hemorrhage (SAH) due to a high prevalence of headache and neck pain. However, it is unclear if this practice may pose a risk for opioid dependence, as long-term opioid use in this population remains unknown. We sought to determine the prevalence of opioid use in SAH survivors, and to identify potential risk factors for opioid utilization. METHODS: We analyzed a cohort of consecutive patients admitted with non-traumatic and suspected aneurysmal SAH to an academic referral center. We included patients who survived hospitalization and excluded those who were not opioid-naïve. Potential risk factors for opioid prescription at discharge, 3 and 12 months post-discharge were assessed. RESULTS: Of 240 SAH patients who met our inclusion criteria (mean age 58.4 years [SD 14.8], 58% women), 233 (97%) received opioids during hospitalization and 152 (63%) received opioid prescription at discharge. Twenty-eight patients (12%) still continued to use opioids at 3 months post-discharge, and 13 patients (6%) at 12-month follow up. Although patients with poor Hunt and Hess grades (odds ratio 0.19, 95% CI 0.06-0.57) and those with intraventricular hemorrhage (odds ratio 0.38, 95% CI 0.18-0.87) were less likely to receive opioid prescriptions at discharge, we did not find significant differences between patients who had long-term opioid use and those who did not. CONCLUSION: Opioids are regularly used in both the acute SAH setting and immediately after discharge. A considerable number of patients also continue to use opioids in the long-term. Opioid-sparing pain control strategies should be explored in the future.

Association of Early White Blood Cell Trend with Outcomes in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: An increasing white blood cell (WBC) count in early course of aneurysmal subarachnoid hemorrhage (SAH) can indicate a systemic inflammatory state triggered by the initial insult. We sought to determine the significance of the early WBC trend as a potential predictor of outcomes. METHODS: We analyzed a cohort of consecutive patients with aneurysmal SAH. The WBC values in first 5 days of admission, plus relevant clinical and imaging data, and modified Rankin Scale (mRS) at 3 months after hospital discharge were retrieved and analyzed. Favorable outcome was defined as mRS 0-3. The association between WBC counts and outcomes including mRS and delayed cerebral ischemia (DCI) was determined using binary logistic regression models. We used receiver operating characteristic curve analysis to assess accuracy of WBC in predicting outcomes. RESULTS: We included 167 patients in final analysis. Mean age was 56.4 (standard deviation [SD] 14.8) years, and 65% (109) of patients were female. Peak WBC was greater in patients with poor functional outcome (mean 17 × 109 cells/L, SD 6.4 vs. 13.5 × 109 cells/L SD 4.7). Combining peak WBC with modified Fisher scale slightly increased accuracy in predicting DCI (area under the curve 0.670, 95% confidence interval 0.586-0.755) compared with each component alone. CONCLUSIONS: WBC count in the early course of SAH may have prognostic values in predicting DCI and functional outcome. WBC count monitoring may be used in conjunction with other clinical and radiographic tools to stratify patients with SAH into high- and low-risk groups to tailor neuromonitoring and treatment strategies.

Serum alpha-1 antitrypsin in acute ischemic stroke: A prospective pilot study.

BACKGROUND: Alpha-1 antitrypsin (AAT) is a potent anti-protease enzyme which may play a role in arterial wall stability. A variant of its encoding gene has been recently linked to ischemic stroke due to large artery atherosclerosis (LAA). We sought to explore potential relationships between ischemic stroke mechanisms, atherosclerosis burden and serum AAT levels. METHODS: We performed a prospective observational study of consecutive patients with acute ischemic stroke who were admitted to an academic comprehensive stroke center over a three-month period. Blood samples were collected within 24 h of hospital admission, and stroke subtype classification was determined based on modified TOAST criteria. Modified Woodcock scoring system was used to quantify calcification of major cervico-cranial arteries as a surrogate for atherosclerosis burden. Linear regression analysis was used to assess the association between serum AAT levels and calcification scores, both as continuous variables. RESULTS: Among eighteen patients met our inclusion criteria and were enrolled in our study, 10 patients (56%) were men; mean age was 66 (SD 12.5); median NIH stroke scale was 4 (IQR 9.5); 8 patients (44%) had stroke due to LAA. The median serum level of AAT was 140 mg/dl (IQR 41.7) for patients with LAA-related stroke, and 148.5 mg/dl (IQR 37.7) for patients with other stroke mechanisms (p = 0.26). Higher serum AAT levels was associated with lower modified Woodcock calcification scores. (p-value = 0.038) CONCLUSIONS: Measurement of AAT levels in patients with acute stroke is feasible, and there may be associations between AAT levels and stroke mechanism that warrant further study in larger samples.

Comparison of Intracerebral Hemorrhage Volume Calculation Methods and Their Impact on Scoring Tools.

BACKGROUND: Intracerebral hemorrhage (ICH) volumes are frequently used for prognostication and inclusion of patients in clinical trials. We sought to compare the original ABC/2 method and sABC/2, a simplified version with the planimetric method. METHODS: We retrospectively reviewed admission head CT scans of consecutive ICH patients admitted to a single academic center from July 2012 to April 2013. We assessed ICH volume on the admission. In ABC/2 method, A = greatest hemorrhage diameter by CT, B = diameter perpendicular to A, C = the approximate number of CT slices with hemorrhage multiplied by the slice thickness. C is weighted by area as < 25%, 25-50%, or > 75%. However, in the sABC/2 method, C is the total number of cuts with ICH without any weighting. Bland-Altman plots were generated for both the ABC/2 and sABC/2 methods in comparison to the planimetric method. RESULTS: One hundred thirty-five patients with spontaneous ICH were included in the final analysis. Bland-Altman analysis illustrated that both ABC/2 and sABC/2 were concordant with the planimetric method. ABC/2 had more bias than sABC/2 (47% vs. 5%, respectively) with no evidence of a linear trend. For differentiating a volume threshold of 30 mL, ABC/2 was less sensitive but more specific than sABC/2 (P < .0001). Concordance between planimetry, ABC/2, and sABC/2 was high, evidenced by most coefficients exceeding .90. CONCLUSION: Simplified ABC/2 (sABC/2) method performs better than ABC/2 in calculating ICH volumes. Moreover, it is better in differentiating a volume threshold of 30 mL. These findings may have implications for outcomes prediction and clinical trials inclusion.

Alternate class I MHC antigen processing is inhibited by Toll-like receptor signaling pathogen-associated molecular patterns: Mycobacterium tuberculosis 19-kDa lipoprotein, CpG DNA, and lipopolysaccharide.

Pathogen-associated molecular patterns (PAMPs) signal through Toll-like receptors (TLRs) to activate immune responses, but prolonged exposure to PAMPs from Mycobacterium tuberculosis (MTB) and other pathogens inhibits class II MHC (MHC-II) expression and Ag processing, which may allow MTB to evade CD4(+) T cell immunity. Alternate class I MHC (MHC-I) processing allows macrophages to present Ags from MTB and other bacteria to CD8(+) T cells, but the effect of PAMPs on this processing pathway is unknown. In our studies, MTB and TLR-signaling PAMPs, MTB 19-kDa lipoprotein, CpG DNA, and LPS, inhibited alternate MHC-I processing of latex-conjugated Ag by IFN-gamma-activated macrophages. Inhibition was dependent on TLR-2 for MTB 19-kDa lipoprotein (but not whole MTB or the other PAMPs); inhibition was dependent on myeloid differentiation factor 88 for MTB and all of the individual PAMPs. Inhibition of MHC-II and alternate MHC-I processing was delayed, appearing after 16 h of PAMP exposure, as would occur in chronically infected macrophages. Despite inhibition of alternate MHC-I Ag processing, there was no inhibition of MHC-I expression, MHC-I-restricted presentation of exogenous peptide or conventional MHC-I processing of cytosolic Ag. MTB 19-kDa lipoprotein and other PAMPs inhibited phagosome maturation and phagosome Ag degradation in a myeloid differentiation factor 88-dependent manner; this may limit availability of peptides to bind MHC-I. By inhibiting both MHC-II and alternate MHC-I Ag processing, pathogens that establish prolonged infection of macrophages (>16 h), e.g., MTB, may immunologically silence macrophages and evade surveillance by both CD4(+) and CD8(+) T cells, promoting chronic infection.