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Hitoshi Fukuda, Akira Handa, Masaomi Koyanagi, Benjamin Lo and Sen Yamagata

OBJECTIVE

Although endovascular therapy is favored for acutely ruptured intracranial aneurysms, hematological factors associated with acute subarachnoid hemorrhage (SAH) may predispose to procedure-related ischemic complications. The aim of this study was to evaluate whether an elevated level of plasma D-dimer, a parameter of hypercoagulation in patients with acute SAH, is correlated with increased incidence of thromboembolic events during endovascular coiling of ruptured aneurysms.

METHODS

The authors analyzed data from 103 cases of acutely ruptured aneurysms (in 103 patients) treated with endovascular coil embolization at a single institution. Factors associated with elevated D-dimer level on admission were identified. The authors also evaluated whether D-dimer elevation was independently correlated with increased incidence of perioperative thromboembolic events.

RESULTS

An elevated D-dimer concentration (≥ 1.0 μg/ml) on admission was observed in 70 (68.0%) of 103 patients. Increasing age (p < 0.001, Student t-test) and poor initial neurological grade representing World Federation of Neurosurgical Societies (WFNS) grade IV or V (p = 0.0018, chi-square test) were significantly associated with D-dimer elevation. Symptomatic thromboembolic events occurred in 11 cases (10.7%). Elevated D-dimer levels on admission (OR 1.34, 95% CI 1.10–1.62, p = 0.0029) independently carried a higher risk of thromboembolic events after adjustment for potential angiographic confounders, including wide neck of the aneurysm and large aneurysm size.

CONCLUSIONS

Elevated D-dimer levels on admission of patients with acute SAH were significantly associated with increased incidence of thromboembolic events during endovascular coiling of ruptured aneurysms.

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Hitoshi Fukuda, Kosuke Hayashi, Takafumi Moriya, Satoru Nakashita, Benjamin W. Y. Lo and Sen Yamagata

OBJECT

Intrasylvian hematoma (ISH) is a subtype of intracranial hematoma caused by aneurysmal rupture and often presents with a poor initial neurological grade; it is not well studied. The aim of this study was to elucidate outcomes of aneurysmal subarachnoid hemorrhage (SAH) with ISH.

METHODS

Data for 97 patients with poor-grade SAH (World Federation of Neurosurgical Societies Grade IV or V) were retrospectively analyzed from a single-center, prospective, observational cohort database. Ultra-early surgical clipping, removal of hematoma, external decompression for brain swelling, and prevention of vasospasm by cisternal irrigation with milrinone were combined as an aggressive treatment. Characteristics and clinical courses of SAH with ISH were identified. The authors also evaluated any correlations between poor admission-grade SAH and ISH with good functional outcome.

RESULTS

Patients with poor admission-grade SAH and with ISH were more likely to have initial cerebral edema (p < 0.001, Mann-Whitney U-test), which significantly resolved overtime (p < 0.001, Mann-Whitney U-test). These patients had a better chance of functional survival (modified Rankin Scale scores of 1–3; OR 5.75; 95% CI 1.36–24.3; p = 0.017) at 6 months after hospital discharge, after adjustment for potential confounders such as younger age and better initial neurological grade by multivariable analysis.

CONCLUSIONS

ISH predicted good functional recovery from poor-grade aneurysmal SAH.

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Hitoshi Fukuda, Benjamin Lo, Yu Yamamoto, Akira Handa, Yoshiharu Yamamoto, Yoshitaka Kurosaki and Sen Yamagata

OBJECTIVE

Plasma D-dimer levels elevate during acute stages of aneurysmal subarachnoid hemorrhage (SAH) and are associated with poor functional outcomes. However, the mechanism in which D-dimer elevation on admission affects functional outcomes remains unknown. The aim of this study is to clarify whether D-dimer levels on admission are correlated with systemic complications after aneurysmal SAH, and to investigate their additive predictive value on conventional risk factors for poor functional outcomes.

METHODS

A total of 187 patients with aneurysmal SAH were retrospectively analyzed from a single-center, observational cohort database. Correlations of plasma D-dimer levels on admission with patient characteristics, initial presentation, neurological complications, and systemic complications were identified. The authors also evaluated the additive value of D-dimer elevation on admission for poor functional outcomes by comparing predictive models with and without D-dimer.

RESULTS

D-dimer elevation on admission was associated with increasing age, female sex, and severity of SAH. Patients with higher D-dimer levels had increased likelihood of nosocomial infections (OR 1.22 [95% CI 1.07–1.39], p = 0.004), serum sodium disorders (OR 1.11 [95% CI 1.01–1.23], p = 0.033), and cardiopulmonary complications (OR 1.20 [95% CI 1.04–1.37], p = 0.01) on multivariable analysis. D-dimer elevation was an independent risk factor of poor functional outcome (modified Rankin Scale Score 3–6, OR 1.50 [95% CI 1.15–1.95], p = 0.003). A novel prediction model with D-dimer had significantly better discrimination ability for poor outcomes than conventional models without D-dimer.

CONCLUSIONS

Elevated D-dimer levels on admission were independently correlated with systemic complication, and had an additive value for outcome prediction on conventional risk factors after aneurysmal SAH.

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Pasquale Scotti, Chantal Séguin, Benjamin W. Y. Lo, Elaine de Guise, Jean-Marc Troquet and Judith Marcoux

OBJECTIVE

Among the elderly, use of antithrombotics (ATs), antiplatelets (APs; aspirin, clopidogrel), and/or anticoagulants (ACs; warfarin, direct oral ACs [DOACs; dabigatran, rivaroxaban, apixaban]) to prevent thromboembolic events must be carefully weighed against the risk of intracranial hemorrhage (ICH) with trauma. The goal of this study was to assess the risk of sustaining a traumatic brain injury (TBI), ICH, and poorer outcomes in relation to AT use among all patients 65 years or older presenting to a single institution with head trauma.

METHODS

Data were collected from all head trauma patients 65 years or older presenting to the authors’ supraregional tertiary trauma center over a 24-month period and included age, sex, injury mechanism, medical history, international normalized ratio, Glasgow Coma Scale (GCS) score, ICH presence and type, hospital admission, reversal therapy, surgery, discharge destination, Extended Glasgow Outcome Scale (GOSE) score at discharge, and mortality.

RESULTS

A total of 1365 head trauma patients 65 years or older were included; 724 were on AT therapy (413 on APs, 151 on ACs, 59 on DOACs, 48 on 2 APs, 38 on AP+AC, and 15 on AP+DOAC) and 641 were not. Among all head trauma patients, the risk of sustaining a TBI was associated with AP use after adjusting for covariates. Of the 731 TBI patients, those using ATs had higher rates of ICH (p <0.0001), functional dependency at discharge (GOSE score ≤ 4; p < 0.0001), and mortality (p < 0.0001). Elevated rates of ICH progression on follow-up CT scanning were observed in patients in the warfarin monotherapy (OR 5.30, p < 0.0001) and warfarin + AP (OR 6.15, p = 0.0011). Risk of mortality was not associated with single antiplatelet use but was notably high with 2 APs (OR 4.66, p = 0.0056), warfarin (OR 5.18, p = 0.0003), and DOAC use (OR 5.09, p = 0.0149).

CONCLUSIONS

Elderly trauma patients on ATs, especially combination therapy, are at elevated risk of ICH and poor outcomes compared with those not on AT therapy. While both AP and warfarin use alone and in combination were associated with significantly elevated odds of sustaining an ICH among TBI patients, only warfarin use was a predictor of hemorrhage progression on follow-up scans. The use of a single AP was not associated with mortality; however, the combination of both aspirin and clopidogrel was. Warfarin and DOAC users had comparable mortality rates; however, DOAC users had lower rates of ICH progression, and fewer survivors were functionally dependent at discharge than were warfarin users. DOACs are an overall safer alternative to warfarin for patients at high risk of falls.

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C. Rory Goodwin, Eric W. Sankey, Ann Liu, Benjamin D. Elder, Thomas Kosztowski, Sheng-Fu L. Lo, Charles G. Fisher, Michelle J. Clarke, Ziya L. Gokaslan and Daniel M. Sciubba

OBJECT

Surgical procedures and/or adjuvant therapies are effective modalities for the treatment of symptomatic spinal metastases. However, clinical results specific to the skin cancer spinal metastasis cohort are generally lacking. The purpose of this study was to systematically review the literature for treatments, clinical outcomes, and survival following the diagnosis of a skin cancer spinal metastasis and evaluate prognostic factors in the context of spinal skin cancer metastases stratified by tumor subtype.

METHODS

The authors performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles since 1950 that reported survival, clinical outcomes, and/or prognostic factors for the skin cancer patient population with spinal metastases. The methodological quality of reviews was assessed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) tool.

RESULTS

Sixty-five studies met the preset criteria and were included in the analysis. Of these studies, a total of 25, 40, 25, and 12 studies included patients who underwent some form of surgery, radiotherapy, chemotherapy, or observation alone, respectively. Sixty-three of the 65 included studies were retrospective in nature (Class of Evidence [CoE] IV), and the 2 prospective studies were CoE II. Based on the studies analyzed, the median overall survival for a patient with a spinal metastasis from a primary skin malignancy is 4.0 months; survival by tumor subtype is 12.5 months for patients with basal cell carcinoma (BCC), 4.0 months for those with melanoma, 4.0 months for those with squamous cell carcinoma, 3.0 months for those with pilomatrix carcinoma, and 1.5 months for those with Merkel cell carcinoma (p < 0.0001). The overall percentage of known continued disease progression after spine metastasis diagnosis was 40.1% (n = 244/608, range 25.0%–88.9%), the rate of known recurrence of the primary skin cancer lesion was 3.5% (n = 21/608, range 0.2%–100.0%), and the rate of known spine metastasis recurrence despite treatment for all skin malignancies was 2.8% (n = 17/608, range 0.0%–33.3%). Age greater than 65 years, sacral spinal involvement, presence of a neurological deficit, and nonambulatory status were associated with decreased survival in patients diagnosed with a primary skin cancer spinal metastasis. All other clinical or prognostic parameters were of low or insufficient strength.

CONCLUSIONS

Patients diagnosed with a primary skin cancer metastasis to the spine have poor overall survival with the exception of those with BCC. The median duration of survival for patients who received surgical intervention alone, medical management (chemotherapy and/or radiation) alone, or the combination of therapies was similar across interventions. Age, spinal region, and neurological status may be associated with poor survival following surgery.

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Masaomi Koyanagi, Hitoshi Fukuda, Benjamin Lo, Minami Uezato, Yoshitaka Kurosaki, Nobutake Sadamasa, Akira Handa, Masaki Chin and Sen Yamagata

OBJECTIVE

Delayed cerebral ischemia (DCI) is an important complication after aneurysmal subarachnoid hemorrhage (aSAH). Although intrathecal milrinone injection via lumbar catheter to prevent DCI has been previously reported to be safe and feasible, its effectiveness remains unknown. The goal of this study was to evaluate whether intrathecal milrinone injection treatment after aSAH significantly reduced the incidence of DCI.

METHODS

The prospectively maintained aSAH database was used to identify patients treated between January 2010 and December 2015. The cohort included 274 patients, with group assignment based on treatment with intrathecal milrinone injection or not. A propensity score model was generated for each patient group, incorporating relevant patient variables.

RESULTS

After propensity score matching, 99 patients treated with intrathecal milrinone injection and 99 without treatment were matched on the basis of similarities in their demographic and clinical characteristics. There were significantly fewer DCI events (4% vs 14%, p = 0.024) in patients treated with intrathecal milrinone injection compared with those treated without it. However, there were no significant differences between the 2 groups with respect to their 90-day functional outcomes (46% vs 36%, p = 0.31). The likelihood of chronic secondary hydrocephalus, meningitis, and congestive heart failure as complications of intrathecal milrinone injection therapy was also similar between the groups.

CONCLUSIONS

In propensity score–matched groups, the intrathecal administration of milrinone via lumbar catheter showed significant reduction of DCI following aSAH, without an associated increase in complications.

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Blessing N. R. Jaja, Gustavo Saposnik, Rosane Nisenbaum, Benjamin W. Y. Lo, Tom A. Schweizer, Kevin E. Thorpe and R. Loch Macdonald

Object

The goal of this study was to determine racial/ethnic differences in inpatient mortality rates and the use of institutional postacute care following subarachnoid hemorrhage (SAH) in the US.

Methods

A cross-sectional study of hospital discharges for SAH was conducted using the Nationwide Inpatient Sample for the years 2005–2010. Discharges with a principal diagnosis of SAH were identified and abstracted using the appropriate ICD-9-CM diagnostic code. Racial/ethnic groups were defined as white, black, Hispanic, Asian/Pacific Islander (API), and American Indian. Multinomial logistic regression analyses were performed comparing racial/ethnic groups with respect to the primary outcome of risk of in-hospital mortality and the secondary outcome of likelihood of discharge to institutional care.

Results

During the study period, 31,631 discharges were related to SAH. Race/ethnicity was a significant predictor of death (p = 0.003) and discharge to institutional care (p ≤ 0.001). In the adjusted analysis, compared with white patients, API patients were at higher risk of death (OR 1.34, 95% CI 1.13–1.59) and Hispanic patients were at lower risk of death (OR 0.84, 95% CI 0.72–0.97). The likelihood of discharge to institutional care was statistically similar between white, Hispanic, API, and Native American patients. Black patients were more likely to be discharged to institutional care compared with white patients (OR 1.27, 95% CI 1.14–1.40), but were similar to white patients in the risk of death.

Conclusions

Significant racial/ethnic differences are present in the risk of inpatient mortality and discharge to institutional care among patients with SAH in the US. Outcome is likely to be poor among API patients and best among Hispanic patients compared with other groups.

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Masaomi Koyanagi, Hitoshi Fukuda, Masaaki Saiki, Yoshihito Tsuji, Benjamin Lo, Toshinari Kawasaki, Yoshihiko Ioroi, Ryu Fukumitsu, Ryota Ishibashi, Masashi Oda, Osamu Narumi, Masaki Chin, Sen Yamagata and Susumu Miyamoto

OBJECTIVE

Shunt-dependent hydrocephalus (SDHC) may arise after aneurysmal subarachnoid hemorrhage (aSAH) as CSF resorptive mechanisms are disrupted. Using propensity score analysis, the authors aimed to investigate which treatment modality, surgical clipping or endovascular treatment, is superior in reducing rates of SDHC after aSAH.

METHODS

The authors’ multicenter SAH database, comprising 3 stroke centers affiliated with Kyoto University, Japan, was used to identify patients treated between January 2009 and July 2016. Univariate and multivariate analyses were performed to characterize risk factors for SDHC after aSAH. A propensity score model was generated for both treatment groups, incorporating relevant patient covariates to detect any superiority for prevention of SDHC after aSAH.

RESULTS

A total of 566 patients were enrolled in this study. SDHC developed in 127 patients (22%). On multivariate analysis, age older than 53 years, the presence of intraventricular hematoma, and surgical clipping as opposed to endovascular coiling were independently associated with SDHC after aSAH. After propensity score matching, 136 patients treated with surgical clipping and 136 with endovascular treatment were matched. Propensity score–matched cohorts exhibited a significantly lower incidence of SDHC after endovascular treatment than after surgical clipping (16% vs 30%, p = 0.009; OR 2.2, 95% CI 1.2–4.2). SDHC was independently associated with poor neurological outcomes (modified Rankin Scale score 3–6) at discharge (OR 4.3, 95% CI 2.6–7.3; p < 0.001).

CONCLUSIONS

SDHC after aSAH occurred significantly more frequently in patients who underwent surgical clipping. Strategies for treatment of ruptured aneurysms should be used to mitigate SDHC and minimize poor outcomes.

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Benjamin W. Y. Lo, Abhaya V. Kulkarni, James T. Rutka, Andrew Jea, James M. Drake, Maria Lamberti-Pasculli, Peter B. Dirks and Lehana Thabane

Object

Cephaloceles represent primary axial mesodermal defects, occurring in 0.8–4 per 10,000 live births. Prior studies have reported posterior location, hydrocephalus, microcephaly, seizure, and presence of brain tissue as poor prognostic markers for neurological outcome. However, these studies were small and the results were analyzed using univariate tests. The purpose of this study was to investigate the potential risk factors for the occurrence of developmental delay in patients with cephaloceles, using both univariate and multivariable regression techniques.

Methods

This is a retrospective cohort study of cephalocele cases treated at the Hospital for Sick Children between 1990 and 2006. Two independent investigators collected the data from the Hospital for Sick Children Encephalocele Database and hospital charts. Developmental assessments were made by general pediatricians and neuropsychologists. Both univariate analysis (α = 0.10) and multivariable logistic regression analysis (α = 0.05) were performed.

Results

Eighty-five cases of cephaloceles were identified. The patient group consisted of 48 boys and 37 girls. Sixty-eight lesions were encephaloceles and 17 were meningoceles. The distribution was as follows: frontal (40 lesions), occipital (33), and parietal (12). Associated conditions included hydrocephalus (23), seizure disorder (17), microcephaly (6), corpus callosal abnormalities (15), heterotopias (9), cerebral dysgenesis (11), and myelomeningocele (1). Evaluation of long-term development revealed that 41 patients (48%) had normal development, 9 (11%) had mild delay, 14 (16%) had moderate delay, and 21 (25%) had severe delay. Hydrocephalus, seizure disorder, microcephaly, presence of associated intracranial abnormalities, and presence of brain tissue were significantly associated with poor outcome on univariate analysis. Multivariable analysis revealed hydrocephalus and presence of intracranial abnormalities to be statistically significant predictors of developmental delay.

Conclusions

To the authors' knowledge, this is one of the largest North American cephalocele series documented. Unlike prior studies, location of the cephaloceles is not a significant predictor of outcome. The multivariable regression analysis demonstrates hydrocephalus and the presence of associated intracranial abnormalities as variables with cumulative predictive effects for developmental delay.

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Hitoshi Fukuda, Hitoshi Ninomiya, Yusuke Ueba, Tsuyoshi Ohta, Toshiaki Kaneko, Tomohito Kadota, Fumihiro Hamada, Naoki Fukui, Motonobu Nonaka, Yuya Watari, Shota Nishimoto, Maki Fukuda, Satoru Hayashi, Tomohiko Izumidani, Hiroyuki Nishimura, Akihito Moriki, Benjamin Lo and Tetsuya Ueba

OBJECTIVE

Several environmental factors have been reported to correlate with incidence of spontaneous subarachnoid hemorrhage (SAH). However, because of different patient selection and study designs among these studies, meteorological factors that trigger the incidence of SAH in a short hazard period remain unknown. Among meteorological factors, daily temperature changes may disrupt and violate homeostasis and predispose to cerebrovascular circulatory disturbances and strokes. The authors aimed to investigate whether a decline in the temperature from the highest of the previous day to the lowest of the event day (temperature decline from the previous day [TDP]) triggers SAH in the prefecture-wide stroke database.

METHODS

All 28 participating institutions with primary or comprehensive stroke centers located throughout Kochi Prefecture, Japan, were included in the study. Data collected between January 2012 and December 2016 were analyzed, and 715 consecutive SAH patients with a defined date of onset were enrolled. Meteorological data in this period were obtained from the Kochi Local Meteorological Observatory. A case-crossover study was performed to investigate association of TDP and other environmental factors with onset of SAH.

RESULTS

The increasing TDP in 1°C on the day of the SAH event was associated with an increased incidence of SAH (OR 1.041, 95% CI 1.007–1.077) after adjustment for other environmental factors. According to the stratified analysis, a significant association between TDP and SAH was observed in women, patients < 65 years old, and patients with weekday onset. Among these factors, increasing TDP had a great impact on SAH onset in patients < 65 years old (p = 0.028, Mann-Whitney U-test).

CONCLUSIONS

TDP, temperature decline from the highest of the previous day to the lowest of the day, was correlated with the incidence of spontaneous SAH, particularly in younger patients < 65 years old.