Dexamethasone has been commonly given to patients with a presumed new GBM in relatively large doses (6-16 mg daily for 1-2 weeks) since the 1960s without any rigorous evidence. This treatment with ...dexamethasone before the diagnosis and adjuvant therapy makes GBM patients unique compared to other newly diagnosed cancer patients. While dexamethasone may be beneficial, recent studies suggest that this potent immunosuppressant with pleiotropic effects is harmful in the long term. This perspective article summarizes the disadvantages of perioperative dexamethasone from multiple facets. It concludes that these growing data mandate rigorously testing the benefits of using perioperative dexamethasone.
BACKGROUND AND PURPOSE—Whether prior intravenous thrombolysis provides any additional benefits to the patients undergoing mechanical thrombectomy for large vessel, acute ischemic stroke remains ...unclear.
METHODS—We conducted a meta-analysis of 13 studies obtained through PubMed and EMBASE database searches to determine whether functional outcome (modified Rankin Scale) at 90 days, successful recanalization rate, and symptomatic intracerebral hemorrhage rate differed between patients who underwent mechanical thrombectomy with (MT+IVT) and without (MT−IVT) pre-treatment with intravenous thrombolysis.
RESULTS—MT+IVT patients compared with MT−IVT patients had better functional outcomes (modified Rankin Scale score, 0–2; summary odds ratio OR, 1.27 95% confidence interval (CI), 1.05–1.55; P=0.02; n=1769/1174), lower mortality (OR, 0.71 95% CI, 0.55–0.91; P=0.006; n=1774/1202), and higher rate of successful recanalization (OR, 1.46 95% CI, 1.09–1.96; P=0.01; n=1652/1216) without having increased odds of symptomatic intracerebral hemorrhage (OR, 1.11 95% CI, 0.69–1.77; P=0.67; n=1471/1143). A greater number of MT+IVT patients required ≤2 passes with a neurothrombectomy device to achieve successful recanalization (OR, 2.06 95% CI, 1.37–3.10; P=0.0005; n=316/231).
CONCLUSIONS—Our results demonstrated that MT+IVT patients had better functional outcomes, lower mortality, higher rate of successful recanalization, requiring lower number of device passes, and equal odds of symptomatic intracerebral hemorrhage compared with MT−IVT patients. The results support the current guidelines of offering intravenous thrombolysis to eligible patients even if they are being considered for mechanical thrombectomy. Because the data are compiled from studies where the 2 groups differed based on eligibility for intravenous thrombolysis, randomized trials are necessary to accurately evaluate the added value of intravenous thrombolysis in patients treated with mechanical thrombectomy.
Rigorous evidence generation with randomized controlled trials has lagged for aneurysmal subarachnoid hemorrhage (SAH) compared with other forms of acute stroke. Besides its lower incidence compared ...with other stroke subtypes, the presentation and outcome of patients with SAH also differ. This must be considered and adjusted for in designing pivotal randomized controlled trials of patients with SAH. Here, we show the effect of the unique expected distribution of the SAH severity at presentation (World Federation of Neurological Surgeons grade) on the outcome most used in pivotal stroke randomized controlled trials (modified Rankin Scale) and, consequently, on the sample size. Furthermore, we discuss the advantages and disadvantages of different options to analyze the outcome and control the expected distribution of the World Federation of Neurological Surgeons grades in addition to showing their effects on the sample size. Finally, we offer methods that investigators can adapt to more precisely understand the effect of common modified Rankin Scale analysis methods and trial eligibility pertaining to the World Federation of Neurological Surgeons grade in designing their large-scale SAH randomized controlled trials.
Abstract
BACKGROUND
Ventricular entry during glioblastoma resection and tumor contact with the subventricular zone (SVZ) have both been shown to associate with development of hydrocephalus, ...leptomeningeal dissemination, distant parenchymal recurrence, and decreased survival. However, prior studies did not analyze these variables together in a single-patient population; therefore, it is unknown which is an independent predictor of these outcomes.
OBJECTIVE
To conduct a comparative outcome analysis of surgical ventricular entry and SVZ contact by glioblastoma in a retrospective cohort of 232 patients.
METHODS
Outcomes studied included hydrocephalus, leptomeningeal dissemination, distant tumor recurrences, and progression-free (PFS) and overall (OS) survival. The Cox proportional regression analyses were adjusted for age at diagnosis, preoperative Karnofsky performance status score, extent of resection, temozolomide and radiation treatments, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation).
RESULTS
Surgical ventricular entry, SVZ-contacting glioblastoma, hydrocephalus, leptomeningeal dissemination, and distant recurrences were observed in 85 (36.6%), 114 (49.1%), 19 (8.2%), 78 (33.6%), and 59 (25.4%) patients, respectively. Multivariate, adjusted analysis revealed SVZ tumor contact—but not ventricular entry—associated with hydrocephalus (hazard ratio, HR, 4.20 1.13-15.7, P = .03), leptomeningeal dissemination (HR 1.93 1.14-3.28, P = .01), PFS (HR 2.10 1.53-2.88, P < .001), and OS (HR 1.90 1.35-2.67, P < .001). Distant recurrences were not associated with either. No interaction between the 2 variables was statistically noted.
CONCLUSION
SVZ contact by glioblastoma was independently associated with the development of hydrocephalus, leptomeningeal dissemination, and decreased survival. SVZ tumor contact was associated with ventricular entry during surgical resections, which did not independently correlate with these outcomes.
Current guidelines suggest treating blood pressure above 180/105 mm Hg during the first 24 hours in patients with acute ischemic stroke undergoing any form of recanalization therapy. Currently, no ...studies exist to guide blood pressure management in patients with stroke treated specifically with mechanical thrombectomy. We aimed to determine the association between blood pressure parameters within the first 24 hours after mechanical thrombectomy and patient outcomes.
We retrospectively studied a consecutive sample of adult patients who underwent mechanical thrombectomy for acute ischemic stroke of the anterior cerebral circulation at 3 institutions from March 2015 to October 2016. We collected the values of maximum, minimum, and average values of systolic blood pressure, diastolic blood pressure, and mean arterial pressures in the first 24 hours after mechanical thrombectomy. Primary and secondary outcomes were patients' functional status at 90 days measured on the modified Rankin scale and the incidence and severity of intracranial hemorrhages within 48 hours. Associations were explored using an ordered multivariable logistic regression analyses. A total of 228 patients were included (mean age 65.8±14.3; 104 males, 45.6%). Maximum systolic blood pressure independently correlated with a worse 90-day modified Rankin scale and hemorrhagic complications within 48 hours (adjusted odds ratio=1.02 1.01-1.03,
=0.004; 1.02 1.01-1.04,
=0.002; respectively) in multivariable analyses, after adjusting for several possible confounders.
Higher peak values of systolic blood pressure independently correlated with worse 90-day modified Rankin scale and a higher rate of hemorrhagic complications. Further prospective studies are warranted to identify whether systolic blood pressure is a therapeutic target to improve outcomes.
Abstract Heterozygous loss-of-function SCN1A mutations cause Dravet syndrome, an epileptic encephalopathy of infancy that exhibits variable clinical severity. We utilized a heterozygous Scn1a ...knockout ( Scn1a+/− ) mouse model of Dravet syndrome to investigate the basis for phenotype variability. These animals exhibit strain-dependent seizure severity and survival. Scn1a+/− mice on strain 129S6/SvEvTac (129. Scn1a+/− ) have no overt phenotype and normal survival compared with Scn1a+/− mice bred to C57BL/6J (F1. Scn1a+/− ) that have severe epilepsy and premature lethality. We tested the hypothesis that strain differences in sodium current (INa ) density in hippocampal neurons contribute to these divergent phenotypes. Whole-cell voltage-clamp recording was performed on acutely-dissociated hippocampal neurons from postnatal days 21–24 (P21–24) 129. Scn1a+/− or F1. Scn1a+/− mice and wild-type littermates. INa density was lower in GABAergic interneurons from F1. Scn1a+/− mice compared to wild-type littermates, while on the 129 strain there was no difference in GABAergic interneuron INa density between 129. Scn1a+/− mice and wild-type littermate controls. By contrast, INa density was elevated in pyramidal neurons from both 129. Scn1a+/− and F1. Scn1a+/− mice, and was correlated with more frequent spontaneous action potential firing in these neurons, as well as more sustained firing in F1. Scn1a+/− neurons. We also observed age-dependent differences in pyramidal neuron INa density between wild-type and Scn1a+/− animals. We conclude that preserved INa density in GABAergic interneurons contributes to the milder phenotype of 129. Scn1a+/− mice. Furthermore, elevated INa density in excitatory pyramidal neurons at P21–24 correlates with age-dependent onset of lethality in F1. Scn1a+/− mice. Our findings illustrate differences in hippocampal neurons that may underlie strain- and age-dependent phenotype severity in a Dravet syndrome mouse model, and emphasize a contribution of pyramidal neuron excitability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The clinical and molecular correlates of glioblastomas (GBMs) contacting the subventricular zone (SVZ+ GBM) are unknown. This work aimed to reveal any such correlates that may help explain their ...increased GBM malignancy.
A meta-analysis was, therefore, conducted to assess whether tumor's MGMT promoter methylation status, isocitrate dehydrogenase (IDH) mutation status, volume, and extent of resection as well as patients' age at diagnosis and preoperative Karnofsky performance status score (KPS) correlate with SVZ contact by GBM. In addition, available imaging of GBM patients in The Cancer Imaging Archive was assessed for SVZ contact and their corresponding clinical and molecular variables were obtained through The Cancer Genome Atlas (TCGA) database.
Twenty-one studies were identified through PubMed and EMBASE database search. This review included 257 patients identified from the TCIA/TCGA database. MGMT promoter methylation status (summary odds ratio OD, 1.18 0.84-1.66, P=0.34), IDH mutation status (OD: 0.63 0.20-1.99, P=0.43), and patients' age of diagnosis (summary mean difference, MD, 0.10 years -1.85, 2.05, P=0.92) did not associated with SVZ contact of the GBM. However, SVZ+ GBMs were significantly larger than SVZ- GBMs (MD: 17.3 cm3 8.70-25.8, P<0.0001). SVZ+ GBM patients had lower KPS scores (MD: -3.33 -5.31-(-1.35), P=0.001) and were half as likely to receive a gross total resection (OD: 0.50 0.40-0.64, P<0.00001).
Additional, large studies that rigorously control for all the known clinical and molecular prognosticators, especially extent of resection and preoperative KPS scores, are needed to evaluate whether SVZ contact by GBM independently influences survival.
Background and aims
The aim of this study was to analyze the trends, demographic differences in the type and time to initiation (TTI) of adjunct treatment AT following surgery for anaplastic ...astrocytoma (AA).
Material and methods
The National Cancer Database (NCDB) was queried for patients diagnosed with AA from 2004 to 2016. Cox proportional hazards and modeling was used to determine factors influencing survival, including the impact of time to initiation (TTI) of adjuvant therapy.
Results
Overall, 5890 patients were identified from the database. The use of combined RT + CT temporally increased from 66.3% (2004–2007) to 79% (2014–2016),
p
< 0001. Patients more likely to receive no treatment following surgical resection included elderly (> 60 years old), hispanic patients, those with either no or government insurance, those living > 20 miles from the cancer facility, those treated at low volume centers (< 2 cases/year). AT was received following surgical resection within 0–4 weeks, 4.1–8 weeks, and > 8 weeks in 41%, 48%, and 3%, respectively. Compared to patients who received RT + CT, patients were likely to receive RT only as AT either at 4–8 weeks or > 8 weeks after the surgical procedure. Patients who received AT within 0–4 weeks had the 3-year OS of 46% compared to 56.7% for patients who received treatment at 4.1–8 weeks.
Conclusion
We found significant variation in the type and timing of adjunct treatment following surgical resection of AA in the United States. A considerable number of patients (15%) received no AT following surgery.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The National Institutes of Health Stroke Scale (NIHSS) measured at an early time point is an appealing surrogate marker for long-term functional outcome of stroke patients treated with endovascular ...therapy. However, definitions and analytical methods for an early NIHSS-based outcome measure that optimize power and precision in clinical studies are not well-established.
In this post-hoc analysis of our prospective observational study that enrolled endovascular therapy-treated patients at 12 comprehensive stroke centers across the US, we compared the ability of 24-hour NIHSS, ΔNIHSS (baseline minus 24-hour NIHSS), and percentage change (NIHSS×100/baseline NIHSS), analyzed as continuous and dichotomous measures, to predict 90-day modified Rankin Scale (mRS) using logistic regression (adjusted for age, baseline NIHSS, glucose, hypertension, Alberta Stroke Program Early CT Score, time to recanalization, recanalization status, and intravenous thrombolysis) and Spearman ρ.
Of 485 patients in the BEST (Blood Pressure After Endovascular Stroke Therapy) cohort, 446 (92%) with 90-day follow-up data were included. An absolute 24-hour NIHSS, adjusted for baseline in multivariable modeling, had the highest predictive power of all definitions evaluated (aR
0.368 and adjusted odds ratio 0.79 0.75-0.84,
<0.001 for mRS score 0-2; aR
0.444 and adjusted odds ratio 0.84 0.8-0.86 for ordinal mRS). For predicting mRS score of 0-2 with a cut point, the second most efficient approach, the optimal threshold for 24-hour NIHSS score was ≤7 (sensitivity 80.1%, specificity 80.4%; adjusted odds ratio 12.5 7.14-20,
<0.001), followed by percent change in NIHSS (sensitivity 79%, specificity 58.5%; adjusted odds ratio 4.55 2.85-7.69,
<0.001).
Twenty-four-hour NIHSS, adjusted for baseline, was the strongest predictor of both dichotomous and ordinal 90-day mRS outcomes for endovascular therapy-treated patients. A dichotomous 24-hour NIHSS score of ≤7 was the second-best predictor. Although ΔNIHSS, continuous and dichotomized at ≥4, predicted 90-day outcomes, absolute 24-hour NIHSS definitions performed better.
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