Santosh B. Murthy

A decrease in body mass index is associated with faster progression of motor symptoms and shorter survival in ALS

Abstract Our objective was to test the hypothesis that changes in body mass index (BMI) are associated with changes in the clinical course of ALS. We examined the relationships between BMI at first clinical visit and changes in BMI up to a two-year follow-up, and multiple clinical variables related to ALS: age of onset, rate of progression of motor symptoms, and survival. Baseline BMI was classified according to the World Health Organization (WHO) criteria. Changes in BMI were classified as a loss of >1 unit, no change, or a gain of >1 unit. Our results showed that baseline BMI was not associated with age of onset, rate of progression or survival. In contrast, a loss of BMI >1 over two years was associated with significantly shorter survival and a faster rate of progression. In a multiple regression model, these results were independent of gender, site of onset, history of diabetes mellitus and apolipoprotein (ApoE) genotype. In summary, a change in BMI after ALS diagnosis was significantly associated with rate of progression and survival. This raises the possibility that early changes in BMI may identify patients likely to have a more malignant course of the disease. However, further research is needed to clarify the relationship between BMI and ALS.

ALS disease onset may occur later in patients with pre-morbid diabetes mellitus.

Background  Several metabolic derangements associated with diabetes mellitus type 2 (DM) have been associated with a better outcome in amyotrophic lateral sclerosis (ALS), including hyperlipidemia and obesity. Here, we tested the hypothesis that DM would have a positive effect on the motor and cognitive findings of ALS.

Perihematomal Edema and Functional Outcomes in Intracerebral Hemorrhage Influence of Hematoma Volume and Location

Background and Purpose— Perihematomal edema (PHE) is associated with poor outcomes after intracerebral hemorrhage (ICH). PHE evolves in the early period after ICH, providing a therapeutic target and window for intervention. We studied the effect of PHE volume expansion in the first 72 hours (iPHE) and its relationship with functional outcomes. Methods— We used data contained in the Virtual International Stroke Trials Archive. We included patients who presented within 6 hours of symptom onset, had baseline clinical, radiological, and laboratory data, and further computed tomographic scan data at 72 hours and 90-day functional outcomes. We calculated iPHE and used logistic regression analysis to assess relationships with outcome. We adjusted for confounding variables and the primary outcome measure poor day-90 outcome (defined as modified Rankin Scale score of ≥3. We performed subgroup analyses by location and by volume of ICH. Results— We included 596 patients with ICH. Median baseline hematoma volume was 15.0 mL (IQR, 7.9–29.2) and median baseline PHE volume was 8.7 mL (IQR, 4.5–15.5). Hematoma expansion occurred in 122 (34.9%) patients. Median iPHE was 14.7 mL (IQR, 6.6–30.3). The odds of a poor outcome were greater with increasing iPHE (OR, 1.78; CI, 1.12–2.64 per mL increase). Subgroup analyses showed that iPHE was only related to poor functional outcomes in basal ganglia and small (<30 mL) ICH. Conclusions— Absolute increase in PHE during 72 hours was associated with worse functional outcomes after ICH, particularly with basal ganglia ICH and hematomas <30 mL.

The SILK flow diverter in the treatment of intracranial aneurysms

The SILK flow diverter (SFD; Balt Extrusion, Montmorency, France) is a flow diverting stent used in the endovascular treatment of intracranial aneurysms. It works on the principle of redirecting flow away from the aneurysm sac, leading to occlusion over time. We present a systematic review on the clinical outcomes and complications of the SFD. A literature search for English language articles were conducted on PubMed, Medline and EMBASE for articles on the treatment of intracranial aneurysms with the SILK flow diverter. The inclusion criteria were n>10, use of SFD only, data on complications and aneurysm occlusion rate (AOR). Eight studies with 285 patients and 317 intracranial aneurysms were included. The mean age was 52.7 years and nearly 80% were women. In terms of angiographic distribution, 86.8% of aneurysms were located in the anterior circulation and 13.2% in the posterior circulation. As for the aneurysm size, 37.9% were classed as small, 44.4% as large and 17.7% as giant. Ischemic complications and parent artery occlusion each occurred in 10% of patients. Aneurysm rupture rate was 3.5%, while the cumulative mortality was 4.9%. The main outcome measure, 12 month AOR, was 81.8% with complete occlusion in 216 out of 264 aneurysms. Use of flow diverters for the treatment of intracranial aneurysm with complex morphologies has gained in popularity over the last few years. Our review suggests that SFD achieves comparable AOR to its contemporary, the Pipeline Embolization Device (ev3 Endovascular, Plymouth, MN, USA) but has a higher rate of higher rate of ischemic complications, aneurysm rupture and mortality.

Restarting Anticoagulant Therapy After Intracranial Hemorrhage: A Systematic Review and Meta-Analysis

Background and Purpose— The safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to summarize the associations of anticoagulation resumption with the subsequent risk of ICH recurrence and thromboembolism. Methods— We searched published medical literature to identify cohort studies involving adults with anticoagulation-associated ICH. Our predictor variable was resumption of anticoagulation. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between anticoagulation resumption and our outcomes. Results— Eight studies were eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of anticoagulation was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, 0.25–0.45; Q=5.12, P for heterogeneity=0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% confidence interval, 0.58–1.77; Q=24.68, P for heterogeneity <0.001). No significant publication bias was detected in our analyses. Conclusions— In observational studies, reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk–benefit profile of anticoagulation resumption after ICH.

Neurogenic Stunned Myocardium Following Acute Subarachnoid Hemorrhage Pathophysiology and Practical Considerations

Neurogenic stunned myocardium (NSM) is a triad of transient left ventricular dysfunction, electrocardiogram changes, and elevation in cardiac enzymes, often mimicking a myocardial infarction. It has been described following acute brain injury. The purported mechanism is catecholamine excess resulting in cardiac dysfunction. From the clinical standpoint, the most frequently encountered electrocardiographic changes are QTc prolongation and ST-T changes, with modest elevations in troponin levels. Basal and mid-ventricular segments of the left ventricle are most commonly involved. NSM poses therapeutic challenges when it occurs secondary to aneurysmal subarachnoid hemorrhage, particularly in the setting of coexisting vasospasm. Overall, NSM carries good prognosis if recognized early, with appropriate management of hemodynamic and cardiopulmonary parameters.

Intraventricular Thrombolysis in Intracerebral Hemorrhage Requiring Ventriculostomy A Decade-Long Real-World Experience

Background and Purpose— Intraventricular thrombolysis (IVT) is a promising treatment in facilitating intraventricular clot resolution after intraventricular hemorrhage. We examined in-hospital outcomes and resource utilization after thrombolysis in patients with intraventricular hemorrhage requiring ventriculostomy in a real-world setting. Methods— We identified adult patients with primary diagnosis of nontraumatic intracerebral hemorrhage requiring ventriculostomy from the Nationwide Inpatient Sample from 2002 to 2011. We compared demographic and hospital characteristics, comorbidities, inpatient outcomes, and resource utilization measures between patients treated with IVT and those managed with ventriculostomy, but without IVT. Population estimates were extrapolated using standard Nationwide Inpatient Sample weighting algorithms. Results— We included 34 044 patients in the analysis, of whom 1133 (3.3%) received IVT. The thrombolysis group had significantly lower inpatient mortality (32.4% versus 41.6%; P=0.001) and it remained lower after controlling for baseline demographics, hospital characteristics, comorbidity, case severity, and withdrawal of care status (adjusted odds ratio, 0.670; 95% confidence interval, 0.520–0.865; P=0.002). There was a trend toward favorable discharge (home or rehabilitation) among the thrombolysis cohort (adjusted odds ratio, 1.335; 95% confidence interval, 0.983–1.812; P=0.064). The adjusted rates of bacterial meningitis and ventricular shunt placement were similar between groups. The thrombolysis group had longer length of stay and higher inflation-adjusted cost of care, but cost of care per day length of stay was similar to the non-IVT group. Conclusions— IVT for intracerebral hemorrhage requiring ventriculostomy resulted in lower inpatient mortality and a trend toward favorable discharge outcome with similar rates of inpatient complications compared with the non-IVT group.

Palliative Care Utilization in Nontraumatic Intracerebral Hemorrhage in the United States.

Objectives:Palliative care is now recognized as an essential component of comprehensive care in serious illness that interferes with quality of life. We explored utilization of palliative care in spontaneous intracerebral hemorrhage at a population level using a large national database. Design:Population based cross-sectional study. Setting:Inpatient hospital admissions from the Nationwide Inpatient Sample. Patients:A total of 311,217 patients with intracerebral hemorrhage. Interventions:Palliative care use. Measurements and Main Results:Intracerebral hemorrhage patients with and without palliative care were identified from the 2007–2011 Nationwide Inpatient Sample using International Classification of Diseases, 9th Revision, codes. Demographics, comorbidities, surgical procedures, and hospital characteristics were compared between patients receiving and not receiving palliative care (code V66.7). Resource utilization measures were inflation-adjusted cost of care and length of stay. Pearson chi square and Wilcoxon-Mann-Whitney tests were used for categorical and continuous variables respectively. Logistic regression was used to construct a predictive model of palliative care. Of the 311,217 intracerebral hemorrhage patients, 32,159 (10.3%) received palliative care. Utilization of palliative care increased from 4.3% in 2007 to 16.2% in 2011 (trend p < 0.001). Patients receiving palliative care had higher Charlson comorbidity scores (p < 0.001), higher all-patient refined diagnosis-related group mortality risk (p < 0.001), and lower resource utilization measures compared with those without palliative care. Independent predictors of palliative care use were older age (odds ratio, 4.06; 95% CI, 3.87–4.23; p < 0.001), female sex (odds ratio, 1.17; 95% CI, 1.14–1.20; p < 0.001), Caucasian race (p < 0.001), Medicare insurance (p < 0.001), hospitals in the west and mid-west (p < 0.001), hospital transfer (odds ratio, 1.23; 95% CI, 1.18–1.30; p < 0.001), high intracerebral hemorrhage case volume (p < 0.001), anticoagulant use (odds ratio, 1.24; 95% CI, 1.19–1.31; p < 0.001), higher Charlson comorbidity score, ventriculostomy placement (odds ratio, 1.18; 95% CI, 1.13–1.29; p < 0.001), and mechanical ventilation (odds ratio, 1.44; 95% CI, 1.39–1.49; p < 0.001). Cerebral angiogram, craniotomy, and gastrostomy were independently associated with absence of palliative care use. Conclusions:An apparent increasing trend of palliative care utilization in intracerebral hemorrhage has occurred over the last decade. After clinical severity adjustment, gender and racial differences and hospital characteristics appear to influence palliative care use among intracerebral hemorrhage patients in the United States.

Thrombolysis for Acute Ischemic Stroke in Patients With Cancer: A Population Study

Background and Purpose— The safety of thrombolysis for acute stroke in patients with cancer is not well established. Our aim is to study the outcomes after thrombolysis in patients with stroke with cancer. Methods— Patients with acute ischemic stroke who received thrombolysis were identified from the 2009 and 2010 Nationwide Inpatient Sample. Patients with cancer-associated strokes and noncancer strokes were compared based on demographics, comorbidities, and outcomes. Results— Of the 32 576 strokes treated with thrombolysis, cancer-associated strokes had significantly higher comorbidity indices overall, but fewer vascular risk factors than noncancer strokes. There was no difference in the rates of home discharge and in-hospital mortality, after adjusting for confounders. Subgroup analysis showed that compared with liquid cancers, patients with solid tumors had worse home discharge (odds ratio, 0.178; 95% confidence interval, 0.109–0.290; P<0.001) and higher in-hospital mortality (odds ratio, 3.018; 95% confidence interval, 1.37–6.646; P=0.006) after thrombolysis. Metastatic cancers had poorest outcomes, but intracerebral hemorrhage rates were similar. Conclusions— Thrombolytic therapy for acute stroke in patients with cancer is not associated with increased risk of intracerebral hemorrhage or in-hospital mortality. However, careful consideration of the cancer subtype may help delineate the subset of patients with poor response to thrombolysis. Prospective confirmation is warranted.

Decompressive Hemicraniectomy in Pediatric Patients with Malignant Middle Cerebral Artery Infarction: Case Series and Review of the Literature

OBJECTIVE Malignant middle cerebral artery infarction (mMCAI) is a life-threatening condition in pediatric patients. Despite strong evidence showing decreased morbidity and mortality in adult mMCAI patients with decompressive hemicraniectomy (DCH), there is a paucity of data on the use of DCH in children with similar conditions. Here we report experience from our center and perform a systematic review of published literature on outcomes after use of DCH in pediatric mMCAI patients. METHODS By retrospective chart review, we identified 3 children with large ischemic stroke who underwent DCH for life-threatening cerebral edema. Information was obtained about patient characteristics on admission, radiological features of the stroke, surgical procedures, complications of the DCH and cranioplasty, and functional outcomes during follow-up visits. We also reviewed the current literature on DCH in pediatric stroke. RESULTS DCH was performed in all 3 cases after development of pupillary dilatation. All 3 children survived and were ambulatory at the time of follow-up. Review of literature identified 12 other published case series describing 26 cases of DCH in pediatric patients with ischemic stroke. Descriptive statistical analysis of these cases is presented. Published reports suggest that a good outcome is possible even in the presence of signs of herniation, low preoperative Glasgow Coma Scale score, involvement of multiple vascular territories, or longer time to surgery in pediatric ischemic stroke patients. CONCLUSIONS The current data suggest a role for DCH in the management of cerebral edema in pediatric patients with mMCAI. Factors that help in prognostication for adult stroke patients undergoing DCH do not appear to convey similar information about the pediatric population. This highlights the urgent need for collaboration across institutes to further investigate this potentially life-saving procedure in pediatric stroke.