BACKGROUND: This study investigated whether brief exposure to nitrous oxide (N(2)O) exacerbates levodopa-induced hyperhomocysteinemia, and if co-treatment with folate or entacapone could reduce total plasma homocysteine (tHcy) levels.
METHODS: Male Wistar rats (N=9 per group) were randomly treated with vehicle/N(2)O (GROUP 1), levodopa/nitrogen (group 2), levodopa/N(2)O (group 3), levodopa/N(2)O+folate (group 4), or levodopa/N(2)O+entacapone (group 5). tHcy was measured at 12 min, 4, 8, and 12 h after anesthesia.
RESULTS AND CONCLUSION: The combination of N(2)O-exposure and levodopa treatment significantly increased tHcy in rats. This hyperhomocysteinemia could be prevented by entacapone but not folate co-administration.
The presence of a cerebral cavernous malformation (CM) is generally not regarded as an exclusion criterion to the use of intravenous tissue plasminogen activator (tPA). However, there is a conceivable risk of hemorrhaging with an intracerebral CM, which may dissuade clinicians from treating stroke patients with systemic tPA in the presence of a CM. The case of a 79-year-old man with acute ischemic stroke treated with systemic tPA in the setting of known CM is presented. The patient tolerated intravenous thrombolysis well and remained clinically stable throughout the observation period. This is the first reported case (to our knowledge) supporting the notion that systemic thrombolysis is safe in presence of a previously clinically silent CM.
A 52-year-old man was noted to display “unusual behavior” with transient agitation and blurry vision after otherwise uneventful diagnostic cardiac catheterization. Several hours after same-day discharge from the hospital, he suddenly became comatose, requiring intubation and admission to the intensive care unit. Two days later, he regained consciousness and was noted to have vertical gaze palsy and dysarthria without other neurologic deficits. Magnetic resonance imaging demonstrated bilateral acute medial thalamic ischemic strokes. Magnetic resonance angiography did not display extracranial or intracranial arterial stenosis (not shown). At 3 months' follow-up, he had only mild residual dysarthria.
BACKGROUND: Factors influencing outcome after cerebral artery occlusion are not completely understood. Although it is well accepted that the site of arterial occlusion critically influences outcome, the majority of studies investigating this issue has focused on proximal large artery occlusion. To gain a better understanding of factors influencing outcome after distal large artery occlusion, we sought to assess predictors of outcome following isolated M2 middle cerebral artery occlusion infarcts.
METHODS: We retrospectively analyzed patients with isolated acute M2 occlusion admitted to a single academic center from January 2010 to August 2012. Baseline clinical, laboratory imaging, and outcome data were assessed from a prospectively collected database. Factors associated with a modified Rankin Scale (mRS) score < /=2 in univariable analyses (p < 0.05) were entered into multivariable logistic regression analysis. The Admission National Institutes of Health Stroke Scale (aNIHSS) score, age, and infarct volume were also entered as dichotomized variables. Receiver operating characteristic curves were plotted to determine the optimal aNIHSS score, infarct volume, and age cut points predicting an mRS score < /=2. Optimal thresholds were determined by maximizing the Youden index. Respective multivariable logistic regression analyses were used to identify independent predictors of a good 90-day outcome (mRS score < /=2; primary analysis) as well as 90-day mortality (secondary outcome).
RESULTS: 90 patients with isolated M2 occlusion were included in the final analyses. Of these, 69% had a good 90-day outcome which was associated with age < 80 years (p = 0.007), aNIHSS < 10 (p = 0.002), and infarct volume < /=26 ml (p < 0.001). Notably, 20% of patients (64% of those with a poor outcome) had died by 90 days. Secondary analysis for 90-day mortality was performed. This analysis indicated that infarct volume > 28 ml (OR 11.874, 95% CI 2.630-53.604, p = 0.001), age > 80 years (OR 4.953, 95% CI 1.087-22.563, p = 0.039), need for intubation (OR 7.788, 95% CI 1.072-56.604), and history of congestive heart failure (OR 5.819, 95% CI 1.140-29.695) were independent predictors of 90-day mortality (20% of all included patients).
CONCLUSION: While the majority of patients with isolated M2 occlusion stroke has a good 90-day outcome, a substantial proportion of subjects dies by 90 days, as identified by a unique subset of predictors. The knowledge gained from our study may lead to an improvement in the prognostic accuracy, clinical management, and resource utilization in this patient population.
BACKGROUND AND PURPOSE: Leukoaraiosis (LA) predominantly affects the subcortical white matter, but mounting evidence suggests an association with cortical microvascular dysfunction and potentially decreased cortical ischemic tolerance. Thus, we sought to assess whether preexisting LA is predictive of the cortical infarct volume after middle cerebral artery branch occlusion and whether it relates to a worse outcome.
METHODS: We analyzed data from 117 consecutive patients with middle cerebral artery branch occlusion as documented by admission computed tomography angiography. Baseline clinical, laboratory, and outcome data, as well as final cortical infarct volumes, were retrospectively analyzed from a prospectively collected database. LA severity was assessed on admission computed tomography using the van Swieten scale grading the supratentorial white matter hypoattenuation. Infarct volume predicting a favorable 90-day outcome (modified Rankin Scale score≤2) was determined by receiver operating characteristic curves. Multivariable linear and logistic regression analyses were used to identify independent predictors of the final infarct volume and outcome.
RESULTS: Receiver operating characteristic curve analyses indicated that a final infarct volume of ≤27 mL best predicted a favorable 90-day outcome. Severe LA (odds ratio, 11.231; 95% confidence interval, 2.526-49.926; P=0.001) was independently associated with infarct volume>27 mL. Severe LA (odds ratio, 3.074; 95% confidence interval, 1.055-8.961; P=0.040) and infarct volume>27 mL (odds ratio, 9.156; 95% confidence interval, 3.191-26.270; P < .0001) were independent predictors of a poor 90-day outcome (modified Rankin Scale, 3-6).
CONCLUSIONS: The presence of severe, subcortical LA contributes to larger cortical infarct volumes and worse functional outcomes adding to the notion that the brain is negatively affected beyond LA's macroscopic boundaries.
INTRODUCTION: Although there is sufficient evidence that HMG CoA Reductase Inhibitors reduce stroke recurrence in patients with or ischemic heart disease, it remains unclear whether they also improve outcomes given before or after stroke onset and whether such an effect is more robust with pre-stroke or post-stroke use of statins.
MATERIALS AND METHODS: We carried out a retrospective analysis of a large University Health Consortium Database. Patients with statin use before or after stroke onset were included in the analysis. Twenty patients discontinued statins after stroke onset. The outcome measures were discharge home or long-term care facility and/or death within 45 days.
RESULTS: Patients with prior statin use were more likely to be discharged home (1.67, CI 1.12-2.49), as were post stroke statin patients who had a more robust effect OR 2.63, CI 1.61-4.53).
CONCLUSIONS: Patients started on statins after stroke were more likely to be discharged home versus patients already on statins before stroke onset. However, both groups were also more likely to be discharged home than those patients not on statins.
BACKGROUND AND PURPOSE: It is now well accepted that traumatic white matter injury constitutes a critical determinant of post-traumatic functional impairment. However, the contribution of preexisting white matter rarefaction on outcome following traumatic brain injury (TBI) is unknown. Hence, we sought to determine whether the burden of preexisting leukoaraiosis of presumed ischemic origin is independently associated with outcome after TBI.
METHODS: We retrospectively analyzed consecutive, prospectively enrolled patients of > /=50 years (n = 136) who were admitted to a single neurological/trauma intensive care unit. Supratentorial white matter hypoattenuation on head CT was graded on a 5-point scale (range 0-4) reflecting increasing severity of leukoaraiosis. Outcome was ascertained according to the modified Rankin Scale (mRS) and Glasgow outcome scale (GOS) at 3 and 12 months, respectively.
RESULTS: After adjustment for other factors, leukoaraiosis severity was significantly associated with a poor outcome at 3 and 12 months defined as mRS 3-6 and GOS 1-3, respectively. The independent association between leukoaraiosis and poor outcome remained when the analysis was restricted to patients who survived up to 3 months, had moderate-to-severe TBI [enrollment Glasgow Coma Scale (GCS) < /=12; p = 0.001], or had mild TBI (GCS 13-15; p = 0.002), respectively.
CONCLUSION: We provide first evidence that preexisting cerebral small vessel disease independently predicts a poor functional outcome after closed head TBI. This association is independent of other established outcome predictors such as age, comorbid state as well as intensive care unit complications and interventions. This knowledge may help improve prognostic accuracy, clinical management, and resource utilization.
Prevalence of Pelvic Vein Pathology in Patients with Cryptogenic Stroke and Patent Foramen Ovale Undergoing MRV Pelvis
BACKGROUND: A substantial proportion of ischemic strokes has no any identified underlying cause. Notably, the prevalence of a patent foramen ovale (PFO) is increased in cryptogenic stroke (CS) populations, which may serve as a conduit for paradoxical emboli originating from deep vein thrombosis (DVT) including the pelvic veins. Yet, there are no published guidelines for the assessment of pelvic veins as part of the stroke workup and few studies have systematically investigated pelvic veins as a potential source for paradoxical emboli in CS patients. Further, there is a relative paucity of data regarding pelvic DVT in CS and results have been conflicting. Hence, we sought to determine the prevalence of pelvic DVT in select CS patients with PFO who underwent magnetic resonance venography (MRV).
METHODS: We retrospectively identified patients (n = 50) who underwent contrast-enhanced pelvic MRV at the discretion of the treating physician for the evaluation of CS in the presence of a PFO during hospitalization at a single academic stroke center between January 2011 through December 2013. Multivariable logistic regression analyses were used to assess for factors independently associated with the presence of an abnormal MRV pelvis.
RESULTS: Patients (47 +/- 13 years of age) had MRV performed 4 +/- 3 days after their incident stroke. Nine patients had an abnormal MRV (18%). Of these, four (8%) had pelvic vein thrombosis and 5 (10%) a May-Thurner anatomic variant. All patients with pelvic DVT were subsequently anticoagulated with warfarin (none had abnormal hypercoagulability testing). Clinical clues suggesting paradoxical embolism were present in as many as 40% of patients. On multivariable logistic regression, a history of any risk factors predisposing to DVT (OR 6.7; coefficient 1.9; BCa 95% CI 0.08-20.2; p = 0.014) as well as the number of predisposing risk factors (OR 3.9; coefficient 1.4; BCa 95% CI 0.25-4.2; p = 0.005) predicted the presence of pelvic vein pathology on MRV.
CONCLUSION: We demonstrate a relatively high prevalence of pelvic DVT among select CS patients emphasizing the importance of considering the pelvic veins as a potential source for emboli particularly in the presence of risk factors known to predispose DVT. Because patients were included at the treating physician's discretion, our results reflect 'real-life' practice. Our results may be of clinical importance as inclusion of pelvic vein imaging in CS patients with PFO had impactful therapeutic and nosologic implications. Further study is needed to define patients most likely to benefit from pelvic vein imaging.
Leukoaraiosis Burden Significantly Modulates the Association Between Infarct Volume and National Institutes of Health Stroke Scale in Ischemic Stroke
BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) provides a reliable, quantitative measure of ischemic stroke severity and is predicted by the infarct size. We sought to determine whether leukoaraiosis severity affects the association between infarct size and NIHSS. METHODS: NIHSS and diffusion-weighted imaging-defined infarct volumes from 312 prospectively enrolled patients with supratentorial, ischemic strokes were analyzed. Leukoaraiosis severity was graded according to the Fazekas scale and conceptually defined as absent (0; n=44), mild (1-2; n=106), moderate (3-4; n=105), and severe (5-6; n=57). ANCOVA was used to describe the effect of leukoaraiosis on the association between infarct volume and NIHSS. Multivariable linear regression models were constructed to assess whether the association of leukoaraiosis and infarct volume on NIHSS was independent of other clinically relevant covariates. RESULTS: Overall, there was a significant correlation between the infarct volume and NIHSS (r=0.591; P < 0.001). This correlation significantly attenuated with increasing leukoaraiosis severity from r=0.786 (P < 0.001; absent leukoaraiosis) to r=0.498 (P<0.001; severe leukoaraiosis) and as shown by ANCOVA (P<0.001). Leukoaraiosis (coefficient, 0.107; 95% confidence interval, 0.036-0.179; P=0.016) and infarct volume (coefficient, 0.360; 95% confidence interval, 0.305-0.416; P < 0.001) were independently associated with a greater NIHSS deficit in the fully adjusted multivariable model. CONCLUSIONS: Leukoaraiosis significantly modulates the association between infarct volume and NIHSS. The clinical implications of these findings need further exploration in prospective studies but may be relevant to mitigate outcome differences in patients with stroke by aiding treatment decisions that rely on the NIHSS.
BACKGROUND: Despite its high prevalence, known association with vascular disease and stroke incidence and fatality, little is known about the contribution of vitamin D status to a worse outcome after ischemic stroke. Therefore, we sought to assess whether low serum 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, is predictive of the ischemic infarct volume and whether it relates to a worse outcome.
METHODS: We retrospectively analyzed prospective, consecutive acute ischemic stroke patients evaluated from January 2013 to January 2014 at a tertiary referral center. All patients (n = 96) had a magnetic resonance imaging-proven acute ischemic stroke. Multivariable linear and logistic regression analyses were used to test whether vitamin D represents an independent predictor of infarct volume and poor 90-day outcome (modified Rankin Scale score of > 2).
RESULTS: In univariable analyses, lacunar infarct etiology, lower admission National Institutes of Health Stroke Scale, and higher serum 25(OH)D concentration were associated with smaller infarct volumes (P < .05). The association of 25(OH)D with ischemic infarct volume was independent of other known predictors of the infarct extent (P = .001). Multivariable analyses showed that the risk for a poor 90-day outcome doubled with each 10-ng/mL decrease in serum 25(OH)D.
CONCLUSIONS: Low serum 25(OH)D was independently associated with larger ischemic infarct volume, which may partially explain observed worse outcomes in ischemic stroke patients with poor vitamin D status. Although causality remains to be proven, our results provide the rationale to further explore vitamin D as a promising marker for cerebral ischemic vulnerability and to identify stroke patients at high risk for poor outcome.
Response to Letter Regarding Article, "Leukoaraiosis Burden Significantly Modulates the Association Between Infarct Volume and National Institutes of Health Stroke Scale in Ischemic Stroke"
- Leukoaraiosis Burden Significantly Modulates the Association Between Infarct Volume and National Institutes of Health Stroke Scale in Ischemic Stroke. [Stroke. 2015]
- Letter by Liu et al Regarding Article, "Leukoaraiosis Burden Significantly Modulates the Association Between Infarct Volume and National Institutes of Health Stroke Scale in Ischemic Stroke". [Stroke. 2015]
Pharmacological and device-induced reperfusion therapies have demonstrated increasingly positive outcomes regarding both reperfusion efficacy and 90-day functional outcomes after acute ischemic stroke. However, presently, only a minority of patients are eligible for these treatments. Less than 10 % of all ischemic stroke patients receive intravenous thrombolysis in most centers and it has been projected that only approximately 7-15 % of ischemic stroke patients are eligible for acute endovascular intervention. Making these effective therapies safely available to a much larger number of patients is critical for expanding the benefits of acute ischemic stroke treatment. In this article, we summarize the key results from the clinical trials, challenges, and exciting novel opportunities to increase patient eligibility for these therapies as well as for better outcomes for stroke patients.
BACKGROUND: A new generation of highly navigable large-bore aspiration catheters and retriever devices for intracranial mechanical thrombectomy has markedly improved recanalization rates, time and clinical outcomes. We report collected clinical data utilizing a new technique based on combined large lumen aspiration catheter and partially resheathed stent retriever (ARTS: Aspiration (catheter)-(stent) Retriever Technique for Stroke). This technique is applied, especially in presence of bulky/rubbery emboli, when resistance is felt while retracting the stent retriever; at that point the entire assembly is locked and removed in-toto under continuous aspiration with additional flow arrest.
METHODS: A retrospective data analysis was performed to identify patients with large cerebral artery acute ischemic stroke treated with ARTS. The study was conducted between August 2013 and February 2015 at a single high volume stroke center. Procedural and clinical data were captured for analysis.
RESULTS: Forty-two patients (median age 66 years) met inclusion criteria for this study. The ARTS was successful in achieving Thrombolysis in Cerebral Infarction (TICI) > /=2b revascularization in 97.6% of cases (TICI 2b = 18 patients, TICI 3 = 23 patients). Patients' median National Institutes of Health Stroke Scale score at admission was 18 (6-40). A 3-month follow-up modified Rankin Scale value of 0-2 was achieved in 65.7% of the successfully treated patients (average 2.4). Two patients (4.8%) developed symptomatic intraparenchymal hemorrhages. Six procedure unrelated deaths were observed.
CONCLUSIONS: We found that ARTS is a fast, safe and effective method for endovascular recanalization of large vessel occlusions presenting within the context of acute ischemic stroke.
Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1
Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptorSarm1(sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model.Sarm1(-/-)mice developed fewer beta-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared toSarm1(+/+)mice. Furthermore, mice lackingSarm1had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function inSarm1(-/-)animals. Finally, usingin vivoproton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism inSarm1(-/-)mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury.
Developing a Community-Based Participatory Research Approach to Understanding of the Repeat Use of Psychiatric Emergency Services
Psychiatric emergency services (PES) remain a critical and under-examined component of the community mental health system. We describe how a unique community-academic partnership came together to examine repeat use of PES through the design and conduct of a qualitative study using a CBPR approach. The goals of the project were to: (1) develop a model of research which promoted the inclusion of people who use mental health services in the research process; and (2) design and conduct a study to examine the repeat use of PES through the inclusion of the perspectives and experiences of people who use these services.
Infertility and perinatal loss are common, and associated with lower quality of life, marital discord, complicated grief, major depressive disorder, anxiety disorders, and post-traumatic stress disorder. Young women, who lack social supports, have experienced recurrent pregnancy loss or a history of trauma and / or preexisting psychiatric illness are at a higher risk of experiencing psychiatric illnesses or symptoms after a perinatal loss or during infertility. It is especially important to detect, assess, and treat depression, anxiety, or other psychiatric symptoms because infertility or perinatal loss may be caused or perpetuated by such symptoms. Screening, psychoeducation, provision of resources and referrals, and an opportunity to discuss their loss and plan for future pregnancies can facilitate addressing mental health concerns that arise. Women at risk of or who are currently experiencing psychiatric symptoms should receive a comprehensive treatment plan that includes the following: (1) proactive clinical monitoring, (2) evidence-based approaches to psychotherapy, and (3) discussion of risks, benefits, and alternatives of medication treatment during preconception and pregnancy.
Most women with perinatal depression do not receive depression treatment. The authors describe the development and beta testing of a new program, PRogram In Support of Moms (PRISM), to improve treatment of perinatal depression in obstetric practices. A multidisciplinary work group of seven perinatal and behavioral health professionals was convened to design, refine, and beta-test PRISM in an obstetric practice. Iterative feedback and problem solving facilitated development of PRISM components, which include provider training and a toolkit, screening procedures, implementation assistance, and access to immediate psychiatric consultation. Beta testing with 50 patients over two months demonstrated feasibility and suggested that PRISM may improve provider screening rates and self-efficacy to address depression. On the basis of lessons learned, PRISM will be enhanced to integrate proactive patient engagement and monitoring into obstetric practices. PRISM may help overcome patient-, provider-, and system-level barriers to managing perinatal depression in obstetric settings.
OBJECTIVE: Perinatal depression is common and associated with poor birth, infant and child outcomes. Screening for perinatal depression alone does not improve treatment rates or patient outcomes. This paper describes the development, implementation and outcomes of a new and low-cost population-based program to help providers address perinatal depression, the Massachusetts Child Psychiatry Access Project (MCPAP) for Moms.
METHOD: MCPAP for Moms builds providers' capacity to address perinatal depression through (1) trainings and toolkits on depression screening, assessment and treatment; (2) telephonic access to perinatal psychiatric consultation for providers serving pregnant and postpartum women; and (3) care coordination to link women with individual psychotherapy and support groups.
RESULTS: In the first 18 months, MCPAP for Moms enrolled 87 Ob/Gyn practices, conducted 100 trainings and served 1123 women. Of telephone consultations provided, 64% were with obstetric providers/midwives and 16% were with psychiatrists. MCPAP for Moms costs $8.38 per perinatal woman per year ($0.70 per month) or $600,000 for 71,618 deliveries annually in Massachusetts.
CONCLUSION: The volume of encounters, number of women served and low cost suggest that MCPAP for Moms is a feasible, acceptable and sustainable approach that can help frontline providers effectively identify and manage perinatal depression.