Restless legs syndrome shows increased silent postmortem cerebral microvascular disease with gliosis

Background Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders. The postmortem cortex in patients with RLS was therefore evaluated for evidence of microvascular and immunological changes. Methods and Results Ten microvascular injury samples of precentral gyrus in 5 patients with RLS (3 men, 2 women; mean age, 81 years) and 9 controls (2 men, 7 women; mean age, 90 years) were studied by hematoxylin and eosin stains in a blinded fashion. None of the subjects had a history of stroke or neurologic insults. In a similar manner, the following immunohistochemistry stains were performed: (1) glial fibrillary acidic protein (representing gliosis, reactive change of glial cells in response to damage); (2) CD3 (a T-cell marker); (3) CD19 (a B-cell marker); (4) CD68 (a macrophage marker); and (5) CD117 (a mast cell marker). Patients with RLS had significantly greater silent microvascular disease

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div

Glucose Control in the (Neuro) Intensive Care Unit

The vexing question of optimal glucose level in the intensive care unit has long perplexed intensivists. Hyperglycemia is a natural response to physiologic stress,1 and in the critically ill patient has been attributed to inflammatory processes, insulin counter-regulatory hormones, organ dysfunction, iatrogenic carbohydrate or medication related hyperglycemia, and insulin resistance as evidenced by concurrently elevated insulin levels.1 Hyperglycemia occurs in 50-75% of patients admitted to an ICU, and has been associated with various adverse outcomes including increased mortality, organ dysfunction, susceptibility to infections, and neurological complications.1,2 On the cellular level, tissue/organ damage is theorized to be mediated via the production of toxic polyol metabolites and reactive oxygen species,3 with compromise of mitochondrial/cellular function.1 At the opposite extreme, hypoglycemia is acutely detrimental and clearly mandates avoidance. Glucose variability has also been linked to adverse outcomes,4 and insulin administration itself has been associated with increased mortality.5 As such, it is believed that resolution of hypoglycemia, and not insulin administration, is the determinant of improved outcomes.

Plasma Catecholamine Profile of Subarachnoid Hemorrhage Patients with Neurogenic Cardiomyopathy

Purpose: To investigate the connection between sympathetic function and neurogenic cardiomyopathy (NC), and to determine whether NC is mediated primarily by circulating adrenal epinephrine (EPI) or neuronally transmitted norepinephrine (NE), following subarachnoid hemorrhage (SAH). Methods: This is a prospective observational investigation of consecutive severe-grade SAH patients. All participants had transthoracic echocardiography and serological assays for catecholamine levels - dopamine (DA), NE and EPI - within 48 h of hemorrhage onset. Clinical and serological independent predictors of NC were determined using multivariate logistic regression analyses, and the accuracy of predictors was assessed by receiver operating characteristic (ROC) curves. Multivariate linear regression analyses were used to evaluate correlations among the catecholamines. Results: The investigation included a total of 94 subjects: the mean age was 55 years, 81% were female and 57% were Caucasian. NC was identified in approximately 10% (9/94) of cases. Univariate analyses revealed associations between NC and worse clinical severity (p = 0.019), plasma DA (p = 0.018) and NE levels (p = 0.024). Plasma NE correlated with DA levels (&#x03C1; = 0.206, p = 0.046) and EPI levels (&#x03C1; = 0.392, p Conclusions: Following SAH, the development of NC is primarily related to elevated plasma NE levels. Findings implicate a predominantly neurogenic process mediated by neuronal NE (and not adrenal EPI), but cannot exclude synergy between the catecholamines

Improved Inter-rater Reliability for SAH CT Grading Scales through Application of a Formal Definition of Clot Thickness

Various scales have been devised for the prediction of vasospasm following aneurysmal rupture. Especially prominent in these scales is their reliance upon a subjective assessment of clot thickness which introduces variability in grading across raters. The current study seeks to compare the inter-rater reliability of the traditional Fisher and newer Frontera scale (Modified Fisher) when a rigid definition of thick clot is employed

Challenges and controversies in the medical management of primary and antithrombotic-related intracerebral hemorrhage

Intracerebral hemorrhage (ICH) represents 10–15% of all cerebrovascular events, and is associated with substantial morbidity and mortality. In contrast to ischemic cerebrovascular disease in which acute therapies have proven beneficial, ICH remains a more elusive condition to treat, and no surgical procedure has proven to be beneficial. Aspects pertinent to medical ICH management include cessation or minimization of hematoma enlargement, prevention of intraventricular extension, and treatment of edema and mass effect. Therapies focusing on these aspects include prothrombotic (hemostatic) agents, antihypertensive strategies, and antiedema therapies. Therapies directed towards the reversal of antithrombosis caused by antiplatelet and anticoagulant agents are frequently based on limited data, allowing for diverse opinions and practice styles. Several newer anticoagulants that act by direct thrombin or factor Xa inhibition have no natural antidote, and are being increasingly used for various prophylactic and therapeutic indications. As such, these new anticoagulants will inevitably pose major challenges in the treatment of patients with ICH. Ongoing issues in the management of patients with ICH include the need for effective treatments that not only limit hematoma expansion but also result in improved clinical outcomes, the identification of patients at greatest risk for continued hemorrhage who may most benefit from treatment, and the initiation of therapies during the hyperacute period of most active hemorrhage. Defining hematoma volume increases at various anatomical locations that translate into clinically meaningful outcomes will also aid in directing future trials for this disease. The focus of this review is to underline and discuss the various controversies and challenges involved in the medical management of patients with primary and antithrombotic-related ICH

Candida cerebral abscesses: a case report and review of the literature.

Cerebral abscess caused by Candida spp. is a rare disease, with a nonspecific presentation, little data on treatment, and generally poor outcomes. We present a case of this type of Candida infection in a 57-year-old man with a history of uncontrolled diabetes mellitus and intravenous drug abuse, and review the literature on this disease. Our patient had a good treatment outcome with liposomal amphotericin B and flucytosine, followed by oral fluconazole. Comorbidities include prior antibiotic use (52%), prior surgery (28%), malignancy (28%), stem cell or solid organ transplant (20%), prior corticosteroid use (16%), central venous catheter (CVC) insertion (10%), and burns (7%). Diagnosis requires a high index of suspicion, as clinical presentations and laboratory data can be nonspecific and difficult to differentiate from bacterial cerebral abscesses. In reviewed cases, 55% of blood cultures and 23% of cerebrospinal fluid (CSF) cultures were positive for Candida spp. and outcomes were poor, as the mortality rate of the non-autopsy cases reviewed was 69%