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

A Case of Successful Surgical Treatment of Migraine Headaches in a Patient with Sporadic Pulmonary Arteriovenous Malformations

Pulmonary arteriovenous malformations (PAVMs) are thin-walled aneurysms caused by abnormal communication between the pulmonary arteries and veins. Migraine headaches are sometimes the presenting clinical manifestation of PAVMs. Although embolotherapy, using detachable balloons or stainless steel coils, is generally accepted as the best choice for the treatment of multiple PAVMs, the mode of intervention for solitary PAVMs remains a subject of debate. We present a 43-yr-old woman with a 10-yr history of chronic migraines and dyspnea on exertion. She was discovered to have a large solitary centrally located PAVM, placing her at high risk of complications if she were to undergo percutaneous transcatheter embolization. She underwent successful surgical resection of her right middle lobe without complications, resulting in subsequent symptomatic improvement

Giant High-Flow Type Pulmonary Arteriovenous Malformation: Coil Embolization with Flow Control by Balloon Occlusion and an Anchored Detachable Coil

Pulmonary arteriovenous malformations (PAVMs) are often treated by pushable fibered or non-fibered microcoils, using an anchor or scaffold technique or with an Amplatzer plug through a guiding sheath. When performing percutaneous transcatheter microcoil embolization, there is a risk of coil migration, particularly with high-flow type PAVMs. The authors report on a unique treatment in a patient with a giant high-flow PAVM whose nidus had a maximum diameter of 6 cm. A detachable coil, not detached from a delivery wire (an anchored detachable coil), was first placed in the feeding artery under flow control by balloon occlusion, and then multiple microcoils were packed proximally to the anchored detachable coil. After confirming the stability of the microcoils during a gradual deflation of the balloon, we finally released the first detachable coil. The nidus was reduced in size to 15 mm at one year postoperatively

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

Prior antithrombotic therapy, particularly anticoagulant is associated with unfavorable outcomes in primary spontaneous intracerebral hemorrhage patients receiving craniotomy: A nationwide population-based cohort study.

OBJECTIVE: The impact of antithrombotic agents on primary intracerebral hemorrhage (ICH) patients remains controversial, especially with patients that require emergent craniotomy. This study was to evaluate clinical outcomes in operated ICH patients with and without prior antithrombotic agents. METHODS: This is a retrospective cohort study. Between January 2001 to December 2013, all ICH patients that received emergent craniotomy and is present in Taiwan's National Health Insurance Research Database were screened, and divided into prior antiplatelet therapy, anticoagulant therapy and non-antithrombotic therapy according to patient's healthcare claims data within 3 months of index admission. The primary endpoints included in-hospital mortality and complication, and short-term outcome. RESULTS: Of 18,872 eligible patients, 16,251 (87.1%) patients did not receive any antithrombotic therapy, 2,267 patients had antiplatelet therapy and 354 patients had anticoagulation therapy. After propensity score matching, significantly higher amount of blood transfusion and number of craniectomy was identified in the patients with prior antithrombotic treatment compared with non-antithrombotic therapy. In comparison with the non-antithrombotic treatment cohort, patients under prior anticoagulant treatment had significantly higher in-hospital mortality rate (Odds ratio, 2.12; 95% confidence interval, 1.45-3.10). Furthermore, during the 6-month follow-up period, prior anticoagulant therapy was independently associated with a greater risk of all-cause mortality rates (P = 0.001). Interestingly, the in-hospital and 6-month all-cause mortality of patients with prior antiplatelet treatment was not significantly different to patients with non-antithrombotic treatment. CONCLUSION: These findings suggested an increased risk of in-hospital mortality and poor short-term outcome among operated ICH patients with prior antithrombotic therapy, particularly anticoagulant therapy, but not with antiplatelet therapy

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