Recurrent Cerebral Hemorrhage Research Articles

Abstract 117: Digitally Subtracted Angiogram & Biopsy Negative Recurrent Spontaneous Bilateral Anterior Cerebral Artery Territory Intracranial Hemorrhage

Introduction Up to 18% of spontaneous intracerebral hemorrhages are cryptogenic despite a thorough workup, usually noted in a lobar location. Although undetected on DSA, a significant proportion of these represent ruptured micro‐AVM/AVF or cavernous malformations that ultimately are amenable to surgical resection if detected on biopsy. However, occult cerebral amyloid angiopathy can also present similarly, and their management is markedly different. Methods We present a case of recurrent bilateral medial frontal hemorrhage in a patient without known cerebrovascular disease that evaded diagnosis despite hematologic evaluation, MRI, CTA, two DSAs, three clot evacuations with pathology, and brain biopsy. Results The patient is a 60‐year‐old previously healthy woman who presented with sudden onset right hemiparesis and speech arrest. CT revealed a left parasagittal hemorrhage. She was brought to the OR for clot evacuation. Pathology from the clot revealed blood vessels of multiple sizes consistent with meningeal vessels or underlying AVM/AVF. A 6‐vessel cerebral angiogram as unremarkable. The patient’s inpatient course was complicated by new onset Afib with RVR and asymptomatic DVT with PE, however no etiology of coagulopathy was detected. MRI brain showed no evidence of cerebral microbleed or other underlying pathology, noting only DWI + FLAIR hyperintensity in the left ACA territory. The patient was diagnosed with ACA territory stroke complicated by PH2‐type hemorrhagic conversion. She was initially placed on IV Heparin, before transition to apixaban uneventfully. She continued to recover in the hospital and was eventually discharged to rehab. She re‐presented 1 month later with worsening behavioral arrest and right hemiparesis. CT head revealed recurrence of left parasagittal ICH. She underwent clot evacuation in the OR again and repeat pathology was unrevealing. A repeat MRI showed only the evident bleed and a subtle hyperintensity in the right occipital cortex suspicious for an interval subacute occipital lobe stroke with laminar necrosis, ostensibly from Afib. She improved clinically and was discharged to rehab with a diagnosis of recurrent hemorrhage attributed to anticoagulant use and recent stroke. She was discharged this time on no anticoagulant or antiplatelets. She re‐presented 1 month later with sudden onset speech arrest, but now with left hemiparesis. CT revealed a right parasagittal hemorrhage. She was brought to the OR for emergent clot evacuation and parenchymal biopsy – which was initially normal. A repeat 6‐vessel DSA was again unremarkable as was repeat brain MRI. The patient’s parenchymal biopsy was sent for specific congo‐red and immunohistochemistry for beta‐amyloid. IHC revealed beta‐amyloid plaques in the parenchyma and vessel walls, confirming a diagnosis of CAA. Conclusion Apparently cryptogenic lobar hemorrhage may be caused by both occult micro‐AVM/fistula and CAA. As in this case, when a patient experiences recurrent DSA negative lobar hemorrhages, biopsy should be pursued. This case was particularly challenging given the anatomical plausibility of parasagittal AVM/fistula given its midline location and venous drainage, considering the patient’s evident predisposition to systemic venous thrombosis hemorrhagic venous infarction mimicking lobar ICH is also possible. We present this case to raise awareness of the potential need for early biopsy, especially in patients who may also require anticoagulation or antiplatelet medications.

Impaired retinoic acid signaling in cerebral cavernous malformations

The capillary-venous pathology cerebral cavernous malformation (CCM) is caused by loss of CCM1/Krev interaction trapped protein 1 (KRIT1), CCM2/MGC4607, or CCM3/PDCD10 in some endothelial cells. Mutations of CCM genes within the brain vasculature can lead to recurrent cerebral hemorrhages. Pharmacological treatment options are urgently needed when lesions are located in deeply-seated and in-operable regions of the central nervous system. Previous pharmacological suppression screens in disease models of CCM led to the discovery that treatment with retinoic acid improved CCM phenotypes. This finding raised a need to investigate the involvement of retinoic acid in CCM and test whether it has a curative effect in preclinical mouse models. Here, we show that components of the retinoic acid synthesis and degradation pathway are transcriptionally misregulated across disease models of CCM. We complemented this analysis by pharmacologically modifying retinoic acid levels in zebrafish and human endothelial cell models of CCM, and in acute and chronic mouse models of CCM. Our pharmacological intervention studies in CCM2-depleted human umbilical vein endothelial cells (HUVECs) and krit1 mutant zebrafish showed positive effects when retinoic acid levels were increased. However, therapeutic approaches to prevent the development of vascular lesions in adult chronic murine models of CCM were drug regiment-sensitive, possibly due to adverse developmental effects of this hormone. A treatment with high doses of retinoic acid even worsened CCM lesions in an adult chronic murine model of CCM. This study provides evidence that retinoic acid signaling is impaired in the CCM pathophysiology and suggests that modification of retinoic acid levels can alleviate CCM phenotypes.

Predictive Value of Recurrent Acute Cerebral Hemorrhage: A Study Based on Electrocardiogram

Predictive Value of Recurrent Acute Cerebral Hemorrhage: A Study Based on Electrocardiogram

Predictive Value of Recurrent Acute Cerebral Hemorrhage: A Study Based on Electrocardiogram

Predictive Value of Recurrent Acute Cerebral Hemorrhage: A Study Based on Electrocardiogram

Squamous cell carcinoma invading peripheral cerebral blood vessels and causing repeated cerebral hemorrhage : A case report.

Squamous cell carcinoma (SCC) is known to have less brain metastasis, but the reasons are not well established. Herein, we report the case of an 82-year-old man with recurrent cerebral hemorrhage of unknown cause ; upon brain biopsy, SCC was diagnosed infiltrating peripheral blood vessels of the brain and that it was state of micro-metastasis. It is possible that the blood-brain barrier blocked the infiltration of SCC into the brain parenchyma, and it did not form a mass in the brain parenchyma. In addition, because it did not form a mass, it could not be diagnosed as a metastatic brain tumor by contrast-enhanced magnetic resonance imaging or contrast-enhanced computed tomography. Among cases of recurrent cerebral hemorrhage of unknown cause in a short period, there may be cases of vascular infiltration without crossing the blood-brain barrier. Thus, if similar cases of recurrent cerebral hemorrhage of unknown cause is observed, it is necessary to distinguish metastatic brain tumors even if there is no evidence of suspected tumor on contrast-enhanced magnetic resonance imaging scan. J. Med. Invest. 70 : 276-280, February, 2023.

Early-Onset Cerebral Amyloid Angiopathy and Alzheimer Disease Related to an APP Locus Triplication.

Background and ObjectiveTo report a triplication of the amyloid-β precursor protein (APP) locus along with relative messenger RNA (mRNA) expression in a family with autosomal dominant early-onset cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD).MethodsFour copies of the APP gene were identified by quantitative multiplex PCR of short fluorescent fragments, fluorescent in situ hybridization (FISH), and array comparative genomic hybridization. APP mRNA levels were assessed using reverse-transcription–digital droplet PCR in the proband's whole blood and compared with 10 controls and 9 APP duplication carriers.ResultsBeginning at age 39 years, the proband developed severe episodic memory deficits with a CSF biomarker profile typical of AD and multiple lobar microbleeds in the posterior regions on brain MRI. His father had seizures and recurrent cerebral hemorrhage since the age of 37 years. His cerebral biopsy showed abundant perivascular amyloid deposits, leading to a diagnosis of CAA. In the proband, we identified 4 copies of a 506-kb region located on chromosome 21q21.3 and encompassing the whole APP gene without any other gene. FISH suggested that the genotype of the proband was 3 copies/1 copy corresponding to an APP locus triplication, which was consistent with the presence of 2 APP copies in the healthy mother and with the paternal medical history. Analysis of the APP mRNA level showed a 2-fold increase in the proband and a 1.8 fold increase in APP duplication carriers compared with controls.DiscussionIncreased copy number of APP is sufficient to cause AD and CAA, with likely earlier onset in case of triplication compared with duplication.

Cerebral Amyloid Angiopathy-Related Inflammation/Vasculitis

Cerebral amyloid angiopathy (CAA) is a disorder characterized by the deposition of amyloid in the leptomeningeal and cortical blood vessels. Sporadic amyloid β (Aβ)-type CAA is the most common form of CAA. Although CAA is a well-known cause for recurrent cerebral lobar hemorrhage, inflammation, and vasculitis, CAA-related inflammation/vasculitis (CAA-ri/vasculitis) induced by Aβ deposition on vessel walls is emerging as a treatable condition. The estimated total number of cases of and prevalence of CAA-ri/vasculitis in Japan were 170 and 0.13 per 100 000 population, respectively. Patients with CAA-ri/vasculitis show acute or subacute-onset of cognitive impairment, behavioral changes, and headache. Brain magnetic resonance imaging, showing asymmetrical white matter abnormalities and occasional meningeal enhancement, is a useful tool for the diagnosis of CAA-ri/vasculitis. Moreover, elevation of anti-Aβ antibodies and inflammatory markers in the cerebrospinal fluid can help in clinical diagnosis. Although several clinical diagnostic criteria have been proposed, neuropathological examination of a brain biopsy remains the gold standard for detecting severe Aβ deposition and vasculopathic changes with lymphocytic infiltrations and/or granulomatous vasculitis. No validated treatment regimen has been established to date. Nearly 80% patients with CAA-ri/vasculitis improved after immunosuppressant therapy with corticosteroid and/or cyclophosphamide. Early treatment is essential to prevent irreversible sequelae in the brain.

Cerebral amyloid angiopathy‐related inflammation and dementia

AbstractCerebral amyloid angiopathy (CAA) is a disorder characterized by deposition of amyloid on the leptomeningeal and cortical blood vessels. Sporadic amyloid β (Aβ)‐type CAA is the most common type of CAA. Although CAA is well known as a cause of recurrent cerebral lobar hemorrhage, inflammation and vasculitis (CAA‐related inflammation [CAA‐ri]) induced by deposited Aβ on the vessel walls is emerging as a treatable condition. Furthermore, dementia could develop regardless of the presence of Alzheimer's disease pathology. The estimated total number and prevalence of CAA‐ri in Japan was reported as follows: 170 and 0.13 per 100 000 population, respectively. The estimated total number of CAA‐related intracerebral hemorrhage was 5900. The crude prevalence rate of CAA‐related intracerebral hemorrhage was 4.64 per 100 000 population. The patients with CAA‐ri show acute or subacute‐onset cognitive impairment, behavioral changes and headache. Brain magnetic resonance imaging is a useful tool for the diagnosis of CAA‐ri, showing asymmetrical white matter abnormalities and occasional meningeal enhancement. Furthermore, elevation of anti‐Aβ antibodies and inflammatory markers in the cerebrospinal fluid would be useful for clinical diagnosis. Clinical diagnostic criteria were proposed; however, neuropathological examination obtained by brain biopsy is still warranted to confirm severe Aβ deposition and vasculopathic changes with lymphocytic infiltrations and/or granulomatous vasculitis. No validated protocol of treatment has been established. Nearly 80% of the patients with CAA‐ri improved after immunosuppressant therapy, including corticosteroid and cyclophosphamide. Early treatment is necessary to prevent the development of irreversible sequela in the brain.

Aspirin Versus Clopidogrel Monotherapy for the Secondary Prevention of Recurrent Cerebrovascular Attack Following Previous Ischemic Stroke in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

IntroductionType 2 diabetes mellitus (T2DM) and stroke are two different diseases, but have many aspects in common. Aspirin is recommended as an initial treatment for the secondary prevention of recurrent ischemic stroke in patients with T2DM. However, clopidogrel is an oral antiplatelet drug that might be another choice in case of aspirin intolerance. In this analysis, we aimed to systematically compare aspirin versus clopidogrel monotherapy for the secondary prevention of recurrent cerebrovascular attack following previous ischemic stroke in patients with T2DM.MethodsOnline medical databases including Web of Science, MEDLINE, Cochrane central, EMBASE and http://www.ClinicalTrials.com were searched for published articles that satisfied the inclusion and exclusion criteria of this study. Recurrent stroke, fatal stroke, cerebral hemorrhage, myocardial infarction and mortality were considered the main end points in these patients with T2DM. RevMan 5.3 software was used to statistically analyze the data representing each subgroup. Risk ratios (RRs) with 95% confidence intervals (CIs) were used to represent the results following analysis.ResultsA total of 9218 participants with T2DM who were previously affected by ischemic stroke were included in this analysis, whereby 4917 were assigned to aspirin and 4301 to clopidogrel. This current analysis showed that there was no significant difference in recurrent stroke rate (RR: 0.79, 95% CI: 0.61–1.02; P = 0.07) observed with aspirin versus clopidogrel in these patients with T2DM. The risk of fatal stroke (RR: 0.88, 95% CI: 0.39–1.98; P = 0.76), cerebral hemorrhage (RR: 0.65, 95% CI: 0.38–1.11; P = 0.12), myocardial infarction (RR: 0.88, 95% CI: 0.43–1.79; P = 0.71) and mortality (RR: 1.07, 95% CI: 0.90–1.27; P = 0.44) were also similarly manifested.ConclusionClopidogrel monotherapy was neither inferior nor superior to aspirin monotherapy for the secondary prevention of recurrent cerebrovascular attack following previous ischemic stroke in patients with T2DM. Hence, clopidogrel or aspirin monotherapy is equally safe and effective in these patients with T2DM.

Comparison of Long Term Prognosis between Carotid Endarterectomy versus Stenting; A Korean Population-Based Study Using National Insurance Data.

PurposeAlthough carotid endarterectomy (CEA) is recommended as a treatment for carotid stenosis rather than carotid artery stenting (CAS), CAS has been preferred in Korea. The aim of this study was to analyze long-term outcomes after CAS compared with CEA using Korean nationwide insurance data.Materials and MethodsWe obtained all data from the nationwide database of the Health Insurance Review & Assessment Service (HIRA) during the study period using several codes regarding the procedure or operation. We included the HIRA data, which included at least one-year follow-up after the procedures. The outcomes associated with both procedures were death, recurrence of ischemic stroke, and admission for cerebral hemorrhage.ResultsA total of 16,065 eligible patients who were treated with CAS or CEA between 1 January 2007 and 31 December 2016 were analyzed. The number of patients with CAS and CEA was 12,173 (75.8%) and 3,892 (24.2%), respectively. 8,976 patients (55.9%) were classified as symptomatic patients. CAS was associated with a higher risk of all-cause mortality (adjusted hazard ratio [HR], 1.282; 95% confidence interval [CI], 1.173–1.400). The adjusted rates for recurrent ischemic stroke and cerebral hemorrhage between CAS versus CEA were 24.9% versus 15.9% (HR, 1.474; 95% CI, 1.325–1.639) and 1.5% versus 0.9% (HR, 2.026; 95% CI, 1.322–3.106), respectively. In young symptomatic patients, there was no statistically significant difference in all-cause mortality and cardiovascular death between CAS and CEA.ConclusionOur study using Korean nationwide insurance data demonstrated similar results to previous studies. Until further evidence of CAS is established through prospective studies, CAS should be performed in selected patients according to current guidelines.

Genotype-Phenotype Correlation in Long-Term Cohort of Japanese Patients with Moyamoya Disease

Background: Homozygosity of this p.R4810K founder variant of RNF213moyamoya disease (MMD) susceptibility gene is known to influence the severity of the clinical disease phenotype at disease onset. However, the association between this genotype and long-term clinical manifestations has remained unclear. Objectives: The principal goal of this study was to investigate whether and how the p.R4810K variant of RNF213influences the long-term phenotype in Japanese patients with MMD. Method: This retrospective cohort study included 94 Japanese patients with MMD who underwent direct or combined bypass for revascularization with the p.R4810K genotype determined in our hospital. The following phenotypic parameters were analyzed at disease onset and over a long-term period: age and initial presentation at onset, recurrent stroke after initial revascularization, and final modified Rankin Scale. Results: The p.R4810K genotype was significantly associated with the phenotype at onset, especially in younger patients. Over a median follow-up period of 100 months, recurrent stroke occurred in 6 out of 94 patients: none out of 5 patients with the homozygous variant, 5 out of 64 with the heterozygous variant, and 1 out of 25 in the wild-type group. There were no significant differences among the genotypes. In particular, recurrent cerebral hemorrhage occurred in 5 patients, all possessing the heterozygous variant. The log-rank test showed no difference between the genotypes in the stroke-free survival rate. Furthermore, the p.R4810K genotype was not associated with a poor functional condition. Conclusions: The p.R4810K founder variant of RNF213 affects the phenotype at disease onset. However, the optimal revascularization may be effective, regardless of the genotype, even for the homozygous variant, which has been thought to be the most pathogenic. This genotype may not strongly influence the long-term clinical manifestations or poor prognosis in MMD.

Predicting Recurrent Hypertensive Intracerebral Hemorrhage: Derivation and Validation of a Risk-Scoring Model Based on Clinical Characteristics

To develop and validate a risk-scoring model for predicting recurrent hypertensive cerebral hemorrhage (RHCH) occurring within 1 year after initial hypertensive cerebral hemorrhage and to facilitate preemptive clinical intervention for the prevention of secondary hemorrhage. Patient gender, age, blood pressure, Glasgow Coma Scale (GCS) score, location of cerebral hemorrhage, surgery, past medical history, blood biochemical parameters, and Glasgow Outcome Scale score were analyzed using logistic regression analysis to determine independent predictors of RHCH. A risk-scoring model was constructed by assigning coefficients to each predictor and validating it in another independent cohort. The accuracy of the model was then assessed by the area under the receiver operating characteristic curve (AUC), and the calibration ability of the model was assessed by the Hosmer-Lemeshow test. Of 520 patients in the derivation cohort, 38 developed RHCH within 1 year after discharge. Independent risk factors of RHCH were age >60 years; stage 3 hypertension at admission; GCS score 9-12 (admission); GCS score 3-8 (discharge); history of cerebral ischemic stroke, smoking, alcoholism; and plasma homocysteine (Hcy) level ≥10 μmol/L. The recurrence rates for the low-risk (0-13 points), intermediate-risk (14-26 points), and high-risk (27-39 points) groups were 1.73%, 6.11%, and 57.14%, respectively (P < 0.001). The corresponding rates in the validation cohort, of whom 10/107 (9.35%) developed RHCH, were 3.45%, 7.14%, and 71.43%, respectively (P < 0.001). The risk-scoring model showed good discrimination in both the derivation and validation cohorts, with an AUC of 0.802 versus 0.863. The model also showed good calibration ability (the Hosmer-Lemeshow P values of the two cohorts were 0.532 vs. 0.724). This model will help identify high-risk groups for RHCH in order to facilitate and improve preemptive clinical intervention.

Recurrent Cerebral Hemorrhage Associated with Ulcerative Colitis

Ulcerative colitis (UC) is a rare cause of stroke. Most such cases result from cerebral venous thrombosis, and cerebral vasculitis is one cause of venous thrombus formation. Here, we report a patient with UC who experienced recurrent cerebral hemorrhage. A 53-year-old Japanese woman with UC presented with sudden onset of disorientation and sensory aphasia. Brain computed tomography revealed cerebral hemorrhage in the left temporal lobe. She had a history of UC for two decades but had discontinued her medication. On the fifth hospital day, another cerebral hemorrhage occurred in the right occipital lobe. After steroid therapy, these abnormal findings on MRI improved within a short time, and she was discharged from hospital with no sequelae. Physicians should be alert to cerebral hemorrhage in patients with UC, consider cerebral vasculitis as an etiology, and treat with steroid therapy for a good outcome.

Recurrent Cerebral Hemorrhage in Normal Pregnancy Secondary to Mycotic Pseudoaneurysms Related to Choriocarcinoma.

Choriocarcinoma coexisting with or after normal pregnancy is extremely rare. To our knowledge, our case report is the first time cerebral mycotic pseudoaneurysms from choriocarcinoma have been proven angiographically. A 38-week pregnant 26-year-old woman presented with an acute left frontal hemorrhage. She underwent emergency cesarean section, followed by hematoma evacuation and resection of what grossly appeared to be a medium-sized arteriovenous malformation at the time of surgery. Angiogram before and after resection showed no obvious vascular pathology. One month later, she returned with status epilepticus, and an acute parenchymal hematoma posterior to the surgical resection cavity was identified. Angiography showed a multilobulated pseudoaneurysm along the left middle cerebral artery. This was resected and found on histopathology to have choriocarcinoma within and around the blood vessels. Serum human chorionic gonadotrophin levels increased daily. Pan computed tomography showed a left lung lobular mass. The diagnosis was stage 4 World Health Organization score 9 high-risk metastatic choriocarcinoma requiring radiation followed by multiagent chemotherapy. Two weeks later, she had another seizure. An angiogram showed an unruptured pseudoaneurysm along the right posterior cerebral artery, which was embolized. Metastatic choriocarcinoma is rarely considered during a viable pregnancy but is almost always fatal if unrecognized. Early recognition enhances the chances of cure with chemotherapy. Arteriovenous malformations are typically considered in young women with intracerebral hemorrhages and have higher risk of rupture in pregnant women, but physicians should also be aware of metastatic choriocarcinoma and the development of mycotic aneurysms in peripartum women with intracerebral hemorrhages.

Risk factors and preventive measures of cerebral hyperperfusion syndrome after carotid artery interventional therapy.

This study sought to investigate the risk factors for cerebral hyperperfusion syndrome (CHS) after carotid artery interventional therapy, and to explore potential preventive measures. Three hundred and eighty-two patients treated with carotid artery stenting at the Huanhu Hospital (Tianjin, China) between January 2010 and January 2016 were divided into CHS and non-CHS groups. A retrospective analysis of patient clinical data was made. The CHS group had more patients presenting coronary heart disease, diabetes, progressive neurological disease and transient recurrent cerebral hemorrhage than the non-CHS group. More patients in the CHS group presented stenosis of the internal carotid artery siphon. More CHS group patients showed plaque formation extending >3 cm to the distal end of the internal carotid artery. Finally, more CHS group patients had pressure gradients >60 mmHg (p<0.05). Logistics regression analysis showed that preoperative diabetes mellitus and carotid pressure gradient ≥60 mmHg were independent risk factors for CHS (p<0.05). The ROC curve of carotid pressure gradients ≥60 mmHg were made to predict CHS, with the area under curve being 0.949 (p<0.05). The best cut-off value was 60 mmHg. Therefore, preoperative diabetes and a carotid pressure gradient ≥60 mmHg are risk factors for CHS, and these indicators need to be examined prior to operation.

Recurrent Hypertensive Cerebral Hemorrhages in a Boy Caused by a Reninoma: Rare Manifestations and Distinctive Electron Microscopy Findings

Recurrent cerebral hemorrhages caused by hypertension secondary to reninoma are extremely rare in children. Because of its detrimental effects on children's health, the importance of early diagnosis of and treatment for reninoma should be emphasized. Here, the authors present a 10-year-old boy with intermittent headaches and neurologic deficiency symptoms caused by hypertension. A reninoma in the right kidney was detected and successfully treated with laparoscopic partial nephrectomy. Two cell types were revealed in the tumor tissue under electron microscopy: renin secreting tumor cells and mast cells. This rare case expands our knowledge of hypertension in children and provides direct evidence that mast cells may infiltrate reninoma.

Experience of 97 patients with moyamoya disease: long-term follow-up at a single center

To explore the medium and long-term outcomes of patients with Moyamoya disease (MD) undergoing surgery and conservative treatment at a single institution and analyze the related prognostic factors. A retrospective review was conducted for 97 MD patients at Beijing Tiantan Hospital from January 2000 to December 2007. They were divided into 3 groups according to treatments: superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis (n = 31), indirect vascular revascularization group (n = 38) and conservative treatment group (n = 28). The primary follow-up events included death, recurrent cerebral hemorrhage, new cerebral infarction and transient ischemic attack (TIA). All were available for analysis with the complete follow-up data. The average follow-up period of was 85 ± 38 months. In total, there were 6 deaths with all-cause mortality (6.1%). Among them, 5 (5.1%) patients died from recurrent cerebral hemorrhage. And 17 episodes of rebleeding occurred in 11 patients. Two episodes of intracranial hemorrhage were found in 4 patients. The risk of rebleeding was 17.5%. In the STA-MCA group, 23(74%) cases had excellent recovery, 5 cases fared worse and there was no death case. Among the patients undergoing indirect vascular revascularization, 28 cases recovered favorably, 4 cases progressed and 3 cases died. In the conservative treatment group, 17 patients recovered favorably, 7 progressed, 9 experienced 15 episodes of rebleeding and 3 died. Multivariate Cox regression analysis showed that the method of treatment was an independent prognostic factor for MD and surgical revascularization was superior to conservative treatment. No correlation was found between the patient age, gender, familial history, unilateral or bilateral and prognosis (P > 0.05). Kaplan-Meier stroke risk analysis showed the risk of recurrent hemorrhage in the revascularization surgery group was lower than that in the conservative group. And no difference existed between STA-MCA and indirect arterial anastomoses. Rebleeding is a major cause of poor prognosis, mobility and mortality in MD patients. Surgical revascularization offers better long-term outcomes than conservative treatment. And direct arterial anastomoses may decrease recurrent hemorrhage effectively.

A Nasogastric Tube Inserted into the Gastrocutaneous Fistula

We reported a case in which a nasogastric tube was inserted into the gastrocutaneous fistula, diagnosed by abdominal computed tomography. A 78-year-old man with a history of recurrent cerebral hemorrhage had a percutaneous endoscopic gastrostomy tube due to dysphagia for 2 years. However, soft tissue infection at the gastrostomy site caused the removal of the tube. Immediately, antibiotic agents were infused. For appropriate hydration and medication, a nasogastric tube was inserted. However, there was no significant improvement of the soft tissue infection. Moreover, the amount of bloody exudate increased. Abdominal computed tomography revealed the nasogastric tube placed under the patient's skin via gastrocutaneous fistula. The nasogastric tube was removed, and an antibiotic agents were maintained. After 3 weeks, the signs of infection fully improved, and percutaneous endoscopic gastrostomy was performed again. This case shows necessities of an appropriate interval between removal of the gastrostomy tube and insertion of a nasogastric tube, and suspicion of existence of gastrocutaneous fistula.

Percutaneous Atrial Shunt Closure Using the Novel Occlutech Figulla Device: 6‐Month Efficacy and Safety

The Occlutech Figulla Occluder is a new innovative device for percutaneous closure of a patent foramen ovale (PFO) and an atrial septum defect (ASD). We describe the safety and efficacy of this new device at 6-month follow-up. All 82 consecutive patients (51% female, mean age 49.0 ± 13.6 years) who underwent percutaneous PFO (n = 48) or ASD (n = 34) closure between October 2008 and October 2009 were included. Implantation success was 100%. The in-hospital complications were two new onset supraventricular tachycardia (SVT) (2.4%, both ASD patients), nine minimal groin hematoma's (11.0%, 4 PFO and 5 ASD patients), and one transient ST elevation during the procedure (1.2%, ASD patient). During 6 months follow-up (n = 79), no major complications or reoccurrences of cerebral thrombo-embolic events did occur. Seven patients (8.9%, 6 PFO and 1 ASD patient) experienced a new SVT. One patient developed a recurrent cerebral hemorrhage 5 months after ASD closure, which appeared not to be related to the procedure. Using contrast transthoracic echocardiography 6 months after PFO closure (n = 45), a residual shunt was present in 30.2% of the patients (small 25.6%, moderate 4.6%, severe 0%). In the ASD group (n = 34), a residual shunt was observed in 32.5% (small 17.7%, moderate 14.7%, severe 2.9%). The Occlutech Figulla Occluder appears to be easy to use, effective, and safe for percutaneous closure of PFO and ASD. We report a low complication rate but a relative high percentage of small residual shunts 6 months after closure.

Efficacy and safety of highly purified, doubly virus‐inactivated VWF/FVIII concentrates in inherited von Willebrand’s disease: results of an Italian cohort study on 120 patients characterized by bleeding severity score

The efficacy of highly purified VWF/FVIII concentrates with standardized ristocetin cofactor content (VWF:RCo) has been already proven in patients with von Willebrand's disease (VWD). Aim of this retrospective study is to confirm efficacy and safety of two highly purified, doubly virus-inactivated VWF/FVIII concentrates in a large cohort of patients with VWD who were characterized at enrolment by bleeding severity score. Study drugs Alphanate or Fanhdi were given to 120 cases (51 males, 69 females, median age 50 years, range 6-83 years). Patients had VWD3 (10), VWD2A (19), VWD2B (25), VWD2M (10) and DDAVP-unresponsive VWD1 (56) and a median bleeding severity score of 8 (range 0-27). A total of 114 bleeding episodes in 55 cases and 131 surgical procedures in 85 cases could be analysed. Excellent-good clinical responses were seen in 97% of bleeding episodes and in 99% of surgical procedures. To prevent recurrent gastrointestinal (GI) bleeding, cerebral (CNS) haemorrhage, haemarthroses, urogenital or multisite bleeding in more severe patients, secondary prophylaxis was also carried out in 15 cases with VWD3 (3), VWD2A (3), VWD2B (2), VWD1 (7). A median dose of 42 IU VWF:RCo kg(-1) given every other day or twice a week over a median period of 334 days (range 24-799) prevented bleeding completely in 13 cases and reduced its incidence in the remaining two. These results confirm the efficacy and safety of the study concentrates, not only in the management of bleeding and surgery but also in secondary prophylaxis of severe VWD.