Treatment of ruptured aneurysms of the choroidal collateral system in moyamoya disease: a systematic review and data analysis.

OBJECTIVE: Moyamoya disease (MMD) is a chronic, progressive steno-occlusive condition of the distal internal carotid arteries of unknown etiology. Collateral arterial networks typically develop in MMD, bypassing the steno-occlusion. Aneurysms arising on the collateral networks are a known source of hemorrhage. The choroidal collateral system is the most common location for collateral pathway aneurysms in MMD and associated hemorrhage. The authors performed data collection and analysis to further elucidate the best treatment approaches for ruptured aneurysms of the choroidal collateral system in MMD, which as yet remain unclear. METHODS: A comprehensive data collection and analysis of case reports and case series with ruptured choroidal collateral artery aneurysms (CCAAs) was performed. PRISMA guidelines for systematic reviews were followed and the Medline, Embase, and Scopus databases were searched for relevant studies. A database was created including patients with ruptured CCAA in MMD. Original data from case series were included whenever possible. A previously unreported case of a ruptured choroidal artery aneurysm in MMD treated by the authors was also included. RESULTS: The database comprised 72 patients with ruptured CCAA in MMD. The most common clinical symptoms were headache, nausea, and vomiting (39%). Initially, a conservative treatment approach was chosen in 29% of cases but led to rehemorrhage in 40% of cases; 63% of these rehemorrhages occurred during the first 35 days. Endovascular treatment seemed a safe option for aneurysm exclusion, mainly through parent vessel sacrifice, but had a treatment failure rate of 21%, due to inadequate access. Aneurysm treatment with revascularization as the initial treatment strategy led to aneurysm regression in 82% with no reported rehemorrhage. Aneurysm exclusion through open surgery was effective but was associated with a relatively high complication rate (25%). Outcome after rupture of CCAA was poor, with 41% of patients deceased or permanently disabled. Overall, patient outcomes were better in the endovascular and revascularization treatment group than in the conservative treatment group. CONCLUSIONS: Rupture of CCAA in MMD is associated with high morbidity and rerupture rate requiring urgent treatment.

When the fat hits the brain-salvage STA-MCA bypass for an intracranial ICA occlusion due to a fat embolus.

BACKGROUND: Large fat embolus is a rare but potential reversible cause of ischaemic stroke. METHODS AND RESULTS: We describe the neurosurgical management of a complete right internal carotid artery occlusion due to a large fat embolus, caused by a mitral valve replacement. CONCLUSION: Knowledge of acute cerebral ischaemia due to large fat embolism and its hallmark 'hypodense artery' is mandatory. Extracranial to intracranial bypass is a feasible rescue treatment after failure of endovascular embolectomy.

Risk of First Hemorrhage of Brain Arteriovenous Malformations During Pregnancy: A Systematic Review of the Literature.

BACKGROUND: Recommendations on the management of brain arteriovenous malformations (bAVM) with respect to pregnancy are based upon conflicting literature. OBJECTIVE: To systematically review the reported risk and annualized rate of first intracranial hemorrhage (ICH) from bAVM during pregnancy and puerperium. METHODS: MEDLINE, EMBASE, and Scopus databases were searched for relevant articles in English published before April 2018. Studies providing a quantitative risk of ICH in bAVM during pregnancy were eligible. RESULTS: From 7 initially eligible studies, 3 studies met the criteria for providing quantitative risk of first ICH bAVM during pregnancy. Data from 47 bAVM ICH during pregnancy across 4 cohorts were extracted for analysis. Due to differences in methodology and definitions of exposure period, it was not appropriate to combine the cases. The annualized risk of first ICH during pregnancy for these 4 cohorts was 3.0% (95% confidence interval [CI]: 1.7-5.2%); 3.5% (95% CI: 2.4-4.5%); 8.6% (95% CI: 1.8-25%); and 30% (95% CI: 18-49%). Only the last result from the last cohort could be considered significantly increased in comparison with the nonpregnant period (relative rate 6.8, 95% CI: 3.6-13). The limited number of eligible studies and variability in results highlighted the need for enhanced rigor of future research. CONCLUSION: There is no conclusive evidence of an increased risk of first hemorrhage during pregnancy from bAVM. Because advice to women with bAVM may influence the management of pregnancy or bAVM with significant consequences, we believe that a retrospective multicenter, case crossover study is urgently required.

Laminar Wall Shear Stress in Brain Arteriovenous Malformations: Systematic Review of Literature.

BACKGROUND: Laminar wall sheer stress (LWSS) modulates inflammatory activity of the endothelium and may be a contributing factor in many cerebrovascular pathologies. There is a lack of consensus whether significant differences in LWSS exist between feeding vessels in brain arteriovenous malformation (bAVM) and healthy vessels. A systematic review of LWSS research in bAVM was undertaken, including the methods used and the assumptions made in determining LWSS. METHODS: Ovid MEDLINE, EMBASE, and Scopus electronic databases were systematically searched from inception for articles calculating LWSS in bAVM cases. LWSS values were extracted for comparison between ipsilateral bAVM feeding arteries and healthy contralateral vessels or healthy normative data. RESULTS: Three retrospective cohort studies were identified, reporting on 42 adult and pediatric bAVM cases. Mean LWSS (mLWSS) in healthy vessels (contralateral vessels or normative controls) typically ranged from 1.2-2.7 Pa, while mLWSS values in untreated bAVM feeding arteries typically ranged from 1.6-3.6 Pa. All studies had mixed cohorts of ruptured and unruptured cases, obscuring the relationship between LWSS and bAVM history. CONCLUSIONS: mLWSS values in healthy arteries and bAVM feeding vessels tend to be low and overlapping. Further research of high scientific and methodologic quality is necessary to improve understanding of how LWSS hemodynamics relate to bAVM formation, rupture, and treatment.

De novo brain arteriovenous malformation after tumor resection: case report and literature review.

The congenital origin of brain arteriovenous malformations (bAVMs) has been increasingly challenged by reports of de novo bAVMs in patients previously confirmed to have no vascular malformation. We describe the oldest patient reported in the English language literature harboring a de novo bAVM. An uneventful frontal convexity meningioma resection was performed for a 60-year-old woman, and at 67 years of age, a bAVM was detected by MRI and confirmed by digital subtraction angiography at the site of the previous meningioma resection. This case adds to the growing literature that the etiology of bAVMs is most likely multifactorial.

An Interleukin 13 Polymorphism Is Associated with Symptom Severity in Adult Subjects with Ever Asthma.

Different genes are associated with categorical classifications of asthma severity. However, continuous outcomes should be used to catch the heterogeneity of asthma phenotypes and to increase the power in association studies. Accordingly, the aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) in candidate gene regions and continuous measures of asthma severity, in adult patients from the general population. In the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (www.geird.org), 326 subjects (aged 20-64) with ever asthma were identified from the general population in Verona (Italy) between 2007 and 2010. A panel of 236 SNPs tagging 51 candidate gene regions (including one or more genes) was analysed. A symptom and treatment score (STS) and pre-bronchodilator FEV1% predicted were used as continuous measures of asthma severity. The association of each SNP with STS and FEV1% predicted was tested by fitting quasi-gamma and linear regression models, respectively, with gender, body mass index and smoking habits as potential confounders. The Simes multiple-test procedure was used for controlling the false discovery rate (FDR). SNP rs848 in the IL13 gene region (IL5/RAD50/IL13/IL4) was associated with STS (TG/GG vs TT genotype: uncorrected p-value = 0.00006, FDR-corrected p-value = 0.04), whereas rs20541 in the same gene region, in linkage disequilibrium with rs848 (r(2) = 0.94) in our sample, did not reach the statistical significance after adjusting for multiple testing (TC/CC vs TT: uncorrected p-value = 0.0003, FDR-corrected p-value = 0.09). Polymorphisms in other gene regions showed a non-significant moderate association with STS (IL12B, TNS1) or lung function (SERPINE2, GATA3, IL5, NPNT, FAM13A) only. After adjusting for multiple testing and potential confounders, SNP rs848 in the IL13 gene region is significantly associated with a continuous measure of symptom severity in adult subjects with ever asthma.

IGF-I induces upregulation of DDR1 collagen receptor in breast cancer cells by suppressing MIR-199a-5p through the PI3K/AKT pathway.

Discoidin Domain Receptor 1 (DDR1) is a collagen receptor tyrosine-kinase that contributes to epithelial-to-mesenchymal transition and enhances cancer progression. Our previous data indicate that, in breast cancer cells, DDR1 interacts with IGF-1R and positively modulates IGF-1R expression and biological responses, suggesting that the DDR1-IGF-IR cross-talk may play an important role in cancer. In this study, we set out to evaluate whether IGF-I stimulation may affect DDR1 expression. Indeed, in breast cancer cells (MCF-7 and MDA-MB-231) IGF-I induced significant increase of DDR1 protein expression, in a time and dose dependent manner. However, we did not observe parallel changes in DDR1 mRNA. DDR1 upregulation required the activation of the PI3K/AKT pathway while the ERK1/2, the p70/mTOR and the PKC pathways were not involved. Moreover, we observed that DDR1 protein upregulation was induced by translational mechanisms involving miR-199a-5p suppression through PI3K/AKT activation. This effect was confirmed by both IGF-II produced by cancer-associated fibroblasts from human breast cancer and by stable transfection of breast cancer cells with a human IGF-II expression construct. Transfection with a constitutively active form of AKT was sufficient to decrease miR-199a-5p and upregulate DDR1. Accordingly, IGF-I-induced DDR1 upregulation was inhibited by transfection with pre-miR-199a-5p, which also impaired AKT activation and cell migration and proliferation in response to IGF-I. These results demonstrate that, in breast cancer cells, a novel pathway involving AKT/miR-199a-5p/DDR1 plays a role in modulating IGFs biological responses. Therefore, this signaling pathway may represent an important target for breast cancers with over-activation of the IGF-IR axis.

Treatment of a cerebral pial arteriovenous fistula in a patient with sickle cell disease-related moyamoya syndrome: case report.

Sickle cell disease (SCD) is an autosomal recessive hematological disorder, characterized by sickling of the red blood cells in response to a hypoxic stress and vaso-occlusive crises. It is associated with moyamoya-like changes on cerebral angiographic imaging in 43% of patients. Cerebral aneurysms, arteriovenous malformations, and dural arteriovenous fistulas (AVFs) have been described in association with SCD and moyamoya disease. However, the description of a pial AVF (pAVF) in a patient with SCD and/or moyamoya formation has not yet been reported. The authors present the case of a 15-year-old boy with SCD-associated moyamoya disease harboring a pAVF who developed a de novo venous aneurysm 8 months after undergoing indirect superficial temporal artery-middle cerebral artery (MCA) bypass that was complicated by bilateral ischemia of the MCA territory. The pAVF was successfully treated with transarterial embolization using Onyx. The authors describe the possible pathophysiological mechanisms and management strategies for this rare occurrence.

Cerebral sparganosis: case report and review of the European cases.

Sparganosis is a severe parasitic infection caused by the larvae of Spirometra mansoni, also called "sparganum." In human hosts, the Spirometra mansoni larva commonly targets the subcutaneous tissue or muscle. Sometimes it can also migrate into the brain, resulting in cerebral sparganosis, mainly characterized by focal neurological symptoms such as seizures and radiological "wandering lesions" on magnetic resonance images (MRIs). Clinical cases of cerebral sparganosis have been reported worldwide, mainly in Asian countries, but also in North America, South America and Australia. Only two cases have been previously reported in Europe. A 29-year-old male from Bolivia, who lived in Spain, presented to our service for seizures and a multicystic brain lesion, initially suspected to be a dysembryoplastic neuroepithelial tumor (DNET). He underwent gross total resection of the mixed solid/cystic lesion. Pathology revealed gliosis, multiple interconnected cystic cavities with fibrous walls, inflammatory cell infiltration and no necrotizing granulomatous reaction. Inside the cavities, a parasitic form was identified as the larva of the cestode Spirometra mansoni. At 1-year follow-up, the patient had no deficits and was seizure free. Clinicians should be alerted to the possible existence of this rare entity in Europe, especially in patients from endemic areas with a possible infection history as well as "wandering lesions" on the MRI.

Herpes simplex reactivation or postinfectious inflammatory response after epilepsy surgery: Case report and review of the literature.

BACKGROUND: Herpes simplex virus encephalitis (HSVE) is the most morbid clinical syndrome associated with the human herpes virus. Despite treatment with appropriate dosages of acyclovir, neurologic relapse of HSV infection have been reported after cranial surgery. Rarely, neurological deterioration due to postinfectious inflammatory response without demonstrable HSV reactivation may recur following cranial surgery. CASE DESCRIPTION: We report a case of a 17-year-old girl who presented with a HSVE relapse on the 6(th) postoperative day following resective surgery for medically refractory epilepsy and review the literature. Postinfectious inflammatory reaction may be the underlying mechanism in cases with no HSV identified on cerebrospinal fluid (CSF) or brain polymerase chain reaction (PCR), such as in the current case. CONCLUSION: HSVE must be suspected in patients with previous history of HSVE and postoperative fever associated with an altered state of consciousness and/or seizures. Considering the high mortality and morbidity rates associated with HSVE, an adequate prophylactic administration of acyclovir should be considered for patients with previous history of HSVE undergoing neurosurgical procedures, especially when surgery involves the site of a previous herpetic lesion.

Cognitive correlates in amyotrophic lateral sclerosis: a population-based study in Italy.

BACKGROUND: There is less data available regarding the characteristics of cognitive impairment in patients with amyotrophic lateral sclerosis (ALS) in a population-based series. METHODOLOGY: Patients with ALS incident in Piemonte, Italy, between 2009 and 2011 underwent an extensive neuropsychological battery. Cognitive status was classified as follows: normal cognition, frontotemporal dementia (ALS-FTD), executive cognitive impairment (ALS-ECI), non-executive cognitive impairment (ALS-NECI), behavioural impairment (ALS-Bi), non-classifiable cognitive impairment. We also assessed 127 age-matched and gender-matched controls identified through patients' general practitioners. RESULTS: Out of the 281 incident patients, 207 (71.9%) underwent the neuropsychological testing; of these, 19 were excluded from the analysis due previous conditions affecting cognition. Ninety-one (49.7%) patients were cognitively normal, 23 (12.6%) had ALS-FTD, 36 (19.7%) ALS-ECI, 10 (5.5%) ALS-NECI, 11 (6.0%) ALS-Bi and 11 (6.0%) non-classifiable cognitive impairment, 1 had comorbid Alzheimer's disease. Patients with ALS-FTD were older, had a lower education level, and had a shorter survival than any other cognitive group. Of the nine cases with C9ORF72 mutation, six had ALS-FTD, two ALS-ECI and one was cognitively normal; one of the five patients with SOD1 mutations and one of the five patients with TARBDP mutations had ALS-Bi. CONCLUSIONS: About 50% of Italian patients with ALS had some degree of cognitive impairment, in keeping with a previous Irish study, despite the largely different genetic background of the two populations. The lower educational attainment in patients with ALS-FTD indicated a possible role of cognitive reserve in ALS-related cognitive impairment. ALS-ECI and ALS-NECI may represent discrete cognitive syndromes in the continuum of ALS and FTD.