The FRESH Study: Treatment of Intracranial Aneurysms with the New FRED X Flow Diverter with Antithrombotic Surface Treatment Technology-First Multicenter Experience in 161 Patients.

BACKGROUND AND PURPOSE: Flow diverters with antithrombotic coatings are increasingly used to improve the safety of flow diverter treatments of intracranial aneurysms. This study aimed to investigate the safety and short-term efficacy of the new FRED X flow diverter. MATERIALS AND METHODS: Medical charts and procedural and imaging data of a consecutive series of patients with intracranial aneurysms who were treated with the FRED X at 9 international neurovascular centers were retrospectively analyzed. RESULTS: One hundred sixty-one patients (77.6% women; mean age, 55 years) with 184 aneurysms (11.2% acutely ruptured) were included in this study. Most aneurysms were located in the anterior circulation (77.0%), most frequently at the ICA (72.7%). The FRED X was successfully implanted in all procedures. Additional coiling was performed in 29.8%. In-stent balloon angioplasty was necessary in 2.5%. The rate of major adverse events was 3.1%. Thrombotic events occurred in 7 patients (4.3%) with 4 intra- and 4 postprocedural in-stent thromboses, respectively (1 patient had both peri- and postprocedural thrombosis). Of these thrombotic events, only 2 (1.2%) led to major adverse events (ischemic strokes). Postinterventional neurologic morbidity and mortality were observed in 1.9% and 1.2%, respectively. The rate of complete aneurysm occlusion after a mean follow-up of 7.0 months was 66.0%. CONCLUSIONS: The new FRED X is a safe and feasible device for aneurysm treatment. In this retrospective multicenter study, the rate of thrombotic complications was low, and the short-term occlusion rates are satisfactory.

Learning Curve for Flow Diversion of Posterior Circulation Aneurysms: A Long-Term International Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Flow diversion has gradually become a standard treatment for intracranial aneurysms of the anterior circulation. Recently, the off-label use of the flow diverters to treat posterior circulation aneurysms has also increased despite initial concerns of rupture and the suboptimal results. This study aimed to explore the change in complication rates and treatment outcomes across time for posterior circulation aneurysms treated using flow diversion and to further evaluate the mechanisms and variables that could potentially explain the change and outcomes. MATERIALS AND METHODS: A retrospective review using a standardized data set at multiple international academic institutions was performed to identify patients with ruptured and unruptured posterior circulation aneurysms treated with flow diversion during a decade spanning January 2011 to January 2020. This period was then categorized into 4 intervals. RESULTS: A total of 378 procedures were performed during the study period. Across time, there was an increasing tendency to treat more vertebral artery and fewer large vertebrobasilar aneurysms (P = .05). Moreover, interventionalists have been increasingly using fewer overlapping flow diverters per aneurysm (P = .07). There was a trend toward a decrease in the rate of thromboembolic complications from 15.8% in 2011-13 to 8.9% in 2018-19 (P = .34). CONCLUSIONS: This multicenter experience revealed a trend toward treating fewer basilar aneurysms, smaller aneurysms, and increased usage of a single flow diverter, leading to a decrease in the rate of thromboembolic and hemorrhagic complications.

A Rare and Successfully Managed Complication of Stem Cell Transplantation in an Adult Patient With Sickle Cell Disease: Bone Marrow Necrosis.

Sickle cell disease is the most common genetic disorder in the Eastern Mediterranean region where our transplant center is located. Today, adult patients with sickle cell disease can also be successfully treated with allogeneic hematopoietic stem cell transplantation. Bone marrow necrosis is a rare and serious clinical condition. Herein, we present this complication for the first time in the literature, which developed in the course of allogeneic hematopoietic stem cell transplantation and was successfully managed with additional bone marrow support. The recognition, prevention, and management of this rare and potentially fatal complication, bone marrow necrosis, are vitally important, especially in regions with high prevalence of sickle cell disease.

Treatment of Ruptured Blister-Like Aneurysms with the FRED Flow Diverter: A Multicenter Experience.

BACKGROUND AND PURPOSE: Treatment of ruptured blister-like aneurysms is technically challenging. This study aimed at analyzing the safety and efficacy of the Flow-Redirection Endoluminal Device (FRED) in the treatment of ruptured blister-like aneurysms. MATERIALS AND METHODS: In a retrospective multicenter study, all patients treated with the FRED due to a ruptured intracranial blister-like aneurysm between January 2013 and May 2019 were analyzed. The primary end points for clinical safety were mRS 0-2 at 6 months after treatment and the absence of major ipsilateral stroke or death. The primary end points for efficacy were the absence of rebleeding after treatment and complete angiographic occlusion according to the O'Kelly-Marotta classification at 6 months after treatment. RESULTS: In total, 30 patients with 30 ruptured blister-like aneurysms were treated. Immediate complete aneurysm obliteration (O'Kelly-Marotta classification D) with the FRED was achieved in 10 patients (33%). Of the 26 patients with follow-up, complete obliteration was achieved in 21 patients (80%) after 6 months and in 24 patients (92%) in the final follow-up (median, 22 months). Twenty-three patients (77%) achieved mRS 0-2 at 6 months. Major stroke or death occurred in 17%. Two patients died due to pneumonia, and 2 patients died due to infarction following cerebral vasospasm. There was no case of rebleeding after FRED implantation. There was 1 case of delayed asymptomatic stent occlusion. CONCLUSIONS: Treatment of ruptured blister-like aneurysms with the FRED is safe and effective.

The FRED for Cerebral Aneurysms of the Posterior Circulation: A Subgroup Analysis of the EuFRED Registry.

BACKGROUND AND PURPOSE: Flow diversion for the posterior circulation remains a promising treatment option for selected posterior circulation aneurysms. The Flow-Redirection Intraluminal Device (FRED) system has not been previously assessed in a large cohort of patients with posterior circulation aneurysms. The purpose of the present study was to assess safety and efficacy of FRED in this location. MATERIALS AND METHODS: Consecutive patients with posterior circulation aneurysms treated at 8 centers participating in the European FRED study (EuFRED) between April 2012 and January 2019 were retrospectively reviewed. Complication and radiographic and functional outcomes were evaluated. RESULTS: Eighty-four patients (median age, 54 years) with 84 posterior circulation aneurysms were treated with the FRED. A total of 25 aneurysms (29.8%) had previously ruptured, even though most aneurysms were diagnosed incidentally (45.2%). The intradural vertebral artery was the most common location (50%), and saccular, the most common morphology (40.5%). The median size was 7 mm. There were 8 (9.5%) symptomatic thromboembolic and no hemorrhagic complications. Thromboembolic complications occurred mostly (90.9%) in nonsaccular aneurysms. On last follow-up at a median of 24 months, 78.2% of aneurysms were completely occluded. Functional outcome at a median of 27 months was favorable in 94% of patients. All mortalities occurred in patients with acute subarachnoid hemorrhage and its sequelae. CONCLUSIONS: The largest cohort of posterior circulation aneurysms treated with the FRED to date demonstrated favorable safety and efficacy profiles of the device for this indication. Treatment in the setting of acute subarachnoid hemorrhage was strongly related to mortality, regardless of whether procedural complications occurred.

The diagnostic value of quantitative texture analysis of conventional MRI sequences using artificial neural networks in grading gliomas.

AIM: To explore the value of quantitative texture analysis of conventional magnetic resonance imaging (MRI) sequences using artificial neural networks (ANN) for the differentiation of high-grade gliomas (HGG) and low-grade gliomas (LGG). MATERIALS AND METHODS: A total of 181 patients, 97 with HGG (53.5%) and 84 with LGG (46.5%) with brain MRI having T2-weighted (W) fluid attenuation inversion recovery (FLAIR), and contrast-enhanced T1W images were enrolled in the present study. Histogram parameters and high-order texture features were extracted using manually placed regions of interest (ROIs) on T2W-FLAIR and contrast-enhanced T1W images covering the whole volume of the tumours. The reproducibility of the features was assessed by interobserver reliability analyses. The cohort was divided into training (n=121) and test partitions (n=60). The training set was used for attribute selection and model development, and the test set was used to evaluate the diagnostic performance of the pre-trained ANNs in discriminating HGG and LGG. RESULTS: In the test cohort, the ANN models using texture data of T2W-FLAIR and contrast-enhanced T1W images achieved an area under the receiver operating characteristic curve (AUC) of 0.87 and 0.86, respectively. The combined ANN model with selected texture features achieved the highest diagnostic accuracy equating 88.3% with an AUC of 0.92. CONCLUSIONS: Quantitative texture analysis of T2W-FLAIR and contrast-enhanced T1W enhanced by ANN can accurately discriminate HGG from LGG and might be of clinical value in tailoring the management strategies in patients with gliomas.

Intracranial Serpentine Aneurysms: Spontaneous Changes of Angiographic Filling Pattern.

BACKGROUND AND PURPOSE: Serpentine aneurysms are partially thrombosed aneurysms with an eccentrically located tortuous intra-aneurysmal vascular channel. The large size, distinctive neck anatomy, and supply of the brain parenchyma by the outflow tract pose technical challenges in treatment. The aim of this study was to discuss the endovascular treatment results and illustrate the dynamic nature of serpentine aneurysms. Spontaneous transformation of saccular and fusiform aneurysms into serpentine morphology, along with a case of serpentine-into-fusiform aneurysm transformation during follow-up, is presented. MATERIALS AND METHODS: A retrospective analysis from 3 institutions revealed 15 patients with serpentine aneurysms who underwent diagnostic evaluation and endovascular treatment. Nine of the 15 patients underwent endovascular occlusion of the parent vessel with detachable balloon or coils. Six of the 15 patients underwent aneurysm and parent artery occlusion with coiling. RESULTS: In 11 patients, improvement or resolution of symptoms was achieved by an endovascular approach without any treatment-related morbidity. Morbidity related to treatment in the immediate postoperative period was seen in 3 patients, with resolution of the deficits at long-term follow-up in 2 patients and persistence of a mild deficit in 1 patient. Endovascular treatment failed to achieve resolution of symptoms in a case with a basilar tip aneurysm treated by aneurysm coiling. CONCLUSIONS: Serpentine aneurysms are dynamic structures with spontaneous transformation possible from a saccular or fusiform shape into a serpentine configuration. An endovascular approach by parent vessel occlusion or intra-aneurysmal occlusion is a successful treatment technique for serpentine aneurysms.

European Multicenter Study for the Evaluation of a Dual-Layer Flow-Diverting Stent for Treatment of Wide-Neck Intracranial Aneurysms: The European Flow-Redirection Intraluminal Device Study.

BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow-diverting stents represents a widely accepted technique for the treatment of complex intracranial aneurysms. This European registry study analyzed the initial experience of 15 neurovascular centers with the Flow-Redirection Intraluminal Device (FRED) system. MATERIALS AND METHODS: Consecutive patients with intracranial aneurysms treated with the FRED between February 2012 and March 2015 were retrospectively reviewed. Complications and adverse events, transient and permanent morbidity, mortality, and occlusion rates were evaluated. RESULTS: During the defined study period, 579 aneurysms in 531 patients (median age, 54 years; range, 13-86 years) were treated with the FRED. Seven percent of patients were treated in the acute phase (≤3 days) of aneurysm rupture. The median aneurysm size was 7.6 mm (range, 1-36.6 mm), and the median neck size 4.5 mm (range, 1-30 mm). Angiographic follow-up of >3 months was available for 516 (89.1%) aneurysms. There was progressive occlusion witnessed with time, with complete occlusion in 18 (20%) aneurysms followed for up to 90 ± 14 days, 141 (82.5%) for 180 ± 20 days, 116 (91.3%) for 1 year ± 24 days, and 122 (95.3%) aneurysms followed for >1 year. Transient and permanent morbidity occurred in 3.2% and 0.8% of procedures, respectively. The overall mortality rate was 1.5%. CONCLUSIONS: This retrospective study in real-world patients demonstrated the safety and efficacy of the FRED for the treatment of intracranial aneurysms. In most cases, treatment with a single FRED resulted in complete angiographic occlusion at 1 year.

Multicenter Experience with FRED Jr Flow Re-Direction Endoluminal Device for Intracranial Aneurysms in Small Arteries.

BACKGROUND AND PURPOSE: Flow diverters are emerging as an endovascular treatment alternative for proximally located intracranial aneurysms. However, treatment of aneurysms at and beyond the circle of Willis is not well-established. We assessed the clinical safety and efficacy of the Flow Re-Direction Endoluminal Device Jr (FRED Jr) dedicated to small-vessel diameters between 2.0 and 3.0 mm. MATERIALS AND METHODS: This was a multicenter observational clinical study of 42 patients with 47 aneurysms treated by a flow-direction technique with the FRED Jr. The primary end point for clinical safety was the absence of death, major or minor stroke, and TIA. The primary end point for treatment efficacy was complete and near-complete occlusion according to the O'Kelly-Marotta grading scale at follow-up after 1, 6, and 12 months. RESULTS: The FRED Jr deployment was technically successful in all cases. In 39/42 (93%) patients, the primary safety end point was reached; in the 3 remaining patients, 1 disabling ischemic stroke, 1 minor stroke with complete recovery at discharge, and 1 TIA were observed. Two asymptomatic, completely reversible side-branch occlusions occurred. Angiographic (DSA or flat panel CT) and clinical follow-up were available after 1 month in 41/47 (87%), 6 months in 27/47 (57%), and 12 months in 11/47 (23%) aneurysms. The primary efficacy end point was reached at 1 month in 27/41 (66%), at 6 months in 21/27 (78%), and at 12 months in 11/11 (100%) aneurysms. CONCLUSIONS: Deployment of the FRED Jr is safe and effective in the treatment of intracranial aneurysms located in small vessels.

Neuroimaging and clinical characterization of Sotos syndrome.

Sotos syndrome is a well-known overgrowth syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability. This disorder is caused by mutations or deletions in NSD1 gene. The aim of this study is to examine the relationship between the neuroimaging and clinical features of children with Sotos syndrome. Six Turkish children with Sotos syndrome were followed up about 3-7 years. The diagnosis was confirmed with molecular genetic analysis. We identified the pathogenic NSD1 mutation including three novel in all patients. All the patients had a characteristic facial gestalt of Sotos syndrome consisting of triangular face with prominent forehead, frontoparietal sparseness of hair and small nose. However, the degree of psychomotor and intellectual development was variable. Severe learning defect and speech delay were remarkable in two patients. The neuroimaging analysis showed abnormalities in four of six patients including bilateral large ventricles, thinning of the corpus callosum and persistent cavum septum pellucidum et vergae. Typical craniofacial appearance is the primary finding for the diagnosis of the disease even in the infantile period. However, the degree of psychomotor and intellectual development is very variable and does not correlate with the neuroimaging findings.

Successful treatment of aortic rupture with endovascular stent grafting in a patient with mantle cell lymphoma.

PURPOSE: To present a case of spontaneous aortic rupture in the course of mantle cell lymphoma and successful management with endovascular repair. CASE REPORT: A 69-year-old woman presented with a cervical mass. The patient was found to have stage IIIA and Mantle Cell Lymphoma International Prognostic Index (MIPI) 4. She was placed in an intermediate-risk group. The patient received an initial cycle of systemic chemotherapy consisting of rituximab, anthracycline, vincristine and methyl prednisolone. During follow-up, she developed abdominal aortic rupture secondary to intramural hematoma which was successfully managed with endovascular exclusion. CONCLUSION: Hemodynamic changes can be seen during the course of lymphoma subsequent to systemic chemotherapy. These changes might be related to the spontaneous rupture of the main vessels. Endovascular repair may be a more appropriate treatment option than open surgery, especially in a patient with multiple comorbidities.

Kaposi's Sarcoma following Chronic Lymphocytic Leukemia: A Rare Entity.

Cutaneous manifestations can occur in the wide range of internal malignancy. They can occur by metastases or local spread, direct infiltration, or a site of primary malignancy itself. Sometimes these manifestations are related with an underlying malignancy but they do not contain malignant cells as paraneoplastic dermatological syndromes. Chronic lymphocytic leukemia (CLL) is the most common leukemia all over the world. Cutaneous lesions occur in up to 25% of patients. Most commonly seen cutaneous lesions in CLL are those of infectious or hemorrhagic origin. Skin cancer risk was also increased eightfold in CLL when compared with normal population, so cutaneous lesions in CLL can be the first manifestation of secondary skin malignancy. Herein, we report an interesting case of Kaposi's sarcoma which was diagnosed during the course of CLL.

Primary adrenal non-Hodgkin's lymphoma: report of two cases.

Primary adrenal lymphoma is very rare. It is characterized by a high incidence of bilateral adrenal involvement of diffuse large B-cell lymphoma. It can be diagnosed with endocrine evaluation, imaging studies and histopathological examination. We present two cases of primary adrenal lymphoma. One is a 74-year-old female patient with right primary adrenal lymphoma and the other is a 62-year-old male patient with bilateral primary adrenal lymphoma associated with normal adrenal function. In both cases, radiological features led to an initial misdiagnosis. The surgical exploration demonstrated masses invading the retroperitoneal space, and the biopsy revealed diffuse large B-cell lymphoma. In conclusion, primary adrenal lymphoma should be kept in mind in the differential diagnosis of adrenal masses. In cases of suspicious primary adrenal lymphoma, percutaneous computerized tomography or ultrasonography-guided needle biopsy can help to avoid unnecessary surgeries.

Immunohistochemical prognostic criteria in xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare inheritable disease characterized by severe sun sensitivity and early development of skin cancers. We compared the expression of cell proliferation markers and cell cycle checkpoint regulators in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) from patients with and without XP. Immunostaining for p53, Ki-67, and proliferating cell nuclear antigen (PCNA) was determined in SCCs and BCCs from 18 XP patients and 30 controls. Nine of the 18 XP patients had SCC and BCC, and the other nine had only SCC. In the control group, 15 moderately differentiated SCCs and 15 BCCs were evaluated. Expressions of p53, Ki-67 and PCNA in XP and non-XP patients were assessed statistically by using the Chi-square method. Expression of Ki-67 and PCNA was found to be greater in SCC from XP patients than controls (P = 0.021 and P = 0.033, respectively). Expression of PCNA and p53 by BCCs was greater in XP patients (P < 0.001 and P = 0.027, respectively). There was a significant difference in Ki-67 (P < 0.001) and PCNA (P = 0.001) expression between the lesions of the XP patients who died during the follow up and XP patients who survived. In XP patients, SCCs with more than 10% Ki-67 expression and %50 PCNA expression have a poor prognosis. Our results suggest that increased Ki-67 and PCNA expression may be a predictor for recurrence of nonmelanocytic skin cancer and a poor prognosis.

Intrathecal gadolinium-enhanced MR cisternography in the evaluation of CSF leakage.

BACKGROUND AND PURPOSE: Radiologic identification of the location of the CSF leakage is important for proper surgical planning and increases the chance of dural repair. This article describes our experience in analyzing clinically suspected cranial CSF fistulas by using MR imaging combined with the intrathecal administration of a gadolinium-based contrast agent. MATERIALS AND METHODS: A total of 85 consecutive patients with suspected CSF fistulas who presented with persistent or intermittent rhinorrhea or otorrhea lasting for more than 1 month between 2003 and 2007 were included in this study. RESULTS: We observed objective CSF leakage in 64 of 85 patients (75%). The CSF leak was located in the ethmoidal region in 37 patients (58%), in the superior wall of the sphenoid sinus in 8 patients (13%), in the posterior wall of the frontal sinus in 10 patients (15%), in the superior wall of the mastoid air cells in 6 patients (9%), and from the skull base into the infratemporal fossa in 1 patient (2%). Two patients (3%) showed leakage into >1 paranasal sinus. CONCLUSIONS: MR cisternography after the intrathecal administration of gadopentate dimeglumine represents an effective and minimally invasive method for evaluating suspected CSF fistulas along the skull base. It provides multiplanar capabilities without risk of radiation exposure and is an excellent approach to depict the anatomy of CSF spaces and CSF fistulas.

Detecting methylation patterns of p16, MGMT, DAPK and E-cadherin genes in multiple myeloma patients.

Multiple myeloma (MM) is a B-cell neoplasia characterized by the clonal proliferation of plasma cells. Besides known genetic abnormalities, epigenetic changes are also known to effect MM pathogenesis. DNA methylation is an epigenetic mechanism that silences genes by adding methyl groups to cytosine-guanine dinucleotides at the promoter regions. In this study, the methylation status of four genes; p16, O6-methyl guanine DNA methyl transferase (MGMT), death-associated protein kinase (DAPK) and E-cadherin (ECAD); at the time of diagnosis was investigated using methylation-specific polymerase chain reaction (MS-PCR). In the 20 cases studied; methylation of the promoter regions of p16, MGMT, DAPK and ECAD genes was detected in 10%, 40%, 10% and 45% of the cases, respectively. In 65% (13/20) of cases, at least one of the genes studied had promoter methylation; while 35% of cases (7/20) had methylated promoters of more than one gene. There was a significant correlation between promoter hypermethylation of MGMT and the presence of extramedullary involvement; but for the other genes no correlation was found regarding disease properties like age, disease stage, clinical course and the presence of lytic bone lesions. Determining the methylation profiles of genes in MM, could lead to a new understanding of the disease pathogenesis and guide the assessment of treatment options.

Extramedullary plasmacytoma of the septum.

PROBLEM: Extramedullary plasmacytoma of the head and neck is a rare neoplasm characterized by monoclonal proliferation of plasma cells. The nasal cavity and nasal septum are the most common sites of occurrence and the neoplasm can be solitary or multiple. Extramedullary plasmacytoma is associated with the initial appearance of multiple myeloma and may precede overt manifestations of systemic disease by months or years. METHODOLOGY: A seventy-year-old female presented to our clinic with a one-month history of nasal obstruction. We performed a systematic approach to diagnosis using clinical, laboratory, and radiologic investigations in order to exclude systemic involvement. RESULTS: The patient was diagnosed with extramedullary plasmacytoma and the mass was excised completely via transnasal endoscopy. CONCLUSION: Extramedullary plasmacytoma of the nasal cavity is rare and should be considered in the differential diagnosis of nasal cavity masses.