Cumulative surgical morbidity in patients with multiple cerebellar and medullary hemangioblastomas.

Objective: Patients affected with von Hippel-Lindau disease often develop multiple hemangioblastomas in the cerebellum and spinal cord. Timing of surgical intervention is difficult and depends largely on the anticipated surgical morbidity. However, data regarding surgical outcome after multiple cerebellar and medullary surgeries are scarce.

Von Hippel-Lindau Disease: Current Challenges and Future Prospects.

Understanding of molecular mechanisms of tumor growth has an increasing impact on the development of diagnostics and targeted therapy of human neoplasia. In this review, we summarize the current knowledge on molecular mechanisms and their clinical implications in von Hippel-Lindau (VHL) disease. This autosomal dominant tumor syndrome usually manifests in young adulthood and predisposes affected patients to the development of benign and malignant tumors of different organ systems mainly including the nervous system and internal organs.

Hemangioblastoma and von Hippel-Lindau disease: genetic background, spectrum of disease, and neurosurgical treatment.

Introduction: Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. Children or adults with VHL disease have one of > 300 known germline mutations of the VHL gene located on chromosome 3. They are prone to develop hemangioblastomas, extremely rarely starting at age 6, rarely at age 12-18, and, typically and almost all, as adults.

Predictors of dopamine agonist resistance in prolactinoma patients.

Background: Surgical resection of prolactinomas resistant to dopamine agonists is frequently incomplete due to fibrotic changes of the tumour under pharmacological therapy. In order to identify a subgroup of patients who may benefit from early surgery, we thought to investigate possible predictive factors of pharmacological resistance of prolactinomas to dopamine agonists.

Methods: We retrospectively analyzed a database of a Belgian tertiary reference center for patients with pituitary tumours from 2014 to 2016.

Minimally invasive resection of spinal hemangioblastoma: feasibility and clinical results in a series of 18 patients.

Objective: Hemangioblastomas are benign, highly vascularized tumors that can occur sporadically or as part of von Hippel-Lindau (VHL) disease. Traditionally, spinal hemangioblastomas have been surgically treated via an open approach. In recent years, however, minimally invasive techniques using tubular retractors have been increasingly applied in spine surgery.

Polyglobulia in patients with hemangioblastomas is related to tumor size but not to serum erythropoietin.

Background: Hemangioblastomas are associated with elevated hemoglobin (Hb) levels (polyglobulia), which is associated with a higher risk for cerebral stroke, cardiac infarction and pulmonary embolism. The pathomechanism of polyglobulia remains unclear and different theories have been postulated. Among those are elevated serum erythropoietin (EPO) levels caused by secretion of the tumor or associated tumor cyst.

Posterior approach for anteriorly located cervical spinal cord hemangioblastomas: technical note.

The surgical management of anteriorly located spinal cord hemangioblastomas remains a challenge. Different approaches have been published, of which the anterior approach seems to be the most obvious and commonly used. A posterior approach might be more suitable in certain patients, especially in cases of cystic hemangioblastomas.

Central nervous system gadolinium accumulation in patients undergoing periodical contrast MRI screening for hereditary tumor syndromes.

Background: Patients with hereditary tumor syndromes undergo periodical magnetic resonance imaging (MRI) screening with Gadolinium contrast. Gadolinium accumulation has recently been described in the central nervous system after repeated administrations. The prevalence and rate of accumulation in different subgroups of patients are unknown.

International multicentre validation of the arteriovenous malformation-related intracerebral haemorrhage (AVICH) score.

Objective: The recently published arteriovenous malformation-related intracerebral haemorrhage (AVICH) score showed better outcome prediction for patients with arteriovenous malformation (AVM)-related intracerebral haemorrhage (ICH) than other AVM or ICH scores. Here we present the results of a multicentre, external validation of the AVICH score.

Methods: All participating centres (n=11) provided anonymous data on 325 patients to form the Spetzler-Martin (SM) grade, the supplemented SM (sSM) grade, the ICH score and the AVICH score.

Outcome of Surgical or Endovascular Treatment of Giant Intracranial Aneurysms, with Emphasis on Age, Aneurysm Location, and Unruptured Aneuryms--A Systematic Review and Meta-Analysis.

Background: Designing treatment strategies for unruptured giant intracranial aneurysms (GIA) is difficult as evidence of large clinical trials is lacking. We examined the outcome following surgical or endovascular GIA treatment focusing on patient age, GIA location and unruptured GIA.

Methods: Medline and Embase were searched for studies reporting on GIA treatment outcome published after January 2000.

Characterization of endolymphatic sac tumors and von Hippel-Lindau disease in the International Endolymphatic Sac Tumor Registry.

Background: Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel-Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking.

Methods: Systematic registration of ELSTs from international centers of otorhinolaryngology and from multidisciplinary VHL centers' registries was performed.

VHL-deficient vasculogenesis in hemangioblastoma.

Hemangioblasts are capable of differentiation into vascular structures and blood. Patients with von Hippel-Lindau (VHL) disease develop hemangioblastomas which are composed of VHL-deficient tumor cells with protracted hemangioblastic differentiation potential. In a subset of these tumors, hemangioblastic differentiation is characterized by different stages of red blood cell formation.

Renal cancer in von Hippel-Lindau disease and related syndromes.

Sporadic and hereditary forms of renal cell carcinoma (RCC), von Hippel-Lindau (VHL) disease and the familial paraganglioma syndromes are closely related in terms of their clinical, molecular, and genetic aspects. Most RCCs occur sporadically and the heritable fraction of RCC is estimated to be just 2-4%. An understanding of the molecular genetic basis, the disease-specific and gene-specific biology and the clinical characteristics of these cancer syndromes is of utmost importance for effective genetic diagnosis and appropriate treatment.

Associations of collagen type I α2 polymorphisms with the presence of intracranial aneurysms in patients from Germany.

Objective: Subarachnoid hemorrhage from ruptured intracranial aneurysms is associated with a severe prognosis. Preventive treatment of unruptured intracranial aneurysms is possible and recommended. However, the identification of risk patients by genetic analyses is not possible because of lack of candidate genes.

Autosomal dominant polycystic kidney disease: prevalence of renal neoplasias in surgical kidney specimens.

Background: The role of autosomal dominant polycystic kidney disease (ADPKD) as a risk factor for renal cell carcinoma (RCC) is still under discussion. Data on prevalence of RCC in ADPKD are limited, especially on a large population scale. The aim of this study was to analyze the prevalence of RCC in ADPKD kidneys and characterize the clinical features of this coincidence.

Sequence variations in the von Hippel-Lindau tumor suppressor gene in patients with intracranial aneurysms.

Background: The rupture of intracranial aneurysms leads to subarachnoid hemorrhage, which is often associated with poor outcome. Preventive treatment of unruptured intracranial aneurysms is possible and recommended. However, the lack of candidate genes precludes identifying patients at risk by genetic analyses.

Predictors of severity of cerebral vasospasm caused by aneurysmal subarachnoid hemorrhage.

Background: Cerebral vasospasm is one of the leading causes of poor outcome after aneurysmal subarachnoid hemorrhage. The risk factors for the development of vasospasm have been evaluated in many clinical studies. However, it remains unclear if vasospasm severity can be predicted.

Hemangioblastomas and neurogenic polyglobulia.

Background: Neurogenic polyglobulia occurs with central nervous system hemangioblastomas. Among the suggested mechanisms are extramedullary hematopoiesis in the tumor tissue and germline mutations of the von Hippel-Lindau (VHL) tumor suppressor gene.

Objective: To determine the frequency and driving mechanisms of polyglobulia in central nervous system hemangioblastomas.

Nervous system involvement in von Hippel-Lindau disease: pathology and mechanisms.

Patients with von Hippel-Lindau disease carry a germline mutation of the Von Hippel-Lindau (VHL) tumor-suppressor gene. We discuss the molecular consequences of loss of VHL gene function and their impact on the nervous system. Dysfunction of the VHL protein causes accumulation and activation of hypoxia inducible factor (HIF) which can be demonstrated in earliest stages of tumorigenesis and is followed by expression of VEGF, erythropoietin, nitric oxide synthase and glucose transporter 1 in VHL-deficient tumor cells.

Epidemiology of autosomal-dominant polycystic kidney disease: an in-depth clinical study for south-western Germany.

Background: As we emerge into the genomic medicine era, the epidemiology of diseases is taken for granted. Accurate prevalence figures, especially of rare diseases (RDs, ≤50/100,000), will become even more important for purposes of health care and societal planning. We noticed that the numbers of affected individuals in regionally established registries for mainly hereditary RDs do not align with published estimated and expected prevalence figures.