A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome

Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents. DOI: http://dx.doi.org/10.7554/eLife.08648.00

Pyogenic brain abscess, ventriculitis and diffuse meningitis with fatal outcome in an adult: Radiologic–pathologic correlation☆,#

Rupture of brain abscesses with evolution into ventriculitis with meningitis may result in sudden and dramatic worsening of the clinical situation. We present a 57-year-old man with such an event and fatal outcome. Multiple imaging modalities including computed tomography and advanced magnetic resonance imaging were correlated with gross specimen and histologic images. The differential diagnosis of multiple lesions with ring enhancement and prominent perifocal edema includes mainly infectious and neoplastic processes, such as brain abscess, metastasis, and multicentric glioblastoma. Pyogenic ventriculitis is an uncommon manifestation of severe intracranial infection that might be clinically obscure. We discuss the characteristic magnetic resonance findings of brain abscess and its complications, including meningitis and ventriculitis with emphasis on the role of diffusion-weighted and fluid-attenuated inversion recovery imaging. Keywords: Brain abscess, Meningitis, Ventriculitis, Diffusion, AIR

Neurofibromatosis Type 2 (NF2) and the Implications for Vestibular Schwannoma and Meningioma Pathogenesis

Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in the NF2 gene, specifically with loss of function in a tumor-suppressor protein that has a number of synonymous names, including: Merlin, Neurofibromin 2, and schwannomin. Merlin is a 70 kDa protein that has 10 different isoforms. The Hippo Tumor Suppressor pathway is regulated upstream by Merlin. This pathway is critical in regulating cell proliferation and apoptosis, characteristics that are important for tumor progression. Mutations of the NF2 gene are strongly associated with NF2 diagnosis, leading to benign proliferative conditions such as vestibular schwannomas and meningiomas. Unfortunately, even though these tumors are benign, they are associated with significant morbidity and the potential for early mortality. In this review, we aim to encompass meningiomas and vestibular schwannomas as they pertain to NF2 by assessing molecular genetics, common tumor types, and tumor pathogenesis

Neurofibromatosis Type 2 (NF2) and the Implications for Vestibular Schwannoma and Meningioma Pathogenesis.

Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in th

Imaging in Neurological Disease of Hospitalized COVID-19 Patients: An Italian Multicenter Retrospective Observational Study

Of 725 consecutive hospitalized patients with coronavirus disease 2019, 108 (15%) had acute neurologic symptoms necessitating neurologic imaging