Heritable and non-heritable uncommon causes of stroke.

Despite intensive investigations, about 30% of stroke cases remains of undetermined origin. After exclusion of common causes of stroke, there is a number of rare heritable and non-heritable conditions, which often remain misdiagnosed, that should be additionally considered in the diagnosis of cryptogenic stroke. The identification of these diseases requires a complex work up including detailed clinical evaluation for the detection of systemic symptoms and signs, an adequate neuroimaging assessment and a careful family history collection.

Correction: The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1-6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7-34 pathogenic variant.

This Article was originally published under Nature Research's License to Publish, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the Article have been modified accordingly.

Views and practices of Australian optometrists regarding driving for patients with central visual impairment.

Background: Eye-care practitioners are often required to make recommendations regarding their patients' visual fitness for driving, including patients with visual impairment. This study aimed to understand the perspectives and management strategies adopted by optometrists regarding driving for their patients with central visual impairment.

Method: Optometrists were invited to participate in an online survey (from April to June 2012).

In-Depth Characterization of Protein Disulfide Bonds by Online Liquid Chromatography-Electrochemistry-Mass Spectrometry.

Disulfide bonds are an important class of protein post-translational modifications, yet this structurally crucial modification type is commonly overlooked in mass spectrometry (MS)-based proteomics approaches. Recently, the benefits of online electrochemistry-assisted reduction of protein S-S bonds prior to MS analysis were exemplified by successful characterization of disulfide bonds in peptides and small proteins. In the current study, we have combined liquid chromatography (LC) with electrochemistry (EC) and mass analysis by Fourier transform ion cyclotron resonance (FTICR) MS in an online LC-EC-MS platform to characterize protein disulfide bonds in a bottom-up proteomics workflow.

APOE ɛ2 is associated with white matter hyperintensity volume in CADASIL.

Apolipoprotein E (APOE) increases the risk for Alzheimer’s disease (ɛ4 allele) and cerebral amyloid angiopathy (ɛ2 and ɛ4), but its role in small vessel disease (SVD) is debated. Here we studied the effects of APOE on white matter hyperintensity volume (WMHV) in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a nonamyloidogenic angiopathy and inherited early-onset form of pure SVD. Four hundred and eighty-eight subjects were recruited through a multicenter consortium.

Characteristic brain magnetic resonance imaging pattern in patients with macrocephaly and PTEN mutations.

We describe an MRI phenotype seen in a series of patients with mutations in PTEN who have clinical features consistent with PTEN hamartoma tumor syndrome (PHTS). Retrospective review of clinical data and MRI was performed in 23 subjects evaluated in four different tertiary care centers with clinical programs in inherited disorders of the white matter. Patients were referred due to abnormal MRI features and abnormal PTEN sequencing was identified.

Ranibizumab is a potential prophylaxis for proliferative vitreoretinopathy, a nonangiogenic blinding disease.

Proliferative vitreoretinopathy (PVR) exemplifies a disease that is difficult to predict, lacks effective treatment options, and substantially reduces the quality of life of an individual. Surgery to correct a rhegmatogenous retinal detachment fails primarily because of PVR. Likely mediators of PVR are growth factors in vitreous, which stimulate cells within and behind the retina as an inevitable consequence of a breached retina.

Air versus gas tamponade in retinal detachment surgery.

Objective: To compare the outcome of air tamponade with gas tamponade in primary vitrectomy for the treatment of rhegmatogenous retinal detachment (RRD).

Methods: We examined the records of 524 cases of 523 patients that underwent primary vitrectomy for RRD with air or sulphur hexafluoride 20% gas tamponade and a follow-up of at least 3 months, excluding cases with inferior retinal breaks.

Results: 318 cases were treated with gas and 128 cases with air.

Variability in photocoagulation treatment of diabetic macular oedema.

Purpose: To establish whether differences in the assessment of diabetic macular oedema (DME) with either optical coherence tomography (OCT) or stereoscopic biomicroscopy lead to variability in the photocoagulation treatment of DME.

Methods: The differences in the assessment of DME with either OCT or stereoscopic biomicroscopy were analysed by calculating the surface areas and the overlap of retinal thickening. Photocoagulation treatment plans of retinal specialists were compared by evaluating the number and location of planned laser spots.

Retinal breaks in vitrectomy for retained lens fragments.

Purpose: To describe the incidence and outcome of retinal breaks in vitrectomy for retained lens fragments.

Methods: This is a retrospective noncomparative interventional case series. Medical records of consecutive cases of vitrectomy for retained lens fragments over a period of 4 years were reviewed.

Pars plana vitrectomy for the repair of primary, inferior rhegmatogenous retinal detachment associated to inferior breaks. A comparison of a 25-gauge versus a 20-gauge system.

Background: To compare anatomical, functional outcomes and complications of high-speed 25-gauge (G) pars plana vitrectomy (PPV) versus 20-G PPV for the management of primary inferior rhegmatogenous retinal detachment (RRD) associated to inferior breaks/holes.

Methods: Eighty-five eyes from 85 patients with a minimum follow-up of 3 months were retrospectively evaluated. Forty-one patients underwent 25-G and 44 patients underwent 20-G PPV.

Cell proliferation in human epiretinal membranes: characterization of cell types and correlation with disease condition and duration.

Purpose: To quantify the extent of cellular proliferation and immunohistochemically characterize the proliferating cell types in epiretinal membranes (ERMS) from four different conditions: proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, post-retinal detachment, and idiopathic ERM.

Methods: Forty-six ERMs were removed from patients undergoing vitrectomy and immediately fixed in paraformaldehyde. The membranes were processed whole and immunolabeled with either anti-MIB-1 or anti-SP6 to detect the K(i)-67 protein in proliferating cells, in combination with anti-glial fibrillary acidic protein or anti-vimentin to identify glia, anti-ezrin to identify retinal pigment epithelial cells, Ricinus communis to identify immune cells, and Hoechst to label nuclei.

CADASIL and migraine: A narrative review.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke, cognitive decline, psychiatric disturbances and migraine. The prevalence of migraine in CADASIL is slightly higher than in the general population, and the proportion of migraine with aura is much higher. The pathophysiological mechanism that leads to increased aura prevalence in CADASIL is unknown.

Primary retinectomy in proliferative vitreoretinopathy.

Purpose: To describe the functional and anatomic results of retinectomy without scleral buckling for anterior proliferative vitreoretinopathy in eyes that did not undergo previous buckling surgery.

Design: Retrospective, nonrandomized, interventional case series.

Methods: We reviewed the results of 123 consecutive cases of retinectomy for rhegmatogenous retinal detachment complicated by anterior proliferative vitreoretinopathy.

A homozygous deletion of a normal variation locus in a patient with hearing loss from non-consanguineous parents.

Background: International databases with information on copy number variation of the human genome are an important reference for laboratories using high resolution whole genome screening. Genomic deletions or duplications which have been detected in the healthy population and thus marked as normal copy number variants (CNVs) can be filtered out using these databases when searching for pathogenic copy number changes in patients. However, a potential pitfall of this strategy is that reported normal CNVs often do not elicit further investigation, and thus may remain unrecognised when they are present in a (pathogenic) homozygous state.

Peters Plus syndrome is a new congenital disorder of glycosylation and involves defective Omicron-glycosylation of thrombospondin type 1 repeats.

Peters Plus syndrome is an autosomal recessive disorder characterized by anterior eye chamber defects, disproportionate short stature, developmental delay, and cleft lip and/or palate. It is caused by splice site mutations in what was thought to be a beta1,3-galactosyltransferase-like gene (B3GALTL). Recently, we and others found this gene to encode a beta1,3-glucosyltransferase involved in the synthesis of the disaccharide Glc-beta1,3-Fuc-Omicron-that occurs on thrombospondin type 1 repeats of many biologically important proteins.

No influence of moderate hepatic impairment on the pharmacokinetics of lumiracoxib, an oral COX-2 selective inhibitor.

The aim of this study was to evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of the novel cyclooxygenase-2 (COX-2) selective inhibitor lumiracoxib (Prexige), so that dose recommendations for clinical use can be provided. This was an open-label, single dose, case-controlled study in which eight subjects with liver cirrhosis classed as moderate hepatic impairment (Child-Pugh score: 7-9) and eight demographically-matched healthy subjects received a single oral 400 mg dose of lumiracoxib. Routine safety assessments were made and blood samples were taken for determination of lumiracoxib concentrations for 96 h post dose.

[From gene to disease; from Notch3 to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy].

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy' (CADASIL) is an autosomal dominant inherited arteriopathy leading to brain infarcts and dementia at middle age with extensive cerebral white matter changes on MRI. CADASIL is caused by mutations in the Notch3 gene on chromosome 19.

Diagnostic Notch3 sequence analysis in CADASIL: three new mutations in Dutch patients. Dutch CADASIL Research Group.

To confirm the clinical diagnosis in individual Dutch patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), we performed direct sequence analysis of the abnormal gene, Notch3, in patients from 11 families without prior linkage analysis to chromosome 19. Eleven missense mutations involving the loss or gain of a cysteine residue were found, of which 3 are new. Exon 4 is a mutation hotspot (9 of 11 families).