Neuro-ophthalmological emergencies: which ocular signs or symptoms for which diseases?

There are five possible ocular signs or complaints of a life or sight threatening neuro-ophthalmological condition: diplopia, isolated anisocoria, transient visual loss, severe pain in head or neck (with or without photophobia) and oscillopsia/nystagmus. In this review, the ocular signs and symptoms of neuro-ophthalmological emergencies are described together with their practical work-up and the risks associated with missing the diagnosis. Concerning diplopia, the associated signs pointing to a possible threatening condition are emphasized. Six focus points resuming core messages are displayed throughout this review.JOURNAL ARTICLESCOPUS: re.jinfo:eu-repo/semantics/publishe

Elevating high-density lipoprotein cholesterol in apolipoprotein E-deficient mice remodels advanced atherosclerotic lesions by decreasing macrophage and increasing smooth muscle cell content.

BACKGROUND: HDL cholesterol levels are inversely correlated with coronary heart disease risk in humans, and in animal studies, HDL elevation decreases formation and progression of foam-cell lesions. The potential for HDL to affect preexisting advanced atherosclerotic lesions is not known. To approach this issue, we used a novel mouse aortic transplantation model. METHODS AND RESULTS: ApoE-deficient (EKO) mice were fed a Western-type diet for 6 months, and thoracic aortic segments containing advanced lesions replaced segments of the abdominal aorta of 4-month-old EKO syngeneic mice not expressing (plasma HDL cholesterol approximately 26 mg/dL) or expressing (HDL approximately 64 mg/dL) a human apoAI (hAI) transgene. Both types of recipients had comparable non-HDL cholesterol levels. Five months after transplantation, mice were killed and grafts analyzed. Compared with lesion area in pretransplant mice (0.14+/-0.04 mm(2), mean+/-SEM), there was progression in the EKO recipients (0.39+/-0.06 mm(2), P<0.01). Compared with EKO recipients, hAI/EKO recipients had retarded progression (0.24+/-0.04 mm(2), P<0.05). Immunostaining for CD68 and other macrophage-associated proteins, monocyte chemoattractant protein-1, acyl coenzyme A:cholesterol acyltransferase, and tissue factor, in lesions of pretransplant and EKO recipient mice showed abundant macrophages. In contrast, compared with any other group, lesional macrophage area in hAI/EKO mice decreased >80% (P<0.003), and smooth muscle cell content (alpha-actin staining) increased >300% (P<0.006). The decrease in macrophages and increase in smooth muscle cells was primarily in the superficial subendothelial layer. CONCLUSIONS: Increasing HDL cholesterol levels in EKO mice retards progression of advanced atherosclerotic lesions and remodels them to a more stable-appearing phenotype

High-density lipoproteins retard the progression of atherosclerosis and favorably remodel lesions without suppressing indices of inflammation or oxidation.

OBJECTIVE: Protective properties of high-density lipoproteins (HDL) may include reverse cholesterol transport and suppression of oxidation and inflammation. These were investigated in vivo, as were the effects of HDL on the characteristics of atherosclerotic lesions. METHODS AND RESULTS: Male apolipoprotein E knockout (apoE-/-) and apoE-/- mice expressing human apolipoprotein AI (hAI/apoE-/-) were studied up to 20 weeks after commencing a high-fat diet. Plasma HDL cholesterol was twice as high in hAI/apoE-/- mice. Over time, aortic root lesion area remained less in hAI/apoE-/- mice, although plaques became complex. In advanced lesions, plaque lipid was higher in apoE-/- mice, whereas plaque collagen and alpha actin were increased in hAI/apoE-/- mice. In nonlesional aorta, mRNA abundance for pro-inflammatory proteins (vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule-1 [ICAM-1], monocyte chemoattractant protein-1 [MCP-1]) increased between 4 and 16 weeks in apoE-/- (but not wild-type) mice, and were not reduced by elevated HDL. Autoantibodies to malondialdehyde low-density lipoprotein (LDL) increased progressively in apoE-/- mice, with similar results in hAI/apoE-/- mice. CONCLUSIONS: HDL retarded plaque size progression despite greatly elevated plasma cholesterol. This effect was over a wide range of lesion severity. Expression of hAI reduced plaque lipid and increased the proportion of plaque occupied by collagen and smooth muscle cells, but did not affect indicators of inflammation or LDL oxidation

Effects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice.

OBJECTIVE: To test the non-lipid-lowering effects of simvastatin on the response to injury in normolipidemic and hyperlipidemic mice. METHODS AND RESULTS: Wild-type (WT) mice (n = 40) and hyperlipidemic apolipoprotein-E-deficient (apoE(-/-)) mice (n = 40) received normal chow or chow containing simvastatin 100 mg/kg/day prior to bilateral femoral artery wire injury. Intimal hyperplasia and plasma cholesterol concentration were quantified after 4 weeks. Plasma cholesterol in WT mice treated or untreated with simvastatin was similar (100.9 +/- 6.6 vs. 94.3 +/- 17.5 mg/dl). Simvastatin did not affect intimal hyperplasia. In apoE(-/-) mice, intimal hyperplasia was increased 2.3-fold relative to WT mice (17090 +/- 4998 vs. 39490 +/- 16190; p < 0.001). In apoE(-/- )mice, simvastatin caused a paradoxical increase in plasma cholesterol (1094 +/- 60.3 vs. 658 +/- 66.8 mg/dl; p < 0.001), confirmed by FPLC. This was associated with a further increase in intimal area (39490 +/- 16190 vs. 55420 +/- 22590 mm(2); p < 0.01). CONCLUSIONS: (1). Simvastatin had no effect on plasma cholesterol or the response to arterial injury in normolipidemic WT mice; (2). hyperlipidemia was associated with markedly increased intimal hyperplasia, and (3). simvastatin treatment of apoE(-/-) mice caused paradoxical hyperlipidemia and increased intimal hyperplasia