Superficial siderosis of the central nervous system: report of three cases and review of the literature.

We present 3 cases and a review of the literature to demonstrate the current state of clinical diagnosis and therapy of superficial siderosis of the central nervous system. Typical symptoms were progressive cerebellar ataxia, spasticity and hearing loss. Repeated subarachnoid hemorrhage was indicated by persistent xanthochromia of the cerebrospinal fluid and confirmed by the presence of erythrophages, siderophages and iron-containing pigments. Deposition of free iron and hemosiderin in pial and subpial structures leads to intoxication of the central nervous system and represents the pathophysiological mechanism of superficial siderosis. Hypointensity of the marginal zones of the central nervous system on T2 weighted MR images indicates an iron-induced susceptibility effect and seems pathognomonic for superficial siderosis. In 39 of the 43 previously described cases superficial siderosis was verified by biopsy or autopsy. Today magnetic resonance imaging enables diagnosis at an early stage of the disease. Therapeutic management requires the elimination of any potential source of bleeding. In patients with unknown etiology no proofed therapy is yet available.     

Oxidized low-density lipoprotein autoantibodies, chronic infections, and carotid atherosclerosis in a population-based study.

OBJECTIVES: We investigated whether associations exist between immune reactions to oxidized low-density lipoproteins (OxLDLs), chronic infections, and carotid atherosclerosis as quantified by ultrasound. BACKGROUND: Atherosclerosis is a chronic immuno-inflammatory disease wherein both oxidized lipids and infectious agents are incriminated as possible contributors. METHODS: We measured immunoglobulin (Ig)G and IgM autoantibody titers to copper-oxidized-LDL and malondialdehyde-LDL (OxLDL-AB), IgG and IgM apolipoprotein B-100-immune complexes (ApoB-IC), and titers of antibodies to Escherichia coli and chlamydial lipopolysaccharide (LPS), mycobacterial heat shock protein 65 (mHSP65), Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus and evaluated their relationship to cardiovascular risk factors, chronic infections, and incident/progressive carotid atherosclerosis in the Bruneck study. RESULTS: The OxLDL-AB and ApoB-IC levels remained stable over time as indicated by strong correlations between 1995 and 2000 measurements (p < 0.001 each). Significant associations existed between all OxLDL markers and antibody titers to pathogens, especially to E. coli-LPS and mHSP65. Both OxLDL-AB and ApoB-IC levels showed a rise with increasing pathogen burden. Notably, OxLDL-ABs were also elevated in subjects with chronic infection as defined by clinical criteria. Titers of IgG, but not IgM, OxLDL-AB, or ApoB-IC inversely correlated with total cholesterol, LDL cholesterol, and apoB concentrations. The IgG OxLDL markers were positively and IgM markers were inversely associated with incident and progressive carotid atherosclerosis in univariate analyses but were not independent predictors in multivariate analyses. CONCLUSIONS: Our study provides evidence for an association between human oxLDL markers and chronic infections. Moreover, in this population-based study, neither IgG nor IgM OxLDL autoantibodies were independently predictive of atherosclerosis progression in the carotid arteries.     

Oxidized phospholipids predict the presence and progression of carotid and femoral atherosclerosis and symptomatic cardiovascular disease: five-year prospective results from the Bruneck study.

OBJECTIVES: The purpose of this work was to determine the predictive value of oxidized phospholipids (OxPLs) present on apolipoprotein B-100 particles (apoB) in carotid and femoral atherosclerosis. BACKGROUND: The OxPLs are pro-inflammatory and pro-atherogenic and may be detected using the antibody E06 (OxPL/apoB). METHODS: The Bruneck study is a prospective population-based survey of 40- to 79-year-old men and women initiated in 1990. Plasma levels of OxPL/apoB and lipoprotein (a) [Lp(a)] were measured in 765 of 826 (92.6%) and 671 of 684 (98.1%) subjects alive in 1995 and 2000, respectively, and correlated with ultrasound measures of carotid and femoral atherosclerosis. RESULTS: The distribution of the OxPL/apoB levels was skewed to lower levels and nearly identical to Lp(a) levels. The OxPL/apoB and Lp(a) levels were highly correlated (r = 0.87, p < 0.001), and displayed long-term stability and lacked correlations with most cardiovascular risk factors and lifestyle variables. The number of apolipoprotein (a) kringle IV-2 repeats was inversely related to Lp(a) mass (r = -0.48, p < 0.001) and OxPL/apoB levels (r = -0.46, p < 0.001). In multivariable analysis, OxPL/apoB levels were strongly and significantly associated with the presence, extent, and development (1995 to 2000) of carotid and femoral atherosclerosis and predicted the presence of symptomatic cardiovascular disease. Both OxPL/apoB and Lp(a) levels showed similar associations with atherosclerosis severity and progression, suggesting a common biological influence on atherogenesis. CONCLUSIONS: This study suggests that pro-inflammatory oxidized phospholipids, present primarily on Lp(a), are significant predictors of the presence and extent of carotid and femoral atherosclerosis, development of new lesions, and increased risk of cardiovascular events. The OxPL biomarkers may provide valuable insights into diagnosing and monitoring cardiovascular disease.     

Profiling of circulating microRNAs: from single biomarkers to re-wired networks

The recent discovery that microRNAs (miRNAs) are present in the circulation sparked interest in their use as potential biomarkers. In this review, we will summarize the latest findings on circulating miRNAs and cardiovascular disease but also discuss analytical challenges. While research on circulating miRNAs is still in its infancy, high analytical standards in statistics and study design are a prerequisite to obtain robust data and avoid repeating the mistakes of the early genetic association studies. Otherwise, studies tend to get published because of their novelty despite low numbers, poorly matched cases and controls and no multivariate adjustment for conventional risk factors. Research on circulating miRNAs can only progress by bringing more statistical rigour to bear in this field and by evaluating changes of individual miRNAs in the context of the overall miRNA network. Such miRNA signatures may have better diagnostic and prognostic value.     

Cardiac sympathetic innervation in Parkinson’s disease versus multiple system atrophy

Purpose

The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine-¹²³-metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson’s disease and multiple system atrophy.

Methods

A prospective study including 19 Parkinson’s disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine-¹²³-metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests.

Results

Co-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson’s disease (p?=?0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson’s disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson’s disease patients (p?<?0.001).

Conclusions

The diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine-¹²³-metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson’s disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson’s disease patients.

     

Distal myasthenia gravis frequency and clinical course in a large prospective series

OBJECTIVES: In Myasthenia gravis (MG) proximal limb, ocular and/or bulbar muscles are most commonly affected, whereas distal extremity muscles are typically spared. The aim of the current study was to assess the frequency of primarily distal MG in the Tyrol and to describe its clinical peculiarities. MATERIAL AND METHODS: Over the past 20 years 84 patients with MG have undergone follow-up at the Department of Neurology of Innsbruck University. Types of presentation, clinical course and treatment response were followed over a period of 20 years (1980-2000). RESULTS: Six of 84 MG patients showed a predominance of muscle weakness and fatigability in distal limb muscles (two at presentation, four over the later course of the illness). There was no difference between distal MG and MG with a more typical distribution of muscle weakness regarding age, gender and response to therapy. CONCLUSIONS: The case series indicates that predominantly distal presentations of otherwise typical MG are more frequent than generally assumed and should be considered in the differential diagnosis of diseases with distal limb weakness.