Reduced ErbB4 Expression in Immune Cells of Patients with Relapsing Remitting Multiple Sclerosis

Background. There is an insufficient remyelination in the lesions of multiple sclerosis (MS). One of the factor that was found to promote remyelination is neuregulin-1 which is the ligand of ErbB4. Immune cells have been implicated in neurogenesis and oligodendrogenesis. Aims. We studied the expression of ErbB4 in the immune cells of patients with relapsing remitting (RR) multiple sclerosis (MS) and healthy controls. Methods. ErB4 expression in immune cells was studied by flow cytometry without stimulation or with stimulation with anti-CD3 and anti-CD28 monoclonal antibodies or in the presence of interferon-g or TNF-α as well as by immunoprecipitation and Western blot, and its mRNA was studied by real-time PCR. Results. We found reduced levels of ErbB4 in the total PBMCs and in T cells, monocytes, and B cells of RR MS patients. Similarly, the ErbB4 RNA levels were reduced in the immune cells of patients with RR-MS. Stimulation via CD3 and CD28 significantly upregulated the expression of ErbB4 on immune cells healthy individuals. This effect was weaker in the patients group. Conclusion. ErbB4 may play a role in the proliferation of oligodendrocyte progenitor cells, differentiation of oligodendrocytes, and remyelination, and, therefore, the reduced ErbB4 expression in immune cells of patients with RR-MS may contribute to insufficient remyelination that occurs in the disease

White Matter Hyperintensities in Parkinson’s Disease: Do They Explain the Disparity between the Postural Instability Gait Difficulty and Tremor Dominant Subtypes?

Background: Brain white matter hyperintensities (WMHs) commonly observed on brain imaging of older adults are associated with balance and gait impairment and have also been linked to cognitive deficits. Parkinson’s disease (PD) is traditionally sub-classified into the postural instability gait difficulty (PIGD) sub-type, and the tremor dominant (TD) sub-type. Considering the known association between WMHs and axial symptoms like gait disturbances and postural instability, one can hypothesize that WMHs might contribute to the disparate clinical sub-types of patients with PD. Methods: 110 patients with PD underwent a clinical evaluation and a 3T MRI exam. Based on the Unified Parkinson Disease Rating Scale, the patients were classified into motor sub-types, i.e., TD or PIGD, and scores reflecting PIGD and TD symptoms were computed. We compared white matter burden using three previously validated methods: one using a semi-quantitative visual rating scale in specific brain regions and two automated methods. Results: Overall, MRI data were obtained in 104 patients. The mean WMHs scores and the percent of subjects with lesions in specific brain regions were similar in the two subtypes, p = 0.678. The PIGD and the TD scores did not differ even when comparing patients with a relatively high burden of WMHs to patients with a relatively low burden. Across most of the brain regions, mild to moderate correlations between WMHs and age were found (r = 0.23 to 0.41; p<0.021). Conversely, no significant correlations were found between WMHs and the PIGD score or disease duration. In addition, depressive symptoms and cerebro-vascular risk factors were similar among the two subtypes. Conclusions: In contrast to what has been reported previously among older adults, the present study could not demonstrate any association between WMHs and the PIGD or TD motor sub-types in patients with PD

Efficacy and safety of Apixaban in the treatment of cerebral venous sinus thrombosis: a multi-center study

BackgroundInformation regarding the safety and efficacy of specific direct oral anticoagulants (DOAC) in the treatment of cerebral sinus and venous thrombosis (CSVT) is scarce. Apixaban is one of the most frequently prescribed DOACs. Therefore, we aimed to compare the safety and efficacy of Apixaban with those of vitamin k antagonists (VKA) in patients with CSVT.MethodsProspective CSVT databases from seven academic medical centers were retrospectively analyzed. Patients treated with Apixaban were compared to those treated with VKA. Data on demographics, clinical presentations, risk factors, radiological and outcome parameters were studied.ResultsOverall, 403 patients were included in the analysis. Of them, 48 (12%) were treated with Apixaban, and 355 (88%) were treated with VKA. Rates of coagulopathies were significantly higher in the VKA-treated patients but no other differences between the groups were found in baseline characteristics and underlying etiology. No significant differences were found between groups in efficacy or safety parameters including the rates of recanalization, favorable outcomes, one-year mortality, seizures, intracranial hemorrhage or CSVT recurrences.ConclusionOur data suggests that Apixaban may be safe and effective for patients with CSVT. These results should be tested in prospective randomized clinical studies

The Association between Low Levels of Low Density Lipoprotein Cholesterol and Intracerebral Hemorrhage: Cause for Concern?

Excessive levels of low-density lipoprotein cholesterol (LDL-C) in the blood are a known risk factor for atherosclerosis, and a common target of treatment for primary and secondary prevention of cerebrocardiovascular disease. As lipid lowering agents including statins, ezetimibe and anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have shown good therapeutic results, the guidelines are constantly lowering the &ldquo;optimal&rdquo; LDL-C goals. However, old and new data point towards an association between low LDL-C and total cholesterol and intracerebral hemorrhage (ICH). In this review we aimed to shed light on this troubling association and identify the potential risk factors of such a potential adverse reaction. With respect to the data presented, we concluded that in patients with high risk of ICH, a cautious approach and individualized therapy strategy are advised when considering aggressive LDL reduction

A Novel Rodent Model of Hypertensive Cerebral Small Vessel Disease with White Matter Hyperintensities and Peripheral Oxidative Stress

Cerebral small vessel disease (CSVD) is the second most common cause of stroke and a major contributor to dementia. Manifestations of CSVD include cerebral microbleeds, intracerebral hemorrhages (ICH), lacunar infarcts, white matter hyperintensities (WMH) and enlarged perivascular spaces. Chronic hypertensive models have been found to reproduce most key features of the disease. Nevertheless, no animal models have been identified to reflect all different aspects of the human disease. Here, we described a novel model for CSVD using salt-sensitive &lsquo;Sabra&rsquo; hypertension-prone rats (SBH/y), which display chronic hypertension and enhanced peripheral oxidative stress. SBH/y rats were either administered deoxycorticosteroid acetate (DOCA) (referred to as SBH/y-DOCA rats) or sham-operated and provided with 1% NaCl in drinking water. Rats underwent neurological assessment and behavioral testing, followed by ex vivo MRI and biochemical and histological analyses. SBH/y-DOCA rats show a neurological decline and cognitive impairment and present multiple cerebrovascular pathologies associated with CSVD, such as ICH, lacunes, enlarged perivascular spaces, blood vessel stenosis, BBB permeability and inflammation. Remarkably, SBH/y-DOCA rats show severe white matter pathology as well as WMH, which are rarely reported in commonly used models. Our model may serve as a novel platform for further understanding the mechanisms underlying CSVD and for testing novel therapeutics