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Granulomatosis with polyangiitis is a multisystem disease characterized by a necrotizing granulomatous vasculitis, typically associated with the presence of anti-neutrophil cytoplasmic antibodies. The lung is the most common organ involved in comparison to other vasculitis, but in the case presented by us the onset is otorhinolaryngology field, with a multitude of symptoms and immunological tests are initially negative. Over time, immunological tests become positive, but all this leading to a delay in diagnosis by 4 years and of course to a delay in treatment. In this paper we emphasize the usefulness of biopsy for diagnosis and use of anti-neutrophil cytoplasmic antibodies to classify the disease.

Transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction resulting from focal brain, spinal cord, or retinal ischemia, without associated infarction. Consequently, a TIA encompasses amaurosis fugax (AF) that is a term used to denote momentary visual loss from transient retinal ischemia. In this review, we use the word TIA to refer to both cerebral TIAs (occurring in the brain) and AF (occurring in the retina). We summarize the key components of a comprehensive evaluation and management of patients presenting with cerebral and retinal TIA.All TIAs should be treated as medical emergencies, as they may herald permanent disabling visual loss and devastating hemispheric or vertebrobasilar ischemic stroke. Patients with suspected TIA should be expeditiously evaluated in the same manner as those with an acute stroke. This should include a detailed history and examination followed by specific diagnostic studies. Imaging of the brain and extracranial and intracranial blood vessels forms the cornerstone of diagnostic workup of TIA. Cardiac investigations and serum studies to evaluate for etiological risk factors are also recommended.The management of all TIAs, whether cerebral or retinal, is similar and should focus on stroke prevention strategies, which we have categorized into general and specific measures. General measures include the initiation of appropriate antiplatelet therapy, encouraging a healthy lifestyle, and managing traditional risk factors, such as hypertension, dyslipidemia, and diabetes. Specific management measures require the identification of a specific TIA etiology, such as moderate-severe (greater than 50% of stenosis) symptomatic extracranial large vessel or intracranial steno-occlusive atherosclerotic disease, aortic arch atherosclerosis, and atrial fibrillation.

Multiple sclerosis is an increasingly prevalent disease, representing the leading cause of non-traumatic neurological disease in Europe and North America. The most common symptoms include gait deficits, balance and coordination impairments, fatigue, spasticity, dysphagia and an overactive bladder. Neurorehabilitation therapeutic approaches aim to alleviate symptoms and improve the quality of life through promoting positive immunological transformations and neuroplasticity. The purpose of this study is to evaluate the current treatments for the most debilitating symptoms in multiple sclerosis, identify areas for future improvement, and provide a reference guide for practitioners in the field. It analyzes the most cited procedures currently in use for the management of a number of symptoms affecting the majority of patients with multiple sclerosis, from different training routines to cognitive rehabilitation and therapies using physical agents, such as electrostimulation, hydrotherapy, cryotherapy and electromagnetic fields. Furthermore, it investigates the quality of evidence for the aforementioned therapies and the different tests applied in practice to assess their utility. Lastly, the study looks at potential future candidates for the treatment and evaluation of patients with multiple sclerosis and the supposed benefits they could bring in clinical settings.

It is a well-known fact that disruptions in the immune system and systemic inflammation are associated with accelerated atherosclerosis in rheumatoid arthritis (RA) patients. Elevated levels of tumor necrosis factor α (TNF-α), a major pro-inflammatory cytokine, are involved in endothelial cell activation of medium and large arteries, leading to increased endothelial permeability, generation of superoxide anion radical and hydrogen peroxide, and decreased availability of nitric oxide (NO). The present study aims to determine the influence of anti-TNF therapy and homocysteine (Hcy) levels on the carotid intima-media thickness (IMT) in patients with RA. Assessments were performed on 115 patients diagnosed with RA on biological treatment to determine the evolution of IMT and Hcy levels. Carotid ultrasonography was used to assess the IMT, as a fast and easy tool for the prediction of cardiovascular events in patients with RA. The first measurement of IMT was noted as IMT1, followed by a second measurement after 1 year, noted as IMT2. The group of patients was divided into approximately three equal groups, each being treated with a different biological product, respectively, etanercept, adalimumab, and infliximab. In the 3 groups, after 1 year of anti-TNF-α therapy, IMT2 progression was significantly reduced compared to baseline. No significant differences were found among the three groups of treatment. A strong association was observed between IMT1-IMT2 in the etanercept group (P0.9 mm at baseline. The results from the present study showed that biological treatment and the low level of homocysteinemia reduced the cardiovascular risk in RA, regardless of the treatment chosen (infliximab, adalimumab, or etanercept).

Background: Cardiovascular disease is the main cause of mortality and morbidity in patients with rheumatoid arthritis (RA). Correlation between vitamin D deficiency and atherosclerosis in patients with rheumatoid arthritis is a subject of medical interest. Objectives: We studied the correlation between vitamin D deficiency, body mass index (BMI) and carotid intima-media thickness (CIMT) in patients with rheumatoid arthritis with anti tumor necrosis factor-alpha (TNF-α) therapy. Methods: Our study included 75 RA patients with anti-TNF-alpha therapy (Adalimumab, Influximab, Etanercept) and 30 RA patients with DMARDs (Methotrexate/Leflunomide). The patients were diagnosed with RA according to ACR/EULAR (2010) classification criteria. CIMT was measured using high-resolution Doppler ultrasonography. CIMT ≥ 0.9 mm is considered as a marker of atherosclerosis. Vitamin D deficiency was defined as serum 25-OH-vitamin D level 5.1: high disease activity). Patients with current use of vitamin D supplements were excluded. Results: The anti-TNF group included 29 patients with Adalimumab (38.7%), 25 with Etanercept (33.3%) and 21 patients in treatment with Infliximab (28%). Their mean age was 52.0 years. We evaluated patients at baseline and after 12 months with treatment. In anti-TNF group we found 9 patients (12%) with normal BMI and normal vitamin D level correlated with high CIMT (p=0.001), 21 patients (28%) with overweight and normal vitamin D level correlated with high CIMT (p=0.003), and 31 patients (41.3%) with overweight and low vitamin D level correlated with high CIMT (p=0.001). 14 patients (18.7%) with normal vitamin D level and normal weight (9) or overweight (5) were correlated with normal CIMT (p=0.01). In DMARDs group we followed the same correlation. Patients with normal BMI and normal vitamin D level had a low correlation with CIMT increase (p=0.01). Patients with overweight and low vitamin D level had a significant correlation with CIMT increase (p=0.003) than group with anti-TNF-alpha therapy. After 12 months of therapy, patients treated with Adalimumab had lower CIMT levels than patients treated with Etanercept. Conclusion: Rheumatoid arthritis patients treated with TNF inhibitors and with vitamin D deficiency but with normal BMI have been correlated with lower increase of CIMT than patients with DMARDs therapy. Normal vitamin D level was associated with low increase of CIMT in these patients. Deficiency of Vitamin D associated with overweight are risk factors for carotid atherosclerosis in patients with RA. Disclosure of Interests: None declared

Background:Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with an important risk factor of osteoporosis. A high serum level of Homocysteine (Hcy) has been recently recognized as a risk factor for osteoporosis and osteoporotic fractures. Treatment with TNF-α blockers might influence bone metabolism and prevent structural bone damage in AS.Objectives:The aim of the study was to evaluate the influence of anti-TNF therapies and hyperhomocysteinemia on bone mineral density in AS patients.Methods:In our retrospective study were enrolled 73 AS patients with anti TNF-α therapies (29 Adalimumab 40mg/2weeks, 24 Etanerceptum50mg/week, 20 Infliximabum5 mg/kg/8 weeks) and 45 AS patients non anti TNF-α therapies. All patients included in this study met the modified New York criteria. The current medications used by the non anti TNF-α therapies patients were nonsteroidal anti-inflammatory drugs.We used Dual energy x ray absorptiometry (DXA) method for measuring bone mineral density (BMD). Osteoporosis is defined as a T score of ≤ −2.5 SD, according to the WHO criteria. BMD of the hip and lumbar spine (L1-L4) was determined at baseline and after 6 months. Hcy concentrations were measured by using a chemiluminescence immunoassay method. The normal serum Hcy level is considered to be below 15mmol/L. In both group we followed the activities disease (C reactive protein-CRP, eritrocytes sedimentation rate-ESR, Bath ankylosing spondylitis disease activity index-BASDAI score) and determined vitamin D3 level.All parameters were determined at baseline and after 6 months.Results:The mean age of study group1 was 47.4±11.1 years and 42±9,8year in group2. The mean disease duration was 11.9 ± 6.1 years. 83,5% of patients were HLA-B27 positive in group1 and 71,1% in group2.BMD measurements revealed more severe osteoporosis in patients with positive HLA-B27 in both groups at baseline. After 6 months in group1 BMD increased by 0.4% at lumbar spine and 0.1% in the hip and in group2 decreased by 0.9% and 0.6% in the same sites. No significant differences between type of anti-TNF therapies and BMD. In group 1, HLA-B27 positive status was positive correlated with decrease BMD(p=0.001) after 6 months. Hcy levels were found significantly increased (14.8 ± 3.8 mg/mL vs. 12.4 ± 4.2 mg/mL; P < 0.001) at baseline in both groups. Serum levels of Hcy were inversely correlated to lumbar spine BMD (p< 0.005) and femur neck BMD(p=0,001) after 6 months in group1. At baseline the mean level of 25-hydroxyvitamin D3 was 22.8 ± 14.1 ng/mL in group1 and 26.6 ± 12.5 ng/mL in group2. In anti TNF patients group, we found a positive correlation between decrease BMD, low level of 25-hydroxyvitamin D3 and high level of Hcy(p=0,001) after six months. No correlation was found between BMD and BASDAI score and inflammatory parameters (ESR, CRP).Conclusion:Bone mineral density measurements revealed more severe osteoporosis in positive HLA-B27 AS patients and hyperhomocysteinemia. Association of low level of 25-hydroxyvitamin D3 and hiperhomocysteinemia is correlated with high-risk fracture in positive HLA-B27 patients. Anti TNF therapies reduce this risk.References:[1]Kim JI, Moon JH, Chung HW, Kong MH, Kim HJ. Association between homocysteine and bone mineral density according to age and sex in healthy adults. J Bone Metab 2016; 23:129-34.[2]Fratoni V, Brandi ML. B Vitamins, homocysteine and bone health. Nutrients 2015; 7:2176-92.[3]Jahn O, Wex T, Klose S, Kropf S, Adolf D, Piatek S, et al. Cathepsin K in treatment monitoring following intravenous zoledronic acid. Biomed Rep 2014; 2:915-7.Disclosure of Interests:None declared.

Background:Homocysteine (Hcy) has been implicated in atherogenesis. High homocysteine level can predict cardiovascular events, including death. Atherosclerosis has a high incidence in patients with Rheumatoid Arthritis (RA).Objectives:The aim of this study is to evaluate the relationship between serum homocysteine levels and carotid atherosclerosis in patients with RA and anti-TNF therapy.Methods:Our study included 80 RA patients divided into two groups: 45 patients were with anti-TNF-alpha therapy (Adalimumab, Infliximab, Etanercept) and 35 RA patients with disease-modifying antirheumatic drugs (DMARDs). The patients were diagnosed with RA used ACR/EULAR 2010 Classification Criteria. We measured carotid intima-media thickness (CIMT) using high-resolution Doppler ultrasonography at baseline and then at 12 months. CIMT above 0.9 mm is an atherosclerosis marker. We considered high levels of homocysteine in the serum above 15 µmol/L. All patients had treatment with hypolipemiant drugs and antiplatelet agents during the 12 months. Other parameters were analyzed at baseline and after 12 months: age, lipid profile (HDL, LDL, and cholesterol), ESR and disease activity score (DAS28>5.1 high disease activity).Results:45 patients received anti-TNF-alpha therapy (mean age 45.50±9.69 years) and 35 RA patients had treatment with DMARDs (mean age 48.3±8.9 years). High Hcy levels were found on 34% patients in DMARDs group and 21% patients in anti-TNF group. After 12 months of treatment, patients with high levels of Hcy and anti-TNF therapy had a significant decrease in CIMT. In patients with low Hcy level the decrease in CIMT was insignificantly statistic. In DMARDs group atherosclerotic plaque was detected to 26 patients (74.29%) and 21 (46.66%) patients were detected into anti-TNF group. After 12 months CIMT was significantly higher in DMARDs group and the difference was statistically significant compared to baseline and to anti-TNF group (p=0.0002). High DAS28 score was associated with increased CIMT and hyperhomocysteinemia in both groups (p=0.0001).Conclusion:Increased Hcy levels were associated with increased CIMT values in both groups. In RA patients with anti-TNF therapy and high Hcy levels, reduction of CIMT was statistically higher than in patients with DMARDs treatment.Disclosure of Interests:None declared

Background Rheumatoid arthritis is a chronic inflammatory autoimmune disease that causes systemic inflammation associated with increased risk of coronary, cerebral and peripheral ischaemic accidents. Biological therapy, by decreasing systemic inflammation, implicitly reduces cardiovascular risk in patients with rheumatoid arthritis. The assessment of carotid atheromatosis in Doppler ultrasound examination can be a useful element in the diagnosis of patients with cardiovascular risk. Objectives We followed the cardiovascular risk as well as the development of the carotid artery plaque by carotid Doppler ultrasound, lipid profile and arterial hypertension in patients with rheumatoid arthritis who have undergone biological treatment with anti-TNF-alpha. We also studied the correlation of the intima-medium thickness index in the carotids with the activity of rheumatic disease (DAS28, CRP, VSH) and the evolution of these parameters under biological therapy. Methods Our study included 37 patients with rheumatoid arthritis in treatment with DMARD’s (group 1) and 50 patients with rheumatoid arthritis in treatment with anti-TNF-alpha (etanercept, adalimumab, infliximab) biological therapy (group 2). The following parameters were assessed in all patients: DAS28, lipid profile (total cholesterol, LDL, HDL, triglycerides), which were followed at 0, 6, and 12 months. The Intima-Medium Thickness Index was measured by Mode B sonography at the level of the common carotid artery, bifurcation of both arteries and the external carotid artery. The value of the index above 0.7 mm was considered pathological. Results In lot 1, after the carotid Doppler ultrasound, of the 37 patients, 21 presented the carotid artery plaque, and in lot 2 of the 50 patients, 34 showed these changes. A full evaluation (DAS28, lipid profile, arterial tension, carotid ultrasound) of all patients was performed at the start of the study. At 6 months, inflammatory markers and DAS28 showed a decrease in baseline values in both groups, more significant in the biological therapy group. Reduction of the intima-medium thickness index and blood pressure was observed in both groups, with no significant differences. At 12 months, CRP and DAS28 in the DMARD-treated group corresponded to disease remission values in 33 patients (89%), and in the group treated with biological therapy, the same remission rates of the disease were recorded in 49 patients (97.7%). The intima-medium thickness index in the DMARD-treated group decreased from the 6 month values. In patients with biological therapy, the reduction in the mid-thickness index recorded a progressive decrease from the previous assessment. Conclusions There is a direct correlation between the markers of inflammation and the evolution of carotid atheromatosis in patients with rheumatoid arthritis. The intima-medium thickness index is a paraclinical feature useful in assessing cardiovascular risk in patients with rheumatoid arthritis. Biological therapy, by controlling the underlying disease, also improves cardiovascular prognosis. Treatment with anti-TNF-alpha makes good control, together with lipid-lowering and antihypertensive medication of associated cardiovascular pathology, in patients with rheumatoid arthritis. Disclosure of Interest None declared

Traditionally, multiple sclerosis (MS) has been considered a white matter disease, but MS lesions are known to occur in grey matter. Recent immunohistochemical studies have demonstrated extensive grey matter demyelination in chronic MS, grossly underestimated by standard hystochemical myelin staining methods. Extensive cortical demyelination is associated with the progressive phases of disease, as less cortical demyelination has been detected in relapsing-remitting MS. The pathology of grey matter lesions differs from that of white matter lesions. Significant axonal transection and neuronal loss have been demonstrated in grey matter MS lesions. Current magnetic resonance imaging (MRI) methods are not sensitive for purely cortical MS lesions. Special MRI techniques permit the visualization of grey matter lesions, and in the future more sensitive MRI methods will help to characterize their clinical significance.

The study of online hemodiafiltration (HDF) benefits over high-flux hemodialysis (HD) raises great interest. The purpose was to compare clinical and laboratory parameters in patients treated with HD who were switched to HDF. Forty-eight HD patients (study group) were switched to HDF, while other 521 patients remained on HD as a control group. During last 6 HD months and during first year of HDF, we determined in both groups the following parameters: monthly–weekly dialysis time, systolic and diastolic blood pressure, body mass index (BMI), interdialytic body weight gain (IBWG), blood flow rate (Qb), weekly erythropoietin-stimulating agents dose (EPO), single-pool Kt/V, calcium, phosphorus (P), hemoglobin and normalized protein catabolic ration (nPCR), plus every 3 months—albumin, parathormone (PTH), ferritin and transferrin saturation (TSAT). In both groups, parameters in the last 6 HD months were compared to those in the first 6 months and, respectively, to those in the first year of HDF. In the study group, albumin and nPCR were significantly higher in the HD period not only compared to the first 6 months of HDF, but also compared to the first year of HDF. IBWG and P were higher with HD compared to the first year of HDF, but not with the first 6 months. PTH, Kt/V, Qb and EPO were higher in both HDF periods. In the control group, albumin was significantly higher in the first 6 months after the switch, but it was significantly lower in the first year. BMI, ferritin, PTH, Kt/V, Qb, TSAT and weekly dialysis time were higher in both HDF periods, while nPCR, EPO, SBP and DBP were lower. IBWG and Hb rose only during the first year after the switch, while P was lower in the first year, but not in the first 6 months. Nutrition, assessed by albumin, nPCR and BMI, was not improved by HDF compared to HD. With HDF, Kt/V and phosphorus control were better, similar results were observed in the control group. A larger EPO dose was needed with HDF for maintaining a similar hemoglobin level.

Wilson's disease (WD) is a rare autosomal recessive disease. More than 500 mutations have been described so far, out of which 29 in exon 14. H1069Q mutation in the exon 14 of ATP7B gene is the most frequently encountered in Europe. The aim of the present study was to evaluate the incidence of mutations occurring in exon 14 of ATP7B gene in Romanian patients referred to a tertiary gastroenterology center, with known or suspected WD and in asymptomatic first degree relatives of index cases.93 patients were included in the study. Exon 14 of ATP7B gene has been amplified by PCR from genomic DNA and mutations identified by sequencing.Only H1069Q missense mutation was detected in our study group. In patients with an established diagnosis of WD (38 cases), 34.2% were heterozygous for H1069Q and 21.1% were homozygous, with an allelic frequency of 38.1%. In paediatric WD patients (12 cases) 25% were heterozygous and 16.7% were homozygous (not significant versus adult population). Among asymptomatic first degree relatives of patients with WD (12 siblings, 25 parents) there were 40.5% cases heterozygous for H1069Q. In patients with suspected WD (17 cases), only 5.9% were heterozygous and no homozygous patient was identified. In our study group, H1069Q screening alone could not raise the Leipzig score to confirm diagnosis in patients with suspected WD or in asymptomatic first degree relatives.H1069Q mutation is highly prevalent in Romanian WD patients and first degree relatives, similar to other central and continental western European populations.

The antiphospholipid syndrome (APS) is defined by the presence of antiphospholipid antibodies (aPL), associated with thrombosis or recurrent spontaneous abortions. APS can occur alone or secondary to other conditions, especially associated to inflammatory systemic autoimmune diseases. Among the neurological manifestations associated with aPL, only ischemic stroke is recognized by the actual classification criteria for APS. Other neurological manifestations have been, however, repeatedly reported in case studies of APS patients. Headache, and especially migraine, was commonly reported in APS patients and is one of the classical features described by Hughes as related to aPL, but studies failed to confirm this association. We studied retrospectively the association between headache syndromes and aPL in 428 patients with inflammatory connective tissue diseases admitted in the Neurology and Internal Medicine Departments of Colentina Hospital-Bucharest. We found that migraine alone, not headache of all types, is significantly associated with aPL in patients with systemic immune disease. We studied the presence of cerebral ischemia in patients with headache and aPL. In SLE patients, headache (all types) is significantly associated with positive titers of aPL, and cerebral ischemic lesions are significantly encountered. Even if both migraine and aPL are conditions with high frequency in patients with immune systemic disease and their association may be coincidental, the presence of ischemic lesions in patients showing this association suggests the need to define a sub-group at risk, for whom headache can be a marker and anticoagulants can be discussed.

The recorded thermoanalytical curves of a natural brucite were used to distinguish the thermal decomposition steps from 20 to 1000°C. In order to identify the crystal phases of the original material as well as of the decomposition intermediates, X-ray diffraction was used. The non-isothermal kinetic parameters of the thermal decompositions of brucite and magnesium carbonate from dolomite were determined.

Vertigo and dizziness are among the most frequent presenting symptoms, not only in neurology, but also in ENT and internal medicine clinics. Vertigo is a spinning sensation or the feeling that the surroundings are spinning. Floating sensation, light headiness, forward, backward – and sideward fall sensation, walking instability, gait hesitation or unsteadiness are other type of dizziness. Several clinical pictures of different etiologies include vertigo and dizziness as underlying complaint. Diagnosis should be based on clinical history and neurotological evaluation. A common perspective of neurologists, ENT doctors and general medicine physicians is needed for a better diagnosis and treatment of vertigo and dizziness patients.

Case report A 41-year-old man with left side hearing impairment since childhood presented with sudden hearing loss in the right ear; mild imbalance and clinical features suggestive of secondary syphilis (skin rash) developed lately. The first choice of treatment in the ENT department was followed after initial favorable evolution by relapsed sudden hearing loss in the right ear, dizziness, vertigo, nausea, and vomiting and gait impairment. The correct diagnosis was made after multiple evaluations in ENT, neurology, dermatology and infectious diseases departments. Combined ENT and infectious diseases treatment resulted in only partial recovery of hearing in the right ear and complete absence of dizziness.