Comorbidity in multiple sclerosis: its temporal relationships with disease onset and dose effect on mortality.

BACKGROUND AND PURPOSE: We aimed to determine the burden of comorbidities at the time of diagnosis of multiple sclerosis (MS), the risk of developing new comorbidities after diagnosis and the effect of comorbidities on mortality in patients with MS. METHODS: This study used data from 2526 patients with incident MS and 9980 age-, sex- and physician-matched controls without MS identified from the UK Clinical Practice Research Datalink. RESULTS: Before the MS diagnosis, the adjusted odds ratio for the association between MS and a Charlson comorbidity index score of 1-2, 3-4 or ≥5 was 131 [95% confidence interval (CI), 1.17-1.47], 1.65 (95% CI, 1.20-2.26) or 3.26 (95% CI, 1.58-6.70), respectively. MS was associated with increased risks of cardiovascular and neurological/mental diseases. After diagnosis, the adjusted hazard ratio for the association between MS and an increased risk of developing comorbidities was 1.13 (95% CI, 1.00-1.29). The risk of developing any comorbidity in terms of neoplasms, musculoskeletal/connective tissue diseases or neurological/mental diseases was higher in MS. Patients with MS had a higher mortality risk compared with controls, with a hazard ratio of 2.29 (95% CI, 1.81-2.73) after adjusting for comorbidities. There was a dose effect of pre-existing comorbidities on mortality. CONCLUSIONS: Patients with MS have an increased risk of developing multiple comorbidities both before and after diagnosis and pre-existing comorbidities have an impact on survival.

Epilepsy and associated mortality in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: We aimed to determine the prevalence of epilepsy in patients with multiple sclerosis (MS) at diagnosis, the risk of developing epilepsy after the diagnosis of MS and the relative risk of mortality associated with epilepsy. METHODS: We used the UK Clinical Practice Research Data-link to identify 2526 patients with incident MS and 9980 age-, sex- and index year-matched non-MS controls from 1997 to 2006. Logistic regression was used to estimate odds ratios [95% confidence interval (CI)] for epilepsy and Cox regression was used to estimate hazard ratios (HRs) (95% CI) for epilepsy and mortality. RESULTS: Patients with incident MS were on average 45 years old and 70.9% were female. At diagnosis, the prevalence of epilepsy in patients with MS was 1.30% compared with 0.57% in non-MS controls. At diagnosis, MS was associated with an adjusted odds ratio (95% CI) of 2.11 (1.36-3.27) for pre-existing epilepsy. Among epilepsy-free patients, the cumulative probabilities of developing epilepsy, first recorded within 10 years of the index date, were 2.77% for patients with MS and 0.90% for controls. MS was associated with an adjusted HR (95% CI) of 6.01 (2.94-12.29) for epilepsy. Among patients with MS, epilepsy was associated with an HR (95% CI) of 2.23 (1.02-4.84) for all-cause mortality. CONCLUSIONS: This population-based study found an increased prevalence of epilepsy in patients with MS at diagnosis when compared with non-MS controls and the risk of developing epilepsy was also higher following the MS diagnosis. Patients with MS with epilepsy had a higher risk of mortality compared with those without.

Decreased interferon-ß induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis.

OBJECTIVES: Interferon-ß (IFN-ß) is used in the treatment of multiple sclerosis (MS). IFN-ß activation of signal transduction and activation of transcription (STAT)-4 is linked to its immunomodulatory effects. Previous studies suggest a type I IFN deficit in immune cells of patients MS, but data on interferon-α/ß receptor (IFNAR) expression and the relationship with treatment response are conflicting. Here, we compare IFN-ß-mediated STAT4 activation in immune cells of untreated patients with MS and controls. MATERIALS AND METHODS: Peripheral blood mononuclear cells from 27 untreated patients with relapsing MS, obtained before the initiation of IFN-ß treatment, and 12 matched controls were treated in vitro with IFN-ß. Total and phosphorylated STAT4 (pSTAT4) and IFNAR were measured by flow cytometry and quantitative PCR. The patients were followed up for 5 years. RESULTS: pSTAT4 induction by IFN-ß was lower in patients with MS than in controls, as was expression of IFNAR. pSTAT4 expression did not correlate with the clinical outcome at 5 years, measured by EDSS change. There was a negative correlation between the baseline IFNAR1 mRNA levels and relapse rate. CONCLUSIONS: The results suggest decreased IFN-ß responsiveness in patients with MS, associated with reduced STAT4 activation and reduced IFNAR expression. This reduced responsiveness does not appear to affect the long-term clinical outcome of IFN-ß treatment.

Alcohol withdrawal syndrome: mechanisms, manifestations, and management.

The alcohol withdrawal syndrome is a well-known condition occurring after intentional or unintentional abrupt cessation of heavy/constant drinking in patients suffering from alcohol use disorders (AUDs). AUDs are common in neurological departments with patients admitted for coma, epileptic seizures, dementia, polyneuropathy, and gait disturbances. Nonetheless, diagnosis and treatment are often delayed until dramatic symptoms occur. The purpose of this review is to increase the awareness of the early clinical manifestations of AWS and the appropriate identification and management of this important condition in a neurological setting.

The endocannabinoid system: a revolving plate in neuro-immune interaction in health and disease.

Studies of the last 40 years have brought to light an important physiological network, the endocannabinoid system. Endogenous and exogenous cannabinoids mediate their effects through activation of specific cannabinoid receptors. This modulatory homoeostatic system operates in the regulation of brain function and also in the periphery. The cannabinoid system has been shown to be involved in regulating the immune system. Studies examining the effect of cannabinoid-based drugs on immunity have shown that many cellular and cytokine mechanisms are modulated by these agents, thus raising the hypothesis that these compounds may be of value in the management of chronic inflammatory diseases. The special properties of endocannabinoids as neurotransmitters, their pleiotropic effects and the impact on immune function show that the endocannabinoid system represents a revolving plate of neural and immune interactions. In this paper, we outline current information on immune effects of cannabinoids in health and disease.

Easy to interpret coordinate based meta-analysis of neuroimaging studies: Analysis of brain coordinates (ABC).

BACKGROUND: Functional MRI and voxel-based morphometry are important in neuroscience. They are technically challenging with no globally optimal analysis method, and the multiple approaches have been shown to produce different results. It is useful to be able to meta-analyse results from such studies that tested a similar hypothesis potentially using different analysis methods. The aim is to identify replicable results and infer hypothesis specific effects. Coordinate based meta-analysis (CBMA) offers this, but the multiple algorithms can produce different results, making interpretation conditional on the algorithm. NEW METHOD: Here a new model based CBMA algorithm, Analysis of Brain Coordinates (ABC), is presented. ABC aims to be simple to understand by avoiding empirical elements where possible and by using a simple to interpret statistical threshold, which relates to the primary aim of detecting replicable effects. RESULTS: ABC is compared to both the most used and the most recently developed CBMA algorithms, by reproducing a published meta-analysis of localised grey matter changes in schizophrenia. There are some differences in results and the type of data that can be analysed, which are related to the algorithm specifics. COMPARISON TO OTHER METHODS: Compared to other algorithms ABC eliminates empirical elements where possible and uses a simple to interpret statistical threshold. CONCLUSIONS: There may be no optimal way to meta-analyse neuroimaging studies using CBMA. However, by eliminating some empirical elements and relating the statistical threshold directly to the aim of finding replicable effects, ABC makes the impact of the algorithm on any conclusion easier to understand.

Screening for tumours in paraneoplastic syndromes: report of an EFNS task force.

BACKGROUND: paraneoplastic neurological syndromes (PNS) almost invariably predate detection of the malignancy. Screening for tumours is important in PNS as the tumour directly affects prognosis and treatment and should be performed as soon as possible. OBJECTIVES: an overview of the screening of tumours related to classical PNS is given. Small cell lung cancer, thymoma, breast cancer, ovarian carcinoma and teratoma and testicular tumours are described in relation to paraneoplastic limbic encephalitis, subacute sensory neuronopathy, subacute autonomic neuropathy, paraneoplastic cerebellar degeneration, paraneoplastic opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome (LEMS), myasthenia gravis and paraneoplastic peripheral nerve hyperexcitability. METHODS: many studies with class IV evidence were available; one study reached level III evidence. No evidence-based recommendations grade A-C were possible, but good practice points were agreed by consensus. RECOMMENDATIONS: the nature of antibody, and to a lesser extent the clinical syndrome, determines the risk and type of an underlying malignancy. For screening of the thoracic region, a CT-thorax is recommended, which if negative is followed by fluorodeoxyglucose-positron emission tomography (FDG-PET). Breast cancer is screened for by mammography, followed by MRI. For the pelvic region, ultrasound (US) is the investigation of first choice followed by CT. Dermatomyositis patients should have CT-thorax/abdomen, US of the pelvic region and mammography in women, US of testes in men under 50 years and colonoscopy in men and women over 50. If primary screening is negative, repeat screening after 3-6 months and screen every 6 months up till 4 years. In LEMS, screening for 2 years is sufficient. In syndromes where only a subgroup of patients have a malignancy, tumour markers have additional value to predict a probable malignancy.

Beta interferons as immunotherapy in multiple sclerosis: a new outlook on a classic drug during the COVID-19 pandemic.

Beta interferons (IFN-ß) are pleiotropic cytokines with antiviral properties. They play important roles in the pathogenesis of multiple sclerosis (MS), an incurable immune-mediated disorder of the central nervous system. The clinical expression of MS is heterogeneous, with relapses of neuroinflammation and with disability accrual in considerable part unrelated to the attacks. The injectable recombinant IFN-ß preparations are the first approved disease-modifying treatments for MS. They have moderate efficacy in reducing the frequency of relapses, but good long-term cost-efficacy and safety profiles, so are still widely used. They have some tolerability and adherence issues, partly mitigated in recent years by the introduction of a PEGylated formulation and use of 'smart' autoinjector devices. Their general impact on long-term disability is modest but could be further improved by developing accurate tools for identifying the patient profile of best responders to IFN-ß. Here, we present the IFN-ß-based immunomodulatory therapeutic approaches in MS, highlighting their place in the current coronavirus disease (COVID-19) pandemic. The potential role of IFN-ß in the treatment of COVID-19 is also briefly discussed.

EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy.

BACKGROUND: Although Wernicke encephalopathy (WE) is a preventable and treatable disease it still often remains undiagnosed during life. OBJECTIVES: To create practical guidelines for diagnosis, management and prevention of the disease. METHODS: We searched MEDLINE, EMBASE, LILACS, Cochrane Library. CONCLUSIONS AND RECOMMENDATIONS: 1 The clinical diagnosis of WE should take into account the different presentations of clinical signs between alcoholics and non alcoholics (Recommendation Level C); although prevalence is higher in alcoholics, WE should be suspected in all clinical conditions which could lead to thiamine deficiency (good practice point - GPP). 2 The clinical diagnosis of WE in alcoholics requires two of the following four signs; (i) dietary deficiencies (ii) eye signs, (iii) cerebellar dysfunction, and (iv) either an altered mental state or mild memory impairment (Level B). 3 Total thiamine in blood sample should be measured immediately before its administration (GPP). 4 MRI should be used to support the diagnosis of acute WE both in alcoholics and non alcoholics (Level B). 5 Thiamine is indicated for the treatment of suspected or manifest WE. It should be given, before any carbohydrate, 200 mg thrice daily, preferably intravenously (Level C). 6 The overall safety of thiamine is very good (Level B). 7 After bariatric surgery we recommend follow-up of thiamine status for at least 6 months (Level B) and parenteral thiamine supplementation (GPP). 8 Parenteral thiamine should be given to all at-risk subjects admitted to the Emergency Room (GPP). 9 Patients dying from symptoms suggesting WE should have an autopsy (GPP).

Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells.

AIMS: To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by pro-inflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS). CB1 and CB2 signalling may be anti-inflammatory and neuroprotective in neuroinflammatory diseases. Cannabinoids can suppress inflammatory cytokines but the effects of these cytokines on CB1 and CB2 expression and function are unknown. METHODS: Immune cells from peripheral blood were obtained from healthy volunteers and patients with MS. Expression of CB1 and CB2 mRNA in whole blood cells, peripheral blood mononuclear cells (PBMC) and T cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Expression of CB1 and CB2 protein was determined by flow cytometry. CB1 and CB2 signalling in PBMC was determined by Western blotting for Erk1/2. RESULTS: Pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α (the latter likely NF-κB dependently) can upregulate CB1 and CB2 on human whole blood and peripheral blood mononuclear cells (PBMC). We also demonstrate upregulation of CB1 and CB2 and increased IL-1ß, IL-6 and TNF-α mRNA in blood of patients with MS compared with controls. CONCLUSION: The levels of CB1 and CB2 can be upregulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS.

Vasopressin neurotransmission and the control of circadian rhythms in the suprachiasmatic nucleus.

Vasopressin (VP) is one of the principal transmitters in the suprachiasmatic nucleus (SCN). Approximately 20% of neurones in the dorsomedial division of the SCN synthesize the peptide and a high proportion of SCN neurones (> 40%) are excited by VP acting through the V1 receptor. This suggests that VP may act as a feedback regulator of electrical activity within the nucleus. Such an intrinsic excitatory signal can be demonstrated by perifusion with a V1 antagonist which reduces spontaneous neural activity. As the synthesis and release of VP occurs in a circadian manner, this leads to a variable feedback excitation which may contribute to the circadian pattern of activity of the neural clock. This role in amplifying rhythmicity is supported by observations that animals deficient in VP show a reduced circadian amplitude of behavioural rhythms (e.g. locomotor and cortical electroencephalographic rhythms). VP expression declines during ageing and although aged animals show no change in the proportion of SCN neurones excited by VP, the rhythm of spontaneous electrical activity shows a progressive decline, consistent with the reduced endogenous excitatory feedback. However, the homozygous Brattleboro rat which lacks any VP expression still maintains rhythms of electrical activity, indicating that VP is not the sole factor generating circadian activity. The generation of this rhythmicity may depend upon the interaction of VP with other transmitter systems, such as the inhibitory transmitters somatostatin and GABA which show a circadian variation in efficacy. In addition to its role in feedback amplification of the endogenous rhythm of electrical activity, VP also functions as part of the efferent signal to the rest of the CNS where it potentially regulates a number of behavioural and physiological rhythms, including the circadian activity of the hypothalamo-pituitary-adrenal axis. Thus, the combined amplification and signalling functions makes VP an important component of the neuronal clock function in mammals.

Hepatitis C virus-mixed cryoglobulinemia-lymphoma relationship.

HCV (hepatitis C virus) chronic hepatitis has become one the most expensive diseases for public health systems all over the world in the past 10-20 years, a real epidemic, the second most frequent, after hepatitis B virus infection. Due to the complex manifestations, one may consider HCV infection as a "systemic" disease. Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of HCV infection, but cryoglobulinemic vasculitis (CV) is considered to be relatively sparse although prevalence studies are needed. Presence of serum cryoglobulins is essential for MC diagnosis, but serum levels do not correlate with the disease activity or prognosis. MC can be defined as a B lymphocyte proliferation disease being characterized by polyclonal activation and antibody synthesis. Evolution to lymphoma should be considered continuous but also other infectious, environmental or genetic factors could be involved. The t (14.18) translocation and Bcl-2 activation in B lymphocytes, B cell-activating factor (BAFF), E2-CD81 interaction, immunoregulatory T CD4+CD25(high) + lymphocytes and type III IFNs might play an important role in MC and lymphoma evolution in HCV patients.

Study of anti-endothelial cell antibodies in SLE patients with acute ischemic stroke.

Endothelial dysfunction is the predominant manifestation of SLE. Anti-endothelial cell antibodies (AECA) are a heterogeneous group of autoantibodies directed against different antigens in endothelial cells. The objective of this study was to assess the possible correlation between the presence of AECA and ischemic stroke manifestations in SLE. The AECA titers in serum from 34 patients with SLE and acute ischemic stroke (8 men and 26 women, mean age 38.37 +/- 3.25 years) and in 32 controls (11 men and 21 women, mean age 37.52 +/- 3.86 years) were tested. The method used was ELISA. The data were expressed as mean +/- SD from indicated number of patients. Comparison between patients and controls was expressed as relative risk with its 95% confidence interval (RR[95% CI]), where lower limit > 1.0 was considered significant. All p values were determined by Fisher's exact test. A value of p < 0.05 was considered statistically significant. AECA were positive in 31 out of 34 patients, mean value 19.2 +/- 16.3 U/mL and in 8 out of 32 controls, mean value 5.5 +/- 2.6 U/mL (RR 7.154 [95% CI 2.801 to 18.274]), p < 0.0001. Patients with SLE and acute ischemic stroke tended to have higher mean values of AECA. AECA play a pivotal role in the pathogenesis of neurologic complications of SLE. AECA titers in SLE patients with acute ischemic stroke support a role for AECA as potential diagnostic marker possibly associated to cerebral manifestations of SLE patients. Further study is needed in order to clarify if AECA presence is related to systemic diseases severity and to situate their importance among other markers of endothelial dysfunction.

Extra-articular Manifestations in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main characteristic is persistent joint inflammation that results in joint damage and loss of function.Although RA is more common in females, extra-articular manifestations of the disease are more common in males. The extra-articular manifestations of RA can occur at any age after onset. It is characterised by destructive polyarthritis and extra-articular organ involvement, including the skin, eye, heart, lung, renal, nervous and gastrointestinal systems. The frequence of extra-articular manifestations in RA differs from one country to another. Extra-articular organ involvement in RA is more frequently seen in patients with severe, active disease and is associated with increased mortality. Incidence and frequence figures for extra-articular RA vary according to study design. Extra-articular involvement is more likely in those who have RF and/or are HLA-DR4 positive. Occasionally, there are also systemic manifestations such as vasculitis, visceral nodules, Sjögren's syndrome, or pulmonary fibrosis present. Nodules are the most common extra-articular feature, and are present in up to 30%; many of the other classic features occur in 1% or less in normal clinic settings. Sjögren's syndrome, anaemia of chronic disease and pulmonary manifestations are relatively common - in 6-10%, are frequently present in early disease and are all related to worse outcomes measures of rheumatoid disease in particular functional impairment and mortality. The occurrence of these systemic manifestations is a major predictor of mortality in patients with RA.This paper focuses on extra-articular manifestations, defined as diseases and symptoms not directly related to the locomotor system.

T helper 17 cell population in lupus erythematosus.

UNLABELLED: Lupus erythematosus (LE) is an autoimmune inflammatory disease that involves many organs and systems. Immunological factors seem to play a key-role in LE pathogenesis. LE patients have T lymphocytes dysfunctions.Th17 is implicated in the pathogenesis of various autoimmune diseases like psoriasis, multiple sclerosis or rheumatoid arthritis. The purpose of this study was to evaluate the circulating Th17 cell population in LE patients. MATERIAL AND METHODS: A total of 15 LE patients were recruited and divided into three groups: systemic lupus erythematosus (SLE), discoid lupus (DLE) and subacute lupus (SCLE). Serum IL-17A, IL-17F and IL-23 were detected. Th17 circulating cells were evaluated by flow cytometry. RESULTS: Serum IL-17A and IL-17F levels were higher in SLE, DLE and SCLE patients compared to healthy controls. The number of Th17 cells were higher in SLE and DLE patients (p<0.05). the number of CD3+IL-17+ cells were higher in SLE, DLE and SCLE patients (p<0.05). CONCLUSION: Th17 lymphocytes are implicated in LE pathogenesis. Our findings suggest that IL-17 is implicated not only in SLE but also in DLE and SCLE immunopathogenesis.

Detection of serum of IgG anti-neuronal antibodies in systemic lupus erythematosus patients with central nervous system manifestations.

The objective of the study was to assess the frequence of serum IgG anti-neuronal antibodies (NA) in SLE patints with CNS manifestations. Serum anti-NA antibodies were measured in 47 patients with SLE with CNS manifestations (CNS-SLE), age 33-52 years, mean age 38.6 years, 18 men and 29 women, as compared to 31 patients with SLE without CNS manifestations, age 28-56 years, mean age 41.2 years, 13 men and 18 women and 56 healthy subjects. Serum IgG antineuronal antibodies were measured by indirect immunofluorescent assay. Thirty-five of out 47 CNS-SLE patients presented anti-NA (74.6%). Anti-NA were observed in 15 out of 15 patients with acute confusional state (100%), in 8 of 8 patients with cerebrovascular disease (100%), in 5 out of 7 patients with seizure disorder (76.3%), and in 4 out of 5 patients in intractable headache (86.8%). Out of 31 nonCNS-SLE patients 1 patient presented anti-NA (3.9%). Serum anti-NA were more frequently observed in CNS-SLE patients as compared to controls (p < 0.000001). The frequence of serum anti-NA was significantly higher in CNS-SLE patients as compared to non CNS-SLE patients (p < 0.00001). In conclusion, serum anti-neuronal antibodies are associated with CNS-SLE. These antibodies are more frequent in CNS-SLE than in nonCNS-SLE patients, demonstrating a strong association between serum anti-NA and CNS involvement of SLE. The presence of serum anti-NA could be a useful diagnostic tool for CNS-SLE, the test could help to distinguish SLE from other diseases with similar symptoms. Further studies are needed to evaluate the predictive value of anti-NA in SLE.

Plasma myeloperoxidase levels in patients with acute ischemic stroke.

Myeloperoxidase (MPO) is a glycoprotein released by activated polymorphonuclear neutrophils, which takes part in the defence of the organism through production of hypochlorous acid (HOCl), a potent oxidant. MPO has a role in pathogenesis of atherosclerosis. The aim of the study was to evaluate the time course of MPO plasma levels in the early stage of ischemic stroke. The study included 78 patients with acute ischemic stroke, 46 females and 32 males, mean age 74.3 +/- 6.8 years. Blood samples for MPO measurement were taken within 24 hours after the onset of ischemic stroke. Seventy-two patients served as matched controls 43 females and 29 males, mean age 71.3 +/- 6.4 years. MPO was measured in plasma using the Abbott Architect platform (Abbott Diagnostics Inc., Abbott Parck IL). Comparisons between patients and controls and patients group were expressed as relative risk with its 95% confidence interval (RR [95% CI]), where a lower limit > 1.0 was considered significant. All p values were determined by Fischer's exact test. A value of p < 0.05 was considered statistically significant. Mean plasma MPO level was in patients with acute ischemic stroke 583 +/- 48 pmol/L. Seventy-one patients out of seventy-eight patients with ischemic stroke presented mean plasma MPO levels greater than the upper of normal (425 +/- 36 pmol/L, p < 0.0001, (RR 8.188, [95% CI 4.038 to 16.600]). Twelve controls presented mean plasma MPO level greater than the upper of normal. In conclusion, plasma MPO levels were statistically significantly higher in patients after ischemic stroke as compared to controls. MPO has been associated with acute ischemic stroke but its direct role in its pathogenesis has not been established. MPO could be proposed as a potential prognostic marker of such lesions rather than a marker of diagnosis. MPO is a new biomarker and a possible future therapeutic target.

Study of antiphospholipid antibodies in type 2 diabetes mellitus with and without diabetic retinopathy.

Antiphospholipid antibodies (aPL) are considered to be contributory factors in the development of thrombotic events. The objective of the study was to determine if aPL are involved in the pathogenesis of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. IgG anticardiolipin antibodies (IgG aCL), lupus anticoagulant (LA), and anti-IgG beta2-glycoprotein I antibodies (anti-beta2-GPI) were prospectively tested in 34 patients with DR (group 1), 20 males and 14 females, range of age 52-79 years, mean age 57 +/- 4.6 years, duration of diabetes 8-15 years, as compared to 29 type 2 diabetic patients without DR (group 2), 19 males and 10 females, range of age 54-77 years, mean age 58 +/- 4.8 years, duration of diabetes 10-13 years, and to 31 controls matched for age and sex (group 3). IgG aCL and anti-beta2-GPI were detected by enzyme-linked immunosorbent assay (ELISA) and LA was detected by activated partial thromboplastin time, kaolin clotting time, dilute Russell's viper venom time, dilute prothrombin time. Comparison between patients and controls and patients group were expressed as relative risk with its 95% confidence interval (RR [95%/CI], where a lower limit > 1.0 was considered significant. All values were determined by Fischer's exact test. A value of p < 0.05 was considered statistically significant. The incidence of IgG aCL positive (low 4-15 GPL U IgG aCL titers) in group 1 was 21/34 (62%) vs. 12/29 (41%) in group 2 (RR 1.460 95% CI [0.9052 to 2.382]), p = 0.1330. The incidence of LA positive in group 1 was 27/34 (79%) vs. 8/29 (28%) in group 2 (RR 3.086 95% CI [1.584 to 6.010]), p < 0.0001. The incidence of anti-IgG beta2-GPI positive in group 1 was 29/34 (85%) vs. 6/29 (21%) in group 2 (RR 4.640 95% CI [2.067-10.418]), p < 0.0001. The results suggest the possible participation of anti-beta2-GPI and LA in the pathogenesis of DR, shifting the hemostatic balance toward a pro-thrombotic state increasing the risk of developing thrombosis.

Changes of magnesium serum levels in patients with acute ischemic stroke and acute infections.

Magnesium (Mg) deficiency seems to be implicated in immune dysfunction, including acute and chronic infections. Magnesium serum levels in 53 patients with acute ischemic stroke and acute bacterial (37 patients) and acute viral infections (16 patients) (29 men and 24 women, mean age 68.6+/-4.7 years) were analyzed as compared to 36 healthy subjects. As Mg is mainly an intracellular ion, assessment of Mg status is difficult. Mg serum levels were determined by the colorimetric method. Data were statistically analyzed. In patients with acute bacterial infections (sepsis, bronchopneumonia, urinary tract infections) a statistically significant decrease of Mg serum concentrations was found (1.26+/-0.12 mEq/L vs 1.69+/-0.14 mEq/L, p<0.001). In patients with acute viral infections, the decrease of Mg serum levels was significantly less (1.64+/-0.13 mEq/L vs 1.69+/-0.14 mEq/L, p<0.05). The change onset of Mg occurred within a few days and persisted for several weeks. These changes seemed to be non-specific and were independent of the agent causing bacterial infection. Patients with sepsis having a high degree of inflammation did not show a positive correlation between the severity of the disease and the changes of Mg. In conclusion, the measurement of Mg serum in bacterial infections is useful and physicians should maintain a high index of suspicion for hypomagnesemia and implement Mg therapy.