H-magnetic resonance spectroscopy. diagnostic tool in recurrent headache in systemic lupus erythematosus. a case report

We describe serial MR-spectroscopy studies in a patient with systemic lupus erythematosus and headache. We used MR-spectroscopy to monitor disease activity during periods with and without headache. MR-spectroscopy investigates metabolic alterations and was used to explore the pathophysiological mechanism involved in the complications of systemic lupus erythematosus. Our patient underwent serial conventional MRI and MR-spectroscopy at times of controlled and uncontrolled headache, with or without visual aura. MR-spectroscopy showed an increase in the choline/creatine ratio in thalamus and posterior white matter only during periods of uncontrolled headache with visual aura. Conventional MRI scans were normal at all times. MR-spectroscopy should be used in the diagnosis and follow-up of headache in patients with systemic lupus erythematosus

Role of brain perfusion SPECT with 99mTc HMPAO in the assessment of response to drug therapy in patients with autoimmune vasculitis: a prospective study

Abstract BACKGROUND: The diagnosis of vasculitis in the brain remains a quite difficult achievement. To the best of our knowledge, there is no imaging method reported in literature which is capable of reaching to a diagnosis of vasculitis with very high sensitivity. AIM: The aim of this study was to determine whether perfusion brain single photon emission computed tomography (SPECT) can be usefully employed in monitoring the treatment of vasculitis, allowing treating only potentially responder patients and avoiding the side effects on patients who do not respond. MATERIALS AND METHODS: Twenty patients (two males and 18 females) suffering from systemic lupus erythematosus (SLE; n = 5), Behcet's disease (BD; n = 5), undifferentiated vasculitis (UV; n = 5), and Sjogren's syndrome (SS; n = 5) were included in the study. All patients underwent a wide neurological anamnestic investigation, a complete objective neurological examination and SPECT of the brain with 99mTc-hexamethyl-propylene-aminoxime (HMPAO). The brain SPECT was then repeated after appropriate medical treatment. The neurological and neuropsychiatric follow-up was performed at 6 months after the start of the treatment. RESULTS: Overall, the differences between the scintigraphic results obtained after and before the medical treatment indicated a statistically significant increase of the cerebral perfusion (CP). In 19 out of 200 regions of interest (ROI) studied, the difference between pre- and post treatment percentages had negative sign, indicating a worsening of CP. This latter event has occurred six times (five in the same patients) in the UV, 10 times (eight in the same patients) in the SLE, never in BD, and three times (two in the same patient) in the SS. CONCLUSION: The reported results seem to indicate the possibility of identifying, by the means of a brain SPECT, responder and nonresponder (unchanged or worsened CP) patients, affected by autoimmune vasculitis, to the therapy

Neurophysiological and functional MRI evidence of reorganization of cortical motor areas in cerebral arteriovenous malformation

Functional magnetic resonance imaging (fMRI) research has shown that brain arteriovenous malformations (AVMs) lead to reorganization of cortical motor areas. Since it is known that blood oxygenation level-dependent signal in fMRI may be influenced by the hemodynamic perturbation associated with the presence of the AVM, in the present study, a combined exploration with fMRI and transcranial magnetic stimulation was performed in a patient with a right rolandic AVM in order to explore the relationship between neuronal and hemodynamic activity. The combined protocol of investigation adopted in this study was able to provide significant information regarding neuronal activity of the different cortical areas that partake to post-lesional reorganization

Moving Buffalo Farming beyond Traditional Areas: Performances of Animals, and Quality of Mozzarella and Forages

An observational case study was designed to highlight issues associated with a possible expansion of dairy buffalo (Bubalus bubalis) farming outside the traditional coastal plains of southern Italy. Twenty pregnant buffaloes were transferred to a hilly inland farm. After calving, production and reproduction data were collected monthly throughout lactation. From 4 to 6 months of lactation, buffaloes were enrolled in a feeding trial to evaluate the effects of locally grown forages (maize silage vs. hay) on milk production and in vivo digestibility. Sensory properties of mozzarella cheese produced at a local dairy were also evaluated. No obvious effects of diet were found. Compared to the data recorded in the previous lactation completed in the farm of origin, milk yield was reduced by 37.2%, and milk protein by 6.1%, whereas milk fat improved (+4.5%). A lower pregnancy rate (−13.3%), increased days open (+122%), and a prolonged intercalving period (+26.9%) were also observed. Lactation length was shorter than the standard value of 270 d. The results showed that peculiar reproductive characteristics, lower environmental temperatures, and the specificity of the mozzarella production process are the main problems to be addressed in an expansion of buffalo farming outside traditional area

Dynamic changes of mmp-9 plasma levels correlate with jvc reactivation and immune activation in natalizumab-treated multiple sclerosis patients

The aim of the study was to investigate the changes of matrix metalloproteinase (MMP)-2 and MMP-9 plasma levels during natalizumab treatment and their correlation with JC virus (JCV) reactivation and T-lymphocyte phenotypic modifications in peripheral blood samples from 34 relapsing-remitting multiple sclerosis (RRMS) patients. MMP-9 levels were assessed by zymography in plasma samples. JCV-DNA was detected through quantitative real time PCR in plasma samples. T-lymphocyte phenotype was assessed with flow cytometry. MMP-9 plasma levels resulted increased from 12 to 24 natalizumab infusions. Stratifying plasma samples according to JCV-DNA detection, MMP-9 plasma levels were significantly increased in JCV-DNA positive than JCV-DNA negative samples. MMP-9 plasma levels resulted positively correlated with JCV viral load. CD4 immune senescence, CD8 immune activation and CD8 effector percentages were positively correlated to MMP-9 plasma levels, whereas a negative correlation between CD8 naïve percentages and MMP-9 plasma levels was found. Our data indicate an increase of MMP-9 plasma levels between 12 and 24 natalizumab infusions and a correlation with JCV-DNA detection in plasma, T-lymphocyte immune activation and senescence. These findings could contribute to understand PML pathogenesis under natalizumab treatment, suggesting a potential role of MMP-9 as a predictive marker of PML in RRMS patients

Disruption of neurite morphology parallels MS progression

Objectives: To apply advanced diffusion MRI methods to the study of normal appearing brain tissue in MS and examine their correlation with measures of clinical disability. Methods: A multi-compartment model of diffusion MRI called neurite orientation dispersion and density imaging (NODDI) was used to study 20 patients with relapsing-remitting (RR-) and 15 with secondary progressive (SP)-MS, and 20 healthy controls. Maps of NODDI were analyzed voxel-wise to assess the presence of abnormalities within the normal appearing brain tissue, and the association with disease severity. Standard diffusion tensor imaging (DTI) parameters were also computed for comparing the two techniques. Results: MS patients showed reduced neurite density and increased orientation dispersion compared to controls in several brain areas (P<0.05), with SPMS patients having more widespread abnormalities. DTI indices were also sensitive to some changes. In addition, SPMS patients showed reduced orientation dispersion in the thalamus and caudate nucleus. These abnormalities were associated with scores of disease severity (P<0.05). The association with the MS functional composite score was higher in SPMS compared to RRMS patients. Conclusions: NODDI and DTI findings are largely overlapping. Nevertheless, NODDI helps to interpret previous findings of increased anisotropy in the thalamus of MS patients, and are consistent with the degeneration of selective axon populations

JC virus-DNA detection is associated with CD8 fffector accumulation in peripheral blood of patients with multiple sclerosis under natalizumab treatment, independently from JC virus serostatus

Although natalizumab (anti-α4 integrin) represents an effective therapy for relapsing remitting multiple sclerosis (RRMS), it is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), caused by the polyomavirus JC (JCV). The aim of this study was to explore natalizumab-induced phenotypic changes in peripheral blood T-lymphocytes and their relationship with JCV reactivation. Forty-four patients affected by RRMS were enrolled. Blood and urine samples were classified according to natalizumab infusion number: 0 (N0), 1-12 (N12), 13-24 (N24), 25-36 (N36), and over 36 (N > 36) infusions. JCV-DNA was detected in plasma and urine. T-lymphocyte phenotype was evaluated with flow cytometry. JCV serostatus was assessed. Ten healthy donors (HD), whose ages and sexes matched with the RRMS patients of the N0 group, were enrolled. CD8 effector (CD8 E) percentages were increased in natalizumab treated patients with detectable JCV-DNA in plasma or urine compared to JCV-DNA negative patients (JCV-) (p < 0.01 and p < 0.001, resp.). Patients with CD8 E percentages above 10.4% tended to show detectable JCV-DNA in plasma and/or urine (ROC curve p = 0.001). The CD8 E was increased when JCV-DNA was detectable in plasma or urine, independently from JCV serology, for N12 and N24 groups (p < 0.01). As long as PML can affect RRMS patients under natalizumab treatment with a negative JCV serology, the assessment of CD8 E could help in the evaluation of JCV reactivation

Hay or silage? How the forage preservation method changes the volatile compounds and sensory properties of Caciocavallo cheese.

The aim of this study was to determine the effect of the forage preservation method (silage vs. hay) on volatile compounds and sensory properties of a traditional Caciocavallo cheese during ripening. A brown-midrib sudangrass hybrid was cultivated on a 7-ha field and at harvesting it was half ensiled in plastic silo bags and half dried to hay. Forty-four lactating cows were equally allotted into 2 groups fed a isonitrogenous and isoenergetic total mixed ration containing as the sole forage either sorghum hay (H group) or sorghum silage (S group). Milk from the 2 groups was used to produce 3 batches/diet of Caciocavallo ripened for 30, 60, and 90 d. Milk yield and composition as well as cheese chemical and fatty acid composition were not markedly affected by the diet treatment and ripening time. By contrast, ripening induced increased levels of the appearance attribute "yellowness," along with the "overall flavor," the odor/flavor attributes "butter" and "hay," the "salty," "bitter," and "umami" tastes, and the texture attribute "oiliness," whereas the appearance attribute "uniformity" and the texture attribute "elasticity" were reduced. The silage-based diet induced higher perceived intensities of several attributes such as "yellowness"; "overall flavor"; "butter"; "grass" and "hay" odor/flavors; "salty," "bitter," and "umami" tastes; and "tenderness" and "oiliness" textures. In S cheese we also observed higher amounts of ketones and fatty acids. Conversely, H cheese showed the terpene α-pinene, which was not detected in S cheese, and a higher intensity of the appearance attribute "uniformity." These differences allowed the trained panel to discriminate the products, determined an increased consumer liking for 90-d ripened cheese, and tended to increase consumer liking for hay cheese

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects

Peripheral blood biomarkers in multiple sclerosis.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc