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Disk battery ingestions in children are increasing worldwide. This condition may cause severe complications, especially if the battery is lodged in the oesophagus. The most dangerous complication with the highest mortality rate is aorto-oesophageal fistula. The tissue damage may appear after 2 hours from the ingestion. The paper reports the case of a 2-year-old girl who was admitted to the Emergency Department 15 days after the ingestion of a disk battery and who presented with an aorto-oesophageal fistula complication.

Magnesium (Mg) is involved in the regulation of metabolism and in the maintenance of the homeostasis of all the tissues, including the brain, where it harmonizes nerve signal transmission and preserves the integrity of the blood–brain barrier. Mg deficiency contributes to systemic low-grade inflammation, the common denominator of most diseases. In particular, neuroinflammation is the hallmark of neurodegenerative disorders. Starting from a rapid overview on the role of magnesium in the brain, this narrative review provides evidences linking the derangement of magnesium balance with multiple sclerosis, Alzheimer’s, and Parkinson’s diseases.

Despite remaining the best in vitro model to resemble the human brain, a weakness of human cerebral organoids is the lack of the endothelial component that in vivo organizes in the blood brain barrier (BBB). Since the BBB is crucial to control the microenvironment of the nervous system, this study proposes a co-culture BBB and cerebral organoids. We utilized a BBB model consisting of primary brain microvascular endothelial cells and astrocytes in a transwell system. Starting from induced Pluripotent Stem Cells (iPSCs) we generated human cerebral organoids which were then cultured in the absence or presence of an in vitro model of BBB. We evaluated if the presence of the BBB influences the maturation of cerebral organoids. By morphological analysis, it emerges that in the presence of the BBB the cerebral organoids are better organized than controls in the absence of the BBB. This effect seems to be driven by Brain Derived Neurotrophic Factor (BDNF), a neurotrophic factor released by the endothelial component of the BBB, which is involved in neurodevelopment, neuroplasticity and neurosurvival.Graphical AbstractThe current culture model of human cerebral organoids does not require the presence of a BBB (left side). However, the BBB is an important source of BDNF, which is crucial for neurodevelopment and brain health. The cerebral organoids co-cultured for 4 days in the presence of the BBB show a higher cortical organization than the organoids cultured in the absence of the BBB, as illustrated on the right.

Antineutrophil cytoplasmic antibody (ANCA) may appear in the course of rheumatic diseases (RD) but the kidney involvement is very rare and the prognosis poorly defined.We retrospectively identified patients with RD among 153 patients with ANCA glomerulonephritis (ANCA-GN). Their clinical/histological presentation and outcome were compared with that of primitive ANCA-GN patients (1:4) matched for sex, age, ANCA type and follow-up.Nine patients (5.9%) were included: three had rheumatoid arthritis, two systemic sclerosis, two psoriatic arthritis, one ankylosing spondylitis and one seronegative spondylarthritis. Seven patients were MPO positive, two PR3 positive. ANCA-GN developed 74 months after RD with microscopic haematuria and acute kidney dysfunction in all but two patients. After 68-month follow-up, four patients (44.4%) achieved response to therapy defined as eGFR60/min/1,73 m2 or stable, no microscopic haematuria and negative ANCA. At ANCA-GN diagnosis, serum creatinine and C-reactive protein were significantly lower in RD-ANCA-GN (2.38 vs. 3.34mg/dl, p=0.05 and 2.3mg/dl vs. 7.2mg/dl; p=0.05, respectively) while haemoglobin was higher (12.3g/dl vs. 9.3g/dl p0.01) than in the 36 primitive ANCA-GN patients of control group. At kidney biopsy, focal forms were more frequent in RD patients (44.45% vs. 18.75%, p=0.11). The treatment between the two groups was not significantly different. At last observation, the percentage of patients with ESKD was lower in RD than in controls (11.1%vs. 30.5%; p=0.23).Patients with RD seem to develop ANCA-GN with less severe clinical/histological kidney involvement, and better long-term kidney survival than primitive ANCA-GN. This is probably due to the strict monitoring of RD patients that allows a prompter ANCA-GN diagnosis and treatment.

Several studies have demonstrated the role of high glucose in promoting endothelial dysfunction utilizing traditional two-dimensional (2D) culture systems, which, however, do not replicate the complex organization of the endothelium within a vessel constantly exposed to flow. Here we describe the response to high glucose of micro- and macro-vascular human endothelial cells (EC) cultured in biomimetic microchannels fabricated through soft lithography and perfused to generate shear stress. In 3D macrovascular EC exposed to a shear stress of 0.4 Pa respond to high glucose with cytoskeletal remodeling and alterations in cell shape. Under the same experimental conditions, these effects are more pronounced in microvascular cells that show massive cytoskeletal disassembly and apoptosis after culture in high glucose. However, when exposed to a shear stress of 4 Pa, which is physiological in the microvasculature, human dermal microvascular endothelial cells (HDMEC) show alterations of the cytoskeleton but no apoptosis. This result emphasizes the sensitivity of HDMEC to different regimens of flow. No significant variations in the thickness of glycocalyx were detected in both human endothelial cells from the umbilical vein and HDMEC exposed to high glucose in 3D, whereas clear differences emerge between cells cultured in static 2D versus microfluidic channels. We conclude that culture in microfluidic microchannels unveils unique insights into endothelial dysfunction by high glucose.

The magnesium transporters TRPM7 and MagT1 are overexpressed in osteoblastogenesis. We have shown that silencing either TRPM7 or MagT1 accelerates the osteogenic differentiation of human bone mesenchymal stem cells. Here we demonstrate that the simultaneous downregulation of TRPM7 and MagT1 inhibits cell growth and activates autophagy, which is required in the early phases of osteoblastogenesis. In TRPM7/MagT1 downregulating cells the expression of two transcription factors required for activating osteogenesis, i.e. RUNX2 and OSTERIX, is induced more than in the controls both in the presence and in the absence of osteogenic stimuli, while COL1A1 is upregulated in co-silencing cells as much as in the controls. This explains why we found no differences in calcium deposition. We conclude that one of the two transporters should be expressed to accelerate osteogenic differentiation.

Mesenchymal stem cells are fundamental for bone formation and repair since they respond to microenvironmental stimuli by undergoing osteogenic differentiation. We show that the kinase and cation channel TRPM7 and the magnesium transporter MagT1 have a role in harmonizing the osteogenic differentiation of human mesenchymal stem cells. TRPM7 and MagT1 are upregulated in osteogenic differentiation and silencing either one accelerates osteogenic differentiation, partly through the activation of autophagy. Intriguingly, similar results were obtained when the cells were cultured under magnesium deficient conditions. These results underpin the contribution of magnesium, TRPM7 and MagT1 to autophagy and osteoblastogenesis.

International audience; Magnesium is an essential element of life, involved in the regulation of metabolism and homeostasis of all the tissues. It also regulates immunological functions, acting on the cells of innate and adaptive immune systems. Magnesium deficiency primes phagocytes, enhances granulocyte oxidative burst, activates endothelial cells and increases the levels of cytokines, thus promoting inflammation. Consequently, a low magnesium status, which is often underdiagnosed, potentiates the reactivity to various immune challenges and is implicated in the pathophysiology of many common chronic diseases. Here we summarize recent advances supporting the link between magnesium deficiency, inflammatory responses and diseases, and offer new hints towards a better understanding of the underlying mechanisms.

A correct magnesium (Mg2+) intake is essential for bone health. In particular, Mg2+ deficiency inhibits the proliferation of osteoblast-like SaOS-2 cells by increasing nitric oxide (NO) production through the upregulation of inducible NO synthase. At the moment, little is known about the expression and the role of TRPM7, a channel/enzyme involved in Mg2+ uptake, and MagT1, a Mg2+ selective transporter, in SaOS-2 cells. Here, we demonstrate that TRPM7 is not modulated by different extracellular concentrations of Mg2+ and its silencing exacerbates growth inhibition exerted by low Mg2+ through the activation of inducible NO synthase and consequent accumulation of NO. Moreover, MagT1 is upregulated in SaOS-2 cultured in high Mg2+ and its silencing inhibits the growth of SaOS-2 cultured in media containing physiological or high Mg2+, without any modulation of NO production. We propose that TRPM7 and MagT1 are both involved in regulating SaOS-2 proliferation through different mechanisms.

International audience; Reduced blood flow, as occurring in ischemia or resulting from exposure to microgravity such as encountered in space flights, induces a decrease in the level of shear stress sensed by the endothelial cells forming the inner part of blood vessels. In the present study, we use a microvasculature-on-a-chip device in order to investigate in vitro the effect of such a reduction in shear stress on shear-adapted endothelial cells. We find that, within one hour of exposition to reduced wall shear stress, human umbilical vein endothelial cells undergo a reorganization of their actin skeleton, with a decrease in the number of stress fibers and actin being recruited into the cells' peripheral band, indicating a fairly fast change in cells' phenotype due to altered flow.

Transient Receptor Potential Melastatin (TRPM)7 is important in maintaining the intracellular homeostasis of magnesium (Mg), which is instrumental for vital cellular functions. Since the upregulation of TRPM7 has been proposed as a marker of endothelial dysfunction, we evaluated the effects of high glucose, which markedly impacts endothelial performance, on TRPM7 and intracellular Mg homeostasis in human macrovascular endothelial cells. We show that glucose-induced free radicals increase the amounts of TRPM7 as well as total intracellular magnesium. On the contrary, the highly selective Mg transporter MagT1 is not modulated by high glucose, hydrogen peroxide and low extracellular magnesium. We conclude that in endothelial cells high glucose alters Mg homeostasis through the upregulation of TRPM7.

Drug resistance remains a major obstacle in cancer treatment. Because mitochondria mediate metabolic reprogramming in cancer drug resistance, we focused on these organelles in doxorubicin sensitive and resistant colon carcinoma cells. We employed soft X-ray cryo nano-tomography to map three-dimensionally these cells at nanometer-resolution and investigate the correlation between mitochondrial morphology and drug resistance phenotype. We have identified significant structural differences in the morphology of mitochondria in the two strains of cancer cells, as well as lower amounts of Reactive oxygen species (ROS) in resistant than in sensitive cells. We speculate that these features could elicit an impaired mitochondrial communication in resistant cells, thus preventing the formation of the interconnected mitochondrial network as clearly detected in the sensitive cells. In fact, the qualitative and quantitative three-dimensional assessment of the mitochondrial morphology highlights a different structural organization in resistant cells, which reflects a metabolic cellular adaptation functional to survive to the offense exerted by the antineoplastic treatment.

Exposure to real or simulated microgravity is sensed as a stress by mammalian cells, which activate a complex adaptive response. In human primary endothelial cells, we have recently shown the sequential intervention of various stress proteins which are crucial to prevent apoptosis and maintain cell function. We here demonstrate that mitophagy contributes to endothelial adaptation to gravitational unloading. After 4 and 10 d of exposure to simulated microgravity in the rotating wall vessel, the amount of BCL2 interacting protein 3, a marker of mitophagy, is increased and, in parallel, mitochondrial content, oxygen consumption, and maximal respiratory capacity are reduced, suggesting the acquisition of a thrifty phenotype to meet the novel metabolic challenges generated by gravitational unloading. Moreover, we suggest that microgravity induced-disorganization of the actin cytoskeleton triggers mitophagy, thus creating a connection between cytoskeletal dynamics and mitochondrial content upon gravitational unloading.

Vascular endothelial growth factor (VEGF) is important for maintaining healthy endothelium, which is crucial for vascular integrity. In this paper, we show that VEGF stimulates the nuclear translocation of endothelial differentiation-related factor 1 (EDF1), a highly conserved intracellular protein implicated in molecular events that are pivotal to endothelial function. In the nucleus, EDF1 serves as a transcriptional coactivator of peroxisome proliferator-activated receptor gamma (PPAR&gamma, ), which has a protective role in the vasculature. Indeed, silencing EDF1 prevents VEGF induction of PPAR&gamma, activity as detected by gene reporter assay. Accordingly, silencing EDF1 markedly inhibits the stimulatory effect of VEGF on the expression of FABP4, a PPAR&gamma, inducible gene. As nitric oxide is a marker of endothelial function, it is noteworthy that we report a link between EDF1 silencing, decreased levels of FABP4, and nitric oxide production. We conclude that EDF1 is required for VEGF-induced activation of the transcriptional activity of PPAR&gamma

Magnesium contributes to the regulation of inflammatory responses. Here, we focus on the role of magnesium in acute inflammation. Although present knowledge is incomplete to delineate an accurate scenario and a schedule of the events occurring under magnesium deficiency, it emerges that low magnesium status favors the induction of acute inflammation by sensitizing sentinel cells to the noxious agent, and then by participating to the orchestration of the vascular and cellular events that characterize the process.

Infections of orthopedic implants are associated with high morbidity. The emergence of antibiotic resistant strains and the tendency of microbes to form biofilms on orthopedic devices prompt the individuation of novel antimicrobial agents. Silver nanoparticles represent an interesting alternative, but their effects on bone cells need to be clarified. We focused on osteoblast-like cells and on bone marrow-mesenchymal stem cells and found that these cells are rather resistant to the cytotoxic effects of silver nanoparticles, with a half maximal inhibitory concentration around 25 µg/mL as detected by MTT assay. Within a month of treatment, osteoblast-like cells adapt to the presence of the nanoparticles by upregulating hsp70 as shown by western blot. Hsp70 overexpression correlates with the restoration of normal cell proliferation. No alterations in the extent and time requirements were detected in mesenchymal stem cell induced to differentiate in osteoblasts in the presence of silver nanoparticles. Because the concentrations of silver nanoparticles which show antimicrobial activity are lower than those exerting toxic effects on bone-forming cells in vitro, we suggest that silver nanoparticles might represent a challenging tool to fight infections in orthopedic implants.

The aim of this study was to establish whether, in a cross-sectional study, the normalized measures of whole and regional brain atrophy correlate better with tests assessing the cognitive function than the absolute brain atrophy measures. The neuropsychological performances and disability have been assessed in 39 patients with relapsing-remitting multiple sclerosis (MS). T1- and T2-lesion load (LL) of total brain and frontal lobes (FLs) were measured using a reproducible semiautomated technique. The whole brain volume and the regional brain parenchymal volume (RBPV) of FLs were obtained using a computerized interactive program, which incorporates semiautomated and automated segmentation processes. Normalized measures of brain atrophy, i.e., brain parenchymal fraction (BPF) and regional brain parenchymal fraction (RBPF) of FLs, were calculated. The scan-rescan, inter- and intrarater coefficient of variation (COV) and intraclass correlation coefficient (ICC) have been estimated. The RBPF of FLs showed an acceptable level of reproducibility which ranged from 1.7% for intrarater variability to 3.2% for scan-rescan variability. The mean ICC was 0.88 (CI 0.82-0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with neuropsychological functioning, disability and quantitative MRI lesion measures than RBPV. These differences were statistically significant: P=0.001 for Stroop Color Word Interference test, P=0.001 for Paced Auditory Serial Addition Test, P=0.04 for Standard Raven Progressive Matrices, P=0.049 for Expanded Disability Status Scale, P=0.01 for T2-LL of FLs and P< 0.001 for T1-LL of FLs. BPF demonstrated significant correlations with tests assessing cognitive functions, whereas BPAV did not. The correlation analysis results were supported by the results of multiple regression analysis which showed that only the normalized brain atrophy measures were associated with tests exploring the cognitive functions. These data suggest that RBPF is a reproducible and sensitive method for measuring frontal parenchymal atrophy. The normalized measures of whole and regional brain parenchymal atrophy should be preferred to absolute measures in future studies that correlate neuropsychological performances and brain atrophy measures in patients with MS.

The objective of this study was to establish whether the time interval of 3 months is sufficient to detect whole-brain atrophy changes in patients with relapsing-remitting (RR) multiple sclerosis (MS). Another aim was to assess the value of monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and of different Gd-enhancement patterns as predictors of brain atrophy. Thirty patients with RRMS (mean disease duration 4.9 years, mean age 34.4 years and mean Expanded Disability Status Scale [EDSS] 1.4) were assessed at baseline and monthly for a period of 3 months with clinical and MRI examinations. Calculations of baseline and monthly absolute and percent changes of MRI measures have been obtained using two semiautomated (Buffalo and Trieste) and one automated (SPM99) segmentation method. Changes of brain parenchymal fraction (BPF) were investigated according to Gd-enhancement patterns. Mean absolute and percent changes of BPF did not significantly differ at any time point in the study for any of the three methods. There was slight but not significant decrease of BPF from baseline to month 3: -0.0004 (0.05%), p=0.093 for Trieste; -0.0006 (0.07%), p=0.078 for Buffalo; and -0.0006 (0.08%), p=0.081 for SPM99 method. In ring-enhancement positive patients, there was a significant difference between baseline and month 3 changes of BPF, EDSS, and number of relapses. Over the study period, we did not demonstrate differences between changes of BPF according to the presence of Gd enhancement. Longitudinally, multiple regression analysis demonstrated that the only clinical or MRI parameter that predicted BPF decrease was the mean absolute change of ring-enhancing lesion load (R=0.62, p=0.003). The noteworthy findings of this study are (1) the observation that a significant brain atrophy progression cannot be detected over a 3-month period in RRMS; (2) the demonstration that the ring-enhancement pattern may contribute to more severe brain tissue loss in the short term; and (3) the lack of relationship between the presence and duration of Gd-enhancement activity and brain volume changes in the short term.

A polymorphism (PM) in the microsatellite of the promoter region of matrix metalloproteinase 9 (MMP-9), modulating its expression, could play a role in susceptibility to multiple sclerosis (MS). MMP-9 PM was determined in 95 patients with MS (MS Group) and 95 ageand sex-matched controls (Control Group). Comparison of allelic frequencies showed that a higher number of CA repeats characterized the MS group ( P < 0.0001) and prevalence of carriers of z22 CA repeats was higher in the MS than in the Control Group (OR 3.4, 95% CI: 1.7–6.8, P < 0.0001). An earlier age at disease onset was a characteristic of patients with >22 CA repeats (33F10 vs. 28F10, P= 0.027). No differences were found in the main MRI parameters.

There is still a controversy regarding the best regional brain atrophy measurements in multiple sclerosis (MS) studies. The aim of this study was to establish whether, in a cross-sectional study, the normalized measurements of regional brain atrophy correlate better with the MRI-defined regional brain lesions than the absolute measurements of regional brain atrophy. We assessed 45 patients with clinically definite relapsing-remitting (RR) MS (median disease duration 12 years), and measured T1-lesion load (LL) and T2-LL of frontal lobes and pons, using a reproducible semi-automated technique. The regional brain parenchymal volume (RBPV) of frontal lobes and pons was obtained by use of a computerized interactive program, which incorporates semi-automated and automated segmentation processes. A normalized measurement, the regional brain parenchymal fraction (RBPF), was calculated as the ratio of RBPV to the total volume of the parenchyma and the cerebrospinal fluid (CSF) in the frontal lobes and in the region of the pons. The total regional brain volume fraction (TRBVF) was obtained after we had corrected for the total volume of the parenchyma and the CSF in the frontal lobes and in the region of the pons for the total intracranial volume. The mean coefficient of variation (CV) for RBPF of the pons was 1% for intra-observer reproducibility and 1.4% for inter-observer reproducibility. Generally, the normalized measurements of regional brain atrophy correlated with regional brain volumes and disability better than did the absolute measurements. RBPF and TRBVF correlated with T2-LL of the pons (r=-0.37, P=0.011, and r= -0.40, P=0.0005 respectively) and with T1-LL of the pons (r=-0.27, P=0.046, and r=-0.31, P=0.04, respectively), whereas RBPV did not (r=-0.18, P = NS). T1-LL of the frontal lobes was related to RBPF (r=-0.32, P=0.033) and TRBVF (r=-0.29, P=0.05), but not to RBPV (R=-0.27, P= NS). There was only a trend of correlation between T2-LL of the frontal lobes and RBPF (r=-0.27, P=0.06) and TRBVF (r=-0.28, P=0.057), and no correlation with RBPV (r=-0.23, P= NS). The magnitude of correlation between the expanded disability status scale (EDSS) and pontine and frontal lobe RBPF and TRBVF was more than twice as high as the correlation between EDSS and RBPV of the same regions. These data suggest that normalized regional brain atrophy measurements are preferable to absolute regional measurements in cross-sectional studies.

The objective of the study was to examine the relationship between HLA genotypes and disease severity as measured by brain MRI quantitative markers of demyelinating and destructive pathology in patients with multiple sclerosis (MS). We studied 100 patients with MS and 122 age, sex-, ethnic- and residence-matched controls. The DNA extraction and the genomic typing (A, B, DRB1 and DQB1 loci) were obtained with sequence-specific oligonucleotide method, using a commercially available reversible line blot assay (INNO-LIPA). All patients underwent a 1.5 tesla MRI examination of the brain. Disease severity was assessed by clinical (Expanded Disability Status Scale (EDSS)) and MRI (T2- and T1-lesion load (LL) and brain parenchymal fraction (BPF)) outcome measures. HLA-DQB1* 02 (OR 19.9, 95% C. I. 16.2-24.3, uncorrected (uncorr)- p

Cornelia de Lange syndrome (CdLS) is a complex genetic disease with skeletal involvement mostly related to upper limb malformations. We report on three males with clinical and molecular diagnoses of CdLS. Besides typical CdLS features, all showed different cervical spine malformations. To the best of our knowledge, this is an unusual malformation in the CdLS phenotypic spectrum.

This article reports on an association between Burkitt lymphoma and Noonan syndrome (NS) due to a RAF1 gene mutation. The patient was a 7-year-old boy with NS, who was included in the first series reporting the association between Noonan and RAF1, and who later presented with a 2-week history of asymptomatic unilateral tonsillar swelling and ipsilateral cervical lymphadenopathy. Histological and biological examinations of the tonsillar biopsy led to the diagnosis of Burkitt lymphoma. While there is a well-established association between NS and solid cell tumors, this is the first case described in the literature of Burkitt lymphoma in a patient with NS, and adds to the growing list of data supporting neoplasia's association with NS. © 2013 Wiley Periodicals, Inc.

Background Brain atrophy, as assessed by magnetic resonance imaging (MRI), has been correlated with disability in patients with multiple sclerosis (MS). Recent evidence indicates that both white matter (WM) and gray matter (GM) are subject to atrophy in patients with MS. Although neurological deficiencies in MS are primarily due to loss of WM, the clinical significance of GM atrophy has not been fully explored in MS. Methods We have undertaken a three-year, open-label study, comparing 26 patients who elected to receive intramuscular interferon beta-1a (IFN β-1a) therapy, with 28 patients who elected not to receive therapy. Both groups had quantitative cranial MRI scans at study entry and after three years, and standardized clinical assessments every six months. Brain parenchymal fraction (BPF), GM fraction (GMF), and WM fraction (WMF) percent changes were calculated, and T2- and T1-lesion volumes (LVs) assessed. Results After three years, mean percent (%) change in BPF favored the IFN β-1a treatment group (IFN β-1a —1.3% versus the control group —2.5%, P=0.009), as did the mean percent change in GMF (+0.2 versus —1.4%, P=0.014), and the mean percent change in T1-LV (—9.3 versus +91.6%, P=0.011). At the end of the study, there was a significant within-patient decrease in BPF for both groups (P=0.02 for the IFN β-1a treatment group, and P Conclusion Over a three-year period, treatment with IFN β-1a significantly slowed the progression of whole-brain and GM atrophy, and of T1-hypointense LV accumulation, when compared with the control group. Multiple Sclerosis 2007; 13: 490-501. http://msj.sagepub.com

To test the effect of serial magnetic resonance (MR) coregistration on short-term brain volume changes using different semiautomated and automated brain volume techniques in patients with relapsing-remitting (RR) multiple sclerosis (MS). Coregistration is frequently used to increase precision in serial MR imaging (MRI) analyses. However, the effect of coregistration on measurement of whole brain volume changes from serial scans in the short term has not been tested in MS patients.Twenty-eight patients with RR MS [mean disease duration: 4.9 years, mean age: 34.4 years and mean expanded disability status scale (EDSS): 1.4] were scanned at baseline and monthly for a period of 3 months with 2D spin-echo T1-weighted sequences obtained with nongapped 3 mm axial slices. Percent brain parenchymal fraction change (PBPFC) was calculated by a semiautomated (Buffalo) and, separately, by two automated (Buffalo automated and SIENAX) techniques, whereas percent brain volume change (PBVC) was calculated by the SIENA technique. For coregistration of serial images we used a robust, fully automated linear image coregistration tool. PBPFC and PBVC were calculated before and after coregistration, comparing scans from the following time periods: (1) baseline to month 3; (2) baseline to month 1; (3) month 1 to 2 and (4) month 2 to 3.The highest median PBPFCs measured on non-coregistered images were detected for the baseline-to-month-3 time period and ranged from -0.11% for Buffalo semiautomated to -0.45% for Buffalo automated (p = ns). On coregistered images, the highest PBPFCs were detected for the baseline-to-month-3 time period and ranged from 0.3% for Buffalo semiautomated, -0.3% for Buffalo automated, 0.02% for SIENAX and -0.02% for SIENA (PBVC). At all time points of the study, no significant differences of median volume changes were measured on coregistered and non-coregistered images when comparing the results among the segmentation algorithms.Over a 3 month period we did not detect short-term changes in normalized brain volumes using different measurement techniques. A longer observation period is needed to assess whether coregistration can affect the measurement of long-term brain volume changes.

To determine the effects of high dose methylprednisolone (HDMP) pulses on bone mineral density (BMD) in patients with multiple sclerosis (MS), we studied 25 MS patients who received regular pulses of HDMP as well as pulses of HDMP for relapses, 18 MS patients who received HDMP at the same dose schedule only for relapses, and 61 healthy controls. We measured BMDs at lumbar spine and femoral neck and we assessed biochemical markers of bone metabolism and turnover. The average lifetime dosage of MP was 75.4 (SD 11.9) g in the pulsed HDMP group and 28.6 (SD 18.3) g in the HDMP for relapses group (P < 0.0001). Two MS patients (4.7%) and four controls (6.6%) had osteoporosis (P = NS), whereas 25 patients with MS (58.1%) and 21 controls (34.4%) had osteopenia (P = 0.016). BMDs measured at lumbar spine and femoral neck and biochemical indices of bone metabolism did not differ in MS patients and controls. BMD measures were not associated with lifetime methylprednisolone dosage. In partial correlation analysis, controlling for age, gender and menopausal status there was a significant inverse correlation between BMD at femoral neck and Expanded Disability Status Scale (EDSS) score (r = -0.31, P = 0.05). In conclusion, treatment with repeated HDMP pulses was not associated with osteoporosis in patients with MS who participated in a trial of methylprednisolone. However, osteopenia was observed more frequently in MS patients than healthy controls. Our data are reassuring, as them suggest that repeated pulses of methylprednisolone do not result in substantially increased risk of osteoporosis in MS patients. Moreover, osteopenia was found only in patients treated for relapses, who had a significantly higher EDSS score than patients in the HDMP group, suggesting that decreased mobility may contribute to bone loss more than corticosteroid use. BMD should be monitored in patients with MS, regardless of the use of methylprednisolone.

We assessed the risk of multiple sclerosis (MS) associated with a series of putative risk factors. We studied 140 patients (90 women) with MS (mean age, 42.1 years; SD= 10.2 years; disease duration, 10.9 years, SD= 7.5 years) and 131 sex-and age-matched controls. Using a structured questionnaire, we collected information related to demographic data, socio-economic status, education, ethnicity, changes of domiciles, migration, occupation, environmental, nutritional and hormonal factors, exposure to various bacterial and viral agents, vaccinations, and family history of diseases. In multiple logistic regression analysis, we found independent risk factors of MS to be: familiarity for MS (OR= 12.1; 95% CI, 1.3-110.7), autoimmune diseases (OR= 3.8; 95% CI, 2.0-7.1) and migraine (OR= 8.7; 95% CI, 1.0-75.4); comorbidity with autoimmune disease (OR= 6.8; 95% CI, 1.4-32.0) and migraine (OR= 13.5; 95% CI, 1.5-116.6); and vaccination against measles (OR= 92.2; 95%, 12.1-700.2). Familial susceptibility to MS, autoimmune diseases and migraine, and vaccination to measles are associated with an increased risk of MS. The data collected in this study are confirmatory and support the hypothesis that etiology of MS constitutes the effect of interplay between genetic and environmental risk factors. However, the relatively small number of cases and controls prevents firm conclusions.

We studied 31 patients with relapsing-remitting (RR) multiple sclerosis (MS) in which we performed an urodynamic study, the pudendal cortical evoked potentials, the tibial cortical evoked potentials and the cranial and cervical spinal cord magnetic resonance imaging (MRI). We calculated the T(1) and T(2) lesion load (LL) and brain parenchymal fraction (BPF) of whole brain, frontal lobes, pons and cervical spinal cord. We also estimated the cross-sectional area at C(2) level. Spearman's rank correlation analysis showed a relationship between symptoms of sexual dysfunction and age (r=0.73, p0.0001), cognitive performances (r=-0.63, p0.0001), level of independence (r=-0.63, p0.0001), disability (r=0.56, p0.001), symptoms of anxiety (r=0.55, p0.001) and depression (r=0.50, p0.005), disease duration (r=0.42, p0.02) and parenchymal atrophy in the pons (r=-0.38, p=0.031). Sexual dysfunction was not correlated with any other MRI measure, urodynamic patterns or cortical evoked potentials. In multiple regression analysis, sexual dysfunction was predicted only by T(1) lesion load of the pons. In conclusion, we confirmed previous correlations of sexual dysfunction with various clinical variables and demonstrated an association between sexual dysfunction and destructive lesions in the pons, as detected by MRI, in patients with relapsing-remitting multiple sclerosis.