T1w/FLAIR ratio standardization as a myelin marker in MS patients.

INTRODUCTION: Calculation of a T1w/T2w ratio was introduced as a proxy for myelin integrity in the brain of multiple sclerosis (MS) patients. Since nowadays 3D FLAIR is commonly used for lesion detection instead of T2w images, we introduce a T1w/FLAIR ratio as an alternative for the T1w/T2w ratio. OBJECTIVES: Bias and intensity variation are widely present between different scanners, between subjects and within subjects over time in T1w, T2w and FLAIR images. We present a standardized method for calculating a histogram calibrated T1w/FLAIR ratio to reduce bias and intensity variation in MR sequences from different scanners and at different time-points. MATERIAL AND METHODS: 207 Relapsing Remitting MS patients were scanned on 4 different 3 T scanners with a protocol including 3D T1w, 2D T2w and 3D FLAIR images. After bias correction, T1w/FLAIR ratio maps and T1w/T2w ratio maps were calculated in 4 different ways: without calibration, with linear histogram calibration as described by Ganzetti et al. (2014), and by using 2 methods of non-linear histogram calibration. The first nonlinear calibration uses a template of extra-cerebral tissue and cerebrospinal fluid (CSF) brought from Montreal Neurological Institute (MNI) space to subject space; for the second nonlinear method we used an extra-cerebral tissue and CSF template of our own subjects. Additionally, we segmented several brain structures such as Normal Appearing White Matter (NAWM), Normal Appearing Grey Matter (NAGM), corpus callosum, thalami and MS lesions using Freesurfer and Samseg. RESULTS: The coefficient of variation of T1w/FLAIR ratio in NAWM for the no calibrated, linear, and 2 nonlinear calibration methods were respectively 24, 19.1, 9.5, 13.8. The nonlinear methods of calibration showed the best results for calculating the T1w/FLAIR ratio with a smaller dispersion of the data and a smaller overlap of T1w/FLAIR ratio in the different segmented brain structures. T1w/T2w and T1w/FLAIR ratios showed a wider range of values compared to MTR values. CONCLUSIONS: Calibration of T1w/T2w and T1w/FLAIR ratio maps is imperative to account for the sources of variation described above. The nonlinear calibration methods showed the best reduction of between-subject and within-subject variability. The T1w/T2w and T1w/FLAIR ratio seem to be more sensitive to smaller changes in tissue integrity than MTR. Future work is needed to determine the exact substrate of T1w/FLAIR ratio and to obtain correlations with clinical outcome.

Discriminating value of HR-pQCT for fractures in women with similar FRAX scores: A substudy of the FRISBEE cohort.

Areal bone mineral density (aBMD) has a low sensitivity to identify women at high fracture risk. The FRAX algorithm, by combining several clinical risk factors, might improve fracture prediction compared to aBMD alone. Several micro-architectural and biomechanical parameters which can be measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) are associated with fracture risk. HR-pQCT in combination or not with finite element analysis (FEA) may be used to improve bone strength prediction. Our aim was to assess whether HR-pQCT measurements (densities, cortical and trabecular microarchitecture, biomechanical proprieties assessed by FEA) had an added value in predicting fractures in a subgroup of women belonging to the Belgian FRISBEE cohort. One hundred nineteen women who sustained a fracture (aged 60 to 85 years) during the initial follow-up of our cohort had a radius and tibia examination by HR-pQCT and were compared with controls matched for their FRAX score at baseline. We found that low distal radius total (OR = 1.41 [1.07-1.86] per SD, p < 0.05) and trabecular densities (OR = 1.45 [1.10-1.90], p < 0.01), trabecular number (OR = 1.32 [1.01-1.72], p < 0.05), intra individual distribution of separation (OR = 0.73 [0.54-0.99], p < 0.05) as several FEA parameters were significantly associated with fractures. At the distal tibia, impaired cortical density (OR = 1.32 [1.03-1.70] per SD, p < 0.05) and thickness (OR = 1.29 [1.01-1.63], p < 0.05) and apparent modulus (OR = 1.30 [1.01-1.66], p < 0.05) were significantly correlated with fractures. A low ultra distal radial aBMD (UDR) measured at the time of HR-pQCT was significantly associated with fractures (OR = 1.67 [1.22-2.28], p < 0.01). Women from both groups were followed further after the realization of the HR-pQCT and 46 new fractures were registered. In this second part of the study, low UDR aBMD (OR = 1.66 [1.18-2.35], p < 0.01), total (OR = 1.48 [1.08-2.03], p < 0.05), cortical (OR = 1.40 [1.04-1.87], p < 0.05) and trabecular (OR = 1.37 [1.01-1.85], p < 0.05) densities or apparent modulus (OR = 1.49 [1.07-2.05], p < 0.05) at the radius were associated with a significant increase of fracture risk. At the tibia, only the cortical density was significantly associated with the fracture risk (OR = 1.34 [1.02-2.76], p < 0.05). These results confirm the interest of HR-pQCT measurements for the evaluation of fracture risk, also in women matched for their baseline FRAX score. They also highlight that UDR aBMD contains pertinent information.

Value of 3T Susceptibility-Weighted Imaging in the Diagnosis of Multiple Sclerosis.

BACKGROUND AND PURPOSE: Previous studies have suggested that the central vein sign and iron rims are specific features of MS lesions. Using 3T SWI, we aimed to compare the frequency of lesions with central veins and iron rims in patients with clinically isolated syndrome and MS-mimicking disorders and test their diagnostic value in predicting conversion from clinically isolated syndrome to MS. MATERIALS AND METHODS: For each patient, we calculated the number of brain lesions with central veins and iron rims. We then identified a simple rule involving an absolute number of lesions with central veins and iron rims to predict conversion from clinically isolated syndrome to MS. Additionally, we tested the diagnostic performance of central veins and iron rims when combined with evidence of dissemination in space. RESULTS: We included 112 patients with clinically isolated syndrome and 35 patients with MS-mimicking conditions. At follow-up, 94 patients with clinically isolated syndrome developed MS according to the 2017 McDonald criteria. Patients with clinically isolated syndrome had a median of 2 central veins (range, 0-19), while the non-MS group had a median of 1 central vein (range, 0-6). Fifty-six percent of patients who developed MS had ≥1 iron rim, and none of the patients without MS had iron rims. The sensitivity and specificity of finding ≥3 central veins and/or ≥1 iron rim were 70% and 86%, respectively. In combination with evidence of dissemination in space, the 2 imaging markers had higher specificity than dissemination in space and positive findings of oligoclonal bands currently used to support the diagnosis of MS. CONCLUSIONS: A single 3T SWI scan offers valuable diagnostic information, which has the potential to prevent MS misdiagnosis.

Osteoporosis treatment gap in a prospective cohort of volunteer women.

Despite the availability of efficient drugs to prevent osteoporotic fractures, only a minority of women receives osteoporosis therapy after a fracture. The high treatment gap in our cohort consisted of unselected volunteer patients highlights the urgent need of additional education, especially for the medical profession, regarding the risk-benefit balance of treatment. INTRODUCTION: Despite the availability of efficient drugs to prevent osteoporotic fractures, only a minority of women receives osteoporosis therapy after a fracture, with a treatment gap around 80%. This can have dramatic consequences for patients and the healthcare systems. METHODS: In this study based on longitudinal data from the FRISBEE (Fracture RIsk Brussels Epidemiological Enquiry) cohort of 3560 volunteer women aged 60 to 85 years, we evaluated the 1-year treatment gap after a first major incident fragility fracture. RESULTS: There were 386 first validated fragility fractures, 285 major osteoporotic fractures (MOF) and 101 "other major" fractures. The rate of untreated patients was 85.0% (82.8% for MOF versus 91.0 % for "other major" fracture sites) (p = 0.04), with a lower rate for spine (70.5%) and hip (72.5%) versus shoulder (91.6%) and wrist (94.1%) (p < 0.0001). More specifically, the treatment gap for patients with osteoporosis, defined by a T-score < - 2.5 SD was 74.6% versus 76.5% for patients with osteoporosis defined by the presence of hip, shoulder, or spine fractures, independently of DXA results. When considering age groups, the rate of untreated women was 87.9% for women 60-70 years old, 88.2% between 70 and 80 years and 77.8% above 80 years (p = 0.03), with a greater difference between women who were younger or older than 80 years at inclusion: 88.1% versus 77.8% (p = 0.009). A diagnosis of osteoporosis (p = 0.01) and age (p = 0.03) were the only clinical risk factors (CRFs) significantly associated with treatment initiation. CONCLUSIONS: This study highlights the urgent need of additional education, especially for the medical profession, regarding the risk-benefit balance of treatment.

Distribution of clinical risk factors for fracture in a Brussels cohort of postmenopausal women: The FRISBEE study and comparison with other major cohort studies.

OBJECTIVES: The estimation of fracture risk using clinical risk factors (CRFs) is of primary concern in osteoporosis management, but only some risk factors have been thoroughly evaluated and incorporated in predictive models. We have launched a large prospective study, the 'Fracture Risk Brussels Epidemiological Enquiry' (FRISBEE), to develop a new predictive model for osteoporotic fractures. The aims of this report are to describe the methodology of the FRISBEE study and to compare the distribution of CRFs in our cohort with those reported in other large studies. STUDY DESIGN: FRISBEE is a new study that prospectively evaluates a cohort of 3560 post-menopausal women (aged 60-85 years) followed yearly for the occurrence of fragility fractures. Multiple validated CRFs, densitometry (DXA) values and intake of medication were systematically registered at baseline. The distribution of the FRISBEE CRFs has been compared with the distributions of CRFs in the cohorts used to develop the FRAX® model as well as in more recent cohorts. For these recent cohorts, we focused on CRFs not included in FRAX®. RESULTS: The most frequently encountered CRFs used in FRAX® were a prior fragility fracture (27.1%) and a parental history of hip fracture (13.4%). The prevalence of some CRFs not integrated in FRAX® was relatively high, such as the use of proton pump inhibitors (20.8%) and a history of fall(s) (19.7%). The prevalence of many CRFs was quite variable between cohorts; for example, the prevalence of 'personal prior fragility fracture' ranged from 9% to 51%. CONCLUSION: We found considerable heterogeneity in the prevalence of CRFs between cohort studies. The impact of these differences on the predictive value of a particular CRF is unknown. We will construct a predictive model calibrated to the Belgian population. More importantly, the FRISBEE study should allow us to determine the predictive value of newly recognized CRFs in addition to the FRAX® algorithm to reliably estimate fracture risk.

[The secondary prevention of osteoporosis needs a multidisciplinary approach]. / La prévention secondaire de l'oséoporose passe par un circuit multidisciplinaire.

Enormous burden for our aging population and health care system, the hip fracture remains a major challenge to public health. Every year, there are over 15.000 hip fractures in Belgium. Nonetheless of the technical progress in surgery and the follow-up for, postoperation, the morbidity linked to this affection remains important because the vast majority of the patients will not recovered their previous autonomy after the fracture. The mortality is also high. Although it represents 14 % of the total osteoporotic fractures, the hip fractures account for 92 % of the costs caused by the disease, corresponding to 150.000.000 euros per year in Belgium. The present demographic evolution suggests that this amount will increase by 7 fold in 2050. Different epidemiological studies show that a large proportion of these fractures should have been avoided if the reason of the bone fragility, osteoporosis, had been previously diagnosed and treated. In this context, since several years, an increasing number of clinical paths - the Fracture Liaison Services (FLS) - have emerged all over the world. Brugmann Hospital has decided to implement such a model - focusing, by a systematic approach, to better connection and communication between available healthcare resources.

Anemia and transfusions in geriatric patients: a time for evaluation.

Anemia is common in the elderly, especially in very old patients who are often frail and may be institutionalized. Senescence, the ageing process, puts the elderly at risk of developing anemia for multiple reasons, but anemia may not be attributed to senescence unless a thorough diagnostic workup has excluded other etiologies. Nutritional deficiencies are common and need to be identified and treated appropriately. Inflammatory diseases and renal failure are also frequent etiological factors and tend to be chronic. Myelodysplastic syndromes increase in frequency with age and may be difficult to diagnose and only a minority of cases respond to appropriate treatment. Anemia is associated with poor outcome and symptomatic treatment with transfusions frequently has to be considered. Red blood cell transfusion has a high therapeutic index and is likely to be effective only if anemia is symptomatic or particularly severe, as a consequence, its use has been restricted to this group. Much of the evidence on usage is limited to younger adults and specific clinical situations. Geriatricians have to deal with a large number of patients with significant anemia but with an absence of well constructed guidelines for the frail and the very old. The object of the present article is to raise awareness that anemia in the geriatric group is multi-factorial and that the patients are more than merely older than those included in most studies, that the results of ongoing trials should be appropriately interpreted and will be important in guiding future practice.

Emerging fermentation technologies: development of novel sourdoughs.

The increasing knowledge of sourdough fermentation generates new opportunities for its use in the bakery field. New fermentation technologies emerged through in depth sourdough research. Dextrans are extracellular bacterial polysaccharides produced mainly by lactic acid bacteria (LAB). These bacteria convert sucrose thanks to an inducible enzyme called dextransucrase into dextran and fructose. The structure of dextran depends on the producing micro-organism and on culture conditions. Depending on its structure, dextran has specific properties which lead to several industrial applications in different domains. The use of dextran is not widely spread in the bakery field even if its impact on bread volume and texture was shown. A new process has been developed to obtain a sourdough rich in dextran using a specific LAB strain able to produce a sufficient amount of HMW dextran assuring a significant impact on bread volume. The sourdough obtained permits to improve freshness, crumb structure, mouthfeel and softness of all kinds of baked good from wheat rich dough products to rye sourdough breads. From fundamental research on dextran technology, a new fermentation process has been developed to produce an innovative functional ingredient for bakery industry.

Impaired cardiovascular autonomic control in newly and long-term-treated patients with Parkinson's disease: involvement of L-dopa therapy.

In idiopathic Parkinson's disease (PD), autonomic dysfunction is frequent, causing orthostatic hypotension. The respective roles of disease progression and dopaminergic treatment remain unclear. In this study, we investigated the autonomic control of cardiovascular functions and its relation to L-dopa therapy in both newly diagnosed (ND) and long-term-treated (LT) patients. Study subjects were: (1) nine ND patients never having undergone treatment with L-dopa; (2) 18 LT patients who had been receiving L-dopa treatment for a long period. ND patients were investigated before L-dopa treatment and after stabilization of their L-dopa dosage. LT patients were investigated once with their regular treatment and once after a 12-h interruption of L-dopa treatment; (3) nine healthy subjects served as controls. At each test session, blood pressure (BP), heart rate (HR), plasma catecholamines, heart rate variability (HRV), and spontaneous baroreflex sensitivity were assessed in the supine and upright positions. Before receiving L-dopa medication, ND patients had reduced E/I ratios (HR response/deep breathing) and lowered HRV when compared to controls; this was evidence of early effects of the disease on autonomic HR control. Introduction of L-dopa treatment reduced BP, HR, and plasma levels of adrenaline and noradrenaline. Similar changes were found in LT patients when contrasting the short-term treatment interruption and the usual L-dopa dosage. The treatment-linked increase in plasma dopamine also correlated with the decrease in noradrenaline. These results showed that mild impairment of autonomic cardiovascular control occurred early in the course of PD. They also provided evidence that the side effects of L-dopa aggravated the impairment of the autonomic control of BP and HR.

Graded vascular autonomic control versus discontinuous cardiac control during gradual upright tilt.

Indexes of heart rate variability (HRV) and the slope of cardiac baroreflex are extensively used for non invasive assessment of circulatory autonomic control in pathophysiology. We performed this study (1) to assess the sensitivity of these indexes towards small graded postural stimulations and (2) to delineate the informations provided about the settings of both vascular tone and cardiac activity. Twenty healthy subjects were randomly tilted for eight minutes at each of the six angles: -10 degrees, 0 degrees (supine), 10 degrees, 30 degrees, 45 degrees, and 60 degrees. Instant RR-interval and finger blood pressure (BP) were continuously recorded, and venous blood was collected at the end of each 8 min position for catecholamines determination. Group average heart rate, noradrenaline and diastolic BP (DBP) increased linearly with head-up tilt angle from 10 degrees. Systolic BP (SBB) ranked only two distinct series -10 degrees, 0 degrees, 10 degrees versus 30 degrees, 45 degrees, 60 degrees, as did the number of spontaneous baroreflex (SBR) sequences. The spectral power of the low-frequency (LF) and high-frequency (HF) of RR variability and the ratio LF/HF changed rather abruptly from either 30 degrees or 45 degrees, depending on each individual. Both HF/tot i.e. the ratio of HF to total spectral RR variability and the slope of SBR decreased markedly from 10 degrees to 30 degrees and less but more gradually from 30 degrees to 60 degrees. Thus, our observations argue for gradual adjustments of vascular tone as reflected by highly consistent changes in plasma noradrenaline and diastolic arterial pressure, contrasting with a main discontinuous autonomic setting of cardiac activity as reflected by changes in the harmonic components of spectral RR variability and in the slope of cardiac baroreflex. The pattern of changes in systolic arterial pressure attested the discontinuous cardiac autonomic control rather than the gradual setting of arterial tone. We submit that these different patterns of autonomic adjustments should be considered when assessing pathophysiological states.

Abnormal autonomic cardiovascular control in ankylosing spondylitis.

OBJECTIVE: This study was aimed at assessing the contribution of the autonomic nervous system to adjustments of cardiovascular function in patients with ankylosing spondylitis (AS). METHODS: In 18 AS patients (mean age: 34.9; mean disease duration: 6.4 years) and 13 healthy controls (mean age: 31.7) the changes of heart rate (HR) with deep breathing (E/I ratio) and standing up (30/15 ratio) were recorded. The slope of cardiac baroreflex, the times series of blood pressure and HR values upon lying and standing, and venous plasma concentrations of catecholamines were also analysed. Erythrocyte sedimentation rate (ESR), plasma C reactive protein (CRP) concentration and a clinical index (BASDAI score) were used to assess the degree of disease activity in patients. RESULTS: In the standing patients, blood pressure was found to decrease progressively (p< 0.001). Furthermore, the patients with a BASDAI score > 5 had a higher heart rate than patients with a BASDAI score < 5 (p<0.02), and there was a trend for a similar difference when patients were classified according to their ESR and CRP. Plasma catecholamine concentrations and the E/I ratio were not different in patients from controls. The 30/15 ratio and the slope of the spontaneous baroreflex during standing were both lower in AS patients than controls (p< 0.01). CONCLUSIONS: This study demonstrated a change in autonomic nervous system function of AS patients, with a decreased parasympathetic activity, as evidenced by higher HR and lower baroreflex slope. As these significant deviances were mainly observed in patients with more active (or more inflammatory) disease, the autonomic nervous system involvement could be related to the inflammatory process. This autonomic strain may be related to the cardiac involvement in AS patients.

Active standing and passive tilting similarly reduce the slope of spontaneous baroreflex in healthy subjects.

Non-invasive assessment of the sensitivity of cardiac baroreflex was performed by recording each RR-interval and each blood pressure cycle (Finapres). In sequences of at least three cardiac cycles in which systolic blood pressure and RR-interval had changed in the same direction, the slope of linear regression of RR duration as a function of the change in systolic arterial pressure was taken for estimating the sensitivity of the spontaneous cardiac baroreflex. This technique was used in healthy humans to examine how a postural change from supine to upright by either active standing up or 60 degrees head-up tilting modified the sensitivity of the spontaneous baroreflex. We observed that the slope of the spontaneous baroreflex averaged 14.6 +/- 2 ms.mm Hg-1 during rest in the supine position, and decreased to 7.8 +/- 1.2 ms.mm Hg-1 (p < 0.05) after active standing, while the number of sequences was significantly increased in the upright as compared to the supine position. Head-up tilting by 60 degrees led to values similar to those following active standing. The adjustment of baroreflex slope to either postural change occurred in a few seconds, so that posture-characteristic values were obtained from five-minute records. We conclude that non-invasive recording of spontaneous sequences of related changes in blood pressure and RR-interval during several minutes provides reproducible values of the slope of cardiac baroreflex in the supine and upright position. This easy and reliable determination of the sensitivity of the cardiac baroreflex might prove to be useful when assessment of baroreflex function is needed.