Familial multiple sclerosis: volumetric assessment in clinically symptomatic and asymptomatic individuals

1999 ◽  
Vol 5 (2) ◽  
pp. 74-77 ◽  
Author(s):  
Jennifer C Fulton ◽  
Robert I Grossman ◽  
Lois J Mannon ◽  
Jayaram Udupa ◽  
Dennis L Kolson
Keyword(s):  
Multiple Sclerosis ◽  
Monozygotic Twins ◽  
Subsequent Development ◽  
Monozygotic Twin ◽  
Lesion Volume ◽  
Sibling Pairs ◽  
Clinically Normal ◽  
Volumetric Assessment ◽  
Significant Difference ◽  
Normal Offspring

A genetic basis for clustering of multiple sclerosis (MS) cases, based on studies of MS families, has been proposed for decades. Few reports provide detailed neurological as well as neuroradiological findings on these patients. We report total T2-weighted intracranial lesion volumes on members of three familial MS cohorts: a mother and father with conjugal MS with one affected son and a neurologically normal son and daughter, one pair of monozygotic twin sisters with MS, and a female sibling pair with MS. We hypothesized that asymptomatic siblings in a family with two affected parents and another affected child might demonstrate clinically silent T2-weighted lesions; and that monozygotic twins with MS are more likely to express similar T2-weighted lesion volumes than non-twin sibling pairs. We found clinically silent lesions in unaffected children of the symptomatic parent couple, with a significant difference in total T2 lesion volume between these unaffected siblings and their parents, as well as their affected brother. In our other sibling pairs, T2 lesion volumes were similar between the twins and significantly different in the non-twin pair, despite similar levels of clinical functioning as determined by EDSS scoring. These results suggest that foci of demyelination might be expected in clinically normal offspring of parents with MS, possibly reflecting a genetic predisposition to subsequent development of MS.

scholarly journals Using dual-calibrated functional MRI to map brain oxygen supply and consumption in multiple sclerosis

2021 ◽  
Author(s):  
Hannah L Chandler ◽  
Rachael C Stickland ◽  
Michael Germuska ◽  
Eleonora Patitucci ◽  
Catherine Foster ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Oxygen Consumption ◽  
Healthy Volunteers ◽  
Oxygen Supply ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Group Differences ◽  
Lesion Volume ◽  
Brain Physiology ◽  
Significant Difference

Evidence suggests that cerebrovascular function and oxygen consumption are altered in multiple sclerosis (MS). Here, we quantified the vascular and oxygen metabolic MRI burden in patients with MS (PwMS) and assessed the relationship between these MRI measures of and metrics of damage and disability. In PwMS and in matched healthy volunteers, we applied a newly developed dual-calibrated fMRI method of acquisition and analysis to map grey matter (GM) cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen consumption (CMRO2) and effective oxygen diffusivity of the capillary network (DC). We also quantified physical and cognitive function in PwMS and controls. There was no significant difference in GM volume between 22 PwMS and 20 healthy controls (p=0.302). Significant differences in CBF (PwMS vs. controls: 44.91 +/- 6.10 vs. 48.90 +/- 5.87 ml/100g/min, p=0.010), CMRO2 (117.69 +/- 17.31 vs. 136.49 +/- 14.48 μmol/100g/min p<0.001) and DC (2.70 +/- 0.51 vs. 3.18 +/- 0.41 μmol/100g/mmHg/min, p=0.002) were observed in the PwMS. No significant between-group differences were observed for OEF (PwMS vs. controls: 0.38 +/- 0.09 vs. 0.39 +/- 0.02, p=0.358). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS compared to healthy volunteers. There was a significant correlation between physiological measures and T2 lesion volume, but no association with current clinical disability. Our findings demonstrate concurrent reductions in oxygen supply and consumption in the absence of an alteration in oxygen extraction that may be indicative of a reduced demand for oxygen (O2), an impaired transfer of O2 from capillaries to mitochondria, and/or a reduced ability to utilise O2 that is available at the mitochondria. With no between-group differences in GM volume, our results suggest that changes in brain physiology may precede MRI-detectable GM loss and thus may be one of the pathological drivers of neurodegeneration and disease progression.

scholarly journals Immune signatures of prodromal multiple sclerosis in monozygotic twins

2020 ◽  
Vol 117 (35) ◽  
pp. 21546-21556 ◽  
Author(s):  
Lisa Ann Gerdes ◽  
Claudia Janoschka ◽  
Maria Eveslage ◽  
Bianca Mannig ◽  
Timo Wirth ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
T Cell Subsets ◽  
Effector T Cell ◽  
Immune Signatures ◽  
Relapsing Remitting ◽  
Immune Traits

The tremendous heterogeneity of the human population presents a major obstacle in understanding how autoimmune diseases like multiple sclerosis (MS) contribute to variations in human peripheral immune signatures. To minimize heterogeneity, we made use of a unique cohort of 43 monozygotic twin pairs clinically discordant for MS and searched for disease-related peripheral immune signatures in a systems biology approach covering a broad range of adaptive and innate immune populations on the protein level. Despite disease discordance, the immune signatures of MS-affected and unaffected cotwins were remarkably similar. Twinship alone contributed 56% of the immune variation, whereas MS explained 1 to 2% of the immune variance. Notably, distinct traits in CD4+effector T cell subsets emerged when we focused on a subgroup of twins with signs of subclinical, prodromal MS in the clinically healthy cotwin. Some of these early-disease immune traits were confirmed in a second independent cohort of untreated early relapsing-remitting MS patients. Early involvement of effector T cell subsets thus points to a key role of T cells in MS disease initiation.

Liver metastases in mCRPC patients post-therapy with abiraterone (Abi) and/or abiraterone/enzalutamide (Enza).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 250-250
Author(s):  
Lahiru Ranasinghe ◽  
Patrick Cotogno ◽  
Elisa M. Ledet ◽  
Allie E. Steinberger ◽  
Allison H. Feibus ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Gleason Score ◽  
Pearson Correlation ◽  
Subsequent Development ◽  
Liver Lesion ◽  
Cancer Center ◽  
Lesion Volume ◽  
Total Liver ◽  
Increased Risk ◽  
Significant Difference

250 Background: Liver metastases (mets) are a particularly poor prognostic group among mCRPC patients. The objective of this study is to characterize mCRPC patients who have had treatment with Abi or Enza to identify risk factors that may be associated with subsequent development of liver mets. Methods: A sample of 67 patients (n = 17 liver mets and 50 non-liver met patients matched by treatment history) seen at Tulane Cancer Center were selected for analysis. All patients had prior Abi and or Abi/Enza. Race, age at PCa diagnosis and Gleason Score at PCa diagnosis were assessed. For patients with liver mets, total liver metastatic volume was measured using CT scans and correlated against PSA, LDH and AST values at the time of the scan. Wilcoxon rank sum tests were run analyzing PSA, LDH and AST at the start of Abi treatment, end of Abi treatment as well the duration of Abi treatment, and the nadir PSA for these patients. Results: Patients were predominantly Caucasian, had a median Gleason Score of 8 at diagnosis and were at a median age of 57 for those with liver mets and 62 for non-liver met at PCa diagnosis. Pearson correlation analysis of the total liver lesion volume and lab values revealed a significant correlation for LDH (R = 0.491, < 0.01) and AST (R = 0.368, p < 0.05), but not for PSA. Further evaluation of PSA and AST values at the start and end of Abi treatment as well as at nadir PSA revealed no statistically significant differences between liver met patients and non-liver met patients. However, there was a significant difference (p = 0.015) between LDH levels at the end of Abi treatment with a median of 347 U/L for liver met and 238 U/L for non-liver met patients. Conclusions: LDH and AST levels correlate with extent of liver metastases. Additionally, elevated LDH at the end of Abi treatment is indicative of an increased risk for developing liver metastases. Larger sample sizes and molecular characterization of these tumors are required to gain more insights into this important patient population.

The effect of cross-talk on MRI lesion numbers and volumes in multiple sclerosis using conventional and turbo spin-echo

1998 ◽  
Vol 4 (6) ◽  
pp. 471-474 ◽  
Author(s):  
Massimo Filippi ◽  
Tarek A Yousry ◽  
Maria A Rocca ◽  
Clodoaldo Pereira ◽  
Hatem Alkadhi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cross Talk ◽  
Spin Echo ◽  
Brain Magnetic Resonance Imaging ◽  
Acquisition Time ◽  
Lesion Volume ◽  
Turbo Spin Echo ◽  
Turbo Spin ◽  
Acquisition Scheme ◽  
Significant Difference

We measured and compared lesion numbers and volumes present on brain magnetic resonance imaging (MRI) scans of patients with multiple sclerosis (MS) acquired with contiguous (scheme A) and interleaved (scheme B) slice acquisition, to evaluate whether there was a gain in sensitivity using the second pattern of acquisition and whether this counterbalanced the doubled acquisition time. Conventional spin-echo (CSE) sequences were performed for eight patient and turbo spin-echo (TSE) sequences for ten. Acquisition scheme B detected 3.8% more lesions than acquisition scheme A (the increase was 3. 1% for CSE and 4.5% for TSE). These differences were not statistically significant. No significant difference in lesion numbers was found when different lesion locations were also considered. Lesion volumes were significantly higher when scheme B was used (P= 0.024). This was due to higher lesion volumes on TSE images (P= 0.006), especially on even-numbered slices (P= 0.008). Inter-slice cross-talk has a negligible effect on lesion numbers and volume estimates in MS for CSE sequence, whilst it cannot be neglected when TSE sequences are used to measure MS lesion volume.

scholarly journals Iron Rims in Patients With Multiple Sclerosis as Neurodegenerative Marker? A 7-Tesla Magnetic Resonance Study

2021 ◽  
Vol 12 ◽  
Author(s):  
A. Dal-Bianco ◽  
R. Schranzer ◽  
G. Grabner ◽  
M. Lanzinger ◽  
S. Kolbrink ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
7 Tesla ◽  
Neuropsychological Performance ◽  
Lesion Volume ◽  
Information Processing Speed ◽  
Tissue Destruction ◽  
Subcortical Structures ◽  
Neurofilament Light Chain ◽  
Lateral Ventricles ◽  
Significant Difference

Introduction: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system, characterized by inflammatory-driven demyelination. Symptoms in MS manifest as both physical and neuropsychological deficits. With time, inflammation is accompanied by neurodegeneration, indicated by brain volume loss on an MRI. Here, we combined clinical, imaging, and serum biomarkers in patients with iron rim lesions (IRLs), which lead to severe tissue destruction and thus contribute to the accumulation of clinical disability.Objectives: Subcortical atrophy and ventricular enlargement using an automatic segmentation pipeline for 7 Tesla (T) MRI, serum neurofilament light chain (sNfL) levels, and neuropsychological performance in patients with MS with IRLs and non-IRLs were assessed.Methods: In total 29 patients with MS [15 women, 24 relapsing-remitting multiple sclerosis (RRMS), and five secondary-progressive multiple sclerosis (SPMS)] aged 38 (22–69) years with an Expanded Disability Status Score of 2 (0–8) and a disease duration of 11 (5–40) years underwent neurological and neuropsychological examinations. Volumes of lesions, subcortical structures, and lateral ventricles on 7-T MRI (SWI, FLAIR, and MP2RAGE, 3D Segmentation Software) and sNfL concentrations using the Simoa SR-X Analyzer in IRL and non-IRL patients were assessed.Results: (1) Iron rim lesions patients had a higher FLAIR lesion count (p = 0.047). Patients with higher MP2Rage lesion volume exhibited more IRLs (p &lt;0.014) and showed poorer performance in the information processing speed tested within 1 year using the Symbol Digit Modalities Test (SDMT) (p &lt;0.047). (2) Within 3 years, patients showed atrophy of the thalamus (p = 0.021) and putamen (p = 0.043) and enlargement of the lateral ventricles (p = 0.012). At baseline and after 3 years, thalamic volumes were lower in IRLs than in non-IRL patients (p = 0.045). (3) At baseline, IRL patients had higher sNfL concentrations (p = 0.028). Higher sNfL concentrations were associated with poorer SDMT (p = 0.004), regardless of IRL presence. (4) IRL and non-IRL patients showed no significant difference in the neuropsychological performance within 1 year.Conclusions: Compared with non-IRL patients, IRL patients had higher FLAIR lesion counts, smaller thalamic volumes, and higher sNfL concentrations. Our pilot study combines IRL and sNfL, two biomarkers considered indicative for neurodegenerative processes. Our preliminary data underscore the reported destructive nature of IRLs.

The Effects of Sibling Relationships on Social Adjustment Among Japanese Twins Compared With Singletons

2012 ◽  
Vol 15 (6) ◽  
pp. 727-736 ◽  
Author(s):  
Mari Nozaki ◽  
Keiko K. Fujisawa ◽  
Juko Ando ◽  
Toshikazu Hasegawa
Keyword(s):  
Social Development ◽  
Social Adjustment ◽  
Sibling Relationships ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Sibling Pairs ◽  
Dizygotic Twins ◽  
Opposite Tendency

This study examined the link between sibling relationships and children's social adjustment by comparing twin siblings and siblings with different ages (singleton siblings), and clarified the role of reciprocity in sibling relationships on children's social development. Mothers of 58 monozygotic twin pairs, 48 dizygotic twin pairs, and 86 singleton sibling pairs reported their children's sibling relationships and social adjustment. This study showed that the effects of sibling relationships on the prosocial behaviors and conduct problems of each child are stronger for twins than for singleton siblings. Moreover, positivity toward one's sibling increased peer problems only among monozygotic twins. The opposite tendency was present among dizygotic twins and singleton siblings. This study suggests the importance for children's social development of having many interactions with siblings and establishing reciprocity in sibling relationships. Moreover, our results suggest that the quality of sibling relationships among monozygotic twins may be different from those among dizygotic twins and singleton siblings.

scholarly journals “Side by side”: Development of twin relationship dimensions from early to middle childhood and the role of zygosity and parenting

2021 ◽  
pp. 026540752110058
Author(s):  
Hila Segal ◽  
Ariel Knafo-Noam
Keyword(s):  
Middle Childhood ◽  
Family System ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Developmental Courses ◽  
Dizygotic Twins ◽  
Significant Difference ◽  
The Impact ◽  
Comprehensive Study

Twin relationships have a significant effect on the twins’ life and their families. In the first comprehensive study of this topic, our purpose was to examine the developmental courses of four dyadic dimensions of twins’ relationships: closeness, dependence, conflict and rivalry, and the impact of zygosity and parenting on their relationships. Parents reported on their twins’ relationships ( N = 1547 mothers and 536 fathers with data from at least one of four measurement points from 3 to 8–9 years of age). The sample included 322 monozygotic twin dyads (sharing virtually 100% of their genes), and 1194 dizygotic twin dyads (sharing 50% of their genetic variance, on average). Our findings indicated that closeness and dependence decreased while rivalry increased through childhood. Dependence and rivalry also presented quadratic change. The twins’ conflict increased only for dizygotic twins. As expected, we found that the twins’ closeness and dependence were highly associated, as did the associations between conflict and rivalry. The mostly nonsignificant associations of closeness with conflict and rivalry reinforced the notion that they are not bi-polar opposites. However, dependence was positively related to the twins’ conflict and rivalry. A zygosity effect was also evident as monozygotic twins had higher levels of closeness and dependence than dizygotic twins through childhood, but there was no significant difference in the levels of their conflict and rivalry. In congruence with family system theories, parental positivity predicted the twins’ closeness and dependence, and parental negativity predicted the twins’ dependence, conflict and rivalry. The results were discussed in light of an evolutionary perspective and the twins’ developmental challenges through childhood.

Concordance for multiple sclerosis in Danish twins: an update of a nationwide study

2005 ◽  
Vol 11 (5) ◽  
pp. 504-510 ◽  
Author(s):  
T Hansen ◽  
A Skytthe ◽  
E Stenager ◽  
H C Petersen ◽  
H Brønnum-Hansen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Factors ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Population Based ◽  
Data Sets ◽  
Dizygotic Twin ◽  
Population Based Study ◽  
Nationwide Study ◽  
Dizygotic Twins

The occurrence of multiple sclerosis (MS) in twins has not previously been studied in complete nationwide data sets. The existence of almost complete MS and twin registries in Denmark ensures that essentially unbiased samples of MS cases among twins can be obtained. In this population-based study, virtually all Danish MS cases among twins born before 1983 with onset of MS after 1948 and diagnosis before 1 January 1997 were identified. Of 13 286 MS cases, 178 were twins and, of these 164 twin pairs were discordant and seven were concordant. We found significantly higher proband-wise concordance among monozygotic twins than dizygotic twins, with estimated proband-wise concordances of 24% (95% confidence interval (CI): 5-39%) for monozygotic and 3% (95% CI: 0-8%) for dizygotic twins. Thus, a monozygotic twin whose co-twin has MS has a 24% risk of developing the disease, while the corresponding risk for a dizygotic twin is only 3%. Our results largely confirm previously published concordance estimates and indicate that genetic factors are of importance in susceptibility to MS.

scholarly journals Metabolites of Gut Microbiome Are Associated With Glucose Metabolism in Non-diabetic Obese Adults: A Chinese Monozygotic Twin Study

2021 ◽  
Author(s):  
Ke Yu ◽  
Cai-Guo Yu ◽  
Xing-Qi Yin ◽  
Zong-Wei Wang ◽  
Xiao-Bo Wang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Gut Microbiome ◽  
Twin Study ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Tryptophan Metabolism ◽  
Obese Adults ◽  
Microbiome Composition ◽  
Significant Difference ◽  
Group A

Abstract BackgroundEvidence suggests gut microbiome is associated with diabetes. However, it’s unclear whether this association remains in non-diabetic subjects. We conducted a monozygotic twin study, in which the participants are without diabetes, and are not taking any medications, to explore the potential association.MethodsNine pairs of adult monozygotic twins were enrolled and divided into two twin-pair groups (a and b). Clinical and laboratory measurements were conducted. Visceral adipose tissue (VAT) was assessed. Fecal samples were collected to analyze the microbiome composition by 16S rDNA gene amplicon sequencing. Liquid chromatography mass spectrometry was performed to detect the metabolites. ResultsThe participants aged 53 years old averagely, with 8 (88.9%) pairs were women. All the participants were obese with VAT higher than 100 cm2 (152.2±31.6). There was no significant difference of VAT between the twin groups (153.6±30.4 cm2 vs. 150.8±29.5 cm2, p=0.54). Other clinical measurements, including BMI, lipid profiles, fasting insulin and blood glucose, were also not significantly different between groups (p≥0.056), whereas HbA1c level of group a is significantly higher than group b(5.8±0.3 % vs. 5.6±0.2 %, p=0.008). The number and richness of OUTs are relatively higher in group a, and 13 metabolites were significantly different between two groups. Furthermore, several of the 13 metabolites could be significantly linked to special taxons. The potential pathway involved drug metabolism-other enzymes, Tryptophan metabolism and Citrate cycle.ConclusionGut microbiome composition and their metabolites may modulate glucose metabolism in obese adults without diabetes, through Tryptophan metabolism, Citrate cycle and other pathways.

scholarly journals The genetic epidemiology of multiple sclerosis

1999 ◽  
Vol 354 (1390) ◽  
pp. 1623-1634 ◽  
Author(s):  
Alastair Compston
Keyword(s):  
Multiple Sclerosis ◽  
Complex Traits ◽  
Meta Analysis ◽  
Susceptibility Gene ◽  
Monozygotic Twins ◽  
Recurrence Risk ◽  
Disease Heterogeneity ◽  
Mediterranean Populations ◽  
Adjusted Risk ◽  
Sibling Pairs

Epidemiological studies have implicated an interplay between genetic and environmental factors in the aetiology of multiple sclerosis (MS). There is a familial recurrence rate of approximately 15%. Meta–analysis of the recurrence risk shows that the rate is highest overall for siblings, then parents and children, with lower rates in second– and third–degree relatives. Recurrence is highest for monozygotic twins. Conversely, the frequency in adoptees is similar to the population lifetime risk. The age–adjusted risk for half siblings is also less than for full siblings. Recurrence is higher in the children of conjugal pairs with MS than the offspring of single affecteds. These classical genetic observations suggest that MS is a complex trait in which susceptibility is determined by several genes acting independently or epistatically. Comparisons between co–affected sibling pairs provide no evidence for correlation with age or year at onset and mode of presentation or disability. Thus far, the identification of susceptibility genes has proved elusive but genetic strategies are now in place which should illuminate the problem. The main dividend will be an improved understanding of the pathogenesis. To date, population studies have demonstrated an association between the class II major histocompatibility complex (MHC) alleles DR15 and DQ6 and their corresponding genotypes. An association with DR4, with or without the primary DR15 link, is seen in some Mediterranean populations. Candidate gene approaches have otherwise proved unrewarding. Four groups of investigators have undertaken a systematic search of the genome. In common with most other complex traits, no major susceptibility gene has been identified but regions of interest have been provisionally identified. These genetic analyses are predicated on the assumption that MS is one disease. Genotypic and phenotypic analyses are beginning to question this assumption. A major part of future studies in the genetics of MS will be to resolve the question of disease heterogeneity.

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