scholarly journals https://www.immunologyresearchjournal.com/articles/association-of-lupus-anticoagulant-with-brain-atrophy-in-gulf-war-illness-gwi.html

2021 ◽  
Vol 5 (2) ◽  
pp. 47-50
Author(s):  
Lisa M. James ◽  
Peka Christova ◽  
Rachel A. Johnson ◽  
Brian E. Engdahl ◽  
Scott M. Lewis ◽  
...  
Keyword(s):  
Gray Matter ◽  
Brain Atrophy ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Brain Volume ◽  
Gulf War ◽  
Cerebral White Matter ◽  
Clotting Time ◽  
Gulf War Illness ◽  
Cortical Gray Matter

Separate lines of research have documented brain atrophy and evidence of autoimmune mechanisms in Gulf War Illness (GWI), including the presence of lupus anticoagulant (LAC), in veterans with GWI. Here we evaluated the possible association of LAC and brain volume in veterans with GWI. The presence of LAC was determined using Silica Clotting Time and dilute Russell’s Viper Venom Time assays. MRI data was acquired using a Philips 3T MR scanner from which total gray matter, total cortical gray matter, total subcortical gray matter, and total cerebral white matter were derived. The results demonstrated a statistically significant reduction of brain volume in all regions tested in GWI veterans with positive LAC, as compared to those without LAC. These findings add to the literature implicating autoimmune mechanisms in GWI and point to the presence of prothrombotic antiphospholipid antibodies as contributing to brain atrophy in GWI.

scholarly journals Lupus Anticoagulant in Gulf War Illness and Autoimmune Disorders: A Common Pathway Toward Autoimmunity

2021 ◽  
Vol 5 (1) ◽  
pp. 14-18
Author(s):  
Lisa James ◽  
Rachel Johnson ◽  
Scott Lewis ◽  
Adam Carpenter ◽  
Brian Engdahl ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Autoimmune Disorders ◽  
Gulf War ◽  
Coagulation System ◽  
Gulf War Illness ◽  
Gulf War Veterans ◽  
Relapsing Remitting ◽  
Autoimmune Conditions ◽  
Relapsing Remitting Multiple Sclerosis

Mounting evidence suggests that autoimmune mechanisms may underlie the chronic symptoms characteristic of Gulf War Illness (GWI). The presence of antiphospholipid antibodies including Lupus Anticoagulant (LA) are often associated with autoimmune disorders. Here we evaluated and compared blood samples from veterans with GWI and veterans with other autoimmune conditions including relapsing remitting multiple sclerosis, rheumatoid arthritis, Sjögren’s syndrome, and lupus for the presence of LA using Silica Clotting Time and dilute Russell’s Viper Venom Time assays. Positive LA was identified in one-quarter of veterans with GWI; this proportion was not statistically different from the proportion of positive LA identified in patients diagnosed with the other autoimmune conditions. The present findings add to the literature implicating autoimmune mechanisms in GWI and point to the presence of prothrombotic antiphospholipid antibodies as a common contributing factor in GWI and other autoimmune disorders. Furthermore, activation of the coagulation system suggests new potential avenues for treatment for LA-positive Gulf War veterans.

scholarly journals Slowing of brain atrophy with teriflunomide and delayed conversion to clinically definite MS

2020 ◽  
Vol 13 ◽  
pp. 175628642097075
Author(s):  
Robert Zivadinov ◽  
Michael G. Dwyer ◽  
Ellen Carl ◽  
Elizabeth M. Poole ◽  
Steve Cavalier ◽  
...  
Keyword(s):  
Gray Matter ◽  
Brain Volume ◽  
Clinically Isolated Syndrome ◽  
Phase Iii ◽  
Percent Reduction ◽  
Bottom Quartile ◽  
Core Study ◽  
Cortical Gray Matter ◽  
In Cis ◽  
The Relationship

Background: We explored the effect of teriflunomide on cortical gray matter (CGM) and whole brain (WB) atrophy in patients with clinically isolated syndrome (CIS) from the phase III TOPIC study and assessed the relationship between atrophy and risk of conversion to clinically definite MS (CDMS). Methods: Patients (per McDonald 2005 criteria) were randomized 1:1:1 to placebo, teriflunomide 7 mg, or teriflunomide 14 mg for ⩽108 weeks (core study). In the extension, teriflunomide-treated patients maintained their original dose; placebo-treated patients were re-randomized 1:1 to teriflunomide 7 mg or 14 mg. Brain volume was assessed during years 1–2. Results: Teriflunomide 14 mg significantly slowed annualized CGM and WB atrophy versus placebo during years 1–2 [percent reduction: month 12, 61.4% (CGM; p = 0.0359) and 28.6% (WB; p = 0.0286); month 24, 40.2% (CGM; p = 0.0416) and 43.0% (WB; p < 0.0001)]. For every 1% decrease in CGM or WB volume during years 1–2, risk of CDMS conversion increased by 14.5% ( p =  0.0004) and 47.3% ( p < 0.0001) during years 1–2, respectively, and 6.6% ( p =  0.0570) and 35.9% ( p = 0.0250) during years 1–5. In patients with the least (bottom quartile) versus most (top quartile) atrophy during years 1–2, risk of CDMS conversion was reduced by 58% (CGM; p = 0.0024) and 58% (WB; p = 0.0028) during years 1–2, and 42% (CGM; p = 0.0138) and 29% (WB; p = 0.1912) during years 1–5. Conclusion: These findings support the clinical relevance of CGM and WB atrophy and early intervention with teriflunomide in CIS.

scholarly journals Subjective cognitive concern in multiple sclerosis is associated with reduced thalamic and cortical gray matter volumes

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731982761 ◽  
Author(s):  
Isaiah Kletenik ◽  
Enrique Alvarez ◽  
Justin M Honce ◽  
Brooke Valdez ◽  
Timothy L Vollmer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Dysfunction ◽  
Gray Matter ◽  
Brain Volume ◽  
Brain Magnetic Resonance Imaging ◽  
Regions Of Interest ◽  
Patient Reported ◽  
Cortical Gray Matter ◽  
Gray Matter Volumes ◽  
The Relationship

Objective Brain atrophy has been correlated with objective cognitive dysfunction in multiple sclerosis but few studies have explored self-reported subjective cognitive concerns and their relationship to brain volume changes. This study explores the relationship between subjective cognitive concerns in multiple sclerosis and reduced brain volume in regions of interest implicated in cognitive dysfunction. Methods A total of 158 patients with multiple sclerosis completed the Quality of Life in Neurologic Disorders Measures (Neuro-QoL) short forms to assess subjective cognitive concerns and underwent brain magnetic resonance imaging. Regional brain volumes from regions of interest implicated in cognitive dysfunction were measured using NeuroQuant automated volumetric quantitation. Linear regression was used to analyze the relationship between subjective cognitive concerns and brain volume. Results Controlling for age, disease duration, gender, depression and fatigue, increased subjective cognitive concerns were associated with reduced thalamic volume (standardized β = 0.223, t150 =2.406, P = 0.017) and reduced cortical gray matter volume (standardized β = 0.240, t150 = 2.777, P = 0.006). Increased subjective cognitive concerns were not associated with any other regions of interest that were analyzed. Conclusions Subjective cognitive concern in MS is associated with reduced thalamic and cortical gray matter volumes, areas of the brain that have been implicated in objective cognitive impairment. These findings may lend neuroanatomical significance to subjective cognitive concerns and patient-reported outcomes as measured by Neuro-QoL.

scholarly journals Effects of ibudilast on MRI measures in the phase 2 SPRINT-MS study

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011314
Author(s):  
Robert T Naismith ◽  
Robert A Bermel ◽  
Christopher S Coffey ◽  
Andrew D Goodman ◽  
Janel Fedler ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Secondary Analysis ◽  
Progressive Multiple Sclerosis ◽  
Whole Brain ◽  
T2 Lesions ◽  
Gray Matter Atrophy ◽  
Inflammatory Processes

OBJECTIVE:For progressive forms of multiple sclerosis, determine whether ibudilast has an effect on brain volume and new lesions.METHODS:A randomized, placebo controlled, blinded study evaluated ibudilast at a dose of up to 100 mg over 96 weeks in primary and secondary progressive multiple sclerosis. In this secondary analysis of a previously reported trial, secondary and tertiary endpoints included gray matter atrophy, new or enlarging T2 lesions as measured every 24 weeks, and new T1 hypointensities at 96 weeks. Whole brain atrophy measured by SIENA was a sensitivity analysis.RESULTS:129 participants were assigned to ibudilast and 126 to placebo. New or enlarging T2 lesions were observed in 37.2% on ibudilast and 29.0% on placebo (p=0.82). New T1 hypointense lesions at 96 weeks were observed in 33.3% on ibudilast and 23.5% on placebo (p=0.11). Gray matter atrophy was reduced by 35% for those on ibudilast vs. placebo (p=0.038). Progression of whole brain atrophy by SIENA was slowed by 20% in the ibudilast group compared with placebo (p=0.08).CONCLUSIONS:Ibudilast treatment was associated with a reduction in gray matter atrophy. Ibudilast treatment was not associated with a reduction in new or enlarging T2 lesions, or new T1 lesions. An effect on brain volume contributes to prior data that ibudilast appears to impact markers associated with neurodegenerative processes, but not inflammatory processes.Classification of Evidence:This study provides Class II evidence that for people with MS, ibudilast does not significantly reduce new or enlarging T2 lesions, or new T1 lesions.

Prothrombin as cofactor for antiphospholipids

Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 37-40 ◽  
Author(s):  
M Galli ◽  
T Barbui
Keyword(s):  
Clinical Relevance ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Anticoagulant Activity ◽  
Low Risk ◽  
Immune Recognition ◽  
Clotting Time ◽  
Glycoprotein I ◽  
Russell’S Viper ◽  
Kaolin Clotting Time

Prothrombin is a common antigenic target of antiphospholipid antibodies, since anti-prothrombin antibodies are detected in about 50-90% of the patients. To allow proper immune recognition, prothrombin must be adsorbed on suitable anionic surfaces. The epitope(s) have not yet been identified: the majority of anti-prothrombin antibodies appear to be of poly- or oligoclonal nature. Anti-prothrombin antibodies, either alone or in combination with anti-β2-glycoprotein I antibodies, are responsible for the lupus anticoagulant activity of about 75% of the cases of phospholipid-dependent inhibitors of coagulation. The two antibodies may be discriminated by means of specific coagulation profiles generated by the comparison of the ratio of the Kaolin Clotting Time (KCT) and the dilute Russell's Viper Venom Time (dRVVT): the KCT profile, which mainly reflects the presence of anti-prothrombin antibodies and the dRVVT profile, which is mostly associated with anti-β2-glycoprotein I antibodies. This distinction, although somewhat artificial, may be clinically useful, since the KCT profile identifies patients at low risk to develop thrombosis. Similarly, most of the studies that measured anti-prothrombin antibodies by ELISA failed to find a significant association with thrombosis. In conclusion, the clinical relevance of these antibodies has not yet been established.

Neurobiology of Schizophrenia

2016 ◽  
Author(s):  
Gil D. Hoftman ◽  
Dean F. Salisbury
Keyword(s):  
Prefrontal Cortex ◽  
Gray Matter ◽  
Negative Symptoms ◽  
Brain Volume ◽  
Symptom Clusters ◽  
Unknown Etiology ◽  
Spine Density ◽  
Complex Disorder ◽  
Dendritic Spine Density ◽  
Cortical Gray Matter

Schizophrenia is a brain disease with unknown etiology; a variety of neurodevelopmental mechanisms contribute to its pathogenesis. In this chapter, we review some of the most salient neurobiological findings that seem to be linked with the pathophysiology of psychosis generally and schizophrenia specifically. Several important findings have been made from neuroimaging and neuropathology, including reduced whole-brain volume, enlarged ventricles, and decreased cortical gray matter. Abnormalities in the prefrontal cortex, such as decreased dendritic spine density, are particularly important for cognitive and negative symptoms in schizophrenia. Functional imaging suggests that patterns of activation may be closely linked to symptom clusters. We will review neurotransmitter abnormalities, especially dopamine but also glutamate and GABA, and relevant circuitry and connectivity problems related to pathology. Finally, we will discuss genetics and heritability, and the challenges of identifying relevant loci in such a complex disorder.

scholarly journals Fractional anisotropy of cerebral white matter and thickness of cortical gray matter across the lifespan

NeuroImage ◽  
2011 ◽  
Vol 58 (1) ◽  
pp. 41-49 ◽  
Author(s):  
P. Kochunov ◽  
D.C. Glahn ◽  
J. Lancaster ◽  
P.M. Thompson ◽  
V. Kochunov ◽  
...  
Keyword(s):  
White Matter ◽  
Fractional Anisotropy ◽  
Gray Matter ◽  
Cerebral White Matter ◽  
Cortical Gray Matter

Subcortical brain atrophy in Gulf War Illness

2017 ◽  
Vol 235 (9) ◽  
pp. 2777-2786 ◽  
Author(s):  
Peka Christova ◽  
Lisa M. James ◽  
Brian E. Engdahl ◽  
Scott M. Lewis ◽  
Adam F. Carpenter ◽  
...  
Keyword(s):  
Brain Atrophy ◽  
Gulf War ◽  
Gulf War Illness ◽  
Subcortical Brain

Detection of Lupus-Like Anticoagulants by an Enzyme-Linked Immunosorbent Assay Using a Partial Thromboplastin as Antigen; A Comparative Study

1990 ◽  
Vol 64 (01) ◽  
pp. 026-031 ◽  
Author(s):  
J Arnout ◽  
E Huybrechts ◽  
M Vanrusselt ◽  
C Falcon ◽  
J Vermylen
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Activated Partial Thromboplastin Time ◽  
The Other ◽  
Quantitative Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Clotting Time ◽  
Coagulation Tests ◽  
Tissue Thromboplastin ◽  
Kaolin Clotting Time

SummaryClotting assays allow qualitative rather than quantitative detection of the lupus anticoagulant. We have therefore studied the usefulness of an ELISA using a commercial partial thromboplastin, Thrombofax, oS antigen; the results obtained on 146 selected patient plasmas were compared to the results of coagulation tests (kaolin clotting time, tissue thromboplastin inhibition test, activated partial thromboplastin time) and of ELISAs using cardiolipin or phosphatidylserine as antigen. While satisfactory agreement was found within the group of coagulation tests or that of ELISAs, only a moderate agreement was obtained between clotting tests and ELISAs, the best being with the partial thromboplastin ELISA using low plasma dilutions. The study further indicates that ELISA techniques cannot entirely replace coagulation tests for the detection of a lupus anticoagulant, even when a partial thromboplastin is used as antigen. On the other hand, coagulation tests are less sensitive than ELISAs for the detection of antiphospholipid antibodies.

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