784 research outputs found
Patient outcomes influenced by reduced lymphocyte counts after dimethyl fumarate initiation
No full textObjective:To examine the temporal profile of absolute and lymphocyte subset data from dimethyl fumarate (DMF) start and relationships to disease behavior.Methods:A retrospective study performed on patients with an existing diagnosis of MS and a history of DMF exposure from a single MS center. Demographic, laboratory, and corresponding clinical relapse and MRI data were recorded from baseline and in 3–4-month intervals after treatment initiation extending to 3 years. The Spearman rank coefficient and mixed-effects models were used to assess longitudinal correlations between cell counts and measures of disease activity.Results:A total of 292 patients with MS (228 women; median age at DMF initiation: 40.6 years, range: 16.1–66.7 years) were identified. An increased risk of disease activity was associated with higher absolute lymphocyte count (ALC) values at 3 months (p = 0.001, OR: 1.82) and at 6 months (p = 0.032, hazard ratio: 1.73). A reduced risk of disease evolution in patients with lower ALC values < 1,200 cells/μL compared with midtier (1,210–1,800 cells/μL) and the highest tertile (>1,810 cells/μL) was observed (p = 0.01).Conclusions:Reductions in ALC values at months 3 and 6 after treatment initiation appear to be associated with improved clinical and radiologic outcomes. These data alone may help to provide a better understanding of both the safety and efficacy of DMF.</jats:sec
JCB908356 Supplemental Material - Supplemental material for Altered task-induced cerebral blood flow and oxygen metabolism underlies motor impairment in multiple sclerosis
No full textSupplemental material, JCB908356 Supplemental Material for Altered task-induced cerebral blood flow and oxygen metabolism underlies motor impairment in multiple sclerosis by Kathryn L West, Dinesh K Sivakolundu, Mark D Zuppichini, Monroe P Turner, Jeffrey S Spence, Hanzhang Lu, Darin T Okuda and Bart Rypma in Journal of Cerebral Blood Flow & Metabolism</p
CANZlO DARIN BEDA
No full textAutor rješava dubioznost i autentičnost autorstva portreta grofa Erdodya te Ivana i Ane Minak (Pomorski i povijesni muzej hrvatskog primorja, Rijeka), portreta mladog muškarca (Gradski muzej, Karlovac) te kopija portreta grofa Lavala Nugenta (Povijesni muzej Hrvatske, Zagreb) signiranih »Canzio Darin«, odnosno »Canzio Darin Beda«. Pretpostavljalo se, da se radilo o jednom, odnosno najviše dvojici autora, međutim autor teksta dokazuje da se radi o tri autora i to Canzio Michele, Da Rin Tommaso i Beda Francesco), koji su - najvjerojatnije u Genovi - imali »bottegu«, gdje su se pod navedenim signaturama izrađivali portreti i njihove kopije.The author solves the enigma of authorship in the portraits of Count Erdody and Ivan and Ana Minak (Maritime and Historical Museum of Hrvatsko Primorje in Rijeka), the portrait of a young man (Civic Museum, Karlovac) and the copy of the portrait of Count Laval Nugent (Historical Museum of Croatia, Zagreb) signed »Canzio Darin« and »Canzio Darin Beda«. lt was supposed that this referred to one or two artists at the most, but the author proves that three authors are referred to here: Canzio Michele, Da Rin Tommaso and Beda Francesco) who had a »bottega«, most likely in Genoa, where portraits and their copies were produced bearing the above mentioned signatures.L'autore cerca di risolvere i dubbi sull'autenticita del ritratto del conte Erdodyedi Giovanni ed Anna Minak (Pomorski i povijesni muzej hrvatskog primorja, Rijeka), ritratto di giovane (Gradski muzej, Karlovac) e coppia del ritratto del conte Leone Nugent (Povijesni muzej Hrvatske, Zagreb) firmati "Canzio Darin«, oppure "Canzio Darin Beda«. Si presupponeva che si trattasse di uno o all piu di due autori, mentre l'autore del testo dimostra che si tratta di tre autori cioe di: Canzio Michele, Da Rin Tommaso e Beda Francesco . I tre provenivano da una stessa bottega, che quasi sicuramente si trovava a Genova, dove si realizavano ritratti originali e coppie firmate
MSJ866605_supplemental_material – Supplemental material for Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis: Evidence for a neurovascular uncoupling hypothesis
No full textSupplemental material, MSJ866605_supplemental_material for Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis: Evidence for a neurovascular uncoupling hypothesis by Dinesh K Sivakolundu, Kathryn L West, Gayathri B Maruthy, Mark Zuppichini, Monroe P Turner, Dema Abdelkarim, Yuguang Zhao, Dylan Nguyen, Jeffrey S Spence, Hanzhang Lu, Darin T Okuda and Bart Rypma in Multiple Sclerosis Journal</p
sj-docx-1-msj-10.1177_13524585221139575 – Supplemental material for Selective vulnerability of brainstem and cervical spinal cord regions in people with non-progressive multiple sclerosis of Black or African American and European ancestry
No full textSupplemental material, sj-docx-1-msj-10.1177_13524585221139575 for Selective vulnerability of brainstem and cervical spinal cord regions in people with non-progressive multiple sclerosis of Black or African American and European ancestry by Darin T Okuda, Thomas Stanley, Morgan McCreary, Alexander Smith, Andrew Wilson, Marco C Pinho, Fang F Yu, Thibo Billiet, Wim Van Hecke, Annemie Ribbens, Burcu Zeydan, Orhun Kantarci, Xiaohu Guo and Tatum M Moog in Multiple Sclerosis Journal</p
sj-docx-2-msj-10.1177_13524585221139575 – Supplemental material for Selective vulnerability of brainstem and cervical spinal cord regions in people with non-progressive multiple sclerosis of Black or African American and European ancestry
No full textSupplemental material, sj-docx-2-msj-10.1177_13524585221139575 for Selective vulnerability of brainstem and cervical spinal cord regions in people with non-progressive multiple sclerosis of Black or African American and European ancestry by Darin T Okuda, Thomas Stanley, Morgan McCreary, Alexander Smith, Andrew Wilson, Marco C Pinho, Fang F Yu, Thibo Billiet, Wim Van Hecke, Annemie Ribbens, Burcu Zeydan, Orhun Kantarci, Xiaohu Guo and Tatum M Moog in Multiple Sclerosis Journal</p
Cerebellar volume loss in radiologically isolated syndrome
No full textRadiologically isolated syndrome (RIS), in which asymptomatic demyelinating-appearing lesions are detected incidentally on MRI, can be a pre-clinical form of multiple sclerosis (MS). In this study, we measured cerebellar volumes on 3D T1-weighted 3T MR images in 21 individuals with RIS and 38 age- and sex-matched healthy controls (HC). Normalized cerebellar white matter volume and the anterior cerebellar gray matter volume were significantly decreased in RIS compared to HC (p = 0.003 and p = 0.005, respectively). Our findings support reports of regional brain atrophy in RIS prior to the development of a seminal attack related to inflammatory demyelination
Dimethyl fumarate preserves brainstem and cervical spinal cord integrity in radiologically isolated syndrome
No full textBackground and PurposeThe first randomized placebo-controlled therapeutic trial in radiologically isolated syndrome (RIS), ARISE, demonstrated that treatment with dimethyl fumarate (DMF) delayed the onset of a first clinical event related to CNS demyelination and was associated with a significant reduction in new and/or newly enlarging T2-weighted hyperintense lesions. The purpose of this study was to explore the effect of DMF on volumetric measures, including whole brain, thalamic, and subcortical gray matter volumes, brainstem and upper cervical spine three-dimensional (3D) volumes, and brainstem and upper cervical spine surface characteristics.MethodsStandardized 3T MRIs including 3D isotropic T1-weighted gradient echo images were acquired at baseline and end-of-study according to the ARISE study protocol. The acquired data were analyzed using Structural Image Evaluation Using Normalization of Atrophy (SIENA), FreeSurfer v7.3, and an in-house pipeline for 3D conformational metrics. Multivariate mixed models for repeated measures were used to analyze rates of change in whole brain, thalamic, subcortical gray matter, as well as change in the 3D surface curvature of the dorsal pons and dorsal medulla and 3D volume change at the medulla-upper cervical spinal cord.ResultsThe study population consisted of 64 RIS subjects (DMF:30, placebo:34). No significant difference was seen in whole brain, thalamic, or subcortical gray matter volumes in treated vs. untreated RIS patients. A significant difference was observed in dorsal pons curvature with the DMF group having a lower least squares mean change of - 4.46 (standard estimate (SE): 3.77) when compared to placebo [6.94 (3.71)] (p = 0.036). In individuals that experienced a first clinical event, a greater reduction in medulla-upper cervical spinal cord volume (p = 0.044) and a decrease in surface curvature was observed at the dorsal medulla (p = 0.009) but not at the dorsal pons (p = 0.443).ConclusionsThe benefit of disease-modifying therapy in RIS may extend to CNS structures impacted by neurodegeneration that is below the resolution of conventional volumetric measures
Three-Dimensional Shape and Surface Features Distinguish Multiple Sclerosis Lesions from Nonspecific White Matter Disease
No full textBACKGROUND AND PURPOSE: There remains a need to further refine the ability of clinicians to differentiate multiple sclerosis (MS) from other disease etiologies. Here, we illustrate the value of 3-dimensional (3D) geometric shape and surface lesion characteristics between disease states. METHODS: Standardized 3-Tesla 3D brain magnetic resonance imaging studies were performed on enrolled MS and nonspecific white matter (NSWM) patients. Focal supratentorial lesions were identified, reconstructed using maximum intensity projection, manually segmented, and 3D printed. Printed 3D models were randomly evaluated by three blinded raters for selected shape and surface characteristics. Regression models adjusting for age, disease duration, and individual patient effects were applied to assess lesion characteristics between patient groups. Patient-level and latent class analyses between groups were performed. RESULTS: A total of 1,001 supratentorial lesions were analyzed (710 MS; 291 NSWM) from 30 patients (19 with confirmed MS [11 female; median age = 33.6 years, range: 26.9-54.5], median disease duration = 2.2 years [.4-19.4]), 11 with verified nonspecific white matter (NSWM) disease without MS (11 female; median age = 55.0 years, range: 27.9-66.2). Lesions originating from MS in comparison to NSWM patients demonstrated a higher percentage of asymmetry (75.9% vs. 43%; OR: 4.39 [2.37-8.12]; P < .001), complex surface morphologies (65.9% vs. 27.8%; OR: 2.3 [1.74-3.05]; P < .001), and were multilobular (11.0% vs. .3%, P < .001), and elongated (12.8% vs. 2.4%, P < .001) in shape. Spatially, these traits were of higher frequency within the juxtacortical, deep white matter, and periventricular regions. CONCLUSION: Three-dimensional lesion data may provide new biologic insights related to injury along with offering another approach for determining the origin of lesion types
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Central neuropathic pain in MS results from distinct upper thoracic spinal cord lesions
No full textA Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.There is central pain complaint of burning cold pain common to patients with multiple sclerosis. Approximately 30‐40% of patients with multiple sclerosis (MS) suffer from central neuropathic pain, usually focused symmetrically in both feet and legs and often accompanied by cold allodynia and deep hyperesthesia [Osterberg et al 2005]. This condition resembles thalamic central pain, which also presents with dysfunctional pain and temperature sensations; however, thalamic pain is strictly contralateral [Craig 2007]. A distinct explanation for bilateral MS central pain likely involves a spinal lesion, yet a correlation has not been found [Svendson et al 2011]. We hypothesized that ascending projections from lumbosacral lamina I neurons to bilateral midthoracic autonomic nuclei are mirrored by descending projections [Craig 2002]; thus, a midthoracic lesion that damaged bilateral autonomic descending projections to lumbosacral lamina I neurons might underlie bilateral central pain in MS. Sympathetic interneurons in the midthoracic IMM/IML project to the brainstem but not the thalamus, implying they could be involved in homeostatic sensory integration at both brainstem and spinal levels. The lower extremity pain could be due to a lesion in the upper thoracic cord, interrupting the homeostatic integration pathway between the parabrachial nucleus in the brainstem, the (intermediomedial) and intermediolateral (IMM/IML) region of T2‐6 segments of the spinal cord, and lumbar lamina 1. To prove the existence of bilateral propriospinal projections between upper thoracic sympathetic interneurons and lumbosacral sensory (“pain”) neurons, anterograde and retrograde labeling with CTb and fluorescent tracers were performed in three animal species. In parallel, MRI analysis of MS patients with bilateral burning cold pain in the lower extremities tested the theory by examining for spinal lesions in the upper thoracic level. We tested this hypothesis with parallel clinical and neuroanatomical studies and identified a striking correspondence; MS patients with central neuropathic pain are distinguished by the presence of a lesion focused in the center of the mid‐thoracic spinal cord, and in three mammalian species neurons with bilateral descending projections to the lumbosacral superficial dorsal horn are concentrated in the autonomic intermediomedial nucleus surrounding the mid‐thoracic central canal. These findings will allow us to devise future treatments based on the newly understood neuroanatomical mechanisms.This item is part of the College of Medicine - Phoenix Scholarly Projects 2013 collection. For more information, contact the Phoenix Biomedical Campus Library at [email protected]
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