Disease-specific mechanisms in cortical multiple sclerosis lesions

Disease-specific mechanisms in cortical multiple sclerosis lesions

e392 Abstracts / Journal of the Neurological Sciences 333 (2013) e358–e421 Results: Out of 82 patients, 19 (21.95%) were diagnosed with AT. Mean EDS...

74KB Sizes 0 Downloads 78 Views

e392

Abstracts / Journal of the Neurological Sciences 333 (2013) e358–e421

Results: Out of 82 patients, 19 (21.95%) were diagnosed with AT. Mean EDSS value is 1.5 in patients with normal thyroid function and 2.0 in AT patients. Conclusions: AT is much more frequent in MS patients than in general population and in Italian MS patients compared to other European series. Although the sample is not sufficiently numerous to identify a clear correlation between high values of EDSS and thyroid dysfunction, our data show a trend in that direction. So, management of MS people should include an endocrinological screening to verify thyroid function. doi:10.1016/j.jns.2013.07.1419

Abstract — WCN 2013 No: 1886 Topic: 6 — MS & Demyelinating Diseases Asymptomatic electrophysiolosic carpal tunnel syndrome in diabetes: Ultrasonographic study J.H. Park, D.H. Jang. Catholic University of Korea, Catholic Medical Center, Seoul, Republic of Korea Background: Carpal tunnel syndrome (CTS) is considered more common in diabetes mellitus (DM) patients. Asymptomatic electrophysiologic CTS is frequently found on screening nerve conduction study (NCS) for DM neuropathy, but the pathophysiology has been little known. We investigated the symptoms, electrophysiologic findings and median nerve ultrasonography (US) findings of DM patients, and compared those between no CTS, asymptomatic CTS and symptomatic CTS group. Method: Thirty four hands with DM were prospectively assessed by three clinical scales, one electrophysiological scale and median nerve cross section area (CSA) through ultrasonography. The clinical scales adopted were the Boston carpal tunnel syndrome questionnaire (BCTQ), quantitative clinical scale by Simovic (Simovic clinical scale) and Historical-Objective (Hi-Ob) scale. The scale for electrophysiological assessment is the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) classification. US was performed in all participants, and CSA of the median nerve at carpal tunnel inlet site was evaluated. Results: There is no valid difference of median nerve bland scales between asymptomatic (2.36) and symptomatic (2.73) electrophysiologic CTS group. The median nerve CSA in non electrophysiologic CTS (0.086 cm2, ±0.012) was smaller than others (p b 0.05), and there is no valid difference of median nerve CSA between asymptomatic (0.117 cm2, ±0.023) and symptomatic electrophysiologic CTS group (0.123 cm2, ±0.031). Conclusion: These findings suggest that asymptomatic electrophysiologic CTS in DM could be a prodromal phase of symptomatic CTS, because they may have the same pathophysiology. Therefore clinicians have to carefully monitor the DM patients with asymptomatic electrophysiologic CTS. doi:10.1016/j.jns.2013.07.1420

Abstract — WCN 2013 No: 1905 Topic: 6 — MS & Demyelinating Diseases Does OCT predict conversion to MS? C. Oreja-Guevaraa, S. Novalb, A. Royoc, C. Valenciaa, J. Alvarez-Linerad. a Neurology, University Hospital San Carlos, Spain; bOphthalmology, University Hospital La Paz, Spain; cRadiology, University Hospital La Paz, Spain; dHospital Ruber Internacional, Madrid, Spain Background: Optical coherence tomography (OCT) is a simple high resolution noninvasive technique to quantify the thickness of retinal

nerve fiber layer (RNFL) and an indirect measurement of axonal damage in multiple sclerosis (MS). Objectives: To determine whether RNFL thickness predicts conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndromes (CIS) over the subsequent three years. Methods: Patients with CIS (McDonald criteria 2005) were recruited in two months after the event and underwent a complete neurological examination. High field brain MRI and cervical MRI were performed within two months of the first attack and after three years. An ophthalmological evaluation including visual acuity and optical coherence tomography (Stratus) was done within the first week after diagnosis and after three years. The sensitivity and specificity of OCT to predict conversion to CDMS were analyzed. Results: 23 patients with CIS with a mean EDSS of 1.72 were recruited and followed during three years. Eight patients did not have demyelinating lesions on baseline cranial MRI. 54.2% of all patients showed the presence of at least one quadrant of an optic nerve with a decreased RNFL thickness. The presence of at least one quadrant of an optic nerve with a RNFL thickness at a P b 5% cut-off value had a sensitivity of 69% and a specificity of 60% for predicting conversion to CDMS in a period of three years. Conclusion: Axonal damage in very early stages of the disease may be useful for predicting conversion in multiple sclerosis and useful for follow-up. doi:10.1016/j.jns.2013.07.1421

Abstract — WCN 2013 No: 1940 Topic: 6 — MS & Demyelinating Diseases Disease-specific mechanisms in cortical multiple sclerosis lesions I. Wimmera, M.T. Fischera, R. Höftbergerb, S. Gerlacha, L. Haidera, T. Zrzavya, S. Hametnera, D. Mahadc, C.J. Binderd, M. Krumbholze, J. Bauera, M. Bradla, H. Lassmanna. aDepartment of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria; b Institute of Neurology, Medical University of Vienna, Vienna, Austria; c Institute for Ageing and Health, Mitochondrial Research Group, Newcastle University, Newcastle Upon Tyne, UK; dDepartment of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria; eInstitute of Clinical Neuroimmunology, Ludwig Maximilian University of Munich, Munich, Germany Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system. Traditionally, research focused on white matter lesions but within the last years, cortical lesions gained importance. Although inflammation appears to play a fundamental role in the formation of cortical MS lesions, disease-specific mechanisms leading to plaque-like primary demyelination and neurodegeneration are poorly understood. We aim at identifying MS-specific mechanisms by combining neuropathological analysis of inflammatory and neurodegenerative diseases with gene expression studies. For immunohistochemistry, archival formalin-fixed and paraffinembedded autopsy tissue was used. Apart from cortical MS tissue, we also included cortical tissue from other inflammatory (tuberculous meningitis, Rasmussen's encephalitis, B-cell lymphoma, and meningitis) and neurodegenerative (Alzheimer's disease) diseases. Whole-genome microarrays were performed using microdissected cortical material from MS, tuberculous meningitis, and Alzheimer's disease patients and control cases. Immunohistochemistry showed that despite complex and fulminant immune responses in many investigated diseases, primary demyelination was only present in MS. Using microarrays, we identified 301 genes being

Abstracts / Journal of the Neurological Sciences 333 (2013) e358–e421

differentially expressed in cortical MS lesions. Of these, 80% were assigned to inflammation, oxidative stress, tissue injury, DNA damage/repair and regenerative processes. Immunohistochemically, we confirmed that significantly more oxidatively damaged neurons were present in cortical MS lesions than in other examined diseases. Additionally, neurons and oligodendrocytes stained positive for DNA strand breaks. Interestingly, oxidative stress-mediated tissue damage seemed to be driven by NADPH oxidases rather than by nitric oxide synthases. We show that MS-specific primary demyelination is driven by mechanisms of tissue injury that differ from any other investigated inflammatory and neurodegenerative disease. doi:10.1016/j.jns.2013.07.1422

Abstract — WCN 2013 No: 731 Topic: 6 — MS & Demyelinating Diseases Psychosocial complications of multiple sclerosis A. Fine. Clinical Social Work/Psychology, Allison Fine, MSW, LICSW — Counseling for Inner Balance, Seattle, WA, USA Background: Multiple sclerosis affects individuals diagnosed on both a physical and cognitive level, as well as an emotional one. Depression, anxiety, grief, other mental health concerns, and environmental factors all affect a patient's life with MS. Understanding this psychosocial impact is necessary to provide the best possible care for the MS patient. Objectives: Recognizing the emotional flux of an MS patient is essential to learn how to both treat and prevent these challenges from impacting the patient physically. Psychotherapy provides insight into an MS patient's life. This work demonstrates the psychosocial challenges many patients face and analyzes how mental health and environmental problems can both be a precursor to and aggravated further by MS. Patients and methods: Three case study examples of MS patients will be used to demonstrate psychosocial impact. All patients engaged in psychotherapy for at least one year to examine concerns related to their illness. Results: The psychosocial impact on those living with MS is clear but inconsistent. These individuals along with many others will continue to need emotional support throughout their illness. Conclusions: Examining the psychosocial component of patients living with MS allows medical professionals to take a more comprehensive look at treating the illness. While there is always no causation between emotional and physical health, the two often correlate. Research examining what happens physically to the patient when emotional health is exacerbated will go a long way in helping medical professionals understand the full impact of emotions on MS. doi:10.1016/j.jns.2013.07.1423

Abstract — WCN 2013 No: 1589 Topic: 6 — MS & Demyelinating Diseases Identification of novel candidate autoantigens in multiple sclerosis by expression cloning M. Moria, M. Mutoa, T. Hiwasab, A. Uzawaa, S. Masudaa, T. Uchidaa, H. Masudaa, S. Kuwabaraa. aNeurology, Graduate School of Medicine, Chiba University, Chiba, Japan; bBiochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan Background: Multiple sclerosis (MS) is an immune-mediated disease characterized by demyelination of the central nervous system. In some part of MS lesions, IgG (antibody) deposition is found. Although many

e393

components of the myelin sheath are suspicious for the targets of autoantibody, the real target molecules are unknown. Objective: To elucidate whether there is a novel specific autoantibody in serum or cerebrospinal fluid (CSF) samples from MS patients using the SEREX (serological identification by cDNA expression cloning) and ELISA (enzyme-linked immunosorbent assays) techniques. Material and methods: The phage expression library constructed from the U-87 MG glioblastoma cell-line was used in SEREX screening. Serum and CSF samples from 41 MS patients during the relapse or remission phases were obtained. Serum samples of 43 normal controls (NC) and CSF samples of 45 disease controls (DC) were used in ELISA. Results: Immunoscreening of cDNA expression libraries with serum from a relapsing–remitting MS patient led to the isolation of several independent antigens including DDX39 (DEAD box polypeptide 39). The results of ELISA revealed that the levels of anti-DDX39 antibody were significantly higher in sera from MS patients than NC, but were not significantly different between CSF samples from MS patients and NC. There were significant differences in serum anti-DDX39 antibody levels during the relapse and remission phases. Conclusion: Anti-DDX39 antibody is a possible target molecule for MS and could be used as a diagnostic biomarker. DDX39 may play some role in the pathogenesis of MS. doi:10.1016/j.jns.2013.07.1424

Abstract — WCN 2013 No: 1883 Topic: 6 — MS & Demyelinating Diseases Epidemiological analysis of multiple sclerosis in Goias and in Brazil from 2008 to 2011 J.A.D. Oliveira Júniora, C.D. Rochaa, M.O.F. Iwamotoa, K.O.F. Iwamotoa, F.O. Gomesa, D.S. Dinizb. aFaculdade de Medicina, Universidade Federal de Goiás, Goiânia, Brazil; bHospital das Clínicas, Universidade Federal de Goiás, Goiânia, Brazil Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease, autoimmune, confined to central nervous system. It affects about two times more women than men and causes great socioeconomic impact by having higher incidence among young adults, which may lead them to early failure. Objectives: To describe and compare profile of patients hospitalized due to MS in Goias and Brazil, according to sex and age, from 2008 to 2011, noting correlation with the literature. Material and methods: An observational, descriptive, retrospective epidemiological approach with qualitative and quantitative data from hospital admissions in Brazil and Goias, from 2008 to 2011, registered by Brazilian Health System based on database (DATASUS). Results: Of the total hospitalizations due to MS in Brazil (6838), 2087 (30.5%) were in males and 4751 (69.5%) in females. Of this total, 4733 (69.2%) occurred between 20 and 49 years. Goias had 219 hospitalizations, 58 (26.5%) in males and 161 (73.5%) in females. In terms of age, 164 (74.9%) were between 20 and 49 years. Conclusion: The state of Goias was responsible for 3.2% of admissions for MS in Brazil. In both scenarios MS predominates among women. In Brazil, there were 2.3 women for every man hospitalized by MS, while in Goiás, that relation was 2.8, which is equivalent to the literature. Age group was also in accord to the literature, varying from 20 to 49 years. The highest number of admissions occurred between 30 and 39 years, the age group with the largest percentage of economically active population in Brazil, justifying the impact of MS. doi:10.1016/j.jns.2013.07.1425