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Neuropsychological correlates of multiple sclerosis across the lifespan

Nunan-Saah, Julia; Paulraj, Selvi R; Waubant, Emmanuelle; Krupp, Lauren B; Gomez, Rowena G
Multiple sclerosis can adversely affect cognitive functioning whether the disease has an adult or pediatric onset. The research thus far suggests that pediatric MS shares many features with adult MS but is also unique in several respects. One particular characteristic of pediatric MS is that, while physical disability develops more slowly as compared with adult patients, the impact of cognitive deficits in children may be more substantial as they are in a period of life during which they acquire many skills that are needed to transition into independently functioning adults. Our review takes a lifespan approach to MS, comparing and contrasting the neuropsychology (i.e., cognitive, psychological, and psychosocial factors) of these two populations. Understanding how MS manifests across the lifespan has important implications for tailoring assessment and treatment for individuals with MS as they transition from childhood to adulthood, and later life.
PMID: 26163074
ISSN: 1477-0970
CID: 1682492

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps

Casper, T Charles; Rose, John W; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda
Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network.
PMCID:4379142
PMID: 25270659
ISSN: 1708-8283
CID: 2153542

Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment [Case Report]

Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle
Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica.
PMID: 25387545
ISSN: 1708-8283
CID: 2153622

Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset

Kavak, Katelyn S; Teter, Barbara E; Hagemeier, Jesper; Zakalik, Karen; Weinstock-Guttman, Bianca; [Edwards, K; Goodman, A; Gottesman, M; Herbert, J; Kister, I; Jubelt, B; Coyle, P; Krupp, Lauren, B; Lenihan, M; Gerber, A; Parel, A; Zivadinov, R; Granger, C]
BACKGROUND: Growing evidence suggests an association between adolescent obesity and increased risk of multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to investigate whether weight or body mass index (BMI) in adolescence and young adulthood was associated with age at MS symptom onset. METHODS: Our cohort is comprised of a sub-group of 184 women enrolled in the New York State MS Consortium registry. Individuals were asked to recall their weight at the time of first menstruation and at age 25. BMI was calculated accordingly for age 25. Regression analyses were carried out to investigate the association between weight or BMI and age at onset. RESULTS: Weight at menarche was significantly related to younger age at symptom onset (beta = -0.073, p = 0.001). These results were also found at age 25 for weight (beta = -0.080, p < 0.001) and BMI (beta = -0.448, p = 0.001). Significantly earlier disease onset (26.9 years +/-9.9) was observed in individuals who were overweight at 25 compared to those who were not overweight (32.1 years +/-9.2, p = 0.006). CONCLUSIONS: Women who reported higher weight in adolescence and BMI in early adulthood were younger at MS onset. Future research should investigate whether there is a causal link between body weight and MS, as prevention lifestyle and dietary interventions could be implemented.
PMID: 25392327
ISSN: 1477-0970
CID: 2237042

Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study

Miller, David H; Fox, Robert J; Phillips, J Theodore; Hutchinson, Michael; Havrdova, Eva; Kita, Mariko; Wheeler-Kingshott, Claudia A M; Tozer, Daniel J; MacManus, David G; Yousry, Tarek A; Goodsell, Mary; Yang, Minhua; Zhang, Ray; Viglietta, Vissia; Dawson, Katherine T; Wilson, Kate; Antel, Jack; Ware, James; Polman, Chris; Kowey, Peter R; Chung, Raymond; Bakris, George; Richert, John; Seibert, Burt; Brandes, David; Brassat, David; Cohen, Bruce; Diem, Ricarda; Goldman, Myla; Herndon, Robert; Miller, Aaron; Tumani, Hayrettin; Alfaro-Vidal, Teresa; Crespo, Carolina; Foster, Jo; Hunter, Kelvin; Garcia-Gomez, Almudena; Santana, Virginia; Kneebone, Christopher; Fedulau, Aliaksandr; Likhachev, Sergey; Mikhailova, Elena; Naumova, Halina; Decoo, Danny; Gaer, Luc Vande; Sindic, Christian; Grgic, Sanja; Sinanovic, Osman; Suljic, Enra Mehmedika; Deleva, Nadezhda; Georgiev, Dimitar; Haralanov, Lyubomir; Ivanova, Sonyia; Manchev, Ivan; Minchev, Dimitar; Stamenova, Paraskeva; Tournev, Ivailo; Vacheva, Elena; Zahariev, Zahari; Bar-Or, Amit; Blevins, Gregg; Kremenchutzky, Marcelo; Veloso, Felix; Witt, Norbert; Vargas Howell, Roberto; Vindas, Alexander Parajeles; Habek, Mario; Rudež, Josip; Soldo-Butković, Silva; Vurdelja, Ranka Baraba; Doležil, David; Havrdova, Eva; Nova'k, Jiří; Vaclavik, Daniel; Antsov, Katrin; Gross-Paju, Katrin; Haldre, Sulev; Palu, Alla; Toomsoo, Toomas; Al Khedr, Abdullatif; Camu, William; Debouverie, Marc; Defer, Gilles; De Seze, Jérôme; Labauge, Pierre; Moreau, Thibault; Pelletier, Jean; Rumbach, Lucien; Daskalovska, Vera; Angnstwurm, Klemens; Benes, Heike; Berthele, Achim; Boldt, Hans-Jürgen; Christopher, Angelika; Derfuß, Tobias; Eisensehr, Ilonka; Emrich, Peter; Feneberg, Wolfgang; Hoffmann, Frank; Hohlfeld, Reinhard; Hüntemann, Reinhard; Kallmann, Boris-Alexander; Kieseier, Bernd; Landefeld, Harald; Lüer, Wilfried; Masri, Sabine; Nelles, Gereon; Oschmann, Patrick; Paschen, Christine; Reifschneider, Gerd; Sailer, Michael; Schimrigk, Sebastian; Spiegel-Meixensberger, Mechthild; Storch-Hagenlocher, Brigitte; Tackenberg, Björn; Tiel-Wilck, Klaus; Karageorgiou, Clementine; Papathanasopoulos, Panagiotis; Thomaides, Thomas; Vlaikidis, Nicholas; Arjundas, Deepak; Behari, Madhuri; Ghosh, Amitabha; Ghosh, Pahari; Ichaporia, Nasli Rustom; Khurana, Dheeraj; Kulkarni, Rahul Vitthal; Kumar, Suresh; Mehndiratta, Man Mohan; Mehta, Neeta Abhay; Misra, Usha Kant; Mukherji, Joy Dev; Nellikunja, Shankara; Salem, Abdul; Sethi, Prahlad Kumar; Shah, Shalin Dipinkumar; Singh, Gagandeep; Singh, Maneesh Kumar; Singh, Yash Pal; Srinivasa, Rangasetty; Vijayan, Krishnan; Sweeney, Bernard; Gilad, Ronit; Shahien, Radi; Paegle, Anita; Delgado, Cesar; Escamilla, Juan; Estañol, Bruno; Lopez, Minerva; Macias, Miguel Angel; Punzo, Guillermo; Quiñones, Sandra; Renteria, Mariela; Santos, Jose; Gavriliuc, Mihail; Groppa, Stanislav; Odainic, Olesea; Timmings, Paul; Czlonkowska, Anna; Dorobek, Malgorzata; Drozdowski, Wieslaw; Fryze, Waldemar; Hertmanowska, Hanka; Kaminska, Anna; Kapelusiak-Pielok, Magdalena; Kleczkowska, Magdalena; Kochanowicz, Jan; Losy, Jacek; Nowacki, Przemyslaw; Nyka, Walenty; Pierzchala, Krystyna; Podemski, Ryszard; Potemkowski, Andrzej; Selmaj, Krzysztof; Stelmasiak, Zbigniew; Szczudlik, Andrzej; Tutaj, Andrzej; Wajgt, Andrzej; Zielinski, Tomasz; Balasa, Rodica; Ionescu-Dimancea, Valentin; Mihancea, Petru; Popescu, Cristian; Protosevici, Liviu Codrut; Miletić Drakulić, Svetlana; Nadj, Congor; Raicevic, Ranko; Vojinovic, Slobodan; Kahancová, Edita; Kurca, Egon; Lisý, L'ubomir; Turčáni, Peter; Arroyo, Rafael; Fernández, Oscar; Guijarro, Cristina; Izquierdo, Guillermo; Lopez, Fernando Sanchez; Montalbán, Xavier; Oreja-Guevara, Celia; Prieto, Jose Maria; Buchakchyys'ka, Nataliya; Chmyr, Galyna; Goloborodko, Alla; Kobys, Tetyana; Kushnir, Grygory; Lebedynets, Volodymyr; Lytvynenko, Nataliya; Moskovko, Sergii; Nehrych, Tetyana; Palamar, Borys; Pasyura, Igor; Ryabichenko, Tatyana; Voloshina, Nataliya; Apperson, Michelle; Applebee, Angela; Asher, Stephen; Ayala, Ricardo; Ayres, Donald; Azizi, S Ausim; Baker, Matthew; Bauer, Brendan; Bomprezzi, Roberto; Buckler, Richard; Carlini, Walter; Chinea, Angel; Cohan, Stanley; Crowell, Giles; Edwards, Keith; Eubank, Geoffery; Felton, Warren 3rd; Fodor, Patricia; Foley, John; Ford, Corey; Fox, Edward; Fox, Robert; Forester, Mary; Freedman, Steven; Garmany, George Jr; Gazda, Suzanne; Giang, Daniel; Glaun, Braeme; Gold, Scott; Gottesman, Malcolm; Gudesblatt, Mark; Herbert, Joseph; Herskowitz, Allan; Honeycutt, William; Huddlestone, John; Hull, Richard; Hunter, Samuel; Hutton, George; Jacobs, Dina; Janicki, Mark; Khatri, Bhupendra; Kinkel, Revere Philip; Kita, Mariko; Krolczyk, Stanley; Krupp, Lauren; LaGanke, Christopher; Levin, Michael; Licht, Jonathan; Luzzio, Christopher; Lynch, Sharon; Mattson, David; Mikol, Daniel; Miller, Tamara; Minagar, Alireza; Mitchell, Galen; Moses, Harold Jr; Negroski, Donald; Newman, Stephen; Pardo, Gabriel; Patel, Malti; Perel, Allan; Phillips, Joseph Jr; Picone, Mary Ann; Rammohan, Kottil; Rao, T Hemanth; Rinker, John 2nd; Sadiq, Saud; Schaeffer, John; Sheremata, William; Shin, Robert; Shubin, Richard; Silverman, Stuart; Smith, Robert; Stein, Lee; Stein, Michael; Steiner, David; Steingo, Brian; Sullivan, Herman; Sunter, William Jr; Vaishnav, Anand; Vasquez, Alberto; Voci, James; Warach, Jonathan; Weinstock-Guttman, Bianca; Williams, Mitzi; Wray, Sibyl
OBJECTIVE:To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. METHODS:CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). RESULTS:DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. CONCLUSIONS:The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.
PMCID:4371413
PMID: 25681448
ISSN: 1526-632x
CID: 5348212

The geographic distribution of pediatric MS in the US [Meeting Abstract]

Lavery, AM; Waldman, AT; Roalstad, S; Ness, J; Gorman, M; Benson, L; Weinstock-Guttman, B; Rubin, J; Schreiner, T; Aaen, G; Tillema, JMendelt; Rodriguez, M; Chitnis, T; Candee, M; Krupp, L; Belman, A; Lotze, T; Graves, J; Graves, B; Mar, S; Casper, C; Rose, J; Simmons, T; Waubant, E
ISI:000365729402284
ISSN: 1477-0970
CID: 2234352

Gut microbiome in early pediatric MS : a case-control study [Meeting Abstract]

Tremlett, H; Fadrosh, D; Lynch, S; Hart, J; Graves, J; Lulu, S; Aaen, G; Belman, Anita; Benson, L; Casper, C; Chitnis, T; Gorman, M; Krupp, Lauren; Lotze, T; Ness, J; Roalstad, S; Rodriguez, M; Rose, J; Mendelt-Tilleman, J; Weinstock-Guttman, B; Waubant, E
ORIGINAL:0011420
ISSN: 1526-632x
CID: 2236632

The Test of Everyday Cognitive Ability (TECA) Links Cognitive Measures to Real-Life Functioning in Adults with Multiple Sclerosis (MS) [Meeting Abstract]

Charvet, Leigh; Shaw, Michael; Kasschau, Margaret; Frontario, Ariana; Fang, Wendy; Sherman, Kathleen; Melville, Patricia; Krupp, Lauren
ISI:000362668600010
ISSN: 1531-8249
CID: 2225182

Pregnancy exposures and risk for paediatric onset MS [Meeting Abstract]

Graves, JS; Chitnis, T; Guttman, BWeinstock; Rubin, J; Nourbakhsh, B; Zeilkovitch, A; Simmons, T; Krupp, L; Belman, A; Ness, J; Mendelt-Tillema, J; Rodriguez, M; Gorman, M; Benson, L; Waldman, A; Aaen, G; Greenberg, B; Schreiner, T; Rose, J; Casper, TC; Waubant, E
ISI:000365729402283
ISSN: 1477-0970
CID: 2234182

Acquisition of early developmental milestones and need for special education services in paediatric-onset multiple sclerosis [Meeting Abstract]

Aaen, GS; Waltz, M; Casper, T; Ness, J; Gorman, M; Makhani, N; Vargas, W; Waubant, E; Chitnis, T; Lotze, T; Graves, J; Benson, L; Tillema, J-M; Rodriguez, M; Rose, J; Weinstock-Guttman, B; Krupp, L; Belman, A; US Network Paediat Multiple
ISI:000365729400145
ISSN: 1477-0970
CID: 2234332