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126 results on '"Krupp, L B"'

1. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author

Kappos, L., Bar-Or, A., Cree, B. A. C., Fox, R. J., Giovannoni, G., Gold, R., Vermersch, P., Arnold, D. L., Arnould, S., Scherz, T., Wolf, C., Wallstrom, E., Dahlke, F., Achiron, A., Achtnichts, L., Agan, K., Akman-Demir, G., Allen, A. B., Antel, J. P., Antiguedad, A. R., Apperson, M., Applebee, A. M., Ayuso, G. I., Baba, M., Bajenaru, O., Balasa, R., Balci, B. P., Barnett, M., Bass, A., Becker, V. U., Bejinariu, M., Bergh, F. T., Bergmann, A., Bernitsas, E., Berthele, A., Bhan, V., Bischof, F., Bjork, R. J., Blevins, G., Boehringer, M., Boerner, T., Bonek, R., Bowen, J. D., Bowling, A., Boyko, A. N., Boz, C., Bracknies, V., Braune, S., Brescia Morra, V., Brochet, B., Brola, W., Brownstone, P. K., Brozman, M., Brunet, D., Buraga, I., Burnett, M., Buttmann, M., Butzkueven, H., Cahill, J., Calkwood, J. C., Camu, W., Cascione, M., Castelnovo, G., Centonze, D., Cerqueira, J., Chan, A., Cimprichova, A., Cohan, S., Comi, G., Conway, J., Cooper, J. A., Corboy, J., Correale, J., Costell, B., Cottrell, D. A., Coyle, P. K., Craner, M., Cui, L., Cunha, L., Czlonkowska, A., da Silva, A. M., de Sa, J., de Seze, J., Debouverie, M., Debruyne, J., Decoo, D., Defer, G., Derfuss, T., Deri, N. H., Dihenia, B., Dioszeghy, P., Donath, V., Dubois, B., Duddy, M., Duquette, P., Edan, G., Efendi, H., Elias, S., Emrich, P. J., Estruch, B. C., Evdoshenko, E. P., Faiss, J., Fedyanin, A. S., Feneberg, W., Fermont, J., Fernandez, O. F., Ferrer, F. C., Fink, K., Ford, H., Ford, C., Francia, A., Freedman, M., Frishberg, B., Galgani, S., Garmany, G. P., Gehring, K., Gitt, J., Gobbi, C., Goldstick, L. P., Gonzalez, R. A., Grandmaison, F., Grigoriadis, N., Grigorova, O., Grimaldi, L. M. E., Gross, J., Gross-Paju, K., Gudesblatt, M., Guillaume, D., Haas, J., Hancinova, V., Hancu, A., Hardiman, O., Harmjanz, A., Heidenreich, F. R., Hengstman, G. J. D., Herbert, J., Herring, M., Hodgkinson, S., Hoffmann, O. M., Hofmann, W. E., Honeycutt, W. D., Hua, L. H., Huang, D., Huang, Y., Hupperts, R., Imre, P., Jacobs, A. K., Jakab, G., Jasinska, E., Kaida, K., Kalnina, J., Kaprelyan, A., Karelis, G., Karussis, D., Katz, A., Khabirov, F. A., Khatri, B., Kimura, T., Kister, I., Kizlaitiene, R., Klimova, E., Koehler, J., Komatineni, A., Kornhuber, A., Kovacs, K., Koves, A., Kozubski, W., Krastev, G., Krupp, L. B., Kurca, E., Lassek, C., Laureys, G., Lee, L., Lensch, E., Leutmezer, F., Li, H., Linker, R. A., Linnebank, M., Liskova, P., Llanera, C., Lu, J., Lutterotti, A., Lycke, J., Macdonell, R., Maciejowski, M., Maeurer, M., Magzhanov, R. V., Maida, E. -M., Malciene, L., Mao-Draayer, Y., Marfia, G. A., Markowitz, C., Mastorodimos, V., Matyas, K., Meca-Lallana, J., Merino, J. A. G., Mihetiu, I. G., Milanov, I., Miller, A. E., Millers, A., Mirabella, M., Mizuno, M., Montalban, X., Montoya, L., Mori, M., Mueller, S., Nakahara, J., Nakatsuji, Y., Newsome, S., Nicholas, R., Nielsen, A. S., Nikfekr, E., Nocentini, U., Nohara, C., Nomura, K., Odinak, M. M., Olsson, T., van Oosten, B. W., Oreja-Guevara, C., Oschmann, P., Overell, J., Pachner, A., Panczel, G., Pandolfo, M., Papeix, C., Patrucco, L., Pelletier, J., Piedrabuena, R., Pless, M., Polzer, U., Pozsegovits, K., Rastenyte, D., Rauer, S., Reifschneider, G., Rey, R., Rizvi, S. A., Robertson, D., Rodriguez, J. M., Rog, D., Roshanisefat, H., Rowe, V., Rozsa, C., Rubin, S., Rusek, S., Sacca, F., Saida, T., Salgado, A. V., Sanchez, V. E. F., Sanders, K., Satori, M., Sazonov, D. V., Scarpini, E. A., Schlegel, E., Schluep, M., Schmidt, S., Scholz, E., Schrijver, H. M., Schwab, M., Schwartz, R., Scott, J., Selmaj, K., Shafer, S., Sharrack, B., Shchukin, I. A., Shimizu, Y., Shotekov, P., Siever, A., Sigel, K. -O., Silliman, S., Simo, M., Simu, M., Sinay, V., Siquier, A. E., Siva, A., Skoda, O., Solomon, A., Stangel, M., Stefoski, D., Steingo, B., Stolyarov, I. D., Stourac, P., Strassburger-Krogias, K., Strauss, E., Stuve, O., Tarnev, I., Tavernarakis, A., Tello, C. R., Terzi, M., Ticha, V., Ticmeanu, M., Tiel-Wilck, K., Toomsoo, T., Tubridy, N., Tullman, M. J., Tumani, H., Turcani, P., Turner, B., Uccelli, A., Urtaza, F. J. O., Vachova, M., Valikovics, A., Walter, S., Van Wijmeersch, B., Vanopdenbosch, L., Weber, J. R., Weiss, S., Weissert, R., West, T., Wiendl, H., Wiertlewski, S., Wildemann, B., Willekens, B., Visser, L. H., Vorobeychik, G., Xu, X., Yamamura, T., Yang, Y. N., Yelamos, S. M., Yeung, M., Zacharias, A., Zelkowitz, M., Zettl, U., Zhang, M., Zhou, H., Zieman, U., Ziemssen, T., Bergmann A., Haas J., Mirabella M. (ORCID:0000-0002-7783-114X), Terzi M., Kappos, L., Bar-Or, A., Cree, B. A. C., Fox, R. J., Giovannoni, G., Gold, R., Vermersch, P., Arnold, D. L., Arnould, S., Scherz, T., Wolf, C., Wallstrom, E., Dahlke, F., Achiron, A., Achtnichts, L., Agan, K., Akman-Demir, G., Allen, A. B., Antel, J. P., Antiguedad, A. R., Apperson, M., Applebee, A. M., Ayuso, G. I., Baba, M., Bajenaru, O., Balasa, R., Balci, B. P., Barnett, M., Bass, A., Becker, V. U., Bejinariu, M., Bergh, F. T., Bergmann, A., Bernitsas, E., Berthele, A., Bhan, V., Bischof, F., Bjork, R. J., Blevins, G., Boehringer, M., Boerner, T., Bonek, R., Bowen, J. D., Bowling, A., Boyko, A. N., Boz, C., Bracknies, V., Braune, S., Brescia Morra, V., Brochet, B., Brola, W., Brownstone, P. K., Brozman, M., Brunet, D., Buraga, I., Burnett, M., Buttmann, M., Butzkueven, H., Cahill, J., Calkwood, J. C., Camu, W., Cascione, M., Castelnovo, G., Centonze, D., Cerqueira, J., Chan, A., Cimprichova, A., Cohan, S., Comi, G., Conway, J., Cooper, J. A., Corboy, J., Correale, J., Costell, B., Cottrell, D. A., Coyle, P. K., Craner, M., Cui, L., Cunha, L., Czlonkowska, A., da Silva, A. M., de Sa, J., de Seze, J., Debouverie, M., Debruyne, J., Decoo, D., Defer, G., Derfuss, T., Deri, N. H., Dihenia, B., Dioszeghy, P., Donath, V., Dubois, B., Duddy, M., Duquette, P., Edan, G., Efendi, H., Elias, S., Emrich, P. J., Estruch, B. C., Evdoshenko, E. P., Faiss, J., Fedyanin, A. S., Feneberg, W., Fermont, J., Fernandez, O. F., Ferrer, F. C., Fink, K., Ford, H., Ford, C., Francia, A., Freedman, M., Frishberg, B., Galgani, S., Garmany, G. P., Gehring, K., Gitt, J., Gobbi, C., Goldstick, L. P., Gonzalez, R. A., Grandmaison, F., Grigoriadis, N., Grigorova, O., Grimaldi, L. M. E., Gross, J., Gross-Paju, K., Gudesblatt, M., Guillaume, D., Haas, J., Hancinova, V., Hancu, A., Hardiman, O., Harmjanz, A., Heidenreich, F. R., Hengstman, G. J. D., Herbert, J., Herring, M., Hodgkinson, S., Hoffmann, O. M., Hofmann, W. E., Honeycutt, W. D., Hua, L. H., Huang, D., Huang, Y., Hupperts, R., Imre, P., Jacobs, A. K., Jakab, G., Jasinska, E., Kaida, K., Kalnina, J., Kaprelyan, A., Karelis, G., Karussis, D., Katz, A., Khabirov, F. A., Khatri, B., Kimura, T., Kister, I., Kizlaitiene, R., Klimova, E., Koehler, J., Komatineni, A., Kornhuber, A., Kovacs, K., Koves, A., Kozubski, W., Krastev, G., Krupp, L. B., Kurca, E., Lassek, C., Laureys, G., Lee, L., Lensch, E., Leutmezer, F., Li, H., Linker, R. A., Linnebank, M., Liskova, P., Llanera, C., Lu, J., Lutterotti, A., Lycke, J., Macdonell, R., Maciejowski, M., Maeurer, M., Magzhanov, R. V., Maida, E. -M., Malciene, L., Mao-Draayer, Y., Marfia, G. A., Markowitz, C., Mastorodimos, V., Matyas, K., Meca-Lallana, J., Merino, J. A. G., Mihetiu, I. G., Milanov, I., Miller, A. E., Millers, A., Mirabella, M., Mizuno, M., Montalban, X., Montoya, L., Mori, M., Mueller, S., Nakahara, J., Nakatsuji, Y., Newsome, S., Nicholas, R., Nielsen, A. S., Nikfekr, E., Nocentini, U., Nohara, C., Nomura, K., Odinak, M. M., Olsson, T., van Oosten, B. W., Oreja-Guevara, C., Oschmann, P., Overell, J., Pachner, A., Panczel, G., Pandolfo, M., Papeix, C., Patrucco, L., Pelletier, J., Piedrabuena, R., Pless, M., Polzer, U., Pozsegovits, K., Rastenyte, D., Rauer, S., Reifschneider, G., Rey, R., Rizvi, S. A., Robertson, D., Rodriguez, J. M., Rog, D., Roshanisefat, H., Rowe, V., Rozsa, C., Rubin, S., Rusek, S., Sacca, F., Saida, T., Salgado, A. V., Sanchez, V. E. F., Sanders, K., Satori, M., Sazonov, D. V., Scarpini, E. A., Schlegel, E., Schluep, M., Schmidt, S., Scholz, E., Schrijver, H. M., Schwab, M., Schwartz, R., Scott, J., Selmaj, K., Shafer, S., Sharrack, B., Shchukin, I. A., Shimizu, Y., Shotekov, P., Siever, A., Sigel, K. -O., Silliman, S., Simo, M., Simu, M., Sinay, V., Siquier, A. E., Siva, A., Skoda, O., Solomon, A., Stangel, M., Stefoski, D., Steingo, B., Stolyarov, I. D., Stourac, P., Strassburger-Krogias, K., Strauss, E., Stuve, O., Tarnev, I., Tavernarakis, A., Tello, C. R., Terzi, M., Ticha, V., Ticmeanu, M., Tiel-Wilck, K., Toomsoo, T., Tubridy, N., Tullman, M. J., Tumani, H., Turcani, P., Turner, B., Uccelli, A., Urtaza, F. J. O., Vachova, M., Valikovics, A., Walter, S., Van Wijmeersch, B., Vanopdenbosch, L., Weber, J. R., Weiss, S., Weissert, R., West, T., Wiendl, H., Wiertlewski, S., Wildemann, B., Willekens, B., Visser, L. H., Vorobeychik, G., Xu, X., Yamamura, T., Yang, Y. N., Yelamos, S. M., Yeung, M., Zacharias, A., Zelkowitz, M., Zettl, U., Zhang, M., Zhou, H., Zieman, U., Ziemssen, T., Bergmann A., Haas J., Mirabella M. (ORCID:0000-0002-7783-114X), and Terzi M.

Abstract

Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative

Published
2018

5. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis

Author

Krupp, L. B., primary, Christodoulou, C., additional, Melville, P., additional, Scherl, W. F., additional, Pai, L.- Y., additional, Muenz, L. R., additional, He, D., additional, Benedict, R. H. B., additional, Goodman, A., additional, Rizvi, S., additional, Schwid, S. R., additional, Weinstock-Guttman, B., additional, Westervelt, H. J., additional, and Wishart, H., additional

Published
2011
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18. A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis

Author

Miller, A. E., primary, Morgante, L. A., additional, Buchwald, L. Y., additional, Nutile, S. M., additional, Coyle, P. K., additional, Krupp, L. B., additional, Doscher, C. A., additional, Lublin, F. D., additional, Knobler, R. L., additional, Trantas, F., additional, Kelley, L., additional, Smith, C. R., additional, La Rocca, N., additional, and Lopez, S., additional

Published
1997
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28. Visual-cognitive processing deficits in pediatric multiple sclerosis.

Author

Smerbeck, A. M., Parrish, J., Serafin, D., Yeh, E. A., Weinstock-Guttman, B., Hoogs, M., Krupp, L. B., and Benedict, R. H. B.

Subjects
MULTIPLE sclerosis in children, COGNITIVE development, COGNITION disorders in children, NEUROPSYCHOLOGY, NEUROPSYCHOLOGICAL tests for children, UNILATERAL neglect, COGNITION disorders in old age, DIAGNOSIS
Abstract

Background: Children with multiple sclerosis (MS) can suffer significant cognitive deficits. This study investigates the sensitivity and validity in pediatric MS of two visual processing tests borrowed from the adult literature, the Brief Visuospatial Memory Test-Revised (BVMTR) and the Symbol Digit Modalities Test (SDMT).Objective: To test the hypothesis that visual processing is disproportionately impacted in pediatric MS by comparing performance with that of healthy controls on the BVMTR and SDMT.Methods: We studied 88 participants (43 MS, 45 controls) using a neuropsychological assessment battery including measures of intelligence, language, visual memory, and processing speed. Patients and demographically matched controls were compared to determine which tests are most sensitive in pediatric MS.Results: Statistically significant differences were found between the MS and control groups on BVMTR Total Learning (t (84) = 4.04, p < 0.001, d = 0.87), BVMTR Delayed Recall (t (84) = 4.45, p < 0.001, d = 0.96), and SDMT (t (38) = 2.19, p = 0.035, d = 0.69). No significant differences were found between groups on confrontation naming or general intellectual ability. Validity coefficients exploring correlation between BVMTR, SDMT, and disease characteristics were consistent with the adult literature.Conclusions: This study found that BVMTR and SDMT may be useful in assessing children and adolescents with MS. [ABSTRACT FROM PUBLISHER]

Published
2011
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29. Cognitive Functioning in Late Lyme Borreliosis

Author

Krupp, L. B., primary, Masur, D., additional, Schwartz, J., additional, Coyle, P. K., additional, Langenbach, L. J., additional, Fernquist, S. K., additional, Jandorf, L., additional, and Halperin, J. J., additional

Published
1991
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30. Protein expression profiles in pediatric multiple sclerosis: potential biomarkers.

Author

Rithidech, K. N., Honikel, L., Milazzo, M., Madigan, D., Troxell, R., and Krupp, L. B.

Subjects
MULTIPLE sclerosis research, MULTIPLE sclerosis in children, DEMYELINATION, CENTRAL nervous system, MASS spectrometry, GEL electrophoresis
Abstract

The diagnosis of pediatric multiple sclerosis (MS) is challenging due to its low frequency and the overlap with other acquired childhood demyelinating disorders of the central nervous system. To identify potential protein biomarkers which could facilitate the diagnosis, we used two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry to identify proteins associated with pediatric MS. Plasma samples from nine children with MS and nine healthy subjects, matched in aggregate by age and gender, were analyzed for differences in their patterns of protein expression. We found 12 proteins that were significantly up regulated in the pediatric MS group: alpha-1-acid-glycoprotein 1, alpha-1-B-glycoprotein, transthyretin, apoliprotein-C-III, serum amyloid P component, complement factor-I, clusterin, gelsolin, hemopexin, kininogen-1, hCG1993037-isoform, and vitamin D-binding protein. These results show that 2-DE in combination with mass spectrometry is a highly sensitive technique for the identification of blood-based biomarkers. This proteomic approach could lead to a new panel of diagnostic and prognostic markers in pediatric MS. [ABSTRACT FROM AUTHOR]

Published
2009
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31. Longitudinal correlates of fatigue in multiple sclerosis.

Author

Patrick, E., Christodoulou, C., and Krupp, L. B.

Subjects
MULTIPLE sclerosis, FATIGUE (Physiology), PAIN, QUALITY of life, NEUROLOGICAL disorders, ALTERED states of consciousness, PHYSIOLOGY
Abstract

Objective To determine the predictors of longitudinal changes in fatigue based on pain, mood, and neurological impairment across multiple sclerosis (MS) subtypes. Background Fatigue is the most common symptom of MS but remains poorly understood. The New York State Multiple Sclerosis Consortium (NYSMSC) database offers a unique opportunity to longitudinally assess a variety of potential fatigue correlates in a very large and diverse MS sample. Design/Methods This study examined baseline and 1-year follow-up data on 2768 patients drawn from the NYSMSC database regarding fatigability, pain, depressive symptoms, MS subtype, and expanded disability status scale (EDSS). Correlates and predictors of fatigue were assessed in correlational and multiple regression analyses. Results Baseline fatigue, pain, and depression accounted for 34.6% of the variance in 1-year follow-up fatigue scores. Fatigue was lower in relapsing-remitting subjects than in other MS subtypes. Fatigue consistently correlated at baseline and follow-up with depressive symptoms, pain severity, and EDSS. Changes in fatigue correlated with changes in other variables. Conclusions Predictors of fatigue at 1 year include baseline fatigue, pain, mood, and EDSS. These symptoms are also correlated at baseline, follow-up, and in change scores. Identifying predictors of fatigue may facilitate patient management. [ABSTRACT FROM AUTHOR]

Published
2009

35. Acquired immunodeficiency syndrome in male prisoners. New insights into an emerging syndrome.

Author

Wormser, Gary P., Krupp, Lauren B., Hanrahan, John P., Gavis, Gustave, Spira, Thomas J., Cunningham-Rundles, Sussana, Wormser, G P, Krupp, L B, Hanrahan, J P, Gavis, G, Spira, T J, and Cunningham-Rundles, S

Subjects
AIDS, PRISONERS, PNEUMOCYSTIS pneumonia, DISEASES
Abstract

Between September 1981 and June 1982, the acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia were diagnosed in seven previously healthy young men incarcerated for 5 to 38 months in New York State correctional facilities. All seven patients were anergic, six were lymphopenic, and all developed oral candidiasis. Immunologic evaluation in vitro showed profound defects in cellular immune function in patients tested, with inversion of the normal ratio of helper to suppressor T-cell populations in four of five patients studied. No underlying immunosuppressive disorder was found in any patient, including three patients who had postmortem examinations. Based on these cases, the incidence of this syndrome among inmates of New York State correctional facilities is estimated to be at least 20 out of 100 000 per year. None of the inmates was homosexual but all had used intravenous drugs extensively before incarceration. If intravenous drug use is a cause of the syndrome, then the epidemiologic findings of this study suggest a prolonged incubation period (mean, 14.6 months) before development of serious opportunistic infection. Recognition that certain prisoners are at high risk for the acquired immunodeficiency syndrome has important implications for the prison health-care system. [ABSTRACT FROM AUTHOR]

Published
1983
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37. Younger children with MS have a distinct CSF inflammatory profile at disease onset

Author

Chabas, D., Ness, J., Belman, A., Yeh, E. A., Kuntz, N., Gorman, M. P., Strober, J B., De Kouchkovsky, I., McCulloch, C., Chitnis, T., Rodriguez, M., Weinstock-Guttman, B., Krupp, L. B., and Waubant, E.

Abstract

The clinical and MRI presentation differs between earlier- and later-onset pediatric multiple sclerosis (MS), whereas the effect of age on the CSF inflammatory profile is unknown and may contribute to delayed diagnosis.

Published
2010
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39. Detection of Borrelia burgdorferiantigens in cerebrospinal fluid

Author

Coyle, P. K., Deng, Z., Schutzer, S. E., Belman, A. L., Benach, J., Krupp, L. B., and Luft, B.

Abstract

We examined CSF for Borrelia burgdorferiantigens using antigen-capture ELISA and Western (immuno) blot. Antigen-capture ELISA was positive in 38 of 77 (49) CSF samples obtained from neurologic patients with presumed B burgdorferiinfection, compared with one of 34 (3) CSF samples obtained from other neurologic disease controls who came from a region endemic for Lyme disease. Western immunoblot was positive for B burgdorferiantigens in 12 of 22 (55) CSF samples from the B burgdorferiinfected groups, compared with none of 11 CSF samples from the control group. CSF antigen detection should prove helpful in evaluating patients for suspected neurologic Lyme disease.

Published
1993

47. Remotely-delivered cognitive remediation in multiple sclerosis (MS): protocol and results from a pilot study.

Author

Charvet LE, Shaw MT, Haider L, Melville P, and Krupp LB

Abstract

Background: Cognitive impairment represents a critical unmet treatment need in multiple sclerosis (MS). Cognitive remediation is promising but traditionally requires multiple clinic visits to access treatment. Computer-based programs provide remote access to intensive and individually-adapted training., Objective: Our goal was to develop a protocol for remotely-supervised cognitive remediation that enables individuals with MS to participate from home while maintaining the standards for clinical study., Methods: MS participants ( n  = 20) were randomized to either an active cognitive remediation program ( n  = 11) or a control condition of ordinary computer games ( n  = 9). Participants were provided study laptops to complete training for five days per week over 12 weeks, targeting a total of 30 hours. Treatment effects were measured with composite change via scores of a repeated neuropsychological battery., Results: Compliance was high with an average of 25.0 hours of program use (80% of the target) and did not differ between conditions (25.7 vs. 24.2 mean hours, p  = 0.80). The active vs. control participants significantly improved in both the cognitive measures (mean composite z-score change of 0.46 ± 0.59 improvement vs. -0.14 ± 0.48 decline, p  = 0.02) and motor tasks (mean composite z-score change of 0.40 ± 0.71improvement vs. -0.64 ± 0.73 decline, p  = 0.005)., Conclusions: Remotely-supervised cognitive remediation is feasible for clinical study with potential for meaningful benefit in MS.

Published
2015
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48. Social cognition in pediatric-onset multiple sclerosis (MS).

Author

Charvet LE, Cleary RE, Vazquez K, Belman AL, and Krupp LB

Subjects
Adolescent, Adult, Age of Onset, Child, Cognition Disorders psychology, Female, Humans, Male, Multiple Sclerosis complications, Multiple Sclerosis psychology, Neuropsychological Tests, Young Adult, Cognition physiology, Cognition Disorders physiopathology, Multiple Sclerosis physiopathology, Social Behavior, Theory of Mind physiology
Abstract

Background: Pediatric-onset multiple sclerosis (MS) patients represent a subpopulation who are diagnosed during the course of development. Social cognitive deficits have recently been recognized in adults with MS. It is critical to identify whether these youngest patients with the disorder are also at risk., Objective: To determine whether pediatric-onset MS is associated with social cognitive deficits., Methods: Consecutively-recruited participants with pediatric-onset MS were compared to a group of age- and gender-matched healthy controls on Theory of Mind (ToM) task performance. Tasks measured facial affect recognition (Reading the Mind in the Eyes Test), detecting social faux pas (Faux Pas Test), and understanding the perspective of another (False Beliefs Task)., Results: Twenty-eight (28) pediatric-onset MS participants (median age 17 years) and 32 healthy controls (median age 16 years) completed the study. The MS participants performed worse than controls on all three ToM tasks: Reading the Mind in the Eyes Test (p = 0.008), the Faux Pas Test (p = 0.009), and the False Beliefs Task (p = 0.06). While more MS than control participants were impaired on a measure of information processing speed (the Symbol Digit Modalities Test; 38% versus 6%), it did not account for the differences in ToM performance., Conclusions: Social cognition may represent an area of cognitive functioning affected by MS in the pediatric-onset population. These processes are especially important to study in younger patients as they may have long range implications for social adjustment, employment, and well-being., (© The Author(s) 2014.)

Published
2014
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49. Longitudinal evaluation of cognitive functioning in pediatric multiple sclerosis: report from the US Pediatric Multiple Sclerosis Network.

Author

Charvet LE, O'Donnell EH, Belman AL, Chitnis T, Ness JM, Parrish J, Patterson M, Rodriguez M, Waubant E, Weinstock-Guttman B, and Krupp LB

Subjects
Adolescent, Child, Cognition physiology, Cognition Disorders etiology, Cognition Disorders psychology, Executive Function physiology, Female, Humans, Language, Longitudinal Studies, Male, Memory, Short-Term physiology, Multiple Sclerosis complications, Multiple Sclerosis psychology, United States, Attention physiology, Cognition Disorders physiopathology, Multiple Sclerosis physiopathology, Neuropsychological Tests
Abstract

Background: Approximately one-third of those with pediatric-onset multiple sclerosis (MS) experience cognitive impairment. Less is known concerning their change in cognitive functioning over time., Objective: Changes in cognitive function over time were measured in the largest pediatric cohort to date through the US Network of Pediatric MS Centers., Methods: A total of 67 individuals with pediatric MS (n=62) or clinically isolated syndrome (CIS, n=5), ranging from 8-17 years of age (mean age ± standard deviation (SD)=14.37 ± 2.02) completed initial and follow-up neuropsychological testing after an average of 1.64 ± 0.63 years apart. The nine tests administered measure general intellect, attention and working memory, verbal memory, visuomotor integration, language, and executive functioning., Results: Rate of impairment (having one-third or more scores in the impaired range) was 37% at baseline and 33% at follow-up. Tests commonly impaired were measures of visuomotor integration, speeded processing, and attention. Most tested did not decline over two years. There was no clear pattern of change on any specific measure., Conclusion: Findings suggest that, over short timeframes, stable or even improved performances on measures of cognitive ability can occur. Pediatric MS may instead prevent expected age-related cognitive gains., (© The Author(s), 2014.)

Published
2014
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50. Copy number variation in pediatric multiple sclerosis.

Author

McElroy JP, Krupp LB, Johnson BA, McCauley JL, Qi Z, Caillier SJ, Gourraud PA, Yu J, Nathanson L, Belman AL, Hauser SL, Waubant E, Hedges DJ, and Oksenberg JR

Subjects
Adolescent, Age of Onset, Child, Comparative Genomic Hybridization, Female, Heat-Shock Proteins genetics, Humans, In Situ Hybridization, Fluorescence, Male, Muscle Spasticity genetics, Spinocerebellar Ataxias congenital, Spinocerebellar Ataxias genetics, Gene Dosage, Multiple Sclerosis genetics
Abstract

Background: Pediatric onset multiple sclerosis (MS) accounts for 2-4% of all MS. It is unknown whether the disease shares the same underlying pathophysiology found in adult patients or an extreme early onset phenotype triggered by distinct biological mechanisms. It has been hypothesized that copy number variations (CNVs) may result in extreme early onset diseases because CNVs can have major effects on many genes in large genomic regions., Objectives and Methods: The objective of the current research was to identify CNVs, with a specific focus on de novo CNVs, potentially causing early onset MS by competitively hybridizing 30 white non-Hispanic pediatric MS patients with each of their parents via comparative genomic hybridization (CGH) analysis on the Agilent 1M CGH array., Results and Discussion: We identified 10 CNVs not overlapping with any CNV regions currently reported in the Database of Genomic Variants (DGV). Fifty-five putatively de novo CNVs were also identified: all but one common in the DGV. We found the single rare CNV was a private variation harboring the SACS gene. SACS mutations cause autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease. Additional clinical review revealed that the patient with the SACS gene CNV shared some features of both MS and ARSACS., Conclusions: This is the first reported study analyzing pediatric MS CNVs. While not yielding causal variation in our initial pediatric dataset, our approach confirmed diagnosis of an ARSACS-like disease in addition to MS in the affected individual, which led to a more complete understanding of the patient's disease course and prognosis.

Published
2013
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