Partners Multiple Sclerosis Center  



MS Natural History Study



Home Blog Post

Comprehensive Longitudinal Investigation of Multiple Sclerosis
at Brigham and Women’s Hospital 



CLIMB Study Group Spring 2014
(listed left to right, back to front)
D. Meier, M.T. Malik, R. Bove, R. Bakshi, S. Tauhid, R. Carruthers, M. Anderson, P. Kivisaak, E. Greeke, B.C. Healy, E. Klawiter, C.R. Guttmann,
A. Chua, R. Chu, V. Oommen, M. Weiner, D. Rotstein, H. Weiner, A. Robbins, Z. Xia, S. Egorova, C. Diaz-Cruz, M. Houtchens,
F. Khalid, G. Little, T. Chitnis, B. Glanz, M. Polgar-Turcsanyi, R. Gandhi


The CLIMB study is a large-scale, long-term study of patients with MS.  It is designed to investigate the course of the disease in the current era of treatment.   The main goals of the study are to:

1. Identify predictors of future disease course when patients are at the beginning of their illness.
2. Determine the effects of treatment on disease progression and accumulation of disability.

Subjects will have neurological exams and MRI yearly.  Subjects will also donate blood samples and complete quality of life and mood questionnaires yearly.

Eligible subjects are those with:
1. Diagnosis of MS or monosymptomatic disease
2. 18 years of age or older
3. Willing to have MRI yearly
4. Willing to donate blood samples and complete questionnaires yearly




Howard Weiner, M.D.

 Director, Partners MS Center


 Tanuja Chitnis, MD

Medical Director, CLIMB Study

Lead Study Staff


Bonnie Glanz, Ph.D

Director, Clinical Research Operations


Mira Weiner, M.B.A.

 Project Manager


Sandra Cook, RN

Research Nurse

Study Coordinators


Emily Greeke, B.A.



Fiona Stuart



Allison Larussa

 Biostatistics Unit


Brian Healy, PhD



Alicia Chua, M.S.


Information Technology

 Mariann Polgar, MS


Adam Polgar


Neuroimaging Research


 Charles Guttman, MD



Rob Bakshi, MD


 Svetlana Egorova, M.D., Ph.D.
Sr. Investigators and Fellows


Riley Bove, MD



  Camilo Diaz-Cruz, MD

 Research Fellow







  1. Addressing Human Subjectivity via Transfer Learning: An Application to Predicting Disease Outcome in Multiple Sclerosis Patients. Zhao Y, Brodley CE, Chitnis T, Healy BC. Proceedings of the 2014 SIAM International Conference on Data Mining. p965-73, 2014.
  2. MRI phenotypes based on cerebral lesions and atrophy in patients with multiple sclerosis. Tauhid S, Neema M, Healy BC, Weiner HL, Bakshi R. Journal of the Neurological Sciences. 2014;346:250-54. PMID: 25220114.
  3. An expanded composite scale of MRI-defined disease severity in multiple sclerosis: MRDSS2. Bakshi R, Neema M, Tauhid S, Healy BC, Glanz BI, Kim G, Miller J, Berkowitz JL, Bove R, Houtchens MK, Severson C, Stankiewicz JM, Stazzone L, Chitnis T, Guttmann CR, Weiner HL, Ceccarelli A. Neuroreport. 2014 Oct 1;25(14):1156-61. PMID: 25100554.
  4. An observational comparison of natalizumab vs. fingolimod using JCV serology to determine therapy. Carruthers RL, Rotstein DL, Healy BC, Chitnis T, Weiner HL, Buckle GJ. Mult Scler. 2014 Sep;20(10):1381-90. PMID: 24852928.
  5. Progression rates and sample size estimates for PPMS based on the CLIMB study population. Raghavan K, Healy BC,Carruthers RL, Chitnis T. Mult Slero. 2014 July 28. In press. PMID: 25070676.
  6. Factors associated with recovery from acute optic neurtis in patiens with multiple sclerosis. Malik MT, Healy BC, Benson LA, Kivisäkk P, Musallam A, Weiner HL, Chitnis T. Neurology. 2014 Jun 17;82(24):2173-9. PMID: 24850491; PubMed Central PMCID: PMC:4113460.
  7. Treatment satisfaction in multple sclerosis. Glanz BI, Musallam A, Rintell DJ, Chitnis T, Weiner HL, Healy BC. Int Journal MS Care. 2014 Summer16(2):68-75. PMID: 25061430; PubMed Central PMCID: PMC4106393.
  8. Low testosterone is associated with disability in men with multiple sclerosis. Bove R, Musallam A, Healy B Raghavan K, Glanz B, Bakshi R, Weiner H, De Jager P, Miller K, Chitnis T. Mult Scler. 2014 Apr 7. [Epub ahead of print]. PMID: 24710799; PubMed Central PMCID: PMC4188801.
  9. Modeling disease severity in multiple sclerosis using electronic health records. Xia Z, Secor E, Chibnik LB, Bove RM, Cheng S, Chitnis T, Cagan A, Gainer VS, Chen PJ, Liao KP, Shaw SY, Ananthakrishnan AN, Szolovits P, Weiner HL, Karlson EW, Murphy SN, Savova GK, Cai T, Churchill SE, Plenge RM, Kohane IS, De Jager PL. PLoS One. 2013 Nov 11;8(11):e78927. eCollection 2013. PubMed PMID: 24244385; PubMed Central PMCID: PMC3823928.
  10. Clinical relevance and functional  consequences of the TNFRSF1A multiple sclerosis locus. Ottoboni L, Frohlich IY, Lee M, Healy BC, Keenan BT, Xia Z, Chitnis T, Guttmann CR, Khoury SJ, Weiner HL, Hafler DA, De Jager PL. Neurology. 2013 Nov 26;81(22):1891-9. Epub 2013 Oct 30. PubMed PMID: 24174586; PubMed Central PMCID: PMC3843384.
  11. Evaluation of circulating osteopontin levels in an unselected cohort of patients with multiple sclerosis: relevance for biomarker development. Kivisäkk P, Healy BC, Francois K, Gandhi R, Gholipour T, Egorova S, Sevdalinova V, Quintana F, Chitnis T, Weiner HL, Khoury SJ. Mult Scler. 2014 Apr;20(4):438-44. Epub 2013 Sep 4. PubMed PMID: 24005026.
  12. Removing Confounding Factors via Constraint-Based Clustering: An Application to Finding Homogeneous Groups of MS Patients. Liu J, Brodley CE, Healy BC, Chitnis T. Data Mining for Healthcare Workshop at ICHI, 2013. 
  13. Increased leptin and A-FABP levels in relapsing and progressive forms of MS. Messina S,Vargas-Lowy D, Musallam A, Healy BC, Kivisakk P, Gandhi R, Bove, R, Gholipou T, Khoury SJ, Weiner HL, Chitnis T. BMC Neurol. 2013 Nov 11;13(1):172. PMID: 2421502; PMCID: PMC3829106
  14. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. International Multiple Sclerosis Genetics Consortium (IMSGC), Beecham AH, atsopoulos NA, Xifara DK, Davis MF, Kemppinen A, Cotsapas C, Shah TS, Spencer C, Booth D, Goris A, Oturai A, Saarela J, Fontaine B, Hemmer B, Martin C, Zipp F, D'Alfonso S, Martinelli-Boneschi F, Taylor B, Harbo HF, Kockum I, Hillert J, Olsson T, Ban M, Oksenberg JR, Hintzen R, Barcellos LF; Wellcome Trust Case Control Consortium 2 (WTCCC2); International IBD Genetics Consortium (IIBDGC), Agliardi C, Alfredsson L, Alizadeh M, Anderson C, Andrews R, Søndergaard HB, Baker A, Band G, Baranzini SE, Barizzone N, Barrett J, Bellenguez C, Bergamaschi  L, Bernardinelli L, Berthele A, Biberacher V, Binder TM, Blackburn H, Bomfim IL,  Brambilla P, Broadley S, Brochet B, Brundin L, Buck D, Butzkueven H, Caillier SJ, Camu W, Carpentier W, Cavalla P, Celius EG, Coman I, Comi G, Corrado L, Cosemans  L, Cournu-Rebeix I, Cree BA, Cusi D, Damotte V, Defer G, Delgado SR, Deloukas P,  di Sapio A, Dilthey AT, Donnelly P, Dubois B, Duddy M, Edkins S, Elovaara I, Esposito F, Evangelou N, Fiddes B, Field J, Franke A, Freeman C, Frohlich IY, Galimberti D, Gieger C, Gourraud PA, Graetz C, Graham A, Grummel V, Guaschino C, Hadjixenofontos A, Hakonarson H, Halfpenny C, Hall G, Hall P, Hamsten A, Harley J, Harrower T, Hawkins C, Hellenthal G, Hillier C, Hobart J, Hoshi M, Hunt SE, Jagodic M, Jelčić I, Jochim A, Kendall B, Kermode A, Kilpatrick T, Koivisto K, Konidari I, Korn T, Kronsbein H, Langford C, Larsson M, Lathrop M, Lebrun-Frenay  C, Lechner-Scott J, Lee MH, Leone MA, Leppä V, Liberatore G, Lie BA, Lill CM, Lindén M, Link J, Luessi F, Lycke J, Macciardi F, Männistö S, Manrique CP, Martin R, Martinelli V, Mason D, Mazibrada G, McCabe C, Mero IL, Mescheriakova J, Moutsianas L, Myhr KM, Nagels G, Nicholas R, Nilsson P, Piehl F, Pirinen M, Price SE, Quach H, Reunanen M, Robberecht W, Robertson NP, Rodegher M, Rog D, Salvetti  M, Schnetz-Boutaud NC, Sellebjerg F, Selter RC, Schaefer C, Shaunak S, Shen L, Shields S, Siffrin V, Slee M, Sorensen PS, Sorosina M, Sospedra M, Spurkland A, Strange A, Sundqvist E, Thijs V, Thorpe J, Ticca A, Tienari P, van Duijn C, Visser EM, Vucic S, Westerlind H, Wiley JS, Wilkins A, Wilson JF, Winkelmann J, Zajicek J, Zindler E, Haines JL, Pericak-Vance MA, Ivinson AJ, Stewart G, Hafler  D, Hauser SL, Compston A, McVean G, De Jager P, Sawcer SJ, McCauley JL. Nat Genet. 2013 Nov;45(11):1353-60. PMID: 24076602, PMCID: PMC3832895.
  15. Elevated relapse rate in pediatric compared to adult MS persis for at least 6 years. Benson LA, Healy BC, Gorman MP, Baruch NF, Gholipour T, Musallam A, Chitnis T. Mult Sler  Relat Disord. 15 Jul 2013.
  16. No sex-specific difference in disease trajectory in multiple sclerosis patients before and after age 50. Bove R, Musallam A, Healy BC, Houtchens M, Glanz BI, Khoury S, Guttmann CR, De Jager PL, Chitnis T. BMC Neurol. 2013 Jul 3;13:73. PMID: 23822612
  17. Assessment of definitions of sustained disease progression in relapsing-remitting multiple sclerosis. Healy BC, Engler D, Glanz B, Musallam A, Chitnis T. Mult Scler Int. 2013;2013:189624. Epub 2013 Mar 10. PMID: 23555057
  18. Evaluation of an online platform for multiple sclerosis research: patient description, validation of severity scale, and exploration of BMI effects on disease course. Bove R, Secor E, Healy BC, Musallam A, Vaughn T, Glanz BI, Greeke E, Weiner HL, Chitnis T, Wicks P, De Jager PL. PLoS One. 2013;8(3):e59707. Epub 2013 Mar 20. PMID: 23527256
  19. Circulating MicroRNAs as biomarkers for disease staging in multiple sclerosis. Gandhi R, HealyB, Gholipour T, Egorova S, Musallam A, Hussain MS, Nejad P, Patel B, Hei H, Khoury S, Quintana F, Kivisakk P, Chitnis T, Weiner HL. Ann Neurol. 2013 Jun;73(6):729-40. Epub 2013 Jul 8. PMID: 23494648
  20. Increased Th17 response to myelin peptides in pediatric MS. Vargas-Lowy D, Kivisakk P, Gandhi R, Raddassi K, Soltany P, Gorman MP, Khoury SJ, Chitnis T. Clin Immunol. 2012 Dec 28;146(3):176-84. PMID: 23352968
  21. Work productivity in relapsing multiple sclerosis: associations with disability, depression, fatigue, anxiety, cognition, and health-related quality of life. Glanz, BI, Degano IR, Rintell DJ, Chitnis T, Weiner HL, Healy BC. Value Health. 2012 Dec;15(8):1029-35. PMCID: PMC23244804
  22. The impact of lesion i n-painting and registrat ion methods on voxel-based morphometry in detecing regional cerebral gray matter atrophy in multiple sclerosis. Cecciarelli A, Jackson JS, Tauhid S, Arora A, Gorky J, Dell'Oglio E, Bakshi A, Chitnis T, Khoury SJ, Weiner HL, Guttmann CR, Bakshi R, Neema M. AJNR Am J Neuroradiol. 2012 Sep;33(8):1579-85. Epub 2012 Mar 29. PMID: 22460341
  23.  An RNA profile identifies two subsets of multiple sclerosis patients differing in disease activity . Ottoboni L, Keenan BT, Tamayo P, Kuchroo M, Mesirov JP, Buckle GJ, Khoury SJ, Hafler DA, Weiner HL, De Jager PL. Sci Transl Med. 2012 Sep 26;4(153):153ra131.
  24. Magnetic resonance disease severity scale (MRDSS) for patients with multiple sclerosis: A longitudinal study.  Moodie J, Healy BC, Buckle GJ, Gauthier SA, Glanz BI, Arora A, Ceccarelli A, Tauhid S, Han XM, Venkataraman A, Chitnis T, Khoury SJ, Guttmann CR, Weiner HL, Neema M, Bakshi R. J Neurol Sci. 2012 Apr 15;315(1-2):49-54. PMCID: PMD22209496
  25. Effect of gender on late-onset multiple sclerosis. Bove RM, Healy B, Augustine A, Musallam A, Gholipour T, Chitnis T. Mult Scler. 2012 Mar 1. PMCID: PMD22383227
  26. The impact of a recent relapse on patient-reported outcomes in subjects with multiple sclerosis. Healy BC, Degano IR, Schreck A, Rintell D, Weiner H, Chitnis T, Glanz BI. Qual Life Res. 2012 Jan 12. PMCID: PMD 22237991
  27. CADASIL and Balo's concentric sclerosis: a link between ischemia and demyelination? Chitnis T, Hollmann T. Neurology. 2012 Jan 17;78(3):221-3. Epub 2012 Jan. 4. PMCID: PMD 2221879
  28. Cognitive deterioration in patients with early multiple sclerosis: a 5-year study.
    Glanz BI, Healy BC, Hviid LE, Chitnis T, Weiner HL.
    J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):38-43. Epub 2011 Jul 11.

  29. Demographic and clinical characteristics of malignant multiple sclerosis.
    Gholipour T, Healy B, Baruch NF, Weiner HL, Chitnis T. Neurology. 2011 Jun 7;76(23):1996-2001.

  30. Improving power to detect disease progression in multiple sclerosis through alternative analysis strategies. Healy B, Chitnis T, Engler D. J Neurol. 2011 Apr 7.
  31. Patient reported outcomes in benign multiple sclerosis. Hviid L, Healy B, Rintell D, Chitnis T, Weiner H, Glanz B. J Mult Scler. 2011 Mar 3. PMID:
  32. Accounting for disease modifying therapy in models of clinical progression in multiple sclerosis . Healy BC, Engler D, Gholipour T, Weiner H, Bakshi R, Chitnis T. J Neurol Sci. 2011 Jan 18.  PMID: 21251671
  33. Population structure and HLA DRB1*1501 in the response of subjects with multiple sclerosis to first-line treatments.Gross R, Healy BC, Cepok S, Chitnis T, Khoury SJ, Hemmer B, Weiner HL, Hafler DA, De Jager PL. J Neuroimmunol. 2010 Nov 27. 
  34. A putative Alzheimer's disease risk allele in PCK1 influences brain atrophy in multiple sclerosis . Xia Z, Chibnik LB, Glanz BI, Liguori M, Shulman JM, Tran D, Khoury SJ, Chitnis T, Holyoak T, Weiner HL, Guttmann CR, De Jager PL. PLoS One. 2010 Nov 30;5(11):e14169. PMID: 21152065
  35. A randomized controlled double-masked trial of albuterol add-on therapy in patients with multiple sclerosis. Khoury SJ, Healy BC, Kivisäkk P, Viglietta V, Egorova S, Guttmann CR, Wedgwood JF, Hafler DA, Weiner HL, Buckle G, Cook S, Reddy S. Arch Neurol. 2010 Sep;67(9):1055-6 
  36. Seasonal prevalence of MS disease activity. Meier DS, Balashov KE, Healy B, Weiner HL, Guttmann CR. Neurology. 2010 Aug 31;75(9):799-806. 
  37. A method for evaluating treatment switching criteria in multiple sclerosis. Healy BC, Glanz BI, Stankiewicz J, Buckle G, Weiner H, Chitnis T. Mult Scler. 2010  Dec;16(12):1483-9. Epub 2010 Aug 24.
  38. HLA B*44: protective effects in MS susceptibility and MRI outcome measures. Healy BC, Liguori M, Tran D, Chitnis T, Glanz B, Wolfish C, Gauthier S, Buckle G, Houtchens M, Stazzone L, Khoury S, Hartzmann R, Fernandez-Vina M, Hafler DA, Weiner HL, Guttmann CR, De Jager PL. Neurology. 2010 Aug 17;75(7):634-40. 
  39. The association between cognitive impairment and quality of life in patients with early multiple sclerosis. Glanz BI, Healy BC, Rintell DJ, Jaffin SK, Bakshi R, Weiner HL. J Neurol Sci. 2010 Mar 15;290(1-2):75-9. Epub 2009 Nov 26. 
  40. Brain MRI Lesion Load at 1.5T and 3T versus Clinical Status in Multiple Sclerosis. Stankiewicz JM, Glanz BI, Healy BC, Arora A, Neema M, Benedict RH, Guss ZD, Tauhid S, Buckle GJ, Houtchens MK, Khoury SJ, Weiner HL, Guttmann CR, Bakshi R. J Neuroimaging. 2009 Nov 3. 
  41.  Incidence and factors associated with treatment failure in the CLIMB multiple sclerosis cohort study.Gauthier SA, Glanz BI, Mandel M, Tsagkaropoulos A, Neema M, Stankiewicz J, Arora A, Duan Y, Liptak Z, Egorova S, Buckle GJ, Bakshi R, Guttmann CR, Khoury SJ, Weiner HL. J Neurol Sci. 2009 Sep 15;284(1-2):116-9. Epub 2009 May 9. PMID: 19428028  
  42. Regional white matter atrophy--based classification of multiple sclerosis in cross-sectional and longitudinal data. Sampat MP, Berger AM, Healy BC, Hildenbrand P, Vass J, Meier DS, Chitnis T, Weiner HL, Bakshi R, Guttmann CR. AJNR Am J Neuroradiol. 2009 Oct;30(9):1731-9. Epub 2009 Aug 20. 
  43. Smoking and disease progression in multiple sclerosis. Healy BC, Ali EN, Guttmann CR, Chitnis T, Glanz BI, Buckle G, Houtchens M, Stazzone L, Moodie J, Berger AM, Duan Y, Bakshi R, Khoury S, Weiner H, Ascherio A. Arch Neurol. 2009 Jul;66(7):858-64. 
  44. Natalizumab treatment is associated with peripheral sequestration of proinflammatory T cells. Kivisäkk P, Healy BC, Viglietta V, Quintana FJ, Hootstein MA, Weiner HL, Khoury SJ. Neurology. 2009 Jun 2;72(22):1922-30. 
  45.  Demographics of pediatric-onset multiple sclerosis in an MS center population from the Northeastern United States. Chitnis T, Glanz B, Jaffin S, Healy B. Mult Scler. 2009 May;15(5):627-31. Epub 2009 Mar 19. PMID: 19299440 
  46. Spinal cord lesions and clinical status in multiple sclerosis: A 1.5 T and 3 T MRI study. Stankiewicz JM, Neema M, Alsop DC, Healy BC, Arora A, Buckle GJ, Chitnis T, Guttmann CR, Hackney D, Bakshi R. J Neurol Sci. 2009 Apr 15;279(1-2):99-105. PMID: 19178916
  47. Rate of brain atrophy in benign vs early multiple sclerosis.  Gauthier SA, Berger AM, Liptak Z, Duan Y, Egorova S, Buckle GJ, Glanz BI, Khoury SJ, Bakshi R, Weiner HL, Guttmann CR.  Arch Neurol. 2009 Feb;66(2):234-7.  PMID: 19204160 
  48. Daclizumab in treatment of multiple sclerosis patients.
    Ali EN, Healy BC, Stazzone LA, Brown BA, Weiner HL, Khoury SJ. Mult Scler. 2009 Feb;15(2):272-4. Epub 2009 Jan 9.
  49. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis.  Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Arch Neurol. 2009 Jan;66(1):54-9. PMID: 19139299 
  50. Deep gray matter involvement on brain MRI scans is associated with clinical progression in multiple sclerosis. Neema M, Arora A, Healy BC, Guss ZD, Brass SD, Duan Y, Buckle GJ, Glanz BI, Stazzone L, Khoury SJ, Weiner HL, Guttmann CR, Bakshi R. J Neuroimaging. 2009 Jan;19(1):3-8 
  51. Predicting clinical progression in multiple sclerosis with the magnetic resonance disease severity scale. Bakshi R, Neema M, Healy BC, Liptak Z, Betensky RA, Buckle GJ, Gauthier SA, Stankiewicz J, Meier D, Egorova S, Arora A, Guss ZD, Glanz B, Khoury SJ, Guttmann CR, Weiner HL.  Arch Neurol. 2008 Nov;65(11):1449-53. 
  52. CTLA4Ig treatment in patients with multiple sclerosis: an open-label, phase 1 clinical trial.  Viglietta V, Bourcier K, Buckle GJ, Healy B, Weiner HL, Hafler DA, Egorova S, Guttmann CR, Rusche JR, Khoury SJ. Neurology. 2008 Sep 16;71(12):917-24. 
  53. Medulla oblongata volume: a biomarker of spinal cord damage and disability in multiple sclerosis.  Liptak Z, Berger AM, Sampat MP, Charil A, Felsovalyi O, Healy BC, Hildenbrand P, Khoury SJ, Weiner HL, Bakshi R, Guttmann CR.AJNR Am J Neuroradiol. 2008 Sep;29(8):1465-70. Epub 2008 Jun 12. 
  54. Estimating Time to Event From Longitudinal Categorical Data: An Analysis of Multiple Sclerosis Progression. Mandel M, Gauthier SA, Guttmann CR, Weiner HL, Betensky RA. J Am Stat Assoc. 2007 Dec;102(480):1254-1266. PMID: 19081806
  55. Predicting short-term disability in multiple sclerosis. Gauthier SA, Mandel M, Guttmann CR, Glanz BI, Khoury SJ, Betensky RA, Weiner HL.  Autoimmun Rev. 2006 Oct;5(8):532-6. Epub 2006 Mar 22. Review. PMID: 17027888
  56. A model for the comprehensive investigation of a chronic autoimmune disease: the mulitple sclerosis CLIMB study. Gauthier SA, Glanz BI, Mandel M, Weiner HL. Autoimmun Rev. 2006 Oct;5(8):532-6. Epub 2006 Mar 22. Review.



© Copyright ® Partners MS Center, 2007, E-Mail Webmaster