PostScript Treatment and prognosis Methylcobalamin (methycobal) is currently the most commonly used vitamin B12 in clinic. Hydroxocobalamin (OHCbl) is recommended for the treatment of cblC7; the effectiveness of methylcobalamin in treating cblC has not been studied. In the present study, all patients exhibited a rapid positive response to methylcobalamin. Psychiatric symptoms subsided in all five patients, and personality and social communication improved or recovered completely. In summary, patients with late-onset cblC typically have a disease of long duration characterised by a subacute or chronic onset and a persistent, fluctuating and recurrent progress. At the onset, symptoms may be non-neurological and patients usually visit a psychiatrist. In our study, we found that treatment with methylcobalamin was effective in alleviating the symptoms of cblC. Since late-onset cblC has a more favourable outcome if treated on time, it is important to make an early and correct diagnosis.
Received 1 April 2014 Revised 19 June 2014 Accepted 16 July 2014 Published Online First 4 August 2014 J Neurol Neurosurg Psychiatry 2015;86:472–475. doi:10.1136/jnnp-2014-308203
REFERENCES 1
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7 1
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Yan-ru Liu, Yang-fei Ji, Ya-li Wang, Bo-ai Zhang,1 Gui-yuan Fang,1 Jing-tao Wang,1 Gui-fang Sun,1 Hong Lu1 1
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China Correspondence to Professor Hong Lu ([email protected]) and Bo-ai Zhang, Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, Zhengzhou 450052, China (zhangboaidoctor@163. com) Contributors Y-rL and Y-fJ contributed equally to this study. Yan-ru Liu and Yang-fei Ji were involved in writing the manuscript. Ya-li Wang was the patients’ consultant psychiatrist, and the other authors were the patients’ consultant neurologists. All authors were involved in the management of the patients. Bo-ai Zhang and Hong Lu were involved in the interpretation and critical revision of the manuscript. Funding This study was supported by a grant from the Foundation of He’nan Educational Committee (No. 14A360010). Competing interests None. Patient consent Obtained. Ethics approval All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Provenance and peer review Not commissioned; externally peer reviewed.
Martinelli D, Deodato F, Dionisi-Vici C. Cobalamin C defect: natural history, pathophysiology, and treatment. J Inherit Metab Dis 2011;34:127–35. Van Hove JL, Van Damme-Lombaerts R, Grunewald S, et al. Cobalamin disorder Cbl-C presenting with late-onset thrombotic microangiopathy. Am J Med Genet 2002;111:195–201. Fischer S, Huemer M, Baumgartner M, et al. Clinical presentation and outcome in a series of 88 patients with the cblC defect. J Inherit Metab Dis 2014 (in press); doi:10.1007/s10545-014-9687-6. Roze E, Gervais D, Demeret S, et al. Neuropsychiatric disturbances in presumed late-onset cobalamin C disease. Arch Neurol 2003;60:1457–62. Wang X, Sun W, Yang Y, et al. A clinical and gene analysis of late-onset combined methylmalonic aciduria and homocystinuria, cblC type, in China. J Neurol Sci 2012;318:155–9. Kanaumi T, Takashima S, Hirose S, et al. Neuropathology of methylmalonic acidemia in a child. Pediatr Neurol 2006;34:156–9. Froese DS, Zhang J, Healy S, et al. Mechanism of vitamin B12-responsiveness in cblC methylmalonic aciduria with homocystinuria. Mol Genet Metab 2009;98:338–43.
Transient gadolinium leakage in natalizumab-treated multiple sclerosis INTRODUCTION Natalizumab (NTZ; Biogen Idec, Cambridge, Massachusetts, USA) is a recombinant humanised immunoglobulin G4 monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS).1 It selectively inhibits the adhesion α4-β1 receptor on the surface of lymphocytes, monocytes, basophils and eosinophils preventing the interaction of immune cells with the integrin vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells and with structures of the extracellular matrix and hindering cells from leaving the vascular compartment of the brain.2 This mainly hinders circulating cells from leaving the vascular compartment but may also have other consequences on signalling and apoptosis.3 We report the case of a patient with NTZ-treated RRMS who developed a new type of atypical lesion on MRI, consisting of a transient and ill-defined gadolinium enhancement without a typically associated T2 or fluid-attenuated inversion recovery (FLAIR) lesion.
Patient To cite Liu Y-ru, Ji Y-fei, Wang Y-li, et al. J Neurol Neurosurg Psychiatry 2015;86:472–475. J Neurol Neurosurg Psychiatry April 2015 Vol 86 No 4
A patient was diagnosed with RRMS in 2004 with, on average, one relapse per
18 months. Treatment was switched from interferon-β1a (IFNβ-1a) 44 mg three times weekly to NTZ. Follow-up imaging was performed 1 year after treatment modification and demonstrated the appearance of two atypical contrast-enhancing lesions. The first lesion appeared in the right temporal white matter adjacent to the ventricular system with a radial orientation following the perivascular spaces and yet unusually ill-defined contrast enhancement and no associated mass effect or signal alterations on T2/ FLAIR or diffusion imaging (figure 1A). The second lesion with identical characteristics appeared in the left superior temporal white matter (figure 1B). On follow-up imaging after 2 months, both lesions almost completely disappeared, and later follow-up imaging demonstrated a complete disappearance of these lesions. The patient was not symptomatic with a stable Expanded Disability Status Scale of 4.
DISCUSSION We describe a novel type of transient and multifocal gadolinium leakage in a patient with multiple sclerosis (MS) under NTZ treatment. These lesions showed transient and ill-defined contrast enhancement, indicating a transient dysfunction of the blood– brain barrier (BBB). However, there was no evidence of the usually associated inflammatory reaction visible as a hyperintense signal alteration on T2/FLAIR and sometimes diffusion imaging, mass effect or oedema. The possibility of mimicking lesions such as venous anomalies was excluded on previous and follow-up imaging. In addition, this type of lesion could be easily differentiated from possible progressive multifocal leucoencephalopathy pathology because of the completely different imaging features and the spontaneous regression.4 Moreover, the radiological differential diagnosis of a telangiectasia was excluded by the appearance and disappearance of the ill-defined contrast enhancement. NTZ notably prevents the interaction of very late antigen (VLA)-4 with VCAM-1 on endothelial cells and thereby prevents in particular the extravasation of activated leucocytes across the BBB into the central nervous system.3 The absent inflammatory changes on T2/FLAIR imaging despite transient contrast enhancement might consequently be an in vivo visualisation of hindered extravasation of activated leucocytes related to NTZ, despite the demonstration of a transient BBB dysfunction and consequently diffuse and transient contrast enhancement. Other inflammatory mediators inhibited by NTZ, including vascular endothelial growth factor,5 could also play a role in this observation. 475
PostScript
Figure 1 A patient with relapsing-remitting multiple sclerosis presenting with a new contrast enhancement in the right temporal periventricular white matter (A) as well as a second contrast enhancement in the left superior temporal white matter with diffuse contrast enhancement following the perivascular spaces (B), yet without mass effect or a corresponding lesion on T2 or FLAIR. Imaging with the appearance of the contrast enhancement and follow-up imaging at 2 months illustrating almost complete regression of the contrast enhancement (FLAIR, fluid-attenuated inversion recovery; T1w Gd, gadolinium-enhanced T1-weighted). The number of new gadolinium enhancing lesions under NTZ treatment was 0.1±1.3 at 1 year and 0.1±1.4 at 2 years in the AFFIRM (Natalizumab Safety and Efficacy in Relapsing-Remitting MS) study.6 Other studies investigated NTZ in combination with IFNα-1a (SENTINEL, Safety and Efficacy of Natalizumab in combination with Avonex (IFNβ-1a) in patients with RRMS)7 and in combination with glatiramer acetate (GLANCE, Glatiramer Acetate and Natalizumab Combination Evaluation).8 While all studies showed a reduction in the number of gadolinium enhancing lesions related to NTZ, none of these studies specifically reported whether some new enhancing lesions had no associated T2/FLAIR alterations. Radiologists and clinicians should be aware of the possibility of transient and multifocal gadolinium leakage during the follow-up imaging of patients with MS under treatment with NTZ. These lesions were asymptomatic in the reported case, yet the clinical significance of these lesions remains to be determined in future follow-up studies. Sven Haller,1 Frederik Barkhof,2 Mike P Wattjes,2 Patrice H Lalive3,4 1
Department of Imaging and Medical Informatics, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland 2 Department of Radiology & Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands 3 Department of Clinical Neurosciences, Division of Neurology, Unit of Neuroimmunology and Multiple Sclerosis, Geneva University Hospital and Faculty of Medicine of the University of Geneva, Geneva, Switzerland 4 Department of Genetic and Laboratory Medicine, Division of Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland 476
Correspondence to Dr Sven Haller, Service neurodiagnostique et neuro-interventionnel DISIM, University Hospitals of Geneva, Rue Gabrielle Perret-Gentil 4, 1211 Geneva 14, Switzerland; [email protected] Contributors SH and PHL were involved in the development of study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content, and study supervision. FB contributed in the analysis and interpretation, and critical revision of the manuscript for important intellectual content. MPW performed the analysis and interpretation, and critical revision of the manuscript for important intellectual content. Competing interests SH is the section editor Neuroradiology, editorial board member Journal of Alzheimer’s Disease and American Journal of Neurodegenerative Disease, principal investigator Swiss National Science Foundation SNF project 320030_147126/1 and VELUX Foundation project 608, co-investigator SNF project 33CM30_140334/1. FB is the editorial board member Brain, Eur Radiology, Neuroradiology, Multiple Sclerosis Journal, Radiology and Neurology; and Consultant for Bayer-Schering Pharma, Sanofi-Aventis, Biogen-Idec, TEVA, Merck-Serono, Novartis, Roche, Synthon BV, Jansen Research and Genzyme; has received Grants Dutch MS Society, EU-FP7. Also, FB has received payment for the development of educational presentations including service on speakers’ bureaus Serono Symposia Foundation, MedScape. MPW is the member of editorial board European Radiology; and Consultant for Biogen Idec. PHL is the principal investigator Swiss National Science Foundation SNF project 310030_153164, and has received grant from the Swiss multiple sclerosis society. PHL has received honoraria for speaking from Biogen-Idec, Merck Serono, Novartis, Sanofi-Aventis and Teva; and consulting fees from Biogen-Idec, Geneuro, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Teva; and research grants from Biogen-Idec, Merck Serono, Novartis. Patient consent Obtained. Ethics approval Ethical committee University Hospital Geneva. Provenance and peer review Not commissioned; externally peer reviewed.
To cite Haller S, Barkhof F, Wattjes M P, et al. J Neurol Neurosurg Psychiatry 2015;86:475–476. Received 24 July 2014 Revised 29 August 2014 Accepted 30 August 2014 Published Online First 22 September 2014 J Neurol Neurosurg Psychiatry 2015;86:475–476. doi:10.1136/jnnp-2014-309069
REFERENCES 1
2
3
4
5
6
7
8
Rudick R, Polman C, Clifford D, et al. Natalizumab: bench to bedside and beyond. JAMA Neurol 2013;70:172–82. Kappos L, Bates D, Edan G, et al. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol 2011;10:745–58. McCormack PL. Natalizumab: a review of its use in the management of relapsing-remitting multiple sclerosis. Drugs 2013;73:1463–81. Wattjes MP, Richert ND, Killestein J, et al. The chameleon of neuroinflammation: magnetic resonance imaging characteristics of natalizumab-associated progressive multifocal leukoencephalopathy. Mult Scler 2013;19:1826–40. Podar K, Zimmerhackl A, Fulciniti M, et al. The selective adhesion molecule inhibitor natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications. Br J Haematol 2011;155:438–48. Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354:899–910. Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006;354:911–23. Goodman AD, Rossman H, Bar-Or A, et al. GLANCE: results of a phase 2, randomized, double-blind, placebo-controlled study. Neurology 2009;72: 806–12.
J Neurol Neurosurg Psychiatry April 2015 Vol 86 No 4
Copyright of Journal of Neurology, Neurosurgery & Psychiatry is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Received 1 April 2014 Revised 19 June 2014 Accepted 16 July 2014 Published Online First 4 August 2014 J Neurol Neurosurg Psychiatry 2015;86:472–475. doi:10.1136/jnnp-2014-308203
REFERENCES 1
2
3
4
5
6
7 1
1
2
Yan-ru Liu, Yang-fei Ji, Ya-li Wang, Bo-ai Zhang,1 Gui-yuan Fang,1 Jing-tao Wang,1 Gui-fang Sun,1 Hong Lu1 1
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China Correspondence to Professor Hong Lu ([email protected]) and Bo-ai Zhang, Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, Zhengzhou 450052, China (zhangboaidoctor@163. com) Contributors Y-rL and Y-fJ contributed equally to this study. Yan-ru Liu and Yang-fei Ji were involved in writing the manuscript. Ya-li Wang was the patients’ consultant psychiatrist, and the other authors were the patients’ consultant neurologists. All authors were involved in the management of the patients. Bo-ai Zhang and Hong Lu were involved in the interpretation and critical revision of the manuscript. Funding This study was supported by a grant from the Foundation of He’nan Educational Committee (No. 14A360010). Competing interests None. Patient consent Obtained. Ethics approval All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Provenance and peer review Not commissioned; externally peer reviewed.
Martinelli D, Deodato F, Dionisi-Vici C. Cobalamin C defect: natural history, pathophysiology, and treatment. J Inherit Metab Dis 2011;34:127–35. Van Hove JL, Van Damme-Lombaerts R, Grunewald S, et al. Cobalamin disorder Cbl-C presenting with late-onset thrombotic microangiopathy. Am J Med Genet 2002;111:195–201. Fischer S, Huemer M, Baumgartner M, et al. Clinical presentation and outcome in a series of 88 patients with the cblC defect. J Inherit Metab Dis 2014 (in press); doi:10.1007/s10545-014-9687-6. Roze E, Gervais D, Demeret S, et al. Neuropsychiatric disturbances in presumed late-onset cobalamin C disease. Arch Neurol 2003;60:1457–62. Wang X, Sun W, Yang Y, et al. A clinical and gene analysis of late-onset combined methylmalonic aciduria and homocystinuria, cblC type, in China. J Neurol Sci 2012;318:155–9. Kanaumi T, Takashima S, Hirose S, et al. Neuropathology of methylmalonic acidemia in a child. Pediatr Neurol 2006;34:156–9. Froese DS, Zhang J, Healy S, et al. Mechanism of vitamin B12-responsiveness in cblC methylmalonic aciduria with homocystinuria. Mol Genet Metab 2009;98:338–43.
Transient gadolinium leakage in natalizumab-treated multiple sclerosis INTRODUCTION Natalizumab (NTZ; Biogen Idec, Cambridge, Massachusetts, USA) is a recombinant humanised immunoglobulin G4 monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS).1 It selectively inhibits the adhesion α4-β1 receptor on the surface of lymphocytes, monocytes, basophils and eosinophils preventing the interaction of immune cells with the integrin vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells and with structures of the extracellular matrix and hindering cells from leaving the vascular compartment of the brain.2 This mainly hinders circulating cells from leaving the vascular compartment but may also have other consequences on signalling and apoptosis.3 We report the case of a patient with NTZ-treated RRMS who developed a new type of atypical lesion on MRI, consisting of a transient and ill-defined gadolinium enhancement without a typically associated T2 or fluid-attenuated inversion recovery (FLAIR) lesion.
Patient To cite Liu Y-ru, Ji Y-fei, Wang Y-li, et al. J Neurol Neurosurg Psychiatry 2015;86:472–475. J Neurol Neurosurg Psychiatry April 2015 Vol 86 No 4
A patient was diagnosed with RRMS in 2004 with, on average, one relapse per
18 months. Treatment was switched from interferon-β1a (IFNβ-1a) 44 mg three times weekly to NTZ. Follow-up imaging was performed 1 year after treatment modification and demonstrated the appearance of two atypical contrast-enhancing lesions. The first lesion appeared in the right temporal white matter adjacent to the ventricular system with a radial orientation following the perivascular spaces and yet unusually ill-defined contrast enhancement and no associated mass effect or signal alterations on T2/ FLAIR or diffusion imaging (figure 1A). The second lesion with identical characteristics appeared in the left superior temporal white matter (figure 1B). On follow-up imaging after 2 months, both lesions almost completely disappeared, and later follow-up imaging demonstrated a complete disappearance of these lesions. The patient was not symptomatic with a stable Expanded Disability Status Scale of 4.
DISCUSSION We describe a novel type of transient and multifocal gadolinium leakage in a patient with multiple sclerosis (MS) under NTZ treatment. These lesions showed transient and ill-defined contrast enhancement, indicating a transient dysfunction of the blood– brain barrier (BBB). However, there was no evidence of the usually associated inflammatory reaction visible as a hyperintense signal alteration on T2/FLAIR and sometimes diffusion imaging, mass effect or oedema. The possibility of mimicking lesions such as venous anomalies was excluded on previous and follow-up imaging. In addition, this type of lesion could be easily differentiated from possible progressive multifocal leucoencephalopathy pathology because of the completely different imaging features and the spontaneous regression.4 Moreover, the radiological differential diagnosis of a telangiectasia was excluded by the appearance and disappearance of the ill-defined contrast enhancement. NTZ notably prevents the interaction of very late antigen (VLA)-4 with VCAM-1 on endothelial cells and thereby prevents in particular the extravasation of activated leucocytes across the BBB into the central nervous system.3 The absent inflammatory changes on T2/FLAIR imaging despite transient contrast enhancement might consequently be an in vivo visualisation of hindered extravasation of activated leucocytes related to NTZ, despite the demonstration of a transient BBB dysfunction and consequently diffuse and transient contrast enhancement. Other inflammatory mediators inhibited by NTZ, including vascular endothelial growth factor,5 could also play a role in this observation. 475
PostScript
Figure 1 A patient with relapsing-remitting multiple sclerosis presenting with a new contrast enhancement in the right temporal periventricular white matter (A) as well as a second contrast enhancement in the left superior temporal white matter with diffuse contrast enhancement following the perivascular spaces (B), yet without mass effect or a corresponding lesion on T2 or FLAIR. Imaging with the appearance of the contrast enhancement and follow-up imaging at 2 months illustrating almost complete regression of the contrast enhancement (FLAIR, fluid-attenuated inversion recovery; T1w Gd, gadolinium-enhanced T1-weighted). The number of new gadolinium enhancing lesions under NTZ treatment was 0.1±1.3 at 1 year and 0.1±1.4 at 2 years in the AFFIRM (Natalizumab Safety and Efficacy in Relapsing-Remitting MS) study.6 Other studies investigated NTZ in combination with IFNα-1a (SENTINEL, Safety and Efficacy of Natalizumab in combination with Avonex (IFNβ-1a) in patients with RRMS)7 and in combination with glatiramer acetate (GLANCE, Glatiramer Acetate and Natalizumab Combination Evaluation).8 While all studies showed a reduction in the number of gadolinium enhancing lesions related to NTZ, none of these studies specifically reported whether some new enhancing lesions had no associated T2/FLAIR alterations. Radiologists and clinicians should be aware of the possibility of transient and multifocal gadolinium leakage during the follow-up imaging of patients with MS under treatment with NTZ. These lesions were asymptomatic in the reported case, yet the clinical significance of these lesions remains to be determined in future follow-up studies. Sven Haller,1 Frederik Barkhof,2 Mike P Wattjes,2 Patrice H Lalive3,4 1
Department of Imaging and Medical Informatics, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland 2 Department of Radiology & Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands 3 Department of Clinical Neurosciences, Division of Neurology, Unit of Neuroimmunology and Multiple Sclerosis, Geneva University Hospital and Faculty of Medicine of the University of Geneva, Geneva, Switzerland 4 Department of Genetic and Laboratory Medicine, Division of Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland 476
Correspondence to Dr Sven Haller, Service neurodiagnostique et neuro-interventionnel DISIM, University Hospitals of Geneva, Rue Gabrielle Perret-Gentil 4, 1211 Geneva 14, Switzerland; [email protected] Contributors SH and PHL were involved in the development of study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content, and study supervision. FB contributed in the analysis and interpretation, and critical revision of the manuscript for important intellectual content. MPW performed the analysis and interpretation, and critical revision of the manuscript for important intellectual content. Competing interests SH is the section editor Neuroradiology, editorial board member Journal of Alzheimer’s Disease and American Journal of Neurodegenerative Disease, principal investigator Swiss National Science Foundation SNF project 320030_147126/1 and VELUX Foundation project 608, co-investigator SNF project 33CM30_140334/1. FB is the editorial board member Brain, Eur Radiology, Neuroradiology, Multiple Sclerosis Journal, Radiology and Neurology; and Consultant for Bayer-Schering Pharma, Sanofi-Aventis, Biogen-Idec, TEVA, Merck-Serono, Novartis, Roche, Synthon BV, Jansen Research and Genzyme; has received Grants Dutch MS Society, EU-FP7. Also, FB has received payment for the development of educational presentations including service on speakers’ bureaus Serono Symposia Foundation, MedScape. MPW is the member of editorial board European Radiology; and Consultant for Biogen Idec. PHL is the principal investigator Swiss National Science Foundation SNF project 310030_153164, and has received grant from the Swiss multiple sclerosis society. PHL has received honoraria for speaking from Biogen-Idec, Merck Serono, Novartis, Sanofi-Aventis and Teva; and consulting fees from Biogen-Idec, Geneuro, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Teva; and research grants from Biogen-Idec, Merck Serono, Novartis. Patient consent Obtained. Ethics approval Ethical committee University Hospital Geneva. Provenance and peer review Not commissioned; externally peer reviewed.
To cite Haller S, Barkhof F, Wattjes M P, et al. J Neurol Neurosurg Psychiatry 2015;86:475–476. Received 24 July 2014 Revised 29 August 2014 Accepted 30 August 2014 Published Online First 22 September 2014 J Neurol Neurosurg Psychiatry 2015;86:475–476. doi:10.1136/jnnp-2014-309069
REFERENCES 1
2
3
4
5
6
7
8
Rudick R, Polman C, Clifford D, et al. Natalizumab: bench to bedside and beyond. JAMA Neurol 2013;70:172–82. Kappos L, Bates D, Edan G, et al. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol 2011;10:745–58. McCormack PL. Natalizumab: a review of its use in the management of relapsing-remitting multiple sclerosis. Drugs 2013;73:1463–81. Wattjes MP, Richert ND, Killestein J, et al. The chameleon of neuroinflammation: magnetic resonance imaging characteristics of natalizumab-associated progressive multifocal leukoencephalopathy. Mult Scler 2013;19:1826–40. Podar K, Zimmerhackl A, Fulciniti M, et al. The selective adhesion molecule inhibitor natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications. Br J Haematol 2011;155:438–48. Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354:899–910. Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006;354:911–23. Goodman AD, Rossman H, Bar-Or A, et al. GLANCE: results of a phase 2, randomized, double-blind, placebo-controlled study. Neurology 2009;72: 806–12.
J Neurol Neurosurg Psychiatry April 2015 Vol 86 No 4
Copyright of Journal of Neurology, Neurosurgery & Psychiatry is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
