562989
research-article2015
MSJ0010.1177/1352458514562989Multiple Sclerosis JournalLanzillo et al.
MULTIPLE SCLEROSIS MSJ JOURNAL
Letter Vitamin K cream reduces reactions at the injection site in patients with relapsing– remitting multiple sclerosis treated with subcutaneous interferon beta – VIKING study
Dear Editor, Multiple sclerosis therapy with injectable drugs is still dogged by possible local side effects (injection site pain, burning, erythema and necrosis), with the danger of poor adherence and consequently low efficacy. Any approach that reduces local reactions serves to increase patient compliance to treatments.1,2 Topical vitamin K seems to be useful to prevent, or at least to reduce, the development of burning sensations. It is thought to act on the production of coagulation factors taking part in a reaction involved in calcium binding and in the interaction between coagulation factors and phospholipid layers.3 Considering this, we designed a 16-week prospective, double cross-over interventional study with vitamin K cream in relapsing–remitting multiple sclerosis patients already treated, or starting therapy, with subcutaneous interferon IFNβ1a (VIKING study) and presenting with burning and redness at the injection site. At weeks 4, 8, 12 and 16, all patients completed VAS (Visual Analogic Scale) for burning and for pain, while the nurse measured, blinded, the maximum width of erythema at the site of the most recent injection. At week 8 cross-over took place: group A discontinued vitamin K cream, and group B received it. We enrolled 123 subjects: 66 patients began with vitamin K (group A) and 57 without (group B). The two groups were demographically and clinically comparable. At baseline the two groups showed comparable burning sensation (41.6 ± 28.2 vs. 42.6 ± 25.9, p = 0.852) and pain (49.0 ± 27.9 vs. 48.3 ± 26.6, p = 0.886) VAS scores. Group A had larger erythematic lesions than group B (30.1 mm ± 12.8 vs. 23.9 mm ± 11.8, p = 0.001). On treatment, patients showed a mean reduction of 3.5 points (CI 95% −3.2; −0.7) (p = 0.014) for burning sensation and 4.3 points (CI 95% −70; −1.5) (p = 0.002) for pain, when compared to those without treatment. Regarding erythema, after the first four
weeks of treatment there was an evident reduction in group A, while it remained constant in group B (p = 0.002). After cross-over, a clear turnaround was evident and group B showed a reduction of erythema while group A remained constant (p = 0.003). Finally, by evaluating our entire population, we found that in the period of treatment there was an average reduction of 3.2 mm (CI 95% = −5.6– −0.8) than without treatment (p = 0.01).
Multiple Sclerosis Journal 2015, Vol. 21(9) 1215–1218 DOI: 10.1177/ 1352458514562989 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
IFN treatment compliance remains a challenging issue of multiple sclerosis. Local pain and erythema are some of the major complaints of IFN-treated patients, frequently affecting adherence and quality of life. We believe that our results show a beneficial effect of local vitamin K application on IFN injection sites, with an absence of side effects. In conclusion, the present study broadens possible interventions to increase tolerability to IFN with vitamin K cream. Conflict of interest The authors declare that there is no conflict of interest. Funding This research received no specific grant from any funding agency in the public, commercial, or not-forprofit sectors.
References 1. Multiple Sclerosis: Symptoms and side effects management. Int J MS Care 2006; 8 (Supplement 1). 2. Bayas A and Rieckmann P. Managing the adverse effects of interferon-beta therapy in multiple sclerosis. Drug Saf 2000; 22: 149–159. 3. Lou WW, et al. Effects of topical vitamin K and retinol on laser-induced purpura on nonlesional skin. Dermatol Surg 1999; 25: 942–944.
Roberta Lanzillo1, Marcello Moccia1, Antonio Carotenuto1, Veria Vacchiano1, Barbara Satelliti1, Valentina Panetta2 and Vincenzo Brescia Morra1 1Multiple
Sclerosis Centre, Federico II University, Italy 2L’altrastatistica srl, Rome, Italy
http://msj.sagepub.com 1215
Downloaded from msj.sagepub.com at Stockholm University Library on August 28, 2015
Multiple Sclerosis Journal 21(9)
Visit SAGE journals online http://msj.sagepub.com
SAGE journals Multiple Sclerosis Journal 2015, Vol. 21(9) 1216
Correspondence to: Roberta Lanzillo Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and
Odontostomatology, Federico II University of Naples, Via Pansini 5, Napoli, 80131, Italy. [email protected] [email protected]
Solitary sclerosis: Experience from three French tertiary care centres
patient received immunosuppressive treatment. Data collection and follow up of these patients is ongoing.
DOI: 10.1177/ 1352458515570405 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Dear Editor, We read with interest the article from Lattanzi et al.1 reporting eight cases of patients with a solitary demyelinating lesion in the cervico-medullary junction. In France, one case of solitary sclerosis was reported in 20132 and this prompted us to collect data about patients followed in French tertiary care multiple sclerosis (MS) centres who presented with the same phenotype. To date, we have collected five cases (three women and two men) followed in three University Centres (Montpellier, Nice and Paris). Mean age at onset was 45.3 years (35–63). The clinical presentation was progressive hemiparesis in four cases and progressive monoparesis in one case. Mean Expanded Disability Status Scale (EDSS) score at onset was 3.2 (2.5–4). The solitary lesion was located in the cervico-medullary junction in three cases and in the upper cervical cord in two cases. One patient had brain Magnetic Resonance Imaging (MRI) spectroscopy of the normal-appearing white matter which revealed an increase of choline and myoinositol compatible with a demyelinating process. In all cases, the paraclinical investigations exclu-ded all potential differential diagnoses. All patients had extensive metabolic, infectious and immunological screening which was unremarkable. Neuro-myelitis optica (NMO) antibodies were negative for all patients. Visual Evoked Potentials (VEP) and Electromyography (EMG) were normal for all patients, as well as thoracic-abdominal pelvis computed tomography scan. In our cohort, all of the patients but one had a positive CSF analysis with detection of oligoclonal bands and this is an important distinction from the cohort reported by Lattanzi et al. and is a major point regarding the documentation of suspected demyelinating disease. Our finding is consistent with previously reported cases in the literature.3
Visit SAGE journals online http://msj.sagepub.com
SAGE journals
Mean follow-up duration in our cohort is 51 months (20–120). Mean EDSS score at last evaluation is 3.8 (3–6.5). We observed a slowly progressive accumulation of disability with no documented relapse. Three patients were treated with corticosteroids with a positive effect in one patient. Two patients responded to fampridine. No
Our preliminary results confirm Lattanzi’s report describing solitary sclerosis as a focal form of MS. However, we suggest that the presence of oligoclonal bands in the CSF study is important to support this diagnosis, and to exclude differential diagnosis such as slowly evolving tumours. Acknowledgements Club Francophone de la Sclérose en Plaques author group: David Laplaud, Faycal Derouiche, Loic Chambaud, Clotilde Boulay, Jean C Ouallet, Lucien Rumbach, Audrey Kopf, Marie Fleury, Irina Malikova, Christian Zaenker, Gilles Edan, Thibault Moreau, Frederic Blanc, Nicolas Collongues, Pascal B Saverne, Pierre Louiset, Sophie Pittion, Pierre Clavelou, Frederic Taithe, Patrick Vermersch, Alain Creange, Olivier Gout, Anne M Guennoc, Marc Coustans, Gregory Taurin, Francois Lallement, Francois Rouhart, William Camu, Eric Thouvenot, Pierre Labauge, Pierrette Seeldrayers. References 1.
Lattanzi S, Logullo F, Di Bella P, et al. Multiple sclerosis, solitary sclerosis or something else? Mult Scler 2014; 20(14): 1819–1824.
2.
Ayrignac X, Carra-Dalliere C, Homeyer P, et al. Solitary sclerosis: Progressive myelopathy from solitary demyelinating lesion. A new entity? Acta Neurol Belg 2013; 113: 533–534.
3.
Schmalstieg WF, Keegan BM and Weinshenker BG. Solitary sclerosis: Progressive myelopathy from solitary demyelinating lesion. Neurology 2012; 78: 540–544.
5
Mikael Cohen, Christine Lebrun Department of Neurology, Hopital Pasteur, France Xavier Ayrignac, Pierre Labauge Hopital Gui de Chauliac, CHU Montpellier, France Rana Assouad Hopital Pitié Salpétrière, Department of Neurology, Paris, France Correspondence to: Mikael Cohen Department of Neurology, Hopital Pasteur, Neurologie, 30 Voie Romaine, 06000 Nice, France. [email protected]
1216 http://msj.sagepub.com
Downloaded from msj.sagepub.com at Stockholm University Library on August 28, 2015
research-article2015
MSJ0010.1177/1352458514562989Multiple Sclerosis JournalLanzillo et al.
MULTIPLE SCLEROSIS MSJ JOURNAL
Letter Vitamin K cream reduces reactions at the injection site in patients with relapsing– remitting multiple sclerosis treated with subcutaneous interferon beta – VIKING study
Dear Editor, Multiple sclerosis therapy with injectable drugs is still dogged by possible local side effects (injection site pain, burning, erythema and necrosis), with the danger of poor adherence and consequently low efficacy. Any approach that reduces local reactions serves to increase patient compliance to treatments.1,2 Topical vitamin K seems to be useful to prevent, or at least to reduce, the development of burning sensations. It is thought to act on the production of coagulation factors taking part in a reaction involved in calcium binding and in the interaction between coagulation factors and phospholipid layers.3 Considering this, we designed a 16-week prospective, double cross-over interventional study with vitamin K cream in relapsing–remitting multiple sclerosis patients already treated, or starting therapy, with subcutaneous interferon IFNβ1a (VIKING study) and presenting with burning and redness at the injection site. At weeks 4, 8, 12 and 16, all patients completed VAS (Visual Analogic Scale) for burning and for pain, while the nurse measured, blinded, the maximum width of erythema at the site of the most recent injection. At week 8 cross-over took place: group A discontinued vitamin K cream, and group B received it. We enrolled 123 subjects: 66 patients began with vitamin K (group A) and 57 without (group B). The two groups were demographically and clinically comparable. At baseline the two groups showed comparable burning sensation (41.6 ± 28.2 vs. 42.6 ± 25.9, p = 0.852) and pain (49.0 ± 27.9 vs. 48.3 ± 26.6, p = 0.886) VAS scores. Group A had larger erythematic lesions than group B (30.1 mm ± 12.8 vs. 23.9 mm ± 11.8, p = 0.001). On treatment, patients showed a mean reduction of 3.5 points (CI 95% −3.2; −0.7) (p = 0.014) for burning sensation and 4.3 points (CI 95% −70; −1.5) (p = 0.002) for pain, when compared to those without treatment. Regarding erythema, after the first four
weeks of treatment there was an evident reduction in group A, while it remained constant in group B (p = 0.002). After cross-over, a clear turnaround was evident and group B showed a reduction of erythema while group A remained constant (p = 0.003). Finally, by evaluating our entire population, we found that in the period of treatment there was an average reduction of 3.2 mm (CI 95% = −5.6– −0.8) than without treatment (p = 0.01).
Multiple Sclerosis Journal 2015, Vol. 21(9) 1215–1218 DOI: 10.1177/ 1352458514562989 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
IFN treatment compliance remains a challenging issue of multiple sclerosis. Local pain and erythema are some of the major complaints of IFN-treated patients, frequently affecting adherence and quality of life. We believe that our results show a beneficial effect of local vitamin K application on IFN injection sites, with an absence of side effects. In conclusion, the present study broadens possible interventions to increase tolerability to IFN with vitamin K cream. Conflict of interest The authors declare that there is no conflict of interest. Funding This research received no specific grant from any funding agency in the public, commercial, or not-forprofit sectors.
References 1. Multiple Sclerosis: Symptoms and side effects management. Int J MS Care 2006; 8 (Supplement 1). 2. Bayas A and Rieckmann P. Managing the adverse effects of interferon-beta therapy in multiple sclerosis. Drug Saf 2000; 22: 149–159. 3. Lou WW, et al. Effects of topical vitamin K and retinol on laser-induced purpura on nonlesional skin. Dermatol Surg 1999; 25: 942–944.
Roberta Lanzillo1, Marcello Moccia1, Antonio Carotenuto1, Veria Vacchiano1, Barbara Satelliti1, Valentina Panetta2 and Vincenzo Brescia Morra1 1Multiple
Sclerosis Centre, Federico II University, Italy 2L’altrastatistica srl, Rome, Italy
http://msj.sagepub.com 1215
Downloaded from msj.sagepub.com at Stockholm University Library on August 28, 2015
Multiple Sclerosis Journal 21(9)
Visit SAGE journals online http://msj.sagepub.com
SAGE journals Multiple Sclerosis Journal 2015, Vol. 21(9) 1216
Correspondence to: Roberta Lanzillo Multiple Sclerosis Centre, Department of Neuroscience, Reproductive Science and
Odontostomatology, Federico II University of Naples, Via Pansini 5, Napoli, 80131, Italy. [email protected] [email protected]
Solitary sclerosis: Experience from three French tertiary care centres
patient received immunosuppressive treatment. Data collection and follow up of these patients is ongoing.
DOI: 10.1177/ 1352458515570405 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Dear Editor, We read with interest the article from Lattanzi et al.1 reporting eight cases of patients with a solitary demyelinating lesion in the cervico-medullary junction. In France, one case of solitary sclerosis was reported in 20132 and this prompted us to collect data about patients followed in French tertiary care multiple sclerosis (MS) centres who presented with the same phenotype. To date, we have collected five cases (three women and two men) followed in three University Centres (Montpellier, Nice and Paris). Mean age at onset was 45.3 years (35–63). The clinical presentation was progressive hemiparesis in four cases and progressive monoparesis in one case. Mean Expanded Disability Status Scale (EDSS) score at onset was 3.2 (2.5–4). The solitary lesion was located in the cervico-medullary junction in three cases and in the upper cervical cord in two cases. One patient had brain Magnetic Resonance Imaging (MRI) spectroscopy of the normal-appearing white matter which revealed an increase of choline and myoinositol compatible with a demyelinating process. In all cases, the paraclinical investigations exclu-ded all potential differential diagnoses. All patients had extensive metabolic, infectious and immunological screening which was unremarkable. Neuro-myelitis optica (NMO) antibodies were negative for all patients. Visual Evoked Potentials (VEP) and Electromyography (EMG) were normal for all patients, as well as thoracic-abdominal pelvis computed tomography scan. In our cohort, all of the patients but one had a positive CSF analysis with detection of oligoclonal bands and this is an important distinction from the cohort reported by Lattanzi et al. and is a major point regarding the documentation of suspected demyelinating disease. Our finding is consistent with previously reported cases in the literature.3
Visit SAGE journals online http://msj.sagepub.com
SAGE journals
Mean follow-up duration in our cohort is 51 months (20–120). Mean EDSS score at last evaluation is 3.8 (3–6.5). We observed a slowly progressive accumulation of disability with no documented relapse. Three patients were treated with corticosteroids with a positive effect in one patient. Two patients responded to fampridine. No
Our preliminary results confirm Lattanzi’s report describing solitary sclerosis as a focal form of MS. However, we suggest that the presence of oligoclonal bands in the CSF study is important to support this diagnosis, and to exclude differential diagnosis such as slowly evolving tumours. Acknowledgements Club Francophone de la Sclérose en Plaques author group: David Laplaud, Faycal Derouiche, Loic Chambaud, Clotilde Boulay, Jean C Ouallet, Lucien Rumbach, Audrey Kopf, Marie Fleury, Irina Malikova, Christian Zaenker, Gilles Edan, Thibault Moreau, Frederic Blanc, Nicolas Collongues, Pascal B Saverne, Pierre Louiset, Sophie Pittion, Pierre Clavelou, Frederic Taithe, Patrick Vermersch, Alain Creange, Olivier Gout, Anne M Guennoc, Marc Coustans, Gregory Taurin, Francois Lallement, Francois Rouhart, William Camu, Eric Thouvenot, Pierre Labauge, Pierrette Seeldrayers. References 1.
Lattanzi S, Logullo F, Di Bella P, et al. Multiple sclerosis, solitary sclerosis or something else? Mult Scler 2014; 20(14): 1819–1824.
2.
Ayrignac X, Carra-Dalliere C, Homeyer P, et al. Solitary sclerosis: Progressive myelopathy from solitary demyelinating lesion. A new entity? Acta Neurol Belg 2013; 113: 533–534.
3.
Schmalstieg WF, Keegan BM and Weinshenker BG. Solitary sclerosis: Progressive myelopathy from solitary demyelinating lesion. Neurology 2012; 78: 540–544.
5
Mikael Cohen, Christine Lebrun Department of Neurology, Hopital Pasteur, France Xavier Ayrignac, Pierre Labauge Hopital Gui de Chauliac, CHU Montpellier, France Rana Assouad Hopital Pitié Salpétrière, Department of Neurology, Paris, France Correspondence to: Mikael Cohen Department of Neurology, Hopital Pasteur, Neurologie, 30 Voie Romaine, 06000 Nice, France. [email protected]
1216 http://msj.sagepub.com
Downloaded from msj.sagepub.com at Stockholm University Library on August 28, 2015
