Bichuetti DB has received speaking honoraria from Bayer Health Care, Merck Serono and Biogen Idec, serves in advisory board meetings by Merck Serono and Sanofi Genzyme and had travel expenses to scientific meetings paid by Bayer Health Care, Merck Serono and TEVA. Souza NA had travel expenses to scientific meetings paid by Bayer Health Care, Merck Serono and TEVA. Oliveira EML received compensations for participating in meetings sponsored by Bayer Health Care, Biogen Idec, Merck Serono, and Teva Pharmaceuticals and serves in advisory board meetings by Biogen Idec and Novartis. Fragomeni MO has nothing to disclose. This is not an industry-sponsored study.
Neuromyelitis optica (NMO) is and autoimmune disease with distinct, clinical,
radiological and genetic profile when compared to multiple sclerosis
(MS)11 Brum DG, Barreira AA, Santos AC, Kaimen-Maciel DR,
Matiello M, Costa RM et al. HLA-DRB association in
neuromyelitis optica is different from that observed in
multiple sclerosis. Mult Scler. 2010;16(1):21-9.
http://dx.doi.org/10.1177/1352458509350741
https://doi.org/10.1177/1352458509350741...
and, although
much is known about its pathophysiology, the influence of environmental
factors in patients with NMO is not well established as in MS22 Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV.
Environmental factors and their timing in adult-onset
multiple sclerosis. Nat Rev Neurol. 2010;6(3):156-66.
http://dx.doi.org/10.1038/nrneurol.2010.1
https://doi.org/10.1038/nrneurol.2010.1...
. It has been previously
demonstrated that patients with MS present a higher birth prevalence for
months in the spring and summer, as well as there is a higher prevalence of
MS relapses in these same months33 Dobson R, Giovannoni G, Ramagopalan S. The month of
birth effect in multiple sclerosis: systematic review,
meta-analysis and effect of latitude. J Neurol Neurosurg
Psychiatry. 2013;84(4):427-32.
http://dx.doi.org/10.1136/jnnp-2012-303934
https://doi.org/10.1136/jnnp-2012-303934...
,44 Damasceno A, Von Glehn F, Deus-Silva L, Damasceno
BP. Monthly variation of multiple sclerosis activity in the
southern hemisphere: analysis from 996 relapses in Brazil.
Eur J Neurol. 2012;19(4):660-2.
http://dx.doi.org/10.1111/j.1468-1331.2011.03543.x
https://doi.org/10.1111/j.1468-1331.2011...
, but the monthly rate of relapses in
patients with NMO has been described in only one study with distinct result
from MS55 Muto M, Mori M, Sato Y, Uzawa A, Masuda S, Kuwabara
S. Seasonality of multiple sclerosis and neuromyelitis
optica exacerbations in Japan. Mult Scler. 2013;19(3):378-9.
http://dx.doi.org/10.1177/1352458512452332
https://doi.org/10.1177/1352458512452332...
and has not been
confirmed with further studies.
To evaluate if there is any yearly variation in the incidence of relapses in
patients with NMO, we reviewed our historical series published in 200966 Bichuetti D, Oliveira E, Souza N, Rivero R, Gabbai
A. Neuromyelitis optica in Brazil: a study on clinical and
prognostic factors. Mult Scler. 2009;15(5):613-9.
http://dx.doi.org/10.1177/1352458508101935
https://doi.org/10.1177/1352458508101935...
, as it contains
detailed information of all relapses suffered by each patient and added
information on 8 patients from a pediatric NMO cohort that is under review
in our center. All patients received regular preventive therapies
recommended at the time they were seen, which included, corticosteroids,
azathioprine, cyclophosphamide, methotrexate, plasma exchange and IV
immunoglobulin77 Bichuetti DB, Oliveira EML, Oliveira DM, Souza NA,
Gabbai AA. Neuromyelitis optica treatment: analysis of 36
patients. Arch Neurol. 2010;67(9):1131-6.
http://dx.doi.org/10.1001/archneurol.2010.203
https://doi.org/10.1001/archneurol.2010....
.
This work is part of an continuous observational project at the
Universidade Federal de São Paulo, has
received local ethic committee approval and patients have given informed
consent for retrospective and prospective data collection.
We retrieved 282 relapses from the 49 patients (41 with adult onset, 41%
NMO-IgG+; and 8 with pediatric onset, 75% NMO-IgG+) with relapsing NMO, but
analyzed only 278 relapses (98%), as four of them did not have the month of
occurrence available in their medical record. The adult onset information
was retrieved from the historical cohort seen from 1994 to 200766 Bichuetti D, Oliveira E, Souza N, Rivero R, Gabbai
A. Neuromyelitis optica in Brazil: a study on clinical and
prognostic factors. Mult Scler. 2009;15(5):613-9.
http://dx.doi.org/10.1177/1352458508101935
https://doi.org/10.1177/1352458508101935...
and the pediatric onset
patients were seen from 2002 to 2013. The statistical analysis was performed
using Prism 5 (GraphPad Software Incorporated®); relapses
were pooled in two groups representing seasonality already observed in MS
studies44 Damasceno A, Von Glehn F, Deus-Silva L, Damasceno
BP. Monthly variation of multiple sclerosis activity in the
southern hemisphere: analysis from 996 relapses in Brazil.
Eur J Neurol. 2012;19(4):660-2.
http://dx.doi.org/10.1111/j.1468-1331.2011.03543.x
https://doi.org/10.1111/j.1468-1331.2011...
:
spring/summer and fall/winter months. The Kolmogorov-Smirnov test was used
to confirm a normal distribution of the sample and the unpaired t test
performed for comparing both groups.
The seasonality for the 278 relapses analyzed was: 21% in spring (September -
November), 24% in summer (December - February), 27% in fall (March -
May) and 28% in winter (June - August) (Figure). Although there seemed to be a higher incidence of
relapses in the fall/winter months as opposed to spring/summer (55% x 45%),
this difference did not reach statistical significance (p = 0.11, unpaired t
test comparing relapses grouped in spring/summer and fall/winter months),
disclosing no differences along the year. This lack of variation could be
due to low sunlight exposure variation (if indeed there really is some
seasonality influence on NMO relapses), as the city of São Paulo is
located in a subtropical climate zone with low sunlight variation when
compared to higher latitude cities (Latitude -23o 32’
51’’S, Longitude -46o 38’
10’’W, 760 meters above sea level), or simply signifies that
sun exposure does not influence relapses in NMO as it does in MS, as also
observed by Muto et al in Japan55 Muto M, Mori M, Sato Y, Uzawa A, Masuda S, Kuwabara
S. Seasonality of multiple sclerosis and neuromyelitis
optica exacerbations in Japan. Mult Scler. 2013;19(3):378-9.
http://dx.doi.org/10.1177/1352458512452332
https://doi.org/10.1177/1352458512452332...
. A similar analysis with MS patients from
Campinas, a city located less than 100 km from Sao Paulo disclosed higher
relapse incidence in the summer/spring months, suggesting that climate
variation in the southeast of Brazil can influence disease activity as
elsewhere44 Damasceno A, Von Glehn F, Deus-Silva L, Damasceno
BP. Monthly variation of multiple sclerosis activity in the
southern hemisphere: analysis from 996 relapses in Brazil.
Eur J Neurol. 2012;19(4):660-2.
http://dx.doi.org/10.1111/j.1468-1331.2011.03543.x
https://doi.org/10.1111/j.1468-1331.2011...
,
corroborating the idea that climate might not influence NMO relapses. Since
this analysis comes from a historical cohort, information on vitamin D
levels was not available and this should be prospectively evaluated together
with other factors, such as the association to common infection and physical
and psychological stress factors. Most of these patients received regular
immunosuppressive treatment with azathioprine with or without prednisone as
part of our regular treatment protocol, with 76% response77 Bichuetti DB, Oliveira EML, Oliveira DM, Souza NA,
Gabbai AA. Neuromyelitis optica treatment: analysis of 36
patients. Arch Neurol. 2010;67(9):1131-6.
http://dx.doi.org/10.1001/archneurol.2010.203
https://doi.org/10.1001/archneurol.2010....
, and thus treatment
biases is expected to not have influenced these results.
In summary, we have evaluated 278 relapses from 49 patients with NMO and demonstrate no association between relapse incidence and seasonal variation, which is distinct to MS.
Acknowledgements
The authors would like to thank the Guthy Jackson foundation staff for bringing up the study idea.
References
-
1Brum DG, Barreira AA, Santos AC, Kaimen-Maciel DR, Matiello M, Costa RM et al. HLA-DRB association in neuromyelitis optica is different from that observed in multiple sclerosis. Mult Scler. 2010;16(1):21-9. http://dx.doi.org/10.1177/1352458509350741
» https://doi.org/10.1177/1352458509350741 -
2Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV. Environmental factors and their timing in adult-onset multiple sclerosis. Nat Rev Neurol. 2010;6(3):156-66. http://dx.doi.org/10.1038/nrneurol.2010.1
» https://doi.org/10.1038/nrneurol.2010.1 -
3Dobson R, Giovannoni G, Ramagopalan S. The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude. J Neurol Neurosurg Psychiatry. 2013;84(4):427-32. http://dx.doi.org/10.1136/jnnp-2012-303934
» https://doi.org/10.1136/jnnp-2012-303934 -
4Damasceno A, Von Glehn F, Deus-Silva L, Damasceno BP. Monthly variation of multiple sclerosis activity in the southern hemisphere: analysis from 996 relapses in Brazil. Eur J Neurol. 2012;19(4):660-2. http://dx.doi.org/10.1111/j.1468-1331.2011.03543.x
» https://doi.org/10.1111/j.1468-1331.2011.03543.x -
5Muto M, Mori M, Sato Y, Uzawa A, Masuda S, Kuwabara S. Seasonality of multiple sclerosis and neuromyelitis optica exacerbations in Japan. Mult Scler. 2013;19(3):378-9. http://dx.doi.org/10.1177/1352458512452332
» https://doi.org/10.1177/1352458512452332 -
6Bichuetti D, Oliveira E, Souza N, Rivero R, Gabbai A. Neuromyelitis optica in Brazil: a study on clinical and prognostic factors. Mult Scler. 2009;15(5):613-9. http://dx.doi.org/10.1177/1352458508101935
» https://doi.org/10.1177/1352458508101935 -
7Bichuetti DB, Oliveira EML, Oliveira DM, Souza NA, Gabbai AA. Neuromyelitis optica treatment: analysis of 36 patients. Arch Neurol. 2010;67(9):1131-6. http://dx.doi.org/10.1001/archneurol.2010.203
» https://doi.org/10.1001/archneurol.2010.203
Publication Dates
-
Publication in this collection
Feb 2015
History
-
Received
18 Aug 2014 -
Reviewed
09 Oct 2014 -
Accepted
29 Oct 2014