ABSTRACT

Late onset multiple sclerosis (LOMS) is when the first symptom starts after 50 years of age, representing 4.5% of multiple sclerosis (MS) patients. This study describes the clinical characteristics of patients with LOMS followed at a specialized MS center in São Paulo. Data was obtained from medical records of 742 patients with MS. The LOMS frequency was 4.18%, median age at onset was 54 years and the predominant disease course was primary progressive (64.3%). The patients reached the disability landmarks of EDSS grades 3.0, 6.0 and 7.0 in the following proportion and time: EDSS 3.0: 77.42% of patients in 3.7 years; EDSS 6.0: 58.06% in 5.1 years and EDSS 7.0: 32.26% in 5.7 years. The comparative analysis with a matched control group of patients with early onset MS showed that late onset, associated with a progressive course, were predictors of reaching EDSS 3.0 and 6.0 in a shorter time.

aging; epidemiology; multiple sclerosis; disease progression

RESUMO

Esclerose múltipla de inicio tardio (EMIT) caracteriza-se pelo início de sintomas aos 50 ou mais anos de idade, representando 4,5% dos pacientes com esclerose múltipla (EM). Este estudo descreve as características clínicas de pacientes com EMIT acompanhados num centro de EM em São Paulo. Dados foram obtidos através de análise de prontuário de 742 pacientes com EM. A frequência de EMIT foi de 4,18%, a mediana da idade de início foi de 54 anos e a forma clínica predominante a primariamente progressiva (64,3%). Os pacientes atingiram os marcos de incapacidade EDSS 3, 6 e 7 nas respectivas proporções e tempo: EDSS 3.0, 77,42% de pacientes em 3.7 anos; EDSS 6.0, 58,06% em 5.1 anos e EDSS 7.0, 32,26% em 5.7 anos. A análise comparativa a um grupo controle de jovens com EM, mostrou que o início tardio associado a forma primariamente progressiva foram preditores para atingir EDSS 3 e 6 num período menor.

envelhecimento; epidemiologia; esclerose múltipla; progressão da doença

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system that predominantly affects young adults between 20 and 40 years of age. Therefore, an uncommon form of MS is one in which symptoms start at 50 plus years of age, called late onset multiple sclerosis (LOMS)¹1. Noseworthy JH, Paty D, Wonnacott T, Feasby T, Ebers G. Multiple sclerosis after age 50. Neurology, 1983;33912):1537-44. https://doi.org/10.1212/WNL.33.12.1537
https://doi.org/10.1212/WNL.33.12.1537... ,²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,³3. White AD, Swingler RJ, Compston DAS. Features of multiple sclerosis in older patients in South Wales. Gerontology. 1990;36(3):159-64. https://doi.org/10.1159/000213192
https://doi.org/10.1159/000213192... ,⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,⁵5. Delalande S, De Seze J, Ferriby D, Stojkovic T, Vermersch P. [Late onset multiple sclerosis]. Rev Neurol (Paris). 2002;158(11):1082-7. French.,⁶6. Seze J, Delalande S, Michelin E, Gauvrit JY, Mackowiak MA, Ferriby D et al. Brain MRI in late-onset multiple sclerosis. Eur J Neurol. 2005;12(4):241-4. https://doi.org/10.1111/j.1468-1331.2004.01103.x
https://doi.org/10.1111/j.1468-1331.2004... ,⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... ,⁸8. Bove R, Musallam A, Healy BC, Houtchens M, Glanz BI, Khoury S et al. No sex-specific difference in disease trajectory in multiple sclerosis patients before and after age 50. BCM Neurology. 2013;13(73):73. https://doi.org/10.1186/1471-2377-13-73
https://doi.org/10.1186/1471-2377-13-73... . It accounts for 1.4% to 9.9% of the MS population in different countries²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,⁵5. Delalande S, De Seze J, Ferriby D, Stojkovic T, Vermersch P. [Late onset multiple sclerosis]. Rev Neurol (Paris). 2002;158(11):1082-7. French.,⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
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https://doi.org/10.1093/brain/awg081... ,¹¹11. Etemadifar M, Abtahi SH, Minagar A, Akbari M, Masaeli A, Tabrizi N. Late-onset multiple sclerosis in Isfahan, Iran. Arch Iran Med. 2012;15(10):596-8.,¹²12. Bove RM, Healy B, Augustine A, Musallam A, Gholipour T, Chitnis T. Effect of gender on late-onset multiple sclerosis. Mult Scler. 2012;18(10):1472-9. https://doi.org/10.1177/1352458512438236
https://doi.org/10.1177/1352458512438236... .

On average, LOMS represents roughly 4.5% of the MS population²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,⁵5. Delalande S, De Seze J, Ferriby D, Stojkovic T, Vermersch P. [Late onset multiple sclerosis]. Rev Neurol (Paris). 2002;158(11):1082-7. French.,⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... , it has a female preponderance¹1. Noseworthy JH, Paty D, Wonnacott T, Feasby T, Ebers G. Multiple sclerosis after age 50. Neurology, 1983;33912):1537-44. https://doi.org/10.1212/WNL.33.12.1537
https://doi.org/10.1212/WNL.33.12.1537... ,²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... ,¹²12. Bove RM, Healy B, Augustine A, Musallam A, Gholipour T, Chitnis T. Effect of gender on late-onset multiple sclerosis. Mult Scler. 2012;18(10):1472-9. https://doi.org/10.1177/1352458512438236
https://doi.org/10.1177/1352458512438236... , its initial presentation is monosymptomatic, with a motor or cerebellar symptom, and the most common clinical course is primary progressive⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,¹³13. Martinelli V, Rodegher M, Moiola L, Comi G. Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis. Neurol Sci. 2004;25(Suppl 4):S350-55.3.,¹⁴14. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol, 2008;255(5):697-702. https://doi.org/10.1007/s00415-008-0778-x
https://doi.org/10.1007/s00415-008-0778-... .

The progression to disability in LOMS has previously been attributed to disease duration time¹⁵15. Liguori M, Marrosu MG, Pugliatti M, Giuliani F, De Robertis F, Cocco E et al. Age at onset in multiple sclerosis. Neurol Sci. 2000;21(4 Suppl 2):S825-9. https://doi.org/10.1007/s100720070020
https://doi.org/10.1007/s100720070020... , to clinical form²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... , gender⁸8. Bove R, Musallam A, Healy BC, Houtchens M, Glanz BI, Khoury S et al. No sex-specific difference in disease trajectory in multiple sclerosis patients before and after age 50. BCM Neurology. 2013;13(73):73. https://doi.org/10.1186/1471-2377-13-73
https://doi.org/10.1186/1471-2377-13-73... , and older age at the time of the patient’s first examination¹³13. Martinelli V, Rodegher M, Moiola L, Comi G. Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis. Neurol Sci. 2004;25(Suppl 4):S350-55.3.. The later onset has been associated with a greater possibility of reaching Expanded Disability Status Scale (EDSS) grade 6.0 in a shorter period¹⁶16. Scalfari A, Neuhaus A, Daumer M, Ebers GC, Muraro PA. Age and disability accumulation in multiple sclerosis. Neurology. 2011;77(13):1246-52. https://doi.org/10.1212/WNL.0b013e318230a17d
https://doi.org/10.1212/WNL.0b013e318230... .

Vascular disease of the central nervous system and cervical spondylotic myelopathy are the main differential diagnoses, due to a higher prevalence at this age and possible similar symptoms¹1. Noseworthy JH, Paty D, Wonnacott T, Feasby T, Ebers G. Multiple sclerosis after age 50. Neurology, 1983;33912):1537-44. https://doi.org/10.1212/WNL.33.12.1537
https://doi.org/10.1212/WNL.33.12.1537... ,⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,¹³13. Martinelli V, Rodegher M, Moiola L, Comi G. Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis. Neurol Sci. 2004;25(Suppl 4):S350-55.3.,¹⁷17. Hooge JP, Redekop WK. Multiple sclerosis with very late onset. Neurology. 1992;42(10):1907-10. https://doi.org/10.1212/WNL.42.10.1907
https://doi.org/10.1212/WNL.42.10.1907... ,¹⁸18. Harding K, Griffiths M, Wardle M, Tomassini V, Pickersgill T, Robertson N. Late-onset multiple sclerosis in south-east wales. J Neurol Neurosurg Psychiatry. 2013;84(11). https://doi.org/10.1136/jnnp-2013-306573.26
https://doi.org/10.1136/jnnp-2013-306573... . Because of previous co-morbid conditions and higher odds of T2-hyperintense lesions on magnetic resonance imaging (MRI) of elderly patients⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... ,¹³13. Martinelli V, Rodegher M, Moiola L, Comi G. Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis. Neurol Sci. 2004;25(Suppl 4):S350-55.3.,¹⁹19. Awad A, Stüve O. Multple sclerosis in the elderly patient. Drugs Aging. 2010;27(4):283-94. https://doi.org/10.2165/11532120-000000000-00000
https://doi.org/10.2165/11532120-0000000... , there is a delay in diagnosis that can reach three to five years in almost 40% of LOMS patients⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... ,¹⁴14. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol, 2008;255(5):697-702. https://doi.org/10.1007/s00415-008-0778-x
https://doi.org/10.1007/s00415-008-0778-... ,²⁰20. Harding K, Loveless S, Wardle M, Tomassini V, Pickers T, Robertson N. Epistatic effects on the phenotype of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013;84(11). http://dx.doi.org/10.1136/jnnp-2013-306573.30
http://dx.doi.org/10.1136/jnnp-2013-3065... .

There is scanty literature concerning what influences the presentation and progression to disability in this age group, and few papers compare this population with young MS adults.

The purpose of this study is to describe the demographic, clinical and laboratory characteristics of patients with LOMS followed at the MS center of the Neurology Department of the Federal University of São Paulo.

METHODS

The Neuroimmunology Clinic of the Federal University of São Paulo is a specialized center for the treatment of patients with MS and other demyelinating diseases. It has maintained a database with information on clinical status, laboratory tests, radiological evaluation and treatment of all patients under follow up, since 1994. Data for this retrospective cohort study was obtained from the medical records of 742 patients with MS.

The LOMS patients were defined by the occurrence of the first MS symptoms after age 50, meeting either Poser’s or the McDonald criteria, depending on the current diagnostic criteria at the moment of their first appointment. According to the current diagnostic criteria, neuromyelitis optica patients were excluded from the analysis.

Information gathered from their clinical records included: demographic characteristics; disease onset and duration; follow-up time; onset, first and last visit symptoms and signs; EDSS scores in the first and last visit; disease course; number of relapses, progression index; MRI data, cerebral spinal fluid (CSF) and evoked potential findings.

Additionally, LOMS patients were compared to a young onset MS (YOMS) control group, matched according to sex and clinical form, in a 2:1 proportion. For this analysis, nine LOMS patients with a follow-up of less than 12 months were excluded.

This study was approved by the local institutional ethics committee (IRB) and registered under number 256958.

Statistical analyses

Continuous variables were tested for normality with the Kolmogorov-Smirnov and Shapiro Wilk tests and the values are expressed as median and percentiles 25 and 75. The categorical data are presented as absolute values and percentages and were tested using Pearson’s χ2 test and Fisher’s exact test, if applicable.

Nonparametric data was compared using the Mann-Whitney U test for two independent samples.

Discrimination of variables was calculated by a receiver operator characteristic curve (ROC curve) utilizing the area under the curve and asymptotic significance. Some continuous variables were categorized through the ROC curve. The cutoff points were calculated using the value with the best sensitivity and specificity.

The Kaplan-Meier model with log-rank test was applied at times, to obtain EDSS values.

A cox proportional model was used to determine predictive factors for reaching specific EDSS milestones and the hazards ratios were calculated.

Statistical significance was considered with p ≤ 0.05 and the analyses were performed using SPSS 19.0.

RESULTS

LOMS population

Of the 742 patients with MS, 31 were LOMS patients, representing a percentage of 4.18%. The gender distribution was 2.1 females to 1 male patient, of whom 19 were Caucasian, three were Afro-descendant, two were of mixed ethnicity and there was no information on seven patients. The median age of initial symptoms was 54, 22 patients (71%) were between 50 and 55 years old, and only two patients were over 60 years old, which is referred to as very late onset MS.

The initial neurological presentation was motor impairment in 54.8% and cerebellar involvement in 29.0%, sensory impairment and brainstem symptoms in 19.4% each, visual in 16.1% and vesical dysfunction in 3.2% A multi-topographic involvement was described in 38.7%, and the most frequent combination was motor and cerebellar.

Three patients did not have enough information to define their clinical course, therefore they were excluded from the LOMS population analysis. Of the remaining 28 patients, 64.3% were primary progressive and 35.7% relapsing-remitting. In our study, there were no secondary progressive cases of LOMS.

The median follow-up period was 2.2 years and 3.1 years for primary progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS), respectively, while median disease time was of 9.2 for PPMS and 4.9 years for RRMS. Considering the RRMS patients, 70% had their second relapse less than a year after the first symptom. The median EDSS scores on the first and last evaluation for the RRMS group was 2.0 on both visits, and for the PPMS group was 2.0 at the initial visit and 7.0 on the last visit. Patients with LOMS reached the disability landmarks of EDSS 3.0, 6.0 and 7.0 in the following proportion and time: EDSS 3.0: 77.42% of patients in 3.7 years; EDSS 6.0: 58.06% in 5.1 years, and EDSS 7.0: 32.26% in 5.7 years (Tables 1 and 2). Of the 31 patients, three deaths occurred during the follow-up: one from gastrointestinal bleeding, one myocardial infarction and one unknown cause.

Descriptions of brain MRI scans were compatible with MS in all patients. Sixteen of them had descriptions of spinal cord MRIs, of which nine (56.3%) had one or more lesions. Only 11 patients had their CSF analyzed, of which 54.5% had oligoclonal bands. Only six had visual evoked potential studies, with altered potentials in five (83.3%).

LOMS versus YOMS

Twenty-two LOMS patients were compared to 44 patients with YOMS, whose initial symptom had started between 20 and 40 years of age.

We found no significant statistical difference between initial symptoms or functional system reported by either group on initial or final evaluation. The predominant initial symptom in RRMS patients was brainstem in the LOMS (44%) and sensitive in the YOMS (39%), while patients with the progressive form in both groups had predominantly motor symptoms.

The progression index (calculated by dividing the EDSS score by the disease duration time) was worse in the LOMS patients, more clearly seen in the PPMS group, 0.55 versus 0.74, for younger and older onset respectively. The annual relapsing rate was higher in the younger group (median of 0.7 versus 0.51). Neither of these differences had statistical significance (Tables 3 and 4).

The median time to reach EDSS 3.0, 6.0 and 7.0 for the older RRMS patients was 3.8, 5.4 and 5.4 years, respectively, and in the younger group was 4.6, 5.6 and 5.6 years. In the PPMS group, the older patients reached EDSS grades 3.0, 6.0 and 7.0 in 3.1, 5.5 and 7.3 years, while the young patients reached these landmarks in 3.0, 6.8 and 9.0 years, respectively (Figure). The three EDSS milestones were reached in less time in the LOMS group compared to the YOMS, but there was no statistical significance (Tables 3 and 4).

The cox regression models were applied to find the predictive factors for reaching the EDSS grades 3.0 and 6.0 in a shorter time. We observed that patients who were 50 years and older and the ones with a primary progressive form, reached EDSS grades 3.0 and 6.0 significantly earlier. These variables were co-dependent (Table 5).

All patients had brain MRI scans that fulfilled dissemination in time and space, compatible with an MS diagnosis at first visit. Spinal MRI was performed in four patients with late onset RRMS, but did not show any spinal cord abnormalities, in contrast to the young group, in which 90% of the scans showed MS lesions. Conversely, within the PPMS patients, spinal inflammatory lesions were found in both age groups at the same proportion. We observed that the positivity of oligoclonal bands in spinal fluid was much higher in the younger group (Table 6).

DISCUSSION

The population of Brazilian LOMS patients described in this retrospective cohort seems to be very similar to previously-published LOMS descriptions. We observed the same frequency of 4.18%, among patients with MS²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,³3. White AD, Swingler RJ, Compston DAS. Features of multiple sclerosis in older patients in South Wales. Gerontology. 1990;36(3):159-64. https://doi.org/10.1159/000213192
https://doi.org/10.1159/000213192... ,⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,⁵5. Delalande S, De Seze J, Ferriby D, Stojkovic T, Vermersch P. [Late onset multiple sclerosis]. Rev Neurol (Paris). 2002;158(11):1082-7. French.,⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... ; a female predominance of 2.1:1¹1. Noseworthy JH, Paty D, Wonnacott T, Feasby T, Ebers G. Multiple sclerosis after age 50. Neurology, 1983;33912):1537-44. https://doi.org/10.1212/WNL.33.12.1537
https://doi.org/10.1212/WNL.33.12.1537... ,²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... ,¹²12. Bove RM, Healy B, Augustine A, Musallam A, Gholipour T, Chitnis T. Effect of gender on late-onset multiple sclerosis. Mult Scler. 2012;18(10):1472-9. https://doi.org/10.1177/1352458512438236
https://doi.org/10.1177/1352458512438236... ,¹⁴14. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol, 2008;255(5):697-702. https://doi.org/10.1007/s00415-008-0778-x
https://doi.org/10.1007/s00415-008-0778-... , a Caucasian preponderance¹²12. Bove RM, Healy B, Augustine A, Musallam A, Gholipour T, Chitnis T. Effect of gender on late-onset multiple sclerosis. Mult Scler. 2012;18(10):1472-9. https://doi.org/10.1177/1352458512438236
https://doi.org/10.1177/1352458512438236... ; a similar age of onset²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... ,¹¹11. Etemadifar M, Abtahi SH, Minagar A, Akbari M, Masaeli A, Tabrizi N. Late-onset multiple sclerosis in Isfahan, Iran. Arch Iran Med. 2012;15(10):596-8.,¹⁴14. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol, 2008;255(5):697-702. https://doi.org/10.1007/s00415-008-0778-x
https://doi.org/10.1007/s00415-008-0778-... and a higher percentage of the primary progressive form, that reached up to 83% in some descriptions¹1. Noseworthy JH, Paty D, Wonnacott T, Feasby T, Ebers G. Multiple sclerosis after age 50. Neurology, 1983;33912):1537-44. https://doi.org/10.1212/WNL.33.12.1537
https://doi.org/10.1212/WNL.33.12.1537... ,²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... ,⁹9. Leibowitz U, Alter M, Halpern L. Clinical studies of multiple sclerosis in Israel. III. Clinical course and prognosis related to age at onset. Neurology. 1964;14(10):926-32. https://doi.org/10.1212/WNL.14.10.926
https://doi.org/10.1212/WNL.14.10.926... ,¹¹11. Etemadifar M, Abtahi SH, Minagar A, Akbari M, Masaeli A, Tabrizi N. Late-onset multiple sclerosis in Isfahan, Iran. Arch Iran Med. 2012;15(10):596-8.,¹⁴14. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol, 2008;255(5):697-702. https://doi.org/10.1007/s00415-008-0778-x
https://doi.org/10.1007/s00415-008-0778-... ,¹⁷17. Hooge JP, Redekop WK. Multiple sclerosis with very late onset. Neurology. 1992;42(10):1907-10. https://doi.org/10.1212/WNL.42.10.1907
https://doi.org/10.1212/WNL.42.10.1907... ,²¹21. Lyon-Caen O, Izquierdo G, Marteau R, Lhermitte F, Castaigne P, Hauw JJ. Late onset multiple sclerosis: a clinical study of 16 pathologically proven cases. Acta Neurol Scand. 1985;72(1):56-60. https://doi.org/10.1111/j.1600-0404.1985.tb01547.x
https://doi.org/10.1111/j.1600-0404.1985... .

Interestingly, very late onset MS (defined as the first symptom at 60 years or above), represented 0.27% of our cohort. This figure is lower when compared to other series, which reported a prevalence of 0.45% to 1.33%²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,³3. White AD, Swingler RJ, Compston DAS. Features of multiple sclerosis in older patients in South Wales. Gerontology. 1990;36(3):159-64. https://doi.org/10.1159/000213192
https://doi.org/10.1159/000213192... ,⁵5. Delalande S, De Seze J, Ferriby D, Stojkovic T, Vermersch P. [Late onset multiple sclerosis]. Rev Neurol (Paris). 2002;158(11):1082-7. French.,⁹9. Leibowitz U, Alter M, Halpern L. Clinical studies of multiple sclerosis in Israel. III. Clinical course and prognosis related to age at onset. Neurology. 1964;14(10):926-32. https://doi.org/10.1212/WNL.14.10.926
https://doi.org/10.1212/WNL.14.10.926... ,¹²12. Bove RM, Healy B, Augustine A, Musallam A, Gholipour T, Chitnis T. Effect of gender on late-onset multiple sclerosis. Mult Scler. 2012;18(10):1472-9. https://doi.org/10.1177/1352458512438236
https://doi.org/10.1177/1352458512438236... ,¹⁷17. Hooge JP, Redekop WK. Multiple sclerosis with very late onset. Neurology. 1992;42(10):1907-10. https://doi.org/10.1212/WNL.42.10.1907
https://doi.org/10.1212/WNL.42.10.1907... . A possible explanation for this finding is the fact that Brazilians may die of other causes before a diagnosis of MS can be made, or since MS is not a common disease in Brazil, the correct diagnosis might be delayed or never made. The few papers that report this age range, emphasize that they have the same clinical characteristics of LOMS patients, but with a larger delay in diagnosis¹⁷17. Hooge JP, Redekop WK. Multiple sclerosis with very late onset. Neurology. 1992;42(10):1907-10. https://doi.org/10.1212/WNL.42.10.1907
https://doi.org/10.1212/WNL.42.10.1907... ,²²22. Marra TR. Multiple sclerosis with onset after age 60. J Am Geriatr Soc. 1984;32(1):16-8. https://doi.org/10.1111/j.1532-5415.1984.tb05144.x
https://doi.org/10.1111/j.1532-5415.1984... ,²³23. Azzimondi G, Stracciari A, Rinaldi R, D’Alessandro R, Pazzaglia P. Multiple sclerosis with very late onset: report of six cases and review of the literature. Eur Neurol. 1994;34(6):332-6. https://doi.org/10.1159/000117073
https://doi.org/10.1159/000117073... . In the future with the aging world population and easier access to MRIs, very late onset MS may be more frequently described²⁴24. Takeuchi T, Ogura M, Sato M, Kawai N, Tanihata H, Takasaka I et al. Late-onset tumefactive multiple sclerosis. Radiat Med. 2008;26(9):549-52. https://doi.org/10.1007/s11604-008-0273-4
https://doi.org/10.1007/s11604-008-0273-... .

Concerning disease duration, late onset PPMS had a median duration time twice as long as late onset RRMS. Conversely, when it comes to follow-up time, the opposite occurs – late onset RRMS patients have a slightly longer follow-up history (3.13 versus 2.15 years). This could be explained by the longer time it usually takes to diagnose the progressive form, with a clear delay from initial symptom to first appointment at the MS clinic (4.12 years versus 1.15 years with the RRMS patients), as seen in Tables 4 and 5. The delay in diagnosis of the primary progressive form of LOMS has been observed by other authors, and may be justified by the fact that other diseases such as vascular disease of the central nervous system and cervical spondylotic myelopathy have a higher prevalence at this age and may present with similar symptoms⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... ,¹³13. Martinelli V, Rodegher M, Moiola L, Comi G. Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis. Neurol Sci. 2004;25(Suppl 4):S350-55.3.,¹⁴14. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol, 2008;255(5):697-702. https://doi.org/10.1007/s00415-008-0778-x
https://doi.org/10.1007/s00415-008-0778-... . Our short follow-up time may be due to the delay in patients being referred to a specialized MS center, and because of abandonment of the follow-up.

Similar to previously-described series, we observed a higher frequency of motor and cerebellar symptoms²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,⁹9. Leibowitz U, Alter M, Halpern L. Clinical studies of multiple sclerosis in Israel. III. Clinical course and prognosis related to age at onset. Neurology. 1964;14(10):926-32. https://doi.org/10.1212/WNL.14.10.926
https://doi.org/10.1212/WNL.14.10.926... ,¹¹11. Etemadifar M, Abtahi SH, Minagar A, Akbari M, Masaeli A, Tabrizi N. Late-onset multiple sclerosis in Isfahan, Iran. Arch Iran Med. 2012;15(10):596-8.,¹²12. Bove RM, Healy B, Augustine A, Musallam A, Gholipour T, Chitnis T. Effect of gender on late-onset multiple sclerosis. Mult Scler. 2012;18(10):1472-9. https://doi.org/10.1177/1352458512438236
https://doi.org/10.1177/1352458512438236... ,¹³13. Martinelli V, Rodegher M, Moiola L, Comi G. Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis. Neurol Sci. 2004;25(Suppl 4):S350-55.3.,¹⁴14. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol, 2008;255(5):697-702. https://doi.org/10.1007/s00415-008-0778-x
https://doi.org/10.1007/s00415-008-0778-... ,²⁵25. Cossburn M, Ingram G, Hirst C, Ben-Shlomo Y, Pickersgill TP, Robertson NP. Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis. Mult Scler. 2012;18(1):45-54. https://doi.org/10.1177/1352458511417479
https://doi.org/10.1177/1352458511417479... ,²⁶26. Amador-Patarroyo MJ, Rodriguez-Rodriguez A, Montoya-Ortiz G. How does age at onset influence the outcome of autoimmune diseases? Autoimmune Dis. 2012;2012:251730. https://doi.org/10.1155/2012/251730
https://doi.org/10.1155/2012/251730... and a high percentage of initial multifocal involvement⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... especially compared to young adults with MS¹⁰10. Confavreux C, Vukusic S, Adeleine P. Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain. 2003;126(4):770-82. https://doi.org/10.1093/brain/awg081
https://doi.org/10.1093/brain/awg081... . A possible explanation is an association of the primary progressive form with a multifocal presentation. Such an hypothesis is corroborated by a study performed exclusively with late onset RRMS patients that reported a multifocal presentation in only 11% of patients²⁵25. Cossburn M, Ingram G, Hirst C, Ben-Shlomo Y, Pickersgill TP, Robertson NP. Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis. Mult Scler. 2012;18(1):45-54. https://doi.org/10.1177/1352458511417479
https://doi.org/10.1177/1352458511417479... .

In our cohort, we observed that 70% of the patients with late onset RRMS had the second relapse in less than a year, in spite of presenting with a low annual relapse rate. Different studies reported a similar low annual relapse rate in the late onset RRMS group, compared to the young onset RRMS group, in spite of a shorter interval between the first and second relapse. This low annual relapse rate in older patients could be attributed to a more inflammatory disease in young patients¹1. Noseworthy JH, Paty D, Wonnacott T, Feasby T, Ebers G. Multiple sclerosis after age 50. Neurology, 1983;33912):1537-44. https://doi.org/10.1212/WNL.33.12.1537
https://doi.org/10.1212/WNL.33.12.1537... ,³3. White AD, Swingler RJ, Compston DAS. Features of multiple sclerosis in older patients in South Wales. Gerontology. 1990;36(3):159-64. https://doi.org/10.1159/000213192
https://doi.org/10.1159/000213192... ,¹²12. Bove RM, Healy B, Augustine A, Musallam A, Gholipour T, Chitnis T. Effect of gender on late-onset multiple sclerosis. Mult Scler. 2012;18(10):1472-9. https://doi.org/10.1177/1352458512438236
https://doi.org/10.1177/1352458512438236... ,¹⁸18. Harding K, Griffiths M, Wardle M, Tomassini V, Pickersgill T, Robertson N. Late-onset multiple sclerosis in south-east wales. J Neurol Neurosurg Psychiatry. 2013;84(11). https://doi.org/10.1136/jnnp-2013-306573.26
https://doi.org/10.1136/jnnp-2013-306573... ,²³23. Azzimondi G, Stracciari A, Rinaldi R, D’Alessandro R, Pazzaglia P. Multiple sclerosis with very late onset: report of six cases and review of the literature. Eur Neurol. 1994;34(6):332-6. https://doi.org/10.1159/000117073
https://doi.org/10.1159/000117073... ,²⁷27. Poser S, Raun NE, Poser W. Age at onset, initial symptomatology and the course of multiple sclerosis. Acta Neurol Scand. 1982;66(3):355-62. https://doi.org/10.1111/j.1600-0404.1982.tb06856.x
https://doi.org/10.1111/j.1600-0404.1982... ,²⁸28. Trojano M, Liguori M, Bosco Zimatore G, Bugarini R, Avolio C, Paolicelli D et al. Age-related disability in multiple sclerosis. Ann Neurol. 2002;51(4):475-80. https://doi.org/10.1002/ana.10147
https://doi.org/10.1002/ana.10147... . Recovery after the first relapse is better in younger patients and the chances of full recovery after a relapse decreases by 1% for each year older the patient is at onset⁹9. Leibowitz U, Alter M, Halpern L. Clinical studies of multiple sclerosis in Israel. III. Clinical course and prognosis related to age at onset. Neurology. 1964;14(10):926-32. https://doi.org/10.1212/WNL.14.10.926
https://doi.org/10.1212/WNL.14.10.926... ,²⁵25. Cossburn M, Ingram G, Hirst C, Ben-Shlomo Y, Pickersgill TP, Robertson NP. Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis. Mult Scler. 2012;18(1):45-54. https://doi.org/10.1177/1352458511417479
https://doi.org/10.1177/1352458511417479... . This could explain why late onset RRMS patients acquire sustained severe neurological disability in a short period of time.

Regarding disability, 25.8% of LOMS patient were already at EDSS 6.0 at their first appointment at the MS clinic, and on final examination, the progressive form showed worse outcomes, concurring with previous series (Tables 4 and 5)²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,²⁰20. Harding K, Loveless S, Wardle M, Tomassini V, Pickers T, Robertson N. Epistatic effects on the phenotype of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013;84(11). http://dx.doi.org/10.1136/jnnp-2013-306573.30
http://dx.doi.org/10.1136/jnnp-2013-3065... ,²⁷27. Poser S, Raun NE, Poser W. Age at onset, initial symptomatology and the course of multiple sclerosis. Acta Neurol Scand. 1982;66(3):355-62. https://doi.org/10.1111/j.1600-0404.1982.tb06856.x
https://doi.org/10.1111/j.1600-0404.1982... ,²⁹29. Cottrell DA, Kremenchutzky M, Rice GPA, et al. The natural History of multiple sclerosis: 5. The clinical features and natural history of primary progressive multiple sclerosis. Brain. 1999;122:625-39. https://doi.org/10.1093/brain/122.4.625
https://doi.org/10.1093/brain/122.4.625... . In RRMS, the median time for LOMS patients to reach EDSS 3.0, 6.0 and 7.0 was almost identical to the younger group. On the other hand, for PPMS, the time to reach EDSS 6.0 and 7.0 was longer for the young group compared to LOMS, and the progression index diverged between LOMS and the younger group, 0.74 and 0.55, respectively, as seen in other studies⁴4. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71. https://doi.org/10.1046/j.1532-5415.2001.49038.x
https://doi.org/10.1046/j.1532-5415.2001... ,¹¹11. Etemadifar M, Abtahi SH, Minagar A, Akbari M, Masaeli A, Tabrizi N. Late-onset multiple sclerosis in Isfahan, Iran. Arch Iran Med. 2012;15(10):596-8.,¹⁴14. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol, 2008;255(5):697-702. https://doi.org/10.1007/s00415-008-0778-x
https://doi.org/10.1007/s00415-008-0778-... ,¹⁷17. Hooge JP, Redekop WK. Multiple sclerosis with very late onset. Neurology. 1992;42(10):1907-10. https://doi.org/10.1212/WNL.42.10.1907
https://doi.org/10.1212/WNL.42.10.1907... ,²⁷27. Poser S, Raun NE, Poser W. Age at onset, initial symptomatology and the course of multiple sclerosis. Acta Neurol Scand. 1982;66(3):355-62. https://doi.org/10.1111/j.1600-0404.1982.tb06856.x
https://doi.org/10.1111/j.1600-0404.1982... . These findings had no statistical significance, probably due to our small sample. We were able to significantly demonstrate that the late disease onset, as well as the primary progressive form, are predicting factors for reaching EDSS 3.0 and 6.0 in a shorter time, as two co-dependent variables, and similar to studies published¹1. Noseworthy JH, Paty D, Wonnacott T, Feasby T, Ebers G. Multiple sclerosis after age 50. Neurology, 1983;33912):1537-44. https://doi.org/10.1212/WNL.33.12.1537
https://doi.org/10.1212/WNL.33.12.1537... ,²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,¹¹11. Etemadifar M, Abtahi SH, Minagar A, Akbari M, Masaeli A, Tabrizi N. Late-onset multiple sclerosis in Isfahan, Iran. Arch Iran Med. 2012;15(10):596-8.,¹²12. Bove RM, Healy B, Augustine A, Musallam A, Gholipour T, Chitnis T. Effect of gender on late-onset multiple sclerosis. Mult Scler. 2012;18(10):1472-9. https://doi.org/10.1177/1352458512438236
https://doi.org/10.1177/1352458512438236... ,¹⁸18. Harding K, Griffiths M, Wardle M, Tomassini V, Pickersgill T, Robertson N. Late-onset multiple sclerosis in south-east wales. J Neurol Neurosurg Psychiatry. 2013;84(11). https://doi.org/10.1136/jnnp-2013-306573.26
https://doi.org/10.1136/jnnp-2013-306573... ,²⁷27. Poser S, Raun NE, Poser W. Age at onset, initial symptomatology and the course of multiple sclerosis. Acta Neurol Scand. 1982;66(3):355-62. https://doi.org/10.1111/j.1600-0404.1982.tb06856.x
https://doi.org/10.1111/j.1600-0404.1982... ,²⁹29. Cottrell DA, Kremenchutzky M, Rice GPA, et al. The natural History of multiple sclerosis: 5. The clinical features and natural history of primary progressive multiple sclerosis. Brain. 1999;122:625-39. https://doi.org/10.1093/brain/122.4.625
https://doi.org/10.1093/brain/122.4.625... . Reaching disability milestones in a shorter period does not infer worse prognosis, considering that LOMS reached these at ages five to 11 years later than the young adults²2. Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954-9. https://doi.org/10.1212/01.wnl.0000237475.01655.9d
https://doi.org/10.1212/01.wnl.000023747... ,¹⁸18. Harding K, Griffiths M, Wardle M, Tomassini V, Pickersgill T, Robertson N. Late-onset multiple sclerosis in south-east wales. J Neurol Neurosurg Psychiatry. 2013;84(11). https://doi.org/10.1136/jnnp-2013-306573.26
https://doi.org/10.1136/jnnp-2013-306573... . Some authors state that disability is influenced by the age at which the patient was first evaluated, thus patients older than 50 years, tend to have the same disabilities, regardless of the age of disease onset¹³13. Martinelli V, Rodegher M, Moiola L, Comi G. Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis. Neurol Sci. 2004;25(Suppl 4):S350-55.3.,¹⁵15. Liguori M, Marrosu MG, Pugliatti M, Giuliani F, De Robertis F, Cocco E et al. Age at onset in multiple sclerosis. Neurol Sci. 2000;21(4 Suppl 2):S825-9. https://doi.org/10.1007/s100720070020
https://doi.org/10.1007/s100720070020... ,²⁸28. Trojano M, Liguori M, Bosco Zimatore G, Bugarini R, Avolio C, Paolicelli D et al. Age-related disability in multiple sclerosis. Ann Neurol. 2002;51(4):475-80. https://doi.org/10.1002/ana.10147
https://doi.org/10.1002/ana.10147... .

In our LOMS population, oligoclonal bands proved not to assist in the MS diagnosis. Only five out of the 10 LOMS patients were oligoclonal band positive. This lower percentage compared to previous series¹1. Noseworthy JH, Paty D, Wonnacott T, Feasby T, Ebers G. Multiple sclerosis after age 50. Neurology, 1983;33912):1537-44. https://doi.org/10.1212/WNL.33.12.1537
https://doi.org/10.1212/WNL.33.12.1537... ,⁷7. Arias M, Dapena D, Arias-Rivas S, Costa E, López A, Prieto JM et al. Late onset multiple sclerosis. Neurologia. 2011;26(5):291-6. https://doi.org/10.1016/j.nrl.2010.09.008
https://doi.org/10.1016/j.nrl.2010.09.00... ,¹⁴14. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol, 2008;255(5):697-702. https://doi.org/10.1007/s00415-008-0778-x
https://doi.org/10.1007/s00415-008-0778-... ,¹⁷17. Hooge JP, Redekop WK. Multiple sclerosis with very late onset. Neurology. 1992;42(10):1907-10. https://doi.org/10.1212/WNL.42.10.1907
https://doi.org/10.1212/WNL.42.10.1907... ,¹⁸18. Harding K, Griffiths M, Wardle M, Tomassini V, Pickersgill T, Robertson N. Late-onset multiple sclerosis in south-east wales. J Neurol Neurosurg Psychiatry. 2013;84(11). https://doi.org/10.1136/jnnp-2013-306573.26
https://doi.org/10.1136/jnnp-2013-306573... is possibly due to differences in laboratory techniques or to the disease period in which the test was done. However, our finding is in agreement with the hypothesis that older patients have lower levels of inflammatory and neurodegenerative biomarkers in their CSF³⁰30. Khademi M, Dring AM, Gilthorpe JD, Wuolikainen A, Al Nimer F, Harris RA et al. Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers. PLoS One. 2013;8(5):e63172. https://doi.org/10.1371/journal.pone.0063172
https://doi.org/10.1371/journal.pone.006... . Spinal MRI seems to be an important additional diagnostic tool in LOMS patients who usually show signs of microangiopathy on brain MRI. We observed that 50% of the 12 LOMS patients submitted to spinal MRI had lesions, thus helping to differentiate between MS and vascular diseases¹¹11. Etemadifar M, Abtahi SH, Minagar A, Akbari M, Masaeli A, Tabrizi N. Late-onset multiple sclerosis in Isfahan, Iran. Arch Iran Med. 2012;15(10):596-8.,¹⁴14. Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol, 2008;255(5):697-702. https://doi.org/10.1007/s00415-008-0778-x
https://doi.org/10.1007/s00415-008-0778-... ,¹⁸18. Harding K, Griffiths M, Wardle M, Tomassini V, Pickersgill T, Robertson N. Late-onset multiple sclerosis in south-east wales. J Neurol Neurosurg Psychiatry. 2013;84(11). https://doi.org/10.1136/jnnp-2013-306573.26
https://doi.org/10.1136/jnnp-2013-306573... . Our study demonstrated that spinal MRI may be a helpful diagnostic tool only in the primary progressive LOMS group, in which we found 75% of clusters with lesions shown in spinal MRI, a high percentage, as expected in this clinical course⁶6. Seze J, Delalande S, Michelin E, Gauvrit JY, Mackowiak MA, Ferriby D et al. Brain MRI in late-onset multiple sclerosis. Eur J Neurol. 2005;12(4):241-4. https://doi.org/10.1111/j.1468-1331.2004.01103.x
https://doi.org/10.1111/j.1468-1331.2004... ,¹¹11. Etemadifar M, Abtahi SH, Minagar A, Akbari M, Masaeli A, Tabrizi N. Late-onset multiple sclerosis in Isfahan, Iran. Arch Iran Med. 2012;15(10):596-8.,¹⁸18. Harding K, Griffiths M, Wardle M, Tomassini V, Pickersgill T, Robertson N. Late-onset multiple sclerosis in south-east wales. J Neurol Neurosurg Psychiatry. 2013;84(11). https://doi.org/10.1136/jnnp-2013-306573.26
https://doi.org/10.1136/jnnp-2013-306573... .

Clearly, there are limitations to our study. It is a description of a small population based on a retrospective review of medical records. It covers 20 years and the changes in diagnostic criteria may have introduced a bias in the comparison of the different groups of patients. Nonetheless, it is the first Latin America description of a LOMS population and we demonstrated its similarities to other cohorts previously described. The LOMS patients represent almost 5% of the MS population, and it is important to better understand its characteristics, pattern of disability progression and disease-modifying factors, such as treatment. Further studies are warranted, especially to determine how age influences the clinical course, treatment response and permanent neurological disability.

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