In 1.2–6% of multiple sclerosis (MS) cases, the onset of disease is before 16 years of age [
There have been no longitudinal magnetic resonance imaging (MRI) studies in EOMS to establish progression on the basis of imaging and to compare these data with AOMS.
Most studies on EOMS either have been based on a small number of cases and have not allowed obtaining exhaustive information on its prognosis or have been compared to a previous retrospective study [
A prospective cohort of 46 patients in whom the disease onset occurred before 16 years of age, diagnosed with MS according to the McDonald’s diagnostic criteria [
Family history and associated diseases were investigated in all MS patients. Twenty-three percent of AOMS and 24% of EOMS patients were under disease-modifying treatments at baseline. Only 1 EOMS patient and 2 AOMS patients were treated with azathioprine add-on therapy.
Those patients who showed only recurrent transverse myelopathy, recurrent optic neuritis, or recurrent brainstem symptoms were excluded. Patients who were serologically positive for rheumatoid factor, antidouble stranded DNA antibody, were also excluded. All of the patients were negative for anticardiolipin antibody (aCL) and antineutrophil cytoplasmic antibody (ANCA). Patients were screened for sarcoidosis.
Clinical assessment of patients was done with Expanded Disability Status Scale (EDSS) and multiple sclerosis functional composite (MSFC). The EDSS [
The MSFC, which has been shown to be very effective to demonstrate the disability change for treatment effect [
Patients were also compared on the basis of magnetic resonance imaging (MRI) data. Diagnostic MRI had been performed for all patients at the time of the first clinical attack or during the clinical course, and serial MRI had been carried out in several patients to evaluate the disease activity. For MRI assessment, the same MRI machine with 1.5 T was used for both baseline and year five. T2 hyperintense lesions, Gd-enhanced lesions, and T1 hypointense lesions (black holes) were calculated.
The same physician administered the MSFC to a given patient at each study visit. All examining technicians were trained neurologists, and each neurologist was blinded to the other results of tests, MRI findings or disease history. The physician assessing EDSS score of study group was blinded to control results. MRI lesions were also assessed by a physician who was blinded to clinical findings.
Patients on steroid treatment one month of the assessment were not included, and they were reassessed.
When analyzing changes in the individual MSFC components, we used the change in
General demographic and clinical features were summarized in Table
Comparison of demographic features of EOMS and AOMS at baseline.
EOMS | AOMS |
| |
---|---|---|---|
|
46 | 64 | |
Age at onset years ± SD | 11.7 ± 3.28 | 29.6 ± 6.8 | 0.002 |
(range) | (8–16) | (19–41) | |
Disease duration years ± SD | 8.54 ± 6.65 | 7.97 ± 3.78 | NS |
Disease Course (%) | |||
RR | 71.1 | 76.5 | NS |
SP | 24.4 | 18.7 | NS |
PP | 4.5 | 4.8 | NS |
EDSS at baseline | 3.19 ± 2.71 | 3.46 ± 1.9 | NS |
EOMS: early onset multiple sclerosis, AOMS: adult onset multiple sclerosis, RR: relapsing remitting, SP: secondary progressive, PP: primary progressive, and EDSS: expanded disability status scale.
Although MSFC score seemed to be better in EOMS than AOMS group at baseline, it worsened more in childhood onset group than adult onset population at the end of the study (year 5). Difference in MSFC between baseline and at the end of the 5th year was significantly worse in EOMS population (
MSFC in the follow-up period (MSFC at baseline versus the 5th year,
PASAT in the follow-up period (PASAT at baseline versus the 5th year,
There was no difference between childhood and adult onset MS, based on number of T2 hyperintense (24.94 and 27.8, resp.), Gd-enhanced (2.02 and 2.45, resp.), and T1 hypointense lesions (3.0 and 3.12, resp.) at baseline. Differences between baseline and end of the 5th year on the basis of T2 hyperintense lesions (
T1 hypointense lesions at baseline versus the 5th year, (
Correlation between the baseline overall MSFC and number of T2 lesions and Gd-enhanced lesions was moderately strong (
Multiple sclerosis is best recognized for its relapsing and remitting clinical course. In fact, in both children and adults, RRMS is the most common form, followed by the secondary and primary progressive forms. However, the prognosis of childhood onset MS remains controversial. There has been some evidence that patients with childhood onset MS have a slower accumulation of irreversible disability compared to patients with AOMS. But there is also conflicting evidence indicating that patients with childhood onset reach disability at a younger age than patients with adult onset [
There have been two opposite opinions regarding the impact on cognitive functioning in patients with childhood MS. It can be even more dramatic than adult onset cases, because the pathological process develops during early CNS myelinogenesis. Thus, it may negatively affect ongoing maturation of white matter pathways which can lead to neurodegeneration of neural networks involved in cognition. Amato et al. commented that this status might interfere with present and future academic achievements [
The definition EOMS used in previous studies has been variable. Some groups have used under the age of 18 and some others under 16. Although there has been seemed to have no significant differences, we used under age 16, because observations indicate that the closer the age to adulthood, the more the patients have similar features with adult onset MS [
In the present study, we used MSFC in addition to EDSS for clinical assessment, because of EDSS’s well-recognizeed disadvantages. Our results indicated that childhood and juvenile onset MS patients had a poorer prognosis than adult onset patients based on MSFC. Although there was no significant difference between EOMS and AOMS groups at baseline, MSFC significantly more worsened in childhood onset group than adult population at the end of the year 5. This difference seemed to be originated from PASAT scores. The mean number of correct responses was significantly less in EOMS patients than AOMS patients. Although 9HPT and T25WT scores were also worsened, they were not statistically significant, that is, trend only. Comparison of EDSS differences was also insignificant. As a most widely used screening test for cognition in MS, PASAT imposes high demands on the subject’s working memory capacity, requiring controlled information processing (e.g., attention), visual memory, good auditory functioning, and calculating ability [
Magnetic resonance imaging is the most sensitive paraclinical method supporting the diagnosis of multiple sclerosis. It detects areas of increased signal, predominantly in the white matter, on T2-weighted imaging and discloses abnormalities in 95% of patients with clinically definite MS. There have been no longitudinal MRI studies in EOMS to establish whether there is progressive atrophy of the brain or the appearance of black holes, which may reflect permanent disability. Although we did not perform atrophy assessment, our MRI data has novel evidence regarding prognosis in EOMS. Patients with early onset have significantly more T1 hypointense lesions (i.e., “black holes”) at the end of the year 5 followup comparing with AOMS patients. Difference in number of T1 lesions in year 5 followup was significantly more in early onset patients than adult onset. Moreover, significant correlations were established between PASAT and both T1 hypointense lesions at baseline and difference in number of T1 hypointense lesions at followup.
In conclusion, although we need some support with longer followup, our results indicate that early onset MS seems to have worse prognosis than adult onset MS on the basis of clinical manifestation, assessed by MSFC, cognitive impairment, and MRI parameters. Therefore, patients with early onset should be treated with immunomodulatory agents as early as possible to try to limit the process.