Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans

Background

Between 3% and 5% of all cases with multiple sclerosis, a demyelinating and progressive disease of the central nervous system, are diagnosed below the age of 18. ^{1 -5} Recent studies suggest that immunological and radiological abnormalities can differ between pediatric-onset and adult-onset. ^{6 -11} Disease characteristics are likely to be influenced by environmental and genetic factors; therefore, it is important to investigate cohorts with multiple sclerosis from similar racial and ethnic backgrounds. ^{1,12 -18}

Hispanics or Latinos are considered to have a lower rate of multiple sclerosis compared to non-Hispanic groups. ^{19 -21} Nevertheless, adult Hispanics in the United States, predominantly of Mexican background, have been reported to have greater prevalence of optic neuritis and spinal cord syndromes at presentation compared to non-Hispanic groups. ^3,20,22 Differences have been noted by birth region where US-born Hispanics appear to have less disability than immigrants. ¹⁴ The objective of our study was to compare clinical characteristics, treatment patterns, and disability levels of pediatric-onset multiple sclerosis and adult-onset multiple sclerosis who received care in the same academic center and assess if place of birth has a relationship with disability. Prior publications have focused on examining these differences in mostly non-Hispanic white cohorts of European background or have combined multiple ethnic and racial groups with limited inclusion of Hispanic Americans. ^{17,23 -26} Thus, we compared the clinical characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in only Hispanic background.

Methods

Results

Demographic information is presented in Table 1 (n=363). Information was collected on 110 pediatric-onset multiple sclerosis and 253 adult-onset multiple sclerosis. Most were of the relapsing remitting form of multiple sclerosis and were US born. The cohort of pediatric-onset multiple sclerosis consisted of almost equal distribution of female and male participants with a mean ± standard deviation age at the time of diagnosis of 14.7 ± 2.5 years (range 5-18 years). There were no differences in the female-to-male ratio by prepubertal age (Table 2). The cohort of adult-onset multiple sclerosis had a female predominance, with a mean ± standard deviation age at the time of diagnosis of 32.1 ± 9.8 years (19-66 years). Interestingly we found 2.7% of pediatric-onset multiple sclerosis to have a diagnosis of acute disseminated encephalomyelitis (ADEM) initially. The average age of children diagnosed initially with ADEM was 9.7 years (age range 5-13), whereas the average age of the pediatric multiple sclerosis cohort was 14.7. The average lag time from initial event fulfilling ADEM criteria to diagnosis of multiple sclerosis was 10.6 months.

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Table 1.

Demographics.

Characteristics	Adult onset	Pediatric onset	P value
	n = 253	n = 110
Age, y, M (SD)	42.4 (11.1)	25.9 (10)	<.0001
Age at first symptom, y, M (SD)	32.1 (9.8)	14.7 (2.5)	<.0001
Age at diagnosis, y, M (SD)	34 (10.4)	16.5 (4.1)	<.0001
Disease duration, y, M (SD)	10.3 (6.9)	11.2 (10)	.31
Female, n (%)	160 (63)	51 (46)	.001
Lag time,* y, M (SD)	1.9 (3.5)	1.9 (3.7)	.1
US-born, n (%)	197 (77)	99 (90)	.002
EDSS score >6, n (%)	112 (55.7)	29 (26.4)	<.0001

*Lag time was defined as time between age of first symptom to diagnosis.

Abbreviations: EDSS, Expanded Disability Status Scale; M, mean; SD, standard deviation.

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Table 2.

The Gender Distribution in Pediatric-Onset Multiple Sclerosis by Age Range.

Gender distribution by age rangea	>10 to <18 y	≤10 y
	n = 104	n = 6
Female, n (%)	46 (46%)	3 (50%)

^aAge at diagnosis.

The most common presenting demyelinating event in both groups was optic neuritis, with no significant difference by group (Figure 1). Transverse myelitis was the second most common presentation, and it was more frequent in the adult-onset cases (25% vs 18%, P < .001). As expected, polyfocal symptoms at presentation (17% vs 8%, P < .001), was more common in pediatric onset as was cognitive changes and seizures at onset.

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Figure 1.

Presenting symptoms by age of onset.

The type of disease modifying treatments for multiple sclerosis varied across both groups. A majority of patients with pediatric-onset multiple sclerosis were on glatiramer acetate, whereas this medication was used significantly less frequently in the adults (43% vs 32%; P value < .001) (Figure 2). Pediatric-onset multiple sclerosis patients and adult-onset multiple sclerosis patients had similar rates of treatment with immunosuppressive treatments (ie, rituximab, cyclophosphamide, azathioprine, alemtuzumab). There was no difference in the frequency of treatment with interferon.

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Figure 2.

Treatment patterns for pediatric-onset multiple sclerosis vs adults. (A) Pediatric-onset multiple sclerosis disease-modifying treatment. (B) Adult disease-modifying treatment.

Pediatric-onset multiple sclerosis had overall lower EDSS scores than did the adult-onset multiple sclerosis (Table 1). Adults were also found to have significantly more severe (EDSS >6) ambulatory disability than pediatric-onset cases despite similar disease duration and lag time to diagnosis (Figure 3). Using a logistic regression model to correct for gender, age of first symptom, and disease duration, individuals with adult-onset multiple sclerosis still had significantly more ambulatory disability than did those with pediatric-onset multiple sclerosis (P = .004). However, younger age at first symptoms (P = .004) and being born in the United States (P = .006) were less likely to have ambulatory disability (Table 3).

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Figure 3.

Expanded Disability Status Scale score by age at diagnosis.

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Table 3.

Factors Affecting Disability.

	Unadjusted		Adjusted
Factors	OR (95% CI)	P value	OR (95% CI)	P value
Pediatric onset	0.33 (0.16-0.69)	.003	0.33 (0.16-0.71)	.004
Age at diagnosis, y	1.01(1-1.04)	.30	1.02 (1-1.1)	.14
Sex (female)	0.87 (0.53-1.4)	.57	0.80 (0.51-1.4)	.47
Disease duration, y	1.1(1.10-1.20)	<.0001	0.10 (1.1-1.2)	<.0001
Lag time	0.88 (0.81-0.95)	.0006	0.88 (0.82-0.95)	.009

Abbreviations: CI, confidence interval; OR, odds ratio.

Discussion

This is the first study to compare pediatric-onset multiple sclerosis to adult-onset multiple sclerosis in an all Hispanic American cohort. Our results show age-related differences in Hispanic Americans with multiple sclerosis, a group that is generally considered to have a lower incidence of disease but higher incidence of optic neuritis and possibly transverse meyltiis. ^17,20 Specifically, we found that adult-onset multiple sclerosis are more likely to have severe ambulatory disability compared to pediatric-onset multiple sclerosis independent of other factors. Furthermore, place of birth was an important factor. Although optic neuritis was seen equally across both groups, a higher frequency of polyfocal and cognitive symptoms at presentation were seen in the pediatric-onset multiple sclerosis, whereas spinal cord involvement was significantly more common in the adult-onset multiple sclerosis.

Optic neuritis and spinal cord involvement was the most frequent presentation, which is not surprising. We, as well as others, have observed optic neuritis to be the most common presentation in Hispanic Americans, particularly those who reside in Southern California and are of Mexican background. ^{20,30 -34} Langer-Gould et al ³⁵ investigated the presenting symptom across 468 multiple ethnic and racial backgrounds with multiple sclerosis and found that Hispanics (n=149) were more likely to present with optic neuritis (P = .006). Although a recent study that focuses on Hispanics of Caribbean background in the United States reported sensory symptoms to be the most common presentation. ³⁶ This could be partly explained by the genetic and/or cultural background, which differs within Hispanics of different origins. Nevertheless, transverse myelitis was more common in adult-onset multiple sclerosis. This could suggest that age of onset might be involved in the regional distribution of multiple sclerosis. Not surprisingly, the long-term effect of spinal cord disease at presentation could be responsible for observed difference between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in ambulatory disability. ³⁵

Irrespective of presentation, more ambulatory disability in the adult-onset multiple sclerosis was observed compared to pediatric-onset multiple sclerosis, which is in concert with other studies that have reported less disability in pediatric-onset multiple sclerosis. ^{37 -40} Despite this, there were no statistically significant differences between pediatric-onset and adult-onset multiple sclerosis in disease duration. Therefore, the higher disability scores of adult-onset multiple sclerosis are unlikely to be solely the result of longer disease duration. This suggests that there are likely other factors (ie, environmental and/or genetic), including the possibility that spinal cord presentation, which appears to be more common in adult-onset multiple sclerosis, places them at risk of more prominent disease severity in adult-onset multiple sclerosis compared to pediatric-onset multiple sclerosis. In addition, pediatric-onset multiple sclerosis has been reported to have less accumulation of irreversible disability over time. ^{39 -44} Gorman et al ³⁹ report increased relapse rates in a multiethnic pediatric-onset multiple sclerosis cohort compared to adult-onset multiple sclerosis; however, the pediatric group did not have the same degree of disability as the adults. These results, however, do not eliminate the concern that pediatric-onset multiple sclerosis are at risk of reaching disability at an earlier age compared to the adult-onset cases and could be at risk of poorer outcomes. ⁴⁰

One difference between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis is the majority of the pediatric-onset multiple sclerosis cohort was reported as US born whereas statistically more of adult-onset multiple sclerosis were born outside of the United States. A recognized factor involved in early age of onset of multiple sclerosis is birth at higher latitudes. ^{37,42 -44} Long-term outcomes, including disability are likely to be impacted by this as well. We recently reported that late timing of migration to the United States appears to be a risk factor in disability progression in Hispanic multiple sclerosis immigrants compared to US born. ¹⁴ This was found to be irrespective of socioeconomic status, which was assessed by place of health care access. Although this may partially be due to differences in environment (ie, vitamin D deficiency, infections) and less so genetics; socioeconomic and cultural factors are also recognized to play a role in influencing health outcomes and should be further explored. Whether outcomes in multiple sclerosis are related to age of onset, however, are still unresolved.

Although the frequency of second-line treatments was similar between pediatric-onset and adult-onset multiple sclerosis, the distribution of disease-modifying treatments by age of onset can only provide an overall view that may be the result of patient, parent, and physician preference and/or disease activity. Future studies should examine treatment by disability level to better understand that relationship in absence of guidelines.

Limitations of our study include the cross-sectional design, the convenience sample, and overrecruitment of pediatric-onset cases. Thus, this study should not be interpreted as a prevalence study. The cross-sectional nature of the study also did not allow for examining longitudinal changes between groups. In addition, the predominantly Mexican background in this Hispanic cohort, which is representative of our geography, may not apply to other Hispanic groups. Nevertheless, Mexican background is the largest Hispanic group in the United States and any finding related to this population is likely to influence the care of Hispanics with multiple sclerosis. Future studies should compare Hispanics to other racial and ethnic groups such as non-Hispanic whites and African Americans. The strengths of this study include the large sample size and the consistent characteristic findings that have been reported in the pediatric multiple sclerosis cohorts and adult Hispanics with multiple sclerosis in the United States.

Conclusions

In summary, this is a large sample that compared adult-onset multiple sclerosis to pediatric-onset multiple sclerosis within a Hispanic American cohort. Both have optic neuritis as the most common presenting symptom and, compared with pediatric-onset multiple sclerosis, immigrants with adult-onset multiple sclerosis have more ambulatory disability. Continued efforts to study age-related factors, place of birth, and minority populations are needed in order to better understand the long-term clinical implications and potential mechanisms behind these findings.