JNNP: Early predictor of multiple sclerosis disability in children

Multiple sclerosis (MS) is relatively rare in children, with an incidence of 0.
13 to 0.
66 per 100,000 children
.
In children, its clinical course is highly inflammatory and often worsens (relapses), especially in the first years
after the onset of symptoms.
The long-term prognosis for pediatric-onset multiple sclerosis is often poor, with severe limitations
in physical capacity reported as early as the third decade of life.
With the advent of more effective disease-modifying therapies (DMTs), significant advances
have been made in the clinical treatment of multiple sclerosis in adults over the past decade.
These therapies are most effective
in preventing long-term disability at the onset of clinical multiple dementia at an early stage (often a highly active few years).
Two observational studies and a randomized clinical trial have recently provided new insights that will help guide the treatment of pediatric onset MS, paving the way
for wider use of more effective DMT.
Early identification of children at risk of faster deterioration of disability is necessary for the early use of these treatments in a targeted manner with the aim of optimizing the long-term prognosis of
paediatric multiple sclerosis.
Previous studies have identified several potential imaging and clinical prognostic markers for pediatric-onset multiple dementia, and this study used a large transnational cohort to identify predictors of disability as early as the first year after the clinical onset of paediatric multiple sclerosis, considering its potential to guide more efficient DMT use
, and to identify early predictors of rapid disability in patients with paediatric multiple sclerosis.
This article was published in the Journal of Neurology, Neurosurgery & Psychiatry
.

Through the Global MSBase Registry, patients
younger than 18 years of age at the onset of MS symptoms were identified.
Clinical demographic characteristics that are predictors of future MS severity scores (MSSS) include sex, age at symptom onset, absence of disability at initial assessment, maximum extended disability status score (EDSS) score, frequency of relapse, and brainstem, pyramidal, visual, or cerebellar symptoms
in the first year.
The data were analyzed using a Bayesian lognormal generalized linear mixed model, which was adjusted
for the cumulative time ratio of DMT.
Early activity on brain MRI was classified as having no new lesions / the presence of at least one new high-intensity T2 lesion or gadolinium-enhanced T1 lesions / not being recorded
in the first 12 months of disease.
The MSBase study protocol recommends annual MRI of
the brain.
The scanning protocol used reflects local clinical practice and represents a wide range
of variations from 2D (no gaps or gaps) or 3D protocols (including T2/FLAIR/proton density and T1/MPRAGE sequences).

Research process

672 patients (70% women) participated in 9357 visits
.
The median age at symptom onset was 16 years
.
The older age at which symptoms appeared in the first year (exp(β) = 1.
10 (95% CI 1.
04 to 1.
17)), the higher the EDSS score (1.
22 (1.
12 to 1.
34)), the cone (1.
31 (1.
11 to 1.
55)), visual (1.
25 (1.
10 to 1.
44)), or cerebellar (1.
18 (1.
01 to 1.
38)) Symptoms were associated
with high levels of MSSS.
For every 24% increase in more effective DMT, MSSS decreased by 4% (0.
96 (0.
93 to 0.
99)).

Spending longer on more effective DMT is associated with
improved disease outcomes.
It is estimated that MSSS decreased by 4% (0.
96 (0.
93 to 0.
99)) and the proportion of time patients spent on more effective DMT increased by 24% (1SD).

It is estimated that the risk of reaching EDSS score 3 was reduced by 41% and the proportion of time spent for more effective DMT increased by 28%.

Studies have shown that some clinical features observed in the first year of onset can predict more severe disability
in children and adolescents under 18 years of age with pediatric MS.
These factors include older age at onset of multiple sclerosis, more severe disability in the first year of onset, and the presence of pyramidal, visual, or cerebellar symptoms or signs, all of which predict a higher level of disability (quantified in MSSS and taking into account the time after the onset of multiple dementia).

In MSBase centers in (A) World and (B) Europe and the Middle East, there is a
difference in the use of more effective DMT in children with multiple sclerosis.

The older the age of onset of MS, the higher the EDSS score, and the onset of pyramidal symptoms is associated
with more severe disability in the future.
Recently, early cerebellar symptoms have been found to predict a higher
level of MSSS disability in childhood MSSS.
This observation complements the negative prognostic value
of early cerebellar signs in adult MS patients.
Previous studies of adult MS have found lower
rates of complete recovery from pyramidal and cerebellar relapses.
In the current study, there was a weak
correlation between early recurrence frequency and disability outcomes after the onset of multiple sclerosis.
This suggests that the regenerative capacity within a child's central nervous system may be large shortly after the onset of MS, mitigating the short- to medium-term effects
of early onset of inflammation on long-term deterioration of nerve function.
A significant number of patients in this study started taking natalizumab, fingolimod, or dimethyl fumarate before the age of 18
.
Importantly, the proportion of time patients received more effective DMT treatment was consistently associated with milder disability across all of our analyses.

Childhood multiple sclerosis has a relatively late onset, a high rate of disability in the first year, and a marked worsening of pyramidal, visual, or cerebellar symptoms, indicating a severe deterioration
of disability in patients with childhood multiple sclerosis.
Continued use of more effective DMT is associated with
reduced rates of disability deterioration.