Клинический спектр приобретенных синдромов демилинизации у детей: опыт третичной больницы.

Key Summary Points

Why carry out this study?
Personalized treatment plans for each patient with acquired demyelinating syndrome (ADS) based on the specific requirements and goals of the individual are essential. The aim of this study was to present the clinical features of ADS among Saudi children because pediatric ADS is an uncommon presentation and no regional epidemiological statistics are available.
What was learned from the study?
There are distinct differences in age of onset, clinical presentation, and imaging patterns between multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), clinically isolated syndrome (CIS), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) subtypes. Onset of MS and MOGAD is later than CIS. There are unique patterns in initial attacks and imaging features such as callososeptal interface lesions in MS and posterior fossa hyperintensities in MOGAD. Clinicians often face difficulties in differentiating between CIS and other diagnoses such as MS, MOGAD, and neuromyelitis optica spectrum disorder (NMOSD) because of the inherent overlap in their clinical presentation.

Introduction

Acquired demyelinating syndromes (ADS) comprise a group of immune-mediated disorders characterized by inflammatory damage to the myelin sheath in the central nervous system (CNS). These disorders include multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), acute hemorrhagic leukoencephalitis (AHLE), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and are relatively rare in the pediatric population [ 1 , 2 ].

Internationally, ADS occur with an annual incidence ranging from 0.5 to 1.66 per 100,000 children [ 1 , 2 ], though the incidence and prevalence of these disorders vary by condition. There is limited but emerging data on the incidence and prevalence of pediatric ADS in Saudi Arabia. In 2021, data from the National Saudi MS Registry revealed that pediatric-onset multiple sclerosis (POMS) in the Saudi pediatric population had an incidence of 2.73 per 100,000, with an overall projected prevalence of 14.33 per 100,000, and a mean age of diagnosis at 15.7 years [ 3 ]. Globally, the pooled incidence of pediatric MS is 0.87 per 100,000 annually, while its prevalence is 8.11 per 100,000 individuals [ 4 ].

While MS is more frequent in older children and adolescents, pediatric MOGAD is seen more frequently in younger age groups. It has gained recognition in recent years, though data on its exact prevalence are still evolving. The estimated incidence is 0.1–0.2 per 100,000 children per year, with a prevalence of approximately 0.5–1 per 100,000 children [ 5 ]. These figures may change as diagnostic capabilities expand and recognition of the disorder increases. Acute disseminated encephalomyelitis is more common than pediatric-onset MS in children under the age of 10, with an annual incidence of 0.2–0.4 per 100,000 children [ 6 ]. Although less common, neuromyelitis optica spectrum disorder (NMOSD) can also occur in children, with population-based studies suggesting an incidence ranging from 0.05 to 4.0 per 100,000 per year, and a prevalence ranging from 0.5 to 4.4 per 100,000 [ 7 ]. The incidence and prevalence of ADS in children show significant variation across studies, emphasizing the importance of early diagnosis and management.

Diagnosing ADS in children presents significant clinical challenges due to overlapping symptoms between disorders, difficulties distinguishing monophasic from recurrent demyelinating events, and the absence of established diagnostic criteria for many conditions. While pediatric MS is the most extensively studied among these disorders—thanks in part to efforts by the International Pediatric MS Study Group (IPMSSG) to develop diagnostic criteria—other ADS entities lack standardized diagnostic frameworks.

The neurological manifestations of ADS can range from monofocal to diffuse symptoms, depending on the extent of CNS lesions. The disease course may be monophasic, as seen in ADEM, or multiphasic and recurrent, as in MS or NMO. Differentiating between these entities is crucial for guiding management plans, prognostication, and decisions regarding the initiation of maintenance disease-modifying therapies. Despite multiple attempts to establish distinguishing criteria [ 8 ], overlapping clinical presentations continue to complicate diagnosis. Advances such as the identification of novel antibodies (e.g., anti-MOG) and the recognition of new clinical subtypes have enhanced diagnostic precision.

Overall, treating ADS is complex and requires a multidisciplinary approach. Individualized treatment plans that address the specific needs and goals of each patient are essential. Ongoing research continues to develop new and more effective therapies for these disorders. Given the rarity of pediatric ADS and the lack of local epidemiological data, our study aims to describe the clinical spectrum of ADS in children at our tertiary hospital. By analyzing local clinical data, this will contribute to a better understanding of these disorders in our region, improve diagnostic accuracy, and inform management strategies.

Methods

Study Design and Settings

A retrospective observational study was conducted at King Abdulaziz Medical City (KAMC) and King Abdullah Specialized Children Hospital (KASCH) in Riyadh, Saudi Arabia between January 2016 and December 2022. Written informed consent was obtained from the parents or legal guardians of all patients included in the study.

Study Population

We included all patients that presented with a monofocal or polyfocal clinical CNS event with presumed inflammatory demyelinating cause, and then further classified them into ADS groups such as CIS, MS, ADEM, and MOGAD. Clinically isolated syndrome (CIS) was further classified into monophasic transverse myelitis or optic neuritis, using criteria and definitions proposed by IPMSSG 2012 criteria and the International MOGAD Panel proposed criteria in 2023 [ 4 , 8 – 10 ].

Study Outcomes

Information was obtained from a detailed review of patients’ medical records during their admission and follow-up visits in outpatient service where the patients were seen on a regular basis. Apart from demographic parameters, we collected the age at onset of clinical event, presenting symptoms and signs, preceding illness/vaccination, neuroimaging, and laboratory workup, specifically serum and CSF antibodies if available (AQP4-ab, MOG-ab, and oligoclonal bands). All patients with CIS underwent CSF analysis to confirm their diagnosis. For patients with ADEM, MOG-ab tested negative. Treatment options used in these patients included both acute treatment and long-term disease-modifying treatment. We assessed clinical outcome in follow-up visits through Expanded Disability Status Scale (EDSS) to quantify disability in these cases; EDSS is a scale widely used to express clinical disability. We classified it into minimal disability, score 1–1.5, indicating “abnormal signs only” without disability such as having pyramidal signs, disc pallor, or any functional score grade I; moderate disability, score 2–4; and significant disability, score > 5.

Ethical Approval

The Ethics Committee of King Abdullah International Medical Research Center approved the study (NRC23R/344/06). This study was conducted in accordance with the Declaration of Helsinki and local regulations. Written informed consent was obtained from the parents or legal guardians of all patients included in the study.

Statistical Analysis

All statistical analyses were performed using SPSS Software Version 29. To assess the normality of the data, the Shapiro–Wilk test was performed. Student t  test and analysis of variance (ANOVA) were used to examine the difference in normally distributed continuous variables. Mann–Whitney test and Kruskal–Wallis test were used to examine the difference in non-normally distributed continuous variables. Fisher’s exact test and chi-squared test were used to examine the difference in the proportion of categorical variables. To control for the risk of type I error due to multiple comparisons, the Bonferroni correction was applied. Results were reported as percentages and p  value; p  values less than 0.05 were considered significant.

Results

Demographics and Clinical Characteristics

This study included 45 pediatric patients presenting with monofocal or polyfocal CNS events presumed to be of inflammatory demyelinating origin. Of these, 30 patients (66.7%) were female, and 15 patients (33.3%) were male. The demographic and clinical characteristics are summarized in Table  1 .

Table 1 Demographic and clinical characteristics Characteristic MS CIS MOGAD ADEM p value n  = 30 n  = 7 n  = 5 n  = 3 Gender distribution (male/female ratio) 1:3 3:4 3:2 2:1 0.161 Age distribution (years, mean) Median (min–max) 18.94 19 (10–26) 15.43 16 (9–19) 9.6 8 (6–14) 13.67 14 (10–17) < 0.0001* Age at onset (years, mean) Median (min–max) 14.03 15 (8–16) 10.86 11 (6–14) 6.60 6 (3–11) 9.33 9 (5–14) < 0.0001* Reported illness < 4 weeks prior, % 10.0% 28.57% 40.0% 66.67% 0.095 Presence of familial autoimmune diseases, % 2.17% 0 0 0 – First attack (description, %) Ataxia/Focal deficit 60% TM 57.14% ON 60% Encephalopathy 66.67% < 0.0001* Frequency of attacks (mean ± SD) Median (min–max) 1.7 ± 0.86 19 (10–26) 1.0 ± 0.0 16 (9–19) 1.0 ± 0.49 8 (6–14) 1.0 ± 0.0 14 (10–17) 0.0514 MS multiple sclerosis, CIS clinically isolated syndrome, ADEM acute disseminated encephalomyelitis, MOGAD myelin oligodendrocyte glycoprotein antibody, TM transverse myelitis, ON optic neuritis disease, n number of cases * p  value less than 0.05 is considered statistically significant

Demographic and clinical characteristics

Age distribution (years, mean)

Median (min–max)

18.94

19 (10–26)

15.43

16 (9–19)

9.6

8 (6–14)

13.67

14 (10–17)

Age at onset (years, mean)

Median (min–max)

14.03

15 (8–16)

10.86

11 (6–14)

6.60

6 (3–11)

9.33

9 (5–14)

Ataxia/Focal deficit

60%

TM

57.14%

ON

60%

Encephalopathy

66.67%

1.7 ± 0.86

19 (10–26)

1.0 ± 0.0

16 (9–19)

1.0 ± 0.49

8 (6–14)

1.0 ± 0.0

14 (10–17)

MS multiple sclerosis, CIS clinically isolated syndrome, ADEM acute disseminated encephalomyelitis, MOGAD myelin oligodendrocyte glycoprotein antibody, TM transverse myelitis, ON optic neuritis disease, n number of cases

* p  value less than 0.05 is considered statistically significant

Among the 45 subjects, the majority were diagnosed with MS ( n  = 30), followed by monophasic CIS ( n  = 7) of which four were transverse myelitis and three optic neuritis cases, anti-MOGAD ( n  = 5), and ADEM ( n  = 3). As a result of the small sample size of the ADEM group, statistical analyses were conducted after excluding this group.

The median age at initial presentation was 15 years (range 8.00–16.00 years) for the MS group and 11 years (range 6.00–14.00 years) for the CIS group. The MOGAD group had a younger median age of onset at 6 years (range 3.00–11.00 years). Comparative analysis of age at onset among the three most common groups revealed that the MS group had the highest mean and median age at onset (14.03 and 15.00 years, respectively), while the MOGAD group had the lowest mean age at onset (6.60 years) with greater variability due to the small sample size (Fig.  1 ). Significant differences in age at onset were observed between the MS and both the CIS and MOGAD groups ( p  = 0.0002).

Age at presentation. MS multiple sclerosis, CIS clinically isolated syndrome, ADEM acute disseminated encephalomyelitis, MOGAD myelin oligodendrocyte glycoprotein antibody

The initial clinical CNS attacks were categorized as optic neuritis, transverse myelitis, encephalopathy, ataxia, focal deficits, and diplopia. Optic neuritis was most frequently observed in the MS group, accounting for 40% of cases presenting with this symptom. Transverse myelitis was predominantly seen in the CIS group, representing 80% of such cases. Ataxia was mainly found in the MS group, with only one patient in the MOGAD group presenting with ataxia. Focal deficits and diplopia were exclusively observed in the MS group. Fisher’s exact test indicated a significant difference in the type of first attack stratified by ADS diagnosis ( p  < 0.0001), suggesting that certain initial attack types are more likely to occur with specific ADS types (Fig.  2 ).

Initial attack types stratified by ADS types. MS multiple sclerosis, CIS clinically isolated syndrome, MOG myelin oligodendrocyte glycoprotein

The MS group exhibited a higher average number of attacks with greater variability compared to the CIS and ADEM groups, which typically reported a consistent number of attacks per patient. A family history of autoimmune diseases was rare across the dataset, with only 1 out of 45 cases (2.2%) in the MS group reporting such a history. Regarding preceding illnesses, the ADEM group had the highest percentage of cases reporting a preceding illness (66.7%). The MOGAD and CIS groups showed moderate levels of preceding illness reports at 40.0% and 28.6%, respectively. Despite being the largest group, the MS group had a relatively low percentage of preceding illness reports.

Laboratory and Neuroimaging

In our retrospective analysis of ADS in children, laboratory data were only available for a subset of patients because of missing records. CSF leukocytosis counts were analyzed across the groups. In the MS group, 65.2% (15 out of 23) of patients did not exhibit CSF leukocytosis, while 34.8% (8 out of 23) did. The MOGAD group had the highest proportion of CSF leukocytosis, with 42.9% (3 out of 5) of patients. The CIS and ADEM groups each showed CSF leukocytosis in one patient in each group. Statistical analysis using the chi-squared test revealed no significant differences in CSF leukocytosis proportions among the groups ( p  = 0.32).

CSF oligoclonal band testing was performed in a subset of patients. Positive CSF oligoclonal bands were found in 64.3% (9 out of 14) of patients with MS, indicating intrathecal immunoglobulin synthesis. Only one patient (14.3%) in the MOGAD group had positive CSF oligoclonal bands. Serum oligoclonal bands were present in 15.4% (2 out of 13) of patients with MS and were absent in the CIS, MOGAD, and ADEM groups. The higher prevalence of CSF oligoclonal bands in the MS group was statistically significant ( p  = 0.04).

All patients in the MOGAD group (100%) tested positive for MOG antibodies, confirming the diagnosis. Notably, one patient (7.7%) in the MS group demonstrated transient MOG antibody positivity, which resolved on subsequent testing. This finding may suggest a transient immune response or assay variability. It is worth mentioning that patients with CIS who had presented with an isolated episode of optic neuritis and/or myelitis (including long segment) were not all tested for antibodies (AQP4, MOG). Serial neuroimaging studies were thoroughly reviewed by an experienced neuroradiologist. Representative MRI images were selected to illustrate the characteristic features of each ADS group (Images 1–5 in supplementary material).

Treatment and Outcome

During acute attacks, most of the patients with ADS received first-line immunotherapies, including intravenous pulse steroids, intravenous immunoglobulin (IVIG), and plasma exchange (PLEX). Intravenous pulse steroids were administered as first-line therapy in almost all cases across ADS groups, including 66.7% (20 out of 30) of patients in the MS group. IVIG therapy usage varied, with high rates in MOGAD (80.00%) and ADEM (66.67%), moderate rates in CIS (14.29%), and minimal use in MS. PLEX was predominantly used in patients with ADEM, administered to 66.7% (2 out of 3) of patients, minimally in the MS group (percentage and number), and was not used in the CIS or MOGAD groups.

An orally administered prednisolone taper was commonly used following acute therapy, particularly in MOGAD (80.0% (4 out of 5) of patients), CIS (71.4% (5 out of 7) of patients), and ADEM (66.7% (2 out of 3) of patients). Second-line acute therapy, mainly rituximab, was administered to some patients across all groups except CIS, with the highest usage observed in MS and MOGAD at 16.7% and 20.0%, respectively. Overall, rituximab was administered to 13.0% (6 out of 46) of the total cohort. On the other hand, disease-modifying therapy (DMT) was predominantly utilized in the MS group. The most frequently used DMTs were ocrelizumab, administered to 43.3% (13 out of 30) of patients with MS, and interferon beta, administered in 40.0% (12 out of 30) of patients with MS.

Disability outcomes were measured using the EDSS. The MS group had a low mean EDSS score, with a median of 0, suggesting that most patients experienced minimal or no disability. Patients with CIS and MOGAD exhibited similar EDSS distributions, reflecting moderate levels of disability. The ADEM group had the highest mean EDSS score, 2.50 ± 3.54, indicating a higher level of disability. Notably, one out of three patients with ADEM had an EDSS score of 5, signifying significant disability, and another patient was lost to follow-up.

We further analyzed the type of residual deficits among different groups and found that approximately 50% of patients with MS (15 out of 30) had only abnormal signs, i.e., pyramidal signs or disc pallor (EDSS scores of 1.0–1.5), indicating minimal disability, while patients with CIS with residual deficits primarily exhibited bladder dysfunction or motor deficits which were seen in transverse myelitis cases. The MOGAD group was specifically associated with cognitive deficits. In the ADEM group only one case had a poor EDSS score of 5, associated with both motor and visual deficits, indicating significant disability. It is important to note that there was no standardized follow-up period across patients. This variability in follow-up times could influence the EDSS scores, as some patients were assessed at different intervals post discharge. This lack of a fixed follow-up period may impact the comparability of EDSS scores and the interpretation of long-term disability outcomes.

Discussion

This study aimed to review the demographics, clinical characteristics, imaging findings, treatment approaches, and outcomes of various ADS in a pediatric population. By comparing these findings with existing literature, we sought to identify patterns that could aid in the early recognition and management of ADS in children.

In our cohort the median age at initial presentation was 15 years for the MS group, which was older than for the CIS (mean age 11 years) and MOGAD (mean age 6 years) groups. This difference in age at onset was statistically significant, suggesting that MS may exhibit a distinct age pattern compared to other ADS types. Our findings align with previous studies [ 11 – 13 ]. Additionally, we observed a higher female-to-male ratio in the MS and CIS groups, while men were more prevalent in both the MOGAD and ADEM groups. However, the gender distribution differences across ADS types were not statistically significant, as suggested in previous research [ 11 – 13 ].

In our study, the most common presenting symptoms during the first acute demyelinating attack were ataxia and focal deficits in patients with MS, while optic neuritis was predominant in MOGAD cases. In contrast, the ADEM group exhibited a broad range of symptoms, with encephalopathy present in all cases. These patterns are consistent with previous reports in the literature. Notably, optic neuritis was a frequent presentation across all groups, most observed in patients with MS (40% of cases), followed by the CIS and MOGAD groups. Transverse myelitis was primarily associated with CIS (80% of cases), while encephalopathy was exclusive to the ADEM and MOGAD groups. These differences in presentation types among the groups were statistically significant, underscoring the importance of recognizing these patterns for early diagnosis and treatment [ 14 , 15 ].

Presence of a preceding illness prior to a demyelinating attack was investigated among our population; ADEM had the highest percentage of cases (66.67%) reporting a preceding illness, though these differences were not statistically significant, possibly as a result of our small sample size. This might suggest a potential link between prior inflammatory events and the onset of ADEM, which is a link found in other studies as well. A study conducted in Turkey in 2021 by Kilic et al. showed that most of their patients with ADEM had a preceding illness, and in one patient Epstein-Barr virus (EBV) was the infectious agent isolated [ 15 ]. Regarding family history of an autoimmune disease, despite high consanguinity rates in our population there was a low occurrence of reported familial autoimmune history, which might suggest that family history may not be a significant factor in these conditions.

Imaging and laboratory differences are important differentiation measures that aid in refining diagnoses. Characteristic imaging patterns, such as callososeptal interface lesions in MS, diffuse white matter lesions in ADEM, and posterior fossa hyperintensities in MOGAD, provide important diagnostic markers [ 16 ]. Laboratory findings, including a higher prevalence of CSF leukocytosis in MOGAD, underscore the role of thorough diagnostic workups in identifying specific ADS subtypes. These clinical and diagnostic insights are essential for developing tailored diagnostic approaches for these less prevalent pediatric disorders.

It worth mentioning that clinicians often face difficulties in differentiating between CIS and other diagnosis such as MS, MOGAD, and NMOSD because of the inherent overlap in their clinical presentation [ 17 ]. However, in our cohort, all patients with CIS underwent CSF analysis and MOG-IgG antbodies testing in order to exclude other diagnoses. Large, bilateral, poorly defined lesions affecting both white and gray matter are common features seen in ADEM. Patients with MOGAD frequently exhibit longitudinally widespread optic neuritis or myelitis along with symptoms resembling ADEM. MS lesions are characterized by distinctive Dawson’s fingers, are smaller, well defined, and frequently periventricular or juxtacortical. Differential diagnosis is guided by these MRI patterns. This highlights the importance of performing comprehensive diagnosis for all patients presenting with monophasic demyelinating events and not basing decisions solely on the clinical features of the patients [ 18 – 22 ].

Lumbar puncture was not performed as a routine investigation for all patients in our cohort. Clinical presentation and radiological results were the main factors considered when making decisions and diagnoses. Among those who underwent CSF analysis, leukocytosis was more common in the MOGAD group (3 out of 5 patients), consistent with findings from other studies, suggesting underlying pathophysiological differences in MOGAD [ 20 ]. CSF oligoclonal bands (OCBs) were primarily observed in the MS group, with 9 out of 14 patients with MS testing positive. Interestingly, only one patient from the non-MS groups (a patient with MOGAD) tested positive for CSF OCBs. A previous study in Japan found that MOGAD cases with OCB positivity had a higher tendency for recurrence. In our cohort, the patient with MOGAD remained monophasic during the follow-up period [ 23 ].

The primary treatment during the first attack in almost all patients was pulse steroid therapy, with 66.7% of patients with MS receiving it. IVIG usage varied significantly, being most frequently used in the MOGAD (80%) and ADEM (66.7%) groups, and less so in CIS (14.3%) and patients with MS. PLEX was predominantly used in patients with ADEM and minimally in MS, with no use in the other groups. Second-line therapy, primarily rituximab, was administered to some patients across all groups except CIS, with the highest use in MOGAD for acute therapy and in MS for maintenance disease-modifying therapy. The selective use of therapies like PLEX and rituximab in specific ADS groups aligns with existing treatment protocols, reflecting disease severity and relapse rates. The treatment of ADS depends on the specific disorder, its severity, and symptom duration. First-line therapies often include corticosteroids to reduce inflammation, while plasma exchange may be utilized to remove pathogenic antibodies. Immunomodulatory drugs are used to prevent relapses or treat acute attacks [ 10 , 24 ]. Symptomatic treatments and rehabilitation therapies are also integral to improving patient quality of life. For conditions like MS, disease-modifying therapies aim to slow disease progression and prevent relapses by altering immune system activity [ 25 , 26 ].

Outcomes were assessed using the EDSS at the last follow-up. The ADEM group had the highest EDSS score, with one patient reaching a score of 5, indicating significant disability. Both CIS and MOGAD exhibited similar EDSS distributions, reflecting moderate levels of disability, while the MS group had a low mean EDSS score with a median of 0, suggesting minimal or no disability in most patients. The lack of statistical significance in EDSS scores across groups suggests that differences in disability levels may be due to random variation rather than true differences in disease severity. It is worth noting that the variability in follow-up periods and patient dropouts might have influenced these results. We tried to further analyze the outcome by addressing the residual deficit in each group, in MS, EDSS of 1 “abnormal signs only” was the most common residual deficit, indicating persistent neurological signs without clear functional deficits. The CIS group showed an equal prevalence of motor deficits and bladder dysfunction mainly in patients with transverse myelitis.

While the MOGAD group was uniquely associated with cognitive deficits, this was observed in only one patient who underwent neuropsychological testing. This finding suggests a potential impact of MOGAD on cognitive function. A recent 2024 study further supports this association, reporting that patients with MOGAD disease exhibited significant reductions in visuomotor processing speed and semantic fluency, particularly in cases with cerebral lesions. Similarly, the patient in our cohort demonstrated cerebral/cortical lesions and had epilepsy, aligning with these findings [ 27 , 28 ]. This highlights the need for cognitive assessments in patients with MOGAD disease, especially those with cerebral involvement, to guide early interventions and improve outcomes.

In summary, our study provides valuable insights into the demographics, clinical characteristics, laboratory findings, treatment approaches, and outcomes of pediatric ADS. The findings underscore the importance of recognizing specific patterns in age at onset, presenting symptoms, and treatment responses. Although some differences in outcomes were observed among the ADS types, further research with larger cohorts and standardized follow-up is needed to better understand the long-term implications of these conditions. Our study contributes to the growing body of literature on pediatric ADS, emphasizing the need for early recognition and tailored management strategies to optimize patient outcomes.

Limitations and Future Directions

The limitations of this study include potential biases due to missing data and the relatively small sample size, which reduces the statistical power, possibly obscuring meaningful differences between groups, and limits the generalizability of the findings and the ability to detect significant differences between subtypes. Variability in follow-up periods could have impacted the assessment of long-term outcomes, and the lack of standardized follow-up times may have influenced the reported EDSS scores, complicating comparisons across ADS subtypes. Additionally, we were unable to assess the effects of specific treatments on outcomes as a result of variability in treatment strategies and the study’s retrospective design. Other limitations are the lack of data related to number of leukocytes for each condition and number of patients with a clear intrathecal synthesis of OCB (pattern 2 and 3).

Future studies with standardized treatment protocols and prospective designs are needed to identify optimal management strategies for each ADS subtype. To further advance knowledge, larger, multicenter, longitudinal studies with more diverse cohorts should focus on capturing comprehensive clinical data with standardized follow-ups. This would help clarify the natural history of these conditions, identify biomarkers for early diagnosis, and refine treatment protocols to improve patient outcomes.

Conclusion

This study provides a comprehensive analysis of pediatric ADS, revealing key differences and similarities among MS, ADEM, CIS, and anti-MOGAD. Significant variations in age of onset were observed, with MS presenting later than CIS and MOGAD. These variations help guide differential diagnosis and enable better counselling regarding the risk of recurrence. Additionally, the statistical differences in the types of first attacks across MS, CIS, and MOGAD highlight the importance of comprehensive clinical evaluations for early and accurate diagnosis. Differences in attack frequency and residual deficits across ADS subtypes, particularly the more variable course of MS, have important implications for long-term management. Individualized treatment strategies based on specific clinical presentations and disease patterns are critical to optimizing outcomes. To further improve management strategies and patient outcomes, ongoing research with long-term follow-up studies and larger cohorts is essential for understanding the natural course and therapeutic needs of pediatric ADS.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 1470 KB)

Author Contributions

Mohammed Almuqbil, Lama Aljomah, Nora Almahmoud, Waleed Altuwaijri, Ahmad Alrumayyan, Muhammad T. Alrifai contributed to the study investigation and manuscript writing and revision. Mohammed Almuqbil, Waleed Altuwaijri, Ahmad Alrumayyan, Muhammad T. Alrifai contributed to supervision, data analysis, study conceptualization, and original draft writing. All the authors have read and approved the final manuscript and have agreed to be accountable for all aspects of the work.

Funding

No funding or sponsorship was received for this study or publication of this article. The Rapid Service Fee was funded by the authors.

Data Availability

All data are available from the corresponding author upon reasonable request.

Declarations

Conflict of Interest

Mohammed Almuqbil, Lama Aljomah, Nora Almahmoud, Waleed Altuwaijri, Ahmad Alrumayyan and Muhammad T. Alrifai have nothing to disclose.

Ethical Approval

The Ethics Committee of King Abdullah International Medical Research Center approved the study (NRC23R/344/06). This study was conducted in accordance with the Declaration of Helsinki and local regulations. Written informed consent was obtained from the parents or legal guardians of all patients included in the study.

References

Associated Data

Supplementary Materials

Supplementary file1 (PDF 1470 KB)

Data Availability Statement

All data are available from the corresponding author upon reasonable request.