ABSTRACT
Background
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system
(CNS) characterized by demyelinating lesions of the CNS, which cause focal neurological symptoms and signs disseminated in time and space. MS usually affects young adults between 20 and 40 years of age. However, 2%-10% of all MS patients have their first clinical event in childhood, therefore pediatric health care providers must be aware of the clinical features and management of this disease.
Despite increased awareness and research in the field of pediatric MS (pMS) in the past 10 years, the diagnosis of pMS remains a challenge due to overlapping signs and symptoms with other diseases.
Pediatric MS patients reach a comparable degree of disability 10 years earlier than patients with adult-onset of the disease. Therefore, early diagnosis and recognition of particular clinical characteristics associated with pMS is of importance for long-term management and patient well-being.
There are only few published studies in the field of pMS. There are no data about epidemiological and clinical characteristics of pMS in Slovenia.
The aim of this study was to evaluate the incidence of pMS in Slovenia and to describe
clinical, cerebrospinal (CSF) and magnetic resonance imaging (MRI) findings at the onset of MS in pediatric patients in Slovenia.
Hypothesis
We assume that incidence of pMS in Slovenia is in a range 0,15-0,6/100 000 children per year. We expect earlier onset of MS and more severe course of the disease in children with positive family history of demyelinating disease. We assume that children with MS have commonly an associated second autoimmune disease. We expect rare progression of acute disseminated encephalomyelitis to clinically definite MS and that younger patients with MS have more often polysymptomatic onset of the disease.
Methods
In this retrospective nation-wide study, we collected data from all patients with an established diagnosis of MS, whose first symptoms related to a demyelinating lesion appeared before 18 years of age and who were treated at the Department of Child, Adolescent and Developmental Neurology at the University Children’s Hospital Ljubljana between January 1, 1992 and June 30, 2017.
Department of Child, Adolescent and Developmental Neurology is the only department for treating patients with MS under 18 years in Slovenia, so this study includes the entire pMS population in Slovenia from the last 25.5 years.
All cases fulfilled McDonald’s diagnostic criteria, and the recommendations of the expert consensus for diagnosing pMS.
Case records were reviewed for gender, age at first symptoms of pMS, time to diagnosis, symptoms at onset, disease course at presentation (relapsing-remitting or progressive), family history of MS, associated secondary disease, cerebrospinal fluid (CSF) findings, magnetic resonance imaging (MRI) findings at the first demyelinating event and data about prescribed treatments. We have subdivided the patients into two age groups, the childhood-onset group (12 years or younger) and the adolescent-onset group (older than 12 years).
Student’s t-test was used for continuous data. Where data were not normally distributed, the Mann-Whitney U test was used for 2-group comparisons to get exact 2-tailed p values. A p value of <0.05 was considered as statistically significant.
To estimate the incidence of pMS in Slovenia, demographical data of the Statistical Office of the Republic of Slovenia were used.
Results
The estimated incidence of pMS in Slovenia is 0.66/100,000 children per year. Sixty-one patients were included in our study. There were 47 (77%) girls and 14 (23%) boys, median 15,4 years at disease onset. In 4 patients, onset of pMS was before the age of 12 years (childhood-onset pMS). Relapsing-remitting multiple sclerosis was most prevalent, with only 2 patients presenting with a primary progressive pMS. A concomitant autoimmune disease was found in 4 children (6% of patients). Out of 61 children, 11 (18%) had at least one first-degree family member with MS. The first presentation was polysymptomatic in 59% of patients, with motoric symptoms (48%), sensory disturbances (44%), cerebellar symptoms (33%), and brainstem symptoms (26%) as common initial manifestations. All patients in the childhood-onset group presented with polysymptomatic manifestation. Only 2 patients were initially diagnosed with acute disseminated encephalomyelitis (ADEM). In the cerebrospinal fluid, 88% of patients had positive oligoclonal bands, 58% mononuclear pleocytosis and 61% had an elevated IgG index. Brain magnetic resonance imaging (MRI) showed a predominant supratentorial involvement (100% of patients). Seventy percent of patients were treated with high dose corticosteroids at first relapse. Forty-six patients (75%) had received immunomodulatory therapy at some point during their disease. Concerning differences between the childhood-onset and adolescent-onset groups, the MRI and and CSF findings were similar in both groups.
Conclusions
Our study provides new data on pMS characteristics in Slovenia and, to our knowledge, this is the first study characterizing pMS in our country. The estimated incidence of pMS in Slovenia is in expected range and is very close to those previously reported in other countries. The clinical pattern of pMS in our cohort of patients was characterized by polysymptomatic presentation and predominantly sensory symptoms at onset, and with relapsing-remitting course of the disease. We could not confirm that genetic factor influences the age at the onset of the disease or the course of the disease.
These results may help increase awareness of pMS symptoms and age dependent risk for MS, subsequently leading to an early and correct diagnosis of pMS and early start of adequate treatment.
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