Discussion

Multiple sclerosis is a chronic inflammatory and demyelinating disease of the central nervous system that usually occurs in young adults in the 3rd and 4th decades. Sometimes, the first symptoms appear before the age of 18. The form of disease appears before age of 18 is called paediatric multiple sclerosis. In the review of Brola and Steinborn in 2020, it was reported that 3–5 % of multiple sclerosis patients started in childhood. ^{Reference Brola and Steinborn1} In 2009 Gorman et al., in their comparative study, stated the features that distinguish paediatric multiple sclerosis from adult multiple sclerosis. It is typical that the course of the disease is in the form of relapsing–remitting. The primary progressive form is very rare. The interval between disease onset and subsequent recurrences is shorter. It has a higher recurrence rate compared to adult multiple sclerosis. ^{Reference Gorman, Healy, Polgar-Turcsanyi and Chitnis2} The disease is relatively difficult to treat. The effectiveness of disease-modifying therapy drugs in children and adolescents is generally based on observational studies. Therefore, the number of drugs accepted for disease-modifying therapy is limited. In a multicentre study conducted in 2006, it was recommended to start the first-line treatment in pulse methylprednisolone with interferon beta or glatiramer acetate which is more safe. ^{Reference Banwell, Reder and Krupp3} Transition to second-line therapy should be considered in the presence of rapidly progressing severe multiple sclerosis or when the first-line therapy is not effective. Fingolimod is a second-line disease-modifying therapy agent approved by the FDA in 2008 for the treatment of children aged 10 years and older with relapsing–remitting form of disease. In a clinical study conducted in 2018, it was observed that fingolimod significantly reduced annual MRI activity and brain volume loss compared to interferon beta-Ia. However, it has been stated that the frequency of serious side effects can be seen. ^{Reference Chitnis, Arnold and Banwell4} While fingolimod pharmacologically exerts a non-selective agonistic effect on sphingosine-1 receptors, it shows functional antagonism to the sphingosine-1 receptors-1 subtype by inducing receptor down-regulation. ^{Reference Huwiler and Zangemeister-Wittke5} Fingolimod has been approved by the FDA and EMA in patients with relapsing–remitting paediatric multiple sclerosis. However; in a small patient population, transient asymptomatic bradycardia has been reported upon initiation of therapy. Asymptomatic bradycardia with or without atrioventricular block is usually self-limited. Petruzzo et al. reported that arrhythmia developed in the first 6 hours after the administration of the first oral dose of fingolimod in their case report in 2021. Therefore, they recommended that patients starting treatment should be monitored during this initial period to identify any changes in their electrocardiogram and heart rate which may require further treatment. ^{Reference Petruzzo and Lanzillo6} In addition, fingolimod is contraindicated in patients with cardiac diseases ranging from cardiac conduction defects to ischaemic heart disease and heart failure. ^{Reference Franklin, Happe, Dillman and Marshall7}

In the report of two cases by Zanetta et al. in 2021, it was stated that Fingolimod is an effective disease-modifying therapy agent especially in the control of relapsing–remitting paediatric multiple sclerosis disease. Fingolimod has an important place in clinical treatment, especially in paediatric age group, due to the lack of drugs with proven efficacy in resistant remitting–relapsing type multiple sclerosis disease. Close rhythm monitorisation is required, especially at the beginning of the first dose, to avoid complications related to rhythm disorders such as bradycardia with or without atrioventricular block, which is one of the predictable side effects of the drug and to give treatment when necessary. ^{Reference Zanetta, Filippi and Moiola8}