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The management of acute demyelinating attacks in the Swiss pediatric population
The management of an acute demyelinating attack in children is based on personal experience and
expert opinions. While the majority would agree to treat an acute demyelinating attack with i.v.
steroids, there is little consensus whether to taper or not with oral Prednisone. It is unknown if
we over treat these children if we taper them off or if we risk a relapse if we decide not to taper
them. I am interested in reaching a consensus for the most frequent demyelinating attacks in the
pediatric population. As a first step I aim to identify the practice in managing acute demyelinating
attacks here in Switzerland.
The use of oral prednisone taper in the management of acute demyelinating attacks in children
Demyelinating diseases are distinct entities amongst the inflammatory brain diseases (IBrainD)1. Myelin – the substantial part of the white matter of the CNS – is the target of the acute demyelinating attack. The etiology of an acute demyelinating attack is often para- /postinfectious or idiopathic. The latter are also known as primary inflammatory demyelinating diseases of the CNS. Pathophysiologically a disruption of the blood-brain- barrier leads to invasion of inflammatory cells and cytokines into the CNS leading to an inflammatory reaction, myelin edema and disruption of myelin2-4. If the inflammation hits eloquent regions in the CNS, the inflammatory process leads to clinical symptoms of the various acquired demyelinating syndromes.
The most common acquired demyelinating syndromes (ADS) are optic neuritis (ON), transverse myelitis (TM), and acute disseminated encephalomyelitis (ADEM)1. The incidence of an acquired demyelinating syndrome in childhood is 1/100’0005, 6, with approximately 25% of these patients being diagnosed with multiple sclerosis (MS) over the following 2-5 years. MS is the most common neurologic disease in the adult population with a prevalence of 150/100’000. In Switzerland, approximately 10’000 people have a diagnosis of MS. Pediatric onset MS, i.e. MS patients experiencing their first attack 18 years of age, accounts for approximately 3-5% of the total MS population7. The disease burden of pediatric onset MS has been realized over the past decade8. Pediatric onset MS is characterized by a higher relapse frequency compared to adult onset MS patients9, 10. The potentially devastating impact of relapsing inflammatory attacks to the developing brain has yet to be determined. Therefore, optimizing the management of acute demyelinating attacks is of utmost importance when caring for children and adolescents with demyelinating diseases.
The acute demyelinating attack – to taper or not to taper: that’s the questionEvidence based guidelines regarding the treatment of acute demyelinating attacks in the pediatric population are lacking. A consensus statement based on expert opinions recommends the use of high dose (20-30mg/kg/die) i.v. methylprednisolone (MP) for 3-5 days in the case of an acute demyelinating attack7, 11, 12. However, there is clinical equipoiseif an oral prednisone taper following the i.v. MP treatment has any influence on outcome. A recent study evaluating the management of pediatric CNS demyelinating disorders in the United States has shown, that an oral prednisone taper is considered by 50-60% of the treating neurologists in patients suffering from ON, TM, ADEM or relapsing MS11. However, recommendations differ amongst centers and continents. While the IPMSSG (International Pediatric MS Study Group) recommends a prednisone taper for those patients not fully recovered after the i.v. MP course, the pediatric MS center in Göttingen (Germany) does not use a prednisone taper7.
A retrospective study on adult MS patients even concluded that the use of an oral prednisone taper after i.v. MP did not improve disability or recovery in MS related relapses13. If this also applies to pediatric MS patients, is unknown. The pathophysiologic rationale for an oral prednisone taper is relatively weak. From an endocrinological point of view, a treatment with high dose i.v. MP for 3-5 days does not – as previously thought – require a prednisone taper and can be easily discontinued14. The clinical hypothesis of preventing relapses by using an oral prednisone taper has never been investigated. The increased use of immunomodulatory treatment in patients with relapsing demyelinating attacks makes this hypothesis more and more questionable. Prolonged steroid treatment is known for its side effects such as weight gain, elevated blood pressure, hyperglycemia, and sleep/mood disturbances15, 16. Furthermore, steroid treatment is known to cause brain atrophy which is thought to be temporary17, 18. The impact of oral prednisone taper on brain atrophy is unknown. However, it is important to avoid unnecessary prolonged steroid treatment.
In summary, the treatment regimen of an acute demyelinating attack in the pediatric population – especially the role of oral prednisone taper – needs further assessment. To improve the care of children and adolescents with acute demyelinating attacks it is important to identify and distinguish patients who will benefit from a prolonged steroid treatment form those where a prednisone taper is unnecessary. Questions arising in this context are: Does an oral prednisone taper have any beneficial influence on outcome in pediatric patients suffering from an acute demyelinating attack? Which patients with an acute demyelinating attack will benefit from an oral prednisone taper? Does the oral prednisone taper have any influence on the degree of steroid induced brain atrophy? These questions are ideally answered with a randomized controlled non-inferiority trial. However,the current local (=European) management of acute demyelinating attacks in children and the agreement on key components of the trial have to be identified first.
Given the low incidence of pediatric demyelinating diseases, an international multicenter approach is needed. A parent’s willingness to enroll a child in such a trial is influenced by the recommendation of the treating physician19. A strong commitment is necessary for broad enrolment, requiring a high agreement amongst the specialists on inclusion criteria, treatment regimen and outcome assessment to be used in the trial. Therefore, a two-step approach will be performed in preparation of the trial.
Aim 1: To evaluate the current management of pediatric acute demyelinating attacks
Aim 2: To develop consensus on a randomized controlled trial protocol assessing the role of oral prednisone taper in acute pediatric demyelinating attacks
By Sandra Bigi, MS Msc and Seline Hofer, cand.med
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