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New ways to speed up the diagnosis and treatment of severe pediatric neurological diseases

Study shows immunotherapy to be effective in MOG antibody-positive neurology patients.

Researchers at SJD Barcelona Children's Hospital and Hospital Clínic-IDIBAPS have led a study showing that the detection of an antibody against myelin oligodendrocyte glycoprotein (MOG) improves diagnosis and treatment in a group of severe childhood neurological diseases. The work has been published by the scientific journal The Lancet Neurology.

The coordinators of the study are Thaís Armangué, head of the Neuroimmunology Unit at SJD, and Josep Dalmau, coordinator of the SJD Barcelona Children's Hospital and Hospital Clínic Neuroimmunology Programme and Catalan Institution for Research and Advanced Studies (ICREA) lecturer for the August Pi i Sunyer Biomedical Research Institute (IDIBAPS).

The researchers concluded that the MOG antibodies are associated with a larger number of serious pediatric autoimmune neurological disorders than previously thought. This means not only demyelinating diseases but also the different types of encephalitis. "Although we have increased understanding of the syndromes associated with MOG antibodies in children, we have yet to identify the full range of diseases they cause", says Josep Dalmau.

Over the last ten years, a large number of studies have found MOG antibodies to be associated with different demyelinating diseases, including optic neuritis, myelitis and acute disseminated encephalomyelitis (ADEM), and determined that these patients often improve with immunotherapy.

Until a decade ago, it was believed that children with these demyelinating diseases had atypical forms of multiple sclerosis and they were not therefore treated properly.

MOG antibodies damage the protective covering (myelin sheath) that surrounds nerve fibres in the brain, optic nerves and spinal cord, meaning the nerves cannot effectively transmit messages. Poor transmission can cause loss of vision and impaired coordination and sensitivity

According to Thaís Armangué, many children only experience one episode caused by MOG antibodies and have no further symptoms. "However, some patients may have new episodes months or even years later". 

Most children who tested positive for MOG antibodies responded to treatment with immunotherapy 

The researchers conducted a prospective study including 535 children (average age of 6 years) with demyelinating diseases of the central nervous system and encephalitis from 40 hospitals in Spain. Of these, 116 tested positive for MOG antibodies. Clinical and radiological characteristics were analysed and the patients were closely monitored for an average of 3 and a half years, assessing their response to treatment and any new episodes during follow-up.

Of the children who tested positive for MOG antibodies and received appropriate immunotherapy, 85% (99 out of 116) made a complete or almost complete recovery, although 15% (17) had moderate to severe disease-related sequelae, such as cognitive impairment, epilepsy or loss of vision.

"Many of these patients, especially those with encephalitis, would not have been diagnosed if it were not for the prospective design of our study", Armangué points out. "Identifying these patients is important because most children who tested positive for MOG antibodies responded to treatment with immunotherapy". 

The research also showed that among patients with encephalitis, MOG antibodies were the most common biomarkers, more common than all the other neuronal antibodies combined. This suggests that the MOG antibody test should be performed on all children with encephalitis, after ruling out the most easily recognisable causes.

The findings also suggest that the youngest children with MOG antibody-related syndromes tend to have clinical features of ADEM, an inflammatory condition mainly affecting the brain. In contrast, older patients are more likely to have optic neuritis (loss of vision, eye pain) or myelitis (numbness, weakness in both legs).

Despite advances in the diagnosis of encephalitis, up to half of cases have no clear cause. "Our findings reveal that the spectrum of MOG-antibody disease is broader than previously thought and includes autoimmune encephalitis, as well as multiple demyelinating syndromes. In view of the results, the current classifications and terminology for syndromes associated with MOG antibodies need to be updated", concludes Josep Dalmau.