MOG Antibodies in Pediatric Neurology^[*]

Disorders associated with myelin oligodendrocyte glycoprotein antibodies (MOG abs) are the newest members in the growing family of inflammatory demyelinating syndromes. In their review, “MOG spectrum disorders and role of MOG antibodies in clinical practice” in this issue of Neuropediatrics, Hennes and coworkers provided an excellent overview of the current knowledge on the clinical significance of MOG abs in pediatric neurology.[1] While several important aspects of MOG spectrum disorders are still unclear, many studies, including several by Hennes and coworkers, have helped to clarify some issues.

Clinical spectrum: MOG abs can be detected in monophasic demyelinating disorders particularly in acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis (TM), and neuromyelitis optica (NMO). In the majority of these patients, MOG abs decline to an undetectable level in the months following the acute attack and outcome is favorable in most cases. In a group of patients, for reasons unknown so far, MOG abs persist and the majority of these patients experience a recurrent demyelinating disorder. In children under 5 years of age, the most frequent presentation is recurrent ADEM, while in older children and adolescents, recurrent ON, TM, or NMO is more common. However, a combination of these syndromes or the switch from one to other is also possible. The interval between the attacks is extremely variable ranging from months to years. In patients with recurrent disease, the outcome is less favorable than observed in the monophasic syndromes, as recurrent attacks may lead to accumulating disability, such as paresis, ataxia, or functional blindness.

Diagnosis: MOG abs should be tested in serum using live cell-based assays. Unfortunately, this is currently not harmonized among diagnostic laboratories leading to conflicting results in many patients. On cranial MRI, widespread, poorly demarcated lesions, frequently without contrast enhancement, serve as the hallmark of MOG spectrum disorders. Typically, these lesions dissolve over time. On spinal MRI, longitudinal extensive transverse myelitis is frequent. CSF analysis often exhibits pleocytosis during an acute attack, while oligoclonal bands are negative in most patients. The latter is an important finding, as many patients with recurrent MOG spectrum disorders are falsely diagnosed with multiple sclerosis (MS) due to their often fulfilling the diagnostic criteria for MS. However, disease-modifying therapies used in the treatment of MS have been found ineffective in MOG spectrum disorders. A patient with suspected MS who is negative for oligoclonal bands in CSF should therefore be tested for MOG abs.

Therapy: Treatment of the acute attack in an MOG ab spectrum disorder, either monophasic or recurrent, is similar to that in MS or NMO. Intravenous steroids and intravenous immunoglobulins (IVIGs) are effective in most cases. In very severe cases or those without adequate improvement after steroid therapy, plasmapheresis or immunoabsorption is often beneficial.

Unfortunately, several important questions remain unanswered to date: First, how frequent are recurrent MOG spectrum disorders among pediatric patients with MOG abs? In a recent study by Jarius and coworkers on adult patients, 80% had a recurrent course, which increased to 92% in patients with long-term follow-up.[2] The numbers might be lower in pediatric patients, especially those aged < 5 years with ADEM; nevertheless, one has to assume that many patients will have recurrent disease. Second, is a recurrent MOG abs spectrum disorder self-limiting or is it a lifelong disease like MS? As MOG abs spectrum disorders were first described only in 2011, long-term follow-up is missing. However, Jarius and coworkers found in their cohort that the vast majority stayed positive for MOG abs during follow-up. Furthermore, they described patients with recurrent demyelinating events for up to 13 years, who were found positive for MOG abs.[3] I also know a patient with a MOG spectrum disorder who first manifested with ADEM at the age of 8 years and who now, at the age of 21 years, still has frequent attacks of ON indicating that at least a subset of patients have a long-lasting disease course. Disease duration, obviously, has important implications for the third so far unanswered question: How to treat recurrent MOG abs spectrum disorders on a long-term basis? Hennes and coworkers suggest regular IVIG as maintenance therapy; however, in my experience, which is similar to the descriptions of Jarius and coworkers, most patients will experience breakthrough attacks despite long-term immunotherapy, including regular IVIG. Most likely, a personalized treatment regime, taking into account both severity and frequency of the attacks, should to be developed.

In short, we know how to diagnose MOG abs spectrum disorders and have gained considerable knowledge about their clinical spectrum. Furthermore, we possess sufficient knowledge to treat the acute attack. However, we still are not aware of the long-term prognosis of recurrent MOG abs spectrum disorders and are still very unsure about the most adequate long-term treatment approach.

^* This article is an editorial comment on “MOG Spectrum Disorders and Role of MOG-Antibodies in Clinical Practice” by Hennes et al (Neuropediatrics 2017; doi: 10.1055/s-0037-1604404).

• References

• 1 Hennes E, Baumann M, Lechner C, Rostásy K. MOG spectrum disorders and role of MOG antibodies in clinical practice. Neuropediatrics 2017 DOI: 10.1055/s-0037-1604404
• 2 Jarius S, Ruprecht K, Kleiter I. , et al; In cooperation with the Neuromyelitis Optica Study Group (NEMOS). MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation 2016; 13 (01) 280
• 3 Jarius S, Ruprecht K, Kleiter I. , et al; In cooperation with the Neuromyelitis Optica Study Group (NEMOS). MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflammation 2016; 13 (01) 279