There is work left to do
BERLIN –
Michele G. Sullivan/MDedge News
Dr. Georgina Arrambide
The increased accuracy largely hinged on a positive finding of oligoclonal bands in cerebrospinal fluid – a diagnostic hallmark that was not included in the earlier criteria, Georgina Arrambide, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“Application to children of the new diagnostic criteria is limited,” said Dr. Arrambide, of the University Hospital Vall d’Hebron Multiple Sclerosis Centre of Catalonia, Barcelona. “And there are still some uncertainties with regard to fluid biomarkers and how they predict or confirm a diagnosis of MS in children, and also their relationship to the disease evolution.”
The updated McDonald criteria are intended to boost early, definitive MS diagnosis, leading to earlier initiation of therapy. They are intended primarily for patients aged 11 years and older who present with a typical clinically isolated syndrome and high probability of MS (Lancet Neurol. 2018;17[2]:162-73).
Dr. Arrambide and her colleagues used the revamped criteria to reassess MS diagnoses in a prospective Spanish cohort of children who experienced an acute first demyelinating event and were diagnosed with the 2010 criteria. The Kids-METOMS-MOGBCN Study enrolls children aged younger than 18 years within 1 year of a first acute demyelinating episode. It includes demographic, clinical, and imaging data, as well as data on oligoclonal bands and antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MoG). Of these fluid biomarkers, only oligoclonal bands are included in the new McDonald criteria.
The 55 children in Dr. Arrambide’s analysis were followed for a mean of 16 months. They included 25 (45%) girls with an overall median age of 6 years at the first acute event. Oligoclonal bands were present in 56%, and both anti-MoG and anti–aquaporin-4 antibodies in 82%.
All children had abnormal brain MRI at baseline, with about 33% having gadolinium-enhancing brain lesions. Spinal cord MRI was abnormal in 50%, with 39% having gadolinium-enhancing lesions. According to the 2010 criteria, only three had a definitive MS diagnosis at baseline. The diagnosis was acute disseminated encephalomyelitis in 51%, clinically isolated syndrome in 31%, radiologically isolated syndrome in 2%, and nonencephalopathic disseminated encephalomyelitis in the remainder.
At baseline, three of those had a definitive MS diagnosis, displaying dissemination in both space and time as required by both the 2010 and 2017 criteria. The addition of oligoclonal band positivity added one more patient over the 2010 criteria, and assessing the cohort with the complete 2017 criteria added three more definitive diagnoses. This was a significant increase in definitive MS diagnoses when compared against the earlier criteria (70% vs. 30%).
Diagnoses changed in 10 other patients during follow-up. The single patient with radiologically isolated syndrome was definitively diagnosed with MS. Of the seven with clinically isolated syndrome, six were diagnosed with MS and one with a relapsing optic neuritis. Of the 28 with a nonencephalopathic encephalitis, 2 were diagnosed with optic neuritis.
The study also confirmed the benefit of adding oligoclonal bands as a diagnostic marker in children. Of those with an MS diagnosis at last follow-up, 71% were positive for the cerebrospinal fluid finding, compared with just 4% of those with a non-MS diagnosis. However, none of those children had anti-MoG antibodies, compared with 58% of those with a non-MS diagnosis. None of the patients were positive for anti–aquaporin-4, regardless of diagnosis.
That finding does not necessarily mean that the absence of anti-MoG antibodies can rule out an MS diagnosis in children, Dr. Arrambide cautioned. Nevertheless, the finding is a useful clinical marker during a diagnostic work-up.
“The presence of oligoclonal bands and the absence of MOG-IgG are both useful biomarkers when evaluating the risk of MS in children with a first demyelinating event,” she said.
She disclosed financial relationships with several pharmaceutical companies.
SOURCE: Arrambide G et al. ECTRIMS 2018, Abstract 64