Multiple Sclerosis Risk After Childhood Optic Neuritis
Abstract & Commentary
By Wendy S. Vargas, MD
Instructor in Neurology in Pediatrics, Weill Cornell Medical College
Dr. Vargas reports no financial relationships relevant to this field of study.
Synopsis:Similar to adults, children with brain MRI abnormalities and positive oligoclonal bands at onset of optic neuritis are at high risk of developing multiple sclerosis.
Source: Heussinger N, et al. Predicting multiple sclerosis following isolated optic neuritis in children. Eur J Neurol 2013;20:1292-1296.
Optic neuritis is a common initial manifestation of multiple sclerosis (MS). Based on the Optic Neuritis Treatment Trial (ONTT), the 10-year risk of developing MS following optic neuritis is 56% if the baseline MRI shows a single brain lesion.1 However, this trial is not generalizable to children because only patients 18 years or older were included. Given the limited data in calculating pediatric MS risk, Heussinger et al recently reported on the role of brain MRI, oligoclonal bands (OCB), and visual evoked potentials (VEPs) as predictive markers for MS in children with optic neuritis.
This retrospective study included children between 4 and 17 years of age. Thirty-four children with isolated optic neuritis were identified from a pool of 159 total patients presenting with rapid onset visual failure. The authors used the 2005 McDonald criteria for the diagnosis of MS. Data were collected from the patient’s medical record or via telephone contact with the patient. MRI of the brain, VEPs, and lumbar puncture for examination of OCB were performed in all 34 children at onset of optic neuritis. Using the 2005 McDonald criteria, nine of the 34 patients converted to clinically definite MS. The authors analyzed whether age, sex, follow-up time, pathological VEPs at baseline, optic neuritis type (unilateral, bilateral, or recurrent), cranial MRI at baseline, and OCB at baseline could predict MS in this subgroup of patients. Following univariate analysis, only abnormal brain MRI and the presence of OCB were identified as significant predictors of disease progression to MS (odds ratio [OR], 20.5; 95% confidence interval [CI], 2.15-196.1; and OR, 12.0; 95% CI, 0.23-8.2, respectively). When multivariate analysis was performed, only abnormal brain MRI at baseline remained a statistically significant predictor of progression to MS (OR, 19.9; 95% CI, 1.8-219). VEPs at baseline were not a statistically significant predictor.
The rate of conversion to MS after childhood clinically isolated syndrome has not been clearly defined. This is the first study to specifically analyze the utility of brain MRI, OCB, and VEPs for predicting progression to clinically definite MS in children with optic neuritis. Clinically, such information is invaluable. As neurologists caring for these children, surely we will be asked to comment on this risk. This study lends credence to the importance of obtaining MRI and OCB after initial presentation with optic neuritis in children. Not surprisingly, these same tests are useful for risk stratification in older patients. In adults with optic neuritis, the presence of white matter lesions on brain MRI and OCB in the cerebrospinal fluid (CSF) were identified as risk factors for the development of MS by the ONTT study group.1 The results of the current study confirm the predictive value of brain MRI and OCB in optic neuritis patients under the age of 18. VEPs did not predict which children went on to develop MS after isolated optic neuritis. Similar VEP findings have been reported in adults.
A major strength of this study lies in the long-term follow-up of these children (mean 5 years), allowing for a quantitative MS risk prediction model after optic neuritis in a child. Nevertheless, the study is subject to certain limitations. First, it is a retrospective chart review. Moreover, for certain cases, data were obtained from the patient over the telephone and not the medical record. This study design can lend itself to recall bias. Second, selection bias is certainly a possibility as patients were screened from a child neurology unit and milder cases may not have been referred to a neurologist. Third, the small sample size led to very wide confidence intervals, making the real effects difficult to estimate reliably. Lastly, the authors claim that their findings have not been previously described in the literature. In a large, prospective, cohort study in a Canadian population of children with incident demyelination, MS was strongly associated with baseline MRI evidence of one or more brain lesions or CSF OCBs.2 Nevertheless, the current data suggest that cranial MRI and OCB form the basis of a prediction model through which pediatric patients’ risk of conversion to MS might be quantified. Large, multicenter, prospective studies in this area are needed.
- Beck RW, et al. High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: Experience of the Optic Neuritis Treatment Trial. Arch Ophthalmol 2003;121:944-949.
- Banwell B, et al. Clinical, environmental and genetic determinants of multiple sclerosis in children with acute demyelination: A prospective national cohort study. Lancet Neurol 2011;10:436-445.