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CNS Factors in Children May Predict MS


In an analysis of data from a retrospective study, investigators describe how MRI and CSF data can help predict which children develop MS after a first attack of inflammatory demyelination.

Diagnosing multiple sclerosis (MS) in adults can be complicated, and even more so in children. Few studies have been conducted in children and some elements of the differential diagnosis are unique for young patients.


DR. ROGIER Q. HINTZEN said that in cases of suspected CNS demyelination in children, an MRI should be done and CSF should be examined for oligoclonal band testing.

Now, however, new findings in a retrospective study in the Sept. 23 issue of Neurology describe how MRI and CSF data can help predict which children develop MS after a first attack of inflammatory demyelination. These findings are similar to prognostic factors established in adults.

The study investigators, led by Rogier Q. Hintzen, MD, PhD, head of the MS Center at Erasmus University in the Netherlands, reported that at least three of the Barkhof and KIDMUS (Kids with Multiple Sclerosis) Study Group prognostic criteria for MS were highly specific and predictive of MS disease progression in children, 10 and older. [For more specifics, see “Prognostic Criteria for MS.”]

The criteria by Barkhof were 92 percent specific and for KIDMUS, 96-percent specific for MS progression. But both sets of criteria showed low sensitivity for MS progression in children younger than 10 years old.

Specifically, clinicians can look for such definite MS predictors as well-defined lesions, lesions perpendicular to the corpus callosum, monofocal onset, presence of CSF oligoclonal bands, and elevated IgG index — all prognostic factors in adults.

In children (but not adults) MS can cause a syndrome with fever, headache, and encephalopathy that mimics encephalitis, the study authors noted. In the current study, however, encephalopathy was not a statistically significant predictor for MS progression.

The take-home message for clinicians, according to Dr. Hintzen, is that in cases of suspected CNS demyelination, an MRI scan should be done and CSF should be examined for oligoclonal band testing, not only for differential diagnosis, but also to help distinguish monophasic variants from progressive, relapsing MS.

Several experts, who were not involved with the study, commented that although the ideal management for these children is still not clear, the results provide a major advance for detecting pediatric MS.


Investigators reviewed CSF and MRI data on 117 children, aged 16 or younger who had an attack compatible with a demyelinating CNS disease. After a mean follow-up of 54 months, nearly one-third of the 117 patients were diagnosed with MS.

Forty-six percent of the children had had an initial attack, or clinically isolated syndrome (CIS), involving single lesions in the optic nerve, brainstem, cerebellum, or spinal cord; 44 percent had a second attack and were diagnosed with MS.

Nearly 54 percent of the children had multiple CNS lesions, but only 21 percent of this group had a second MS-defining attack. Generally, these children were younger and they also had encephalopathy, fever, headache, seizures, and an infection four weeks prior to symptom-onset of the first attack.


Sean J. Pittock, MD, a specialist in autoimmune neurology at the Mayo Clinic in Rochester, MN, who was not involved in the study, said early prognostic factors for MS progression would be helpful for neurologists and also for patients — particularly because there is often debate about which immunodulatory therapies to use and when to start treatment.

“The most reasonable approach is to explain the options for low-risk CIS patients and allow them to make an informed decision, whether to commit to disease-modifying agents or follow a watchful clinical and radiologic approach,” Dr. Pittock said. High-risk patients, such as those with higher disease burden on imaging — more than nine T2 lesions and three periventricular lesions, infratentorial or juxtacortical — should be advised to consider immunomodulatory therapy.

Dr. Pittock pointed out those children with multiple lesions, even without encephalopathy, are unlikely to develop MS, according to the study. This, he said, “argues for a watchful waiting approach with clinical and MRI follow-up for those children.”

Lauren B. Krupp, MD, professor of neurology at the State University of New York at Stony Brook and director of the university's pediatric MS Center, said the study results will refine and strengthen the definitions of acute demyelinating events in childhood. But, she added, since the MRI and CNS predictors aren't absolute, they need to be communicated cautiously and clinical follow-up remains the standard for a definite diagnosis.

The study authors noted that strengths of the study included the substantial number of multicenter, young subjects and the inclusion of CSF data. But they acknowledged that, among limitations, the study was retrospective and there was no standardized protocol for the MRI and CSF testing.

Previous studies have reported that the absence of any lesion on brain MRI is the most favorable outcome measure in adults with CIS, Dr. Pittock said, but data regarding specific numbers of lesions in this study were lacking. Also, the study did not investigate whether the type of CIS (optic neuritis or transverse myelitis) or presence or absence of signs (such as focal weakness) were predictive of outcome.

Still, Dr. Hintzen said, this study sets the stage for more patient-oriented pediatric MS research in Europe and collaborations in North America. He noted that a nationwide Dutch multicenter study group is now confirmed.


  • On MRI, lesions perpendicular to the corpus callosum and other well-defined and small lesions were found significantly more often in children with MS.
  • Lesions of diameter more than 2 cm in the basal ganglia and thalamic regions were seen significantly less frequently in children with MS; this difference was seen only in children age 10 and older.
  • Elevated IgG CSF index — above 0.68 — was observed in 66 percent of the children diagnosed with MS, indicating its usefulness as a diagnostic tool. In adults, elevated CSF IgG index is also predictive of MS.


The Barkhof criteria, first developed by Frederik Barkhof, MD, and colleagues at the VU Medical Centre in Amsterdam, the Netherlands, include:

  • at least one gadolinum-enhancing lesion or at least nine
  • lesions on T2 weighted images;
  • at least three periventricular lesions;
  • at least one juxtacortical lesion;
  • at least one infratentorial lesion.

KIDMUS criteria include:

  • the presence of lesions perpendicular to the corpus callosum;
  • well-defined lesions on MRI, defined by an abrupt decrease in intensity of T2-weighted signal at the borderline between the lesion and surrounding brain tissue.


• Neuteboom RF, Boon M, Hintzen RQ, et al. Prognostic factors after a first attack of inflammatory CNS demyelination in children. Neurology 2008;71:967–973.
• Barkhof F, Fillipi M, Miller DH, et al. Comparsion of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 1997;120:2059–2069.
• Yann Mikaeloff, Adamsbaum C, Suissa S, et al., for the KIDMUS Study Group on Radiology. MRI prognostic factors for relapse after acute CNS inflammatory demyelination in childhood. Brain 2004;9:1942–1947.