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I would like to clarify several statements mistakenly attributed to me in my comments about a Sept. 23 study in Neurology by Rogier Q. Hintzen, MD, PhD, and colleagues (“CNS Factors in Children May Predict MS,” Oct. 6).

It is difficult to predict the course of a child with a clinically isolated demyelinating syndrome (CIS), and who will benefit most from early initiation of treatment. The study by Dr. Hintzen and colleagues provides further evidence that children with a monofocal CIS (rather than polyfocal) who have abnormalities found on head MRI (at least three positive Barkhof criteria) and elevated IgG indices in CSF are more likely to develop definite MS. In contrast, the authors showed that children with a polyfocal CIS accompanied by multiple CNS lesions — with acute disseminated encephalomyelitis (ADEM) or without encephalopathy — are less likely to develop MS (21 percent).

Since the advent of immunomodulatory therapy for MS, and recent trials reporting potential benefit of early treatment, considerable controversy has arisen regarding “who and when” to treat. This controversy is further fueled by disagreement concerning the magnitude of clinical benefit and long-term efficacy in terms of disability and quality of life, not to mention the cost and parenteral mode of administration. In sum these uncertainties make management of CIS a confusing topic for the practicing neurologist, and create significant anxiety for patients and their families.

An acceptable approach for low risk CIS patients may be to explain the options and allow the child and the parents to make an informed decision, whether to commit to disease-modifying agents or follow a watchful clinical and radiologic approach.

On the other hand, high risk patients, such as those reported by Hintzen and colleagues with monofocal CIS and higher disease burden on imaging (≥9 T2 lesions, ≥3 periventricular lesions, infratentorial or juxtacortical) should be advised to consider immunomodulatory therapy. Because children with a polyfocal CIS implicating multiple CNS lesions with ADEM or without encephalopathy have low likelihood of developing MS, a watchful waiting approach with close clinical and MRI follow up may be reasonable for those children. Assisting patients to make an informed decision should increase their compliance and satisfaction and decrease their uncertainty and anxiety. There is no doubt that larger, prospective studies will help clarify these issues.

Sean J. Pittock, MD

Department of Neurology, Mayo Clinic, Rochester, MN