LETTERS:

PUBLISHED

Paraneoplastic Movement Disorders in Childhood Bohrer et al.1 present an interesting pediatric case of chorea/dystonia associated with a cardiac fibroelastoma, which resolved after tumor resection. A few comments deserve mentioning. First, paraneoplastic syndromes are indeed rare, but the authors’ assertion that literature/data on childhood paraneoplastic syndromes with movement disorders are scarce is overstated. Opsoclonus-myoclonus syndrome (OMS) is the best known, most studied, prototypic, paraneoplastic movement disorder in childhood.2 Acute gait ataxia and irritability are the earliest signs, followed by myoclonus, involuntary darting eye movements, insomnia, and dysarthria. Later, attention deficit disorder and cognitive impairment may appear. In contrast to adult-onset OMS, the only commonly associated tumor in pediatric OMS is neuroblastoma, which is located along the sympathetic chain. We have now reported data on more than 300 new cases of pediatric OMS, reviewed 200 cases in the world literature, and published patient videotapes in several journals, including this one.3 Second, how typical was the authors’ predicament: an apt clinical diagnosis of “paraneoplastic” in the setting of a tumor without corroborating immunological evidence? Although most neurological paraneoplastic syndromes are immunologically mediated, routine studies for autoimmune markers, even paraneoplastic antibodies and oligoclonal bands, can be negative. In this patient, the syndrome resolved with surprising rapidity without immunotherapy, which is unusual, although not unheard of. Immunological staining of the tumor was not reported, but some tumors in paraneoplastic syndromes display lymphocytic infiltration. The case illustrates the difficulty in searching for neuroinflammation with sole reliance on routine laboratory testing. Third, there are better options for detecting neuroinflammation in such cases. In OMS, neuroinflammation can be systematically “staged” by flow cytometry to identify lymphocyte subsets in cerebrospinal fluid (CSF), despite the absence of pleocytosis.4 A biomarker-guided approach represents a paradigm shift in thinking about OMS, rather than relying on empiric use of conventional immunotherapy. This strategy identified increased CSF B-cell frequency, B-cell attractant-1 (CXCL13), and B-cell-activating factor (BAFF)

ARTICLE

as biomarkers of disease activity,5 as well as T-cell dysregulation. The biomarker approach led to the introduction of anti-B-cell therapy, which confers long-lasting depletion of CSF B-cells. The multimodal combination as “FLAIR” immunotherapy (front-loaded adrenocorticotropic hormone, intravenous immunoglobulin, rituximab) for OMS is particularly effective at inducing neurological remission early in the disease,3 which has been confirmed in a phase I/II clinical trial. Finally, we advocate biomarker approaches in the investigation of pediatric paraneoplastic disorders. They may have provided useful information in this case. Immunophenotyping of CSF lymphocytes can be performed at most medical centers that routinely use flow cytometry and follow our published method,4 and it is billable to insurance. Regarding the other biomarkers, which are not commercially available, our laboratory can lend assistance in paraneoplastic cases. Michael R. Pranzatelli, MD, 1,2,3* and Elizabeth D. Tate, FNP-C, MN1,3 1 National Pediatric Myoclonus Center, Southern Illinois University School of Medicine, Springfield, Illinois, USA 2 Neuroimmunology Laboratory, Southern Illinois University School of Medicine, Springfield, Illinois, USA 3 Department of Neurology, Southern Illinois University School of Medicine, Springfield, Illinois, USA

References 1.

Bohrer S, De La Villeon G, Carneiro M, et al. Acute-onset chorea, dystonia, and cardiac fibroelastoma in a child: a paraneoplastic association? Mov Disord 2013;28:250-251.

2.

Pranzatelli MR, Tate ED. Opsoclonus-myoclonus syndrome. In Russell CD, Vincent A. editors. Clinics in Developmental Medicine No. 184-185. Inflammatory and Autoimmune Disorders of the Nervous System in Children, Chapter 10. London, UK: Mac Keith Press/Cambridge University Press; 2010:152-173.

3.

Pranzatelli MR, Tate ED, Swan JA, et al. B cell depletion therapy for new-onset opsoclonus-myoclonus. Mov Dis 2010;25:238242.

4.

Pranzatelli MR, Travelstead AL, Tate ED, Allison TJ, Verhulst SJ. CSF B-cell expansion in opsoclonus-myoclonus syndrome: a biomarker of disease activity. Mov Dis 2004;19:770-777.

5.

Pranzatelli MR, Tate ED, McGee NR, et al. Key role of CXCL13/ CXCR5 axis for cerebrospinal fluid B cell recruitment in pediatric OMS. J Neuroimmunol 2012;243(1-2):81-88.

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*Correspondence to: Dr. Michael R. Pranzatelli, Founder and Director, National Pediatric Myoclonus Center, SIU School of Medicine, PO Box 19643, Springfield, IL 62794-9643; [email protected]

Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 4 March 2013; Revised: 10 April 2013; Accepted: 20 October 2013 Published online 4 November 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25743

Movement Disorders, Vol. 29, No. 2, 2014

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Paraneoplastic movement disorders in childhood.

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