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NEUROLOGY 2008;71:1361-1367
© 2008 American Academy of Neurology

Cerebellar leukoencephalopathy

Most likely histiocytosis-related

M. S. van der Knaap, MD, PhD, W.F.M. Arts, MD, PhD, J. Y. Garbern, MD, PhD, G. Hedlund, DO, F. Winkler, MD, C. Barbosa, MD, M. D. King, FRCPI, FRCPCH, A. Bjørnstad, MD, N. Hussain, MRCPCH, M. K. Beyer, MD, PhD, C. Gomez, MD, M. C. Patterson, MD, P. Grattan-Smith, MD, M. Timmons, MD and P. van der Valk, MD, PhD

From the Departments of Child Neurology (M.S.v.d.K.) and Neuropathology (P.v.d.V.), VU University Medical Center, Amsterdam, The Netherlands; Department of Pediatric Neurology (W.F.M.A.), Erasmus Medical Center–Sophia Children’s Hospital, Rotterdam, The Netherlands; Department of Neurology and Center for Molecular Medicine and Genetics (J.Y.G.), Wayne State University, Detroit, MI; Pediatric Medical Imaging Department (G.H.), Primary Children’s Medical Center, Salt Lake City, UT; Department of Neurology (F.W.), Ludwig-Maximilians University, Munich, Germany; Department of Pediatrics (C.B.), Neuropediatrics Unit, Hospital Pedro Hispano, Matosinhos, Portugal; Department of Neurology (M.D.K.), Children’s University Hospital, Temple St Dublin, Ireland; Division of Paediatrics (A.B.), Rikshospitalet University Hospital, Oslo, Norway; Department of Paediatric Neurology (N.H.), Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, Nottingham, UK; Department of Radiology (M.K.B.), Stavanger University Hospital, Stavanger, Norway; Department of Neurology (C.G.), University of Chicago Medical Center, IL; Departments of Neurology, Pediatric and Adolescent Medicine, and Medical Genetics (M.C.P.), Mayo Clinic, Rochester, MN; Department of Neurology (P.G.-S.), Sydney Children’s Hospital, Randwick, Australia; and Developmental and Metabolic Neurology Branch (M.T.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

Address correspondence and reprint requests to Dr van der Knaap, Department of Child Neurology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ms.vanderknaap{at}vumc.nl

Background: Histiocytosis, both Langerhans and non-Langerhans cell type, can be associated with cerebellar white matter abnormalities, thought to be paraneoplastic. The associated clinical picture consists of ataxia, spasticity, and cognitive decline. Hormonal dysfunction is frequent. MRI shows cerebellar white matter abnormalities, as well as brainstem and basal ganglia abnormalities. This so-called "neurodegenerative syndrome" may occur years before or during manifest histiocytosis and also years after cure. We discovered similar MRI abnormalities in 13 patients and wondered whether they could have the same syndrome.

Methods: We reviewed the clinical and laboratory information of these 13 patients and evaluated their brain MRIs. Seven patients underwent spinal cord MRI.

Results: All patients were isolated cases; 10 were male. They had signs of cerebellar and pyramidal dysfunction, behavioral problems, and cognitive decline. MRI showed abnormalities of the cerebellar white matter, brainstem, basal ganglia, and, to a lesser extent, cerebral white matter. Three patients had spinal cord lesions. Three patients had laboratory evidence of hormonal dysfunction. No evidence was found of an underlying metabolic defect. In two patients biopsy of nodular brain lesions revealed histiocytic infiltrates.

Conclusions: Considering the striking clinical and MRI similarities between our patients and the patients with this neurodegenerative syndrome in the context of proven histiocytosis, it is likely that they share the same paraneoplastic syndrome, although we cannot exclude a genetic disorder with certainty. The fact that we found histiocytic lesions in two patients substantiates our conclusion. Patients with cerebellar white matter abnormalities should be monitored for histiocytosis.

Abbreviations: LCH = Langerhans cell histiocytosis; nLCH = non-Langerhans cell histiocytosis.

Supplemental data at www.neurology.org

M.S.v.d.K. is supported by the Dutch Organization for Scientific Research (ZonMw, TOP grant 9120.6002) and the Optimix Foundation for Scientific Research. J.G. is supported by the National Multiple Sclerosis Society (RG3204).

Disclosure: The authors report no disclosures.

Received April 5, 2008. Accepted in final form July 16, 2008.






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