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ARTICLES: M. S. van der Knaap, W.F.M. Arts, J. Y. Garbern, G. Hedlund, F. Winkler, C. Barbosa, M. D. King, A. Bjørnstad, N. Hussain, M. K. Beyer, C. Gomez, M. C. Patterson, P. Grattan-Smith, M. Timmons, and P. van der Valk Cerebellar leukoencephalopathy: Most likely histiocytosis-related Neurology 2008; 71: 1361-1367 [Abstract] [Full text] [PDF]

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Cerebellar leukoencephalopathy: Most likely histiocytosis-related

Brett J. Theeler   (16 January 2009)

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Marjo S. van der Knaap   (16 January 2009)

Cerebellar leukoencephalopathy: Most likely histiocytosis-related 16 January 2009
Brett J. Theeler, Department of Medicine, Neurology Service, Madigan Army Medical Center 9040A Fitzsimmons Drive, Tacoma, WA 98431 Send Correspondence to journal: Re: Cerebellar leukoencephalopathy: Most likely histiocytosis-related btheeler{at}hotmail.com Brett J. Theeler	I read the article by van der Knaap et al. with great interest. [1] After six months of progressive dysarthria, dysphagia, and ataxia, a 59-year-old Caucasian man was transferred to our facility for further work-up for progressive leukoencephalopathy. He had stage III melanoma and a left axillary dissection 5 years prior. CT chest and fluorodeoxyglucose PET done 2 months after onset of neurologic symptoms showed increased uptake in the left axilla. Pathology from a repeat axillary dissection was negative for recurrence of melanoma. A CD 68 positive, histiocytic infiltrate was seen in the lymphoid tissues, but was felt to be a reactive process related to prior surgery (CD1a, S100 testing not performed). Surgical pathology from stereotactic biopsy of the right cerebellar white matter performed 5 months after onset of neurologic symptoms revealed demyelination and scattered perivascular and parenchymal CD8 positive lymphocytes. There was no evidence of neoplasia, infection, vasculitis, or granulomatous disease. Laboratory evaluations for paraneoplastic, inflammatory, infectious, nutritional, metabolic, and degenerative disorders were unremarkable. A lumbar puncture including cytology revealed mildly elevated protein. The patient had refractory hyponatremia and hyperprolactinemia suggesting hypothalamic-pituitary dysfunction. Brain MRI revealed T2 hyperintensities in the pontine tegmentum, middle and superior cerebellar peduncles, and in the cerebellar white matter, predominantly in the dentate hilus with no significant cerebellar atrophy. These areas enhanced heterogenously. Cortical T1 hyperintensities were seen in the right mesial and anterior temporal region with no mass effect. The patient received pulsed IV steroids, 6 weeks of oral steroids, and 2 grams per kilogram of IV immune globulin. The patient continued to worsen and became bed-bound. Two months after admission, MRI revealed worsening of the patient’s leukoencephalopathy with extension to the midbrain, basis pons, and upper medulla. Repeat fluorodeoxyglucose PET revealed diffuse uptake in the right temporal lobe, brainstem, cerebellum, spleen, adrenals, and kidneys consistent with a systemic inflammatory process. The patient deferred any further evaluation and died one year after the onset of neurologic symptoms. The neuroimaging and neuropathology in our case, particularly the involvement of the dentate hilus and the supratentorial T1 hyperintensities, are similar to those patients observed in van der Knaap et al’s study. The histiocytic infiltrate seen on the axillary biopsy was considered benign but a histiocytosis was not excluded. I believe our patient had a paraneoplastic leukoencephalopathy, most likely histiocytosis-related, followed by systemic involvement with a more fulminant clinical course than seen by the authors. [1] References 1. van der Knaap MS, Arts WF, Garbern JY, et al. Cerebellar leukoencephalopathy: most likely histiocytosis-related. Neurology. 2008;71:1361-1367. Disclosure: The author reports no disclosures.
Reply from the author 16 January 2009
Marjo S. van der Knaap, Department of Child Neurology, VU University Medical Center De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands Send Correspondence to journal: Re: Reply from the author ms.vanderknaap{at}vumc.nl Marjo S. van der Knaap	We appreciate Dr. Theeler’s interest in our article. We agree with the conclusion that his patient had a clinical picture and MRI findings similar to our patients. [1] In his patient, axillary dissection revealed a histiocytic infiltrate in the lymphoid tissues, biopsy of the right cerebellar white matter demonstrated myelin loss and scattered perivascular and parenchymal CD8 positive lymphocytes without evidence of neoplasia, infection, vasculitis or granulomatous disease. These histopathologic results are consistent with those seen in our patients. [1] The findings in Dr. Theeler’s patient further confirm our conclusion that cerebellar leukoencephalopathy can be histiocytosis-related. [1] Disclosure: The author reports no disclosures.