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Spontaneous Recovery from Progressive Multifocal Leukoencephalopathy in a Patient with Non-Active Sarcoidosis

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Spontaneous Recovery from Progressive Multifocal Leukoencephalopathy in a Patient with Non-Active Sarcoidosis International Journal of Infectious Diseases 14S (2010) e313–e316 Contents lists available at ScienceDirect International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid Case Report Spontaneous recovery from progressive multifocal leukoencephalopathy in a patient with non-active sarcoidosis Annemarie Goldbecker a,*, Argyro Tountopoulou a, Ulrich Wurster a, Frank Donnerstag b, Almuth Brandis c, Catharina Bonnemann a, Karin Weissenborn a a Department of Neurology and Neurophysiology, Hannover Medical School, Carl-Neuberg Straße 1, 30625 Hannover, Germany b Institute for Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany c Institute for Pathology, Hannover Medical School, Hannover, Germany ARTICLE INFO SUMMARY Article history: We report the case of a 50-year-old female patient with non-active sarcoidosis and no kind of Received 24 February 2009 immunosuppression, admitted to our hospital because of increasing confusion and focal neurological Received in revised form 3 October 2009 deficits. Initially a tumor, herpes encephalitis, or neurosarcoidosis were suspected, but surprisingly Accepted 25 February 2010 biopsy revealed progressive multifocal leukoencephalopathy, additionally confirmed by JC-positive PCR Corresponding Editor: William Cameron, in cerebrospinal fluid. Cases of sarcoidosis and progressive multifocal leukoencephalopathy have been Ottawa, Canada reported before. This is the first case of a patient with no sign of active sarcoidosis and without immunosuppressive therapy who recovered spontaneously with a follow-up time of nearly 3 years. Keywords: ß 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. Progressive multifocal leukoencephalopathy Sarcoidosis Magnetic resonance imaging 1. Introduction methotrexate had been given from 1992 to 1993 and occasional therapy with corticosteroids between 1988 and 1997. Clinical Progressive multifocal leukoencephalopathy (PML) is a nor- examination revealed sensory–motor dysphasia, apraxia, sac- mally fatal demyelinating disease of the central nervous system, cadic eye movements, and rigor and tremor, especially on the caused by human polyomavirus JCV, rarely affecting immunocom- right side. petent persons. The seroprevalence of JCV is up to 80%; the route of Magnetic resonance imaging (MRI) demonstrated cortical and infection is unknown.1 We report the first case of a patient with subcortical hyperintense lesions predominately in the left no sign of active sarcoidosis and without immunosuppressive hemisphere on a T2-weighted fluid attenuated inversion recovery therapy who recovered spontaneously with a follow-up time of (T2-FLAIR) sequence. The fronto-temporal lesion on the left side nearly 3 years. included the U-fibers and showed minimal mass effect (Figure 1A). Diffusion weighted images (DWI) depicted restricted diffusion in 2. Case report the subcortical frontal white matter (Figure 1B). Gliomatosis cerebri was suspected and the patient was treated with A 50-year-old woman with speech disturbances and changes dexamethasone for reduction of edema. Thereafter she became psychotic with hallucinations, anxiety, and aggressive behavior. A of personality was admitted to our clinic in April 2006 under the suspicion of a brain tumor. An ambulant computer tomography second MRI one week later showed no significant differences. The suspected diagnosis was changed to encephalitis and a lumbar of the brain had already revealed a left fronto-parietal hypodense area. She had a 20-year medical history of sarcoidosis with puncture was performed. Cerebrospinal fluid (CSF) was normal with regard to cell count, cell differential, total protein concentra- pulmonary and joint involvement and had undergone resection of a basalioma 16 years ago. Immunosuppressive treatment with tion, and albumin quotient, but showed high intrathecal IgG (60%) and IgM (79%) synthesis and positive oligoclonal bands. Investiga- tion of the CSF for herpes simplex virus (HSV) type 1 found PCR to * Corresponding author. Tel.: +49 511 532 2391; fax: +49 511 532 3115. be borderline positive, though not quantifiable, and no intrathecal E-mail address: [email protected] (A. Goldbecker). antibody production against HSV, with an antigen antibody index 1201-9712/$36.00 – see front matter ß 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2010.02.2257 e314[(Figure_1)TD$IG] A. Goldbecker et al. / International Journal of Infectious Diseases 14S (2010) e313–e316 Figure 1. Magnetic resonance imaging (MRI) findings: (A) Early after admission T2-weighted fluid attenuated inversion recovery (FLAIR) showed cortical and subcortical hyperintense lesions in the left frontal lobe with minimal mass effect involving the U-fibers. (B) Diffusion weighted imaging (DWI) showed restricted diffusion in the subcortical white matter at the same level as in (A) with reduced apparent diffusion coefficient (ADC) values. (C) A follow-up MRI after one month depicted a cortical hyperintense cortex and subcortical edema involving the basal ganglia on T1-weighted images without contrast media. (D) With contrast media a juxtacortical enhancement was noted. (E) T2-weighted FLAIR one year after onset showed marked substance loss in the involved white matter with residual hyperintense signal consistent with gliosis. (F) Compared to (C) a marked volume loss of the cortex and subcortical white matter was seen one year after onset of symptoms. The hyperintense signal of the cortex was reduced. (AI) of 0.7 (normal: <1.5). Despite the equivocal findings, herpes and viral hepatitis were negative, as were intrathecal AI for encephalitis was assumed and the patient was treated with cytomegalovirus, measles, rubella, and varicella zoster virus. A acyclovir 10 mg/kg body weight for 14 days. As the patient’s follow-up MRI four weeks after the first one showed hyperintense condition continued to worsen, a second lumbar puncture was cortex in the frontal lobe without signs of hemorrhage or performed 11 days later. A slight pleocytosis with 10 Â 106 cells/l calcification on T2*-weighted images (Figure 1C). Cortical and (82% lymphocytes, 10% eosinophils) was found. Local IgG and IgM subcortical contrast enhancement including the U-fibers was synthesis was still increased at similar levels and oligoclonal bands noted (Figure 1D). were unaltered. Herpes encephalitis was now definitely excluded A stereotactic brain biopsy was then performed. Histology by a normal HSV antibody specificity index (ASI) and negative PCR, revealed inflammation with infiltration of mainly cytotoxic T- and neurosarcoidosis was subsequently considered. Tests for HIV lymphocytes and demyelination in the cortex and subcortex with [(Figure_2)TD$IG] Figure 2. Neuropathological findings: (A) Necrosis (*) with macrophage infiltration and marked gliosis with reactive astrocytes with prominent cytoplasm (b), as well as oligodendrocytes with abnormal big dark nuclei ( ) (hematoxylin–eosin, original magnification Â200). (B) Immunohistochemistry with positive reaction for SV40-antigen in astroglial cells. A. Goldbecker et al. / International Journal of Infectious Diseases 14S (2010) e313–e316 e315 astrogliosis (Figure 2A). Granulomas were not found. An immu- free, inactive sarcoidosis and PML, who improved without any nohistochemical assay was positive for Simian virus 40 (SV40) specific antiviral treatment, with a follow-up of nearly 3 years. No (Figure 2B). Antibodies against SV40 show cross-reactivity with similar case with similar clinical symptoms and course of disease the JC virus (JCV), the agent responsible for PML. After confirmation has been described in patients with a history of sarcoidosis, but has of JCV in the CSF by PCR, PML was finally diagnosed. A blood count been for example with leukaemia.13 and analysis of lymphocyte subpopulations and CD4/CD8 ratio Our patient was treated with acyclovir because of suspected (1.67, normal 0.9–1.70) were normal. No signs of progression of the herpes encephalitis. Acyclovir is used against infections with sarcoidosis could be detected. viruses of the herpes group; however there are no indications that Surprisingly the patient improved after the biopsy, while all it may also be active against JCV. medication had been stopped. Aphasia and motor functions The patient is now under olanzapine therapy. It has recently improved and she was completely oriented. Panic and aggression been reported that JCV uses the serotonergic receptor 5HT2A to attacks necessitated temporary treatment with olanzapine. Finally infect human glia cells.14 Antipsychotics have been considered to the patient was discharged to a rehabilitation clinic. be useful in PML therapy, with mirtazapine being the most used 15,16 17 Eight months later the patient developed a pneumonia, which drug. Olanzapine is also an antagonist at the 5HT2A receptor, was treated with antibiotics and for unknown reasons also with although not the most potent compared to other neuroleptics. The steroids. Thereby hallucinations, agitation, and confusion were blocking of the 5HT2A receptor by olanzapine may prevent a new again induced. Cessation of the steroid therapy and commence- eruption of infection in our patient. In our opinion the recurring ment of olanzapine quickly restored her former constitution and psychotic decompensations were not related to new inflammatory she was able to live alone with only minimal assistance. One year activity
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