Bassetti, C.

Fehr, J.

Hermann, D.

RERO DOC Digital Library

J Neurol (2005) 252 : 736–737DOI 10.1007/s00415-005-0744-9D. M. HermannJ. FehrC. L. BassettiEpstein Barr-virus (EBV)associated T-cell clonop-athy mimicking lymphom-atous meningitisReceived: 23 July 2004Received in revised form:17 November 2004Accepted: 23 November 2004Published online: 14 March 2005Sirs: Epstein Barr-virus (EBV)exhibits strong B-cell tropism. Inchronic EBV-infection, T-cells mayalso be affected, which oftenexpand monoclonally and thenmay progress into T-cell lymphoma[2, 3]. We describe a young femalewith EBV-associated T-cellclonopathy presenting twice withmonoclonal infiltration of cranialand spinal nerve roots, which havenot converged into lymphoma bynow after seven years.In 1997, the 20-year-old patientdeveloped fever (≤ 40°C), fatigue,hepatosplenomegaly and mildlymphadenopathy with pancytope-nia (Hb 8.3 g/dl, platelets 80000/µl,neutrophils 500/µl), mildly elevatedCRP (26 mg/l), increased gamma-globulins (22 g/l), thymidin-kinase(59.2 U/l), soluble interleukin-2receptor (sIL-2r) (10696 U/ml) andneopterin (56.9ng/ml). A macro-phage activation syndrome (char-acterized by elevated sIL-2r andneopterin) was suspected and abone-marrow biopsy performed,revealing massive hemophagocy-tosis. The patient was splenec-tomized. Southern blots revealedmonoclonal TCRβ-rearrangementwith singular restriction bandsidentical in bone-marrow, bloodand spleen, PCR singular TCRγ-amplifications identical in bloodand spleen. Based on pediatrictreatment schemes, aiming atmacrophage inhibition, low-doseVP16-chemotherapy (2 150 mg/m2) was initiated. Fever and in-flammation markers declined.Five weeks later, the patientdeveloped fever, ear-pain anddiplopia. Clinical examinationrevealed a mild meningism andright abducens nerve palsy. Threelumbal punctures showed mildpleocytosis (75/µl, reactive T-cells)and elevated protein (1.63 g/l).Blood EBV-VCA IgG/IgM and EBV-EBNA IgG titres were increased.Cranial MRI exhibited meningealcontrast-enhancement alongcranial nerves suggestive of lym-phomatous meningitis. Intrathecalchemotherapy with methotrexate(9 15 mg) and AraC (9 40 mg)was started, followed by dexam-ethasone. CSF cell-counts de-creased to 2/µl, CSF protein to0.49 g/l. Clinical symptoms andneurological abnormalities disap-peared.In 2002, hyposmia, hypoacusisand mild urinary disturbanceswere noted by the patient, followedby dizziness and gait disturbancesthree months later. On clinicalexamination, bilateral L3-S1deficits with areflexia and positiveLasegue’s sign were found. Bloodexaminations showed normal cell-counts and CRP, reduced gamma-globulins (1.5 g/l), increased sIL-2r(1359IU/ml) and neopterin (3.5 ng/ml), normal cyclin-D1 and positiveEBV-PCR (125 DNA copies/ml). Amild CSF pleocytosis (36 cells/µl,reactive T-cells) with elevated CSFprotein (2.6 g/l) and positive CSFEBV-PCR were found. Both theblood and CSF still exhibitedmonoclonal TCRγ-rearrangementwith identical clones as six yearsbefore. MRI revealed contrast-enhancement with dural broaden-ing around cranial and spinalnerve roots (Figure). In the absenceof lymphoma cells in three lumbarpuncture specimens, dexametha-sone (4 8 mg) and intravenousimmunoglobins (3 30 g) werestarted. Clinical symptoms rapidlyimproved. Today, fourteen monthslater, the polyradicular deficitshave normalized. The patientcomplains about mild dizzinessand (sensory) hearing difficulties.In our patient, the recurrentcranial and spinal nerve root in-filtrations reflect a steroid-respon-sive, EBV-related lymphoprolifera-tive disorder. The absence ofmalignant cells in the blood andCSF, the negative tumour markersand clinical course allow the exclu-sion of the presence of a T-celllymphoma. Neurological complica-tions sometimes occur in acute andreactivated EBV, but rarely inchronic active EBV-infection [1].Three patients with chronic activeEBV-infection and encephalitishave been reported [1, 4, 5]. Twopatients had fatal outcomes, allthree patients exhibited brainparenchymal involvement on MRI.Thus, this is the first report of iso-lated meningoradicular infiltrationin chronic active EBV-infection. Inour patient, a gammaglobulindeficiency was detected during thesecond disease manifestation,whereas the first episode developedshortly after chemotherapy. Thus,immunodeficiency may haveplayed a pathogenic role.Monoclonal T-cell expansionfollowing chronic EBV-infection iswidely regarded as a guaranteedprelude to malignant lymphoma. Inmost cases, this is indeed clearlythe case, although our patientshows that long-term survival ispossible in a subset of patients. Atpresent, our patient’s long termprognosis remains unknown. Inconclusion, meningeal monoclonalT-cell infiltration in the presence ofchronic active EBV-infectionshould not mislead one to thediagnosis of T-cell lymphoma,unless a cytological diagnosis isLETTER TO THE EDITORSJON 1744736_737_Hermann_JON_1744  02.06.2005  12:28 Uhr  Seite 736737made. Clinical manifestations maywell respond to steroids, allowingthe avoidance of chemotherapy.■ Acknowledgement We thank our Divi-sion of Neuroradiology (Director: Prof. A.Valavanis) for performing the MR studies.References1. Häusler M, Ramaekers VT, Doenges M,Schweizer K, Ritter K, Schaade L (2002)Neurological complications of acuteand persistent Epstein-Barr virus infec-tion in paediatric patients. J Med Virol68(2):253–2632. Kanegane H, Nomura K, Miyawaki T,Tosato G (2002) Biological aspects ofEpstein-Barr virus (EBV)-infectedlymphocytes in chronic active EBVinfection and associated malignancies.Crit Rev Oncol Hematol 44(3):239–2493. Kasahara Y, Yachie A (2002) Cell typespecific infection of Epstein-Barr virus(EBV) in EBV-associated hemophago-cytic lymphohistiocytosis and chronicactive EBV infection. Crit Rev OncolHematol 44(3):283–2944. Ohga S, Takada H, Honda K, Inamura T,Gondo K, Ohshima K, Yamamoto M,Hara T (1999) Central nervous systemT-cell lymphoproliferative disorder in apatient with chronic active Epstein-Barrvirus infection. J Pediatr Hematol Oncol21(1):42–465. Yamashita S, Murakami C, Izumi Y,Sawada H, Yamazaki Y, Yokota TA,Matsumoto N, Matsukura S (1998)Severe chronic active Epstein-Barr virusinfection accompanied by virus-associ-ated hemophagocytic syndrome, cere-bellar ataxia and encephalitis. Psychia-try Clin Neurosci 52(4):449–452Priv. Doz. Dr. D. M. Hermann () · C. L. BassettiDept. of NeurologyUniversity Hospital Zurich (USZ)Frauenklinikstr. 268091 Zurich, SwitzerlandTel.: +41-1/255-5526Fax: +41-1/255-4507E-Mail: dirk.hermann@usz.chJ. FehrDept. of Internal Medicine/HaematologyUniversity Hospital Zurich (USZ)Zurich, SwitzerlandFig. Gadolinium-enhanced T1-weighted MRI showing massive meningeal contrast enhancement (flashes) along cranial (A) and lumbar spinal (B) nerve roots736_737_Hermann_JON_1744  02.06.2005  12:28 Uhr  Seite 737

Epstein Barr-virus (EBV)associated T-cell clonopathymimicking lymphomatousmeningitis

http://doc.rero.ch/record/311218/files/415_2005_Article_744.pdf

Epstein Barr-virus (EBV)associated T-cell clonopathymimicking lymphomatousmeningitis

Abstract

Similar works

Full text

Available Versions

RERO DOC Digital Library