key: cord-312167-d16ylykc
authors: Lazzarin, Serena Marita; Cannizzaro, Miryam; Russo, Tommaso; Sangalli, Francesca; Callea, Marcella; Colombo, Bruno; Moiola, Lucia; Filippi, Massimo
title: Successful treatment of HIV-associated tumefactive demyelinating lesions with corticosteroids and cyclophosphamide: a case report
date: 2020-11-03
journal: J Neurol
DOI: 10.1007/s00415-020-10296-6
sha: 
doc_id: 312167
cord_uid: d16ylykc

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and onconeural antibodies was negative. Search for VZV, CMV, EBV, syphilis (TPHA), HCV, HBV, M. tuberculosis was negative too. A 4th-generation HIV test was positive, subsequently confirmed by western blotting and polymerase chain reaction, showing plasma HIV-1-RNA levels of 87,900 copies/mL; serum CD4 count was 290/µL. Additional serological tests for toxoplasmosis and cryptococcosis were negative. Combined antiretroviral therapy (cART) with tenofovir alafenamide, emtricitabine and bictegravir was started.

Histology from stereotaxic biopsy of the right frontal lobe lesion demonstrated several areas of demyelination. PCR for JC virus and Toxoplasma gondii on biopsy was negative, as well as Mycobacterium tuberculosis complex and acidalcohol-resistant bacilli tests (Fig. 1) .

Neuroradiological and pathological findings were suggestive of tumefactive demyelinating lesions (TDLs). Intravenous 1-g methylprednisolone was administered for 7 days. Two days after the last dose, a follow-up brain MRI showed dimensional decrease of both frontal lesions, with disappearance of mass effect; gadolinium enhancement was substantially decreased (Fig. 1 ). However, a new small capsulo-lenticular lesion with analogous features was noted. Lumbar puncture showed mild lymphocytic pleocytosis (14/ µL), proteinorachia (84 mg/dL) and no oligoclonal bands; CSF glucose was 58 mg/dL. CSF was negative for infectious agents, including PCR for JC virus; CSF HIV-RNA count was 90 copies/mL.

Due to the persistent inflammatory activity observed at brain MRI, a single dose of cyclophosphamide (800 mg/m 2 i.v.) was administered, with benefit. At hospital discharge, the patient was oriented, with mild persisting memory deficits and sporadic anomia. At 3-month follow-up MRI, a marked reduction of FLAIR hyperintensities and absence of post-contrast enhancement were observed (Fig. 1 ). Neurological examination was normal, as well as cognitive function. A clinical and neuroradiological 6-month follow-up has been scheduled to assess the stability of patient's condition; [4] , but we cannot even exclude a direct role for HIV in the demyelinating process. The co-occurrence of HIV infection and TDLs implies obvious concerns about the treatment of this particular condition. Intravenous high-dose steroid treatment was reported to be successful in sparse cases [2, 3] . However, in literature, no data are available for steroid-unresponsive TDLs in HIV patients [5] .

Given the concern to expose an HIV patient to prolonged lymphopenia, we chose cyclophosphamide to induce a quick-onset and short-duration immunosuppressive effect. We planned to administer a pulse regimen of 800 mg/m 2 every 4 weeks. However, due to the SARS-CoV-2 pandemic, the further doses were not administered. Nevertheless, after 5 months from the first dose, we observed a normalization of neurological examination and a significant improvement of neuroradiological findings.

In conclusion, in our case quick initiation of cART and cyclophosphamide led to a significant clinical and radiological amelioration, likely secondary to the restoration of para-physiological immune function. Based on our experience, a treatment with cyclophosphamide may be a valid alternative in steroid-resistant HIV patients with TDLs.

Author contributions SML contributed to paper conception, data collection, analysis and interpretation, literature review and paper drafting. CM and TR contributed to data collection, analysis and interpretation, literature review and paper drafting. SF, CM, CB and ML contributed to data collection, analysis and critical review. FM contributed to paper conception, supervised data analysis and interpretation, critically reviewed the paper.

Funding Not applicable.

Ethics approval The Ethics Committee of San Raffaele Scientific Institute waived the need for ethics approval for publication of case reports.

Consent to participate Written informed consent was obtained from the patient's spouse for the usage of clinical data in anonymized fashion.

Consent for publication Informed consent for publication was obtained verbally from the spouse. The consent was audio-recorded in the presence of an independent witness. Fig. 1 (1) Serial 1.5-T MRI axial brain scans, performed after admission (a), at one (b) and 3 months (c) after the clinical onset of a frontal lobe syndrome due to large tumefactive demyelinating lesions.

(2) A-D Images of brain parenchyma sample from stereotactic biopsies, haematoxylin and eosin-stained section showing increased cellularity due to the presence of numerous intraparenchymal foamy macrophages (A, ×40); those cells are highlighted by anti-CD163 antibody (B, ×40). Kluver-Barrera staining shows loss of myelin (C and D, ×20). E-G Brain parenchyma sample with perivascular cuff is composed by mononuclear inflammatory cells stained with haematoxylin and eosin (E, ×40); perivascular cuff is made of macrophages immunoreactive for anti-CD163 antibody (F, ×40) and by T lymphocytes highlighted by anti-CD3 antibody (G, ×20).

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