LAUSR

A 43-year-old, previously healthy man presented to the emergency department due to subacute onset, in the previous month, of behavioral changes and speech impairment. Head CT scan revealed two large subcortical hypodense lesions in both frontal lobes, with large perilesional oedema. On admission, disorientation, and attention and memory deficits with failure at the immediate recall test were noted. Spontaneous speech was poor, with anomia and perseverative behaviors. The patient scored 0/18 at the Frontal Assessment Battery [1]. Neuropsychological tests revealed global cognitive impairment and anosognosia. The remaining neurological examination was unremarkable. Brain MRI confirmed two large oedematous lesions in frontal lobes with moderate mass effect and mild midline shift. T1-weighted sequences showed open-ring enhancement of both lesions (Fig. 1). Proton magnetic spectroscopy showed an increased lactate peak, and reduction of N-acetylaspartate levels. Total-body CT scan was negative for systemic malignancies. Complete blood count, standard laboratory tests and autoimmune panel were unremarkable. Serum screening for antiAQP4, anti-MOG, anti-NMDAR, anti-LGI1, anti-CASPR2 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/m2 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; * Massimo Filippi [email protected]