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              <p>Central nervous system mucormycosis (CNS-M) is a severe disease with difficult and often delayed diagnosis, leading to high mortality. The aim of this new study was to assess clinical and radiological presentation according to underlying conditions and dissemination routes, to optimize diagnostic strategies. We conducted a retrospective national study including 54 CNS-M cases diagnosed between 2005 and 2020, with brain imaging reviewed by two neuroradiologists. CNS-M resulted from presumed hematogenous dissemination in 29 patients (54%) and from direct extension in 25 (46%), known as rhino-orbito-cerebral mucormycosis (ROCM). No neurological symptoms were found in 10/54 (19%), regardless of dissemination route. Hematogenous CNS-M mainly affected highly immunocompromised (HM or SOT) patients (90%), including 43% neutropenic. Radiology showed abscesses (87%) and small vessel disease (39%). In ROCM, two patterns emerged depending on osteolysis (19/25, 76%) or its absence (6/25, 24%). ROCM without bone lysis, mostly in severely immunosuppressed patients, caused meningitis without abscess, whereas osteolytic ROCM led to abscess formation (11/18, 60%). Without osteolysis, perineural spread along the optic nerve occurred in 2/3 cases. Serum Mucorales PCR was positive in 91% of hematogenous and 64% of ROCM cases. Fungal co-infections occurred in 26%. This study underscores distinct invasion patterns and the need for extensive workup in CNS-M, highlighting the diagnostic value of MRI with gadolinium and serum Mucorales qPCR based on dissemination route and underlying condition. MRI is particularly useful in ROCM for detecting meningitis (80%), large vessel disease (30%), and perineural involvement (8%).</p>
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