Cerebral Infectious Opportunistic Lesions in a Patient with Acute Myeloid Leukaemia: The Challenge of Diagnosis and Clinical Management

Abstract

Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We report the case of a 48-year-old man with acute myeloid leukaemia and probable pulmonary aspergillosis, who developed hyposthenia of the left upper limb, after achieving leukaemia remission and while on voriconazole. Magnetic resonance imaging (MRI) showed oedematous CNS lesions with a haemorrhagic component in the right hemisphere with lepto-meningitis. After 2 weeks of antibiotics and amphotericin-B, brain biopsy revealed chronic inflammation with abscess and necrosis, while cultures were negative. Clinical recovery was attained, he was discharged on isavuconazole and allogeneic transplant was postponed, introducing azacitidine as a maintenance therapy. After initial improvement, MRI worsened; brain biopsy was repeated, showing similar histology; and 16S metagenomics sequencing analysis was positive (Veilonella, Pseudomonas). Despite 1 month of meropenem, MRI did not improve. The computer tomography and PET scan excluded extra-cranial infectious-inflammatory sites, and auto-immune genesis (sarcoidosis, histiocytosis, CNS vasculitis) was deemed unlikely due to the histological findings and unilateral lesions. We hypothesised possible IFD with peri-lesion inflammation and methyl-prednisolone was successfully introduced. Steroid tapering is ongoing and isavuconazole discontinuation is planned with close follow-up. In conclusion, the management of CNS complications in immunocompromised patients needs an interdisciplinary approach.

Keywords: acute myeloid leukaemia; breakthrough central nervous system infection; cerebral abscesses; invasive fungal diseases.

Figure 1

This is the timeline of lung computer tomography scans: (A) Leukaemia diagnosis, initiation of remission induction chemotherapy: interstitial pneumonia with haemorrhagic alveolitis in the medium lobe. (B) Before first cycle of consolidation chemotherapy: complete atelectasis of the medium lobe with obliteration of the bronchus. (C) Before second cycle of consolidation chemotherapy: reduction in the atelectasis of the medium lobe and appearance of atelectasis of the right inferior lobe sustained by the sub-obstruction of the lumen of the right main and intermediate bronchi. (D) At the onset of opportunistic central nervous system lesions: reduction in atelectasis of both the medium and right inferior lobes. (E) Before starting corticosteroid treatment for central nervous system lesions: resolution of endo-bronchial/pulmonary aspergillosis.

Figure 2

This is the timeline of brain magnetic resonance imaging: (A₁) Axial T2-TSE w.i.: multiple hyperintense subcortical foci of oedema with mass effect in right fronto-parietal region. (A₂) Post-contrast FFE-T1 w.i.: cortico-subcortical frontal and parietal foci of inhomogeneous enhancement, necrosis, and meningeal involvement. (B₁) Axial T2-TSE w.i.: worsening of oedema and mass effect. (B₂) Post-contrast FFE-T1 w.i.: increase in size of frontal and parietal foci of enhancement. (C₁) Axial T2-TSE w.i.: reduction in oedema and mass effect. (C₂) Post-contrast FFE-T1 w.i.: signs of right frontal craniotomy and remarkable reduction in enhancing parietal lesion. (D₁) Axial T2-TSE w.i.: increase in oedema extension. (D₂) Post-contrast FFE-11 w.i.: increase in size of enhancing frontal and parietal lesions. (E₁) Axial T2-TSE w.i.: further progressive extension of oedema in right hemisphere subcortical white matter. (E₂) Post-contrast FFE-T1 w.i.: progressive increase in enhancing frontal and parietal lesions. (F₁) Axial T2-TSE w.i.: partial reabsorption of oedema in right hemisphere and reduction in mass effect. (F₂) Post-contrast FFE-T1 w.i.: decrease in enhancement in both frontal and parietal regions.