Progressive Multifocal Leukoencephalopathy in a Patient With Miliary Tuberculosis: Differential Diagnosis From Tuberculoma

Dear Editor,The human-specific pathogen John Cunningham polyomavirus (JCV) is an established etiological agent of progressive multifocal leukoencephalopathy (PML), a frequently fatal demyelinating disease of the brain. 1 Recently, the spectrum of conditions predisposing to PML has expanded, with rising reports among patients receiving immunomodulatory therapies for autoimmune diseases as well as among those with hematologic malignancies, organ transplantation, and other chronic immunosuppressive states.[1][2][3] In PML, JCV replication causes the lytic injury of oligodendrocytes and induces astrocytic changes, resulting in gradual and widespread degeneration of white matter in the central nervous system.Infection of oligodendrocytes, the main targets of JCV, generally results in productive viral replication.These infected oligodendrocytes show nuclear enlargement with basophilic intranuclear inclusions, which lead to impaired myelin synthesis and eventual extensive white matter demyelination. 1 However, astrocytes infected by JCV show a more variable pattern. 2 Some cells contain late viral genes and are subsequently destroyed, whereas others do not support complete replication and instead develop atypical transformation-like features.3 Infected astrocytes often show notable changes, commonly exhibiting a varied morphology with unusually enlarged nuclei and bizarre forms.PML produces multifocal areas of demyelination, accompanied by reactive gliosis and giant, atypical multinucleated astrocytes within the affected regions.Clinical symptoms, including motor deficits, visual disturbances, cognitive impairment, altered mental status, and personality changes, vary with the site of demyelination.Magnetic resonance imaging (MRI) is the optimal modality for diagnosing PML.On T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI sequences, classical PML lesions show hyperintense signals and are asymmetric, lack contrast enhancement or mass effect, and typically spare the periventricular white matter.[4][5][6] However, atypical features such as ring-enhancing or tumefactive lesions have also been observed, particularly in immune reconstitution inflammatory syndrome, thereby complicating the differential diagnosis due to overlap with infectious or neoplastic pathologies.[6][7][8] Here, we encountered an 85-year-old man who had been receiving antituberculous therapy for 1 month and had recently been diagnosed with miliary tuberculosis confirmed through chest computed tomography (Fig. 1A) and antituberculous tests.The patient had a medical history of ischemic heart disease, dyslipidemia, and hypertension.He presented with progressive dysarthria, left facial weakness, and hemiparesis.Brain MRI revealed a lesion located in the right superior frontal gyrus and centrum semiovale, exhibiting hyperintensity on T2-weighted and FLAIR sequences but no significant enhancement on contrastenhanced T1 images (Fig. 1B-D).Based on the suspicion of active tuberculosis and the imaging characteristics, we assessed for both tuberculoma and PML.Consequently, surgical