Development of demyelinating lesions in progressive multifocal leukoencephalopathy (PML): Comparison of magnetic resonance images and neuropathology of post‐mortem brain

• Published in: Neuropathology Vol. 39; no. 4; pp. 294 - 306
• Main Authors: Ono, Daisuke, Shishido‐Hara, Yukiko, Mizutani, Saneyuki, Mori, Yoko, Ichinose, Keiko, Watanabe, Mutsufusa, Tanizawa, Tohru, Yokota, Takanori, Uchihara, Toshiki, Fujigasaki, Hiroto
• Format: Journal Article
• Language: English
• Published: Melbourne John Wiley & Sons Australia, Ltd 01.08.2019; Wiley Subscription Services, Inc
• Subjects: Acquired immune deficiency syndrome; AIDS; Brain - diagnostic imaging; Brain - pathology; Brain stem; Case Report; Case Reports; Cerebellum; Cerebrospinal fluid; Copy number; Demyelination; Diagnosis; Disease Progression; disease‐modifying therapy (DMT); Encephalitis; Humans; Immunodeficiency; JC virus (JCV); Leukoencephalopathy; Leukoencephalopathy, Progressive Multifocal - diagnostic imaging; Leukoencephalopathy, Progressive Multifocal - pathology; Magnetic Resonance Imaging; magnetic resonance imaging (MRI); Male; Middle Aged; Multiple sclerosis; multiple sclerosis (MS); Neuroimaging; Neuropathology; NMR; Nuclear magnetic resonance; Opportunist infection; Precentral gyrus; Prognosis; Progressive multifocal leukoencephalopathy; progressive multifocal leukoencephalopathy (PML); Putamen; Substantia alba; Tegmentum; Thalamus; Viral infections; White Matter - diagnostic imaging; White Matter - pathology; magnetic resonance imaging (MRI); multiple sclerosis (MS); progressive multifocal leukoencephalopathy (PML); JC virus (JCV); disease-modifying therapy (DMT)
• ISSN: 0919-6544; 1440-1789
• DOI: 10.1111/neup.12562

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by opportunistic infection of JC polyomavirus (JCV). Today, increased attention has been focused on PML development in multiple sclerosis (MS) patients under disease‐modifying therapies (DMT). Although in the acquired immunodeficiency syndrome (AIDS) era, PML was thought to be a rapidly progressive disease with poor prognosis, drug‐associated PML is relatively slow in progress, and a favorable outcome may be expected with early diagnosis. However, early PML diagnosis on magnetic resonance imaging (MRI) is frequently difficult, and JCV DNA copy number in cerebrospinal fluid (CSF) is usually low. To facilitate early PML diagnosis on MRI, the pre‐mortem images were compared with neuropathology of the post‐mortem brain, and underlying pathology corresponding to the MRI findings was evaluated. As a result, PML lesions of the autopsied brain were divided into three parts, based on the disease extension patterns: (A) Progressive white matter lesion in the right frontoparietal lobe including the precentral gyrus. Huge demyelinated lesions were formed with fusions of numerous small lesions. (B) Central lesion including deep gray matters, such as the putamen and thalamus. The left thalamic lesion was contiguous with the pontine tegmentum. (C) Infratentorial lesion of brainstem and cerebellum. Demyelination in the pontine basilar region and in cerebellar white matter was contiguous via middle cerebellar peduncles (MCPs). In addition, (D) satellite lesions were scattered all over the brain. These observations indicate that PML lesions likely evolve with three steps in a tract‐dependent manner: (1) initiation; (2) extension/expansion of demyelinating lesions; and (3) fusion. Understanding of the PML disease evolution patterns would enable confident early diagnosis on MRI, which is essential for favorable prognosis with good functional outcome.