Book contents
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part I Clinical syndromes: general
- Part II Clinical syndromes: head and neck
- Part III Clinical syndromes: eye
- Part IV Clinical syndromes: skin and lymph nodes
- Part V Clinical syndromes: respiratory tract
- Part VI Clinical syndromes: heart and blood vessels
- Part VII Clinical syndromes: gastrointestinal tract, liver, and abdomen
- Part VIII Clinical syndromes: genitourinary tract
- Part IX Clinical syndromes: musculoskeletal system
- Part X Clinical syndromes: neurologic system
- 74 Bacterial meningitis
- 75 Aseptic meningitis syndrome
- 76 Acute viral encephalitis
- 77 Intracranial suppuration
- 78 Spinal epidural abscess
- 79 Myelitis and peripheral neuropathy
- 80 Reye syndrome
- 81 Progressive multifocal leukoencephalopathy
- 82 Cerebrospinal fluid shunt infections
- 83 Prion diseases
- Part XI The susceptible host
- Part XII HIV
- Part XIII Nosocomial infection
- Part XIV Infections related to surgery and trauma
- Part XV Prevention of infection
- Part XVI Travel and recreation
- Part XVII Bioterrorism
- Part XVIII Specific organisms: bacteria
- Part XIX Specific organisms: spirochetes
- Part XX Specific organisms: Mycoplasma and Chlamydia
- Part XXI Specific organisms: Rickettsia, Ehrlichia, and Anaplasma
- Part XXII Specific organisms: fungi
- Part XXIII Specific organisms: viruses
- Part XXIV Specific organisms: parasites
- Part XXV Antimicrobial therapy: general considerations
- Index
- References
81 - Progressive multifocal leukoencephalopathy
from Part X - Clinical syndromes: neurologic system
Published online by Cambridge University Press: 05 April 2015
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part I Clinical syndromes: general
- Part II Clinical syndromes: head and neck
- Part III Clinical syndromes: eye
- Part IV Clinical syndromes: skin and lymph nodes
- Part V Clinical syndromes: respiratory tract
- Part VI Clinical syndromes: heart and blood vessels
- Part VII Clinical syndromes: gastrointestinal tract, liver, and abdomen
- Part VIII Clinical syndromes: genitourinary tract
- Part IX Clinical syndromes: musculoskeletal system
- Part X Clinical syndromes: neurologic system
- 74 Bacterial meningitis
- 75 Aseptic meningitis syndrome
- 76 Acute viral encephalitis
- 77 Intracranial suppuration
- 78 Spinal epidural abscess
- 79 Myelitis and peripheral neuropathy
- 80 Reye syndrome
- 81 Progressive multifocal leukoencephalopathy
- 82 Cerebrospinal fluid shunt infections
- 83 Prion diseases
- Part XI The susceptible host
- Part XII HIV
- Part XIII Nosocomial infection
- Part XIV Infections related to surgery and trauma
- Part XV Prevention of infection
- Part XVI Travel and recreation
- Part XVII Bioterrorism
- Part XVIII Specific organisms: bacteria
- Part XIX Specific organisms: spirochetes
- Part XX Specific organisms: Mycoplasma and Chlamydia
- Part XXI Specific organisms: Rickettsia, Ehrlichia, and Anaplasma
- Part XXII Specific organisms: fungi
- Part XXIII Specific organisms: viruses
- Part XXIV Specific organisms: parasites
- Part XXV Antimicrobial therapy: general considerations
- Index
- References
Summary
Introduction
In their seminal report in 1958, Astrom, Mancall, and Richardson described a progressive neurologic syndrome with a characteristic triad of neuropathologic findings, namely, demyelination, giant astrocytes, and oligodendrocytes with abnormal nuclei. They named the disorder progressive multifocal leukoencephalopathy (PML). The viral etiology of this neurologic disease was not determined until later. Until the advent of the acquired immunodeficiency syndrome (AIDS) pandemic, PML remained a vanishingly rare disorder seen almost exclusively in individuals with underlying immunosuppressive disorders. Prior to the advent of highly active antiretroviral therapy (HAART), PML occurred in approximately 1 in 20 of all human immunodeficiency virus (HIV)-infected persons in developed countries. Although the incidence of AIDS-associated PML appears to have declined since the availability of HAART, it has not declined to the extent observed with other opportunistic infections (Sacktor 2002). Currently, AIDS has been estimated to be the predisposing disorder for about 90% of all PML cases. More recently, monoclonal antibodies, such as natalizumab, an α4 β1 integrin inhibitor, and rituximab, a chimeric monoclonal antibody directed against CD20 receptors on B cells, and other immune-altering pharmacologic agents, such as mycophenolate mofetil, have been associated with PML and carry US Food and Drug Administration (FDA) mandated “black box” warnings of this risk.
JC virus and the pathogenesis of PML
In 1965, Zu Rhein and Chou identified viral particles in glial nuclei resembling papovavirus. Subsequently, Padgett isolated polyomavirus from PML brain in glial cell cultures. The virus has a simple DNA genome of 5.1 kilobases in a double-stranded, supercoiled form, encapsidated in an icosahedral protein structure measuring 40 to 50 nm in diameter. The virus was named the JC virus (JCV) after the initials of the person from whom it was first isolated. JCJCV DNA encodes for three capsid (VP1, VP2, and VP3) proteins and five regulatory proteins (agnoprotein, t, T, T, T’135, T’136, and T’165); the latter three are derived by alternative splicing of early viral mRNA. To date, all cases of PML have been associated with JCV; although there are rare reports of other polyomaviruses, in particular, BK virus, being associated with PML-like disorder in immunosuppressed individuals.
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- Clinical Infectious Disease , pp. 529 - 535Publisher: Cambridge University PressPrint publication year: 2015