Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple sclerosis: a decade of lessons learned

@article{Major2018PathogenesisOP,
  title={Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple sclerosis: a decade of lessons learned},
  author={Eugene O. Major and Tarek A. Yousry and David B Clifford},
  journal={The Lancet Neurology},
  year={2018},
  volume={17},
  pages={467-480}
}
Progressive multifocal leukoencephalopathy (PML) is a rare, devastating demyelinating disease of the CNS caused by the JC virus (JCV) that occurs in patients with compromised immune systems. Detection of PML in systemically immunocompetent patients with multiple sclerosis treated with natalizumab points to a role for this drug in the pathophysiology of PML. Emerging knowledge of the cellular and molecular biology of JCV infection and the pathogenesis of PML-including interplay of this common… Expand
Immune checkpoint blockade for treating progressive multifocal leukoencephalopathy
A case series from the National Institutes of Health and two single case-reports indicate that some cases of progressive multi focal leukoencephalomyelopathy (PML) can benefit from treat ment withExpand
Germline Genetic Risk Variants for Progressive Multifocal Leukoencephalopathy
TLDR
A PML risk prediction test would have clinical utility in all at risk patient groups but would be particularly beneficial in patients considering therapy with immunosuppressant agents known to cause PML, such as natalizumab, rituximab, and others. Expand
Treatment of Progressive Multifocal Leukoencephalopathy Using Immune Restoration
TLDR
A review of the current options for management of PML in typical situations where this disease presents, including several where immune restoration is a standard therapeutic approach, and strategies to monitor and facilitate immune restoration are focused on. Expand
Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy
TLDR
These findings are consistent with the hypothesis that in some patients with PML, pembrolizumab reduces JC viral load and increases CD4+ and CD8+ activity against the JC virus. Expand
Pembrolizumab for progressive multifocal leukoencephalopathy due to primary immunodeficiency
TLDR
Another patient with PML who did not benefit from treatment with pembrolizumab is described, a humanized monoclonal antibody directed against PD-1 that was reported for the first time to be a promising option for PML. Expand
Development of demyelinating lesions in progressive multifocal leukoencephalopathy (PML): Comparison of magnetic resonance images and neuropathology of post‐mortem brain
TLDR
Observations indicate that PML lesions likely evolve with three steps in a tract‐dependent manner: initiation; (2) extension/expansion of demyelinating lesions; and (3) fusion. Expand
Risk Assessment of Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patients during 1 Year of Ocrelizumab Treatment
TLDR
Combined monitoring of ocrelizumab’s effects on JCPyV pathogenicity and on host immunity might offer a complete insight towards predicting PML risk. Expand
Progressive multifocal leukoencephalopathy in a 27-year-old lady with systemic lupus erythematosus - rheumatoid arthritis overlap syndrome.
TLDR
A 27-year-old lady of systemic lupus erythematosus (SLE) - rheumatoid arthritis overlap syndrome with suspected involvement of central nervous system is presented to raise the importance of clinical alertness for the rare but possibly underdiagnosed PML. Expand
[Neurological complications of JC virus infection: A review].
TLDR
The therapeutic objective is to restore host immune responses to JCV, while avoiding immune-reconstitution inflammatory syndrome. Expand
Immune profiling of a patient with alemtuzumab-associated progressive multifocal leukoencephalopathy
TLDR
The first case of an alemtuzumab-treated patient with clinical symptoms and radiological features compatible with PML, and the lack of large T- and B-cell diversity, necessary for JCV recognition, is likely to have concurred to PML insurgence. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 116 REFERENCES
Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain
TLDR
The study of JCV and the elucidation of the underlying causes of PML are important and active areas of research that may lead to new insights into immune function and host antiviral defense, as well as to potential new therapies. Expand
Sorting out the risks in progressive multifocal leukoencephalopathy
TLDR
A categorization of immunosuppressive agents according to their risk of PML is proposed to support a better-informed decision-making process when evaluating the risks and benefits of these therapies. Expand
Risk of natalizumab-associated progressive multifocal leukoencephalopathy.
TLDR
Positive status with respect to anti-JC virus antibodies, prior use of immunosuppressants, and increased duration of natalizumab treatment, alone or in combination, were associated with distinct levels of PML risk in natalIZumab-treated patients with multiple sclerosis. Expand
Progressive multifocal leukoencephalopathy therapy
TLDR
Improved therapy for human immunodeficiency virus and ability to reverse the effects of natalizumab and optimal immune reconstitution to control JC virus without causing brain-damaging immune reconStitution inflammatory syndrome (IRIS) currently is the most practical approach to treat PML. Expand
JC virus persistence following progressive multifocal leukoencephalopathy in multiple sclerosis patients treated with natalizumab
JC virus (JCV) DNA in the cerebrospinal fluid (CSF) provides the laboratory confirmatory diagnosis of progressive multifocal leukoencephalopathy (PML) in patients whose clinical symptoms and magneticExpand
A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes
TLDR
This study found no evidence of anti-JCV activity by mefloquine and an early decrease of CSF JCV DNA load appears to be associated with a better clinical outcome. Expand
B Cells and Progressive Multifocal Leukoencephalopathy: Search for the Missing Link
TLDR
Accumulating evidence suggests that B cells may considerably influence T cell responses through their cytokine secretion, which may play an important role in the control of JCV infection and in the pathogenesis of PML, including rituximab-induced PML. Expand
Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy.
TLDR
A detailed review of possible cases ofPML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalIZumab for a mean of 17.9 months. Expand
Stratification and monitoring of natalizumab-associated progressive multifocal leukoencephalopathy risk: recommendations from an expert group
TLDR
A simple and pragmatic algorithm is presented to support the introduction of anti-JCV antibody index testing and MRI monitoring into standard PML safety protocols, in order to allow some JCV positive patients who wish to begin or continue natalizumab treatment to be managed with a more individualised analysis of their PML risk. Expand
Presymptomatic Diagnosis with MRI and Adequate Treatment Ameliorate the Outcome after Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
TLDR
PML is described in a patient with MS after 44 monthly infusions of natalizumab and the importance of an early, presymptomatic, detection of PML and an adequate treatment is illustrated. Expand
...
1
2
3
4
5
...