Oncological effects on the central nervous system
Anju Sahdev, Sarah J. Vinnicombe in Husband & Reznek's Imaging in Oncology, 2020
The development of new biological and immunotherapies has led to recognition of a wider range of neurotoxicities involving the peripheral, autonomic, and central nervous systems, shown in Figure 37.3. A number of these have well-described neuroimaging features. A comprehensive review of all possible neurotoxicity related to newer treatments is beyond the scope of this chapter. Only those conditions with a distinctive imaging appearance contributing to the diagnosis will be described. Several of the biologic or immune agents, including antibody therapies, carry risks for serious associated neurological disease, such as progressive multifocal leukoencephalopathy (PML), while others predispose to the more benign posterior reversible leukoencephalopathy syndrome (PRES) (10). Stroke and vaso-occlusive effects are associated with a more diverse range of cancer drug treatments (10). The immunosuppressant effect of many cancer treatments increases the risk of CNS infection, as well as predisposing to systemic infection.
Demyelinating syndrome
Michael Y. Wang, Andrea L. Strayer, Odette A. Harris, Cathy M. Rosenberg, Praveen V. Mummaneni in Handbook of Neurosurgery, Neurology, and Spinal Medicine for Nurses and Advanced Practice Health Professionals, 2017
Natalizumab (Tysabri) is a monoclonal antibody infusion with a 67% reduction in relapse rates over 2 years compared to placebo (Polman et al., 2006). It is associated with the development of progressive multifocal leukoencephalopathy (PML), and the patient must be counseled on this risk. Alemtuzumab (Lemtrada) is a CD-52 directed cytolytic antibody infusion with risk for autoimmune reactions, infusion reactions, and malignancy. More than 85% of patients remained free of MRI lesion activity 3 years later (Cohen et al., 2012). Ocrelizumab (Ocrevus) is a monoclonal antibody that depletes CD-20+ B cells approved for RRMS and PPMS. This is the first medication that has been FDA approved for the treatment of progressive MS, showing reduction in disability progression by 25% at 24 weeks when compared to placebo (Montalban et al., 2016, pp. 212–216). In the RRMS clinical trials, ocrelizumab reduced relapse rates by 46% over 2 years when compared to the active comparator (Rebif 44 mcg TIW), and reduced disability progression by 40% at 24 weeks (Hauser et al. 2016, pp. 224–228).
Central nervous system
Dave Maudgil, Anthony Watkinson in The Essential Guide to the New FRCR Part 2A and Radiology Boards, 2017
Are the following statements regarding cerebral HIV/AIDS true or false? If only a single lesion is present then toxoplasmosis is less likely than lymphoma.Cytomegalovirus typically presents with cognitive dysfunction.Hydrocephalus is a recognised presentation of cryptococcosis.Progressive multifocal leukoencephalopathy (PML) lesions are usually diffuse and symmetrical.Toxoplasmosis lesions commonly occur in the basal ganglia.
Infratentorial onset of progressive multifocal leukoencephalopathy in a patient with systematic lupus erythematosus complicated with lymphoma: a case report
Published in Modern Rheumatology Case Reports, 2021
Mita Sakuraba, Shinji Watanabe, Yasuhiro Nishiyama, Kenta Takahashi, Kazuo Nakamichi, Mikito Suzuki, Takashi Nawata, Kota Komai, Takahisa Gono, Mitsuhiro Takeno, Tadaki Suzuki, Kazumi Kimura, Masataka Kuwana
Progressive multifocal leukoencephalopathy (PML) is a progressive demyelinating disease of the central nervous system (CNS) caused by reactivation of JC virus (JCV) in immunocompromised subjects, including those with acquired immunodeficiency syndrome, cancer, organ transplantation, and autoimmune diseases [1]. Recently, antiretroviral therapy has successfully reduced the incidence of PML in human immunodeficiency virus (HIV)-infected individuals [2]. In contrast, the incidence of PML is increasing in patients with autoimmune diseases treated with potent immunosuppressive therapies [3]. Systemic lupus erythematosus (SLE) is the leading underlying disease of PML and comprises approximately two-thirds of reported cases. The incidence of PML in SLE patients has been estimated to range from 1.0 to 2.4 cases/100,000 person-years [4,5].
Reduced expression of L-selectin in T-cells correlates with relative lymphocyte increase in patients with RRMS treated with natalizumab - functional implication towards PML risk
Published in Neurological Research, 2020
Marina Kleopatra Boziki, Theodoros Karapanayotides, Georgios Papadopoulos, Roza Lagoudaki, Pamela Melo, Christos Bakirtzis, Ioannis Nikolaidis, Evdoxia Gounari, Vasiliki Tsavdaridou, Lemonia Skoura, Theodora Afrantou, Theano Tatsi, Eleni Grigoriadou, Eleni Polyzoidou, Nikolaos Mandoras, Virginia Giantzi, Anna Kalogera - Fountzila, Panagiotis Ioannidis, Dimitrios Parissis, Sygkliti-Henrietta Pelidou, Sofia Zoidou, Nikolaos Grigoriadis
Natalizumab (NTZ) is a widely used second-line disease-modifying treatment (DMT) indicated for highly active relapsing-remitting Multiple sclerosis (RRMS). It is a monoclonal antibody to a4-integrin, preventing CD4 + T-cell migration across the blood-brain barrier (BBB) and towards the central nervous system (CNS). NTZ has shown a profound effect in reducing ARR in patients with highly active disease, for which first-line DMTs have failed. However, its use is subjected in restrictions with respect to Progressive Multifocal Leukoencephalopathy (PML), a rare but serious treatment-related side effect. PML is attributed to the active replication of the John Cunningham virus (JCV) in the CNS. It was initially described in patients with hematological cancer [1] and further in patients with HIV/AIDS in association with reduced CD4 + T-cell counts [2]. In patients with HIV/AIDS, reduced lymphocyte and CD4 + T-cell count predisposes to reduced immune-surveillance in the CNS, thus increasing PML risk. L-selectin (CD62L) mediates the sequestration of naive CD4 + T cells to peripheral lymph nodes [3] and expression of L-selectin and CD4 is crucial for the elimination of foreign antigens by T-cells. On HIV-1-infected cells, L-selectin is down-regulated by TCR-negative signals that result from cross-linking between the CD4 molecule and the virus envelope. Thus, in the context of HIV/AIDS, it has been suggested that reduced L-selectin expression in CD4 + T-cells may lead to reduced CD4 + T-cell functional competence towards JCV [4].
The Effect of a Polysaccharide-Based Multinutrient Dietary Supplementation Regimen on Infections and Immune Functioning in Multiple Sclerosis
Published in Journal of Dietary Supplements, 2020
H. Reginald McDaniel, Christopher LaGanke, Laura Bloom, Sharon Goldberg, Lucas C. Lages, Laura A. Lantigua, Steven E. Atlas, Judi M. Woolger, John E. Lewis
Progressive multifocal leukoencephalopathy (PML) is one of the most-feared DMT-associated complications. This irreversible, potentially fatal, neurodegenerative disease results from immunosuppressive reactivation of the JC virus, an otherwise benign virus detected in 50%–60% of the population (Vargas and Tyor 2017). Hundreds of PML cases have been reported with natalizumab use (Vargas and Tyor 2017), and more recently, smaller numbers of cases have been reported with two of the first-line DMTs, fingolimod and dimethyl fumarate (van Oosten et al. 2013; Nieuwkamp et al. 2015; Rosenkranz et al. 2015; van Kester et al. 2015). Many other DMT-associated side effects have also been reported, including hepatotoxicity and elevated liver transaminases, gastrointestinal discomfort, flushing, decreased lymphocyte count, bradyarrhythmias (fingolimod), and teratogenicity (teriflunomide) (Vargas and Tyor 2017).
Related Knowledge Centers
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